Research activity information

• Human Muse cells isolated from preterm- and term-umbilical cord delivered therapeutic effects in rat bleomycin-induced lung injury model without immunosuppressant.

  Kaung Htet Nay Win, Yoshihiro Kushida, Keiji Yamana, Sota Iwatani, Makiko Yoshida, Nanako Nino, Cho Yee Mon, Hiroyuki Ohsaki, Shingo Kamoshida, Kazumichi Fujioka, Mari Dezawa, Noriyuki Nishimura

  BACKGROUND: Bleomycin (BLM)-induced lung injury is characterized by mixed histopathologic changes with inflammation and fibrosis, such as observed in human patients with bronchopulmonary dysplasia, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. Although no curative therapies for these lung diseases exist, stem cell therapy has emerged as a potential therapeutic option. Multilineage-differentiating stress-enduring (Muse) cells are endogenous pluripotent- and macrophage-like stem cells distributed in various adult and fetal tissues as stage-specific embryonic antigen-3-positive cells. They selectively home to damaged tissue by sensing sphingosine-1-phosphate and replace the damaged/apoptotic cells by in vivo differentiation. Clinical trials for some human diseases suggest the safety and therapeutic efficacy of intravenously injected human leukocyte antigen-mismatched allogenic Muse cells from adult bone marrow (BM) without immunosuppressant. Here, we evaluated the therapeutic effects of human Muse cells from preterm and term umbilical cord (UC), and adult BM in a rat BLM-induced lung injury model. METHODS: Rats were endotracheally administered BLM to induce lung injury on day 0. On day 3, human preterm UC-Muse, term UC-Muse, or adult BM-Muse cells were administered intravenously without immunosuppressants, and rats were subjected to histopathologic analysis on day 21. Body weight, serum surfactant protein D (SP-D) levels, and oxygen saturation (SpO2) were monitored. Histopathologic lung injury scoring by the Ashcroft and modified American Thoracic Society document scales, quantitative characterization of engrafted Muse cells, RNA sequencing analysis, and in vitro migration assay of infused Muse cells were performed. RESULTS: Rats administered preterm- and term-UC-Muse cells exhibited a significantly better recovery based on weight loss, serum SP-D levels, SpO2, and histopathologic lung injury scores, and a significantly higher rate of both Muse cell homing to the lung and alveolar marker expression (podoplanin and prosurfactant protein-C) than rats administered BM-Muse cells. Rats receiving preterm-UC-Muse cells showed statistically superior results to those receiving term-UC-Muse cells in many of the measures. These findings are thought to be due to higher expression of genes related to cell migration, lung differentiation, and cell adhesion. CONCLUSION: Preterm UC-Muse cells deliver more efficient therapeutic effects than term UC- and BM-Muse cells for treating BLM-induced lung injury in a rat model.

  May 2024, Stem cell research & therapy, 15(1) (1), 147 - 147, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Differential metabolic secretion between mdx mouse-derived spindle cell sarcomas and rhabdomyosarcomas drives tumor type development.

  Emma Eko Tabe Niba, Hiroyuki Awano, Noriyuki Nishimura, Hiroshi Koide, Masafumi Matsuo, Masakazu Shinohara

  The dystrophin (DMD) gene is recognized for its significance in Duchenne muscular dystrophy (DMD), a lethal and progressive skeletal muscle disease. Some DMD patients, as well as model mice with muscular dystrophy (mdx), spontaneously develop various types of tumors, among which rhabdomyosarcoma (RMS) is the most prominent. By contrast, spindle cell sarcoma (SCS) has rarely been reported in patients or mdx mice. In this study, we aimed to use metabolomics to better understand the rarity of SCS development in mdx mice. Gas chromatography-mass spectrometry was employed to compare the metabolic profiles of spontaneously developed SCS and RMS tumors from mdx mice, and metabolite supplementation assays and silencing experiments were used to assess the effects of metabolic differences in SCS tumor-derived cells. The levels of 75 metabolites exhibited differences between RMS and SCS, 25 of which were significantly altered. Further characterization revealed downregulation of non-essential amino acids, including alanine, in SCS tumors. Alanine supplementation enhanced the growth, epithelial-mesenchymal transition, and invasion of SCS cells. Reduction of intracellular alanine via knockdown of the alanine transporter Slc1a5 reduced the growth of SCS cells. Lower metabolite secretion and reduced proliferation of SCS tumors may explain the lower detection rate of SCS in mdx mice. Targeting of alanine depletion pathways may have potential as a novel treatment strategy.

  Apr. 2024, American journal of physiology. Cell physiology, English, International magazine

  Scientific journal


• Minimal Residual Disease Detected by the 7NB-mRNAs ddPCR Assay Is Associated with Disease Progression in High-Risk Neuroblastoma Patients: A Prospective Multicenter Observational Study in Japan.

  Noriyuki Nishimura, Toshiaki Ishida, Isao Yokota, Kimikazu Matsumoto, Hiroyuki Shichino, Hiroyuki Fujisaki, Takeo Sarashina, Takehiko Kamijo, Tetsuya Takimoto, Tomoko Iehara, Tatsuro Tajiri, On Behalf Of The Jccg Neuroblastoma Committee

  High-risk neuroblastoma (HR-NB) patients remain far from obtaining optimal outcomes, with more than 50% relapse/regrowth rate despite current intensive multimodal therapy. This originated from the activation/proliferation of chemoresistant minimal residual disease (MRD). MRD with a significant prognostic was reported by several quantitative PCR (qPCR) or droplet digital PCR (ddPCR) assays quantitating different sets of NB-associated mRNAs (NB-mRNAs). The 7NB-mRNAs ddPCR assay quantitating CRMP1, DBH, DDC, GAP43, ISL1, PHOX2B, and TH mRNAs was reported to outperform other qPCR assays by a retrospective in-house observational study. In the present study, the Japan Children's Cancer Group (JCCG) Neuroblastoma Committee conducted a prospective multicenter observational study aimed at evaluating a prognostic value of MRD in bone marrow (BM-MRD) and peripheral blood (PB-MRD) detected by 7NB-mRNAs ddPCR assay. Between August 2018 and August 2022, 7 HR-NB patients who registered for JCCG clinical trials (JN-H-11 and JN-H-15) were enrolled. A total of 19 BM and 19 PB samples were collected, and 4/15 BM and 4/15 PB samples were classified as progressive disease (PD)/non-PD samples. BM-MRD and PB-MRD estimated area under curve (AUC) of 0.767 and 0.800 with a significant accuracy (AUC > 0.7). The present study validated a prognostic value of BM-MRD obtained by a previous study (AUC 0.723) and revealed the significant accuracy of PB-MRD as well as BM-MRD.

  Oct. 2023, Biology, 12(10) (10), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Higher levels of minimal residual disease in peripheral blood than bone marrow before 1st and 2nd relapse/regrowth in a patient with high‑risk neuroblastoma: A case report.

  Shotaro Inoue, Kaung Htet Nay Win, Cho Yee Mon, Tomoko Fujikawa, Sayaka Hyodo, Suguru Uemura, Toshiaki Ishida, Takeshi Mori, Daiichiro Hasegawa, Yoshiyuki Kosaka, Akihiro Nishimura, Naoko Nakatani, Nanako Nino, Akihiro Tamura, Nobuyuki Yamamoto, Kandai Nozu, Noriyuki Nishimura

  More than half of patients with high-risk neuroblastoma (HR-NB) experience relapse/regrowth due to the activation of chemoresistant minimal residual disease (MRD). MRD in patients with HR-NB can be evaluated by quantitating neuroblastoma-associated mRNAs (NB-mRNAs) in bone marrow (BM) and peripheral blood (PB) samples. Although several sets of NB-mRNAs have been shown to possess a prognostic value for MRD in BM samples (BM-MRD), MRD in PB samples (PB-MRD) is considered to be low and difficult to evaluate. The present report describes an HR-NB case presenting higher PB-MRD than BM-MRD before 1st and 2nd relapse/regrowth. A 3-year-old female presented with an abdominal mass, was diagnosed with HR-NB, and treated according to the nationwide standard protocol for HR-NB. Following systemic induction and consolidation therapy with local therapy, the patient achieved complete remission but experienced a 1st relapse/regrowth 6 months after maintenance therapy. The patient partially responded to salvage chemotherapy and anti-GD2 immunotherapy but had a 2nd relapse/regrowth 14 months after the 1st relapse/regrowth. Consecutive PB-MRD and BM-MRD monitoring revealed that PB-MRD was lower than BM-MRD at diagnosis (100 times) and 1st and 2nd relapse/regrowth (1,000 and 3 times) but became higher than BM-MRD before 1st and 2nd relapse/regrowth. The present case highlights that PB-MRD can become higher than BM-MRD before relapse/regrowth of patients with HR-NB.

  Sep. 2023, Oncology letters, 26(3) (3), 369 - 369, English, International magazine


• Minimal residual disease detected by droplet digital PCR in peripheral blood stem cell grafts has a prognostic impact on high-risk neuroblastoma patients.

  Nanako Nino, Toshiaki Ishida, Naoko Nakatani, Kyaw San Lin, Kaung Htet Nay Win, Cho Yee Mon, Akihiro Nishimura, Shotaro Inoue, Akihiro Tamura, Nobuyuki Yamamoto, Suguru Uemura, Atsuro Saito, Takeshi Mori, Daiichiro Hasegawa, Yoshiyuki Kosaka, Kandai Nozu, Noriyuki Nishimura

  More than half of high-risk neuroblastoma (NB) patients have experienced relapse due to the activation of chemoresistant minimal residual disease (MRD) even though they are treated by high-dose chemotherapy with autologous peripheral blood stem cell (PBSC) transplantation. Although MRD in high-risk NB patients can be evaluated by quantitative PCR with several sets of neuroblastoma-associated mRNAs (NB-mRNAs), the prognostic significance of MRD in PBSC grafts (PBSC-MRD) is unclear. In the present study, we collected 20 PBSC grafts from 20 high-risk NB patients and evaluated PBSC-MRD detected by droplet digital PCR (ddPCR) with 7NB-mRNAs (CRMP1, DBH, DDC, GAP43, ISL1, PHOX2B, and TH mRNA). PBSC-MRD in 11 relapsed patients was significantly higher than that in 9 non-relapsed patients. Patients with a higher PBSC-MRD had a lower 3-year event-free survival (P = 0.0148). The present study suggests that PBSC-MRD detected by ddPCR with 7NB-mRNAs has a prognostic impact on high-risk NB patients.

  Oct. 2022, Heliyon, 8(10) (10), e10978, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 神戸市東部療育センター診療所の開所後3年間のまとめ

  岡田 由香, 西尾 久英, 阿部 真也, 大山 正平, 永井 正志, 福嶋 祥代, 堀之内 智子, 冨岡 和美, 村尾 真理子, 大東 寧代, 井澗 茎子, 角谷 香緒利, 西村 範行, 高田 哲, 永瀬 裕朗

  (公社)日本小児科学会, Mar. 2022, 日本小児科学会雑誌, 126(3) (3), 552 - 552, Japanese


• Genetic Analysis of UGT1A1 Polymorphisms Using Preserved Dried Umbilical Cord for Assessing the Potential of Neonatal Jaundice as a Risk Factor for Autism Spectrum Disorder in Children.

  Tomoko Horinouchi, Kaori Maeyama, Masashi Nagai, Masami Mizobuchi, Yasuko Takagi, Yuka Okada, Takeshi Kato, Mio Nishimura, Yoko Kawasaki, Mieko Yoshioka, Satoshi Takada, Hisayuki Matsumoto, Yuji Nakamachi, Jun Saegusa, Sachiyo Fukushima, Kazumichi Fujioka, Kazumi Tomioka, Hiroaki Nagase, Kandai Nozu, Kazumoto Iijima, Noriyuki Nishimura

  Neonatal jaundice has been suggested as a perinatal risk factor for autism spectrum disorder (ASD). We examined UGT1A1 polymorphisms to assess the potential of neonatal jaundice as a risk factor for ASD in children by using DNA extracted from preserved umbilical cord. In total, 79 children with ASD were genotyped for UGT1A1*28 (c.-41-40dup), UGT1A1*6 (c.211 G > A), and UGT1A1*27 (c.686 C > A). The allele frequency of UGT1A1*6 (OR = 1.34, p = 0.26) and UGT1A1*28 (OR = 0.80, p = 0.54) and the prevalence of UGT1A1*28/*6 diplotypes did not differ significantly from those in the control population. No UGT1A1*27 allele was detected in the subjects. ASD symptom assessment scores were not associated with UGT1A1*28/*6/*27 genotypes or UGT1A1*28/*6 diplotypes. These results suggest that neonatal jaundice is not significantly associated with ASD.

  Feb. 2022, Journal of autism and developmental disorders, 52(2) (2), 483 - 489, English, International magazine

  Scientific journal


• A case of autoimmune enteropathy with CTLA4 haploinsufficiency.

  Haruka Miyazaki, Namiko Hoshi, Michitaka Kohashi, Eri Tokunaga, Yuna Ku, Haruka Takenaka, Makoto Ooi, Nobuyuki Yamamoto, Suguru Uemura, Noriyuki Nishimura, Kazumoto Iijima, Keisuke Jimbo, Tsubasa Okano, Akihiro Hoshino, Kohsuke Imai, Hirokazu Kanegane, Ichiro Kobayashi, Yuzo Kodama

  Autoimmune enteropathy (AIE) is a rare disease, characterized by intractable diarrhea, villous atrophy of the small intestine, and the presence of circulating anti-enterocyte autoantibodies. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, and mutations in FOXP3, which is a master gene of regulatory T cells (Tregs), are major causes of AIE. Recent studies have demonstrated that mutations in other Treg-associated genes, such as CD25 and CTLA4, show an IPEX-like phenotype. We present the case of a 13-year-old girl with CTLA4 haploinsufficiency, suffering from recurrent immune thrombocytopenic purpura and intractable diarrhea. We detected an autoantibody to the AIE-related 75 kDa antigen (AIE-75), a hallmark of the IPEX syndrome, in her serum. She responded well to a medium dose of prednisolone and a controlled dose of 6-mercaptopurine (6-MP), even after the cessation of prednisolone administration. Serum levels of the soluble interleukin-2 receptor and immunoglobulin G (IgG) were useful in monitoring disease activity during 6-MP therapy. In conclusion, autoimmune-mediated mechanisms, similar to the IPEX syndrome, may be involved in the development of enteropathy in CTLA4 haploinsufficiency. Treatment with 6-MP and monitoring of disease activity using serum levels of soluble interleukin-2 receptor and IgG is suggested for such cases.

  Jan. 2022, Intestinal research, 20(1) (1), 144 - 149, English, International magazine

  Link to Kobe Univ. Repository (Kernel)


• Investigation of patient factors associated with the number of transfusions required during chemotherapy for high-risk neuroblastoma.

  Saori Konno, Ryu Yanagisawa, Noriko Kubota, Yoshifumi Ogiso, Noriyuki Nishimura, Kazuo Sakashita, Minoru Tozuka

  BACKGROUND: Blood transfusion is an important supportive care for high-risk neuroblastoma. When the number of transfusions increases, transfusion-associated adverse reactions may be more problematic. However, the factors determining the degree of myelosuppression and the number of transfusions during chemotherapy for high-risk neuroblastoma remain unclear. MATERIALS AND METHODS: We investigated patient factors determining the number of required transfusions in 15 high-risk neuroblastoma patients who received five courses of chemotherapy. Clinical data, cytokine profile and colony-forming assay with bone marrow samples at diagnosis were analysed. RESULTS: The required number of transfusions of both platelets and erythrocytes decreased once in the second course and then increased as the course progressed. The variability among cases increased as the chemotherapy course progressed. In cases of low peripheral blood platelet count and lower fibrinogen level at diagnosis, the number of platelet transfusions was higher during chemotherapy. In contrast, there was a negative correlation between the forming ability of granulocyte-macrophage or erythroid colonies and the number of erythrocyte transfusions in the latter period. CONCLUSION: In the early stages of chemotherapy, bone marrow infiltration in neuroblastoma and/or coagulopathy complication may cause thrombocytopenia and requirement of platelet transfusion; conversely, in the later stages, the number of erythrocyte transfusions may be defined by the patient's inherent hematopoietic ability. These factors may be useful in predicting the required number of transfusions.

  Jan. 2022, Vox sanguinis, 117(1) (1), 71 - 79, English, International magazine

  Scientific journal


• Usefulness of functional splicing analysis to confirm precise disease pathogenesis in Diamond-Blackfan anemia caused by intronic variants in RPS19.

  Satoru Takafuji, Takeshi Mori, Noriyuki Nishimura, Nobuyuki Yamamoto, Suguru Uemura, Kandai Nozu, Kiminori Terui, Tsutomu Toki, Etsuro Ito, Hideki Muramatsu, Yoshiyuki Takahashi, Masafumi Matsuo, Tomohiko Yamamura, Kazumoto Iijima

  Diamond-Blackfan anemia (DBA) is mainly caused by pathogenic variants in ribosomal proteins and 22 responsible genes have been identified to date. The most common causative gene of DBA is RPS19 [NM_001022.4]. Nearly 180 RPS19 variants have been reported, including three deep intronic variants outside the splicing consensus sequence (c.72-92A > G, c.356 + 18G > C, and c.411 + 6G > C). We also identified one case with a c.412-3C > G intronic variant. Without conducting transcript analysis, the pathogenicity of these variants is unknown. However, it is difficult to assess transcripts because of their fragility. In such cases, in vitro functional splicing assays can be used to assess pathogenicity. Here, we report functional splicing analysis results of four RPS19 deep intronic variants identified in our case and in previously reported cases. One splicing consensus variant (c.411 + 1G > A) was also examined as a positive control. Aberrant splicing with a 2-bp insertion between exons 5 and 6 was identified in the patient samples and minigene assay results also identified exon 6 skipping in our case. The exon 6 skipping transcript was confirmed by further evaluation using quantitative RT-PCR. Additionally, minigene assay analysis of three reported deep intronic variants revealed that none of them showed aberrant splicing and that these variants were not considered to be pathogenic. In conclusion, the minigene assay is a useful method for functional splicing analysis of inherited disease.

  Sep. 2021, Pediatric hematology and oncology, 38(6) (6), 515 - 527, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Minimal residual disease in high-risk neuroblastoma shows a dynamic and disease burden-dependent correlation between bone marrow and peripheral blood.

  Kyaw San Lin, Suguru Uemura, Khin Kyae Mon Thwin, Naoko Nakatani, Toshiaki Ishida, Nobuyuki Yamamoto, Akihiro Tamura, Atsuro Saito, Takeshi Mori, Daiichiro Hasegawa, Yoshiyuki Kosaka, Nanako Nino, China Nagano, Satoru Takafuji, Kazumoto Iijima, Noriyuki Nishimura

  Neuroblastoma (NB) is the most common extracranial solid tumor in children and originates from sympathoadrenal or Schwann cell precursors derived from neural crest. These neural crest derivatives also constitute the hematopoietic and mesenchymal stem cells in bone marrow (BM) that is the most frequent site of NB metastasis and relapse. In NB patients, NB cells have been pathologically detected in BM and peripheral blood (PB), and minimal residual disease (MRD) in BM and PB (BM-MRD and PB-MRD) can be monitored by quantitating several sets of NB-associated mRNAs (NB-mRNAs). Although previous studies have shown varying degrees of correlation between BM-MRD and PB-MRD, the underlying factors and/or mechanisms remains unknown. In the present study, we determined the levels of BM-MRD and PB-MRD by quantitating seven NB-mRNAs in 133 pairs of concurrently collected BM and PB samples from 19 high-risk NB patients with clinical disease evaluation, and examined their correlation in overall and subgroups of sample pairs. The levels of BM-MRD and PB-MRD were moderately (r = 0.418, p < 0.001) correlated with each other in overall sample pairs. The correlation became strong (r = 0.725, p < 0.001), weak (r = 0.284, p = 0.008), and insignificant (p = 0.194) in progression, stable, and remission subgroups of sample pairs, respectively. It also became stronger in subgroups of sample pairs with poor treatment responses and poor prognostic factors. Present study suggests that MRD in high-risk NB shows a dynamic and disease burden-dependent correlation between BM and PB.

  Aug. 2021, Translational oncology, 14(8) (8), 101019 - 101019, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Limited correlation between tumor markers and minimal residual disease detected by seven neuroblastoma-associated mRNAs in high-risk neuroblastoma patients.

  Suguru Uemura, Kyaw San Lin, Khin Kyae Mon Thwin, Naoko Nakatani, Toshiaki Ishida, Nobuyuki Yamamoto, Akihiro Tamura, Atsuro Saito, Takeshi Mori, Daiichiro Hasegawa, Yoshiyuki Kosaka, Nanako Nino, China Nagano, Satoru Takafuji, Kazumoto Iijima, Noriyuki Nishimura

  Vanillylmandelic acid (VMA), homovanillic acid (HVA), neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) are classical tumor markers and are used as standard clinical evaluations for patients with neuroblastoma (NB). Minimal residual disease (MRD) can be monitored by quantifying several sets of NB-associated mRNAs in the bone marrow (BM) and peripheral blood (PB) of patients with NB. Although MRD in BM and PB has been revealed to be a strong prognostic factor that is independent of standard clinical evaluations, its interrelation with tumor markers remains uncharacterized. The present study determined the levels of tumor markers (VMA, HVA, NSE and LDH) and MRD (BM-MRD and PB-MRD) in 133 pairs of concurrently collected BM, PB and urine samples from 19 patients with high-risk NB. The patients were evaluated during the entire course of treatment, which included 10 diagnoses, 32 treatments, 36 post-treatment, 9 relapses and 46 post-relapse sample pairs. The level of BM-MRD and PB-MRD was determined by quantifying 7 NB-mRNAs (collapsin response mediator protein 1, dopamine beta-hydroxylase, dopa decarboxylase, growth-associated protein 43, ISL LIM homeobox 1, pairedlike homeobox 2b and tyrosine hydroxylase) using droplet digital PCR. In overall sample pairs, tumor markers (VMA, HVA, NSE and LDH) demonstrated weak but significant correlations (P<0.011) with BM-MRD and PB-MRD. In subgroups according to each patient evaluation, the degree of correlation between tumor markers and MRD became stronger in patients with adrenal gland tumors, BM metastasis at diagnosis and relapse/regrowth compared with overall sample pairs. In contrast, tumor markers demonstrated variable correlations with MRD in subgroups according to each sample evaluation (BM infiltration at sampling, collection time point and disease status). The results suggested that tumor markers may demonstrate limited correlation with MRD in patients with high-risk NB.

  Jul. 2021, Molecular and clinical oncology, 15(1) (1), 137 - 137, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Catheter-related blood stream infection caused by Mycobacterium chelonae in a child with myeloid leukemia associated with Down syndrome.

  Tomoko Fujikawa, Suguru Uemura, Yuya Aoto, Yoshinori Nambu, China Nagano, Naoko Nakatani, Nanako Nino, Nobuyuki Yamamoto, Takeshi Mori, Noriyuki Nishimura, Kazumoto Iijima

  Rapidly growing nontuberculous mycobacteria should be considered if GPRs gram-positive rods are detected in blood cultures 2-3 days after the blood sample collection.

  Feb. 2021, Clinical case reports, 9(2) (2), 835 - 840, English, International magazine

  Link to Kobe Univ. Repository (Kernel)


• Prognostic Values of Tumor Markers and Minimal Residual Disease Detected by 7NB-mRNAs ddPCR Assay for High-Risk Neuroblastoma Patients

  Suguru Uemura, Toshiaki Ishida, Sanlin Kyaw, Naoko Nakatani, Nanako Nino, Nobuyuki Yamamoto, Daiichiro Hasegawa, Yoshiyuki Kosaka, Kazumoto Iijima, Noriyuki Nishimura

  Dec. 2020, PEDIATRIC BLOOD & CANCER, 67, English


• Soft tissue tumor with novel NR1D1-MAML1 fusion in a pediatric case.

  Masato Komatsu, Nobuyuki Yamamoto, Teruya Kawamoto, Yohei Kawakami, Hitomi Hara, Suguru Uemura, Noriyuki Nishimura, Toshihiro Akisue, Ryosuke Kuroda, Kazumoto Iijima, Naoe Jimbo, Maki Kanzawa, Kazuyoshi Kajimoto, Tomoo Itoh, Takanori Hirose

  We herein describe soft tissue tumor arising in the lower extremity of a pediatric patient. The tumor displayed a unique and wide range of histological features, sheet-like and cohesive growth pattern consisting of enlarged round to epithelioid atypical cells with a large alveolar and pseudopapillary histological architecture, focally mimicking alveolar soft part sarcoma and MiT family translocation renal cell carcinoma. Tumor cells were focally immunoreactive for cytokeratin, S-100, and EMA. RNA sequencing identified a novel in-frame NR1D1 (exon 5)-MAML1 (exon 2) gene rearrangement resulting in the formation of a putative chimeric protein containing the N-terminal C4-type zing finger domains of NR1D1 and the C-terminal MAML1 protein, which was confirmed by subsequent RT-PCR, Sanger sequencing, and FISH assay. To the best of our knowledge, NR1D1-MAML1 fusion has not yet been described in any neoplasms, suggesting the emergence of a novel tumor entity.

  Dec. 2020, Virchows Archiv : an international journal of pathology, 477(6) (6), 891 - 895, English, International magazine

  [Refereed]

  Scientific journal


• Seizure prevalence in children aged up to 3 years: a longitudinal population-based cohort study in Japan.

  Masahiro Nishiyama, Hiroshi Yamaguchi, Yusuke Ishida, Kazumi Tomioka, Hiroki Takeda, Noriyuki Nishimura, Kandai Nozu, Hiroki Mishina, Kazumoto Iijima, Hiroaki Nagase

  OBJECTIVE: To investigate the prevalence of seizures/febrile seizures in children up to 3 years of age and examine the effects of gestational age at birth on the risk for febrile seizures. DESIGN: Retrospective longitudinal population-based cohort study. SETTING: Kobe City public health center, Kobe, Japan, from 2010 to 2018. PARTICIPANTS: Children who underwent a medical check-up at 3 years of age. METHODS: Information regarding seizures was collected from the parents of 96 014 children. We identified the occurrence of seizure/febrile seizure in 74 017 children, whose gestational ages at birth were noted. We conducted a multivariate analysis with the parameter, gestational age at birth, to analyse the risk of seizure. We also stratified the samples by sex and birth weight (<2500 g or not) and compared the prevalence of seizure between those with the term and late preterm births. RESULTS: The prevalence of seizure was 12.1% (11.8%-12.3%), 13.2% (12.2%-14.4%), 14.6% (12.4%-17.7%) and 15.7% (10.5%-22.8%) in children born at 37-41, 34-36, 28-33 and 22-27 gestational weeks, respectively. The prevalence of febrile seizures was 9.0% (8.8%-9.2%), 10.5% (9.5%-11.5%), 11.8% (9.7%-14.5%) and 11.2% (6.9%-17.7%) in children born at 37-41, 34-36, 28-33 and 22-27 gestational weeks, respectively. Male was an independent risk factor for seizures (OR: 1.15, 95% CI 1.09 to 1.20; absolute risk increase 0.014, 95% CI 0.010 to 0.019) and febrile seizures (OR: 1.21, 95% CI 1.15 to 1.28; absolute risk increase 0.016, 95% CI 0.012 to 0.020), respectively. Late preterm birth was not associated with an increased risk of seizure/febrile seizure. CONCLUSIONS: Although very preterm birth may increase the risk of seizure/febrile seizure, the risk associated with late preterm birth is considerably small and less than that associated with male.

  Sep. 2020, BMJ open, 10(9) (9), e035977, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Thiamylal anaesthetic therapy for febrile refractory status epilepticus in children.

  Yusuke Ishida, Masahiro Nishiyama, Hiroshi Yamaguchi, Kazumi Tomioka, Tsukasa Tanaka, Hiroki Takeda, Shoichi Tokumoto, Daisaku Toyoshima, Azusa Maruyama, Yusuke Seino, Kazunori Aoki, Kandai Nozu, Noriyuki Nishimura, Hiroshi Kurosawa, Kazumoto Iijima, Hiroaki Nagase

  PURPOSE: To evaluate barbiturate anaesthetic therapy using thiamylal for febrile refractory status epilepticus (fRSE) in children. METHODS: This was a review of a prospectively-collected database between April 2012-March 2016 for fRSE cases treated with thiamylal anaesthetic therapy in a single paediatric hospital in Japan. The sample comprised 23 children (median age, 23 months) with fRSE that underwent thiamylal anaesthetic therapy for convulsive seizures lasting longer than 60 min, sustained after intravenous administration of benzodiazepine and non-benzodiazepine anticonvulsants. The intervention comprised protocol-based thiamylal anaesthetic therapy with bolus administration. We measured the dose and time required to achieve the burst suppression pattern (BSP) on electroencephalography, seizure recurrence, death, neurological sequelae, and complications. RESULTS: All patients except one reached the BSP. The thiamylal median dose until reaching the BSP was 27.5 mg/kg, and the median time from thiamylal administration to reaching the BSP was 109.5 min. There was one case of immediate treatment failure and one of withdrawal seizure, but no breakthrough seizure. No deaths occurred during treatment, and neurological sequelae occurred in four cases (17%). Vasopressors were administered in all cases. Other complications included 11 cases of pneumonia and one of enterocolitis. CONCLUSION: We revealed the time and dose required to reach the BSP with thiamylal anaesthetic therapy using bolus administration in children. Our results suggested that reaching the BSP with bolus administration requires markedly less time than without bolus administration, rarely causes seizure recurrence in paediatric fRSE, and causes haemodynamic dysfunction and infections as often as observed without bolus administration.

  Aug. 2020, Seizure, 80, 12 - 17, English, International magazine

  [Refereed]

  Scientific journal


• 開発途上国における小児がん診療能力強化事業5年間のまとめ

  七野 浩之, 山中 純子, 鈴木 優里, 瓜生 英子, 加藤 元博, 寺島 慶太, 富沢 大輔, 松本 公一, 副島 俊典, 山本 暢之, 長谷川 大一郎, 西村 範行, 義岡 孝子, 上原 秀一郎, 望月 慎史, 浅妻 伴, 大野 孝, 堤 義之, 菱木 知郎, 米田 光宏

  産業開発機構映像情報メディカル編集部, May 2020, 映像情報medical : a monthly journal of medical imaging and information, 52(5) (5), 40 - 45, Japanese

  [Refereed]


• Retrospective analysis of high-dose chemotherapy followed by autologous stem cell transplantation for high-risk pediatric osteosarcoma.

  Suguru Uemura, Takeshi Mori, Shinya Ishiko, Satoru Takafuji, Nanako Nino, Nobuyuki Yamamoto, Akira Hayakawa, Noriyuki Nishimura, Hitomi Hara, Teruya Kawamoto, Toshihiro Akisue, Kazumoto Iijima

  May 2020, Pediatric hematology and oncology, 37(4) (4), 337 - 343, English, International magazine

  [Refereed]

  Scientific journal


• 当院における小児がん患者の妊孕性温存について

  植村 優, 京野 由紀, 二野 菜々子, 高藤 哲, 山本 暢之, 西村 範行, 岡田 桂輔, 千葉 公嗣, 塩谷 雅英, 飯島 一誠

  (公社)日本小児科学会, Feb. 2020, 日本小児科学会雑誌, 124(2) (2), 293 - 293, Japanese


• NICU退院児における感覚特性,発達障害特性の検討

  村尾 真理子, 前山 花織, 万代 ツルエ, 堀之内 智子, 冨岡 和美, 福嶋 祥代, 阿部 真也, 大山 正平, 藤岡 一路, 野津 寛大, 飯島 一誠, 高木 康子, 加藤 威, 岡田 由香, 溝渕 雅巳, 北山 真次, 永瀬 裕朗, 森岡 一郎, 高田 哲, 西村 範行

  (公社)日本小児科学会, Feb. 2020, 日本小児科学会雑誌, 124(2) (2), 271 - 271, Japanese


• Level of Seven Neuroblastoma-Associated mRNAs Detected by Droplet Digital PCR Is Associated with Tumor Relapse/Regrowth of High-Risk Neuroblastoma Patients.

  Khin K M Thwin, Toshiaki Ishida, Suguru Uemura, Nobuyuki Yamamoto, Kyaw S Lin, Akihiro Tamura, Aiko Kozaki, Atsuro Saito, Kenji Kishimoto, Takeshi Mori, Daiichiro Hasegawa, Yoshiyuki Kosaka, Nanako Nino, Satoru Takafuji, Kazumoto Iijima, Noriyuki Nishimura

  Monitoring of several sets of neuroblastoma-associated mRNAs (NB-mRNAs) by real-time quantitative PCR (qPCR) can be used to evaluate minimal residual disease in NB patients. Droplet digital PCR (ddPCR) is an adaption of qPCR that potentially provides simpler and more reproducible detection of low levels of mRNAs. However, whether minimal residual disease in NB patients can be monitored by ddPCR using a set of NB-mRNAs is not yet tested. In this study, 208 bone marrow (BM) and 67 peripheral blood samples were retrospectively collected from 20 high-risk NB patients with clinical disease evaluation at two Japanese centers between 2011 and 2018, and level of each NB-mRNA (CRMP1, DBH, DDC, GAP43, ISL1, PHOX2B, and TH mRNAs) was determined by ddPCR. Level of 7NB-mRNAs (defined as the combined signature of each NB-mRNA) was higher in BM than peripheral blood, but correlated significantly with each other. In accordance with disease burden, it varied with disease status (remission, stable, or progression) and collection time point (diagnosis, treatment, post-treatment, or relapse). In 73 post-treatment BM samples, it was significantly higher in 17 relapsed/regrown samples than in 56 nonrelapsed/nonregrown samples. Furthermore, ddPCR had a better prognostic value than qPCR in detecting 7NB-mRNAs in the same 73 post-treatment BM samples. This study suggests that ddPCR detection of 7NB-mRNAs is significantly associated with tumor relapse/regrowth in high-risk NB patients.

  Feb. 2020, The Journal of molecular diagnostics : JMD, 22(2) (2), 236 - 246, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• An infant with refractory cytomegalovirus-induced thrombocytopenia.

  Suguru Uemura, Takeshi Mori, Nanako Nino, Nana Sakakibara, Satoru Takafuji, Shota Myojin, Yuichi Takami, Ichiro Morioka, Noriyuki Nishimura, Masaaki Kugo, Kazumoto Iijima

  The present case underscores the importance of considering the association of severe thrombocytopenia or immune thrombocytopenia with cytomegalovirus (CMV) infection because CMV-induced thrombocytopenia occasionally requires antiviral therapy.

  Jan. 2020, Clinical case reports, 8(1) (1), 75 - 78, English, International magazine

  [Refereed]

  Link to Kobe Univ. Repository (Kernel)


• Spontaneously Developed Undifferentiated Sarcoma and Rhabdomyosarcoma in mdx Mice

  Takafuji Satoru, Niba Emma, Khin Thwin, Yamamoto Nobuyuki, Awano Hiroyuki, Fukushima Shoji, Itoh Kyoko, Nishio Hisahide, Matsuo Masafumi, Kyaw Lin, Uemura Suguru, Iijima Kazumoto, Nishimura Noriyuki

  Dec. 2019, PEDIATRIC BLOOD & CANCER, 66, S117 - S118

  [Refereed]


• 神経芽腫の七つのmRNA発現に関する骨髄と末梢血サンプルの相関(Expression of seven neuroblastoma-associated mRNAs is correlated between bone marrow and peripheral blood samples)

  Thwin KhinKyaemon, Lin Kyaw San, Ishida Toshiaki, Hasegawa Daiichiro, Uemura Suguru, 山本 暢之, Nishimura Noriyuki

  日本癌学会, Sep. 2019, 日本癌学会総会記事, 78回, E - 1060, English

  [Refereed]


• Detailed clinical course of fatal acute encephalopathy in children.

  Kazumi Tomioka, Masahiro Nishiyama, Hiroaki Nagase, Yusuke Ishida, Tsukasa Tanaka, Shoichi Tokumoto, Hiroshi Yamaguchi, Daisaku Toyoshima, Azusa Maruyama, Kyoko Fujita, Kazunori Aoki, Yusuke Seino, Kandai Nozu, Noriyuki Nishimura, Hiroshi Kurosawa, Kazumoto Iijima

  OBJECTIVE: Although the mortality among previously healthy children with acute encephalopathy (AE) is approximately 5%, their detailed clinical course has not been clarified. The objective of the present study was to describe the detailed clinical course, in minutes, of fatal AE. METHODS: We retrospectively reviewed the medical records of five patients (from 6 months to 14 years of age) who previously had no neurological disorders and were diagnosed with brain death due to AE between 2002 and 2018 at Kobe Children's Hospital. RESULTS: The initial clinical symptoms were convulsion in three cases and impaired consciousness in two. The earliest noted brain imaging abnormality was 7.5 h after neurological symptom detection. Liver enzymes and creatinine levels increased at initial examination, and sodium elevated gradually. All patients met the criteria of systemic inflammatory response syndrome, disseminated intravascular coagulation, and shock within 14 h of symptom detection. High dose steroids and targeted temperature management were initiated 3.5-14 h after onset. Despite these therapies, patients were diagnosed with brain death from 16 h to 4 days after initial neurological symptoms. AE diagnoses were made between 4 h 29 min and 4 days after initial neurological symptoms and included hemorrhagic shock and encephalopathy syndromes, Reye-like syndrome, and acute necrotizing encephalopathy in two, two, and one patient(s), respectively. CONCLUSIONS: We revealed the time series' of clinical events (e.g. SIRS, shock, DIC, AE diagnosis, brain death, and treatments) and laboratory findings relative to initial neurological symptom in fatal AE.

  Sep. 2019, Brain & development, 41(8) (8), 691 - 698, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Predicting the outcomes of targeted temperature management for children with seizures and/or impaired consciousness accompanied by fever without known etiology.

  Tsukasa Tanaka, Hiroaki Nagase, Hiroshi Yamaguchi, Yusuke Ishida, Kazumi Tomioka, Masahiro Nishiyama, Daisaku Toyoshima, Azusa Maruyama, Kyoko Fujita, Kandai Nozu, Noriyuki Nishimura, Hiroshi Kurosawa, Ryojiro Tanaka, Kazumoto Iijima

  BACKGROUND: Seizures and/or impaired consciousness accompanied by fever without known etiology (SICF) is common in the pediatric emergency setting. No optimal strategy for the management of SICF in childhood currently exists. We previously demonstrated the effectiveness of targeted temperature management (TTM) against SICF with a high risk of morbidity; however, some patients with SICF develop neurological sequelae despite TTM, which necessitate additional neuroprotective treatment. The clinical characteristics of these severe cases have not been studied. Accordingly, the aim of this study was to identify the clinical characteristics of children with SICF who exhibit poor outcomes after TTM. METHODS: The medical records of children admitted to Kobe Children's Hospital (Kobe, Japan) between October 2002 and September 2016 were retrospectively reviewed. Patients with SICF treated using TTM were included and divided into the satisfactory and poor outcome groups. Univariate and multivariate logistic regression analyses were used to compare clinical characteristics and laboratory findings between the two groups. RESULTS: Of the 73 included children, 10 exhibited poor outcomes. Univariate logistic regression analysis revealed that acute circulatory failure before TTM initiation, the use of four or more types of anticonvulsants, methylprednisolone pulse therapy, and an aspartate aminotransferase (AST) level ≥73 IU/L were associated with poor outcomes. Multivariate logistic regression analysis identified an elevated AST level as a significant independent predictor of a poor outcome. CONCLUSIONS: An elevated AST level within 12 h of onset in children with SICF is an independent predictor of a poor outcome after TTM initiated within 24 h of onset.

  Aug. 2019, Brain & development, 41(7) (7), 604 - 613, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 修正18〜24ヵ月のNICU退院児における感覚特性の検討

  村尾 真理子, 前山 花織, 万代 ツルエ, 高木 康子, 加藤 威, 岡田 由香, 溝渕 雅巳, 北山 真次, 冨岡 和美, 永瀬 裕朗, 森岡 一朗, 高田 哲, 西村 範行

  (一社)日本小児精神神経学会, Jun. 2019, 日本小児精神神経学会プログラム・抄録集, 121回, 43 - 43, Japanese

  [Refereed]


• Clinical time course of pediatric acute disseminated encephalomyelitis.

  Masahiro Nishiyama, Hiroaki Nagase, Kazumi Tomioka, Tsukasa Tanaka, Hiroshi Yamaguchi, Yusuke Ishida, Daisaku Toyoshima, Kyoko Fujita, Azusa Maruyama, Kaori Sasaki, Yoshinobu Oyazato, Taku Nakagawa, Yuichi Takami, Kandai Nozu, Noriyuki Nishimura, Ichiro Nakashima, Kazumoto Iijima

  The detailed clinical time course in acute disseminated encephalomyelitis (ADEM) from initial symptoms, through exacerbation, to remission has not been widely reported. Hence, this study aimed to investigate the clinical time course of pediatric ADEM. This was a multicenter retrospective study based on registry data from medical chart reviews. The study included children who met the international consensus diagnostic criteria for ADEM. The patients comprised 18 boys and 6 girls, with a mean age of 5.5 ± 3.3 years at onset. From onset, the time until peak neurological symptoms, time until initial improvement, and time until full recovery was 3.1 ± 3.7 days, 6.0 ± 4.5 days, and 26 ± 34 days, respectively. Twenty-three (96%) patients were treated with high-dose methylprednisolone (mPSL) with a mean duration of 4.1 ± 4.0 days from onset. The condition of 15 patients (65%) improved within 3 days of high-dose mPSL initiation, whereas, that of four patients began to improve after >5 days of high-dose mPSL initiation. Only one patient (4%) did not achieve full recovery despite treatment with high-dose mPSL, intravenous immunoglobulin, and plasma exchange. This study presents the detailed clinical time course in pediatric ADEM in Japan. Progression of neurologic deficits typically lasts a few days, with initial improvement in 1 week leading to full recovery within 1 month.

  Jun. 2019, Brain & development, 41(6) (6), 531 - 537, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• インドネシアにおける小児がん診療の現状と課題

  山本 暢之, 西村 範行

  産業開発機構映像情報メディカル編集部, May 2019, 映像情報medical : a monthly journal of medical imaging and information, 51(5) (5), 62 - 65, Japanese

  [Refereed]


• 開発途上国における小児がんの診療能力強化 : 国際的に注目されつつある課題である小児がんへの対応に関する研修

  七野 浩之, 吉本 優里, 山中 純子, 瓜生 英子, 田中 瑞恵, 佐藤 典子, 加藤 元博, 寺島 慶太, 富澤 大輔, 松井 基浩, 文野 誠久, 菱木 知郎, 土井 崇, 谷ヶ崎 博, 副島 俊典, 浅妻 伴, 大野 孝, 野澤 久美子, 宮崎 治, 山本 暢之, 長谷川 大一郎, 西村 範行, 前田 美穂, 義岡 孝子, 堤 義之, 米田 光宏, 松本 公一

  産業開発機構映像情報メディカル編集部, Apr. 2019, 映像情報medical : a monthly journal of medical imaging and information, 51(4) (4), 42 - 48, Japanese

  [Refereed]


• Nonconvulsive Seizure Detection by Reduced-Lead Electroencephalography in Children with Altered Mental Status in the Emergency Department.

  Hiroshi Yamaguchi, Hiroaki Nagase, Masahiro Nishiyama, Shoichi Tokumoto, Yusuke Ishida, Kazumi Tomioka, Tsukasa Tanaka, Kyoko Fujita, Daisaku Toyoshima, Noriyuki Nishimura, Hiroshi Kurosawa, Kandai Nozu, Azusa Maruyama, Ryojiro Tanaka, Kazumoto Iijima

  OBJECTIVES: To evaluate the proportion of children presenting to the emergency department (ED) with altered mental status who demonstrate nonconvulsive seizures on reduced-lead electroencephalography (EEG), and to further investigate the characteristics, treatment, and outcomes in these patients compared with patients without nonconvulsive seizures. STUDY DESIGN: In this retrospective cohort study, we reviewed the database and medical records of pediatric patients (aged <18 years) in a single ED between May 1, 2016, and April 30, 2018. We first determined the proportion of nonconvulsive seizures among patients with altered mental status (Glasgow Coma Scale <15). We then compared the clinical presentation, demographic data, clinical diagnosis, EEG results, treatment, and outcomes of patients with altered mental status with nonconvulsive seizures and those without nonconvulsive seizures. RESULTS: In total, 16.9% of the patients with altered mental status (41 of 242; 95% CI, 12.2%-21.6%) evaluated by EEG had detectable nonconvulsive seizure, equivalent to 4.4% (41 of 932) of all patients with altered mental status presenting at our hospital. More than 80% of patients monitored for nonconvulsive seizures had a previous history of seizures, often febrile. Patients with nonconvulsive seizures were older (median, 68.5 vs 36.1 months) and had a higher Pediatric Cerebral Performance Category score at presentation (median, 2.0 vs 1.0). In addition, the proportion of patients admitted to the intensive care unit was significantly higher in the patients with nonconvulsive seizures (30.3% vs 15.0%). However, total duration of hospitalization, neurologic sequelae, and 30-day mortality rate did not differ between the 2 groups. CONCLUSIONS: A relatively high percentage of pediatric patients with altered mental status in the ED experience nonconvulsive seizures. The use of reduced-lead EEG monitoring in the ED might facilitate the recognition and treatment of nonconvulsive seizures, especially among patients with a history of seizures.

  Apr. 2019, The Journal of pediatrics, 207, 213 - 219, English, International magazine

  [Refereed]

  Scientific journal


• Isolation and Characterization of Human Umbilical Cord-derived Mesenchymal Stem Cells from Preterm and Term Infants.

  Sota Iwatani, Makiko Yoshida, Keiji Yamana, Daisuke Kurokawa, Jumpei Kuroda, Khin Kyae Mon Thwin, Suguru Uemura, Satoru Takafuji, Nanako Nino, Tsubasa Koda, Masami Mizobuchi, Masahiro Nishiyama, Kazumichi Fujioka, Hiroaki Nagase, Ichiro Morioka, Kazumoto Iijima, Noriyuki Nishimura

  Mesenchymal stem cells (MSCs) have considerable therapeutic potential and attract increasing interest in the biomedical field. MSCs are originally isolated and characterized from bone marrow (BM), then acquired from tissues including adipose tissue, synovium, skin, dental pulp, and fetal appendages such as placenta, umbilical cord blood (UCB), and umbilical cord (UC). MSCs are a heterogeneous cell population with the capacity for (1) adherence to plastic in standard culture conditions, (2) surface marker expression of CD73+/CD90+/CD105+/CD45-/CD34-/CD14-/CD19-/HLA-DR- phenotypes, and (3) trilineage differentiation into adipocytes, osteocytes, and chondrocytes, as currently defined by the International Society for Cellular Therapy (ISCT). Although BM is the most widely used source of MSCs, the invasive nature of BM aspiration ethically limits its accessibility. Proliferation and differentiation capacity of MSCs obtained from BM generally decline with the age of the donor. In contrast, fetal MSCs obtained from UC have advantages such as vigorous proliferation and differentiation capacity. There is no ethical concern for UC sampling, as it is typically regarded as medical waste. Human UC starts to develop with continuing growth of the amniotic cavity at 4-8 weeks of gestation and keeps growing until reaching 50-60 cm in length, and it can be isolated during the whole newborn delivery period. To gain insight into the pathophysiology of intractable diseases, we have used UC-derived MSCs (UC-MSCs) from infants delivered at various gestational ages. In this protocol, we describe the isolation and characterization of UC-MSCs from fetuses/infants at 19-40 weeks of gestation.

  Jan. 2019, Journal of visualized experiments : JoVE, 143(143) (143), e58806, English, International magazine

  [Refereed]

  Scientific journal


• Dynamics of Minimal Residual Disease in Neuroblastoma Patients.

  Suguru Uemura, Toshiaki Ishida, Khin Kyae Mon Thwin, Nobuyuki Yamamoto, Akihiro Tamura, Kenji Kishimoto, Daiichiro Hasegawa, Yoshiyuki Kosaka, Nanako Nino, Kyaw San Lin, Satoru Takafuji, Takeshi Mori, Kazumoto Iijima, Noriyuki Nishimura

  Neuroblastoma is a common extracranial solid tumor of neural crest (NC) origin that accounts for up to 15% of all pediatric cancer deaths. The disease arises from a transient population of NC cells that undergo an epithelial-mesenchymal transition (EMT) and generate diverse cell-types and tissues. Patients with neuroblastoma are characterized by their extreme heterogeneity ranging from spontaneous regression to malignant progression. More than half of newly diagnosed patients present highly metastatic tumors and are stratified into a high-risk group with dismal outcome. As many as 20% of high-risk patients have residual disease that is refractory or progressive during induction chemotherapy. Although a majority of high-risk patients achieve remission, larger part of those patients has minimal residual disease (MRD) that causes relapse even after additional consolidation therapy. MRD is composed of drug-resistant tumor cells and dynamically presented as cancer stem cells (CSCs) in residual tumors, circulating tumor cells (CTCs) in peripheral blood (PB), and disseminated tumor cells (DTCs) in bone marrow (BM) and other metastatic sites. EMT appears to be a key mechanism for cancer cells to acquire MRD phenotypes and malignant aggressiveness. Due to the restricted availability of residual tumors, PB and BM have been used to isolate and analyze CTCs and DTCs to evaluate MRD in cancer patients. In addition, recent technical advances make it possible to use circulating tumor DNA (ctDNA) shed from tumor cells into PB for MRD evaluation. Because MRD can be detected by tumor-specific antigens, genetic or epigenetic changes, and mRNAs, numerous assays using different methods and samples have been reported to detect MRD in cancer patients. In contrast to the tumor-specific gene-rearrangement-positive acute lymphoblastic leukemia (ALL) and the oncogenic fusion-gene-positive chronic myelogenous leukemia (CML) and several solid tumors, the clinical significance of MRD remains to be established in neuroblastoma. Given the extreme heterogeneity of neuroblastoma, dynamics of MRD in neuroblastoma patients will hold a key to the clinical validation. In this review, we summarize the biology and detection methods of cancer MRD in general and evaluate the available assays and clinical significance of neuroblastoma MRD to clarify its dynamics in neuroblastoma patients.

  2019, Frontiers in oncology, 9, 455 - 455, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• A girl with CLOVES syndrome with a recurrent PIK3CA somatic mutation and pancreatic steatosis.

  Hiroaki Hanafusa, Naoya Morisada, Tadashi Nomura, Daisuke Kobayashi, Yoshinobu Akasaka, Ming Juan Ye, Kandai Nozu, Noriyuki Nishimura, Kazumoto Iijima, Hideto Nakao

  CLOVES syndrome is characterized by congenital lipomatous overgrowth, vascular malformation, epidermal nevi, and scoliosis/spinal malformation. It is caused by somatic mosaicism of gain-of-function variants of PIK3CA. Here, we describe a novel case of a 5-year-old Japanese girl with CLOVES and concurrent pancreatic steatosis. She had a recurrent somatic mutation in PIK3CA (NM_006218.3: c.1357G>A, p.Glu453Lys), elevated HbA1c levels, and pancreatic steatosis. This case indicates that pancreatic screening is critical for PIK3CA-related disorders.

  2019, Human genome variation, 6, 31 - 31, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Lipid and thyroid hormone levels in children with epilepsy treated with levetiracetam or carbamazepine: A prospective observational study.

  Masahiro Nishiyama, Yuichi Takami, Yusuke Ishida, Kazumi Tomioka, Tsukasa Tanaka, Hiroaki Nagase, Taku Nakagawa, Shoichi Tokumoto, Hiroshi Yamaguchi, Daisaku Toyoshima, Azusa Maruyama, Kandai Nozu, Noriyuki Nishimura, Kazumoto Iijima

  Although previous studies have investigated the influence of antiepileptic drugs (AEDs) on lipid profiles and thyroid hormone levels, there is little evidence regarding the effects of levetiracetam (LEV). Therefore, we conducted a prospective longitudinal study to evaluate the effects of LEV and carbamazepine (CBZ) treatment on lipid profile and thyroid hormone levels in patients newly diagnosed with epilepsy. Inclusion criteria were as follows: (a) age between 4 and 15 years, (b) diagnosis of epilepsy with at least two focal seizures within a year, and (c) newly treated with LEV or CBZ monotherapy. Serum lipid profile and thyroid hormone levels were measured before and after 1 and 6 months of AED initiation. Among the 21 included patients (LEV: 13 patients, CBZ: 8 patients), all but one patient in the LEV group continued AED monotherapy during the study period. Although triglyceride (TG) levels tended to be increased in the CBZ group (baseline: 58.3 ± 22.0 mg/dl, 1 month: 63.8 ± 21.6 mg/dl, 6 months: 92.3 ± 63.6 mg/dl, p = 0.22, analyses of variance (ANOVA)), there were no significant changes in total cholesterol (TC), TG levels, high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C) in either group. Serum free thyroxine (fT4) levels were significantly decreased in the CBZ group (baseline: 1.15 ± 0.06 ng/dl, 1 month: 1.00 ± 0.16 ng/dl, 6 months: 0.98 ± 0.14 ng/dl, p = 0.03, ANOVA). In contrast, there were no significant changes in fT4 or thyroid-stimulating hormone (TSH) levels in the LEV group. The results of the present study suggest that LEV monotherapy does not affect lipid profile or thyroid function while CBZ monotherapy may cause thyroid dysfunction.

  Jan. 2019, Epilepsy & behavior : E&B, 90, 15 - 19, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Effective response to azacitidine in a child with a second relapse of myeloid leukemia associated with Down syndrome after bone marrow transplantation.

  Suguru Uemura, Takeshi Mori, China Nagano, Satoru Takafuji, Noriyuki Nishimura, Tsutomu Toki, Kiminori Terui, Etsuro Ito, Kazumoto Iijima

  Dec. 2018, Pediatric blood & cancer, 65(12) (12), e27414, English, International magazine

  [Refereed]

  Scientific journal


• Spontaneous Development of Spindle Cell Sarcoma in mdx Mice

  Takafuji Satoru, Niba Emma, Khin Thwin, Yamamoto Nobuyuki, Awano Hiroyuki, Uemura Suguru, Mori Takeshi, Fukushima Shoji, Itoh Kyoko, Nishio Hisahide, Matsuo Masafumi, Iijima Kazumoto, Nishimura Noriyuki

  Nov. 2018, PEDIATRIC BLOOD & CANCER, 65, S95

  [Refereed]


• Evaluation index for asymmetric ventricular size on brain magnetic resonance images in very low birth weight infants.

  Toshihiko Ikuta, Masami Mizobuchi, Yoshinori Katayama, Seiji Yoshimoto, Tomoaki Ioroi, Masayuki Yamane, Takeshi Morisawa, Akihiro Takatera, Masaaki Ueda, Akio Shibata, Kaori Maeyama, Tsurue Mandai, Kazumichi Fujioka, Noriyuki Nishimura, Kazumoto Iijima, Ichiro Morioka

  OBJECTIVE: Asymmetric ventriculomegaly is often evident on brain magnetic resonance imaging (MRI) in very low birth weight infants (VLBWI) and is interpreted as white matter injury. However, no evaluation index for asymmetric left-right and anterior-posterior ventricular sizes has been established. METHODS: In this retrospective multicenter cohort study, brain T2-weighted MRI was performed at term-equivalent ages in 294 VLBWI born between 2009 and 2011. The value of a lateral ventricular index (LVI) to evaluate asymmetric ventricular size, as well as the relationship between the LVI value and walking at a corrected age of 18 months was investigated. At the level of the foramen of Monro in a horizontal slice, asymmetry between the left and right sides and between the anterior and posterior horns was identified by the corrected width and was detected by a low concordance rate and κ statistic value. An LVI representing the sum of the widths of the four horns of the lateral ventricle corrected for cerebral diameter was devised. RESULTS: Asymmetric left-right and anterior-posterior ventricular sizes were confirmed. The LVI value was significantly higher in the non-walking VLBWI group (n = 39) than in the walking VLBWI group (n = 255; 18.2 vs. 15.8, p = 0.02). An LVI cut-off value of 21.5 was associated with non-walking. Multivariate analysis revealed that an LVI value >21.5 was an independent predictor of walking disability at the corrected age of 18 months (odds ratio 2.56, p = 0.008). CONCLUSIONS: The LVI value calculated via MRI may predict walking disability at a corrected age of 18 months in VLBWI.

  Oct. 2018, Brain & development, 40(9) (9), 753 - 759, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Characterization of Sensory Processing Function in Infants/Toddlers with Developmental Disorder

  MAEYAMA KAORI, MAEYAMA KAORI, TAKAGI YASUKO, KATO TAKESHI, MIZOBUCHI MASAMI, KITAYAMA SHINJI, TAKADA SATOSHI, TOMIOKA KAZUMI, NAGASE HIROAKI, NORIYUKI NISHIMURA

  Last, 日本小児精神神経学会, Oct. 2018, 小児の精神と神経, 58(3) (3), 201 - 207, Japanese

  [Refereed]


• Early risk factors for mortality in children with seizure and/or impaired consciousness accompanied by fever without known etiology.

  Kazumi Tomioka, Hiroaki Nagase, Tsukasa Tanaka, Masahiro Nishiyama, Hiroshi Yamaguchi, Yusuke Ishida, Daisaku Toyoshima, Azusa Maruyama, Kyoko Fujita, Mariko Taniguchi-Ikeda, Kandai Nozu, Ichiro Morioka, Noriyuki Nishimura, Hiroshi Kurosawa, Yoshiyuki Uetani, Kazumoto Iijima

  BACKGROUND: Children who present with seizure and/or impaired consciousness accompanied by fever without known etiology (SICF) may be diagnosed with either acute encephalopathy (AE) or febrile seizure (FS). Although approximately 5% of AE cases are fatal, it is difficult to identify fatal cases among children with SICF, which are often critical by the time of diagnosis. Thus, early prediction of outcomes for children with SICF, prior to diagnosis, may help to reduce mortality associated with AE. The aim of the present study was to identify clinical and laboratory risk factors for mortality acquired within 6 h of onset among children with SICF. METHODS: We retrospectively reviewed the medical records of children who had been admitted to Kobe Children's Hospital (Kobe, Japan) with SICF between October 2002 and September 2015. We compared clinical and laboratory characteristics acquired within 6 h of onset and outcomes between survivors and non-survivors using univariate and multivariate analyses. RESULTS: The survivor and non-survivor groups included 659 and nine patients, respectively. All patients in the non-survivor group received a final diagnosis of AE. Univariate analysis revealed significant differences between the groups with regard to seizure duration and the following laboratory parameters: aspartate transaminase (AST), alanine aminotransferase, lactate dehydrogenase, sodium, and lactate. The multivariate analysis identified AST as a significant independent factor associated with mortality. CONCLUSIONS: Elevation of AST within 6 h of onset is independently correlated with mortality in children with SICF. Our result may elucidate earlier intervention for patients with high risk of mortality.

  Aug. 2018, Brain & development, 40(7) (7), 552 - 557, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Human CD134 (OX40) expressed on T cells plays a key role for human herpesvirus 6B replication after allogeneic hematopoietic stem cell transplantation.

  Satoshi Nagamata, Miwako Nagasaka, Akiko Kawabata, Kenji Kishimoto, Daiichiro Hasegawa, Yoshiyuki Kosaka, Takeshi Mori, Ichiro Morioka, Noriyuki Nishimura, Kazumoto Iijima, Hideto Yamada, Shinichiro Kawamoto, Kimikazu Yakushijin, Hiroshi Matsuoka, Yasuko Mori

  BACKGROUND: CD134 (OX40), which is a cellular receptor for human herpesvirus-6B (HHV-6B) and expresses on activated T cells, may play a key role for HHV-6B replication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). OBJECTIVES: Therefore, we examined the CD134 expression on T cells and HHV-6B replication after allo-HSCT, and analyzed the correlation between them. STUDY DESIGN: Twenty-three patients after allo-HSCT were enrolled. The percentages of CD134-positive cells within the CD4+ and CD8+ cell populations were measured by flow cytometry, and the viral copy number of HHV-6B was simultaneously quantified by real-time PCR. The correlation between CD134 and HHV-6B viral load was then statistically analyzed. RESULTS: HHV-6B reactivation occurred in 11 of 23 patients (47.8%). CD134 expression was seen on T cells and was coincident with the time of peak viral load. The percentage of CD134-positive cells decreased significantly when HHV-6B DNA disappeared (p = .005 in CD4+ T cells, p = .02 in CD8+ T cells). In the 4 patients who underwent umbilical cord blood transplantation (UCBT), the viral load varied with the percentage of CD134-positive cells. In the comparison between the HHV-6B reactivation group and non-reactivation group, maximum percentages of CD134-positive cells among CD4+ T cells in reactivation group were significantly higher than those in non-reactivation group (p = .04). CONCLUSIONS: This is the first study to show that a correlation of CD134 expression on T cells with HHV-6B replication after allo-HSCT, especially in UCBT. The results possibly indicate that CD134 on T cells plays a key role for HHV-6B replication after allo-HSCT.

  May 2018, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 102, 50 - 55, English, International magazine

  [Refereed]

  Scientific journal


• Expression of CD134 (OX40) on T cells is a trigger of human herpesvirus 6B reactivation and replication after hematopoietic cell transplantation.

  Nagamata S, Nagasaka M, Kawabata A, Kishimoto K, Hasegawa D, Kosaka Y, Mori T, Morioka I, Nishimura N, Iijima K, Yamada H, Matsuoka H, Mori Y

  May 2018, J Clin Virol., 102, 50 - 55

  [Refereed]


• ETV6-ABL1 fusion combined with monosomy 7 in childhood B-precursor acute lymphoblastic leukemia.

  Suguru Uemura, Noriyuki Nishimura, Daiichiro Hasegawa, Akemi Shono, Kimiyoshi Sakaguchi, Hisayuki Matsumoto, Yuji Nakamachi, Jun Saegusa, Takehito Yokoi, Teppei Tahara, Akihiro Tamura, Nobuyuki Yamamoto, Atsuro Saito, Aiko Kozaki, Kenji Kishimoto, Toshiaki Ishida, Nanako Nino, Satoru Takafuji, Takeshi Mori, Kazumoto Iijima, Yoshiyuki Kosaka

  ETV6-ABL1 fusion is a rare but recurrent oncogenic lesion found in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), without an established chromosomal abnormality, and is associated with poor outcome. In ETV6-ABL1-positive cases, an in-frame fusion produced by a complex rearrangement results in constitutive chimeric tyrosine kinase activity. Monosomy 7 is also a rare and unfavorable chromosomal abnormality in childhood BCP-ALL. Here, we report a 14-year-old female BCP-ALL patient with ETV6-ABL1 fusion combined with monosomy 7. She was admitted to our hospital because of persistent fever. Bone marrow nuclear cell count on admission was 855,000/µL with 90.0% blastic cells of lymphoid morphology. Blasts were positive for CD10, CD19, CD20, CD34, cyCD79a, cyTdT, HLA-DR, and CD66c, had a karyotype of 45, XX, - 7 [18/20] and a split signal for ABL1 FISH probe (92.7%), and were sensitive to tyrosine kinase inhibitors, imatinib and dasatinib, in vitro. ETV6-ABL1 fusion transcript was identified by whole transcriptome sequencing and confirmed by RT-PCR. She was treated with the high-risk protocol based on ALL-BFM 95, achieved complete remission (CR) after induction chemotherapy, and maintained CR for 4 months. To our knowledge, this is the first report of ETV6-ABL1 fusion combined with monosomy 7 in childhood BCP-ALL.

  May 2018, International journal of hematology, 107(5) (5), 604 - 609, English, Domestic magazine

  [Refereed]

  Scientific journal


• Congenital Cytomegalovirus Infection in Children with Autism Spectrum Disorder: Systematic Review and Meta-Analysis.

  Kaori Maeyama, Kazumi Tomioka, Hiroaki Nagase, Mieko Yoshioka, Yasuko Takagi, Takeshi Kato, Masami Mizobuchi, Shinji Kitayama, Satoshi Takada, Masashi Nagai, Nana Sakakibara, Masahiro Nishiyama, Mariko Taniguchi-Ikeda, Ichiro Morioka, Kazumoto Iijima, Noriyuki Nishimura

  Association of congenital cytomegalovirus (CMV) infection with autism spectral disorder (ASD) has been suggested since 1980s. Despite the observed association, its role as a risk factor for ASD remains to be defined. In the present review, we systematically evaluated the available evidence associating congenital CMV infection with ASD using PubMed, Web of Science, Cochrane Library, and Embase databases. Any studies on children with CMV infection and ASD were evaluated for eligibility and three observational studies were included in meta-analysis. Although a high prevalence of congenital CMV infection in ASD cases (OR 11.31, 95% CI 3.07-41.66) was indicated, too few events (0-2 events) in all included studies imposed serious limitations. There is urgent need for further studies to clarify this issue.

  May 2018, Journal of autism and developmental disorders, 48(5) (5), 1483 - 1491, English, International magazine

  [Refereed]

  Scientific journal


• Clinical features predicting group A streptococcal pharyngitis in a Japanese paediatric primary emergency medical centre.

  Masahiro Nishiyama, Ichiro Morioka, Mariko Taniguchi-Ikeda, Takeshi Mori, Kazumi Tomioka, Keita Nakanishi, Junya Fujimura, Noriyuki Nishimura, Kandai Nozu, Hiroaki Nagase, Kazuto Ishibashi, Akihito Ishida, Kazumoto Iijima

  Objectives To identify clinical features that predict Group A streptococcal (GAS) pharyngitis in a Japanese paediatric primary emergency medical centre. Methods The prevalence of GAS pharyngitis according to age and body temperature (BT) was calculated among 3098 paediatric patients with pharyngitis. The numbers of GAS-positive and -negative patients for each clinical parameter, and each point increase in the McIsaac score were compared and likelihood ratios (LRs) were calculated. Results The prevalence of GAS pharyngitis was extremely low in patients aged < 1 (1.2%) and 1 year (3.9%). The GAS-positive rate was significantly higher in patients with a BT < 38.0°C compared with ≥ 38.0°C (30.0% vs. 19.8%). A BT ≥ 38.0°C was not a predictive finding for GAS pharyngitis (positive LR: 0.82). Rash was the most useful individual predictor, and a McIsaac score of 4 or 5 increased the probability; however, the positive LRs were 1.74 and 1.30, respectively. Conclusions The prevalence of GAS pharyngitis is extremely low in patients aged < 1 and 1 year, and a BT ≥ 38.0°C is not a predictive symptom. Although a rash and McIsaac score of 4 or 5 are associated with an increased probability, they cannot be used to confirm GAS infection.

  May 2018, The Journal of international medical research, 46(5) (5), 1791 - 1800, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Diurnal occurrence of complex febrile seizure and their severity in pediatric patients needing hospitalization.

  Hiroshi Yamaguchi, Hiroaki Nagase, Yusuke Ishida, Daisaku Toyoshima, Azusa Maruyama, Kazumi Tomioka, Tsukasa Tanaka, Masahiro Nishiyama, Kyoko Fujita, Taniguchi-Ikeda Mariko, Kandai Nozu, Ichiro Morioka, Noriyuki Nishimura, Hiroshi Kurosawa, Satoshi Takada, Yoshiyuki Uetani, Kazumoto Iijima

  Several studies describing the diurnal occurrence of febrile seizures have reported greater seizure frequency early or late in the evening relative to midnight or early morning. However, no articles have reported on the diurnal occurrence of complex febrile seizure. Moreover, no studies have addressed the relationship between seizure severity and diurnal occurrence. We retrospectively evaluated complex febrile seizures in 462 children needing hospitalization, and investigated the relationship between severity and diurnal occurrence according to four categorized time periods (morning, afternoon, evening, and night). Our study showed that complex febrile seizures occurred most often in the evening, peaking around 18:00 (18:00-18:59), and least often at night (02:00-02:59). In addition, the frequency with which patients developed status epilepticus or needed anticonvulsant treatments was also lower during the night. However, the seizure duration and the proportion of the patients who needed anticonvulsant treatment were the same among the four time periods. Furthermore, we compared three subclasses (repeated episodes of convulsions, focal seizures, and prolonged seizures (≧15min)), two of the complex features (focal seizures and prolonged seizures), and all complex features among the four time periods. However, they were the same among the four time periods. Taken together, our data indicate that although the severity of seizures was stable over a 24-hour period, the occurrence of seizures in our cohort of pediatric patients with complex febrile seizures requiring hospitalization was highest in the evening and lowest at night.

  Mar. 2018, Epilepsy & behavior : E&B, 80, 280 - 284, English, International magazine

  [Refereed]

  Scientific journal


• 5年以上のromiplostim投与後に無治療経過観察に至った幼児慢性免疫血小板減少性紫斑病

  森 健, 植村 優, 二野 菜々子, 榊原 菜々, 高藤 哲, 山本 暢之, 時政 定雄, 西村 範行, 飯島 一誠

  (公社)日本小児科学会, Feb. 2018, 日本小児科学会雑誌, 122(2) (2), 233 - 233, Japanese

  [Refereed]


• Successful Treatment of Transplantation-associated Atypical Hemolytic Uremic Syndrome With Eculizumab.

  Daiichiro Hasegawa, Atsuro Saito, Nanako Nino, Suguru Uemura, Satoru Takafuji, Takehito Yokoi, Aiko Kozaki, Toshiaki Ishida, Keiichiro Kawasaki, Takahiro Yasumi, Naoki Sakata, Yasufumi Ohtsuka, Satoshi Hirase, Takeshi Mori, Noriyuki Nishimura, Mayumi Kusumoto, Yoshiharu Ogawa, Kenta Tominaga, Taku Nakagawa, Kyoko Kanda, Ryojiro Tanaka, Yoshiyuki Kosaka

  We herein reported a 4-month-old boy with transplantation-associated atypical hemolytic uremic syndrome (TA-aHUS) who was successfully treated with eculizumab. The patient diagnosed with type 3 of familial hemophagocytic lymphohistiocytosis underwent cord blood transplantation. After transplantation, he developed TA-aHUS, but plasma exchanges were unsuccessful. We identified deletions in CFH-related gene 1 (del-CFHR1) by the multiplex ligation-dependent probe amplification testing procedure and CFH autoantibodies. Eculizumab has been administered to the patient, with a marked improvement being achieved in thrombocytopenia. He has been well except for the persistent microhematuria for a year after transplantation. Uncontrolled complement activation might be involved in the pathophysiology of TA-aHUS.

  Jan. 2018, Journal of pediatric hematology/oncology, 40(1) (1), e41-e44 - e44, English, International magazine

  [Refereed]

  Scientific journal


• Changes in the numbers of patients with acute gastroenteritis after voluntary introduction of the rotavirus vaccine in a Japanese children's primary emergency medical center

  MORIOKA Ichiro, KAMIYOSHI Naohiro, NISHIYAMA Masahiro, YAMAMURA Tomohiko, MINAMIKAWA Shogo, IWATANI Sota, NAGASE Hiroaki, NOZU Kandai, NISHIMURA Noriyuki, TANIGUCHI-IKEDA Mariko, ISHIBASHI Kazuto, ISHIDA Akihito, IIJIMA Kazumoto

  Dec. 2017, Environmental Health and Preventive Medicine (Web), 22(1) (1), 22:15 (WEB ONLY), English

  [Refereed]

  Scientific journal


• Reemergence of translocation t(11;19)(q23;p13.1) in the absence of clinically overt leukemia.

  Suguru Uemura, Akihiro Tamura, Atsuro Saito, Daiichiro Hasegawa, Nanako Nino, Takehito Yokoi, Teppei Tahara, Aiko Kozaki, Kenji Kishimoto, Toshiaki Ishida, Keiichiro Kawasaki, Takeshi Mori, Noriyuki Nishimura, Minenori Ishimae, Mariko Eguchi, Yoshiyuki Kosaka

  Dec. 2017, International journal of hematology, 106(6) (6), 847 - 851, English, Domestic magazine

  [Refereed]

  Scientific journal


• Evaluation of BiliCare transcutaneous bilirubin device in Japanese newborns

  Keiji Yamana, Ichiro Morioka, Daisuke Kurokawa, Sachiyo Fukushima, Kosuke Nishida, Shohei Ohyama, Noriyuki Nishimura, Kandai Nozu, Mariko Taniguchi-Ikeda, Hiroaki Nagase, Kazumichi Fujioka, Sota Iwatani, Hajime Nakamura, Kazumoto Iijima

  Oct. 2017, PEDIATRICS INTERNATIONAL, 59(10) (10), 1058 - 1063, English

  [Refereed]

  Scientific journal


• Evaluation of BiliCare transcutaneous bilirubin device in Japanese newborns

  Yamana Keiji, Morioka Ichiro, Kurokawa Daisuke, Fukushima Sachiyo, Nishida Kosuke, Ohyama Shohei, Nishimura Noriyuki, Nozu Kandai, Taniguchi-Ikeda Mariko, Nagase Hiroaki, Fujioka Kazumichi, Iwatani Sota, Nakamura Hajime, Iijima Kazumoto

  Oct. 2017, Pediatrics International, 59(10) (10), 1058‐1063, English

  [Refereed]

  Scientific journal


• SGA児の長期予後 SGA児の胎盤における胎盤形成遺伝子Retrotransposon-like1(Rtl1)メチル化異常の検討

  藤岡 一路, 前山 花織, 西田 浩輔, 大山 正平, 福嶋 祥代, 山名 啓司, 黒川 大輔, 岩谷 壮太, 西村 範行, 飯島 一誠, 森岡 一朗

  (一社)日本周産期・新生児医学会, Jun. 2017, 日本周産期・新生児医学会雑誌, 53(2) (2), 476 - 476, Japanese


• 乳幼児期における発達障害児の感覚特性についての検討 自閉症および知的障害特性との関連

  前山 花織, 高木 康子, 吉岡 三惠子, 加藤 威, 溝渕 雅巳, 北山 真次, 高田 哲, 坊 亮輔, 冨岡 和美, 西山 将広, 粟野 宏之, 永瀬 裕朗, 飯島 一誠, 西村 範行

  (一社)日本小児神経学会, May 2017, 脳と発達, 49(Suppl.) (Suppl.), S360 - S360, Japanese


• 胸部CTにより速やかに診断し得たX連鎖性重症複合型免疫不全症の乳児

  鮫島 智大, 藤村 順也, 中西 啓太, 高藤 哲, 坊 亮輔, 山本 暢之, 森 健, 早川 晶, 西村 範行, 藤井 栄一, 宅見 徹, 飯島 一誠

  (公社)日本小児科学会, May 2017, 日本小児科学会雑誌, 121(5) (5), 914 - 914, Japanese

  [Refereed]


• B前駆細胞性急性リンパ性白血病と診断された難治性小児Double-hit lymphoma/leukemiaの治療経験

  植村優, 長谷川大一郎, 横井健人, 二野菜々子, 太原鉄平, 田村彰広, 齋藤敦郎, 神前愛子, 岸本健治, 石田敏章, 川崎圭一郎, 山本暢之, 森健, Nishimura Noriyuki, 小阪嘉之

  The Japanese Society of Hematology, Feb. 2017, 臨床血液, 58(2) (2), 143 - 149, Japanese

  [Refereed]


• Involvement of WNT Signaling in the Regulation of Gestational Age-Dependent Umbilical Cord-Derived Mesenchymal Stem Cell Proliferation.

  Sota Iwatani, Akemi Shono, Makiko Yoshida, Keiji Yamana, Khin Kyae Mon Thwin, Jumpei Kuroda, Daisuke Kurokawa, Tsubasa Koda, Kosuke Nishida, Toshihiko Ikuta, Kazumichi Fujioka, Masami Mizobuchi, Mariko Taniguchi-Ikeda, Ichiro Morioka, Kazumoto Iijima, Noriyuki Nishimura

  2017, Stem cells international, 2017, 8749751 - 8749751, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Changes in the numbers of patients with acute gastroenteritis after voluntary introduction of the rotavirus vaccine in a Japanese children's primary emergency medical center

  Ichiro Morioka, Naohiro Kamiyoshi, Masahiro Nishiyama, Tomohiko Yamamura, Shogo Minamikawa, Sota Iwatani, Hiroaki Nagase, Kandai Nozu, Noriyuki Nishimura, Mariko Taniguchi-Ikeda, Kazuto Ishibashi, Akihito Ishida, Kazumoto Iijima

  2017, ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE, 22(1) (1), English

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Gestational Age-Dependent Increase of Survival Motor Neuron Protein in Umbilical Cord-Derived Mesenchymal Stem Cells.

  Sota Iwatani, Nur Imma Fatimah Harahap, Dian Kesumapramudya Nurputra, Shinya Tairaku, Akemi Shono, Daisuke Kurokawa, Keiji Yamana, Khin Kyae Mon Thwin, Makiko Yoshida, Masami Mizobuchi, Tsubasa Koda, Kazumichi Fujioka, Mariko Taniguchi-Ikeda, Hideto Yamada, Ichiro Morioka, Kazumoto Iijima, Hisahide Nishio, Noriyuki Nishimura

  2017, Frontiers in pediatrics, 5, 194 - 194, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Gestational age-dependency of height and body mass index trajectories during the first 3 years in Japanese small-for-gestational age children.

  Kaori Maeyama, Ichiro Morioka, Sota Iwatani, Sachiyo Fukushima, Daisuke Kurokawa, Keiji Yamana, Kosuke Nishida, Shohei Ohyama, Kazumichi Fujioka, Hiroyuki Awano, Mariko Taniguchi-Ikeda, Kandai Nozu, Hiroaki Nagase, Noriyuki Nishimura, Chika Shirai, Kazumoto Iijima

  Dec. 2016, Scientific reports, 6, 38659 - 38659, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• PET-MRI所見に基づく肺・下鼻甲介・腎生検が原疾患の診断に有効であった二次性血球貪食性リンパ組織球症の1例

  河原 仁守, 尾藤 祐子, 會田 洋輔, 橘木 由美子, 中井 優美子, 清水 奈保子, 眞庭 謙昌, 西井 達矢, 伊藤 智雄, 藤村 順也, 忍頂寺 毅史, 高藤 哲, 坊 亮輔, 山本 暢之, 森 健, 西村 範行, 飯島 一誠

  (一社)日本小児血液・がん学会, Nov. 2016, 日本小児血液・がん学会雑誌, 53(4) (4), 349 - 349, Japanese

  [Refereed]


• Collaboration of cancer-associated fibroblasts and tumour-associated macrophages for neuroblastoma development.

  Okito Hashimoto, Makiko Yoshida, Yu-Ichiro Koma, Tomoko Yanai, Daiichiro Hasegawa, Yoshiyuki Kosaka, Noriyuki Nishimura, Hiroshi Yokozaki

  Oct. 2016, The Journal of pathology, 240(2) (2), 211 - 23, English, International magazine

  [Refereed]

  Scientific journal


• 小児における幹細胞治療の最近の知見

  Nishimura Noriyuki

  兵庫県小児科医会, Oct. 2016, 兵庫県小児科医会報, 65(66) (66), 6 - 9, Japanese

  [Refereed]


• Early detection of tumor relapse/regrowth by consecutive minimal residual disease monitoring in high-risk neuroblastoma patients.

  Satoshi Hirase, Atsuro Saitoh, Tri Budi Hartomo, Aiko Kozaki, Tomoko Yanai, Daiichiro Hasegawa, Keiichiro Kawasaki, Yoshiyuki Kosaka, Masafumi Matsuo, Nobuyuki Yamamoto, Takeshi Mori, Akira Hayakawa, Kazumoto Iijima, Hisahide Nishio, Noriyuki Nishimura

  Aug. 2016, Oncology letters, 12(2) (2), 1119 - 1123, English, International magazine

  [Refereed]

  Scientific journal


• Fluorescent protein-based detection of unconjugated bilirubin in newborn serum.

  Sota Iwatani, Hajime Nakamura, Daisuke Kurokawa, Keiji Yamana, Kosuke Nishida, Sachiyo Fukushima, Tsubasa Koda, Noriyuki Nishimura, Hisahide Nishio, Kazumoto Iijima, Atsushi Miyawaki, Ichiro Morioka

  Jun. 2016, Scientific reports, 6, 28489 - 28489, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Transient hyperphosphatasemia in three pediatric patients treated with cyclosporine.

  Takeshi Mori, Ryojiro Tanaka, Kosuke Nishida, Nobuyuki Yamamoto, Akira Hayakawa, Noriyuki Nishimura, Kandai Nozu, Kazumoto Iijima

  May 2016, Pediatrics international : official journal of the Japan Pediatric Society, 58(5) (5), 429 - 30, English, International magazine

  [Refereed]

  Scientific journal


• 神経芽腫患者の微小残存病変モニタリング

  西村 範行, トゥインキン・キモン, 山本 暢之, 森 健, 早川 晶, 長谷川 大一郎, 川崎 圭一郎, 小阪 嘉之, 西尾 久英, 飯島 一誠

  (公社)日本小児科学会, Feb. 2016, 日本小児科学会雑誌, 120(2) (2), 316 - 316, Japanese

  [Refereed]


• 左鎖骨部腫瘤を呈した生後6ヵ月の乳児例

  森 健, 藤村 順也, 堀之内 智子, 南川 将吾, 平瀬 敏志, 山本 暢之, 久保川 育子, 早川 晶, 西村 範行, 榊原 俊介, 寺師 浩人, 飯島 一誠

  (公社)日本小児科学会, Jan. 2016, 日本小児科学会雑誌, 120(1) (1), 84 - 84, Japanese

  [Refereed]


• Differential expression of minimal residual disease markers in peripheral blood and bone marrow samples from high-risk neuroblastoma patients.

  Nobuyuki Yamamoto, Aiko Kozaki, Tri Budi Hartomo, Tomoko Yanai, Daiichiro Hasegawa, Keiichiro Kawasaki, Yoshiyuki Kosaka, Masafumi Matsuo, Satoshi Hirase, Takeshi Mori, Akira Hayakawa, Kazumoto Iijima, Hisahide Nishio, Noriyuki Nishimura

  Nov. 2015, Oncology letters, 10(5) (5), 3228 - 3232, English, International magazine

  [Refereed]

  Scientific journal


• Absolute lymphocyte count at the end of induction therapy is a prognostic factor in childhood acute lymphoblastic leukemia.

  Satoshi Hirase, Daiichiro Hasegawa, Hironobu Takahashi, Kensuke Moriwaki, Atsuro Saito, Aiko Kozaki, Toshiaki Ishida, Tomoko Yanai, Keiichiro Kawasaki, Nobuyuki Yamamoto, Ikuko Kubokawa, Takeshi Mori, Akira Hayakawa, Noriyuki Nishimura, Hisahide Nishio, Kazumoto Iijima, Yoshiyuki Kosaka

  Nov. 2015, International journal of hematology, 102(5) (5), 594 - 601, English, Domestic magazine

  [Refereed]

  Scientific journal


• 外来化学療法中(ALL B12臨床試験)の中心静脈カテーテルの管理についての検討

  山本 暢之, 堀之内 智子, 藤村 順也, 森 健, 早川 晶, 西村 範行, 飯島 一誠

  (一社)日本小児血液・がん学会, Oct. 2015, 日本小児血液・がん学会雑誌, 52(4) (4), 342 - 342, Japanese

  [Refereed]


• 神経芽腫の発症・進展におけるRab6BとRab28の役割

  西村 範行, 山本 暢之, 長谷川 大一郎

  日本癌学会, Oct. 2015, 日本癌学会総会記事, 74回, J - 1346, English

  [Refereed]


• DENNドメイン蛋白質DENND2Aによる神経芽腫発の発症・進展の制御機構

  山本 暢之, 西村 範行, 長谷川 大一郎

  日本癌学会, Oct. 2015, 日本癌学会総会記事, 74回, P - 3035, English

  [Refereed]


• DENNドメイン蛋白質DENND2Aによる神経芽腫の制御機構(DENN domain protein DENND2A mediates the progression of neuroblastoma)

  山本 暢之, 堀之内 智子, 藤村 順也, 森 健, 早川 晶, 長谷川 大一郎, 小阪 嘉之, 西尾 久英, 飯島 一誠, 西村 範行

  (一社)日本小児血液・がん学会, Oct. 2015, 日本小児血液・がん学会雑誌, 52(4) (4), 257 - 257, English

  [Refereed]


• 高リスク神経芽腫患者の骨髄と末梢血における微小残存病変の発現についての検討(Differential expression of minimal residual disease markers in peripheral blood and bone marrow samples from high-risk neuroblastoma patients)

  植村 優, 山本 暢之, 神前 愛子, 二野 菜々子, 高藤 哲, 横井 健人, 齋藤 敦郎, 石田 敏章, 長谷川 大一郎, 川崎 圭一郎, 小阪 嘉之, 平瀬 聡史, 森 健, 早川 晶, 飯島 一誠, 西尾 久英, 西村 範行

  (一社)日本小児血液・がん学会, Oct. 2015, 日本小児血液・がん学会雑誌, 52(4) (4), 257 - 257, English

  [Refereed]


• Trinucleotide insertion in the SMN2 promoter may not be related to the clinical phenotype of SMA.

  Nur Imma Fatimah Harahap, Atsuko Takeuchi, Surini Yusoff, Koji Tominaga, Takeshi Okinaga, Yukihiro Kitai, Toru Takarada, Yuji Kubo, Kayoko Saito, Nihayatus Sa'adah, Dian Kesumapramudya Nurputra, Noriyuki Nishimura, Toshio Saito, Hisahide Nishio

  Aug. 2015, Brain & development, 37(7) (7), 669 - 76, English, International magazine

  [Refereed]

  Scientific journal


• 平成26年度 地域における疾病並びに医療等に関する研究調査 公衆衛生行政(保健所)医師の育成・確保とその役割に関する研究調査 公衆衛生行政の現状と課題をふまえて

  伊地智 昭浩, 今井 雅尚, 河原 啓二, 佐藤 英之, 中西 絵里奈, 西尾 久英, 西村 範行

  (一社)神緑会, Aug. 2015, 神緑会学術誌, 31, 7 - 11, Japanese

  [Refereed]


• Two Japanese Patients With SMA Type 1 Suggest that Axonal-SMN May Not Modify the Disease Severity.

  Hiroyuki Yamada, Yoshinobu Nishida, Toshiro Maihara, Nihayatus Sa'adah, Nur Imma Fatimah Harahap, Dian Kesumapramudya Nurputra, Mawaddah Ar Rochmah, Noriyuki Nishimura, Toshio Saito, Yuji Kubo, Kayoko Saito, Hisahide Nishio

  Jun. 2015, Pediatric neurology, 52(6) (6), 638 - 41, English, International magazine

  [Refereed]

  Scientific journal


• Attention Deficit/Hyperactivity Disorder (ADHD): age related change of completion time and error rates of Stroop test.

  Cempaka Thursina, Mawaddah Ar Rochmah, Dian Kesumapramudya Nurputra, Indra Sari Kusuma Harahap, Nur Imma Fatimah Harahap, Nihayatus Sa'Adah, Samekto Wibowo, Sri Sutarni, Ahmad Hamim Sadewa, Noriyuki Nishimura, Tsurue Mandai, Kazumoto Iijima, Hisahide Nishio, Shinji Kitayama

  BACKGROUND: Attention Deficit/Hyperactivity Disorder (ADHD) is a common neurobehavioral problem in children throughout the world. The Stroop test has been widely used for the evaluation of ADHD symptoms. However, the age-related change of the Stroop test results has not been fully clarified until now. METHODS: Sixty-five ADHD and 70 age-matched control children aged 6-13 years were enrolled in this study. ADHD was diagnosed based on DSM-IV criteria. We examined the completion time and error rates of the Congruent Stroop test (CST) and Incongruent Stroop test (IST) in ADHD and control children. RESULTS: No significant difference was observed in the completion time for CST or IST between the ADHD and control children at 6-9 years old. However, ADHD children at 10-13 years old showed significantly delayed completion time for the CST and IST compared with controls of the same age. As for the error rates of the CST and IST, ADHD and control children at 6-9 years old showed no difference. However, error rates of CST and IST in the ADHD children at 10-13 years were significantly higher than those of control of the same age. CONCLUSIONS: Age may influence the results of Stroop test in ADHD children. For the ages of 10-13 years old, the Stroop test clearly separates ADHD children from control children, suggesting that it may be a useful screening tool for ADHD among preadolescent children.

  Apr. 2015, The Kobe journal of medical sciences, 61(1) (1), E19-26 - 26, English, Domestic magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 神経芽腫の進展における腫瘍関連炎症細胞と腫瘍関連間質細胞の相互作用の解明

  橋本 興人, 吉田 牧子, 狛 雄一郎, 矢内 友子, 長谷川 大一郎, 小阪 嘉之, 西村 範行, 横崎 宏

  (一社)日本病理学会, Mar. 2015, 日本病理学会会誌, 104(1) (1), 273 - 273, Japanese

  [Refereed]


• Involvement of aldehyde dehydrogenase 1A2 in the regulation of cancer stem cell properties in neuroblastoma.

  Tri Budi Hartomo, Thi Van Huyen Pham, Nobuyuki Yamamoto, Satoshi Hirase, Daiichiro Hasegawa, Yoshiyuki Kosaka, Masafumi Matsuo, Akira Hayakawa, Yasuhiro Takeshima, Kazumoto Iijima, Hisahide Nishio, Noriyuki Nishimura

  Mar. 2015, International journal of oncology, 46(3) (3), 1089 - 98, English, International magazine

  [Refereed]

  Scientific journal


• 化学療法中に血液培養陽性となった急性リンパ球白血病症例の臨床的検討

  山本 暢之, 山村 智彦, 南川 将吾, 平瀬 敏志, 久保川 育子, 森 健, 早川 晶, 西村 範行, 飯島 一誠

  (公社)日本小児科学会, Feb. 2015, 日本小児科学会雑誌, 119(2) (2), 410 - 410, Japanese

  [Refereed]


• SMA screening system using dried blood spots on filter paper: application of COP-PCR to the SMN1 deletion test.

  Nozomu Kato, Nihayatus Sa'Adah, Mawaddah Ar Rochmah, Nur Imma Fatimah Harahap, Dian Kesumapramudya Nurputra, Hideyuki Sato, Ahmad Hamim Sadewa, Indwiani Astuti, Sofia Mubarika Haryana, Toshio Saito, Kayoko Saito, Noriyuki Nishimura, Hisahide Nishio, Atsuko Takeuchi

  BACKGROUND: Spinal muscular atrophy (SMA) is a common neuromuscular disorder caused by mutations in SMN1. More than 95% of SMA patients carry homozygous SMN1 deletions. Thus, the SMN1 deletion test should be performed initially as part of the diagnostic process. However, SMN2, a highly homologous gene, hampers detection of SMN1 deletion. To differentiate between SMN1 and SMN2, many analysis methods have been developed yet they are not all available worldwide. AIM: To establish a simple but accurate SMN1-deletion detection system that can be used worldwide. METHODS: Fifty DNA samples (29 SMA patients and 21 controls) from dried blood spots (DBS) on filter paper were assayed. All participants had previously been screened for SMA by PCR-restriction fragment length polymorphism (PCR-RFLP) using DNA extracted from freshly collected blood. DNA was extracted from DBS that had been stored at room temperature (20-25℃) for between 1 and 8 years. Competitive oligonucleotide priming-PCR (COP-PCR) was performed to distinguish SMN1 and SMN2 exon7. RESULTS: DNA yield from an 11-mm diameter DBS circle was 21,171 ± 7,485 ng (mean ± SD), with an 260/280 OD ratio from 1.49 to 2.1(mean ± SD; 1.67 ±0.13). Nucleotide sequencing confirmed gene-specific amplification of SMN1 and SMN2 by COP-PCR. SMN1 and SMN2 COP-PCR results are completely consistent with those obtained by PCR-RFLP. CONCLUSION: We have combined DNA extraction from DBS on filter paper with COP-PCR that specifically detects SMN1 and SMN2, establishing a new SMN1-deletion detection system with practical application worldwide.

  Jan. 2015, The Kobe journal of medical sciences, 60(4) (4), E78-85 - 85, English, Domestic magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 神経芽腫の細胞分子遺伝学

  Nishimura Noriyuki

  2015, 臨床細胞分子遺伝, 20, 6 - 8, Japanese

  Scientific journal


• A Rapid, Accurate and Simple Screening Method for Spinal Muscular Atrophy: High-Resolution Melting Analysis Using Dried Blood Spots on Filter Paper.

  Nihayatus Sa'adah, Nur Imma Fatimah Harahap, Dian Kesumapramudya Nurputra, Mawaddah Ar Rochmah, Satoru Morikawa, Noriyuki Nishimura, Ahmad Hamim Sadewa, Indwiani Astuti, Sofia Mubarika Haryana, Toshio Saito, Kayoko Saito, Hisahide Nishio

  2015, Clinical laboratory, 61(5-6) (5-6), 575 - 80, English, International magazine

  [Refereed]

  Scientific journal


• The emergence of CD20-/CD19- tumor cells after rituximab therapy for Epstein-Barr virus-associated post-transplant lymphoproliferative disorder complicated with hemophagocytic lymphohistiocytosis.

  Nobuyuki Yamamoto, Noriyuki Nishimura, Mai Takeuchi, Tomoo Ito, Hiroshi Yokozaki, Satoshi Hirase, Ikuko Kubokawa, Takeshi Mori, Tomoko Yanai, Akira Hayakawa, Yasuhiro Takeshima, Hisahide Nishio, Masafumi Matsuo, Ken-Ichi Imadome, Kazumoto Iijima

  Dec. 2014, European journal of pediatrics, 173(12) (12), 1615 - 8, English, International magazine

  [Refereed]

  Scientific journal


• Intragenic mutations in SMN1 may contribute more significantly to clinical severity than SMN2 copy numbers in some spinal muscular atrophy (SMA) patients.

  Tomoto Yamamoto, Hideyuki Sato, Poh San Lai, Dian Kesumapramudya Nurputra, Nur Imma Fatimah Harahap, Satoru Morikawa, Noriyuki Nishimura, Takashi Kurashige, Tomohiko Ohshita, Hideki Nakajima, Hiroyuki Yamada, Yoshinobu Nishida, Soichiro Toda, Jun-Ichi Takanashi, Atsuko Takeuchi, Yumi Tohyama, Yuji Kubo, Kayoko Saito, Yasuhiro Takeshima, Masafumi Matsuo, Hisahide Nishio

  Nov. 2014, Brain & development, 36(10) (10), 914 - 20, English, International magazine

  [Refereed]

  Scientific journal


• 化学療法中に虫垂炎を発症した小児悪性腫瘍症例の検討(Acute appendicitis of cancer children during chemotherapy: A single center experience)

  山本 暢之, 山村 智彦, 平瀬 敏志, 久保川 育子, 森 健, 早川 晶, 西村 範行, 會田 洋輔, 久松 千恵子, 前田 貢作, 飯島 一誠

  (一社)日本小児血液・がん学会, Oct. 2014, 日本小児血液・がん学会雑誌, 51(4) (4), 233 - 233, English

  [Refereed]


• 神経芽腫がん幹細胞の発生・分化における細胞内小胞輸送の制御因子Rab6Bの役割(Role of a membrane traffic regulator Rab6B in the development of cancer stem cells in neuroblastoma)

  西村 範行, ファム・ティファン・ヒュエン, ハルトモトリブディ, 山本 暢之, 平瀬 敏志, 早川 晶, 矢内 友子, 長谷川 大一郎, 川崎 圭一郎, 小阪 嘉之, 松尾 雅文, 飯島 一誠, 西尾 久英

  (一社)日本小児血液・がん学会, Oct. 2014, 日本小児血液・がん学会雑誌, 51(4) (4), 250 - 250, English

  [Refereed]


• 神経芽腫微小残存病変(MRD)の評価法に関する研究

  Nishimura Noriyuki, 小阪嘉之, 長谷川大一郎, 早川晶, 森健

  (一社)兵庫県医師会, Mar. 2014, 兵庫県医師会医学雑誌, 56(2) (2), 52 - 52, Japanese

  [Invited]


• Spinal muscular atrophy: from gene discovery to clinical trials.

  Dian K Nurputra, Poh San Lai, Nur Imma F Harahap, Satoru Morikawa, Tomoto Yamamoto, Noriyuki Nishimura, Yuji Kubo, Atsuko Takeuchi, Toshio Saito, Yasuhiro Takeshima, Yumi Tohyama, Stacey K H Tay, Poh Sim Low, Kayoko Saito, Hisahide Nishio

  Sep. 2013, Annals of human genetics, 77(5) (5), 435 - 63, English, International magazine

  [Refereed]

  Scientific journal


• Minimal residual disease monitoring in neuroblastoma patients based on the expression of a set of real-time RT-PCR markers in tumor-initiating cells.

  Tri Budi Hartomo, Aiko Kozaki, Daiichiro Hasegawa, Thi Van Huyen Pham, Nobuyuki Yamamoto, Atsuro Saitoh, Toshiaki Ishida, Keiichiro Kawasaki, Yoshiyuki Kosaka, Hiroki Ohashi, Tomoto Yamamoto, Satoru Morikawa, Satoshi Hirase, Ikuko Kubokawa, Takeshi Mori, Tomoko Yanai, Akira Hayakawa, Yasuhiro Takeshima, Kazumoto Iijima, Masafumi Matsuo, Hisahide Nishio, Noriyuki Nishimura

  Minimal residual disease (MRD) is derived from tumor-initiating cells (TICs) and is responsible for tumor relapse. Neuroblastoma is characterized by extreme tumor heterogeneity, and more than half of high-risk patients experience tumor relapse. To overcome tumor heterogeneity and achieve more sensitive detection of MRD, several sets of real-time RT-PCR markers have been reported for MRD monitoring in neuroblastoma patients from different centers. However, these markers vary across centers and are still being validated. In the present study, we validated the ability of 14 commonly used real-time RT-PCR markers to detect MRD based on their expression in neuroblastoma TICs, and we developed a novel MRD detection protocol, which scored the samples as MRD-positive when the expression of one of the 11 real-time RT-PCR markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) exceeded the normal range. By using this protocol, we prospectively monitored MRD in 73 bone marrow (BM), 12 peripheral blood stem cell and 8 peripheral blood samples from 14 neuroblastoma patients treated at a single center. We scored 100, 56, 56 and 57% BM cytology-positive, elevated vanillylmandelic acid (VMA), elevated homovanillic acid (HVA) and elevated neuron-specific enolase (NSE) samples as MRD-positive, respectively. MRD was also positive in 48, 45, 46 and 43% of the BM cytology-negative and normal VMA, normal HVA and normal NSE samples, respectively. These results suggest that the present MRD detection protocol based on the expression of a set of 11 real-time RT-PCR markers in neuroblastoma TICs achieves sensitive MRD monitoring in neuroblastoma patients.

  Apr. 2013, Oncology reports, 29(4) (4), 1629 - 36, English, International magazine

  [Refereed]

  Scientific journal


• 神経芽腫症例におけるmultiple real-time RT-PCR markerを用いた微小残存病変(MRD)解析

  田中 愛子, 長谷川 大一郎, Hartomo Tri Budi, 山本 暢之, 宮田 憲二, 越智 聡史, 斎藤 敦郎, 山下 達也, 石田 敏章, 川崎 圭一郎, 松尾 雅文, Pham Thi Van Huyen, 大橋 浩基, 森 健, 矢内 友子, 早川 晶, 竹島 泰弘, 小阪 嘉之, 飯島 一誠, 西尾 久英, 西村 範行

  (NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, Nov. 2012, 日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 54回・10回・17回, 291 - 291, Japanese

  [Refereed]


• Rab15 alternative splicing is altered in spheres of neuroblastoma cells.

  Thi Van Huyen Pham, Tri Budi Hartomo, Myeong Jin Lee, Daiichiro Hasegawa, Toshiaki Ishida, Keiichiro Kawasaki, Yoshiyuki Kosaka, Tomoto Yamamoto, Satoru Morikawa, Nobuyuki Yamamoto, Ikuko Kubokawa, Takeshi Mori, Tomoko Yanai, Akira Hayakawa, Yasuhiro Takeshima, Kazumoto Iijima, Masafumi Matsuo, Hisahide Nishio, Noriyuki Nishimura

  Jun. 2012, Oncology reports, 27(6) (6), 2045 - 9, English, International magazine

  [Refereed]

  Scientific journal


• SMN2遺伝子量解析による予測よりも軽症の経過をとった脊髄性筋萎縮症患者に対するプロモーター解析

  森川 悟, 中川 卓, 富永 康仁, 沖永 剛志, 西村 範行, 竹島 泰弘, 松尾 雅文, 西尾 久英

  (一社)日本小児神経学会, May 2012, 脳と発達, 44(Suppl.) (Suppl.), S216 - S216, Japanese


• Epigallocatechin gallate inhibits sphere formation of neuroblastoma BE(2)-C cells.

  Noriyuki Nishimura, Tri Budi Hartomo, Thi Van Huyen Pham, Myeong Jin Lee, Tomoto Yamamoto, Satoru Morikawa, Daiichiro Hasegawa, Hiroki Takeda, Keiichiro Kawasaki, Yoshiyuki Kosaka, Nobuyuki Yamamoto, Ikuko Kubokawa, Takeshi Mori, Tomoko Yanai, Akira Hayakawa, Yasuhiro Takeshima, Kazumoto Iijima, Masafumi Matsuo, Hisahide Nishio

  OBJECTIVES: A growing number of epidemiological studies have demonstrated that the consumption of green tea inhibits the growth of a variety of cancers. Epigallocatechin gallate (EGCG), the most abundant catechin in green tea, has been shown to have an anti-cancer effect against many cancers. Most cancers are believed to be initiated from and maintained by a small population of tumor-initiating cells (TICs) that are responsible for chemotherapeutic resistance and tumor relapse. In neuroblastoma, an aggressive pediatric tumor that often relapses and has a poor prognosis, TICs were recently identified as spheres grown in a serum-free non-adherent culture used for neural crest stem cell growth. Although EGCG has been reported to induce growth arrest and apoptosis in neuroblastoma cells, its effect on neuroblastoma TICs remains to be defined. METHODS: Gene expression was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR). The effects of EGCG on cell proliferation, apoptosis, and sphere formation were determined by cell counting, propidium iodide staining, and sphere (>100 μm in diameter) counting, respectively. RESULTS: Neuroblastoma BE(2)-C cells showed increased expression of stem cell markers (nanog homeobox [NANOG] and octamer-binding transcription factor 4 [OCT4]), as well as decreased expression of neuronal differentiation markers (Cu(2+)-transporting ATPase alpha polypeptide [ATP7A] and dickkopf homolog 2 [DKK2]) in spheres grown in serum-free non-adherent culture, compared to parental cells grown in conventional culture. Although EGCG induced growth arrest and apoptosis in the parental cells in a dose-dependent manner, it was not effective against spheres. However, EGCG potently inhibited sphere formation in the BE(2)-C cells. CONCLUSIONS: The present results suggest that EGCG may inhibit the development of TICs in BE(2)-C cells.

  May 2012, Environmental health and preventive medicine, 17(3) (3), 246 - 51, English, International magazine

  [Refereed]

  Scientific journal


• Valproic acid increases SMN2 expression and modulates SF2/ASF and hnRNPA1 expression in SMA fibroblast cell lines.

  Indra Sari Kusuma Harahap, Toshio Saito, Lai Poh San, Naoko Sasaki, Gunadi, Dian Kesuma Pramudya Nurputra, Surini Yusoff, Tomoto Yamamoto, Satoru Morikawa, Noriyuki Nishimura, Myeong Jin Lee, Yasuhiro Takeshima, Masafumi Matsuo, Hisahide Nishio

  Mar. 2012, Brain & development, 34(3) (3), 213 - 22, English, International magazine

  [Refereed]

  Scientific journal


• 臨床的に脊髄性筋萎縮症と診断された患者のSMN遺伝子解析

  西尾 久英, 西村 範行, 森川 悟, 山本 友人, ディアン・ヌルプトラ, 中川 卓, 竹島 泰弘, 飯島 一誠, 松尾 雅文, 齊藤 利雄

  (一社)日本衛生学会, Feb. 2012, 日本衛生学雑誌, 67(2) (2), 329 - 329, Japanese


• 茶カテキンの神経芽腫がん幹細胞に対する抗がん作用の検討

  西村 範行, Hartomo Tri Budi, 李 明鎭, 長谷川 大一郎, 小阪 嘉之, 早川 晶, 竹島 泰弘, 飯島 一誠, 松尾 雅文, 西尾 久英

  (一社)日本衛生学会, Feb. 2012, 日本衛生学雑誌, 67(2) (2), 270 - 270, Japanese

  [Refereed]


• Spinal muscular atrophy patient detection and carrier screening using dried blood spots on filter paper.

  Nur Imma Fatimah Harahap, Indra Sari Kusuma Harahap, Richard Hideki Kaszynski, Dian Kesuma Pramudya Nurputra, Tri Budi Hartomo, Huyen Thi Van Pham, Tomoto Yamamoto, Satoru Morikawa, Noriyuki Nishimura, Imam Rusdi, Retno Widiastuti, Hisahide Nishio

  Feb. 2012, Genetic testing and molecular biomarkers, 16(2) (2), 123 - 9, English, International magazine

  [Refereed]

  Scientific journal


• 初診時急性白血病様所見を呈した胞巣型横紋筋肉腫の1例

  山本 暢之, 平瀬 敏志, 松野下 夏樹, 森 健, 矢内 友子, 早川 晶, 西村 範行, 竹島 泰弘, 飯島 一誠, 松尾 雅文

  (NPO)日本小児がん学会, Nov. 2011, 小児がん, 48(プログラム・総会号) (プログラム・総会号), 341 - 341, Japanese

  [Refereed]


• Diagnosis of spinal muscular atrophy via high-resolution melting analysis symmetric polymerase chain reaction without probe: a screening evaluation for SMN1 deletions and intragenic mutations.

  Satoru Morikawa, Indra Sari Kusuma Harahap, Richard Hideki Kaszynski, Tomoto Yamamoto, Dian Kesuma Pramudya, Huyen Thi Van Pham, Tri Budi Hartomo, Myeong Jin Lee, Ichiro Morioka, Noriyuki Nishimura, Naoki Yokoyama, Yasuhiro Ueno, Masafumi Matsuo, Hisahide Nishio

  Oct. 2011, Genetic testing and molecular biomarkers, 15(10) (10), 677 - 84, English, International magazine

  [Refereed]

  Scientific journal


• 小児医学最近の進歩 脊髄性筋萎縮症とSMN蛋白と低分子量リボ核蛋白合成

  Nishio Hisahide, Morikawa Aatoru, Nishimura Noriyuki, Takeshima Yasuhiro

  金原出版(株), Oct. 2011, 小児科, 52巻, 11号, pp. 1535-1542(11) (11), 1535 - 1542, Japanese

  [Refereed]


• Rab15 expression correlates with retinoic acid-induced differentiation of neuroblastoma cells.

  Noriyuki Nishimura, Thi Van Huyen Pham, Tri Budi Hartomo, Myeong Jin Lee, Daiichiro Hasegawa, Hiroki Takeda, Keiichiro Kawasaki, Yoshiyuki Kosaka, Tomoto Yamamoto, Satoru Morikawa, Nobuyuki Yamamoto, Ikuko Kubokawa, Takeshi Mori, Tomoko Yanai, Akira Hayakawa, Yasuhiro Takeshima, Hisahide Nishio, Masafumi Matsuo

  Jul. 2011, Oncology reports, 26(1) (1), 145 - 51, English, International magazine

  [Refereed]

  Scientific journal


• Herbal Medicine Containing Licorice May Be Contraindicated for a Patient with an HSD11B2 Mutation.

  Indra Sari Kusuma Harahap, Naoko Sasaki, Gunadi, Surini Yusoff, Myeong Jin Lee, Satoru Morikawa, Noriyuki Nishimura, Tomohiro Sasaki, Seiichiro Usuki, Midori Hirai, Mika Ohta, Yutaka Takaoka, Takashi Nishimoto, Hisahide Nishio

  2011, Evidence-based complementary and alternative medicine : eCAM, 2011, 646540 - 646540, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Molecular characterization of the 5'-UTR of retinal dystrophin reveals a cryptic intron that regulates translational activity.

  Ikuko Kubokawa, Yasuhiro Takeshima, Mitsunori Ota, Masahiro Enomoto, Yo Okizuka, Takeshi Mori, Noriyuki Nishimura, Hiroyuki Awano, Mariko Yagi, Masafumi Matsuo

  Dec. 2010, Molecular vision, 16(277-79) (277-79), 2590 - 7, English, International magazine

  [Refereed]

  Scientific journal


• SMN1遺伝子の片側アレルの欠失を認め、もう一方のアレルに点突然変異を認めた脊髄性筋萎縮症の1例

  森川 悟, 山本 友人, 西村 範行, 西尾 久英, 竹島 泰弘, 松尾 雅文

  (公社)日本小児科学会, Dec. 2010, 日本小児科学会雑誌, 114(12) (12), 1946 - 1946, Japanese


• 小児医学最近の進歩 脊髄性筋萎縮症up to date 医学的管理

  Nishio Hisahide, Nishimura Noriyuki, Morikawa Aatoru, Takeshima Yasuhiro

  金原出版(株), Dec. 2010, 小児科, 51(13) (13), 1797 - 1806, Japanese

  [Refereed]


• 小児医学最近の進歩 脊髄性筋萎縮症up to date 遺伝子診断

  Nishio Hisahide, Nishimura Noriyuki, Morikawa Aatoru, Matsuo Masafumi

  金原出版(株), Nov. 2010, 小児科, 51(12) (12), 1687 - 1695, Japanese

  [Refereed]


• 小児医学最近の進歩 脊髄性筋萎縮症up to date 遺伝子診断

  西尾 久英, 西村 範行, 森川 悟, 山本 友人, 松尾 雅文

  金原出版(株), Oct. 2010, 小児科, 51(11) (11), 1535 - 1542, Japanese

  [Refereed]


• Persistent detection of a novel MLL-SACM1L rearrangement in the absence of leukemia.

  Takeshi Mori, Noriyuki Nishimura, Daiichiro Hasegawa, Keiichiro Kawasaki, Yoshiyuki Kosaka, Kazuko Uchide, Tomoko Yanai, Akira Hayakawa, Yasuhiro Takeshima, Hisahide Nishio, Masafumi Matsuo

  Oct. 2010, Leukemia research, 34(10) (10), 1398 - 401, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Generalized epilepsy with febrile seizures plus (GEFS+) spectrum: clinical manifestations and SCN1A mutations in Indonesian patients.

  Elisabeth Siti Herini, Gunadi, Indra Sari Kusuma Harahap, Surini Yusoff, Satoru Morikawa, Suryono Yudha Patria, Noriyuki Nishimura, Sunartini, Sutaryo, Satoshi Takada, Masafumi Matsuo, Hisahide Nishio

  Jun. 2010, Epilepsy research, 90(1-2) (1-2), 132 - 9, English, International magazine

  [Refereed]

  Scientific journal


• A polymorphic mutation, c.-3279T>G, in the UGT1A1 promoter is a risk factor for neonatal jaundice in the Malay population.

  Surini Yusoff, Atsuko Takeuchi, Chitose Ashi, Masako Tsukada, Nur H Ma'amor, Bin A Zilfalil, Narazah M Yusoff, Tsutomu Nakamura, Midori Hirai, Indra S K Harahap, Gunadi, Myeong J Lee, Noriyuki Nishimura, Yutaka Takaoka, Satoru Morikawa, Ichiro Morioka, Naoki Yokoyama, Masafumi Matsuo, Hisahide Nishio, Hans van Rostenberghe

  Apr. 2010, Pediatric research, 67(4) (4), 401 - 6, English, International magazine

  [Refereed]

  Scientific journal


• Genetic disorders associated with neonatal jaundice

  Morioka Ichiro, Morikawa Satoru, Nishimura Noriyuki, Nishio Hisahide

  2010, Eastern Journal of Medicine, Vol. 15, No. 4, pp. 155-162, English

  [Refereed]


• Rab family small G proteins in regulation of epithelial apical junctions.

  Noriyuki Nishimura, Takuya Sasaki

  Jan. 2009, Frontiers in bioscience, 14, 2115 - 29, English, International magazine

  [Refereed]

  Scientific journal


• Interaction of Rab3B with microtubule-binding protein Gas8 in NIH 3T3 cells.

  Noriyuki Nishimura, Kunihiko Araki, Wakako Shinahara, Yumiko Nakano, Kaho Nishimura, Hironori Higashio, Takuya Sasaki

  Jun. 2008, Archives of biochemistry and biophysics, 474(1) (1), 136 - 42, English, International magazine

  [Refereed]

  Scientific journal


• Involvement of actinin-4 in the recruitment of JRAB/MICAL-L2 to cell-cell junctions and the formation of functional tight junctions.

  Hiroyoshi Nakatsuji, Noriyuki Nishimura, Rie Yamamura, Hiro-Omi Kanayama, Takuya Sasaki

  May 2008, Molecular and cellular biology, 28(10) (10), 3324 - 35, English, International magazine

  [Refereed]

  Scientific journal


• Doc2 alpha and Munc13-4 regulate Ca(2+) -dependent secretory lysosome exocytosis in mast cells.

  Hironori Higashio, Noriyuki Nishimura, Hiroyoshi Ishizaki, Jun Miyoshi, Satoshi Orita, Ayuko Sakane, Takuya Sasaki

  Apr. 2008, Journal of immunology, 180(7) (7), 4774 - 84, English, International magazine

  [Refereed]

  Scientific journal


• The interaction of JRAB/MICAL-L2 with Rab8 and Rab13 coordinates the assembly of tight junctions and adherens junctions.

  Rie Yamamura, Noriyuki Nishimura, Hiroyoshi Nakatsuji, Seiji Arase, Takuya Sasaki

  Mar. 2008, Molecular biology of the cell, 19(3) (3), 971 - 83, English, International magazine

  [Refereed]

  Scientific journal


• Involvement of Rab13 and JRAB/MICAL-L2 in epithelial cell scattering

  I. Kanda, N. Nishimura, H. Nakatsuji, R. Yamamura, H. Nakanishi, T. Sasaki

  Mar. 2008, Oncogene, 27(12) (12), 1687 - 1695, English

  [Refereed]

  Scientific journal


• Regulation of epithelial cell adhesion and repulsion: role of endocytic recycling.

  Noriyuki Nishimura, Takuya Sasaki

  A proper balance between cell adhesion and repulsion is essential for cellular morphogenesis during epithelial-mesenchymal transition and mesenchymal-epithelial transition. A number of ligand-receptor pairs including hepatocyte growth factor/scatter factor-Met and semaphorin-plexin are known to control this balance through the complex intracellular signaling pathways. Cell adhesion to other cells and extracellular matrix (ECM) is mediated by cell adhesion molecules (CAMs) and ECM receptors, respectively, which are associated with cytoskeleton through a variety of plaque proteins strengthening and/or weakening adhesion activities. Cell repulsion requires the downregulation of cell adhesion and the extensive changes in cytoskeletal dynamics. The endocytic recycling of CAMs and ECM receptors has recently emerged as an important mechanism to control the balance between cell adhesion and repulsion. Molecule interacting with CasL (MICAL) family proteins are originally identified as a plaque protein associated with ECM receptors integrins and implicated in semaphorin-plexin dependent repulsive axon guidance. We have recently shown that MICAL family protein JRAB/MICAL-L2 functions as an effector protein for Rab family small G protein Rab13 and regulates the endocytic recycling of tight junctional CAM occludin and controls the adhesion and repulsion of epithelial cells.

  Feb. 2008, The journal of medical investigation : JMI, 55(1-2) (1-2), 9 - 16, English, Domestic magazine

  [Refereed]

  Scientific journal


• Identification and characterization of JRAB/MICAL-L2, a junctional Rab13-binding protein.

  Noriyuki Nishimura, Takuya Sasaki

  2008, Methods in enzymology, 438, 141 - 53, English, International magazine

  [Refereed]

  Scientific journal


• Cell-surface biotinylation to study endocytosis and recycling of occludin.

  Noriyuki Nishimura, Takuya Sasaki

  The dynamic turnover of adherens junctions (AJs) and tight junctions (TJs) is essential for epithelial morphogenesis during normal development and differentiation. Although the endocytic recycling of E-cadherin is characterized and implicated in AJ turnover, the molecular basis for TJ turnover is poorly understood. Occludin and claudins are distinct transmembrane proteins localized to the TJs. Although claudins are an indispensable structural component of TJ strands, depletion of occludin in mice reveals well-developed TJ strands and complex histological abnormalities. To examine the intracellular transport of transmembrane proteins to and from the cell surface, cell-surface biotinylation is a proven powerful method. Using this method, we successfully demonstrated that occludin was endocytosed and recycled back to the cell surface in both fibroblastic baby hamster kidney (BHK) and epithelial MTD-1A cells. The endocytic recycling of occludin as well as the formation of functional TJs was dependent on Rab13 and a junctional Rab13-binding protein (JRAB)/molecule interacting with CasL-like 2 (MICAL-L2). We describe the method to study the intracellular transport of occludin to and from the cell surface in both fibroblastic and epithelial cells.

  2008, Methods in molecular biology (Clifton, N.J.), 440, 89 - 96, English, International magazine

  [Refereed]

  Scientific journal


• JRAB/MICAL-L2 is a junctional Rab13-binding protein mediating the endocytic recycling of occludin.

  Tomoya Terai, Noriyuki Nishimura, Ikuno Kanda, Natsuo Yasui, Takuya Sasaki

  May 2006, Molecular biology of the cell, 17(5) (5), 2465 - 75, English, International magazine

  [Refereed]

  Scientific journal


• Recycling of cell adhesion molecule

  西村 範行, 東尾 浩典, 佐々木 卓也

  株式会社医学書院, Apr. 2006, 生体の科学, 57(2) (2), 128 - 133, Japanese

  [Refereed]


• Rab13 mediates the continuous endocytic recycling of occludin to the cell surface.

  Shinya Morimoto, Noriyuki Nishimura, Tomoya Terai, Shinji Manabe, Yasuyo Yamamoto, Wakako Shinahara, Hidenori Miyake, Seiki Tashiro, Mitsuo Shimada, Takuya Sasaki

  Jan. 2005, The Journal of biological chemistry, 280(3) (3), 2220 - 8, English, International magazine

  [Refereed]

  Scientific journal


• 細胞内小胞輸送のしくみ

  西村 範行, 佐々木 卓也

  Lead, (株)先端医学社, Jun. 2004, G.I.Research, 12(3) (3), 242 - 248, Japanese

  [Refereed]


• Identification and characterization of Noc2 as a potential Rab3B effector protein in epithelial cells.

  Shinji Manabe, Noriyuki Nishimura, Yasuyo Yamamoto, Hiroko Kitamura, Shinya Morimoto, Mayu Imai, Shinji Nagahiro, Susumu Seino, Takuya Sasaki

  Mar. 2004, Biochemical and biophysical research communications, 316(1) (1), 218 - 25, English, International magazine

  [Refereed]

  Scientific journal


• PS-086-1 Rabファミリー低分子量G蛋白質Rab13によるタイトジャンクションの接着分子Occludinの小胞輸送制御機構

  森本 慎也, 西村 範行, 佐々木 卓也, 田代 征記

  一般社団法人日本外科学会, Mar. 2004, 日本外科学会雑誌, 105, 472 - 472, Japanese


• 【細胞内輸送研究の最前線】 細胞内輸送の異常と疾患 シナプス可塑性を支える小胞輸送の制御機構

  Nishimura Noriyuki

  (株)羊土社, Sep. 2003, 実験医学, 21(14) (14), 2032 - 2038, Japanese

  [Refereed]


• Distinct roles of Rab3B and Rab13 in the polarized transport of apical, basolateral, and tight junctional membrane proteins to the plasma membrane.

  Yasuyo Yamamoto, Noriyuki Nishimura, Shinya Morimoto, Hiroko Kitamura, Shinji Manabe, Hiro-omi Kanayama, Susumu Kagawa, Takuya Sasaki

  Aug. 2003, Biochemical and biophysical research communications, 308(2) (2), 270 - 5, English, International magazine

  [Refereed]

  Scientific journal


• 【トランスレーショナルリサーチ ここまで近づいた基礎研究と臨床の現場】 徳島発の臨床応用を目指した基礎研究 トランスレーショナルリサーチを視野にいれた「小胞輸送」研究

  Nishimura Noriyuki

  徳島医学会, Apr. 2003, 四国医学雑誌, 59(1〜2) (1〜2), 2 - 6, Japanese

  [Refereed]

  Scientific journal


• Presenilin-binding protein forms aggresomes in monkey kidney COS-7 cells.

  Kazuhiko Namekata, Noriyuki Nishimura, Hideo Kimura

  A novel presenilin-binding protein (PBP) is specifically expressed in the brain, and its level in the soluble fraction of Alzheimer's disease (AD) brains is much less than that in the age-matched controls. Recently, several proteins, including presenilin (PS), have been found to form structures of aggregated proteins, called aggresomes, when the production of the proteins exceeds their rate of degradation by proteasomes. Based on these observations it has been proposed that the aggresome may represent one of the mechanisms forthe formation of cytoplasmic deposits which are linked to the pathogenesis of neurodegenerative disorders including AD. It is shown here that the overexpression of PBP or the suppression of proteasome activity in monkey kidney COS-7 cells leads to the accumulation of detergent-insoluble and multiubiquitinated PBP aggregates. PBP also forms aggregates in primary cultures of neurons in the presence of a proteasome inhibitors. PBP aggregates have the characteristics of aggresomes, including the localization to microtubule organization centers and the disruption of intermediate filaments. These observations suggest that the malfunctioning of the proteasome can cause the formation of PBP aggresomes, which may lead to AD.

  Aug. 2002, Journal of neurochemistry, 82(4) (4), 819 - 27, English, International magazine

  [Refereed]

  Scientific journal


• The delta subunit of AP-3 is required for efficient transport of VSV-G from the trans-Golgi network to the cell surface.

  Noriyuki Nishimura, Helen Plutner, Klaus Hahn, William E Balch

  Vesicular stomatitis virus glycoprotein (VSV-G) is a transmembrane protein that functions as the surface coat of enveloped viral particles. We report the surprising result that VSV-G uses the tyrosine-based di-acidic motif (-YTDIE-) found in its cytoplasmic tail to recruit adaptor protein complex 3 for export from the trans-Golgi network. The same sorting code is used to recruit coat complex II to direct efficient transport from the endoplasmic reticulum to the Golgi apparatus. These results demonstrate that a single sorting sequence can interact with sequential coat machineries to direct transport through the secretory pathway. We propose that use of this compact sorting domain reflects a need for both efficient endoplasmic reticulum export and concentration of VSV-G into specialized post-trans-Golgi network secretory-lysosome type transport containers to facilitate formation of viral coats at the cell surface.

  May 2002, Proceedings of the National Academy of Sciences of the United States of America, 99(10) (10), 6755 - 60, English, International magazine

  [Refereed]

  Scientific journal


• A Di-acidic (DXE) Code Directs Concentration of Cargo during Export from the Endoplasmic Reticulum

  Noriyuki Nishimura, Sergei Bannykh, Sarah Slabough, Jeanne Matteson, Yoram Altschuler, Klaus Hahn, William E. Balch

  American Society for Biochemistry & Molecular Biology (ASBMB), May 1999, Journal of Biological Chemistry, 274(22) (22), 15937 - 15946

  [Refereed]

  Scientific journal


• Molecular Role for the Rab Binding Platform of Guanine Nucleotide Dissociation Inhibitor in Endoplasmic Reticulum to Golgi Transport

  Shih-Kwang Wu, Peng Luan, Jeanne Matteson, Ke Zeng, Noriyuki Nishimura, William E. Balch

  American Society for Biochemistry & Molecular Biology (ASBMB), Oct. 1998, Journal of Biological Chemistry, 273(41) (41), 26931 - 26938

  [Refereed]

  Scientific journal


• Getting into the Golgi

  Sergei I. Bannykh, Noriyuki Nishimura, William E. Balch

  Elsevier BV, Jan. 1998, Trends in Cell Biology, 8(1) (1), 21 - 25

  [Refereed]

  Scientific journal


• A Di-Acidic Signal Required for Selective Export from the Endoplasmic Reticulum

  Nishimura N, Balch WE

  Lead, American Association for the Advancement of Science (AAAS), Jul. 1997, Science, 277(5325) (5325), 556 - 558

  [Refereed]

  Scientific journal


• P21 (WAF1/Cip1/Sdi1/Pic1) mRNA is expressed in neuroblastoma cell lines but not in Ewing's sarcoma and primitive neuroectodermal tumor cell lines

  Taro Maeda, Noriyuki Nishimura, Hajime Nakamura, Kimihiko Sano

  Wiley, 1997, Pediatrics International, 39(5) (5), 590 - 594, English

  [Refereed]

  Scientific journal


• Cloning of a Brain-type Isoform of Human Rab GDI and Its Expression in Human Neuroblastoma Cell Lines and Tumor Specimens

  Noriyuki Nishimura, Junko Goji, Hajime Nakamura, Kimihiko Sano, Satoshi Orita, Yoshimi Takai

  Lead, Nov. 1995, Cancer Research, 55(22) (22), 5445 - 5450, English

  [Refereed]

  Scientific journal


• Molecular cloning and chromosomal assignment of the human brain-type phosphodiesterase I/nucleotide pyrophosphatase gene (PDNP2)

  Hiroyuki Kawagoe, Osamu Soma, Junko Goji, Noriyuki Nishimura, Masaaki Narita, Joji Inazawa, Hajime Nakamura, Kimihiko Sano

  Elsevier BV, 1995, Genomics, 30(2) (2), 380 - 384, English

  [Refereed]

  Scientific journal


• Molecular cloning and characterization of two rab GDI species from rat brain: Brain-specific and ubiquitous types

  Noriyuki Nishimura, Hajime Nakamura, Yoshimi Takai, Kimihiko Sano

  Lead, May 1994, Journal of Biological Chemistry, 269(19) (19), 14191 - 14198, English

  [Refereed]

  Scientific journal


• Donarth-Landsteiner 抗体が IgM に属し抗I特異性を示した発作性寒冷血色素尿症の1例

  西村 範行, 近平 佳美, 永木 聖子

  (公社)日本小児科学会, May 1992, 日小児会誌, 96(5) (5), 1270 - 1273, Japanese

  [Refereed]


• 1児にWilson-Mikity症候群,他の2児に異なる先天奇形を伴った超未熟児の五胎例

  西村 範行, 米谷 昌彦, 河合 徹

  (一社)日本周産期・新生児医学会, Mar. 1992, 日本新生児学会雑誌, 28(1) (1), 120 - 125, Japanese

  [Refereed]


• Clinical Study of Mean Platelet Volume in Patients Treated with Antiepileptic Drugs.

  Nishimura Noriyuki, Tanaka Kazuhiro, Nagaki Shoko, Tanaka Rika, Minato Toshinori, Nakamura Yutaka, Uemura Kanjirou

  JAPAN EPILEPSY SOCIETY, Mar. 1992, Journal of the Japan Epilepsy Society, 10(1) (1), 28 - 33, Japanese

  [Refereed]


• Inhibition of DNA synthesis by protein kinase C-activating phorbol esters in NIH/3T3 cells

  Takeshi Yamamoto, Terutaka Tsuda, Yasuo Hamamori, Noriyuki Nishimura, Yoshimi Takai

  Oxford University Press, 1988, Journal of Biochemistry, 104(1) (1), 53 - 56, English

  [Refereed]

  Scientific journal

• 市中病院小児科外来の新型コロナウイルス感染症流行後1年間におけるワクチン接種の動向

  若林 尚子, 中口 尚始, 高谷 知史, 本田 順子, 西村 範行

  (公社)日本小児保健協会, May 2023, 小児保健研究, 82(講演集) (講演集), 108 - 108, Japanese


• 新型コロナウイルス感染症流行が市中病院における小児のワクチン接種に及ぼした影響

  若林 尚子, 中口 尚始, 高谷 知史, 本田 順子, 西村 範行

  (公社)日本小児保健協会, May 2023, 小児保健研究, 82(3) (3), 304 - 312, Japanese


• Down症児における感覚特性と発達特性に関する研究

  中村 豊, 宮井 文美, 野中 路子, 西村 範行

  (一社)日本小児精神神経学会, Apr. 2023, 小児の精神と神経, 63(1) (1), 73 - 80, Japanese


• 汎血球減少と斜指を契機に診断したMECOM関連症候群の女児

  平場 裕美, 二野 菜々子, 相馬 健人, 増田 知佳, 北角 英晶, 中谷 尚子, 呉 東祐, 高寺 明弘, 田村 彰広, 山本 暢之, 森沢 猛, 西村 範行, 野津 寛大

  (公社)日本小児科学会, Apr. 2023, 日本小児科学会雑誌, 127(4) (4), 625 - 625, Japanese


• 血性鼻汁をきっかけに診断したLCHの男児

  石川 達大, 井上 翔太郎, 西村 明紘, 中谷 尚子, 二野 菜々子, 田村 彰広, 山本 暢之, 西村 範行, 野津 寛大

  (公社)日本小児科学会, Apr. 2023, 日本小児科学会雑誌, 127(4) (4), 632 - 632, Japanese


• COVID-19を契機に溶血発作を発症したグルコース6リン酸脱水素酵素欠損症

  上杉 裕紀, 井上 翔太郎, 今川 幸人, 西村 明紘, 中谷 尚子, 二野 菜々子, 田村 彰広, 山本 暢之, 西村 範行, 野津 寛大

  兵庫県小児科医会, 2023, 兵庫県小児科医会報, (79) (79), 13 - 17, Japanese


• 進行期神経芽腫に対する化学療法実施時に必要となる輸血回数を予測する因子の検討

  紺野 沙織, 柳沢 龍, 久保田 紀子, 小木曽 嘉文, 西村 範行, 坂下 一夫, 戸塚 実

  (一社)日本輸血・細胞治療学会, Apr. 2022, 日本輸血細胞治療学会誌, 68(2) (2), 261 - 261, Japanese


• 神戸市東部療育センター診療所の開所後3年間のまとめ

  岡田 由香, 西尾 久英, 阿部 真也, 大山 正平, 永井 正志, 福嶋 祥代, 堀之内 智子, 冨岡 和美, 村尾 真理子, 大東 寧代, 井澗 茎子, 角谷 香緒利, 西村 範行, 高田 哲, 永瀬 裕朗

  (公社)日本小児科学会, Mar. 2022, 日本小児科学会雑誌, 126(3) (3), 552 - 552, Japanese


• 特別支援学校に通うことで児童生徒の家族に生じる体験に関する研究

  中口 尚始, 本田 順子, 西村 範行

  日本家族看護学会, Sep. 2021, 日本家族看護学会学術集会プログラム・抄録集, 28回, 55 - 55, Japanese


• 当科における小児造血細胞移植患者の精子保存(The sperm preservation in pediatric patients who underwent hematopoietic stem cell transplantation)

  藤川 朋子, 植村 優, 中谷 尚子, 二野 菜々子, 山本 暢之, 西村 範行, 岡田 桂輔, 千葉 公嗣, 塩谷 雅英, 飯島 一誠

  (一社)日本血液学会, Sep. 2021, 日本血液学会学術集会, 83回, PS - 2, English


• 特別支援学校に通うことで児童生徒の家族に生じる体験に関する研究

  中口 尚始, 本田 順子, 西村 範行

  (一社)日本家族看護学会, Sep. 2021, 日本家族看護学会学術集会プログラム・抄録集, 28回, 55 - 55, Japanese


• The sperm preservation in pediatric patients who underwent hematopoietic stem cell transplantation(和訳中)

  藤川 朋子, 植村 優, 中谷 尚子, 二野 菜々子, 山本 暢之, 西村 範行, 岡田 桂輔, 千葉 公嗣, 塩谷 雅英, 飯島 一誠

  (一社)日本血液学会, Sep. 2021, 日本血液学会学術集会, 83回, PS - 2, English


• 進行期神経芽腫に対する化学療法実施時に必要となる輸血回数を予測する因子の検討

  紺野 沙織, 柳沢 龍, 久保田 紀子, 小木曽 嘉文, 西村 範行, 坂下 一夫, 戸塚 実

  (一社)日本輸血・細胞治療学会, May 2021, 日本輸血細胞治療学会誌, 67(2) (2), 307 - 307, Japanese


• 多発乳児血管腫に対するプロプラノロール投与

  金 潔駿, 二野 菜々子, 中谷 尚子, 植村 優, 山本 暢之, 西村 範行, 飯島 一誠, 野村 正, 松本 尚子, 佐伯 啓介

  (公社)日本小児科学会, Apr. 2021, 日本小児科学会雑誌, 125(4) (4), 681 - 681, Japanese


• 高リスク神経芽腫における微小残存病変(MRD)と腫瘍マーカーの相関に関する臨床的検討(Clinical analysis of the correlation between minimal residual disease and tumor markers in high-risk neuroblastoma)

  植村 優, Lin Kyaw San, Thwin Khin Kyaemon, 中谷 尚子, 石田 敏章, 山本 暢之, 田村 彰広, 斉藤 敦郎, 森 健, 長谷川 大一郎, 小阪 嘉之, 二野 菜々子, 高藤 哲, 青砥 悠哉, 長野 智那, 飯島 一誠, 西村 範行

  (公社)日本小児科学会, Feb. 2021, 日本小児科学会雑誌, 125(2) (2), 250 - 250, English


• 予防接種の際に顔面蒼白を指摘されHb2.3g/dLであった1歳6ヵ月女児

  林 佳菜恵, 植村 優, 石河 慎也, 高藤 哲, 森 健, 西村 範行, 飯島 一誠

  (公社)日本小児科学会, Jun. 2020, 日本小児科学会雑誌, 124(6) (6), 1028 - 1028, Japanese


• 最近当科で経験した上咽頭癌の2例

  植村 優, 森 健, 高藤 哲, 西村 範行, 飯島 一誠

  (公社)日本小児科学会, Jun. 2020, 日本小児科学会雑誌, 124(6) (6), 1035 - 1035, Japanese


• 医療技術等国際展開推進事業 小児がんの診療能力強化(前編) 開発途上国における小児がん診療能力強化事業5年間のまとめ

  七野 浩之, 山中 純子, 鈴木 優里, 瓜生 英子, 加藤 元博, 寺島 慶太, 富沢 大輔, 松本 公一, 副島 俊典, 山本 暢之, 長谷川 大一郎, 西村 範行, 義岡 孝子, 上原 秀一郎, 望月 慎史, 浅妻 伴, 大野 孝, 堤 義之, 菱木 知郎, 米田 光宏

  産業開発機構(株), May 2020, 映像情報Medical, 52(5) (5), 40 - 45, Japanese


• Three Cases of Nasopharyngeal Carcinoma in a Single Institute

  Shotaro Inoue, Suguru Uemura, Nanako Nino, Satoru Takahuji, Nobuyuki Yamamoto, Noriyuki Nishimura, Toshiaki Ishida, Takeshi Mori, Daiichiro Hasegawa, Yoshiyuki Kosaka, Kazumoto Iijima

  Dec. 2019, PEDIATRIC BLOOD & CANCER, 66, S50 - S51, English

  Summary international conference


• Level of Seven Neuroblastoma-Associated mRNAs Analyzed by ddPCR is Correlated Between Bone Marrow and Peripheral Blood in High-risk Neuroblastoma

  Suguru Uemura, Toshiaki Ishida, Kyaemonthwin Khin, Sanlin Kyaw, Nobuyuki Yamamoto, Akihiro Tamura, Atsuro Saito, Kenji Kishimoto, Takeshi Mori, Daiichiro Hasegawa, Yoshiyuki Kosaka, Nanako Nino, Satoru Takafuji, Kazumoto Iijima, Noriyuki Nishimura

  Dec. 2019, PEDIATRIC BLOOD & CANCER, 66, S81 - S82, English

  Summary international conference


• 修正18〜24ヵ月のNICU退院児における感覚特性の検討

  村尾 真理子, 前山 花織, 万代 ツルエ, 高木 康子, 加藤 威, 岡田 由香, 溝渕 雅巳, 北山 真次, 冨岡 和美, 永瀬 裕朗, 森岡 一朗, 高田 哲, 西村 範行

  (一社)日本小児精神神経学会, Oct. 2019, 小児の精神と神経, 59(3) (3), 269 - 270, Japanese


• Quantitation of Minimal Residual Disease by Droplet Digital PCR in High-Risk Neuroblastoma Patients

  Noriyuki Nishimura, Toshiaki Ishida, Khin Thwin, Suguru Uemura, Nobuyuki Yamamoto, Akihiro Tamura, Nanako Nino, Aiko Kozaki, Atsuro Saito, Kenji Kishimoto, Daiichiro Hasegawa, Yoshiyuki Kosaka, Satoru Takafuji, Takeshi Mori, Kazumoto Iijima

  Nov. 2018, PEDIATRIC BLOOD & CANCER, 65, S38 - S39, English

  Summary international conference


• A pediatric ETV6-ABL1-positive acute lymphoblastic leukemia case with ETV6-ABL1-independent resistance to tyrosine kinase inhibitor

  Suguru Uemura, Daiichiro Hasegawa, Akemi Shono, Khin Kyae, Mon Thwin, Nanako Nino, Satoru Takafuji, Takeshi Mori, Akihiro Tamura, Nobuyuki Yamamoto, Atsuro Saito, Kenji Kishimoto, Toshiaki Ishida, Yoshiyuki Kosaka, Kazumoto Iijima, Noriyuki Nishimura

  Oct. 2018, CANCER RESEARCH, 78(19) (19), English

  Summary international conference


• 乳幼児感覚プロファイルを用いた発達障害児の感覚特性に関する検討

  前山花織, 高木康子, 吉岡三惠子, 加藤威, 溝渕雅巳, 北山真次, 高田哲, 松本真明, 永井正志, 坊亮輔, 冨岡和美, 西山将広, 粟野宏之, 永瀬裕朗, 飯島一誠, 西村範行

  2018, 日本小児科学会雑誌, 122(4) (4)


• 乳幼児期における発達障害特性と感覚特性との関連についての検討

  前山花織, 前山花織, 高木康子, 加藤威, 溝渕雅巳, 北山真次, 北山真次, 高田哲, 冨岡和美, 永瀬裕朗, 飯島一誠, 西村範行, 西村範行

  2017, 日本小児精神神経学会プログラム・抄録集, 117th, 49, Japanese


• 臍帯由来間葉系幹細胞を用いた脊髄性筋萎縮症の病態解析の試み

  岩谷 壮太, 福嶋 祥代, 徳田 央士, 西田 浩輔, 前山 花織, 山名 啓司, 黒川 大輔, 長坂 美和子, 香田 翼, 森岡 一朗, 西尾 久英, 飯島 一誠, 西村 範行

  (一社)日本周産期・新生児医学会, Jun. 2016, 日本周産期・新生児医学会雑誌, 52(2) (2), 643 - 643, Japanese


• PET-MRI所見に基づく肺・下鼻甲介・腎生検が原疾患の診断に有効であった二次性血球貪食性リンパ組織球症の1例

  河原仁守, 尾藤祐子, 會田洋輔, 橘木由美子, 中井優美子, 清水奈保子, 眞庭謙昌, 西井達矢, 伊藤智雄, 藤村順也, 忍頂寺毅史, 高藤哲, 坊亮輔, 山本暢之, 森健, 西村範行, 飯島一誠

  2016, 日本小児血液・がん学会雑誌(Web), 53(4) (4)


• G-CSF投与と自家末梢血幹細胞移植を併用しbi-weekly VDC-IE療法を完遂し得た切除不能ユーイング肉腫例

  山本暢之, 坊亮輔, 高藤哲, 森健, 西村範行, 江島泰生, 深瀬直政, 原仁美, 河本旭哉, 秋末敏宏, 飯島一誠

  2016, 日本小児血液・がん学会雑誌(Web), 53(4) (4)


• 細胞移植の新たな展開 臍帯組織中に存在する多能性幹細胞Muse細胞の多能性の解析

  串田 良祐, 若尾 昌平, 明石 英雄, 西村 範行, 岩谷 壮太, 香田 翼, 森岡 一朗, 溝渕 雅巳, 飯島 一誠, 出澤 真理

  (一社)日本臓器保存生物医学会, Oct. 2015, Organ Biology, 22(3) (3), 43 - 43, Japanese


• UBアナライザーとビリルビン誘導蛍光タンパク質(UnaG)を用いた新たなアンバウンドビリルビン測定法の開発

  岩谷 壮太, 中村 肇, 福嶋 祥代, 徳田 央士, 西田 浩輔, 藤田 花織, 山名 啓司, 黒川 大輔, 長坂 美和子, 香田 翼, 西村 範行, 飯島 一誠, 森岡 一朗

  (一社)日本新生児成育医学会, Sep. 2015, 日本新生児成育医学会雑誌, 27(3) (3), 579 - 579, Japanese


• Contribution of cancer-associated fibroblasts and M2-polarized macrophages to neuroblastoma development

  O. Hashimoto, M. Yoshida, Y. Koma, T. Yanai, D. Hasegawa, Y. Kosaka, N. Nishimura, H. Yokozaki

  Sep. 2015, EUROPEAN JOURNAL OF CANCER, 51, S20 - S20, English

  Summary international conference


• Absolute Lymphocyte Counts at the End of Induction Is a Prognostic Indicator in Childhood Acute Lymphoblastic Leukemia

  Daiichiro Hasegawa, Satoshi Hirase, Hironobu Takahashi, Atsuro Saito, Aiko Kozaki, Toshiaki Ishida, Tomoko Yanai, Keiichiro Kawasaki, Noriyuki Yamamoto, Ikuko Kubokawa, Takeshi Mori, Akira Hayakawa, Noriyuki Nishimura, Kazumoto Iijima, Yoshiyuki Kosaka

  Dec. 2014, BLOOD, 124(21) (21), English

  Summary international conference


• Induction of ALDH1A2 expression is critical for cancer stem cell properties in neuroblastoma

  Noriyuki Nishimura, Tri Budi Hartomo, Thi Van Huyen Pham, Nobuyuki Yamamoto, Satoshi Hrase, Akira Hayakawa, Daiichiro Hasegawa, Keiichiro Kawasaki, Yoshiyuki Kosaka, Masafumi Matsuo, Yasuhiro Takeshima, Kazumoto Iijima, Hisahide Nishio

  Oct. 2014, CANCER RESEARCH, 74(19) (19), English

  Summary international conference


• Rab13 mediates the continuous endocytic recycling of occludin to the cell surface. (vol 280, pg 2220, 2005)

  S Morimoto, N Nishimura, T Terai, S Manabe, Y Yamamoto, W Shinahara, H Miyake, S Tashiro, M Shimada, T Sasaki

  Sep. 2005, JOURNAL OF BIOLOGICAL CHEMISTRY, 280(36) (36), 32048 - 32048, English

  Others


• Rabファミリー低分子量G蛋白質によるタイトジャンクション膜蛋白質の小胞輸送の制御機構

  森本慎也, 西村範行, 北村弘子, 品原和加子, 山本恭代, 寺井智也, 坂根亜由子, 真鍋進治, 田代征記

  日本癌学会, 25 Aug. 2003, 日本癌学会総会記事, 62nd, 305 - 305, Japanese


• Rab3BとRab13低分子量G蛋白質によるゴルジ体 細胞膜間小胞輸送の制御機構

  山本 恭代, 西村 範行, 森本 慎也, 北村 弘子, 真鍋 進治, 佐々木 卓也, 金山 博臣, 香川 征

  徳島医学会, Apr. 2003, 四国医学雑誌, 59(1〜2) (1〜2), 110 - 111, Japanese


• Two Cases of Hemorrhagic Shock and Encephalopathy Syndrome.

  Minato Toshinori, Uemura Kanjiroh, Tanaka Kazuhiro, Nishimura Noriyuki, Mori Yumiko, Maehara Kouzi, Isida Akihito, Kuroda Eizou

  A 10-month-old male infant (case 1) and another male infant aged 1 year and 11 months (case 2) were admitted to our department because of fever, watery diarrhea and convulsion. On admission, they were unconscious and showed rigidity of the limbs. Laboratory examination revealed a marked increase in GOT and GPT, a decrease in platelet and antithrombin III and an increase in FDP. Metabolic acidosis was found by blood gas analysis. Brain CT showed an extensive area of low density in case 1, and low density centering on the cerebral basal ganglia and brainstem in case 2. Rotavirus was detected in case 2 by fecal examination. The clinical pictures in these cases closely resembled those of hemorrhagic shock and encephalopathy (HSE) reported by Levin et al. in 1983. The etiology of this disease is currently unknown, and its prognosis in poor. The relationship between this disease and rotavirus should be examined in future studies. 症例1は10カ月の男児, 症例2は1歳11カ月の男児.ともに発熱, 水様性下痢, 痙攣を主訴に当科に入院した.入院時, 意識なく四肢硬直していた.検査所見では, GOT, GPTが著明に上昇し, また血小板の減少, fibrinogen degradation products (FDP) の上昇, アンチトロンビンIIIの低下を認めた.血液ガス分析で代謝性アシドーシスを呈した.頭部CTにて症例1では広範囲にわたって低吸収領域を, 症例2では大脳基底核, 脳幹部を中心に低吸収領域を認めた.症例2の糞便検査にてロタウイルスを証明した.この臨床像は, 1983年にLevinらが提唱したhemorrhagic shock and encephalopathy (HSE) と酷似した.現在のところ原因不明であり予後不良の疾患であるがロタウイルスとの関係について今後検討を重ねていく必要があると考えられた.

  THE JAPANESE SOCIETY OF CHILD NEUROLOGY, 1992, NO TO HATATSU, 24(1) (1), 71 - 77, Japanese

• 先天性サイトメガロウィルス感染は自閉症スペクトラム障害のリスク因子か？

  西村範行, 前山花織, 冨岡和美, 永瀬裕朗, 高木康子, 加藤威, 岡田由香, 溝渕雅巳, 北山真次, 西田浩輔, 藤岡一路, 堀之内智子, 西山将広, 森岡一朗, 高田哲, 吉岡美恵子, 飯島一誠

  第30回日本疫学会学術総会, Feb. 2020, Japanese

  Poster presentation


• Level of seven neuroblastoma-associated mRNAs analyzed by droplet digital PCR is correlated between bone marrow and peripheral blood in high-risk neuroblastoma

  Uemura S, Ishida T, Thwin KK, Lin KS, Yamamoto N, Tamura A, Kishimoto K, Mori T, Hasegawa D, Kosaka Y, Nino N, Takafuji S, Iijima K, Nishimura N

  第61回日本小児血液・がん学会学術集会, Nov. 2019, Japanese

  Oral presentation


• Spontaneously developed undifferentiated sarcoma and rhabdomyosarcoma in mdx mice

  Takafuji S, Niba ET, Thwin KK, Yamamoto N, Awano H, Fukushima S, Itoh K, Nishio H, Matsuo M, Lin KS, Uemura S, Iijima K, Nishimura N

  第61回日本小児血液・がん学会学術集会, Nov. 2019, Japanese

  Poster presentation


• Three cases of nasopharyngeal carcinoma in a single institute

  Inoue S, Uemura S, Nino N, Takafuji S, Yamamoto N, Nishimura N, Ishida T, Mori T, Hasegawa D, Kosaka Y, Iijima K

  第61回日本小児血液・がん学会学術集会, Nov. 2019, Japanese

  Oral presentation


• Expression of seven neuroblastoma-associated mRNAs is correlated between bone marrow and peripheral blood in high-risk neuroblastoma patients

  Thwin KK, Lin KS, Ishida T, Uemura S, Yamamoto N, Nishimura N

  第78回日本癌学会学術総会, Sep. 2019, English

  Oral presentation


• 修正18～24ヶ月のNICU退院児における感覚特性の検討

  村尾真理子, 前山花織, 万代ツルエ, 高木康子, 加藤威, 岡田由香, 溝渕雅巳, 北山真次, 冨岡和美, 永瀬裕朗, 森岡一朗, 高田哲, 西村範行

  第121回日本小児精神神経学会, Jun. 2019, Japanese

  Oral presentation


• 小児術前検査における凝固異常の頻度

  森健, 植村優, 髙藤哲, 石河 真也, 青砥 悠哉, 西村範行, 飯島一誠

  122回日本小児科学会学術集会, Apr. 2019, Japanese

  Poster presentation


• 化学療法中に発症した水腎症に対しDouble-Jカテーテル留置を要したALL男児

  植村優, 森健, 髙藤哲, 西村範行, 飯島一誠

  第122回日本小児科学会学術集会, Apr. 2019, Japanese

  Poster presentation


• 臍帯組織由来Muse細胞の栄養膜細胞への分化の可能性

  串田良祐, 若尾昌平, 西村範行, 岩谷壮太, 香田翼, 森岡一朗, 溝渕雅巳, 飯島一誠, 出澤真里

  第124回日本解剖学会, Mar. 2019, Japanese

  Oral presentation


• 臍帯組織由来Muse細胞の栄養膜細胞への分化

  串田良祐, 若尾昌平, 西村範行, 岩谷壮太, 香田翼, 森岡一朗, 溝渕雅巳, 飯島一誠, 出澤真里

  第18回日本再生医療学会総会, Mar. 2019, Japanese

  Oral presentation


• 移植後の混合キメラに対してデキサメサゾン投与が奏効した家族性血球貪食リンパ組織球症3型の1例

  植村優, 森健, 高藤哲, 藤岡一路, 八角高裕, 西村範行, 飯島一誠

  第41回日本造血細胞移植学会総会, Mar. 2019, Japanese

  Poster presentation


• The Retrospective Analysis of High-Dose Chemotherapy and Autologous Stem Cell Transplantation for High-Risk Padiatric Osteosarcoma

  Uemura S, Mori T, Takafuji S, Nishimura N, Iijima K

  13th St. Jude-VIVA Forum in Pediatric Oncology, Feb. 2019, English

  Poster presentation


• 予防接種の際に顔面蒼白を指摘されHb2.3g/dLであった1歳6か月女児

  林佳菜恵, 植村優, 石河慎也, 高藤哲, 森健, 西村範行, 飯島一誠

  第276回日本小児科学会兵庫県地方会, Feb. 2019, Japanese

  Oral presentation


• DMD transcription profiling in spontaneously developed tumor from three mdx mice revealed extensive intron retentions and Dp71 isoform expression

  Tabe Epse Niba, Emma Eko, Noriyuki Nishimura, Satoru Takafuji, Khin Kyae Mon Thwin, Nobuyuki Yamamoto, Hiroyuki Awano, Shoji Fukushima, Kyoko Itoh, Hisahide Nishio, Masafumi Matsuo

  ASCB/EMBO 2018 meeting, Dec. 2018, English, San Diego, International conference

  Poster presentation


• Spontaneous development of spindle cell sarcoma in mdx mice

  Satoru Takafuji, TABE EPSE NIBA, EMMA EKO, Khin Kyae Mon Thwin, Nobuyuki Yamamoto, Hiroyuki Awano, Suguru Uemura, Takeshi Mori, Sachiyo Fukushima, Kyoko Itoh, Hisahide Nishio, Masafumi Matsuo, Kazumoto Iijima, Noriyuki Nishimura

  第60回日本小児血液・がん学会学術集会, Nov. 2018, English, 京都市, Domestic conference

  Poster presentation


• Quantitation of minimal residual disease by droplet digital PCR in high-risk neuroblastoma patients

  Noriyuki Nishimura, Toshiaki Ishida, Khin Kyae Mon Thwin, Suguru Uemura, Nobuyuki Yamamoto, Akihiro Tamura, Nanako Nino, Aiko Kozaki, Atsuro Saito, Kenji Kishimoto, Daiichiro Hasegawa, Yoshiyuki Kosaka, Satoru Takafuji, Takeshi Mori, Kazumoto Iijima

  第60回日本小児血液・がん学会学術集会, Nov. 2018, English, 京都市, Domestic conference

  Oral presentation


• EXPRESSION PROFILES OF SEVEN MINIMAL RESIDUAL DISEASE MARKERS IN BONE MARROW AND PERIPHERAL BLOOD OF PATIENTS WITH HIGH‑RISK NEUROBLASTOMA

  Khin Kyae Mon Thwin, Toshiaki Ishida, Suguru Uemura, Nobuyuki Yamamoto, Akihiro Tamura, Aiko Kozaki, Atsuro Saito, Kenji Kishimoto, Daiichiro Hasegawa, Yoshiyuki Kosaka, Nanako Nino, Satoru Takafuji, Takeshi Mori, Kazumoto Iijima, Noriyuki Nishimura

  The 50th Congress of the International Society of Paediatric Oncology, Nov. 2018, English, 京都市, International conference

  Poster presentation


• ダウン症候群に伴う小児骨髄性白血病の第二再発にアザシチジンが奏功した一例

  植村 優, MORI TAKESHI, TAKAFUJI SATORU, NISHIMURA NORIYUKI, 土岐 力, 照井 君典, 伊藤 悦朗, IIJIMA KAZUMOTO

  第80回日本血液学会学術集会, Oct. 2018, Japanese, 大阪市, Domestic conference

  Poster presentation


• Detection of minimal residual disease in high-risk neuroblastoma patients by digital PCR

  Noriyuki Nishimura, Toshiaki Ishida, Suguru Uemura, Nobuyuki Yamamoto, Daiichiro Hasegawa, Satoru Takafuji, Takeshi Mori, Nanako Nino, Akihiro Tamura, Aiko Kozaki, Atsuro Saito, Kenji Kishimoto, Yoshiyuki Kosaka, Kazumoto Iijima

  第77回日本癌学会学術総会, Sep. 2018, English, 大阪市, Domestic conference

  Oral presentation


• When does SMN shortage become evident in spinal muscular atrophy patients?

  Noriyuki Nishimura, Sota Iwatani, Keiji Yamana, Masashi Nagai, Ryousuke Bou, Hiroyuki Awano, Kaori Maeyama, Masahiro Nishiyama, Hiroaki Nagase, Masami Mizobuchi, Kazumichi Fujioka, Ichiro Morioka, Kazumoto Iijima, Hisahide Nishio

  第60回日本小児神経学会学術集会, Jun. 2018, English, 千葉市, Domestic conference

  Oral presentation


• Is congenital cytomegalovirus infection associated with autism spectrum disorder?

  Noriyuki Nishimura, Kaori Maeyama, Kazumi Tomioka, Hiroaki Nagase, Mieko Yoshioka, Yasuko Takagi, Takeshi Kato, Masami Mizobuchi, Shinji Kitayama, Satoshi Takada, Masashi Nagai, Nana Sakakibara, Masahiro Nishiyama, Ichiro Morioka, Kazumoto Iijima

  第60回日本小児神経学会学術集会, Jun. 2018, English, 千葉市, Domestic conference

  Oral presentation


• Mycobacterium chelonaeによる菌血症を発症したダウン症候群に伴う骨髄性白血病の女児例

  植村 優, TAKAFUJI SATORU, MORI TAKESHI, NISHIMURA NORIYUKI, IIJIMA KAZUMOTO

  第274回日本小児科学会兵庫県地方会, May 2018, Japanese, 神戸市, Domestic conference

  Oral presentation


• Elevated minimal residual disease marker expression in peripheral blood of three high‑risk neuroblastoma cases

  Khin Kyae Mon Thwin, Toshiaki Ishida, Suguru Uemura, Nobuyuki Yamamoto, Akihiro Tamura, Aiko Kozaki, Atsuro Saito, Kenji Kishimoto, Daiichiro Hasegawa, Yoshiyuki Kosaka, Nanako Nino, Satoru Takafuji, Takeshi Mori, Kazumoto Iijima, Noriyuki Nishimura

  Neuroblastoma Research Association 2018, May 2018, English, San Francisco, International conference

  Poster presentation


• 日齢38で発症した後天性サイトメガロウイルス感染による血小板減

  植村 優, MORI TAKESHI, 二野 菜々子, 榊原 菜々, TAKAFUJI SATORU, 明神 翔太, 高見 勇一, 藤田 秀樹, 森岡 一朗, NISHIMURA NORIYUKI, 久呉 真章, IIJIMA KAZUMOTO

  第121回日本小児科学会学術集会, Apr. 2018, Japanese, 福岡市, Domestic conference

  Poster presentation


• プロプラノロールシロップで治療した乳児血管腫9例の検討

  TAKAFUJI SATORU, MORI TAKESHI, 植村 優, 二野 菜々子, 榊原 菜々, NISHIMURA NORIYUKI, IIJIMA KAZUMOTO

  第121回日本小児科学会学術集会, Apr. 2018, Japanese, 福岡市, Domestic conference

  Poster presentation


• 5年以上のRomiplostim投与後に無治療経過観察に至った幼児慢性免疫血小板減少性紫斑病

  MORI TAKESHI, 植村 優, 二野 菜々子, 榊原 菜々, TAKAFUJI SATORU, 山本 暢之, 時政 定雄, NISHIMURA NORIYUKI, IIJIMA KAZUMOTO

  第121回日本小児科学会学術集会, Apr. 2018, Japanese, 福岡市, Domestic conference

  Oral presentation


• A pediatric ETV6-ABL1-positive acute lymphoblastic leukemia case with ETV6-ABL1-indepent acquired resistance to tyrosine kinase inhibitor

  Uemura S, Hasegawa D, Shono Akemi, Thwin KKM, Nino N, Takafuji S, Mori Takeshi, Tamura A, Yamamoto N, Saito A, Kishimoto K, Ishida Tatsuro, Kosaka Y, Iijima Kazumoto, Nishimura Noriyuki

  AACR Pediatric Cancer Research: From Basic Science to the Clinic, Dec. 2017, English, American association for cancer research, Atlanta, USA, International conference

  Poster presentation


• Genotype-phenotype correlation in patients with chromosome 13q partial deletion

  Fujita Kaori, Morisada N, Nagai M, Sakakibara N, Takagi Y, Nishimura Noriyuki, Yoshioka M, Iijima Kazumoto

  日本人類遺伝学会 第62回大会, Nov. 2017, Japanese, 日本人類遺伝学会, 神戸, Domestic conference

  Poster presentation


• 単一施設における骨肉腫に対する大量化学療法についての後方視的検討

  UEMYRS SUGURU, MORI TAKESHI, TAKAFUJI SATORU, NISHIMURA NORIYUKI, IIJIMA KAZUMOTO

  第59回日本小児血液・がん学会学術集会, Nov. 2017, Japanese, 京都市, Domestic conference

  Oral presentation


• Pediatric acute lymphoblastic leukemia with ETV6-ABL1

  植村優, 長谷川大一郎, 田村彰広, 山本暢之, 齋藤敦郎, 中村さやか, 藤原隆弘, 神前愛子, 岸本健治, 石田敏章, 坂口公祥, 中町佑司, Mori Takeshi, Nishimura Noriyuki, Iijima Kazumoto, 小阪嘉之

  第79回日本血液学会学術集会, Oct. 2017, Japanese, 日本血液学会, 東京, Domestic conference

  Poster presentation


• 発達の遅れを機にアレイCGHで診断したSmith-Magenis症候群の1例

  Fujita Kaori, 森貞直哉, 榊原菜々, 高木康子, 加藤威, 吉岡三惠子, Nishimura Noriyuki, Iijima Kazumoto

  第272回日本小児科学会兵庫県地方会, Sep. 2017, Japanese, 日本小児科学会, 姫路, Domestic conference

  Oral presentation


• 日齢38で発症した血小板減少症の男児

  植村優, 二野菜々子, 高藤哲, 榊原菜々, Mori Takeshi, Nishimura Noriyuki, 吉本啓修, 明神翔太, 高見勇一, 藤田秀樹, 久呉真章, Iijima Kazumoto

  第272回日本小児科学会兵庫県地方会, Sep. 2017, Japanese, 日本小児科学会, 姫路, Domestic conference

  Oral presentation


• UBアナライザーとニホンウナギ由来の蛍光タンパク質（UnaG）を用いた新たなアンバウンドビリルビン測定法の開発

  岩谷壮太, 中村肇, 大山正平, Nishida Kosuke, Yamana Keiji, 黒川大輔, Nishimura Noriyuki, Iijima Kazumoto, Morioka Ichiro

  第53回日本周産期・新生児医学会学術集会, Jul. 2017, Japanese, 日本周産期・新生児医学会, 横浜, Domestic conference

  Public symposium


• SGA児の胎盤における胎盤形成遺伝子Retrotransposon-like1(Rtl1)メチル化異常の検討

  Fujita Kaori, Nishida Kosuke, 大山正平, 福嶋祥代, Yamana Keiji, 黒川大輔, 岩谷壮太, Nishimura Noriyuki, Iijima Kazumoto, Morioka Ichiro

  第53回日本周産期・新生児医学会学術集会, Jul. 2017, Japanese, 日本周産期・新生児医学会, 横浜, Domestic conference

  Public symposium


• Expression of CD134(OX40) on T cells is a trigger of human herpesvirus 6B reactivation and replication after hematopoietic cell transplantation

  Satoshi Nagamata, Miwako Nagasaka, Kawabata Akiko, Kenji Kishimoto, Daiichiro Hasegawa, Yoshiyuki Kosaka, Mori Takeshi, Morioka Ichiro, Nishimura Noriyuki, Iijima Kazumoto, Yamada Hideto, kimiikazu Yakushijin, Matsuoka Hiroshi, Mori Yasuko

  10th International Conference on HHV-6&7, Jul. 2017, English, 10th International Conference on HHV-6&7, ベルリン, ドイツ, International conference

  Poster presentation


• 乳幼児期における発達障害特性と感覚特性との関連についての検討

  Fujita Kaori, 高木康子, 加藤威, 溝渕雅巳, 北山真次, Takada Satoshi, Nagase Hiroaki, Iijima Kazumoto, Nishimura Noriyuki

  第117回日本小児精神神経学会, Jun. 2017, Japanese, 日本小児神経学会, 東京, Domestic conference

  Oral presentation


• 乳幼児期における発達障害児の感覚特性についての検討～自閉症および知的障害特性との関連～

  Fujita Kaori, 高木康子, 吉岡三惠子, 加藤威, 溝渕雅巳, 北山真次, Takada Satoshi, Nishiyama Masahiro, Hiroyuki Awano, Nagase Hiroaki, Iijima Kazumoto, Nishimura Noriyuki

  第59回日本小児神経学会学術集会, Jun. 2017, Japanese, 日本小児神経学会, 大阪, Domestic conference

  Oral presentation


• 造血幹細胞移植後のT細胞におけるCD134(OX40）の発現が、移植後HHV-6B再活性化および増殖の誘因となる

  長坂 美和子, Kawabata Akiko, 岸本 健治, 長谷川 大一郎, 小阪 嘉之, Mori Takeshi, Morioka Ichiro, Nishimura Noriyuki, Iijima Kazumoto, Yamada Hideto, Yakushijin Kimikazu, Matsuoka Hiroshi, Mori Yasuko

  第31回ヘルペスウイルス研究会, Jun. 2017, Japanese, 第31回ヘルペスウイルス研究会, 松江, Domestic conference

  Oral presentation


• 臍帯組織中に存在する非腫瘍性多能性幹細胞Muse細胞の機能解析

  串田良祐, 若尾昌平, Nishimura Noriyuki, 岩谷壮太, 香田 翼, Morioka Ichiro, 溝渕雅巳, Iijima Kazumoto, 出澤真理

  第16回日本再生医療学会総会, May 2017, Japanese, 日本再生医療学会, 仙台, Domestic conference

  Oral presentation


• 乳幼児感覚プロファイルを用いた発達障害児の感覚特性に関する検討

  Fujita Kaori, 高木康子, 吉岡三惠子, 加藤威, 溝渕雅巳, 北山真次, Takada Satoshi, 松本真明, Nishiyama Masahiro, Hiroyuki Awano, Nagase Hiroaki, Iijima Kazumoto, Nishimura Noriyuki

  270回 日本小児科学会兵庫県地方会, May 2017, Japanese, 日本小児科学会, 尼崎, Domestic conference

  Oral presentation


• 早産児の臍帯由来間葉系幹細胞の増殖におけるWNTシグナル経路の役割

  岩谷壮太, Shono Akemi, Yamana Keiji, Khin Kyae Mon Thwin, 黒川大輔, Nishida Kosuke, Nishiyama Masahiro, 生田寿彦, 吉田牧子, 溝渕雅巳, Morioka Ichiro, Iijima Kazumoto, Nishimura Noriyuki

  第16回日本再生医療学会総会, May 2017, Japanese, 日本再生医療学会, 仙台, Domestic conference

  Oral presentation


• 前処置なしで造血幹細胞移植を行い混合キメラで推移しているX連鎖重症複合免疫不全症

  Mori Takeshi, 高藤 哲, 山本暢之, Nishimura Noriyuki, 金兼弘和, Iijima Kazumoto

  第30回近畿小児科学会, May 2017, Japanese, 日本小児科学会, 大阪, Domestic conference

  Oral presentation


• ブレオマイシン誘発肺障害モデルラットにおける臍帯由来間葉系幹細胞の効果

  Yamana Keiji, 岩谷壮太, 黒川大輔, Khin Kyae Mon Thwin, Nishida Kosuke, Nishiyama Masahiro, Shono Akemi, 生田寿彦, 吉田牧子, 溝渕雅巳, Morioka Ichiro, Iijima Kazumoto, Nishimura Noriyuki

  第16回日本再生医療学会総会, May 2017, Japanese, 日本再生医療学会, 仙台, Domestic conference

  Oral presentation


• A new evaluation index for left-right unequal ventriculomegaly in very low birth weight infants: Association with walking disabilities at 1.6 years of corrected age

  Ikuta T, Mizobuchi M, Katayama Yoshio, Yoshimoto S, Ioroi T, Yamane M, Morisawa T, Takatera A, Ueda M, Shibata A, Fujita Kaori, Nishimura Noriyuki, Iijima Kazumoto, Morioka Ichiro

  The 2nd Congress of joint European Neonatal Society, May 2017, English, MCA Scientific Events, Venice, Italy, International conference

  Poster presentation


• 臍帯由来間葉系幹細胞のWntシグナル経路の遺伝子発現は児の在胎週数により異なる

  Iwatani Souta, Kurokawa Daisuke, Yamana Keiji, 大山正平, Nishida Kosuke, 生田寿彦, 溝渕雅巳, Morioka Ichiro, Iijima Kazumoto, Nishimura Noriyuki

  第61回日本新生児成育医学会, Dec. 2016, Japanese, 日本新生児成育医学会, 大阪, Domestic conference

  Oral presentation


• PET-MRI所見に基づく肺・下鼻甲介・腎生検が原疾患の診断に有効であった二次性血球貪食リンパ組織球症の1例

  河原仁守, Bito Yuko, 会田洋輔, 橘木由美子, 中井優美子, Shimizu Nahoko, 真庭謙昌, Nishii Tatsuya, Itoh Tomoo, 藤村順也, Ninchoji Takeshi, 高藤 哲, 坊 亮輔, Yamamoto Nobuyuki, Mori Takeshi, Nishimura Noriyuki, Iijima Kazumoto

  第58回日本小児血液・がん学会学術集会, Dec. 2016, Japanese, 日本小児血液・がん学会, 東京, Domestic conference

  Poster presentation


• G-CSF投与と自家末梢血幹細胞移植を併用しbi-weekly VDC-IE療法を完遂し得た切除不能ユーイング肉腫例

  Yamamoto Nobuyuki, 坊 亮輔, 高藤 哲, Mori Takeshi, Nishimura Noriyuki, Ejima Yasuo, Hara Hitomi, Kawamoto Teruya, Akisue Toshihiro, Iijima Kazumoto

  第58回日本小児血液・がん学会学術集会, Dec. 2016, Japanese, 日本小児血液・がん学会, 東京, Domestic conference

  Oral presentation


• Reemergence of a translocation t(11;19)(q23;p13.1) in the absence of leukemia

  Saito A, Hasegawa D, Uemura S, Nino N, Takafuji S, Yokoi T, Tahara T, Tamura A, Kozaki A, Kishimoto K, Ishida Tatsuro, Kawasaki K, Yamamoto Nobuyuki, Mori Takeshi, Nishimura Noriyuki, Kosaka Y

  第79回日本血液学会学術集会, Oct. 2016, Japanese, 日本血液学会, 横浜, Domestic conference

  Poster presentation


• Aggressive double-hit leukemia/lymphoma with t(14;18)(q32;q21) and t(8;21)(q24;q11.2)

  Uemura S, Hasegawa D, Nino N, Takafuji S, Yokoi T, Tahara T, Tamura A, Saito A, Kozaki A, Kishimoto K, Ishida Tatsuro, Kawasaki K, Yamamoto Nobuyuki, Mori Takeshi, Hayakawa A, Nishimura Noriyuki, Kosaka Y

  第78回日本血液学会学術集会, Oct. 2016, Japanese, 日本血液学会, 横浜, Domestic conference

  Poster presentation


• 臍帯由来間葉系幹細胞を用いた脊髄性筋萎縮症の病態解析の試み

  Iwatani Souta, 福嶋祥代, 德田央士, Nishida Kosuke, Fujita Kaori, Yamana Keiji, Kurokawa Daisuke, 長坂美和子, 香田翼, Morioka Ichiro, Nishio Hisahide, Iijima Kazumoto, Nishimura Noriyuki

  第52回日本周産期・新生児医学会学術集会, Jul. 2016, Japanese, 日本周産期・新生児医学会, 富山, Domestic conference

  Poster presentation


• 極低出生体重児の正期産相当時頭部MRIにおける側脳室拡大と修正1歳6ヶ月時歩行確立との関連性

  生田寿彦, 溝渕雅巳, 芳本誠司, 五百蔵智明, 山根正之, 森沢猛, 片山義規, 高寺明弘, 上田雅章, 柴田暁男, 前山(藤田)花織, Nishimura Noriyuki, Morioka Ichiro

  第52回日本周産期・新生児医学会学術集会, Jul. 2016, Japanese, 日本周産期・新生児医学会, 富山, Domestic conference

  Oral presentation


• Rab6B mediates the progression of neuroblastoma through the interaction with MTMR5

  Nishimura Noriyuki, Pham TVH, Thwin KK, Yamamoto Nobuyuki, Mori Takeshi, Hayakawa A, Nishio Hisahide, Matsuo M, Hasegawa D, Kawasaki K, Kosaka Y, Iijima Kazumoto

  Advances in Neuroblastoma Research Conference 2016, Jun. 2016, English, Advances in Neuroblastoma Research Conference, Cairns, Australia, International conference

  Poster presentation


• DENN domain protein DENND2A regulates the progression of neuroblastoma.

  Yamamoto Nobuyuki, Thwin KK, Fujimura J, Nakanishi K, Mori Takeshi, Hayakawa A, Nishio Hisahide, Matsuo M, Hasegawa D, Kawasaki K, Kosaka Y, Iijima Kazumoto, Nishimura Noriyuki

  Advances in Neuroblastoma Research Conference 2016, Jun. 2016, English, Advances in Neuroblastoma Research Conference, Cairns, Australia, International conference

  Poster presentation


• Minimal residual disease monitoring in neuroblastoma patients.

  Nishimura Noriyuki, トゥインキン キモン, Yamamoto Nobuyuki, Mori Takeshi, 早川 晶, 長谷川 大一郎, 川崎 圭一郎, 小阪 嘉之, Nishio Hisahide, Iijima Kazumoto

  The 119th Annual Meeting of the Japan Pedeatric Society, May 2016, Japanese, Japan Pediatric Society, 札幌, Domestic conference

  Oral presentation


• 次世代シークエンサーによる重症心身障害者施設での原因遺伝子解析

  森貞直哉, 加藤 威, 加藤神奈, Shima Ai, Fujita Kaori, Nishimura Noriyuki, Nishio Hisahide, 和田博子, Iijima Kazumoto

  第119回日本小児科学会学術集会, May 2016, Japanese, 日本小児科学会, 札幌, Domestic conference

  Oral presentation


• 臍帯由来間葉系幹細胞における児の在胎週数による転写制御解析

  Iwatani Souta, 黒川大輔, Nishiyama Masahiro, 庄野朱美, 吉田牧子, 溝渕雅巳, Morioka Ichiro, Iijima Kazumoto, Nishimura Noriyuki

  第15回日本再生医療学会, Mar. 2016, Japanese, 日本再生医療学会, 大阪, Domestic conference

  Oral presentation


• 臍帯組織中に存在する多能性幹細胞Muse細胞の自己複製能と多分化能の検証

  串田良祐, 若尾昌平, 明石英雄, Nishimura Noriyuki, Iwatani Souta, Koda Tsubasa, Morioka Ichiro, 溝渕雅巳, Iijima Kazumoto, 出澤真理

  第15回日本再生医療学会, Mar. 2016, Japanese, 日本再生医療学会, 大阪, Domestic conference

  Oral presentation


• Differential expression of minimal residual disease markers in peripheral blood and bone marrow samples from high-risk neuroblastoma patients

  植村 優, Yamamoto Nobuyuki, 神前 愛子, 二野 菜々子, 高藤 哲, 横井 健人, 齋藤 敦郎, 石田 敏章, 長谷川 大一郎, 川崎 圭一郎, 小阪 嘉之, 平瀬 聡史, Mori Takeshi, Hayakawa Akira, Iijima Kazumoto, Nishio Hisahide, Nishimura Noriyuki

  The 57th Annual Meeting of the Japanese Society of Pediatric Hematology / Oncology, Nov. 2015, Japanese, The Japanese Society of Pediatric Hematology / Oncology, 甲府市, Domestic conference

  Oral presentation


• 外来化学療法中（ALL B12臨床試験）の中心静脈カテーテルの管理についての検討

  Yamamoto Nobuyuki, 堀之内智子, 藤村順也, Mori Takeshi, Hayakawa Akira, Nishimura Noriyuki, Iijima Kazumoto

  第57回日本小児血液がん学会学術集会, Nov. 2015, Japanese, 日本小児血液がん学会, 山梨, Domestic conference

  Poster presentation


• 「細胞移植の新たな展開」臍帯組織中に存在する多能性幹細胞Muse細胞の多能性の解析

  串田良祐, 若尾昌平, 明石英雄, Nishimura Noriyuki, Iwatani Souta, Koda Tsubasa, Morioka Ichiro, 溝渕雅巳, Iijima Kazumoto, 出澤真理

  第42回日本臓器保存生物医学会学術集会, Nov. 2015, Japanese, 日本臓器保存生物医学会, 盛岡, Domestic conference

  Public symposium


• Differential expression of minimal residual disease markers in peripheral blood and bone marrow samples from high-risk neuroblastoma patients.

  Suguru Uemura, Yamamoto Nobuyuki, Aiko Kozaki, Nanako Nino, Satoshi Takafuji, Takehito Yokoi, Atsuro Saito, Toshiaki Ishida, Daiichiro Hasegawa, Keiichiro Kawasaki, Yoshiyuki Kosaka, Mori Takeshi, Hayakawa Akira, Iijima Kazumoto, Nishio Hisahide, Nishimura Noriyuki

  第57回日本小児血液がん学会学術集会, Nov. 2015, Japanese, 日本小児血液がん学会, 山梨, Domestic conference

  Oral presentation


• DENN domain protein DENND2A mediates the progression of neuroblastoma

  Yamamoto Nobuyuki, 堀之内 智子, 藤村 順也, Mori Takeshi, Hayakawa Akira, 長谷川 大一郎, 小阪 嘉之, Nishio Hisahide, Iijima Kazumoto, Nishimura Noriyuki

  The 57th Annual Meeting of the Japanese Society of Pediatric Hematology / Oncology, Nov. 2015, Japanese, The Japanese Society of Pediatric Hematology / Oncology, 甲府市, Domestic conference

  Oral presentation


• 神戸市における成長ホルモン治療の適応と想定されるSGA性低身長症の発生頻度

  Morioka Ichiro, Fujita Kaori, Nagasaka Miwako, Koda Tsubasa, Iwatani Souta, Nishimura Noriyuki, 伊藤善也, 内野栄子, 白井千香, Iijima Kazumoto

  第49回日本小児内分泌学会学術集会, Oct. 2015, Japanese, 日本小児内分泌学会, 東京, Domestic conference

  Oral presentation


• 神戸市におけるLate-preterm児の3歳時低身長の発生頻度

  Morioka Ichiro, Nagasaka Miwako, Fujita Kaori, Koda Tsubasa, Iwatani Souta, Nishimura Noriyuki, 伊藤善也, 内野栄子, 白井千香, Iijima Kazumoto

  第49回日本小児内分泌学会学術集会, Oct. 2015, Japanese, 日本小児内分泌学会, 東京, Domestic conference

  Oral presentation


• 神経芽腫の発症・進展におけるRab6BとRab28の役割

  Nishimura Noriyuki, Yamamoto Nobuyuki, 長谷川大一郎

  第74回日本癌学会学術総会, Oct. 2015, Japanese, 日本癌学会, 名古屋, Domestic conference

  Oral presentation


• UBアナライザーとビリルビン誘導蛍光タンパク質（UnaG）を用いた新たなアンバウンドビリルビン測定法の開発

  Iwatani Souta, 中村 肇, 福嶋祥代, 德田央士, 西田浩輔, Fujita Kaori, 山名啓司, 黒川大輔, Nagasaka Miwako, Koda Tsubasa, Nishimura Noriyuki, Iijima Kazumoto, Morioka Ichiro

  第60回日本新生児成育医学会・学術集会, Oct. 2015, Japanese, 日本新生児成育医学会, 盛岡, Domestic conference

  Poster presentation


• Small-for-gestational age児の身長のキャッチアップ率：神戸市のpopulation-based縦断研究

  Morioka Ichiro, Fujita Kaori, Nagasaka Miwako, Koda Tsubasa, Iwatani Souta, Nishimura Noriyuki, 伊藤善也, 内野栄子, 白井千香, Iijima Kazumoto

  第49回日本小児内分泌学会学術集会, Oct. 2015, Japanese, 日本小児内分泌学会, 東京, Domestic conference

  Poster presentation


• Small-for-gestational ageを伴うlate-preterm児の3歳時低身長発生における出生身長の影響

  Morioka Ichiro, Nagasaka Miwako, Fujita Kaori, Koda Tsubasa, Iwatani Souta, Nishimura Noriyuki, 伊藤善也, 内野栄子, 白井千香, Iijima Kazumoto

  第49回日本小児内分泌学会学術集会, Oct. 2015, Japanese, 日本小児内分泌学会, 東京, Domestic conference

  Poster presentation


• Persistent MRSE infection and CV line-related thrombosis in AML patient in neutropenic phase.

  Mori Takeshi, Minamikawa Syogo, Yamamura S, Fujimura Junya, Horinouchi Tomoko, Yamamoto Nobuyuki, Hirase T, Kubokawa Ikuko, Hayakawa Akira, Nishimura Noriyuki, Iijima Kazumoto

  第77回日本血液学会学術集会, Oct. 2015, Japanese, 日本血液学会, 金沢, Domestic conference

  Oral presentation


• DENNドメイン蛋白質DENND2Aによる神経芽腫発の発症・進展の制御機構

  Yamamoto Nobuyuki, Nishimura Noriyuki, 長谷川大一郎

  第74回日本癌学会学術総会, Oct. 2015, Japanese, 日本癌学会, 名古屋, Domestic conference

  Oral presentation


• Contribution of cancer-associated fibroblasts and M2-polarized macrophages to neuroblastoma development

  Okito Hashimoto, Makiko Yoshida, Yu-Ichiro Koma, Tomoko Yanai, Daiichiro Hasegawa, Yoshiyuki Kosaka, Nishimura Noriyuki, Yokozaki Hiroshi

  18th ECCO - 40th ESMO European Cancer Congress, Sep. 2015, English, ECCO/ESMO, Vienna, Austria, International conference

  Poster presentation


• 臍帯組織中に存在する多能性幹細胞Muse細胞の多能性の解析

  串田良祐, 若尾昌平, 明石英雄, Nishimura Noriyuki, Iwatani Souta, Koda Tsubasa, Morioka Ichiro, 溝渕雅巳, Iijima Kazumoto, 出澤真理

  日本解剖学会第61回東北・北海道連合支部学術集会, Aug. 2015, Japanese, 日本解剖学会, 盛岡, Domestic conference

  Oral presentation


• Analysis of pluripotency in Muse cells derived from human umbilical cord tissue.

  Kushida Yoshihiro, Wakao Syohei, Akashi Hideo, Nishimura Noriyuki, Iwatani Sota, Koda Tsubasa, Morioka Ichiro, Mizobuchi Masami, Iijima Kazumoto, Dezawa Mari

  International society for stem cell research annual meeting, Jun. 2015, English, ISSCR, Stockholm, スウェーデン, International conference

  Poster presentation


• 左鎖骨部腫瘤を呈した生後6ヶ月の乳児例

  Mori Takeshi, 藤村順也, 堀之内智子, 南川将吾, 平瀬敏志, Yamamoto Nobuyuki, 久保川育子, Hayakawa Akira, Nishimura Noriyuki, Sakakibara Shunsuke, Terashi Hiroto, Iijima Kazumoto

  第265 回 日本小児科学会兵庫県地方会, May 2015, Japanese, 日本小児科学会兵庫県地方会, 神戸, Domestic conference

  Oral presentation


• 神経芽腫の進展における腫瘍関連炎症細胞と腫瘍関連間質細胞の相互作用の解明

  橋本興人, 吉田牧子, Koma Yuichiro, 矢内友子, 長谷川大一郎, 小坂嘉之, Nishimura Noriyuki, Yokozaki Hiroshi

  第104回日本病理学会総会, Apr. 2015, Japanese, The Japanese Sciety of Pathology, 名古屋, Domestic conference

  Oral presentation


• Two high-risk neuroblastoma cases with early detection of tumor relapse/re-growth by consecutive minimal residual disease monitoring.

  Saito Atsuro, Hirase Satoshi, Kozaki Aiko, Yanai Tomoko, Hasegawa Daiichiro, Kawasaki Keiichiro, Kosaka Yoshiyuki, Hayakawa Akira, Iijima Kazumoto, Nishio Hisahide, Nishimura Noriyuki

  The 11th Asian Society for Pediatric Research, Apr. 2015, English, Asian Society for Pediatric Research, 大阪, International conference

  Poster presentation


• Neuroblastoma minimal residual disease markers are differentially expressed in peripheral blood and bone marrow samples.

  Uemura Suguru, Yamamoto Nobuyuki, Kozaki Aiko, Yanai Tomoko, Hasegawa Daiichiro, Kawasaki K, Kosaka Yoshiyuki, Hayakawa Akira, Iijima Kazumoto, Nishio Hisahide, Nishimura Noriyuki

  The 11th Asian Society for Pediatric Research, Apr. 2015, English, Asian Society for Pediatric Research, 大阪, International conference

  Poster presentation


• A novel measurement method for serum unconjugated bilirubin concentrations using a bilirubin-inducible fluorescent protein.

  Iwatani Sota, Nakamura Hajime, Nishida Kosuke, Fujita Kaori, Yamana Keiji, Kurokawa Daisuke, Nagasaka Miwako, Koda Tsubasa, Osawa Kayo, Nishimura Noriyuki, Nishio Hisahide, Iijima Kazumoto, Kumagai Akiko, Miyawaki Atsushi, Morioka Ichiro

  Pediatric Academic Societies Annual Meeting, Apr. 2015, English, Pediatric Academic Societies, San Diego, アメリカ, International conference

  Poster presentation


• Identification of ALDH1A2 as a critical ALDH isoform in neuroblastoma cells with cancer stem cell phenotype

  Tri Budi Hartomo, Thi Van Huyen Pham, Yamamoto Nobuyuki, Satoshi Hirase, Hayakawa Akira, Daiichiro Hasegawa, Keiichiro Kawasaki, Yoshiyuki Kosaka, Masafumi Matsuo, Takeshima Yasuhiro, Iijima Kazumoto, Nishio Hisahide, Nishimura Noriyuki

  Pediatric Cancer at The Crossroad, Nov. 2013, English, American Association for Cancer Research, San Diego, USA, Purpose: Neuroblastoma is the most common extra-cranial solid tumor that accounts for ~15% of all cancer-related deaths in children. Despite current aggressive therapies, more than half of high-risk neuroblastoma patients have experienced a tumor relapse leading to mostly cancer-related deaths. As in most cancers, recurrent neuroblastoma is primarily driven by chemoresistant ca, International conference

  Poster presentation


• 神経芽腫症例におけるmultiple real-time RT-PCR markerを用いた微小残存病変(MRD)解析

  田中愛子, 長谷川大一郎, Tri Budi Hartomo, Yamamoto Nobuyuki, 宮田憲二, 越智智史, 斎藤敦郎, 山下達也, 石田敏章, 川崎圭一郎, 松尾雅文, Thi Van Huyen Pham, 大橋浩基, Mori Takeshi, 矢内友子, Hayakawa Akira, Takeshima Yasuhiro, 小阪嘉之, Iijima Kazumoto, Nishio Hisahide, Nishimura Noriyuki

  第54回日本小児血液・がん学会学術集会, Dec. 2012, Japanese, 日本小児血液・がん学会, 横浜, 【諸言】神経芽腫の予後は全体的には改善したが、進行例の長期予後は未だ不良であり、微小残存病変 (MRD) の正確 な評価が予後改善には不可欠である。今回我々は、MRD 検索の感度向上のため、multiple real-time RT-PCR marker を 用いた MRD 測定系を樹立し、各マーカーの感度、臨床情報との相関について解析を行った。【方法】既報の 11 の MRD マーカー (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B, TH) について、神経芽腫 tumor initiating cells を段階的に希釈して検量線を作成し 、基準値を設定した。倫理委員会の 承認の下、2011 年 2 月から 2012 年 6 月までに当科で経験した, Domestic conference

  Oral presentation


• Salbutamol modulates SMN2 expression in SMA fibroblast

  Harahap Imma, Nurputra Dian, 山本友人, 森川悟, Nishimura Noriyuki, Nishio Hisahide

  日本人類遺伝学会 第57回大会, Oct. 2012, English, The Japan Society of Human Genetics, 東京, [Background] Spinal muscular atrophy (SMA) is an autosomal recessive inherited neuromuscular disease that is caused by loss of the survival motor neuron gene, SMN1. Every SMA patient retains SMN2 which encodes the same protein (SMN) as SMN1 does. However, alternative splicing of SMN2 produces much amount of exon 7-lacking (△7) SMN2 transcript and hampers the production of ful, Domestic conference

  Oral presentation


• Rab15 alternative splicing correlates with differentiation of neuroblastoma cells.

  Hartomo TB, Pham TV, Hasegawa D, Kosaka Y, Hayakawa Akira, Takeshima Yasuhiro, Iijima Kazumoto, Matsuo M, Nishio Hisahide, Nishimura Noriyuki

  Advances in Neuroblastoma Research 2012 Conference, Jun. 2012, English, Tronto, Background: Neuroblastoma is characterized by its tumor heterogeneity driven by the differentiation of tumor-initiating cells (TICs) that can be isolated as spheres. Although many diagnostic and/or prognostic biomarkers have been proposed, the response of, International conference

  Poster presentation


• Minimal residual disease monitoring in neuroblastoma patients by a set of real-time RT-PCR markers.

  Tanaka A, Hasegawa D, Hartomo TB, Ishida Tatsuro, Kawasaki K, Kosaka Y, Iijima Kazumoto, Matsuo M, Nishio Hisahide, Nishimura Noriyuki

  Advances in Neuroblastoma Research 2012 Conference, Jun. 2012, English, Tronto, Background: Minimal residual disease (MRD) is derived from tumor-initiating cells (TICs) consisting of only a small population of tumor, and its activation leads to tumor relapse. Because over 50% of high-risk neuroblastoma patients experience tumor relap, International conference

  Poster presentation


• SMN2遺伝子量解析による予測よりも軽症の経過をとった脊髄性筋萎縮症患者に対するプロモーター解析

  森川 悟, Nakagawa Taku, 富永 康仁, 沖永 剛志, Nishimura Noriyuki, Takeshima Yasuhiro, 松尾 雅文, Nishio Hisahide

  The 54th Annual Meeting of the Japanese Sciety of Child Neurology, May 2012, Japanese, The Japanese Society of Child Neurology, 北海道, 【目的】脊髄性筋萎縮症（SMA）は，SMN2遺伝子コピー数が少なければ重症化することが報告されてきたが，SMN2遺伝子コピー数が少ない軽症例も存在する．一方，SMN1/2遺伝子プロモーターの塩基配列はすべて同一であると報告されてはいるが，十分には研究されてこなかった．今回，我々は，SMN2遺伝子コピー数以外の症状修飾因子を明らかにする目的で，SMN2遺伝子コピー数による予測よりも軽症の経過をとった症例について，プロモーター解析を行った．また，SMNI/2遺伝子プロモーター多型性の頻度についても報告する．【症例と方法】症例は2歳男児．1歳6か月時には伝い歩きが可能であった．遺伝子解析の結果，SMN1遺伝子は欠失し，SMN2遺伝子は2コピー存在していた．（1）症例のSMN2遺伝子プロモーター領域のダイレクトシークエンスを行った．（2）SMN1遺伝子欠失群, Domestic conference

  Oral presentation


• Molecular analysis of SMN genes in the patients who were clinically diagnosed as habing SMA.

  Nishio Hisahide, Nishimura Noriyuki, 森川悟, 山本友人, ヌルプトラ ディアン, Nakagawa Taku, Takeshima Yasuhiro, Iijima Kazumoto, 松尾雅文, 齊藤利雄

  第82回日本衛生学会総会, Mar. 2012, Japanese, 日本衛生学会, 京都, Domestic conference

  Poster presentation


• A study on anti-cancer effect of tea catechin against neuroblastoma fumor initiating cells.

  Nishimura Noriyuki, HARTOMO Tri Budi, 李明鎭, 長谷川大一郎, 小阪嘉之, Hayakawa Akira, Takeshima Yasuhiro, Iijima Kazumoto, 松尾雅文, Nishio Hisahide

  第82回日本衛生学会総会, Mar. 2012, Japanese, 日本衛生学会, 京都, Domestic conference

  Oral presentation


• A case of alveolar rhabdomyosarcoma mimicking acute leukemia of admission

  Yamamoto Nobuyuki, Yamamoto Nobuyuki, 平瀬 敏志, 平瀬敏志, 松野下夏樹, Mori Takeshi, Mori Takeshi, 矢内 友子, 矢内友子, Hayakawa Akira, Hayakawa Akira, Nishimura Noriyuki, Nishimura Noriyuki, Takeshima Yasuhiro, Takeshima Yasuhiro, Iijima Kazumoto, Iijima Kazumoto, 松尾雅文, 松尾 雅文

  第53回日本小児血液・がん学会学術集会, Nov. 2011, Japanese, 日本小児血液・がん学会, 前橋, Domestic conference

  Poster presentation


• SMN1遺伝子の片側アレルの欠失を認め、もう一方のアレルに点突然変異を認めた脊髄性筋萎縮症の1例

  Morikawa Aatoru, Nishimura Noriyuki, Nishio Hisahide

  日本小児科学会雑誌, Dec. 2010, Japanese


• SMN1遺伝子の片側アレルの欠失を認め、もう一方のアレルに点突然変異を認めた脊髄性筋委縮症の1例

  森川 悟, 山本 友人, Nishimura Noriyuki, Nishio Hisahide, Takeshima Yasuhiro, 松尾 雅文

  第250回日本小児科学会兵庫県地方会, May 2010, Japanese, 神戸, Domestic conference

  Oral presentation


• Rab8/13-JRAB/MICAL-L2 complexes control epithelial apical junctions

  Noriyuki Nishimura, Takuya Sasaki

  第81回日本生化学会大会・第31回日本分子生物学会年会合同大会, Dec. 2008, Japanese

  [Invited]


• 高次細胞機能発現におけるエキソサイトーシス系Rab ファミリー低分子量G蛋白質の作用機構

  佐々木卓也, 西村範行, 坂根亜由子

  第60回日本細胞生物学会大会, Jun. 2008, Japanese


• Actinin-4によるJRAB/MICAL-L2の細胞膜局在の制御機構

  中逵弘能, 西村範行, 山村里恵, 金山博臣, 佐々木卓也

  第66回日本癌学会総会, Oct. 2007, Japanese


• タイトジャンクションとアドヘレンスジャンクションの形成におけるJRAB/MICAL-L2とRab8/13の役割

  山村里恵, 西村範行, 中逵弘能, 荒瀬誠治, 佐々木卓也

  第66回日本癌学会総会, Oct. 2007, Japanese


• JRAB/MICAL-L2の細胞膜局在におけるactinin-4の役割

  中逵弘能, 西村範行, 山村里恵, 金山博臣, 佐々木卓也

  第59回日本細胞生物学会, May 2007, Japanese


• Doc2α modulates secretory lysosome exocytosis in mast cells

  東尾浩典, 西村範行, 石崎宏好, 三好淳, 坂根亜由子, 佐々木卓也

  第59回日本細胞生物学会, May 2007, Japanese


• Rab13結合蛋白質JRABによるタイトジャンクション形成の制御機構

  西村範行, 寺井智也, 神田郁乃, 佐々木卓也

  第65回日本癌学会総会, Sep. 2006, Japanese


• 上皮細胞の細胞分散(cell scattering)におけるRab13-JRAB系の役割

  神田郁乃, 西村範行, 寺井智也, 中西秀樹, 佐々木卓也

  第65回日本癌学会総会, Sep. 2006, Japanese


• Rabファミリー低分子量G蛋白質による細胞極性・接着の制御機構

  西村範行, 寺井智也, 坂根亜由子, 神田郁乃, 佐々木卓也

  第45回日本生化学会中国・四国支部例会, May 2004, Japanese


• Rabファミリー低分子量G蛋白質Rab13によるタイトジャンクションの接着分子Occludinの小胞輸送制御機構

  森本慎也, 西村範行, 佐々木卓也, 田代征記

  第104回日本外科学会定期学術集会, Apr. 2004, Japanese


• Rabファミリー低分子量G蛋白質によるタイトジャンクション膜蛋白質の小胞輸送の制御機構

  森本慎也, 西村範行, 北村弘子, 品原和加子, 山本恭代, 寺井智也, 坂根亜由子, 真鍋進治, 田代征記, 佐々木卓也

  第62回日本癌学会総会, Sep. 2003, Japanese


• 細胞極性と接着を支える小胞輸送の制御機構：Rabファミリー低分子量G蛋白質の役割

  佐々木卓也, 西村範行

  第56回日本細胞生物学会大会, May 2003, Japanese

• 神経芽腫のがん微小環境制御における間葉系幹細胞の役割に関する研究

  西村 範行, 山本 暢之

  日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 01 Apr. 2021 - 31 Mar. 2024

  神経芽腫は、神経堤細胞が交感神経系へ分化する過程で発生する代表的な小児難治性固形がんで、小児がん死亡の約1/6を占めている。特に、高リスク神経芽腫患者の大部分は、一旦は治療に反応して寛解を達成するが、その半数以上が再発して極めて治療困難になり、その長期生存率は未だ50%に達していない。これには、治療後に微小残存病変(MRD)として体内に残存したがん細胞が再活性化し、異なる形質を示すようになることが重要だと考えられる。化学療法や放射線療法は、治療後に亜致死となったがん細胞および微小環境中の間質細胞に細胞老化を誘導(治療誘発細胞老化：TIS)し、エクソソームやサイトカイン等の分泌(細胞老化随伴分泌現象：SASP)を促していることが明らかになり、治療困難のメカニズムを理解するためには、がん細胞の異なる形質の発現を担う分泌因子の同定が必須だと考えられる。これまでに申請者らは、MRDの新規評価法を開発してその動態を明らかにすると共に、神経芽腫細胞と微小環境の主要な構成細胞で分泌活性の高い間葉系幹細胞(MSC)との相互作用を明らかにしてきた。そこで本研究では、MSCのSASPによって分泌される分子を同定し、その機能を明らかにすることを試みる。本年度の研究では、高リスク神経芽腫治療に用いられるシスプラチン(CDDP)やテモゾロミド(TMZ)によるMSCのSASPによって分泌される分子群を同定した。


• Myostatin antisense nucleic acid therapy for rhabdomyosarcoma

  前田 和宏, 西村 範行, 松尾 雅文

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe Gakuin University, 01 Apr. 2021 - 31 Mar. 2024

  横紋筋肉腫(Rhabdomyosarcoma:RMS)は、筋原性の高悪性腫瘍で集学的治療により予後は改善した。しかし、治療抵抗群もあり、より効果的な治療法の開発が喫緊の課題である。ミオスタチンは筋肉の増殖を抑制するミオカインで、筋萎縮の治療法としてミオスタチン阻害に関する研究が盛んである。申請者は、ミオスタチン遺伝子(MSTN)のスプライシングを阻害してミオスタチンの産出を抑えるアンチセンス核酸(MSTN-ASO)の開発に成功した。このMSTN-ASOは想定通り筋芽細胞の増殖を促進した。一方で、同じMSTN-ASOがRMS細胞の増殖を阻害することを示唆する結果が得られていた。 今年度は、まず、RMS細胞でMSTN-ASOが増殖を阻害することを明確にした。RMS細胞のASOによる増殖阻害とMSTN発現レベルを比較した結果、MSTN-ASOによる増殖阻害はMSTNが発現しているRMS細胞でみられることが示された。MSTN-ASOによる増殖阻害がみられたRMS細胞ではMSTN-ASOによるMSTN mRNAの産生抑制と、ミオスタチンシグナルの低下が観察された。次にRMS細胞の増殖阻害を細胞周期に注目して検討を行った。細胞周期インジケーターFast-Fucciを利用し細胞周期停止を検証したところ、S期の進行が阻害されていることが示唆された。今後は細胞周期停止に関わる因子の同定とマウスxenograftモデルでの解析を進める。


• Role of Rab family small G proteins in the regulation of neuroblastoma microenvironment

  Nishimura Noriyuki

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2017 - 31 Mar. 2020, Principal investigator

  High-risk neuroblastoma causes more than 50% relapse and shows therapy resistance. This is mainly due to tumor heterogeneity that is induced by tumor microenvironment and therapy stress and controlled by Rab family small G proteins (Rabs), key regulators of membrane traffic. In the present study, we have identified some members of Rabs, which potentially control the secretion of growth factors and tumor markers in neuroblastoma microenvironment.

  Competitive research funding


• Dystrophin intron retention analysis to identify new targets for Antisense Oligonucleotide mediated RNA modulation in Rhabdomyosarcoma

  NIBA TABE EMMA EKO, AWANO HIROYUKI, NISHIMURA NORIYUKI

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), 01 Apr. 2016 - 31 Mar. 2019

  Dystrophin is regarded as a potential tumor suppressor gene because it was shown to be mutated in a variety of rhabdomyosarcoma and DMD patients sometimes develop some kind of tumors. Therefore, this project was intended to understand the significance of dystrophin as a tumor suppressor in rhabdomyosarcoma. In this project, the applicants showed that dystrophin intron retention was an important factor of rhabdomyosarcoma formation. They next, designed an antisense oligonucleotide to target the removal of this retained intron. Abolishment of the retained intron was successful. In addition, they showed that abolishing intron retention, increased dystrophin production of a carboxyl-terminal dystrophin isoform. Moreover, the cell proliferation of the rhabdomyosarcoma reduced drastically when intron retention was abolished. They equally demonstrated the cell specificity, sensitivity and specie specificity of the antisense oligonucleotide. This is antisense could be potential drug for RMS


• Role of DENND2A for development of neuroblastoma

  YAMAMOTO NOBUYUKI, Nishimura Noriyuki, Mori Takeshi, Kosaka Yoshiyuki

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B), Grant-in-Aid for Young Scientists (B), Kobe University, 01 Apr. 2016 - 31 Mar. 2018

  Neuroblastoma is a typical recurrent and refractory tumor in children and its long-term survival remains less than 40%. Neuroblastoma relapse is caused by activation of chemo-resistant cancer stem cells (CSCs). Key regulators of intracellular vesicle trafficking, DENN domain proteins, were implicated in this process. In this study, a member of DENND domain proteins DENND2A and its target Rab family small G protein Rab9B were found to be involved in the development and progression of neuroblastoma.


• Mesenchymal stem cell therapy for neonatal hypoxic ischemic encephalopathy

  Koda Tsubasa, IWATANI Sota, MORIOKA Ichiro, NISHIMURA Noriyuki

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B), Grant-in-Aid for Young Scientists (B), Kobe University, 01 Apr. 2014 - 31 Mar. 2017

  Treatments for neonatal hypoxic ischemic encephalopathy have been limited. Mesenchymal stem cells (MSCs) have significant potential for use in cell therapy for various diseases, through their ability to home to sites of injury, suppress immune responses, and undergo self-renewal and differentiation. The objective of this study is to characterize the gestational age-dependent change in MSCs from fetal tissues and to assess whether the MSCs could be useful for neonatal brain injury due to hypoxia or ischemia. First, we isolated umbilical cord-derived MSCs(UC-MSCs) from infants delivered at 22 to 40 weeks gestational age. UC-MSCs from preterm infants showed high proliferative capacity with increased levels of Wnt signaling pathway gene expression compared with those from term infants. Second, the lung injuries on rat model of bleomycin-induced hypoxemia and pulmonary fibrosis could be reduced by UC-MSCs, regardless of origin’s gestation.


• Targeting Rab family small G proteins as a novel neuroblastoma therapeutic approach

  Nishimura Noriyuki

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2014 - 31 Mar. 2017, Principal investigator

  More than half of high-risk neuroblastoma patients have experienced tumor relapses and their overall survival rates remain less than 40%. To improve their prognosis, it is necessary to develop a novel therapeutic approach targeting minimal residual disease (MRD) comprised of chemoresistant cancer stem cells (CSCs). In the present study, we have identified a member of Rab family small G proteins (Rabs), which control the development of neuroblastoma CSCs, and its effector protein. We have then characterized their upstream/downstream signaling pathways.

  Competitive research funding


• Role of DENN domain proteins in the development of neuroblastoma cancer stem cells.

  Yamamoto Nobuyuki, Nishimura Noriyuki, Hayakawa Akira, Kosaka Yoshiyuki, Yanai Tomoko

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B), Grant-in-Aid for Young Scientists (B), Kobe University, 01 Apr. 2014 - 31 Mar. 2016

  More than half of high-risk neuroblastoma patients experience tumor relapses and less than 40% can expect a long-term survival. Intracellular vesicle transport seems to play an important role on the development of neuroblastoma cancer stem cells that are responsible for tumor relapses. In this study, we focused on DENN domain proteins, regulators of intracellular vesicle transport, and revealed that a member of DENN domain proteins is involved in the progression of neuroblastoma.


• The development of new therapy for neonatal chronic lung disease using mesenchymal stem cells derived from fetal appendages.

  Mizobuchi Masami, NISHIMURA Noriyuki, MORIOKA Ichiro

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2013 - 31 Mar. 2016

  Chronic lung disease (CLD) of prematurity is a common and serious complication in preterm infants. To date, there is no effective treatment for CLD. Perinatal inflammation and regulation of the immune responses have been reported to play a crucial role in the development of CLD. Mesenchymal stem cells (MSCs) are multipotent stromal cells that can differentiate into a variety of cell types, including osteocytes, adipocytes and chondrocytes. Recently, MSCs have been reported to secrete a variety of factors that promote tissue repair and decrease inflammatory and immune reactions. The objective of study was to develop new therapy for CLD using MSCs isolated from fetal appendages in premature infants. In this study, we successfully established a simple and efficient method isolating MSCs from umbilical cord. Furthermore, to determine the effectiveness of MSCs for CLD, we developed an experimental animal model of intra-tracheal bleomycin-induced lung injury.


• Drug treatment for spinal muscular atrophy activating signal transduction pathways

  Nishio Hisahide, NISHIMURA Noriyuki, MORIKAWA Satoru

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2013 - 31 Mar. 2016

  Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder. SMA is caused by the loss of the SMN1 gene. Although the SMN2 gene also produces SMN protein, it is not enough to compensate for the loss of the SMN1 gene. Salbutamol (adrenergic drug) was reported to improve SMA symptoms. To clarify the mechanism, we treated SMA fibroblasts lacking the SMN1 gene with salbutamol, and analyzed SMN2 mRNA and SMN protein levels. Salbutamol increased SMN protein levels in a dose-dependent manner, although SMN2 mRNA levels were not changed. The salbutamol-induced increase in SMN protein level was blocked by PKA inhibitor and deubiquitinase inhibitor. Immunoprecipitation assay using HeLa cells showed that salbutamol decreased ubiquitinated SMN protein levels, suggesting that salbutamol inhibited ubiquitination. These findings suggest that salbutamol increases SMN protein levels in SMA cells by inhibiting ubiquitin-mediated SMN degradation via activating β2-adrenergic receptor-PKA pathways.

  Competitive research funding


• Role of Rab family small G proteins in the development of neuroblastoma cancer stem cells

  NISHIMURA Noriyuki, HAYAKAWA Akira, NISHIO Hisahide

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 2011 - 2013, Principal investigator

  More than 50% of high-risk neuroblastoma patients have experienced tumor relapses caused by chemoresistant cancer stem cells (CSCs). Consequently, their overall survival rates remain less than 40%. To improve their prognosis, it is essential to understand the molecular mechanism of how CSCs are generated and maintained in neuroblastoma. In the present study, we have focused on the key regulators of membrane traffic, Rab family small G proteins (Rabs), and identified a member of Rabs controlling the development of neuroblastoma CSCs.

  Competitive research funding


• Establishment of treatment strategy for spinal muscular atrophybased on the SMN2gene transcription control

  NISHIO Hisahide, TAKESHIMA Yasuhiro, NISHIMURA Noriyuki

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 2010 - 2012

  More than 95 % of spinal muscular atrophy (SMA) patients show homozygous deletion of SMN1. SMN2, a highly homologous gene of SMN1, compensates for the SMN1deletion to some degree; copy number of SMN2is inversely correlated to the clinical severity of SMA. Although the promoter sequences of the two genes are almost identical, c.-318 GCC insertion has been identified as a specific polymorphism to the SMN1 promoter. In this study, we found c.-318 GCC insertion polymorphism in the SMN2 promoter of an SMN1-deleted SMA patient with milder phenotype than expected for low copy number of SMN2. However, transcript amount of SMN2in the white blood cells was smaller than other five SMN1-deleted SMA patients, suggesting that the polymorphism did not increase the transcriptional activity. Besides, reporter gene assay using plasmid constructs with or without c.-318 GCC insertion polymorphism demonstrated that the polymorphism had a slightly negative effect on the transcription efficiency. In conclusion,c.-318 GCC insertion polymorphism in the SMN2 promoter may not be associated with the milder phenotype of the patient, suggesting the presence of non-SMN2-related modifying factors of SMA severity. Our experimental data using plasmid constructs with or without c.-318 GCC insertion polymorphism suggested that in thecase of medical treatment for SMA, it is necessary to change the kind and quantity of the SMN2 -activating medicine by the presence of c.-318 GCC insertion polymorphism.


• Role of Rab family small G proteins in determining the prognosis of neuroblastoma patients

  LEE Myeongjin, NISHIMURA Noriyuki, NISHIO Hisahide

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 2009 - 2011

  Neuroblastoma is an aggressive solid tumor that accounts for approximately 15% of all cancer-related deaths in children. More than half of high-risk neuroblastoma patients are estimated to experience relapses and their overall survival rates remain less than 40%. Identification of a new prognostic factor is essential to improve the prognosis of neuroblastoma patients. Aberrant alternative splicing is intimately associated with an increasing number of cancers, and its use as a new diagnostic and/or prognostic biomarker has attracted considerable attention. In the present study, we identified four alternatively spliced isoforms of Rab15, originally isolated as a brain-specific Rab protein. Rab15 isoform balance correlated with differentiation of neuroblastoma tumor-initiating cells(TICs) and Rab15 alternative splicing may serve as a biomarker to discriminate TICs from non-TICs in neuroblastoma.

  Competitive research funding


• Role of Rab13 binding protein JRAB/MICAL-L2 in regulating cell polarity and adhesion

  NISHIMURA Noriyuki

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), The University of Tokushima, 2008 - 2010

  Dynamic rearrangement of epithelial cell junctions, tight junction (TJ) and adherens junction (AJ), is essential to maintain the homeostasis of the organism in response to various stimuli. The transport of integral TJ and AJ proteins, claudins, occludins and cadherins, to and/or from the plasma membrane enables this rearrangement. We previously revealed that Rab13 and JRAB/MICAL-L2 (JRAB) mediated the endocytic recycling of occludin. In the present study, we identified Rab8 and actinin-4 as JRAB-binding proteins by using yeast two-hybrid screening. Rab13 and Rab8 competed with each other for the binding to JRAB and functionally associated with JRAB at the plasma membrane and recycling endosome, respectively. Furthermore, Rab13-bound JRAB was targeted to the plasma membrane through its binding to actinin-4. These results suggest that JRAB regulates epithelial cell polarity and adhesion through its binding to Rab13, Rab8 and actinin-4.


• ＳＭＮ２遺伝子転写制御を中核技術とする脊髄性筋萎縮症治療法の開発

  西尾 久英

  科学研究費補助金／基盤研究(C), 2010

  Competitive research funding


• Ｒａｂ１３結合蛋白質ＪＲＡＢ／ＭＩＣＡＬーＬ２による細胞極性・接着の制御機構

  西村 範行

  科学研究費補助金／基盤研究(C), 2009, Principal investigator

  Competitive research funding


• Role of Rab 13 and its effector in establishing cell polarity

  NISHIMURA Noriyuki

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), The University of Tokushima, 2006 - 2007

  Tight junction (TJ) and adherens junction (AJ) are located at the apical end of the basolateral membrane of polarized epithelial cells. During polarization, epithelial cells first form spot-like primordial AJ at the tips of the initial cell-cell contacts and develop belt-like mature AJ. In parallel with the maturation of AJ, TJ is formed at the apical side of AJ. Whereas epithelial polarization entails a complex interplay between the coordinated TJ and AJ assembly and several fundamental cellular processes, the transport of integral TJ and AJ proteins to and/or from the plasma membrane is essential for the control of TJ and AJ assembly. We previously reported that Rab 13 and a junctional Rab13-binding protein(JRAB)/molecule interacting with CasL-like 2 (MICAL-L2) mediated the endocytic recycling of an integral TJ protein occludin and the formation of functional TJ. In the present study, we examined the role of Rab13 and JRAB/MICAL-L2 in the transport of other integral TJ and AJ proteins claudin-1 and E-cadherin to the plasma membrane. Although knockdown of Rab13 specifically inhibited claudin-1 and occludin but not E-cadherin transport, knockdown of JRAB/MICAL-L2 and expression of its Rab13-binding domain(JRAB/MICAL-L2-C)retarded claudin-1, occludin, and E-cadherin transport. We then identified Rab8 as another JRAB/MICAL-L2-C-binding protein. Knockdown of Rab8 inhibited the Rab13-independent transport of E-cadherin to the plasma membrane. Rab13 and Rab8 competed with each other for the binding to JRAB/MICAL-L2 and functionally associated with JRAB/MICAL-L2 at the plasma membrane and recycling endosome, respectively. These results suggest that the interactions of JRAB/MICAL-L2 with Rab13 and Rab8 play a crucial role in establishing cell polarity.


• 多細胞生物の可塑性を支える小胞輸送の制御機構

  佐々木 卓也, 西村 範行

  日本学術振興会, 科学研究費助成事業 特定領域研究, 特定領域研究, 徳島大学, 2003 - 2007

  本研究では、Rabファミリー低分子量G蛋白質を中心とした細胞内小胞輸送の制御分子群に焦点を絞って解析し、多細胞生物の可塑性を支える小胞輸送の制御機構について解析を行った。情報の可塑性については、Rab3の活性制御蛋白質であるRab3GEPに直接結合し、Rab3GAPに間接的に結合するシナプス小胞蛋白質Rabconnection-3についてマウス個体と海馬の初代神経培養細胞を用いた解析を行い、本蛋白質がシナプス形成に関与している可能性を示す結果を得ている。一方、形態の可塑性については、これまでに私どもはタイトジャンクション(TJ)の細胞間接着分子であるoccludinのリサイクリングを制御するRab13-JRAB系を見出しているが、本年度はRab13-JRAB系がTJの今ひとつの接着分子claudinの輸送にも関与することを示した。さらに、JRABはRab13以外にRab8とも結合し、Rab8-JRAB系は、アドヘレンスジャンクションの接着分子E-cadherinの細胞膜への輸送に関与することを明らかにした。一方、これまでにJRABがアクチン細胞骨格系に沿って局在することを示していたが、本年度の本研究で、JRABがアクチン結合蛋白質のひとつであるアクチニン4と直接結合することを示した。また、JRABはアクチニン4と結合することによって細胞膜にリクルートされて接着分子の輸送に機能すること、その結合はRab13により促進されることを示した。このように、本年度の本研究は順調に進展し、当初の目的はほぼ達成できた。


• Role of Rab13 in regulating cell polarity and adhesion

  NISHIMURA Noriyuki

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), The University of Tokushima, 2004 - 2005

  Tight junctions (TJs) are continuous, circumferential belt-like structures located at the apical end of the intercellular space, where they delineate the boundaries between the apical and basolateral domains of the plasma membrane of epithelial cells. TJs are composed of integral TJ proteins and TJ plaque proteins. While integral TJ proteins including occludin and claudins mediate cell-cell adhesion and create physical intercellular barrier, TJ plaque proteins cluster integral TJ proteins and form an organizing platform for a variety of scaffolding, signaling, and vesicular transport proteins. Rab13 is identified as a TJ plaque protein in epithelial cells and is implicated in the assembly of functional TJs. We previously demonstrated that Rab13 specifically mediated the endocytic recycling of occludin. In the present study, we have identified MICAL-L2 (molecule interacting with CasL-like 2) as a novel Rab13-binding protein and renamed it as JRAB (junctional Rab13-binding protein). Immunoprecipitation and immunofluorescence microscopy showed that JRAB specifically bound to the GTP-bound form of Rab13 via its C-terminus, which contained a coiled-coil domain, and localized at TJs in epithelial MTD-1A cells. Recycling assay demonstrated that a JRAB mutant lacking the Rab13-binding domain (JRAB-N) specifically inhibited the endocytic recycling of occludin, but not transferrin receptor. Ca^<2+>-switch assay further revealed that JRAB-N as well as Rab13 Q67L inhibited the recruitment of occludin to the plasma membrane, the development of transepithelial electrical resistance, and the formation of a paracellular diffusion barrier. JRAB was displaced from TJs upon actin depolymerization in MTD-1A cells and was distributed along stress fibers in fibroblastic NIH3T3 cells. These results suggested that JRAB mediated the endocytic recycling of occludin and the formation of functional TJs by linking Rab13 to actin cytoskeleton.


• メンブレントラフィックにおけるタイトジャンクション膜タンパク質の選別機構

  西村 範行

  日本学術振興会, 科学研究費助成事業 特定領域研究, 特定領域研究, 徳島大学, 2003 - 2004

  タイトジャンクション(TJ)は、物理的に隣り合う細胞間隙の物質透過を制限し、細胞膜を頂端側と側基底側に分離すると共に、細胞膜上の膜ドメインとしてシグナル伝達分子を集積することによって、細胞極性を形成・維持している。TJを構成する膜タンパク質であるクローディンやオクルーディンは、細胞膜まで小胞輸送されてTJを形成すると考えられる。細胞内小胞輸送の代表的な制御系であるRabファミリー低分子量Gタンパク質(Rab)には60以上のメンバーが同定されており、個々のメンバーが特定の細胞内膜系に局在して小胞輸送および膜ドメインの形成を制御している。これまでに、TJ膜タンパク質と頂端側および側基底側膜タンパク質との選別機構を明らかにする目的で、TJに局在するRab13が、クローディンのゴルジ体から細胞膜への輸送およびオクルーディンのエンドソームから細胞膜へのリサイクリングを特異的に制御することを明らかにしてきた。そこで、本年度の研究では、Rab13の作用機構を明らかにする目的で、Rab13の標的タンパク質の同定を試み、以下の結果を得た。1)酵母Two-hybrid法を用いて、GTP結合型Rab13に特異的に結合する分子としてJRABを同定した。2)JRABは脳、肝臓、腎臓、肺に発現し、マウス乳腺上皮(MTD-1A)細胞のTJに局在した。3)JRABのRab13結合領域欠失変異体(JRAB-N)は、オクルーディンの細胞膜へのリサイクリングを特異的に抑制した。4)JRAB-Nは、カルシウムスイッチしたMTD-1A細胞における機能的TJの形成を抑制した。これらの結果から、Rab13は、標的タンパク質JRABを用いて、TJ膜タンパク質と頂端側および側基底側膜タンパク質との選別を制御していることが示唆された。このように、本年度の研究は予想以上に進展し、当初の目的はほぼ達成できた。


• Role of the Rab family small G proteins in cell polarity and adhesion

  NISHIMURA Noriyuki

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), The University of Tokushima, 2002 - 2003

  Tight junctions (TJs) are points of adhesion between epithelial cells that ensure the development and maintenance of the apical and basolateral plasma membrane (PM) domains. Proteins constituting TJs include the transmembrane proteins mediating cell-cell adhesion and the cytosolic plaque proteins linking to the cytoskeleton and participating in the intracellular signaling. Occludin and claudins constitute the transmembrane proteins in TJs. The Rab family small G proteins, which consist of more than 60 family members in mammalian cells, play a crucial role in etermining the specificity of vesicular transport pathways. Two Rab family members, Rab3B and Rab13, localize to TJs in polarized epithelial cells and cytoplasmic vesicular structures in non-polarized fibroblasts, but their functions are poorly understood. In the present study, we have examined the role of Rab3B and Rab13 in regulating the vesicular transport of TJ transmembrane proteins. In the exocytotic pathways, we found that Rab3B and Rab13 direct th cell-surface transport of a basolateral transmembrane protein, low-density lipoprotein receptor, and claudin-1, respectively. We also found that a pool of occludin was continuously endocytosed and recycled back to the cell-surface in epithelial cells. Our results indicated that Rabl3, but not Rab3B, specifically regulated the endocytic recycling of occludin. Biochemical endocytosis and recycling assays demonstrated that Rab13 directed the recycling of endocytosed occludin, but not its endocytosis. Furthermore, we found that Rab13 did not affect the recycling of transferrin receptor, that was recycled to the basolateral PM domain. We isolated a protein that was specifically interacted with GTP-bound form of Rab13, but not its GDP-bound form. Our results suggested that Rab13 was a crucial regulator for the transport of occludin and claudins to TJs.


• 小胞体における積み荷タンパク質の選別機構?輸送シグナルをプローベとして

  西村 範行

  日本学術振興会, 科学研究費助成事業 特定領域研究, 特定領域研究, 徳島大学, 2002 - 2002

  細胞膜タンパク質は、小胞体において積み荷として選別され、さらにゴルジ体の最もトランス側に位置するトランスゴルジ(TGN)において、異なる輸送小胞へ選別されて細胞膜へ輸送される。これまでに、水疱性口内炎ウィルスの糖タンパク質(VSV-G)を細胞膜タンパク質のモデルとして、小胞体〜ゴルジ体間の小胞輸送はシグナル依存的な選択的輸送であること、および、VSV-Gの小胞体からの輸送シグナル(YxDxEシグナル)は、小胞体から発芽するCOPII輸送小胞へVSV-Gを濃縮していることを明らかにしてきた。そこで、本年度の本研究では、YxDxEシグナルの作用機構を明らかにする目的で、YxDxEシグナルを認識する分子の同定を試み、以下の結果を得た。1)酵母Two-hybrid法を用いて、アダプター複合体AP-3のδサブユニットをYxDxEシグナルに結合する分子として同定した。2)YxDxEシグナルとδサブユニットとの結合は、酸性のアスパラギン酸とグルタミン酸のみならずタイロシンにも依存した。3)δサブユニットのVSV-G結合領域を含む欠失変異体は、VSV-Gの小胞体〜ゴルジ体間輸送には作用せず、ゴルジ体〜細胞膜間輸送を特異的に抑制した。4)δサブユニットを欠失したMochaマウスから調製したfibroblastsでは、VSV-Gの小胞体〜ゴルジ体間輸送は正常で、ゴルジ体〜細胞膜間輸送に障害が認められた。5)VSV-Gは、アダプター複合体AP-3依存的にライソソームへ輸送されるLAMP1を細胞膜へミスターゲッティングさせた。これらの結果から、YxDxEシグナルは、小胞体においてはCOPIIコートを、TGNにおいてはアダプター複合体AP-3をシークエンシャルにそれぞれリクルートして、VSV-Gの細胞膜への輸送を制御していることが示唆された。このように、本年度の研究は予想以上に進展し、当初の目的はほぼ達成できた。

• 神経芽腫の微小残存病変を評価するために用いられる試薬、およびそれを用いた生体試料の分析方法

  西村 範行

  JP2017045715, 20 Dec. 2017, 国立大学法人神戸大学, WO2018-123764, 05 Jul. 2018

  Patent right

  IRI