Increased IgE-dependent mast cell activation and anaphylactic responses in mice lacking the calcium-activated nonselective cation channel TRPM4
Mast cells are key effector cells in allergic reactions. Aggregation of the receptor FcεRI in mast cells triggers the influx of calcium (Ca 2+ ) and the release of inflammatory mediators. Here we show that transient receptor potential TRPM4 proteins acted as calcium-activated nonselective cation cha...
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| Veröffentlicht in: | Nature Immunology 2007-03, Vol.8 (3), p.312-320 |
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| container_title | Nature Immunology |
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| creator | Vennekens, Rudi Freichel, Marc Olausson, Jenny Meissner, Marcel Bloch, Wilhelm Mathar, Ilka Philipp, Stephan E Schmitz, Frank Weissgerber, Petra Nilius, Bernd Flockerzi, Veit |
| description | Mast cells are key effector cells in allergic reactions. Aggregation of the receptor FcεRI in mast cells triggers the influx of calcium (Ca
2+
) and the release of inflammatory mediators. Here we show that transient receptor potential TRPM4 proteins acted as calcium-activated nonselective cation channels and critically determined the driving force for Ca
2+
influx in mast cells.
Trpm4
−/−
bone marrow–derived mast cells had more Ca
2+
entry than did
TRPM4
+/+
cells after FcεRI stimulation. Consequently,
Trpm4
−/−
bone marrow–derived mast cells had augmented degranulation and released more histamine, leukotrienes and tumor necrosis factor.
Trpm4
−/−
mice had a more severe IgE-mediated acute passive cutaneous anaphylactic response, whereas late-phase passive cutaneous anaphylaxis was not affected. Our results establish the physiological function of TRPM4 channels as critical regulators of Ca
2+
entry in mast cells. |
| doi_str_mv | 10.1038/ni1441 |
| format | Article |
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2+
) and the release of inflammatory mediators. Here we show that transient receptor potential TRPM4 proteins acted as calcium-activated nonselective cation channels and critically determined the driving force for Ca
2+
influx in mast cells.
Trpm4
−/−
bone marrow–derived mast cells had more Ca
2+
entry than did
TRPM4
+/+
cells after FcεRI stimulation. Consequently,
Trpm4
−/−
bone marrow–derived mast cells had augmented degranulation and released more histamine, leukotrienes and tumor necrosis factor.
Trpm4
−/−
mice had a more severe IgE-mediated acute passive cutaneous anaphylactic response, whereas late-phase passive cutaneous anaphylaxis was not affected. Our results establish the physiological function of TRPM4 channels as critical regulators of Ca
2+
entry in mast cells.</description><identifier>ISSN: 1529-2908</identifier><identifier>EISSN: 1529-2916</identifier><identifier>EISSN: 1365-2567</identifier><identifier>DOI: 10.1038/ni1441</identifier><identifier>PMID: 17293867</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Anaphylaxis ; Anaphylaxis - immunology ; Anaphylaxis - metabolism ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Bone marrow ; Bone Marrow Cells - immunology ; Bone Marrow Cells - metabolism ; Calcium ; Calcium - metabolism ; Histamine ; Immunoglobulin E ; Immunoglobulin E - immunology ; Immunology ; Infectious Diseases ; Ion channels ; Mast cells ; Mast Cells - immunology ; Mast Cells - metabolism ; Membrane Potentials ; Mice ; Patch-Clamp Techniques ; Physiological aspects ; Physiology ; Receptors, IgE - immunology ; Receptors, IgE - metabolism ; TRPM Cation Channels - metabolism</subject><ispartof>Nature Immunology, 2007-03, Vol.8 (3), p.312-320</ispartof><rights>Springer Nature America, Inc. 2007</rights><rights>COPYRIGHT 2007 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Mar 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c619t-b684960b0a5e485c572d063ce5229ed25175e2bc95600b5d662f2606d6fd9ba23</citedby><cites>FETCH-LOGICAL-c619t-b684960b0a5e485c572d063ce5229ed25175e2bc95600b5d662f2606d6fd9ba23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2727,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17293867$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vennekens, Rudi</creatorcontrib><creatorcontrib>Freichel, Marc</creatorcontrib><creatorcontrib>Olausson, Jenny</creatorcontrib><creatorcontrib>Meissner, Marcel</creatorcontrib><creatorcontrib>Bloch, Wilhelm</creatorcontrib><creatorcontrib>Mathar, Ilka</creatorcontrib><creatorcontrib>Philipp, Stephan E</creatorcontrib><creatorcontrib>Schmitz, Frank</creatorcontrib><creatorcontrib>Weissgerber, Petra</creatorcontrib><creatorcontrib>Nilius, Bernd</creatorcontrib><creatorcontrib>Flockerzi, Veit</creatorcontrib><title>Increased IgE-dependent mast cell activation and anaphylactic responses in mice lacking the calcium-activated nonselective cation channel TRPM4</title><title>Nature Immunology</title><addtitle>Nat Immunol</addtitle><addtitle>Nat Immunol</addtitle><description>Mast cells are key effector cells in allergic reactions. Aggregation of the receptor FcεRI in mast cells triggers the influx of calcium (Ca
2+
) and the release of inflammatory mediators. Here we show that transient receptor potential TRPM4 proteins acted as calcium-activated nonselective cation channels and critically determined the driving force for Ca
2+
influx in mast cells.
Trpm4
−/−
bone marrow–derived mast cells had more Ca
2+
entry than did
TRPM4
+/+
cells after FcεRI stimulation. Consequently,
Trpm4
−/−
bone marrow–derived mast cells had augmented degranulation and released more histamine, leukotrienes and tumor necrosis factor.
Trpm4
−/−
mice had a more severe IgE-mediated acute passive cutaneous anaphylactic response, whereas late-phase passive cutaneous anaphylaxis was not affected. Our results establish the physiological function of TRPM4 channels as critical regulators of Ca
2+
entry in mast cells.</description><subject>Anaphylaxis</subject><subject>Anaphylaxis - immunology</subject><subject>Anaphylaxis - metabolism</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Bone marrow</subject><subject>Bone Marrow Cells - immunology</subject><subject>Bone Marrow Cells - metabolism</subject><subject>Calcium</subject><subject>Calcium - metabolism</subject><subject>Histamine</subject><subject>Immunoglobulin E</subject><subject>Immunoglobulin E - immunology</subject><subject>Immunology</subject><subject>Infectious Diseases</subject><subject>Ion channels</subject><subject>Mast cells</subject><subject>Mast Cells - immunology</subject><subject>Mast Cells - metabolism</subject><subject>Membrane Potentials</subject><subject>Mice</subject><subject>Patch-Clamp Techniques</subject><subject>Physiological aspects</subject><subject>Physiology</subject><subject>Receptors, IgE - immunology</subject><subject>Receptors, IgE - metabolism</subject><subject>TRPM Cation Channels - metabolism</subject><issn>1529-2908</issn><issn>1529-2916</issn><issn>1365-2567</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>eNqFkt-K1DAUxoso7jrqE4gEBcWLrkmapM3lsqw6sKKs63VJk9OZrG1ak1Tcp_CVTZ2yw6goIeTP-Z0vfDknyx4TfEJwUb12ljBG7mTHhFOZU0nE3ds9ro6yByFcY0xYKdj97IiUVBaVKI-zH2unPagABq0357mBEZwBF1GvQkQaug4pHe03Fe3gkHImTTVub7r5ViMPYRxcgICsQ73VgFLgi3UbFLeAtOq0nfp8UUhvuBnuYD7P4V-iequcgw5dXX58zx5m91rVBXi0rKvs85vzq7N3-cWHt-uz04tcCyJj3oiKSYEbrDiwimteUoNFoYFTKsFQTkoOtNGSC4wbboSgLRVYGNEa2SharLKXO93RD18nCLHubZjtKgfDFOqKEyYIZzP54p-kkJgQRsh_QSK5ZKkyCXz2G3g9TN4luzWltCwqyXiCnu-gjeqgtq4dold6VqxPiSy5rFgq_Co7-QuVhoFUjcFBa9P9QcKrg4TERPgeN2oKoV5_ujxkF0PaDyF4aOvR2175m5rgeu66etd1CXy6GJqaHsweW9ps_9shhdwG_N7xH1JPdqRTcfJwK7WEfwI1RuaF</recordid><startdate>20070301</startdate><enddate>20070301</enddate><creator>Vennekens, Rudi</creator><creator>Freichel, Marc</creator><creator>Olausson, Jenny</creator><creator>Meissner, Marcel</creator><creator>Bloch, Wilhelm</creator><creator>Mathar, Ilka</creator><creator>Philipp, Stephan E</creator><creator>Schmitz, Frank</creator><creator>Weissgerber, Petra</creator><creator>Nilius, Bernd</creator><creator>Flockerzi, Veit</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</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>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</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>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20070301</creationdate><title>Increased IgE-dependent mast cell activation and anaphylactic responses in mice lacking the calcium-activated nonselective cation channel TRPM4</title><author>Vennekens, Rudi ; Freichel, Marc ; Olausson, Jenny ; Meissner, Marcel ; Bloch, Wilhelm ; Mathar, Ilka ; Philipp, Stephan E ; Schmitz, Frank ; Weissgerber, Petra ; Nilius, Bernd ; Flockerzi, Veit</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c619t-b684960b0a5e485c572d063ce5229ed25175e2bc95600b5d662f2606d6fd9ba23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Anaphylaxis</topic><topic>Anaphylaxis - immunology</topic><topic>Anaphylaxis - metabolism</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Bone marrow</topic><topic>Bone Marrow Cells - immunology</topic><topic>Bone Marrow Cells - metabolism</topic><topic>Calcium</topic><topic>Calcium - metabolism</topic><topic>Histamine</topic><topic>Immunoglobulin E</topic><topic>Immunoglobulin E - immunology</topic><topic>Immunology</topic><topic>Infectious Diseases</topic><topic>Ion channels</topic><topic>Mast cells</topic><topic>Mast Cells - immunology</topic><topic>Mast Cells - metabolism</topic><topic>Membrane Potentials</topic><topic>Mice</topic><topic>Patch-Clamp Techniques</topic><topic>Physiological aspects</topic><topic>Physiology</topic><topic>Receptors, IgE - immunology</topic><topic>Receptors, IgE - metabolism</topic><topic>TRPM Cation Channels - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vennekens, Rudi</creatorcontrib><creatorcontrib>Freichel, Marc</creatorcontrib><creatorcontrib>Olausson, Jenny</creatorcontrib><creatorcontrib>Meissner, Marcel</creatorcontrib><creatorcontrib>Bloch, Wilhelm</creatorcontrib><creatorcontrib>Mathar, Ilka</creatorcontrib><creatorcontrib>Philipp, Stephan E</creatorcontrib><creatorcontrib>Schmitz, Frank</creatorcontrib><creatorcontrib>Weissgerber, Petra</creatorcontrib><creatorcontrib>Nilius, Bernd</creatorcontrib><creatorcontrib>Flockerzi, Veit</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</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 Edition)</collection><collection>ProQuest Central UK/Ireland</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 Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature Immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vennekens, Rudi</au><au>Freichel, Marc</au><au>Olausson, Jenny</au><au>Meissner, Marcel</au><au>Bloch, Wilhelm</au><au>Mathar, Ilka</au><au>Philipp, Stephan E</au><au>Schmitz, Frank</au><au>Weissgerber, Petra</au><au>Nilius, Bernd</au><au>Flockerzi, Veit</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased IgE-dependent mast cell activation and anaphylactic responses in mice lacking the calcium-activated nonselective cation channel TRPM4</atitle><jtitle>Nature Immunology</jtitle><stitle>Nat Immunol</stitle><addtitle>Nat Immunol</addtitle><date>2007-03-01</date><risdate>2007</risdate><volume>8</volume><issue>3</issue><spage>312</spage><epage>320</epage><pages>312-320</pages><issn>1529-2908</issn><eissn>1529-2916</eissn><eissn>1365-2567</eissn><abstract>Mast cells are key effector cells in allergic reactions. Aggregation of the receptor FcεRI in mast cells triggers the influx of calcium (Ca
2+
) and the release of inflammatory mediators. Here we show that transient receptor potential TRPM4 proteins acted as calcium-activated nonselective cation channels and critically determined the driving force for Ca
2+
influx in mast cells.
Trpm4
−/−
bone marrow–derived mast cells had more Ca
2+
entry than did
TRPM4
+/+
cells after FcεRI stimulation. Consequently,
Trpm4
−/−
bone marrow–derived mast cells had augmented degranulation and released more histamine, leukotrienes and tumor necrosis factor.
Trpm4
−/−
mice had a more severe IgE-mediated acute passive cutaneous anaphylactic response, whereas late-phase passive cutaneous anaphylaxis was not affected. Our results establish the physiological function of TRPM4 channels as critical regulators of Ca
2+
entry in mast cells.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>17293867</pmid><doi>10.1038/ni1441</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Journals; Nature; Wiley Online Library Free Content; IngentaConnect Free/Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Anaphylaxis Anaphylaxis - immunology Anaphylaxis - metabolism Animals Biomedical and Life Sciences Biomedicine Bone marrow Bone Marrow Cells - immunology Bone Marrow Cells - metabolism Calcium Calcium - metabolism Histamine Immunoglobulin E Immunoglobulin E - immunology Immunology Infectious Diseases Ion channels Mast cells Mast Cells - immunology Mast Cells - metabolism Membrane Potentials Mice Patch-Clamp Techniques Physiological aspects Physiology Receptors, IgE - immunology Receptors, IgE - metabolism TRPM Cation Channels - metabolism |
| title | Increased IgE-dependent mast cell activation and anaphylactic responses in mice lacking the calcium-activated nonselective cation channel TRPM4 |
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