October Medical Journal Review（10月の医学雑誌レビュー）
WAO Now: What's New in the World of WAO（WAO最新ニュース）
And In Other News（その他のニュース）
　

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October 2006 World Medical Journal Review（医学雑誌レビュー）

Mark C. Glaum, M.D., Ph.D., WAO Guest Editor, Assistant Professor of Medicine and Pediatrics, University of South Florida College of Medicine, reviewed premier October medical journal articles for practicing allergists.

南フロリダ大学小児科助教授のGlaum博士によるアレルギー臨床医のための10月の医学雑誌レビュー

1. ALENDRONATE IS MORE EFFECTIVE THAN ALFACALCIDOL IN PREVENTING GLUCOCORTICOID-INDUCED BONE LOSS
Subjects (n=201) who were starting glucocorticoids at a daily dose equivalent to 7.5 mg of prednisone secondary to rheumatic disease were enrolled in double-blind, placebo-controlled trial for an 18-month period. Subjects were randomized to receive alendronate (10 mg) plus placebo or alfacalcidol (1 mg) plus placebo daily. Measurement of bone mineral density and incidence of morphometric vertebral deformities were primary and secondary outcomes, respectively. In subjects receiving alendronate, lumbar spine bone mineral density scores increased by 2.1% while lumbar spine bone mineral density scores decreased by 1.9% in the alfacalcidiol group. Editor’s comment: Alendronate effectively inhibits bone loss due to sustained glucocorticoid use. De Nijs RNJ, Jacobs JWG, Lems WF, et al. N Engl J Med 2006; 355:675-84

アレンドロネート（アレンドロン酸ナトリウム水和物）は，骨表面に結合し破骨細胞による骨吸収を抑制する窒素含有のビスホスホネートである．プレドニゾン7.5mg内服を開始した201名の患者に対するアレンドロネートの有効性に関するダブルブラインドでプレセボまたはalfacalcidolを対照とする比較試験が18ヶ月間実施された．骨密度測定を第一アウトカム，脊椎変形を第２アウトカムとした．腸骨棘の骨密度は，アレンドロネート投与群では2.1%増加した．一方，alfacalcidiol投与群では1.9%の増加であった．

2. MAST CELLS REGULATE T CELL TOLERANCE
Mast cells are known to propagate allergic inflammation in response to allergen challenge. Observations that successful skin grafts in mice become infiltrated with T regulatory cells (T_reg) and mast cells led to the hypothesis that T_reg - mast cell interactions may mediate graft tolerance. To evaluate this, investigators attempted to induce therapeutic tolerance in genetically engineered, mast cell-deficient mice by skin graft transplantation. All transplant attempts in mast cell deficient mice were quickly rejected. Reconstitution of mast cell populations in deficient mice restored the host’s ability to accept grafts for prolonged periods of time. Editor’s comment: Mast cells may possess immunomodulatory functions that go well beyond their established role in allergy. Please see excellent accompanying editorial. Lu L, Lind EF, Gondek DC, et al. Nature 2006;442:997-1002, Waldmann H, 987-8

マスト細胞はIgE抗体を介してアレルギー炎症を惹起することはよく知られている．ところが，マウスの皮膚移植の実験において，マスト細胞は炎症を抑制する方向に作用することがわかった．生着皮膚移植片の周囲にはCD4+CD25+Foxp3+制御性T細胞(Treg)とマスト細胞の著しい浸潤が認められる．著者らはマスト細胞欠損マウスを使用してこの皮膚移植実験を行ったところ，いずれの条件においても皮膚移植片は速やかに拒絶された．しかし，培養マスト細胞を使って，このマスト細胞欠損マウスのマスト細胞を再構築したところ，移植片は拒絶されなかった．活性化TregはIL-9を分泌し，IL-9はマスト細胞を活性化させた．IL-9を中和したところ移植片は拒絶された．したがって，同種皮膚移植片の免疫寛容には，まずTregが動員され，IL-9を分泌する．IL-9はマスト細胞を活性化し，移植拒絶反応をひきおこすTh1細胞の作用を遮断する何らかの物質を遊離させる．以上の機序が関係すると想定された．

3. ANTI-INFLAMMATORY EFFECTS OF AZITHROMYCIN IN COPD
Macrolide antibiotics may possess anti-inflammatory properties. Chronic obstructive pulmonary disease (COPD) is associated with increased apoptosis and impaired phagocytosis in the airways. Alveolar macrophages were obtained by bronchoalveolar lavage (BAL) from 9 subjects with COPD and 10 healthy controls. Alveolar macrophages were purified, then ability to phagocytose apoptotic epithelial cells or neutrophils was measured by flow cytometry in the presence or absence of aziththromycin (500 ng/ml^-1). Phagocytosis by alveolar macrophages was reduced in subjects with COPD as compared to healthy controls. Incubation of alveolar macrophages from COPD subjects in azithromycin improved phagocytosis of epithelial cells and neutrophils to levels near those of healthy controls. Editor’s comment: Low dose azithromycin may serve as an adjunct therapy in COPD by promoting increased alveolar macrophage phagocytosis. Hodge S, Hodge G, Brozyna H, et al. Eur Resp J 2006; 28:486-95

マクロライド抗生物質は抗炎症作用を有する可能性がある．この研究では著者らはCOPD患者にアジスロマイシンを使用し有効性を検討し，気管支肺胞洗浄を施行し肺胞マクロファージの貪食能を検討した．肺胞マクロファージの貪食能はCOPD患者では正常対照よりも低下していたがアジスロマイシンを使用すると正常並に回復した．

4. WAIT AND SEE PRESCTIPTION LIMITS ANTIBIOTIC USE IN ACUTE OTITIS MEDIA
Two-hundred and eighty-three pediatric patients diagnosed with acute otitis media in an emergency department were randomized to receive a "wait and see prescription" (only to be filled if symptoms were unchanged or worse in 48 hours) or a standard prescription for antibiotics. Structured phone interviews were conducted 4 to 6, 11 to 14, and 30 to 40 days after enrollment to determine outcomes. Parents of subjects who received a wait and see prescription were more likely not to fill the antibiotic prescription than parents who received a standard prescription (62% vs. 13% p < 0.001). There was no difference between groups in regard to frequency of subsequent fever, otalgia or unscheduled visits for medical care. Editor’s comment: Watchful waiting reduces antibiotic usage in acute otitis media. Spiro DM, Tay K, Arnold DH, et al. JAMA 2006; 296:1235-41

283人の急性中耳炎と診断された小児患者に対し，通常の抗生物質をした群と”様子見処方箋”(48時間たって症状が不変または悪化したら実際に処方する)を与えた群に分けてその後の中耳炎の経過を観察した．その結果，抗生物質は様子見処方箋群の62%に実際に処方されなかった．また，急性中耳炎のその後の症状には違いは認めなかった．

5. PROLONGED BREASTFEEDING ASSOCIATED WITH INCREASED RISK OF ATOPIC DERMATITIS
Two-hundred healthy newborns were enrolled in a prospective 20-year follow-up study to determine if prolonged breastfeeding (greater than 6 months) conferred additional protection against the development of atopy. Mothers of subjects were encouraged to exclusively breastfeed for as long as possible. Subjects were examined and skin prick tested at ages 5, 11 and 20 years. Exclusive breastfeeding for nine months or more was associated with higher incidence of atopic dermatitis (p = 0.002) at age 5. Editor’s comment: Breastfeeding for the first six months of life is currently recommended; prolonged breastfeeding greater than nine months may promote development of atopic dermatitis. Pesonen M, Kallio MJT, Ranki A, Siimes MA. Clin Exp Allergy 2006; 36:1011-18

200名の健康な新生児に対し母乳を生後9ヶ月以降も継続して与え，離乳食を遅延させること（排他的母乳遷延群）がアレルギー疾患発症に対してどのように影響を与えるか20年間観察した．その結果，排他的母乳遷延群のうちアレルギー家族歴陽性者では５歳時点でアトピー性皮膚炎の罹患率と食物アレルギーの罹患率が，11歳時点で食物アレルギーの罹患率が，それぞれ有意に高かった．しかし，20歳の時点では有意差を消失した．また，皮膚プリックのテストの結果では排他的母乳遷延群と対照群との間に有意差をみられなかった．訳者注：離乳食を遅らせて母乳を9ヶ月以上与え続けると皮膚炎症状が増えるという意外な結果であった．しかし，その影響は僅かなものであり，また生後6ヶ月まで母乳を与えるべきであるというWHOの勧告に反する結果ではなく，冷静に判断すべきである．

6. SELF-REPLICATING DNA VACCINE ENCODING Phl p5 PREVENTS ALLERGIC SENSITIZATION
Immunization with DNA-based allergen vaccines has yielded promising results as a potentially novel modality of immunotherapy. Limitations to this approach include reduced immunologic responses in humans and relatively high concentrations of DNA vaccine required to induce immunity. Investigators examined the effectiveness of using a self-replicating (replicon) DNA vaccine to induce protection against allergenic sensitization in a mouse model. Mice were immunized intradermally with replicon Phl p5 DNA or conventional DNA vaccines followed by sensitization and intranasal challenge with Phl p5. Titers of IgG1, IgG2a and IgE were measured from sera, while eosinophil counts and cytokine levels were measured from BAL fluid. Lung sections were analyzed for presence of inflammatory infiltrates, increased mucus production and epithelial damage. Replicon DNA vaccination with Phl p5 resulted in reduced expression of specific IgE, Th1-biased cytokine expression, fewer eosinophils and reduced markers of airway inflammation at a dose 100-fold less than a comparable conventional DNA vaccine. Editor’s comment: Self-replicating DNA vaccines may pave the way for usage of DNA allergen vaccines in humans. Gabler M, Scheiblhofer S, Kern K, et al. J Allergy Clin Immunol 2006; 118:734-41

プラズミドDNAに病原体などの抗原を入れて作成するDNAワクチンはその強力で持続的なTh1細胞活性化作用によりマウスでは極めて有効であるが，ヒトではさほど有効性を示さない．このことはヒトとマウスにおけるToll様受容体(TLR)9の分布の違いによると想定される．一方，レプリカーゼをもちいたDNAワクチンでは二本鎖RNAが形成されTLR3などTLR9以外の経路も刺激される．著者らはカモガヤ抗原Phl p5感作に対するPhl p5封入レプリカーゼによる自己複製DNAワクチンの効果をプラズミドDNAワクチンと比較して検討した．その結果，レプリカーゼDNAワクチンではIgE抗体産生，気道好酸球数などがプラズミドDNAに比較して100分の1となった．訳者注：レプリカーゼ自己複製DNAワクチンはおそらくヒトにおいても有用であると推測される．

7. EVIDENCE FOR SUPERANTIGENS IN CHRONIC RHINOSINUSITIS
Superantigens have been implicated as a cause of chronic rhinosinusitis through the oligoclonal expansion of T cell populations with subsequent mucosal inflammation. Eighteen subjects with chronic rhinosinusitis with nasal polyposis scheduled for surgery were prospectively recruited. Nasal polyp tissue and blood samples were analyzed by flow cytometry for the distribution of 24 specific T cell receptor (TCR) Vβ domains typically associated with a superantigen response. Each of the 18 subjects demonstrated expansion of nasal polyp lymphocytes expressing TCRs with specific Vβ domains. The average number of Vβ clones was greater in nasal polyps as compared to peripheral blood lymphocytes implicating the nasal mucosa as an antigen source. Editor’s comment: Staphylococcal toxins may be central to the development of chronic rhinosinusitis with nasal polyposis. Conley DB, Tripathi A, Seiberling KA, et al. Am J Rhinol 2006; 20:451-5

副鼻腔炎患者の鼻茸組織中のT細胞β鎖のレパトアを調べたところ特定のクローンが増加していた．鼻粘膜の細菌のスーパー抗原に対する反応の関与が示唆された．

8. AIRWAY RETICULAR BASEMENT MEMBRANE THICKENING IN ASTHMA IS DISTINCT FROM THAT SEEN IN FIBROSIS
Airway reticular basement membrane (RBM) thickening in asthma is thought to be a consequence of subepithelial fibrosis that is characterized by an irreversible accumulation of interstitial collagen. Abnormal thickening of the RBM in asthma can be seen as early as age 4 and may be maximally thickened by ages 6-16 in severely asthmatic children, although this may be partially reversible. Asthmatic adults (n =10), children (aged 6-10 yrs (n = 10)), and infants (aged 0.3-2 yrs (n = 10)) as well as age-matched non-asthmatic controls were recruited. All subjects underwent bronchoscopy and endobronchial biopsy. Specimens were examined by electron microscopy. Histologic examination of the thickened RBM in asthmatics revealed a normal ratio of fibrils to matrix and the fibrils did not resemble those of interstitial collagen. These features were comparable to age-matched controls. Editor’s comment: Airway remodeling in asthma may result from a different process than that seen in fibrotic lung disease. Saglani S, Molyneux C, Gong H, et.al. Eur Resp J 2006; 28:505-12

気道リモデリングの要素のうち最も初期からみられる上皮網状基底膜層の肥厚は，その後顕在化する上皮下の繊維化と関連していると考えられていた．著者らは乳児から成人までの喘息患者において検討した結果，網状基底膜層の肥厚は可逆的であり上皮下の繊維化とは関連していないことを見いだした．

9. REVIEW OF VIRAL INFECTIONS, CHEMOKINE EXPRESSION AND ASTHMA
This article reviews the current literature supporting the role for chemokines in promoting airway inflammation during viral upper respiratory tract infections. Excessive airway inflammation driven by viral-induced chemokine expression is thought to contribute to asthma exacerbations in certain individuals. Commonly implicated viruses and associated chemokine profiles are discussed. Editor’s comment: Inflammation driven by viral infection often flares asthma. Schaller M, Hogaboam CM, Lukacs N, Kunkel SL. J Allergy Clin Immunol 2006;118:295-302

喘息病態におけるウイルス感染とケモカインの役割に関する総説．

10. REVIEW OF ASPIRIN-INDUCED ASTHMA
This is a clearly written, concise review of aspirin-exacerbated respiratory disease. History of the disease, epidemiology, pathogenesis, and desensitization protocols are discussed. Editor’s comment: Aspirin sensitivity should be considered in the evaluation of asthmatic patients because desensitization provides an effective means of disease control. Culp JA, Borish L, Mozena JD. J Respir Dis 2006:27(7):282-90. No abstract is available.

アスピリン誘発喘息に関する総説．

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WAO Now: What's New in the World of WAO （最新ニュース）

Reminder: Applications for US GLORIA for 2007 are still being accepted from regional, state and local societies.

WAO Board Visits the Asia-Pacific Region

Japanese Society of Allergology Fall Meeting, Tokoyo, Japan
Michael Kaliner, WAO President, G. Walter Canonica, WAO President-Elect, and WAO Board Member Lanny Rosenwasser participated in the Japanese Society of Allergology (JSA) Fall Meeting, 2-4 November 2006. They held discussions with the leadership of JSA about future collaborations and also took the opportunity to meet with local sponsors for the World Allergy Congress 2007 in Bangkok, Thailand. The hospitality of JSA was most welcoming and for that WAO would like to express sincere thanks.

WAO会長のMichael Kaliner氏と次期会長のWalter Canonica氏，WAO評議員のLanny Rosenwasser氏は日本アレルギー学会のため来日し，国際交流委員会のメンバーとバンコクで行われる2007年のWAO会議のスポンサーなどを含めてWAOにおける日本アレルギー学会の位置づけ，リーダーシップのあり方について討論をおこなった．

Joint WAO and KAAACI symposium, Seoul, Korea
WAO’s Board of Directors met in Seoul, Korea, 3 November 2006. The meeting was organized to coincide with the Korean Academy of Asthma, Allergy and Clinical Immunology (KAAACI) and WAO Joint Congress 2006 and the 9th West Pacific Allergy Symposium (WPAS) in Seoul, 3-5 November 2006. Members from WAO’s Board of Directors participated in an excellent scientific program that showcased ongoing research in Korea and its neighboring countries from the Asia-Pacific Region. Special lectures were presented by WAO President, Michael Kaliner, who spoke on Global Management of Rhinitis, Sinusitis and Asthma, and by WAO Board Member Jean Bousquet, who introduced the World Health Organization’s Global Alliance Against Chronic Respiratory Diseases program, of which WAO is a founding member. Keynote lectures presented by Korean experts included Viral Infection and Asthma, presented by Joon Sung Le. You-Young Kim’s special lecture discussed the Practical Implementation of an Easy Asthma Management Program. The Congress presented an opportunity to provide information to local allergists about plans for the World Allergy Congress in Bangkok. WAO would like to extend warm thanks to KAAACI and the West Pacific Allergy Organization for their hospitality and collaboration.

韓国アレルギー学会とWAO共催の会議がソウルにて11月3-5日開催された．WAOは韓国アレルギー学会の温かいもてなしに感謝する．

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And In Other News （その他のニュース）

Allergy Book Reviews

Immunogenomics and Human Disease
Editor: Andras Falus

　

今月の本の紹介は免疫ゲノム科学に関する書籍である．先端的であるばかりでなく，SNPに関する記載など日常臨床に役立つ内容となっている．としている．

ISBN #: ISBN: 0-470-03324-X

List price: $180.00 USD
Available from: Wiley

Reviewer: Gary Hellermann, PhD
University of South Florida College of Medicine, Tampa, FL, USA

Description:
This is a collection of 23 articles by an international group of authors focusing on the use of bioinformatics in studying human disease. The content includes discussions and examples of the use of new technology for studying the pathology of immune diseases such as asthma, lupus and arthritis, and the role of the immune system in cancer biology.

Purpose:
The editor refers to the specific area of bioinformatics as immunogenomics, the application of new laboratory methods and computing technology to the study of variations in the human genome as they relate to diseases involving the immune system. The use of individual human DNA sequence information for disease research, designing new drugs and therapies and individually tailoring treatments is of the highest importance in this century. The breadth and depth of the subject presents a daunting task to any editor hoping to produce a useful work, but this collection has succeeded in covering the field in sufficient detail and variety to match that hope.

Audience:
Although primarily aimed at researchers, others such as clinicians, students and those engaged in drug discovery will also profit from reading this collection of articles. Dr Falus is professor and chairman of the Department of Genetics, Cell and Immunobiology at Semmelweis University in Budapest, Hungary. He is a member of the Hungarian Academy of Sciences and is the author of over 250 scientific papers.

Features:
We are still in the midst of the genomic revolution arising from the sequencing of the human genome and the understanding of this wealth of data at the level of proteins and pathways is the next great challenge. Immunogenomics, the analysis of genomic variations in relation to specific immune system responses, is the focus of this collection of articles by internationally known experts in immunology and bioinformatics. As one of the book's authors put it, "The genome tells us what could happen, the transcriptome tells us what might happen and the proteome tells us what does happen." Obtaining the gene sequence is only the first stage in a complex, multi-step process that is brought out here through detailed description, example and illustration.

Assessment:
The book is not only an up-to-date review, but includes practical information on identifying single nucleotide polymorphisms, using arrays for genomic analysis, photoaffinity labeling, human monocytes and dendritic cells as model systems, identifying diagnostic markers, and much more. Its usefulness also stems from the individual authors' attempts to define the terms, concepts and methods employed in bioinformatics. A standardization of the language used in this complex area should greatly facilitate communication. From the general to the specific, this book provides a comprehensive cross-section of current knowledge on the rapidly changing field of genomics as it applies to the immune system.

The Immune Response: Basic and Clinical Principles
By: Tak W. Mak and Mary E. Saunders
もう一冊の紹介書籍は基礎から臨床におよぶ広い範囲の免疫学に関する本である．学生を含め対象が広いとしている．
ISBN-13: 978-0-12-088451-3
ISBN-10: 0-12-088451-8

List price: $139.95 USD
Available from: Elsevier

Reviewer:  Sam Mehr, MBBS, BMedSci
The Children’s Hospital at Westmead, Westmead, NSW, Australia

Description:
The majority of individuals studying or working in the field of Immunology would be familiar with the texts of Roitt, Abbas and Janeway. Outside of these texts, there are few other textbooks that are able to provide a comprehensive overview of Basic and Clinical Immunology. This textbook is an important contribution, providing the reader with a clear, complete and concise overview of the immune system in both health and disease.

Purpose:
The book is divided into two parts, Basic Immunology (Part I) and Clinical Immunology (Part II). The purpose is to introduce the reader to the basic concepts of immunology before delving into more advanced immunological topics. The establishment of these concepts enables the reader to understand how derangements of these basic mechanisms can then lead to clinical disease.

Audience:
The target audience is wide, and includes undergraduates, graduates and seasoned clinical and laboratory Immunologists.

Features:
The authors have written all the chapters and have had chapters reviewed by sub-specialists in the field. Each chapter starts with a table of contents outlining the material to be covered. Historical notes are often provided at the start of each chapter, enabling the reader to comprehend how various immunological concepts came into being and how these have changed with time. The text is clear and succinct and this combined with the excellent illustrations and tables make this an easy read. The authors direct the reader to other suggested reading material at the end of each chapter for those who require an even more meticulous level of detail.

Assessment:
This is a valuable book for any veteran immunologist or student of immunology.  The authors’ ability to make difficult concepts easy to understand through clear explanations and illustrations is its major attraction.

Find more allergy book reviews on the WAO Website here.