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2008 Fiscal Year Annual Research Report

小児中耳炎の難治化の病態解明と自然免疫および特異的免疫の賦活に関する研究

Research Project

Project/Area Number 19591987
Research InstitutionWakayama Medical University

Principal Investigator

山中 昇  Wakayama Medical University, 医学部, 教授 (10136963)

Co-Investigator(Kenkyū-buntansha) 藤原 啓次  和歌山県立医科大学, 医学部, 准教授 (80326371)
田村 真司  和歌山県立医科大学, 医学部, 講師 (10244724)
保富 宗城  和歌山県立医科大学, 医学部, 講師 (90336892)
島田 純  和歌山県立医科大学, 医学部, 助教 (90326372)
Keywords中耳炎 / 薬剤耐性菌 / 肺炎球菌表面蛋白抗原 / PspA / 母体免疫 / インフルエンザ菌 / バイオフィルム / 難治化
Research Abstract

[目的]肺炎球菌表面蛋白抗原PspAを用いた母体免疫による特異的免疫能の誘導および感染予防について検討し、難治化の原因として、インフルエンザ菌のバイオフィルム形成能にっいて検討した。
[結果]1)PspA母体経鼻免疫により、母マウス母乳及び血清、新生児マウスの血清中に抗PspA特異的IgG抗体が誘導された。またPspA免疫群の新生児マウスは、非免疫群に比べて全身感染後の生存時間が延長された。2)小児急性中耳炎症例より採取した無莢膜型インフルエンザ菌臨床分離株において、安定したバイオフィルム測定システムを確立することができた。この測定システムにより中耳炎分離株70株のうち59株(84%)にバイオフィルム形成を認めた。薬剤感受性とバイオフィルム形成との関連を見ると、ABPCの耐性株に比較して、感受性が高い株ほどバイオフィルム形成株を多く認めた。急性中耳炎の臨床経過とバイオフィルム形成との関連について検討すると、抗菌薬治療非改善例から分離されたインフルエンザ菌では,抗菌薬治療改善例からの分離菌よりも有意に高いバイオフィルム形成能を認めた。
[考察及び結論]PspAの母体経鼻免疫免疫により、免疫能の未熟な乳幼児期に特異的免疫応答が誘導可能であり、肺炎球菌感染症の予防方法として有用と考えられた。さらに急性中耳炎患児から分離された無莢膜型インフルエンザ菌がバイオフィルム形成を行うことが明らかとなり、加えて無莢膜型インフルエンザ菌のバイオフィルム形成が、抗菌薬治療に抵抗し遷延・難治化する急性中耳炎の臨床経過に重要な役割を果たすことが示された。

  • Research Products

    (41 results)

All 2008

All Journal Article (23 results) (of which Peer Reviewed: 22 results) Presentation (14 results) Book (4 results)

  • [Journal Article] Clinical bacteriology and immunology in acute otitis media inchildren2008

    • Author(s)
      Yamanaka N, Hotomi M, Billal DS
    • Journal Title

      J Infect Chemother 14

      Pages: 180-187

    • Peer Reviewed
  • [Journal Article] Serotype distribution and penicillin resistance of Streptococcus pneumoniae isolates from middle ear fluids of pediatric patients with acute otitis medi a in Japan. Advanced Treatment for Otitis Media Study Group (ATOMS).2008

    • Author(s)
      Hotomi M, et al.
    • Journal Title

      J Clin Microbiol 46

      Pages: 3808-3810

    • Peer Reviewed
  • [Journal Article] Protection against systemic fatal pneumococcal infection by maternal intranasal immunization with pneumococcal surface prote in A (PspA)2008

    • Author(s)
      Katsurahara T, et al.
    • Journal Title

      J Infect Chemother 14

      Pages: 393-398

    • Peer Reviewed
  • [Journal Article] Prevalence of streptococcus invasive locus (sil) and its relationship with macrolide resistance among group A Streptococcusstrains.2008

    • Author(s)
      Billal DS, et al.
    • Journal Title

      J Clin Microbiol 46

      Pages: 1563-1564

    • Peer Reviewed
  • [Journal Article] Wealth and child survival : India and Bangladesh.2008

    • Author(s)
      Billal DS, et al.
    • Journal Title

      Lancet 25

      Pages: 1459-1459

    • Peer Reviewed
  • [Journal Article] Rotavirus vaccine for developing countries.2008

    • Author(s)
      Billal DS, et al.
    • Journal Title

      Lancet 9

      Pages: 444-444

    • Peer Reviewed
  • [Journal Article] Determination of Pneumococcal Serotypes/Genotypes in Nasopharyngeal Secretions of Otitis Media Children by Multiplex Polymerase Chain Reaction.2008

    • Author(s)
      Billal DS, et al.
    • Journal Title

      European Journal of pediatrics 167

      Pages: 401-407

    • Peer Reviewed
  • [Journal Article] Effects of intramuscular and peritonsillar injection of tramadol before tonsillectomy : a double blind, randomized, placebo controlled clinical trial.2008

    • Author(s)
      Ugur MB, et al.
    • Journal Title

      Int J Pediatr Otorhinolaryngol 72

      Pages: 241-248

    • Peer Reviewed
  • [Journal Article] Deletion at Dickkopf (dkk) -3 locus (llpl5. 2)is related with lower lymph node metastasis and better prognosis in head and neck squamous cell carcinomas.2008

    • Author(s)
      Katase N, et al.
    • Journal Title

      Oncol Res 17

      Pages: 273-282

    • Peer Reviewed
  • [Journal Article] Lack of B-RAF mutations in head and neck squamous cell carcinoma.2008

    • Author(s)
      Al Sheikh Ali M, et al.
    • Journal Title

      Folia Biol (Praha) 54

      Pages: 157-161

    • Peer Reviewed
  • [Journal Article] Expression and mutation analysis of epidermal growth factorreceptor in head and neck squamous cell carcinoma.2008

    • Author(s)
      Sheikh Ali MA, et al.
    • Journal Title

      Cancer Sci. 99

      Pages: 1589-1594

    • Peer Reviewed
  • [Journal Article] Loss of heterozygosity at chromosome 14q is associated with poor prognosis in head and neck squamous cell carcinomas.2008

    • Author(s)
      Pehlivan D, et al.
    • Journal Title

      J Cancer Res Clin Oncol 134

      Pages: 1267-1276

    • Peer Reviewed
  • [Journal Article] Involvement of EphA2 in head and neck squamous cell carcinoma : mRNA expression, loss of heterozygosity and immunohistochemical studies.2008

    • Author(s)
      Rivera RS
    • Journal Title

      Oncol Rep. 19

      Pages: 1079-1084

    • Peer Reviewed
  • [Journal Article] Downregulation of ING3 mRNA expression predicts poor prognosis in head and neck cancer.2008

    • Author(s)
      Gunduz M
    • Journal Title

      Cancer Sci 99

      Pages: 531-538

    • Peer Reviewed
  • [Journal Article] 急性咽喉頭炎、急性扁桃炎および急性鼻副鼻腔炎に対するazithromycin単回投与製剤の多施設共同、非盲検非対照試験2008

    • Author(s)
      山中 昇, 保富宗城, 藤原啓次
    • Journal Title

      日本化学療法学会雑誌 56

      Pages: 525-537

    • Peer Reviewed
  • [Journal Article] β-ラクタマーゼ非産生アンピシリン耐性(BLNAR)インフルエンザ菌2008

    • Author(s)
      山中 昇, 保富宗城
    • Journal Title

      KEY WORD感染症

      Pages: 132-133

    • Peer Reviewed
  • [Journal Article] 肺炎球菌による小児急性中耳炎の疾病負担と小児用7価肺炎球菌結合型ワクチンの医療経済効果2008

    • Author(s)
      山中 昇, 保富宗城, 杉田麟也
    • Journal Title

      小児科臨床 61

      Pages: 2221-2232

    • Peer Reviewed
  • [Journal Article] 小児用7価肺炎球菌結合型ワクチンの医療経済効果2008

    • Author(s)
      神谷 齋, 岩田 敏, 石和田稔彦, 山中 昇, 杉田麟也
    • Journal Title

      小児科臨床 61

      Pages: 2233-2241

    • Peer Reviewed
  • [Journal Article] 耳鼻咽喉科感染症に対するsitafloxacinの有効性、安全性および組織移行性.2008

    • Author(s)
      馬場俊吉, 鈴木賢二, 山中 昇山下裕司, 黒野祐一, 堀 誠治
    • Journal Title

      日本化学療法学会雑誌 56

      Pages: 110-119

  • [Journal Article] ガチフロキサシンのIL-8・TNF-αに対する影響に関する検討2008

    • Author(s)
      小林政美, 保富宗城, 島田 純藤原啓次, 山中 昇
    • Journal Title

      耳鼻臨床 101

      Pages: 803-809

    • Peer Reviewed
  • [Journal Article] 耐性菌時代の耳鼻咽喉科感染症の治療戦略 なぜ細菌は耐性化するのか 耐性化のメカニズムと耐性菌の現状2008

    • Author(s)
      保富宗城, 山中 昇
    • Journal Title

      日本耳鼻咽喉科感染症研究会会誌 26

      Pages: 271-275

    • Peer Reviewed
  • [Journal Article] 急性鼻副鼻腔炎に対するgatifloxacinの有用性 スコアリングシステムを用いた評価2008

    • Author(s)
      保富宗城, 藤原啓次, 山中 昇, 他
    • Journal Title

      日本化学療法学会雑誌 56

      Pages: 7-15

    • Peer Reviewed
  • [Journal Article] 急性中耳炎から分離された肺炎球菌の莢膜血清型とワクチンカバー率の検討.2008

    • Author(s)
      小上真史, 保富宗城, 山中 昇, 他
    • Journal Title

      日本耳鼻咽喉科感染症研究会会誌 26

      Pages: 207-210

    • Peer Reviewed
  • [Presentation] Burden of illness and cost -effective analysis of PCV7 for acute otitis media.2008

    • Author(s)
      Yamanaka N, et al.
    • Organizer
      SPIKER
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2008-12-13
  • [Presentation] The distribution and drug resista nt pathogens in acute otitismedia (ATOMS surveillance).2008

    • Author(s)
      Ogami M, Hotomi M, YamanakaN
    • Organizer
      SPIKER
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2008-12-13
  • [Presentation] Current Status of Antimicrobial Resistant Pathogens and Their Clonal Spread in Upper Respiratory Tract Infections in Japan.2008

    • Author(s)
      Hotomi M, Yamanaka N
    • Organizer
      11th Western Pacific Congress on Chemotherapy and Infectious Diseases
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      2008-11-29
  • [Presentation] MAL Gene as a Metastasis Suppressor for Head and Neck SquamousCell Carcinomas.2008

    • Author(s)
      Beder L, Gunduz M, et al.
    • Organizer
      7^<th> International Conference on Head and neek Cancer
    • Place of Presentation
      San Francisco USA
    • Year and Date
      2008-07-19
  • [Presentation] Clinical Significance of Testin Expression in Head and NeckSquamous Cell Carcinomas.2008

    • Author(s)
      Gunduz M, et al.
    • Organizer
      7th International Conference on Head and neek Cancer
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2008-07-19
  • [Presentation] Maternal intranasal immunization against H. influenzae and S. pneumoniae2008

    • Author(s)
      Yamanaka N, et al.
    • Organizer
      6^<th> International Symposium on Pneumococci and Pneumococcal Diseases
    • Place of Presentation
      Reykjavik, Iceland
    • Year and Date
      2008-06-08
  • [Presentation] Rapid detection of pneumococcal antigen by immunochromatography test.2008

    • Author(s)
      Yamauchi K, et al.
    • Organizer
      6^<th> International Symposium on Pneumococci and Pneumococcal Diseases.
    • Place of Presentation
      Reykjavik, Iceland
    • Year and Date
      2008-06-08
  • [Presentation] Rapid Detection of Pneumococcal Antigen by Immunochromatography Test.2008

    • Author(s)
      Yamanaka N, et al.
    • Organizer
      108^<th> General Meeting
    • Place of Presentation
      Boston, USA
    • Year and Date
      2008-06-01
  • [Presentation] Serotype Distributions and Penicillin Resistance of Streptococcus pneumoniae Isolates from Middle Ear Fluids of Pediatric Acute Otitis Media in Japan.2008

    • Author(s)
      Billal DS, Hotomi M, Yamanaka N
    • Organizer
      108^<th> General Meeting
    • Place of Presentation
      Boston, USA
    • Year and Date
      2008-06-01
  • [Presentation] Production of Biofilm by Haemophilus influenzae Isolated fromPediatric Intractable Otitis Media.2008

    • Author(s)
      Moriyama S, Hotomi M, BillalDS, Yamanaka N
    • Organizer
      108^<th> General Meeting
    • Place of Presentation
      Boston, USA
    • Year and Date
      2008-06-01
  • [Presentation] Molecular identification and clonal dissemination of Hemophilus haemolyticus in acute pharyngotonsillitis.2008

    • Author(s)
      Yamanaka N, et al.
    • Organizer
      European Congress of Clinical Microbiologyand Infectious Diseases.
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2008-04-19
  • [Presentation] Molecular biological study of infectious mechanisms in Conjunctivitis, Otitis media, and Rhinosinusitis in young children.2008

    • Author(s)
      Sugita R, et al.
    • Organizer
      European Congress of Clinical Microb iologyand Infectious Diseases.
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2008-04-19
  • [Presentation] How to select and use antimicrobial agents for intractable otorhinolaryngological infections?2008

    • Author(s)
      Yamanaka N
    • Organizer
      12^<th> Japan-Korea Joint Meeting of Otorhinolaryngology- Head and Neck Surgery.
    • Place of Presentation
      Nara, Japan
    • Year and Date
      2008-04-03
  • [Presentation] A New Metastasis Suppressor candidate in Head and Neck cancers : MAL gene.2008

    • Author(s)
      Beder L, Gunduz M, et al.
    • Organizer
      The 12^<th> Japan -Korea Joint Meeting of Otorhinolaryngology - Head and Neck Surgery
    • Place of Presentation
      Nara Japan
    • Year and Date
      2008-04-03
  • [Book] 今日の耳鼻咽喉科・頭頸部外科治療指針2008

    • Author(s)
      山中 昇
    • Total Pages
      663
    • Publisher
      医学書院
  • [Book] 今日の治療薬20082008

    • Author(s)
      山中 昇
    • Total Pages
      1323
    • Publisher
      南江堂
  • [Book] すぐに役立つ外来耳鼻咽喉科疾患診療のコツ2008

    • Author(s)
      田村真司, 山中 昇
    • Total Pages
      353
    • Publisher
      全日本病院出版会
  • [Book] 小児内科2008

    • Author(s)
      島田 純, 山中 昇
    • Total Pages
      1574
    • Publisher
      東京医学社

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Published: 2010-06-11   Modified: 2016-04-21  

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