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Research on underlying mechanisms of Stevens-Johnson syndrome

Research Project

Project/Area Number 17390470
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

SOTOZONO Chie  Kyoto Prefectural University of Medicine, Graduates School of Medicine, Assistant Professor, 医学研究科, 講師 (30216585)

Co-Investigator(Kenkyū-buntansha) KINOSHITA Shigeru  Kyoto Prefectural University of Medicine, Graduates School of Medicine, Professor, 医学研究科, 教授 (30116024)
UETA Mayum  Kyoto Prefectural University of Medicine, University Hospital, Postdoctoral fellow, 附属病院, 専攻医 (60398386)
TASHIRO Kei  Kyoto Prefectural University of Medicine, Graduates School of Medicine, Professor, 医学研究科, 教授 (10263097)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥15,500,000 (Direct Cost: ¥15,500,000)
Fiscal Year 2006: ¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 2005: ¥8,000,000 (Direct Cost: ¥8,000,000)
KeywordsStevens-Johnson syndrome / Visual disturbance / histocompatibility antigen(HLA) / innate immune response / single-nucleotide-polymorphism / toll-like receptors (TLR) / bacterial flora / drug adverse reactions / Toll like receptor(TLR) / 角膜上皮幹細胞 / マイボーム腺圧出油脂異常 / 角膜混濁 / 血管侵入 / 瘢痕性結膜上皮 / Thioredoxin
Research Abstract

1. We enrolled 73 patients (138 eyes) with Stevens-Johnson syndrome at chronic stage. Complications were categorized as corneal-, conjunctival-, and eyelid complications and 13 components were evaluated and graded on a scale from 0 to 3 according to their severity. The most severe complication components were loss of the palisades of Vogt (114 eyes, 82.6%) and meibomian gland involvement (102 eyes, 73.9%). Visual acuity in 74 of the 138 eyes (53.6 %) was worse than 20/200. Multivariable regression analysis showed that corneal neovascularization, opacification, keratinization, and cataracts significantly affected logMAR (p<0.0001, p<0.0001, p=0.0142, and p=0.0375, respectively). 2. We examined the histocompatibility antigen genes HLA-A,-B, and-C of 40 Japanese SJS/TEN patients with ocular complications and 113 healthy Japanese volunteers. We clarified that HLA-A*0206 is strongly associated with SJS/TEN with ocular complications in the Japanese. 3. The Japanese single-nucleotide-polymorphism (JSNP) database reports 7 polymorphisms consisting of 7 SNPs in the human Toll-like receptor (TLR) 3 gene ; 3 of the 7 SNPs are coded in exon regions, and the other 4 are coded in intron regions. These 7 SNPs were analysed in 57 Japanese patients with SJS/TEN with ocular surface complications and in 160 Japanese healthy controls. SNP 299698T/G and the genotype patterns of 293248A/A and 299698T/T were strongly associated with SJS/TEN. The results suggested that polymorphisms in the TLR3 gene could be associated with SJS/TEN in the Japanese population. 4. We found that bacterial strains not only from different subjects but also from multiple ocular surface sites of the same subject exhibited different PFGE patterns. The data demonstrated the polyclonality of S. epidermidis on the healthy ocular surface.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (22 results)

All 2007 2006 2005

All Journal Article (19 results) Book (3 results)

  • [Journal Article] A comparison between cultivated and conventional limbal stem cell transplantation for Stevens-Johnson syndrome.2007

    • Author(s)
      Ang LP, Sotozono C, Kinoshita S et al.
    • Journal Title

      American Journal of Ophthalmolgy 143

      Pages: 178-180

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Strong association between HLA-A*0206 and Stevens-Johnson syndrome in the Japanese.2007

    • Author(s)
      Ueta M, Sotozono C, Tokunaga K, Kinoshita S et al.
    • Journal Title

      American Journal of Ophthalmolgy 143

      Pages: 367-368

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Polyclonality of Staphylococcus epidermidis residing on the healthy ocular surface.2007

    • Author(s)
      Ueta M, Sotozono C, Kinoshita S et al.
    • Journal Title

      J Med Microbiol 56

      Pages: 77-82

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A new grading system for the evaluation of chronic ocular manifestations in patients with Stevens-Johnson syndrome.2007

    • Author(s)
      Sotozono C, Ueta M, Kinoshita S et al.
    • Journal Title

      Ophthalmology (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Toll like receptor 3 gene polymorphisms in Japanese patients with Stevens-Johnson syndrome.2007

    • Author(s)
      Ueta M, Sotozono C, Kinoshita S et al.
    • Journal Title

      British Journal of Ophthalmolgy (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] 再生医学による重症角膜疾患の新規治療法開発への戦略的研究.2007

    • Author(s)
      木下 茂, 外園千恵, 上田真由美ら
    • Journal Title

      最新医学 62

      Pages: 132-180

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Polyclonality of Staphylococcus epidermidis residing on the healthy ocular surface.2007

    • Author(s)
      Ueta M, Iida T, Sakamoto M, Sotozono C, Takahashi J, Kojima K, Okada K, Chen X, Kinoshita S, Honda T.
    • Journal Title

      J Med Microbiol. 56

      Pages: 77-82

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A comparison between cultivated and conventional limbal stem cell transplantation for Stevens-Johnson syndrome.2007

    • Author(s)
      Ang LP, Sotozono C, Koizumi N, Suzuki T, Inatomi T, Kinoshita S.
    • Journal Title

      Am J Ophthalmol. 143(1)

      Pages: 178-80

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Strong association between HLA-A*0206 and Stevens-Johnson syndrome in the Japanese.2007

    • Author(s)
      Ueta M, Sotozono C, Tokunaga K, Yabe T, Kinoshita S.
    • Journal Title

      Am J Ophthalmol 143

      Pages: 367-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Toll like receptor 3 gene polymorphisms in Japanese patients with Stevens-Johnson syndrome.2007

    • Author(s)
      Ueta M, Sotozono C, Inatomi T, Kojima K, Tashiro K, Hamuro J, Kinoshita S.
    • Journal Title

      Br J Ophthalmol Feb 21:(Epub ahead of print)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A new grading system for the evaluation of chronic ocular manifestations in patients with Stevens-Johnson syndrome.2007

    • Author(s)
      Sotozono C, Ang LPK, Koizumi N, Higashihara H, Ueta M, Inatomi T, Yokoi N, Kaido M, Dogru M, Shimazaki J, Tsubota K, Yamada M, Kinoshita S.
    • Journal Title

      Ophthalmology Apr 30:(Epub ahead of print)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Strong association between HLA-A^*0206 and Stevens-Johnson syndrome in the Japanese.2007

    • Author(s)
      Ueta M, Sotozono C, Tokunaga K, Yabe T, Kinoshita S
    • Journal Title

      American Journal of Ophthalmolgy 143

      Pages: 367-368

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Polyclonality of Staphylococcus epidermidis residing on the healthy ocular surface.2007

    • Author(s)
      Ueta M, Sotozaono C, Kinoshita S, Honda T et al.
    • Journal Title

      J Med Microbiol 56

      Pages: 77-82

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Functional visual acuity in Stevens-Johnson syndrome.2006

    • Author(s)
      Kaido M, Sotozono C, Kinoshita S, Tsubota K et al.
    • Journal Title

      American Journal of Ophthalmolgy 142

      Pages: 917-922

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Functional visual acuity in Stevens-Johnson syndrome.2006

    • Author(s)
      Kaido M, Dogru M, Yamada M, Sotozono C, Kinoshita S, Shimazaki J, Tsubota K
    • Journal Title

      Am J Ophthalmol. 142(6)

      Pages: 917-22

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Spontaneous Ocular Surface Inflammation and Goblet Cell Disapperance in IκBζ Gene-Disrupted Mice.2005

    • Author(s)
      Ueta M., Hamuro J, et al.
    • Journal Title

      Investigative Ophthalmology & Visual and Ophthalmology. 46(2)

      Pages: 579-588

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Spontaneous Ocular Surface Inflammation and Goblet Cell Disapperance in IκBζ Gene-Disrupted Mice.2005

    • Author(s)
      Ueta M, Hamuro J, Yamamoto M, Kaseda K, Akira S, Kinoshita S.
    • Journal Title

      Invest Ophthalmol Vis Sci. 46

      Pages: 579-88

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Spontaneous Ocular Surface Inflammation and Goblet Cell Disapperance in IκBζ Gene-Disrupted Mice.2005

    • Author(s)
      Ueta M.at.el.
    • Journal Title

      Investigative Ophthalmology & Visual and Ophthalmology. 46(2)

      Pages: 579-588

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Triggering of TLR3 by polyI : C in human corneal epithelial cells to induce inflammatory cytokines2005

    • Author(s)
      Ueta M.at.el.
    • Journal Title

      Biochemical and Biophysical Research Communications 331

      Pages: 285-294

    • Related Report
      2005 Annual Research Report
  • [Book] 皮膚科診療プラクティス 薬疹を極める(塩原哲夫編)2006

    • Author(s)
      外園千恵
    • Total Pages
      301
    • Publisher
      文光堂
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 皮膚科心療プラクティス 薬疹を極める(塩原哲夫編)2006

    • Author(s)
      外園千恵
    • Total Pages
      301
    • Publisher
      文光堂
    • Related Report
      2006 Annual Research Report
  • [Book] 角膜疾患-外来でこう診てこう治せ-(木下茂編)2005

    • Author(s)
      外園千恵
    • Total Pages
      296
    • Publisher
      メジカルビュー
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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