Therapeutic effect of surfactant protein D in allergic inflammation of mite-sensitized mice
Summary Background Surfactant protein D (SP‐D) is involved in the innate immunity within the lung and may have important roles in modulating the inflammatory process of asthma. Objective To examine the potential immunomodulating role of SP‐D on the allergic response in mice, and its interaction with...
Gespeichert in:
Veröffentlicht in: | Clinical and experimental allergy 2005-04, Vol.35 (4), p.515-521 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 521 |
---|---|
container_issue | 4 |
container_start_page | 515 |
container_title | Clinical and experimental allergy |
container_volume | 35 |
creator | Liu, C.-F. Chen, Y.-L. Shieh, C.-C. Yu, C.-K. Reid, K. B. M. Wang, J.-Y. |
description | Summary
Background
Surfactant protein D (SP‐D) is involved in the innate immunity within the lung and may have important roles in modulating the inflammatory process of asthma.
Objective
To examine the potential immunomodulating role of SP‐D on the allergic response in mice, and its interaction with the alveolar macrophages (AMs) during allergic inflammation.
Methods
A recombinant 60 kDa fragment of human SP‐D (rfh SP‐D), Survanta, and budesonide were administrated, respectively, to Der p‐sensitive BALB/c mice before or after allergen challenge (AC). Total and differential cell counts, levels of cytokines in bronchoalveolar lavage fluids(BALFs), and levels of Der p‐specific IgE and IgG1 antibodies in sera, were assayed. The production of nitric oxide (NO), and inducible NO synthase (iNOS) expression, in AMs, were determined by ELISA and RT‐PCR, respectively.
Results
Instillation of rfh SP‐D to sensitized mice 6 h after AC (therapeutic), but not 24 h before AC (preventive), markedly reduced infiltration of eosinophils, and also reduced levels of IL‐4, IL‐5, eotaxin, and TNF‐α but elevated levels of IFN‐γ in the BALF. These effects were comparable with those obtained with budesonide treatment, whereas Survanta did not have a suppressive effect, either before or after AC. There was significant inhibition of NO production in the rfh SP‐D pre‐treated AMs of allergen‐sensitized mice, but not in naïve mice.
Conclusions
These results indicate that rfh SP‐D has a therapeutic effect on allergen‐induced bronchial inflammation, and that this might be because of its inhibitory effect on NO and TNF‐α production by AMs, and it thus prevents the development of T‐helper type 2 cytokine response. |
doi_str_mv | 10.1111/j.1365-2222.2005.02205.x |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67749456</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>831632591</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5595-8c050333a730a863fddc054fddd933bf61bcefcbb5ea7baf83d06da783e7aaa3</originalsourceid><addsrcrecordid>eNqNkU2LFDEQhoMo7rj6F6QR9NZjetL5OnhYxnVXWBVxQMFDqE5XNGN_jEkaZ_31pneGXfCidajKx_MWlbyEFBVdVjlebpcVE7xc5ViuKOVLulrlvL9HFrcX98mCal6XUun6hDyKcUspZVyrh-Sk4ooJKVYL8nXzHQPscEreFugc2lSMrohTcGATDKnYhTGhH4rXRU7QdRi-ZdQProO-h-THYRb0PmEZcYg--d_Y5r3Fx-SBgy7ik2M9JZs355v1ZXn14eLt-uyqtJxrXipLOWWMgWQUlGCubfNJnUurGWucqBqLzjYNR5ANOMVaKlqQiqEEAHZKXhza5kl_ThiT6X202HUw4DhFI6Ssdc3FP8Eqc3kGlsFnf4HbcQpDfoOptFZSalFlSB0gG8YYAzqzC76HcG0qamaXzNbMZpjZDDO7ZG5cMvssfXrsPzU9tnfCoy0ZeH4EIFroXIDB-njHCSE1veFeHbhfvsPr_x7ArM_P5lXWlwe9jwn3t3oIP_KvMcnN5_cX5pO6rNfvPmrzhf0BFVe9WA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>199877961</pqid></control><display><type>article</type><title>Therapeutic effect of surfactant protein D in allergic inflammation of mite-sensitized mice</title><source>MEDLINE</source><source>Wiley Journals</source><creator>Liu, C.-F. ; Chen, Y.-L. ; Shieh, C.-C. ; Yu, C.-K. ; Reid, K. B. M. ; Wang, J.-Y.</creator><creatorcontrib>Liu, C.-F. ; Chen, Y.-L. ; Shieh, C.-C. ; Yu, C.-K. ; Reid, K. B. M. ; Wang, J.-Y.</creatorcontrib><description>Summary
Background
Surfactant protein D (SP‐D) is involved in the innate immunity within the lung and may have important roles in modulating the inflammatory process of asthma.
Objective
To examine the potential immunomodulating role of SP‐D on the allergic response in mice, and its interaction with the alveolar macrophages (AMs) during allergic inflammation.
Methods
A recombinant 60 kDa fragment of human SP‐D (rfh SP‐D), Survanta, and budesonide were administrated, respectively, to Der p‐sensitive BALB/c mice before or after allergen challenge (AC). Total and differential cell counts, levels of cytokines in bronchoalveolar lavage fluids(BALFs), and levels of Der p‐specific IgE and IgG1 antibodies in sera, were assayed. The production of nitric oxide (NO), and inducible NO synthase (iNOS) expression, in AMs, were determined by ELISA and RT‐PCR, respectively.
Results
Instillation of rfh SP‐D to sensitized mice 6 h after AC (therapeutic), but not 24 h before AC (preventive), markedly reduced infiltration of eosinophils, and also reduced levels of IL‐4, IL‐5, eotaxin, and TNF‐α but elevated levels of IFN‐γ in the BALF. These effects were comparable with those obtained with budesonide treatment, whereas Survanta did not have a suppressive effect, either before or after AC. There was significant inhibition of NO production in the rfh SP‐D pre‐treated AMs of allergen‐sensitized mice, but not in naïve mice.
Conclusions
These results indicate that rfh SP‐D has a therapeutic effect on allergen‐induced bronchial inflammation, and that this might be because of its inhibitory effect on NO and TNF‐α production by AMs, and it thus prevents the development of T‐helper type 2 cytokine response.</description><identifier>ISSN: 0954-7894</identifier><identifier>EISSN: 1365-2222</identifier><identifier>DOI: 10.1111/j.1365-2222.2005.02205.x</identifier><identifier>PMID: 15836762</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Allergens - immunology ; Allergic diseases ; alveolar macrophage ; Animals ; Anti-Inflammatory Agents - immunology ; Antigens, Dermatophagoides - immunology ; asthma murine model ; Biological and medical sciences ; Biological Products - immunology ; Bronchoalveolar Lavage Fluid - immunology ; Budesonide - immunology ; Chemokine CCL11 ; Chemokines, CC - immunology ; Chemotactic Factors, Eosinophil - immunology ; Eosinophils - immunology ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Immunopathology ; Interferon-gamma - immunology ; Interleukin-4 - immunology ; Interleukin-5 - immunology ; Lipopolysaccharides - immunology ; Macrophages, Alveolar - immunology ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Nitric Oxide - biosynthesis ; Pulmonary Surfactant-Associated Protein D - immunology ; Pulmonary Surfactant-Associated Protein D - therapeutic use ; Pulmonary Surfactants - immunology ; Pulmonary Surfactants - therapeutic use ; Recombinant Proteins - immunology ; Recombinant Proteins - therapeutic use ; Respiratory Hypersensitivity - drug therapy ; Respiratory Hypersensitivity - immunology ; surfactant protein D ; Tumor Necrosis Factor-alpha - immunology</subject><ispartof>Clinical and experimental allergy, 2005-04, Vol.35 (4), p.515-521</ispartof><rights>2005 INIST-CNRS</rights><rights>Copyright Blackwell Publishing Apr 2005</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5595-8c050333a730a863fddc054fddd933bf61bcefcbb5ea7baf83d06da783e7aaa3</citedby><cites>FETCH-LOGICAL-c5595-8c050333a730a863fddc054fddd933bf61bcefcbb5ea7baf83d06da783e7aaa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-2222.2005.02205.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2222.2005.02205.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16679062$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15836762$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, C.-F.</creatorcontrib><creatorcontrib>Chen, Y.-L.</creatorcontrib><creatorcontrib>Shieh, C.-C.</creatorcontrib><creatorcontrib>Yu, C.-K.</creatorcontrib><creatorcontrib>Reid, K. B. M.</creatorcontrib><creatorcontrib>Wang, J.-Y.</creatorcontrib><title>Therapeutic effect of surfactant protein D in allergic inflammation of mite-sensitized mice</title><title>Clinical and experimental allergy</title><addtitle>Clin Exp Allergy</addtitle><description>Summary
Background
Surfactant protein D (SP‐D) is involved in the innate immunity within the lung and may have important roles in modulating the inflammatory process of asthma.
Objective
To examine the potential immunomodulating role of SP‐D on the allergic response in mice, and its interaction with the alveolar macrophages (AMs) during allergic inflammation.
Methods
A recombinant 60 kDa fragment of human SP‐D (rfh SP‐D), Survanta, and budesonide were administrated, respectively, to Der p‐sensitive BALB/c mice before or after allergen challenge (AC). Total and differential cell counts, levels of cytokines in bronchoalveolar lavage fluids(BALFs), and levels of Der p‐specific IgE and IgG1 antibodies in sera, were assayed. The production of nitric oxide (NO), and inducible NO synthase (iNOS) expression, in AMs, were determined by ELISA and RT‐PCR, respectively.
Results
Instillation of rfh SP‐D to sensitized mice 6 h after AC (therapeutic), but not 24 h before AC (preventive), markedly reduced infiltration of eosinophils, and also reduced levels of IL‐4, IL‐5, eotaxin, and TNF‐α but elevated levels of IFN‐γ in the BALF. These effects were comparable with those obtained with budesonide treatment, whereas Survanta did not have a suppressive effect, either before or after AC. There was significant inhibition of NO production in the rfh SP‐D pre‐treated AMs of allergen‐sensitized mice, but not in naïve mice.
Conclusions
These results indicate that rfh SP‐D has a therapeutic effect on allergen‐induced bronchial inflammation, and that this might be because of its inhibitory effect on NO and TNF‐α production by AMs, and it thus prevents the development of T‐helper type 2 cytokine response.</description><subject>Allergens - immunology</subject><subject>Allergic diseases</subject><subject>alveolar macrophage</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - immunology</subject><subject>Antigens, Dermatophagoides - immunology</subject><subject>asthma murine model</subject><subject>Biological and medical sciences</subject><subject>Biological Products - immunology</subject><subject>Bronchoalveolar Lavage Fluid - immunology</subject><subject>Budesonide - immunology</subject><subject>Chemokine CCL11</subject><subject>Chemokines, CC - immunology</subject><subject>Chemotactic Factors, Eosinophil - immunology</subject><subject>Eosinophils - immunology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Immunopathology</subject><subject>Interferon-gamma - immunology</subject><subject>Interleukin-4 - immunology</subject><subject>Interleukin-5 - immunology</subject><subject>Lipopolysaccharides - immunology</subject><subject>Macrophages, Alveolar - immunology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Nitric Oxide - biosynthesis</subject><subject>Pulmonary Surfactant-Associated Protein D - immunology</subject><subject>Pulmonary Surfactant-Associated Protein D - therapeutic use</subject><subject>Pulmonary Surfactants - immunology</subject><subject>Pulmonary Surfactants - therapeutic use</subject><subject>Recombinant Proteins - immunology</subject><subject>Recombinant Proteins - therapeutic use</subject><subject>Respiratory Hypersensitivity - drug therapy</subject><subject>Respiratory Hypersensitivity - immunology</subject><subject>surfactant protein D</subject><subject>Tumor Necrosis Factor-alpha - immunology</subject><issn>0954-7894</issn><issn>1365-2222</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU2LFDEQhoMo7rj6F6QR9NZjetL5OnhYxnVXWBVxQMFDqE5XNGN_jEkaZ_31pneGXfCidajKx_MWlbyEFBVdVjlebpcVE7xc5ViuKOVLulrlvL9HFrcX98mCal6XUun6hDyKcUspZVyrh-Sk4ooJKVYL8nXzHQPscEreFugc2lSMrohTcGATDKnYhTGhH4rXRU7QdRi-ZdQProO-h-THYRb0PmEZcYg--d_Y5r3Fx-SBgy7ik2M9JZs355v1ZXn14eLt-uyqtJxrXipLOWWMgWQUlGCubfNJnUurGWucqBqLzjYNR5ANOMVaKlqQiqEEAHZKXhza5kl_ThiT6X202HUw4DhFI6Ssdc3FP8Eqc3kGlsFnf4HbcQpDfoOptFZSalFlSB0gG8YYAzqzC76HcG0qamaXzNbMZpjZDDO7ZG5cMvssfXrsPzU9tnfCoy0ZeH4EIFroXIDB-njHCSE1veFeHbhfvsPr_x7ArM_P5lXWlwe9jwn3t3oIP_KvMcnN5_cX5pO6rNfvPmrzhf0BFVe9WA</recordid><startdate>200504</startdate><enddate>200504</enddate><creator>Liu, C.-F.</creator><creator>Chen, Y.-L.</creator><creator>Shieh, C.-C.</creator><creator>Yu, C.-K.</creator><creator>Reid, K. B. M.</creator><creator>Wang, J.-Y.</creator><general>Blackwell Science Ltd</general><general>Blackwell</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>200504</creationdate><title>Therapeutic effect of surfactant protein D in allergic inflammation of mite-sensitized mice</title><author>Liu, C.-F. ; Chen, Y.-L. ; Shieh, C.-C. ; Yu, C.-K. ; Reid, K. B. M. ; Wang, J.-Y.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5595-8c050333a730a863fddc054fddd933bf61bcefcbb5ea7baf83d06da783e7aaa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Allergens - immunology</topic><topic>Allergic diseases</topic><topic>alveolar macrophage</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - immunology</topic><topic>Antigens, Dermatophagoides - immunology</topic><topic>asthma murine model</topic><topic>Biological and medical sciences</topic><topic>Biological Products - immunology</topic><topic>Bronchoalveolar Lavage Fluid - immunology</topic><topic>Budesonide - immunology</topic><topic>Chemokine CCL11</topic><topic>Chemokines, CC - immunology</topic><topic>Chemotactic Factors, Eosinophil - immunology</topic><topic>Eosinophils - immunology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Immunopathology</topic><topic>Interferon-gamma - immunology</topic><topic>Interleukin-4 - immunology</topic><topic>Interleukin-5 - immunology</topic><topic>Lipopolysaccharides - immunology</topic><topic>Macrophages, Alveolar - immunology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Nitric Oxide - biosynthesis</topic><topic>Pulmonary Surfactant-Associated Protein D - immunology</topic><topic>Pulmonary Surfactant-Associated Protein D - therapeutic use</topic><topic>Pulmonary Surfactants - immunology</topic><topic>Pulmonary Surfactants - therapeutic use</topic><topic>Recombinant Proteins - immunology</topic><topic>Recombinant Proteins - therapeutic use</topic><topic>Respiratory Hypersensitivity - drug therapy</topic><topic>Respiratory Hypersensitivity - immunology</topic><topic>surfactant protein D</topic><topic>Tumor Necrosis Factor-alpha - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, C.-F.</creatorcontrib><creatorcontrib>Chen, Y.-L.</creatorcontrib><creatorcontrib>Shieh, C.-C.</creatorcontrib><creatorcontrib>Yu, C.-K.</creatorcontrib><creatorcontrib>Reid, K. B. M.</creatorcontrib><creatorcontrib>Wang, J.-Y.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical and experimental allergy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, C.-F.</au><au>Chen, Y.-L.</au><au>Shieh, C.-C.</au><au>Yu, C.-K.</au><au>Reid, K. B. M.</au><au>Wang, J.-Y.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Therapeutic effect of surfactant protein D in allergic inflammation of mite-sensitized mice</atitle><jtitle>Clinical and experimental allergy</jtitle><addtitle>Clin Exp Allergy</addtitle><date>2005-04</date><risdate>2005</risdate><volume>35</volume><issue>4</issue><spage>515</spage><epage>521</epage><pages>515-521</pages><issn>0954-7894</issn><eissn>1365-2222</eissn><abstract>Summary
Background
Surfactant protein D (SP‐D) is involved in the innate immunity within the lung and may have important roles in modulating the inflammatory process of asthma.
Objective
To examine the potential immunomodulating role of SP‐D on the allergic response in mice, and its interaction with the alveolar macrophages (AMs) during allergic inflammation.
Methods
A recombinant 60 kDa fragment of human SP‐D (rfh SP‐D), Survanta, and budesonide were administrated, respectively, to Der p‐sensitive BALB/c mice before or after allergen challenge (AC). Total and differential cell counts, levels of cytokines in bronchoalveolar lavage fluids(BALFs), and levels of Der p‐specific IgE and IgG1 antibodies in sera, were assayed. The production of nitric oxide (NO), and inducible NO synthase (iNOS) expression, in AMs, were determined by ELISA and RT‐PCR, respectively.
Results
Instillation of rfh SP‐D to sensitized mice 6 h after AC (therapeutic), but not 24 h before AC (preventive), markedly reduced infiltration of eosinophils, and also reduced levels of IL‐4, IL‐5, eotaxin, and TNF‐α but elevated levels of IFN‐γ in the BALF. These effects were comparable with those obtained with budesonide treatment, whereas Survanta did not have a suppressive effect, either before or after AC. There was significant inhibition of NO production in the rfh SP‐D pre‐treated AMs of allergen‐sensitized mice, but not in naïve mice.
Conclusions
These results indicate that rfh SP‐D has a therapeutic effect on allergen‐induced bronchial inflammation, and that this might be because of its inhibitory effect on NO and TNF‐α production by AMs, and it thus prevents the development of T‐helper type 2 cytokine response.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>15836762</pmid><doi>10.1111/j.1365-2222.2005.02205.x</doi><tpages>7</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0954-7894 |
ispartof | Clinical and experimental allergy, 2005-04, Vol.35 (4), p.515-521 |
issn | 0954-7894 1365-2222 |
language | eng |
recordid | cdi_proquest_miscellaneous_67749456 |
source | MEDLINE; Wiley Journals |
subjects | Allergens - immunology Allergic diseases alveolar macrophage Animals Anti-Inflammatory Agents - immunology Antigens, Dermatophagoides - immunology asthma murine model Biological and medical sciences Biological Products - immunology Bronchoalveolar Lavage Fluid - immunology Budesonide - immunology Chemokine CCL11 Chemokines, CC - immunology Chemotactic Factors, Eosinophil - immunology Eosinophils - immunology Fundamental and applied biological sciences. Psychology Fundamental immunology Immunopathology Interferon-gamma - immunology Interleukin-4 - immunology Interleukin-5 - immunology Lipopolysaccharides - immunology Macrophages, Alveolar - immunology Medical sciences Mice Mice, Inbred BALB C Nitric Oxide - biosynthesis Pulmonary Surfactant-Associated Protein D - immunology Pulmonary Surfactant-Associated Protein D - therapeutic use Pulmonary Surfactants - immunology Pulmonary Surfactants - therapeutic use Recombinant Proteins - immunology Recombinant Proteins - therapeutic use Respiratory Hypersensitivity - drug therapy Respiratory Hypersensitivity - immunology surfactant protein D Tumor Necrosis Factor-alpha - immunology |
title | Therapeutic effect of surfactant protein D in allergic inflammation of mite-sensitized mice |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T08%3A17%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Therapeutic%20effect%20of%20surfactant%20protein%20D%20in%20allergic%20inflammation%20of%20mite-sensitized%20mice&rft.jtitle=Clinical%20and%20experimental%20allergy&rft.au=Liu,%20C.-F.&rft.date=2005-04&rft.volume=35&rft.issue=4&rft.spage=515&rft.epage=521&rft.pages=515-521&rft.issn=0954-7894&rft.eissn=1365-2222&rft_id=info:doi/10.1111/j.1365-2222.2005.02205.x&rft_dat=%3Cproquest_cross%3E831632591%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=199877961&rft_id=info:pmid/15836762&rfr_iscdi=true |