Department of Pediatrics
Department of Developmental Pediatrics
Professor
Takashi Igarashi, M.D., Ph.D.
Associate Professor
Tsutomu Iwata, M.D., Ph.D., Masashi Mizuguchi, M.D., Ph.D.
Lecturers
Hiroshi Watanabe, M.D., Ph.D., Hitoshi Kato, M.D., Ph.D.
Masaru Takamizawa, M.D., Ph.D., Takashi Sekine, M.D., Ph.D.
Associates
Fusako Komoda, M.D., Kazuhiko Shibuya, M.D., Ph.D.
Komei Ida, M.D., Yoshitaka Yokoyama, M.D.
Hiroko Sugimura, M.D., Junko Takita, M.D., Ph.D.
Katsuyoshi Ko, M.D., Keiji Goishi, M.D.
Jun Inatomi, M.D., Sunao Tomita, M.D.
Masahisa Toda, M.D., Ph.D., Hiroshi Ono, M.D.
Utako Fukuoka, M.D., Fumie Tateshita, M.D.
Nobuyasu Shimizu, M.D., Ryo Inuzuka, M.D.

Introduction
The former Department of Pediatrics developed into Department of Pediatrics and Department of Developmental Pediatrics, which comprise subgroups of the Group of Reproductive, Developmental and Aging Medicines, Graduate School of Medicine, the University of Tokyo.
Our staff consist of 1 professor, 2 associate professors, 4 lecturers, 16 associates, 6 residents, 1 clinical fellow, 1 research fellow, 12 graduate students and 1 foreign pediatrician as of Dec 1, 2004.
The outpatient clinic of our department is located on the second floor of the outpatient clinic building. The inpatient ward and conference rooms are located on the second floor of the inpatient clinic building. Offices are on the second and third floors of the East Research Building. Our laboratories are located on the second, third and fourth floors of the Research Building of Internal Medicine and on the second and third floors of the East Research Building.

Education
The staff members and the visiting lecturers give lectures of general pediatrics and pediatric diagnosis for 36 hours to the second year students, and clinical bedside learning in the inpatient ward for 2 weeks to the third year students. During bedside learning for 2 weeks, specialized teaching sessions, which are a kind of seminar, are held every day. In the outpatient learning, medical students take histories and perform physical examinations of patients under the supervision of the teaching staff. On the second and third days of the outpatient clinic, each student visits the local pediatricians or local hospitals in and around Tokyo. On the last day of clinical learning, the Professor and an Associate Professor evaluate the students' achievements. We have an elective clinical clerkship course for the third year students.

Research
Our departments have the following research groups as cardiology, hematology/oncology, neurology, endocrinology, immunology, nephrology, hepatology and international medical cooperation. We also have multidisciplinary research groups and laboratories such as cell biology, genetic molecular biology and epidemiology. The main subjects of research during the last few years are listed as follows: molecular and epidemiological analysis of cancer disposition, molecular analysis of hereditary renal diseases, primary immunodeficiency, neuromuscular diseases and certain syndromes with and without congenial cardiac defects, hemodynamics of pulmonary circulation, and electrophysiological studies of epidemic disorders. The Kanto district registration center for children's cancer is located in our Department.

Clinical Activities
We have specialized outpatient clinics covering all pediatric fields in addition to general pediatrics. In the pediatric and pediatric surgery ward, there are 96 beds including 9 beds in the neonatal intensive care unit (NICU), 6 beds in the growth care unit (GCU) and 26 beds in the high care unit (HCU). In NICU we are taking care of small premature babies weighing 400g to 3,000g with or without various complications. A variety of patients with diseases such as hematological/oncological disorders (acute leukemia, neuroblastoma, Ewing sarcoma, osteosarcoma, brain tumors, etc.), cardiac disorders (congenital heart diseases and Kawasaki disease), neuromuscular disorders, metabolic disorders, immunological/allergic disorders (common variable immunodeficiency, chronic granulomatous disease, bronchial asthma, etc.), renal and urinary tract diseases (nephrotic syndrome, chronic glomeluronephritis, purpura nephritis and renal and urinary tract anomalies), endocrinological disorders and psychosomatic diseases are admitted in the wards. So far 70 patients received hematopoietic stem cell transplantation. There are patients with severe combined immunodeficiency, aplastic anemia-myelodysplastic syndrome, acute lymphocytic leukemia with high-risk features, acute myelogenous leukemia, non-Hodgkin lymphomas, disseminated neuroblastoma and brain tumors.
We have a clinical conference and a grand round once a week. We also join in conferences several times a month with cardiac surgeons, obstetricians, pediatric surgeons and pediatric psychologists. In addition, each subspecialty group has its own meeting and clinical round.
Many patients with significant disorders inevitably stay for a long time in the hospital. We provide an official in-hospital school "Kodama Gakkyu" where patients receive education and have chances to communicate with each other and their parents in the hospital. "Niko-niko Volunteer" members, an official volunteer group in the hospital, visit the pediatric ward every weekday to play with the patients and help their mothers. It is a great pleasure for both the patients and their mothers. We also provide various activities for the patients in the hospital such as the Tanabata festival, a Christmas party and music concerts. All the residents, fellows and nurses participate in these activities.
(As of Dec 1, 2004)

References
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  2. Babu E, Takeda M, Narikawa S, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Sakthisekaran D, Endou H : Human organic anion transporters mediate the transport of tetracycline. Jpn J Pharmacol 88:69-76, 2002
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  4. Chandler WL, Jelacic S, Boster D, Ciol M, Watkins S, Igarashi T, Tarr PI: Prothrombotic coagulation abnormalities preceding the hemolytic uremic syndrome.New Eng J Med 246: 23-32, 2002
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  14. Kano H, Mizuta K, Sakakihara Y, Kato H, Miki Y, Shibuya N, Saito M, Narita M, Kawarasaki H, Igarashi T, Hasizume K, Iwata T. Efficacy and safety of immunization for pre- and post- liver transplant children. Transplantation 74: 543-550, 2002
  15. Kitagawa Y, Inoue K, Sasaki S, Hayashi Y, Matsuo Y, Lieber MR, Mizoguchi H, Yokota J, Kohno T. Prevalent involvement of illegitimate V(D)J recombination in chromosome 9p21 deletions in Lymphoid Leukemia. J Biol Chem. 277: 46289-46297, 2002
  16. Kobayashi Y, Hirokawa N, Ohshiro N, Sekine T, Sasaki T, Tokuyama S, Endou H, Yamamoto T: Differential gene expression of organic anion transporters in male and female rats. Biochem Biophys Res Commun 290:482-487, 2002
  17. Kobayashi Y, Ohshiro N, Shibusawa A, Sasaki T, Tokuyama S, Sekine T, Endou H, Yamamoto T: Isolation, characterization and differential gene expression of multispecific organic anion transporter 2 in mice. Mol Pharmacol 62:7-14, 2002
  18. Kojima R, Sekine T, Kawachi M, Cha SH, Suzuki Y, Endou H: Immunolocalization of multispecific organic anion transporters, OAT1, OAT2, and OAT3, in rat kidney. J Am Soc Nephrol 13:848-857, 2002
  19. Kobayashi Y, Hirokawa N, Ohshiro N, Sekine T, Sasaki T, Tokuyama S, Endou H, Yamamoto T: Differential gene expression of organic anion transporters in male and female rats. Biochem Biophys Res Commun 290:482-487, 2002
  20. Kuroki K, Tsuchiya N, Tsao BP, Grossman JM, Fukazawa T, Hagiwara K, Kano H, Takazoe M, Iwata T, Hashimoto H, Tokunaga K. Polymorphisms of human CD19 gene: possible association with susceptibility to systemic lupus erythematosus in Japanese. Genes Immun 3 (Suppl 1): S21-S30, 2002
  21. Macara IG, Baldarelli R, Field CM, Glotzer M, Hayashi Y, Hsu SC, Kennedy MB, Kinoshita M, Longtine M, Low C, Maltais LJ, McKenzie L, Mitchison TJ, Nishikawa T, Noda M, Petty EM, Peifer M, Pringle JR, Robinson PJ, Roth D, Russell SE,Stuhlmann H, Tanaka M, Tanaka T, Trimble WS, Ware J, Zeleznik-Le NJ, Zieger B. Mammalian septins nomenclature. Mol Biol Cell 13:4111-4113, 2002
  22. Norden AGW, Lapsley M, Christensen EI, Igarashi T, Matsuyama T, Shiraga H, Kelleher CL, Lee P, Scheinman SJ, Thakker RV, Unwin RJ, Verroust P, Wrong O, Moestrup S: Urinary megalin deficiency implicates abnormal tubular endocytic receptor trafficking in the Fanconi syndrome. J Am Soc Nephrol 13: 125-133, 2002
  23. Ono R, Taki T, Taketani T, Kawaguchi H, Taniwaki M, Okamura T, Kawa K, Hanada R, Kobayashi M, Hayashi Y. SEPTIN6, a human homologue to mouse septin 6, is fused to MLL in infant acute myeloid leukemia with complex chromosomal abnormalities involving 11q23 and Xq24. Cancer Res 62:333-337, 2002.
  24. Ono R, Taki T, Taketani T, Taniwaki M, Kobayashi H, Hayashi Y. LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23). Cancer Res. 62:4075-4080., 2002
  25. Saito M, Fukushima Y, Tatsumi K, Lin B, Fujiki Y, Iwamori M, Igarashi T, Sakakihara Y. Molecular cloning of Chinese hamster ceramide glucosyltransferase and its enhanced expression in peroxisome-defective mutant Z65 cells. Archives of Biochemistry and Biophysics 403:171-178, 2002
  26. Shibuya N, Shibuya K, Kato H, Yanagisawa M: Kawasaki disease before Kawasaki at Tokyo University Hospital. Pediatrics: 110:e17, 2002
  27. Sugatani J, Komiyama N, Mochizuki T, Hoshino M, Miyamoto D, Igarashi T, Hoshi S, Miwa M: Urinary concentrating defect in rats given Shiga toxin: elevation in urinary AQP2 level associated with polyuria. Life Sci 71:171-189, 2002
  28. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther 302:666-671, 2002
  29. Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Endou H : Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther 300:918-924, 2002
  30. Takeshita K, Nagamine T, Thuy DHD, Satow T, Matsuhashi M. Yamamoto J, Takayama M, Fujiwara N, Shibasaki H: Maturational change of parallel auditory processing in school-aged children revealed by simultaneous recording of magnetic and electric cortical responses. Clin Neurophysiol 113:1470-1484, 2002
  31. Taketani T, Taki T, Shibuya N, Ito E, Kitazawa J, Terui K, Hayashi Y: The HOXD11 gene is fused to the NUP98 gene in acute myeloid leukemia with the t(2;11)(q31;p15). Cancer Res 62:33-37, 2002
  32. Taketani T, Taki T, Ono R, Kobayashi Y, Ida K, Hayashi Y. The t(7;11)(p15;p15) n acute myeloid leukemia results in fusion of the NUP98 gene with a HOXA cluster gene, HOXA13, but not HOXA9. Genes Chromosomes Cancer 34: 437-443, 2002
  33. Taketani T, Taki T, Shibuya N, Kikuchi A, Hanada R, Hayashi Y: Novel NUP98-HOXC11 fusion gene resulted from a chromosomal break within exon 1 of HOXC11 in acute myeloid leukemia with t(11;12)(p15;q13). Cancer Res. 62:4571-4574, 2002
  34. Taketani T, Taki T, Takita J, Ono R, Horikoshi Y, Kaneko Y, Sako M, Hanada R, Hongo T, Hayashi Y. Mutation of the AML1/RUNX1 gene in a transient myeloproliferative disorder patient with Down syndrome. Leukemia. 16:1866-1867, 2002
  35. Tran TD, Inui K, Hoshiyama M, Lam K, Kakigi R: Conduction velocity of the spinothalamic tract following CO2 laser stimulation in humans. Pain 95: 125-131, 2002
  36. Uno K, Takita J, Yokomori K, Tanaka Y, Ohta S, Shimada H, Gilles FH, Sugita K, Abe S, Sako M, Hashizume K, Hayashi Y. Aberrations of the hSNF5/INI1 gene are restricted to malignant rhabdoid tumors or atypical teratoid/rhabdoid tumors in pediatric solid tumors. Genes Chromosomes Cancer 34: 33-41,2002
  37. Yoshimura C, Yamaguchi M, Iikura M, Izumi S, Kudo K, Nagase H, Ishii A, Walls AF, Ra C, Iwata T, Igarashi T, Yamamoto K, and Hirai K: Activation markers of human basophils: CD69 expresshin is strongly and preferentially induced by IL-3. J Allergy Clin Immunol 109: 817-823, 2002
  38. Araki S, Hayashi M, Tamagawa K, Saito M, Kato S, Komori T, Sakakihara Y, Mizutani T, Oda M: Neuropathological analysis in spinal muscular atrophy type I, Acta Neuropathol (Berl) 106:441-448, 2003
  39. Chen YY, Takita J, Chen YZ, Yang HW, Hanada R, Yamamoto K, Hayashi Y. Genomic structure and mutational analysis of the human KIF1Balpha gene located at 1p36.2 in neuroblastoma. Int J Oncol. 23: 737-744, 2003
  40. Echlin-Bell DR, Smith LL, Li L, Strissel PL, Strick R, Gupta V, Banerjee J, Larson R, Relling MV, Raimondi SC, Hayashi Y, Taki T, Zeleznik-Le N, Rowley JD. Polymorphisms in the MLL breakpoint cluster region (BCR). Hum Genet 113: 80-91, 2003
  41. Hayashi Y: Gene expression profiling in childhood acute leukemia; Progress and perspectives. Int J Hematol 78:414-420, 2003
  42. Hirose H, Arayama T, Takita J, Igarashi T, Hayashi Y, Nagao Y. A family of episodic ataxia type 2: no evidence of genetic linkage to the CACNA1A gene. Int J Mol Med. 11: 187-189, 2003
  43. Hirose H, Kubota M, Kimura I, Yumoto M, Sakakihara Y: N100m in children possessing absolute pitch. Neuro Report 14:899-903, 2003
  44. Hirose Y, Kudo K, Kiyoi H, Hayashi Y, Naoe T, Kojima S. Comprehensive analysis of gene alterations in acute megakaryoblastic leukemia of Down's syndrome. Leukemia. 17: 2250-2252, 2003
  45. Hiwatari M, Taki T, Taketani T, Taniwaki M, Sugita K, Okuya M, Eguchi M, Ida K, Hayashi Y: Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23). Oncogene. 22: 2851-2855, 2003
  46. Kato H, Katori T, Nakamura Y, Kawarasaki H: Moderate-Term Effect of Epoprostenol on Severe Portopulmonary Hypertension. Pediadric Cardiology. 24:50-53, 2003
  47. Moulin P, Igarashi T, Van der Smissen P, Cosyns JP, Verroust P, Thakker RV, Scheinman SJ, Courtoy PJ, Devuyst O: Altered polarity and expression of H+-ATPase without ultrastructural changes in kidney of Dent's disease patients. Kidney Int 63: 1285-1295, 2003
  48. Nagura M, Nagao Y, Takita J, Igarashi T, LeGuern E, Hayashi Y. The kinesin superfamily protein Rab6KIFL is not involved in the pathophysiology of Charcot-Marie-Tooth disease type 4C. Int J Mol Med 11: 45-47, 2003
  49. Obana K, Yang HW, Piao HY, Taki T, Hashizume K, Hanada R, Yamamoto K, Tanaka Y, Toyoda Y, Takita J, Tsuchida Y, Hayashi Y: Aberrations of p16INK4A, p14ARF and p15INK4B genes in pediatric solid tumors. Int J Oncol 23: 1151-1157, 2003
  50. Ozawa H, Kodama H, Kawaguchi H, Mochizuki T, Kobayashi M, Igarashi T: Renal function in patients with Menkes disease. Eur J Pediatr 162: 51-52, 2003
  51. Satoh H, Moriyama N, Hara C, Yamada H, Horita S, Kunimi M, Tsukamoto K, Iso-O N, Inatomi J, Kawakami H, Kudo A, Endou H, Igarashi T, Goto A, Fujita T, Seki G: Localization of Na+/HCO3- cotransporter (pNBC-1) variants in rat and human pancreas. Am J Physiol Cell Physiol 284: C729-C737, 2003
  52. Taketani T, Taki T, Takita J, Tsuchida M, Hanada R, Hongo T, Kaneko T, Manabe A, Ida K, Hayashi Y. AML1/RUNX1 mutations are infrequent, but related to AML-M0, acquired trisomy　21, and leukemic transformation in pediatric hematologic malignancies. Genes Chromosomes Cancer 38: 1-7, 2003.
  53. Terui K, Kitazawa J, Takahashi Y, Tohno C, Hayashi Y, Taketani T, Taki T, Ito E. Successful treatment of acute myelomonocytic leukaemia with NUP98-HOXD11 fusion transcripts and monitoring of minimal residual disease. Br J Haematol. 120: 274-276, 2003
  54. Tsutsumi S, Taketani T, Nishimura K, Ge X, Taki T, Sugita K, Ishii E, Hanada R, Ohki M, Aburatani H, Hayashi Y: Two distinct gene expression signatures in pediatric acute lymphoblastic leukemia with MLL rearrangements. Cancer Res. 63: 4882-4887, 2003
  55. Xinh PT, Tri NK, Nagao H, Nakazato H, Taketazu F, Fujisawa S, Yagasaki F, Chen YZ, Hayashi Y, Toyoda A, Hattori M, Y Sakaki Y, Tokunaga K, Sato Y: The breakpoints at 1p36.3 detected with BAC/PAC probes in three MDS/AML(M4) patients with t(1;3)(p36;q21) translocation: in the first intron and in the 5' region of MEL1, Genes Chromosomes Cancer 36: 313-317, 2003
  56. Xu G, Nagano M, Kanezaki R, Toki T, Hayashi Y, Taketani T, Taki T, Mitui T, Koike K, Kato K, Imaizumi M, Sekine I, Ikeda Y, Hanada R, Sako M, Kudo K, Kojima S, Ohneda O, Yamamoto M, Ito E: Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down's syndrome. Blood. 102: 2960-2968, 2003
  57. Yoshimura-Uchiyama C, Yamaguchi M, Nagase H, Fujisawa T, Ra C, Matsushima K, Iwata T, Igarashi T, Yamamoto K, Hirai K: Comparative effects of basophil-directed growth factors. Biochem Biophys Res Comm 302: 301-206, 2003
  58. Yoshimura-Uchiyama C, Yamaguchi M, Nagase H, Matsushima K, Igarashi T, Iwata T, Yamamoto K, Hirai K: Changing expression of IL-3 and IL-5 receptors in cultured human eosinophils. Biochem & Biophy Res Comm 309:26-31, 2003
  59. Basnet NB, Kato H, Nakamura Y, Watanabe H, Igarashi T: Newspaper reporting on child raising in Japan. J Pediatr Nursing 19: 113-120, 2004
  60. Jouret F, Igarashi T, Gafflot F, Wilson PD, Karet FE, Thakker R, Devuyst O: Comparative ontogeny, processing, and segmental distribution of the renal chloride channel, ClC-5. Kidney Int 65: 198-208, 2004
  61. Kano H, Ito Y, Matsuoka K, Nakajima T, Iwata T, Kohsaka T, Saito H, and Abe J: Critical role of T cell migration in bacterial superantigen-mediated shock in mice. Clinical Immunology 110:159-171, 2004
  62. Kitanaka S, Miki Y, Hayashi Y, Igarashi T: Promotor-specific repression of hepatocyte nuclear factor (HNf)-1 beta and NHF-1alpha transcriptional activity by an HNF-1 beta missense mutant associated with Type 5 maturity-onset diabetes of the young with hepatic and biliary manifestations. J Clin Endcrinol Metab 89:1369-1378, 2004
  63. Matsuyama T, Awazu M, Oikawa T, Inatomi J, Sekine T, Igarashi T: Molecular and clinical studies of Dent's disease in Japan: biochemical examination and renal ultrasonography do not predict carrier state. Clin Nephrol 61: 231-237, 2004
  64. Nagura M, Saito M, Iwamori M, Sakakihara Y, Igarashi T: Alterations of fatty acid metabolism and membrane fluidity in peroxisome-defective mutant ZP102 cells. Lipids 39:43-50, 2004
  65. Ohta T, Sakano T, Igarashi T, Itami N, Ogawa T: Exercise-induced acute renal failure associated with renal hypouricemia: results of a questionnaire-based survey in Japan. Nephrol Dial Transplant 19:1447-1453, 2004
  66. Komoda F, Sekine T, Inatomi J, Enomoto A, Endou H, Ota T, Matsuyama T, Ogata T, Ikeda M. Awadzu M, Muroya K, Kamimaki I, Igarashi T: The W258X mutation in SLC22A is the predominant cause of Japanese renal hypouricemia. Pediatr Nephrol 19:728-733, 2004
  67. Inatomi J, Horita S, Braverman N, Sekine T, Yamada H, Suzuki Y, Kawahara K, Moriyama N, Kudo A, Kawakami H, Shimadzu M, Endou H, Fujita T, Seki G, Igarashi T: Mutational and functional analysis of SLC4A4 in a patient with proximal renal tubular acidosis. Pfluger Arch Eur J Physiol 448:438-444, 2004
  68. Basnet NB, Noma S, Basnet SB, Igarashi T: Neonatal intensive care unit hospitalization of very low birth weight Japanese infants with congenital heart disease. J Nepal Med Asso 43:28-30, 2004
  69. Miyazaki H, Sekine T, Endou H: The multispecific organic anion transporter family: properties and pharmacological significance. Trends Pharmacol Sci 25:654-662, 2004
  70. Mizuguchi M, Mori M, Nozaki Y, Momoi MY, Itoh M, Takashima S, Hino O. Absence of allelic loss in cytomegalic neurons of cortical tuber in the Eker rat model of tuberous sclerosis. Acta Neuropathologica 107:47-52, 2004
  71. Saito Y, Yamamoto T, Ohtsuka-Tsurumi E, Oka A, Mizuguchi M, Itoh M, Voit T, Kato Y, Kobayashi M, Saito K, Osawa M. Fukutin expression in non-muscle somatic organs: distribution pattern in mouse and its relationship to the hypoglycosylation of??-dystroglycan in Fukuyama-type congenital muscular dystrophy. Brain and Development 26: 469-479, 2004
  72. Wei J, Chiriboga L, Mizuguchi M, Yee H, Mittal K. Expression profile of tuberin and some potential tumorigenic factors in 60 patients with uterine leiomyomata. Modern Pathology 2004 (in press)
  73. Mizuguchi M, Itoh S, Ozawa H. An 11-month-old girl with arrested psychomotor development and lactic acidosis. Neuropathology 24:103-106, 2004
     
Annual Report of the Graduate School of Medicine and The Faculty of Medicine The University of Tokyo Reports for the Period April 2002 - March 2004