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2001 Fiscal Year Final Research Report Summary

Pathophysiology and pathogenesis of childhood-onset insulin-dependent diabetes mellitus (IDDM)

Research Project

Project/Area Number 11470175
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionKitasato University

Principal Investigator

MATSUURA Nobuo  Kitasato Univ. School of Medicine, Department of Pediatrics, Professor, 医学部, 教授 (50002332)

Co-Investigator(Kenkyū-buntansha) KAZAHARI Kouji  Kitasato Univ. School of Medicine, Department of Pediatrics, Research Associate, 医学部, 助手 (90214288)
NOMA Tsuyoshi  Kitasato Univ. School of Medicine, Department of Pediatrics, Assistant Professor, 医学部, 講師 (60208387)
Project Period (FY) 1999 – 2001
KeywordsHLA antigen genes / DRβ genes / DQα genes / CTLA-4 gene / NeuroD / BETA2 gene / IDDMK_<1,2>-22 / Childhood diabetes / Qoβ gene
Research Abstract

1. HLA-DR, DQ beta genes and DQ alpha genes analysis
We analyzed HLA antigen genes in 146 patients with IDDM and 97 controls. The patients were divided into three groups, that is, group E, A, and S, depending on the age at onset and clinical course of the disease. We found significantly decreased frequency in DRB1 150X(D) in all diabetic groups, and increased in 0405(S), 0901(V) in groups in A and E.. Moreover, 0802(D) was significantly increased in group A. DQA1(301), DQB1(303), DRB1(901) genotype was found most susceptibility (RR=7.29 , 3.79, 2.82 in groups E, A, E respectively) in Japanese pat.
2. CTLA-4 and NeuroD/BETA2 polymorphism associated with Japanese childhood IDDM patients.: We found the significant increase in G/G phenotype, decreas A/A phenotype in group E compared with control. The relationship between HLA DRB1 405 and 901 and CTLA-4 polymorphism was evaluated. Odds ratio(OR) in 0901(+) vs 0901(-) and 0910(+)/CTLA4(G+) vs 0910(-)/CTLA4(G-) as well as 504 was significantly increased in diabetic groups suggested the both genes are additive but independently for the development of IDDM in Japanese children. There was no significant diference in NeuroD/BETA2 polymorphism in Japanese children.
3. Idenfication of nonsynonymous polymorphism in the superantigen(SPA)-coding region of IDDMK_<1,2>-22 and association with IDDM: We identified two nonsynony-mous A/G polymorphism at the 339- and 510- in the SPA-coding region of IDDM-K_<1,2>-22 retrovirus. We found significant G/G polymorphism at 510- in group E and G/A phenotype at 339- in group S. Future study will be necessary for conclusions.

  • Research Products

    (48 results)

All Other

All Publications (48 results)

  • [Publications] Matsuura N: "Effects of dioxins and polychlorinated biphenyls (PCBs) on thyroid function in infants born in Japan-Report from research on environmental health"Clin Pediatr Endocrinol. 10. 1-6 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsuura N: "Effects of dioxins and polychlorinated biphenyls (PCBs) on thyroid function in infants born in Japan The second report from research on environmental health"Chemosphere. 45(8). 1167-1171 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sugimoto J: "Transcriptionally active HERV-K Genes : Identification"Genomic. 72(1). 137-144 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hishinuma A: "Polymorphism of the polyalanine tract of thyroid transcription factor-2 gene in patients with thyroid dysgenesis"Eur J Endocrinal. 143(3). 385-389 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsuura N: "The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT): Initial aims and impact of the family history of type 1 diabetes mellitus in Japanese children"Pediatric Diabetes. 2(4). 160-169 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kinjyo Y: "Identification of nonsynonymous polymorphisms in the superantigen-coding region of IDDMK1,2 22 and a pilot study on the association between IDDMK1,2 22and type 1 diabetes"J Hum Genet. 46(12). 712-716 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Danne T: "Persistent center differences over 3 years in glycemic control and hypoglycemia in a study of 3,805 children and adolescents with type 1 diabetes from the Hvidore Study Group"Diabetes care. 24(8). 1342-1347 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura T: "Population pharmacokinetics of panipenem in neonates and retrospective evaluation of dosage"J Antimicrobial Chemotherapy. 47(1). 51-59 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawasaki E: "Association between IA-2 autoantibody epitope specificities and age of onset in Japanese patients with autoimmune diabetes"J Clin Endocrinol Metab 86. 86. (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Holl RW: "Insulin Injection Regimens and Metabolic Control in an International Survey of Adolescents with Type-1-Diabetes over 3 years: Results from the Hvidore Study Group"Diabetologia. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hoey H: "Good Metabolic Control is Associated with Better Quality of Life in 2,101 Adolescents with Type 1 Diabetes"Diabetes care. 24(11). 1923-1928 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hasegawa H: "Analysis of α-synuclein, Parkin, tau, and UCH-L1 in a Japanese family with autosomal dominant Parkinsonism"Eur Neurol. 46. 20-24 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ihara K: "Association studies of CTLA-4, CD28, and ICOS gene polymorphisms with type 1 diabetes in the Japanese population"Immunogenetics. 53. 447-454 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Misu Y: "Clinicopathological features of pediatric functional adrenocortical carcinoma diagmosed by Weiss criteria; An analysis of four cases"Clin Pediatric Endocrinol. 10(2). 141-146 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Noma T: "Functional human IgE specific for Dermalophagoides farimae antigen is produced in SCID mice reconstituted with peripheral mononuclear cells derived from healthy persons and patients with athma"Allergy. 55. 1-7 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka: "Growth-promoting effects of growth hormone treatment at various doses in children with intrauterine growth retardation"Clin Pediatric Endocrinol. 10(supl.15). 712-716 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 宮本茂樹: "1型糖尿病におけるインスリン療法中の重症低血糖について"小児科臨床. 54(3). 319-321 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 木村利美: "新生児におけるパニペネム薬物動態のNONMEM解析"日本小児臨床薬理学会誌. 13(1). 113-115 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 松浦信夫: "甲状腺中毒症と甲状腺機能亢進症.小児疾患の診断治療基準"小児内科. 33(増). 216-217 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 松浦信夫: "小児の糖尿病In糖尿病診療Q&Aマニュアル,第3版"医歯薬出版馬場茂明,土井邦紘(編集). 12 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 松浦信夫: "ライフステージ別の課題と療養指導In日本糖尿病療養指導士受験ガイドブック2001"メディカルレビュー社日本糖尿病療養指導士認定機構(編集). 5 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 松浦信夫: "小児の糖尿病In糖尿病のマネージメント.チームアプローチと療養指導の実際第3版"医学書院松岡健平,河盛隆造,岩本安彦(編集). 8 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsuura N, Suzuki S, Yokota Y, Kazahari K, Kazahari M, Toyota T, Hirai M, Okuno A, Harada S, Fukushima N, Koike A, Itho Y, Hotsubo T: "The prevalence of mitochondrial gene mutations in childhood diabetes in Japan"J. Pediatr Endocrinol Metab. 12(1). 27-30 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sera Y, Kawaski E, Abiru N, Ozaki M, Abe T, Sakamaki H, Takino H, Kondo H, Yamasaki H, Yamaguchi Y, Akazawa S, Nagataki S, Uchigata Y, Matsuura N, Eguchi K: "Autoanti-bodies to multiple islet autoantigens in patients with abrupt onset type 1 diabetes and diabetes diagnosed with urinary glucose screenings"J of Autoimmunity. 13(2). 257-265 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Noma T, Hayashi M, Kawano Y, Yoshizawa I, Isghikawa Y, Saeki T, Aoki K, Matsuura N: "Functional interleukin-5 activity in peripheral blood mononuclear cells from adolescents with mite athma in remission. 29:780-785,1999"Clin Exp Allergy. 36. 505-514 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshinaga Takayama, Fumio Takada, Masahiko Nowatari, Masaya Kawakami, Nobuo Matsuua: "Gene structure of the P100 serine-protease component of the human Ra-reactive factor"Mol Immunol. 36. 505-514 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hishinuma A, Takamatsu J, Ohyama Y, Yokozawa T, Kanno Y, Kuma K, Yoshida S, Matsuura N, leiri T: "Two novel cysteine substitutions(C1263R and C1995S) of thyroglobulin cause a defect in intracellular transport of thyroglobulin in patients with congenital goiter and the variant type or adenomatous goiter"J Clin Endocrinol Metab. 84(4). 1438-1444 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Deguchi K, Oguchi K, Matsuura N, Armstrong DD, Takashima K: "Periventicular leukomalacia: Relation to gestational age and axonal injury"Pediatr Neurology. 20. 370-374 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kizaki T, Ookawara T, Haga S, Matsuura N, Ohno H: "Effects of aging on generation of ED^<2hight> MHC class II^+ macrophages during cold stress"Scand J Immunol. 51(1). 36-44 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Eiji Kawasaki, Yasunori Sera, Kenichi Yamakawa, Takahiro Abe, Masako Ozaki, Shigeo Uotani, Hirofumi Takino, Shigeyuki Ohtsu, Hironori Yamasaki, Yoshihiko Yamaguchi, Nobuo Matsuura, Katsumi Eguchi: "Identification and functional analysis of mutations in the Hepatocyte Nuclear Factor-1 α in Japanese diabetic patients initially classified as having Type 1 diabetes"J Clin Endocrinol Metab. 85(1). 331-335 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Aono S, Matsuura N, Amemiya S, Igarashi Y, Uchigata Y Urakami T, Kida K, Sasaki N, Miki Y, Miyamoto S: "Marriage rate and number of children among young adults with insulin-dependent diabetes mellitus in Japan"Diab Res Clini Prac. 49(2). 135-141 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kizaki T, Ookawara T, Iwabuchi K, Onoe K, Day NK, Good RA, Maruyama N, Haga S, Matsuura N, Ohira Y, Ohno H: "Age-associated increase of basal corticosterone levels decrease ED2^<high>, NF-κB^<high> activated macrophages"J Leukoc Biol. 68(1). 21-30 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ookawara T, Matsuura N, Oh-ishi T, Okazaki M, Kizaki T, Suzuki K, Hitomi Y, Suzuki K, Ohno H: "Serum extracellular superoxide dismutase in pecliatric paients with various diseases as judged by ELISA"Res Comm Mol Path Pharm. 107. 291-296 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura T, Kokubun H, Nowatari M, Matsuura N, Sunagawa K, Kubo H: "Population pharmacokinetics of panipenem in neonates and retrospective evaluation of dosage"J Antimicrobial Chemotherapy. 47(1). 51-59 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuura N, Uchiyama T, Tada H, Nakamura Y, Kondo N, Morita M, Fukushi M: "Effects of dioxins and polychlorinated biphenyls(PCBs) on thyroid function in infants born in Japan-Report from research on environmental health"Clin Pediatr Endocrinol. 10. 1-6 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuura N, Uchiyama T, Tada H, Nakamura Y, Kondo N Morita M, Fukushi M: "Effects of dioxins and polychlorinated biphenyls(PCBs) on thyroid function in infants born in Japan-The second report from research on environmental health"Chemosphere. 45(8). 1167-1171 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Jun Sugimoto, Nobuo Matsuura, Yoshino Kinjo, Nobuyuki Takasu, Takaya Oda, Yoshihiro Jinno: "Transcriptionally active HERV-K Genes: Identification"Genomic. 72(1). 137-144 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Eiji Kawasaki, Yasunori Sera, Kikako Yamauchi, Masako Ozaki, Takahiro Abe, Kenichi Yamakawa, Shigeo Uotani, Hirofumi Takino, Shigeyuki Ohtsu, Hironori Yamasaki, Yoshihiko Yamaguchi, Yasuko Uchigata, Nobuo Matsuura, Katsumi Eguchi: "Association between IA-2 autoantibody epitope specificities and age of onset in Japanese patients with autoimmune diabetes"J Clin Endocrinol Metab. 86. (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Danne T, Mortensen HB, Hougaad P, Lynggaard H, Aanstoot HJ, Chiaelli F, Darneman D, Dorchy H, Garandeau P, Greene S, Hoey H, Holl RW, Kaprio EA, Kocova M, Martul P, Matsuura N, Robertson KJ, Schoenle EJ, Sovik O, Swift PGF, Tsou RM, Vanelli M, Aman J, for Hvidore Study Group on Childhood Diabetes: "Persistent center differences over 3 years in glycemic control and hypoglycemia in a study of 3,805 children and adolescents with type 1 diabetes from the Hyidore Study Group"Diabetes care. 24(8). 1342-1347 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hilary Hoey, H-J. Aanstoot, F. Chiarelli, D. Daneman, T. Danne, B. Dinesen, H. Dorchy, M. Fitzgerald, P. Garandeau, S. Greene, R.W. Holl, P. Hougaard, E.A. Kaprio, M. Kocova, H. Lynggaard, P. Martul, N. Matsuura, Hannah McGee, Henrik B. Mortensen, K.J. Robertson, E.J. Schoenle, O. Sovik, P. Swift, R.M Tsou, M. Vanelli, J. Aman for the Hvidore Study Group on Childhood Diabetes: "Good Metabolic Control is Associated with Better Quality of Life in 2,101 Adolescents with Type 1 Diabetes"Diabetes care. 24(11). 1923-1928 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hasegawa H, Funayama M, Matsuura N, Furusawa H, Sakai F, Kowa H, Obata F: "Analysis of α-synuclein, Parkin, tau, and UCH-L1 in a Japanese family with autosomal dominant Parkinsonism"Eur Neurol. 46. 20-24 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Noma T, Yoshizawa I, Kawano Y, Matsuura N, Nakajima T, Aoki K: "Functional human IgE specific for Dermatophagoides farimae antigen is produced in SCID mice reconstituted with peripheral mononuclear cells derived from healthy persons and patients with athma"Allergy. 55. 1-7 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akira Hishinuma, Yoshihide Ohyama, Takeo Kuribayashi, Narumi Nagakubo, Takashi Namatame, Keiko Shibayama, Osamu Arisaka, Nobuo matsuura, Tamio Ieiri: "Polymorphism of the polyalanine tract of thyroid transcription factor-2 gene in patients with thyroid dysgenesis"Eur J Endocrinol. 143(3). 385-389 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Misu Y, Jian Shi-Xu, Yokota Y, Shibata M, Shinohara O, Kameya T, Matsuura N: "Clinicopathological features of pediatric functional adrenocortical carcinoma diagmosed by Weiss criteria; An analysis of four cases"Clin Pediatric Endocrinol. 10(2). 141-146 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka T, on behalf of the Study Groups (SM study and NN study) on GH treatment in lUGR: "Growth-promoting effects of growth hormone treatment at various does in children intrauterine growth retardation"Clin Pediatric Endocrinol. 10(suppl 15). 15-23 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kenji Ihara, Saifuddin Ahmed, Futoshi Nakao, Naoki Kinukawa, Ryoichi Kuromaru, Nobuo Matsuura, Isao Iwasa, Seiho Nagafuchi, Hiroshi Kohno, Toshiro Hara: "Association studies of CTLA-4, CD28, and ICOS gene polymorphisms with type I diabetes in the Japanese population"Immunogenetics. 53. 447-454 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kinjyo y, Matsuura N, Yokota Y, Ohtsu S, Nomoto K, Komiya I, Sugimoto J, Jinno. Y, Takasu N: "Identification of nonsynonymous polymorphisms in the superantigen-coding region of IDDMK.1,2 22 and a pilot study on the association between IDDMK1,2 22and type 1 diabetes"J Hum Genet. 46(12). 712-716 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nobuo Matsuura, Yukifumi Yokota, Kouji Kazahari, Nozomu Sasaki, Shin Amemiya, Yoshiya Ito, Naoki Fukushima, Akemi Koike, Yutaka Igarashi, Takeki Hirano, Shigetaka Sugihara, Yuko Miki, Tatsuhiko Urakami, Yasuko Uchigata, Sachiko Kanematsu, Yukashi Ohki, Masaro Takesue, Yukihiro Hasegawa, Shigeki Miyamoto, Masatoshi Fujimoto l, Satoshi Fujitsuka, Tetsuo Mori, Haruo Ogawa, Makoto Uchiyama, Kazumichi Onigata, Katsuhiko Tachibana, Nobuyuki Kikuchi, Tokuo Taketani, Hitoshi Kohno, Yoshihito Kasahara, Gen Isshiki, Masakuni Tokuda, Toshikazu Takahashi, Susumu Kanzaki, Ichiro Yokota, Kaichi Kida, Taisuke Okada, Soroku Nishiyama, Hidenari Masuda, Akihiko Kinugasa, Osamu Nukada: "The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT): Initial aims and impact of the family history of type 1 diabetes mellitus in Japanese children"Pediatric Diabtes. 2(4). 160-169 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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