Inhibition of Airway Smooth Muscle Adhesion and Migration by the Disintegrin Domain of ADAM-15
Disintegrin and metalloprotease proteins (ADAMs) are membrane-anchored glycoproteins involved in cell adhesion, cell fusion, protein ecto-domain shedding, and intracellular signaling. We examined whether the disintegrin domain of ADAM-15 (named ddADAM-15) containing an Asp-Gly-Asp (RGD) integrin-bin...
Gespeichert in:
| Veröffentlicht in: | American journal of respiratory cell and molecular biology 2007-10, Vol.37 (4), p.494-500 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 500 |
|---|---|
| container_issue | 4 |
| container_start_page | 494 |
| container_title | American journal of respiratory cell and molecular biology |
| container_volume | 37 |
| creator | Lu, Dong Xie, ShaoPing Sukkar, Maria B Lu, Xinjie Scully, Michael F Chung, Kian Fan |
| description | Disintegrin and metalloprotease proteins (ADAMs) are membrane-anchored glycoproteins involved in cell adhesion, cell fusion, protein ecto-domain shedding, and intracellular signaling. We examined whether the disintegrin domain of ADAM-15 (named ddADAM-15) containing an Asp-Gly-Asp (RGD) integrin-binding motif could interfere with airway smooth muscle cell (ASMC) adhesion and migration. Recombinant ddADAM-15 adhered to human ASMCs with saturation kinetics, and was beta(1)-integrin dependent. ddADAM-15 inhibited the binding of fibrinogen but not of fibronectin to ASMCs. ddADAM-15 also inhibited platelet-derived growth factor (PDGF)-induced ASMC migration, and this was reversed by an anti-beta(1)-integrin antibody. PDGF induced the activation of phosphoinositol-3-kinase (PI3K) and p38 mitogen-activated protein kinase (MAPK), and selective inhibitors of these kinases inhibited PDGF-induced ASMC migration. ddADAM-15 did not inhibit PDGF-induced activation of PI3K or p38, thereby excluding these kinase pathways as a mechanism by which ddADAM-15 inhibits ASMC migration. ADAM-15 mRNA and protein were expressed under basal conditions, and both gene and protein expression were inhibited by PDGF. In summary, ddADAM-15 inhibits ASMC adhesion and migration through the beta(1)-integrin, without modulating signaling pathways involved in ASMC migratory responses. |
| doi_str_mv | 10.1165/rcmb.2006-0364OC |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_68270888</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1339575741</sourcerecordid><originalsourceid>FETCH-LOGICAL-c357t-2d8fb154651a445bbed6843cc85c9568e8cb113068e4e4fc47d6ccf79f9cca283</originalsourceid><addsrcrecordid>eNpdkEtLxDAURoMovveuJLgQN9WkzavLYcYXOLhQt4Y0TacZ2kaTlmH-vakdEFzduzjfdy8HgAuMbjFm9M7rtrhNEWIJyhh5ne-BY0wzmpBc5PtxR4QkmJL8CJyEsEYIpwLjQ3CEOeUUcXEMPp-72ha2t66DroIz6zdqC99a5_oaLoegGwNnZW3CCKiuhEu78uoXL7awrw1c2GC73qy87eDCtcpORYvZMp4-AweVaoI5381T8PFw_z5_Sl5eH5_ns5dEZ5T3SVqKqoiPMooVIbQoTMkEybQWVOeUCSN0gXGG4kYMqTThJdO64nmVa61SkZ2C66n3y7vvwYRetjZo0zSqM24IkomUIyFG8OofuHaD7-JvMkWcCswYixCaIO1dCN5U8svbVvmtxEiO4uUoXo7i5SQ-Ri53vUPRmvIvsDMdgZsJqO2q3lhvZGhV00QcS7Ue-zIuiSQ5yX4AmUWMQQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>207581666</pqid></control><display><type>article</type><title>Inhibition of Airway Smooth Muscle Adhesion and Migration by the Disintegrin Domain of ADAM-15</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><source>EZB Electronic Journals Library</source><source>Journals@Ovid Complete</source><creator>Lu, Dong ; Xie, ShaoPing ; Sukkar, Maria B ; Lu, Xinjie ; Scully, Michael F ; Chung, Kian Fan</creator><creatorcontrib>Lu, Dong ; Xie, ShaoPing ; Sukkar, Maria B ; Lu, Xinjie ; Scully, Michael F ; Chung, Kian Fan</creatorcontrib><description>Disintegrin and metalloprotease proteins (ADAMs) are membrane-anchored glycoproteins involved in cell adhesion, cell fusion, protein ecto-domain shedding, and intracellular signaling. We examined whether the disintegrin domain of ADAM-15 (named ddADAM-15) containing an Asp-Gly-Asp (RGD) integrin-binding motif could interfere with airway smooth muscle cell (ASMC) adhesion and migration. Recombinant ddADAM-15 adhered to human ASMCs with saturation kinetics, and was beta(1)-integrin dependent. ddADAM-15 inhibited the binding of fibrinogen but not of fibronectin to ASMCs. ddADAM-15 also inhibited platelet-derived growth factor (PDGF)-induced ASMC migration, and this was reversed by an anti-beta(1)-integrin antibody. PDGF induced the activation of phosphoinositol-3-kinase (PI3K) and p38 mitogen-activated protein kinase (MAPK), and selective inhibitors of these kinases inhibited PDGF-induced ASMC migration. ddADAM-15 did not inhibit PDGF-induced activation of PI3K or p38, thereby excluding these kinase pathways as a mechanism by which ddADAM-15 inhibits ASMC migration. ADAM-15 mRNA and protein were expressed under basal conditions, and both gene and protein expression were inhibited by PDGF. In summary, ddADAM-15 inhibits ASMC adhesion and migration through the beta(1)-integrin, without modulating signaling pathways involved in ASMC migratory responses.</description><identifier>ISSN: 1044-1549</identifier><identifier>EISSN: 1535-4989</identifier><identifier>DOI: 10.1165/rcmb.2006-0364OC</identifier><identifier>PMID: 17575078</identifier><identifier>CODEN: AJRBEL</identifier><language>eng</language><publisher>United States: Am Thoracic Soc</publisher><subject>ADAM Proteins - chemistry ; ADAM Proteins - genetics ; ADAM Proteins - metabolism ; ADAM Proteins - pharmacology ; Cell Adhesion - drug effects ; Cell Movement - drug effects ; Gene Expression Regulation - drug effects ; Humans ; Integrins - metabolism ; Membrane Proteins - chemistry ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Membrane Proteins - pharmacology ; Mitogen-Activated Protein Kinases - metabolism ; Mutant Proteins - pharmacology ; Myocytes, Smooth Muscle - cytology ; Myocytes, Smooth Muscle - drug effects ; Myocytes, Smooth Muscle - enzymology ; Phosphatidylinositol 3-Kinases - metabolism ; Phosphorylation - drug effects ; Platelet-Derived Growth Factor - pharmacology ; Protein Binding - drug effects ; Protein Structure, Tertiary ; Respiratory System - cytology ; Respiratory System - drug effects ; Respiratory System - enzymology</subject><ispartof>American journal of respiratory cell and molecular biology, 2007-10, Vol.37 (4), p.494-500</ispartof><rights>Copyright American Thoracic Society Oct 2007</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c357t-2d8fb154651a445bbed6843cc85c9568e8cb113068e4e4fc47d6ccf79f9cca283</citedby><cites>FETCH-LOGICAL-c357t-2d8fb154651a445bbed6843cc85c9568e8cb113068e4e4fc47d6ccf79f9cca283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17575078$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lu, Dong</creatorcontrib><creatorcontrib>Xie, ShaoPing</creatorcontrib><creatorcontrib>Sukkar, Maria B</creatorcontrib><creatorcontrib>Lu, Xinjie</creatorcontrib><creatorcontrib>Scully, Michael F</creatorcontrib><creatorcontrib>Chung, Kian Fan</creatorcontrib><title>Inhibition of Airway Smooth Muscle Adhesion and Migration by the Disintegrin Domain of ADAM-15</title><title>American journal of respiratory cell and molecular biology</title><addtitle>Am J Respir Cell Mol Biol</addtitle><description>Disintegrin and metalloprotease proteins (ADAMs) are membrane-anchored glycoproteins involved in cell adhesion, cell fusion, protein ecto-domain shedding, and intracellular signaling. We examined whether the disintegrin domain of ADAM-15 (named ddADAM-15) containing an Asp-Gly-Asp (RGD) integrin-binding motif could interfere with airway smooth muscle cell (ASMC) adhesion and migration. Recombinant ddADAM-15 adhered to human ASMCs with saturation kinetics, and was beta(1)-integrin dependent. ddADAM-15 inhibited the binding of fibrinogen but not of fibronectin to ASMCs. ddADAM-15 also inhibited platelet-derived growth factor (PDGF)-induced ASMC migration, and this was reversed by an anti-beta(1)-integrin antibody. PDGF induced the activation of phosphoinositol-3-kinase (PI3K) and p38 mitogen-activated protein kinase (MAPK), and selective inhibitors of these kinases inhibited PDGF-induced ASMC migration. ddADAM-15 did not inhibit PDGF-induced activation of PI3K or p38, thereby excluding these kinase pathways as a mechanism by which ddADAM-15 inhibits ASMC migration. ADAM-15 mRNA and protein were expressed under basal conditions, and both gene and protein expression were inhibited by PDGF. In summary, ddADAM-15 inhibits ASMC adhesion and migration through the beta(1)-integrin, without modulating signaling pathways involved in ASMC migratory responses.</description><subject>ADAM Proteins - chemistry</subject><subject>ADAM Proteins - genetics</subject><subject>ADAM Proteins - metabolism</subject><subject>ADAM Proteins - pharmacology</subject><subject>Cell Adhesion - drug effects</subject><subject>Cell Movement - drug effects</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Humans</subject><subject>Integrins - metabolism</subject><subject>Membrane Proteins - chemistry</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Membrane Proteins - pharmacology</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Mutant Proteins - pharmacology</subject><subject>Myocytes, Smooth Muscle - cytology</subject><subject>Myocytes, Smooth Muscle - drug effects</subject><subject>Myocytes, Smooth Muscle - enzymology</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Phosphorylation - drug effects</subject><subject>Platelet-Derived Growth Factor - pharmacology</subject><subject>Protein Binding - drug effects</subject><subject>Protein Structure, Tertiary</subject><subject>Respiratory System - cytology</subject><subject>Respiratory System - drug effects</subject><subject>Respiratory System - enzymology</subject><issn>1044-1549</issn><issn>1535-4989</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpdkEtLxDAURoMovveuJLgQN9WkzavLYcYXOLhQt4Y0TacZ2kaTlmH-vakdEFzduzjfdy8HgAuMbjFm9M7rtrhNEWIJyhh5ne-BY0wzmpBc5PtxR4QkmJL8CJyEsEYIpwLjQ3CEOeUUcXEMPp-72ha2t66DroIz6zdqC99a5_oaLoegGwNnZW3CCKiuhEu78uoXL7awrw1c2GC73qy87eDCtcpORYvZMp4-AweVaoI5381T8PFw_z5_Sl5eH5_ns5dEZ5T3SVqKqoiPMooVIbQoTMkEybQWVOeUCSN0gXGG4kYMqTThJdO64nmVa61SkZ2C66n3y7vvwYRetjZo0zSqM24IkomUIyFG8OofuHaD7-JvMkWcCswYixCaIO1dCN5U8svbVvmtxEiO4uUoXo7i5SQ-Ri53vUPRmvIvsDMdgZsJqO2q3lhvZGhV00QcS7Ue-zIuiSQ5yX4AmUWMQQ</recordid><startdate>20071001</startdate><enddate>20071001</enddate><creator>Lu, Dong</creator><creator>Xie, ShaoPing</creator><creator>Sukkar, Maria B</creator><creator>Lu, Xinjie</creator><creator>Scully, Michael F</creator><creator>Chung, Kian Fan</creator><general>Am Thoracic Soc</general><general>American Thoracic Society</general><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope></search><sort><creationdate>20071001</creationdate><title>Inhibition of Airway Smooth Muscle Adhesion and Migration by the Disintegrin Domain of ADAM-15</title><author>Lu, Dong ; Xie, ShaoPing ; Sukkar, Maria B ; Lu, Xinjie ; Scully, Michael F ; Chung, Kian Fan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c357t-2d8fb154651a445bbed6843cc85c9568e8cb113068e4e4fc47d6ccf79f9cca283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>ADAM Proteins - chemistry</topic><topic>ADAM Proteins - genetics</topic><topic>ADAM Proteins - metabolism</topic><topic>ADAM Proteins - pharmacology</topic><topic>Cell Adhesion - drug effects</topic><topic>Cell Movement - drug effects</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Humans</topic><topic>Integrins - metabolism</topic><topic>Membrane Proteins - chemistry</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Membrane Proteins - pharmacology</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Mutant Proteins - pharmacology</topic><topic>Myocytes, Smooth Muscle - cytology</topic><topic>Myocytes, Smooth Muscle - drug effects</topic><topic>Myocytes, Smooth Muscle - enzymology</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Phosphorylation - drug effects</topic><topic>Platelet-Derived Growth Factor - pharmacology</topic><topic>Protein Binding - drug effects</topic><topic>Protein Structure, Tertiary</topic><topic>Respiratory System - cytology</topic><topic>Respiratory System - drug effects</topic><topic>Respiratory System - enzymology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lu, Dong</creatorcontrib><creatorcontrib>Xie, ShaoPing</creatorcontrib><creatorcontrib>Sukkar, Maria B</creatorcontrib><creatorcontrib>Lu, Xinjie</creatorcontrib><creatorcontrib>Scully, Michael F</creatorcontrib><creatorcontrib>Chung, Kian Fan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest - Health & Medical Complete保健、医学与药学数据库</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of respiratory cell and molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lu, Dong</au><au>Xie, ShaoPing</au><au>Sukkar, Maria B</au><au>Lu, Xinjie</au><au>Scully, Michael F</au><au>Chung, Kian Fan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of Airway Smooth Muscle Adhesion and Migration by the Disintegrin Domain of ADAM-15</atitle><jtitle>American journal of respiratory cell and molecular biology</jtitle><addtitle>Am J Respir Cell Mol Biol</addtitle><date>2007-10-01</date><risdate>2007</risdate><volume>37</volume><issue>4</issue><spage>494</spage><epage>500</epage><pages>494-500</pages><issn>1044-1549</issn><eissn>1535-4989</eissn><coden>AJRBEL</coden><abstract>Disintegrin and metalloprotease proteins (ADAMs) are membrane-anchored glycoproteins involved in cell adhesion, cell fusion, protein ecto-domain shedding, and intracellular signaling. We examined whether the disintegrin domain of ADAM-15 (named ddADAM-15) containing an Asp-Gly-Asp (RGD) integrin-binding motif could interfere with airway smooth muscle cell (ASMC) adhesion and migration. Recombinant ddADAM-15 adhered to human ASMCs with saturation kinetics, and was beta(1)-integrin dependent. ddADAM-15 inhibited the binding of fibrinogen but not of fibronectin to ASMCs. ddADAM-15 also inhibited platelet-derived growth factor (PDGF)-induced ASMC migration, and this was reversed by an anti-beta(1)-integrin antibody. PDGF induced the activation of phosphoinositol-3-kinase (PI3K) and p38 mitogen-activated protein kinase (MAPK), and selective inhibitors of these kinases inhibited PDGF-induced ASMC migration. ddADAM-15 did not inhibit PDGF-induced activation of PI3K or p38, thereby excluding these kinase pathways as a mechanism by which ddADAM-15 inhibits ASMC migration. ADAM-15 mRNA and protein were expressed under basal conditions, and both gene and protein expression were inhibited by PDGF. In summary, ddADAM-15 inhibits ASMC adhesion and migration through the beta(1)-integrin, without modulating signaling pathways involved in ASMC migratory responses.</abstract><cop>United States</cop><pub>Am Thoracic Soc</pub><pmid>17575078</pmid><doi>10.1165/rcmb.2006-0364OC</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1044-1549 |
| ispartof | American journal of respiratory cell and molecular biology, 2007-10, Vol.37 (4), p.494-500 |
| issn | 1044-1549 1535-4989 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68270888 |
| source | MEDLINE; Alma/SFX Local Collection; EZB Electronic Journals Library; Journals@Ovid Complete |
| subjects | ADAM Proteins - chemistry ADAM Proteins - genetics ADAM Proteins - metabolism ADAM Proteins - pharmacology Cell Adhesion - drug effects Cell Movement - drug effects Gene Expression Regulation - drug effects Humans Integrins - metabolism Membrane Proteins - chemistry Membrane Proteins - genetics Membrane Proteins - metabolism Membrane Proteins - pharmacology Mitogen-Activated Protein Kinases - metabolism Mutant Proteins - pharmacology Myocytes, Smooth Muscle - cytology Myocytes, Smooth Muscle - drug effects Myocytes, Smooth Muscle - enzymology Phosphatidylinositol 3-Kinases - metabolism Phosphorylation - drug effects Platelet-Derived Growth Factor - pharmacology Protein Binding - drug effects Protein Structure, Tertiary Respiratory System - cytology Respiratory System - drug effects Respiratory System - enzymology |
| title | Inhibition of Airway Smooth Muscle Adhesion and Migration by the Disintegrin Domain of ADAM-15 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T14%3A19%3A51IST&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=Inhibition%20of%20Airway%20Smooth%20Muscle%20Adhesion%20and%20Migration%20by%20the%20Disintegrin%20Domain%20of%20ADAM-15&rft.jtitle=American%20journal%20of%20respiratory%20cell%20and%20molecular%20biology&rft.au=Lu,%20Dong&rft.date=2007-10-01&rft.volume=37&rft.issue=4&rft.spage=494&rft.epage=500&rft.pages=494-500&rft.issn=1044-1549&rft.eissn=1535-4989&rft.coden=AJRBEL&rft_id=info:doi/10.1165/rcmb.2006-0364OC&rft_dat=%3Cproquest_cross%3E1339575741%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=207581666&rft_id=info:pmid/17575078&rfr_iscdi=true |