Domain 5 of cleaved high molecular weight kininogen inhibits endothelial cell migration through Akt
Summary Domain 5 (D5) of cleaved high molecular weight kininogen (HKa) inhibits angiogenesis in vivo and endothelial cell migration in vitro , but the cell signaling pathways involved in HKa and D5 inhibition of endothelial cell migration are incompletely delineated. This study examines the mechanis...
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| Veröffentlicht in: | Thrombosis and haemostasis 2005-09, Vol.94 (3), p.606-614 |
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| creator | Katkade, Vaibhav Soyombo, Abigail A. Isordia-Salas, Irma Bradford, Harlan N. Gaughan, John P. Colman, Robert W. Panetti, Tracee S. |
| description | Summary
Domain 5 (D5) of cleaved high molecular weight kininogen (HKa) inhibits angiogenesis in vivo and endothelial cell migration
in vitro
, but the cell signaling pathways involved in HKa and D5 inhibition of endothelial cell migration are incompletely delineated. This study examines the mechanism of HKa and D5 inhibition of two potent stimulators of endothelial cell migration, sphingosine 1-phosphate (S1P) and vascular endothelial growth factor (VEGF), that act through the PI3-kinase-Akt signaling pathway. HKa and D5 inhibit bovine pulmonary artery endothelial cell (BPAE) or human umbilical vein endothelial cell chemotaxis in the modified-Boyden chamber in response to VEGF or S1P. The inhibition of migration by HKa is reversed by antibodies to urokinase-type plasminogen activator receptor. Both HKa and D5 decrease the speed of BPAE cell migration and alter the morphology in live, time-lapse microscopy after stimulation with S1P or VEGF. HKa and D5 reduce the localization of paxillin to the focal adhesions after S1P and VEGF stimulation. To better understand the intracellular signaling pathways, we examined the effect of HKa on the phosphorylation of Akt and its downstream effector, GSK-3α.HKa and D5 inhibit phosphorylation of Akt and GSK-3α after stimulation withVEGF and S1P. Inhibitors of Akt and PI3-kinase, the upstream activator of Akt, block endothelial cell migration and disrupt paxillin localization to the focal adhesions after stimulation with VEGF and S1P. Therefore we suggest that HKa through its D5 domain alters PI3-kinase- Akt signaling to inhibit endothelial cell migration through alterations in the focal adhesions. |
| doi_str_mv | 10.1160/TH04-12-0834 |
| format | Article |
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Domain 5 (D5) of cleaved high molecular weight kininogen (HKa) inhibits angiogenesis in vivo and endothelial cell migration
in vitro
, but the cell signaling pathways involved in HKa and D5 inhibition of endothelial cell migration are incompletely delineated. This study examines the mechanism of HKa and D5 inhibition of two potent stimulators of endothelial cell migration, sphingosine 1-phosphate (S1P) and vascular endothelial growth factor (VEGF), that act through the PI3-kinase-Akt signaling pathway. HKa and D5 inhibit bovine pulmonary artery endothelial cell (BPAE) or human umbilical vein endothelial cell chemotaxis in the modified-Boyden chamber in response to VEGF or S1P. The inhibition of migration by HKa is reversed by antibodies to urokinase-type plasminogen activator receptor. Both HKa and D5 decrease the speed of BPAE cell migration and alter the morphology in live, time-lapse microscopy after stimulation with S1P or VEGF. HKa and D5 reduce the localization of paxillin to the focal adhesions after S1P and VEGF stimulation. To better understand the intracellular signaling pathways, we examined the effect of HKa on the phosphorylation of Akt and its downstream effector, GSK-3α.HKa and D5 inhibit phosphorylation of Akt and GSK-3α after stimulation withVEGF and S1P. Inhibitors of Akt and PI3-kinase, the upstream activator of Akt, block endothelial cell migration and disrupt paxillin localization to the focal adhesions after stimulation with VEGF and S1P. Therefore we suggest that HKa through its D5 domain alters PI3-kinase- Akt signaling to inhibit endothelial cell migration through alterations in the focal adhesions.</description><identifier>ISSN: 0340-6245</identifier><identifier>EISSN: 2567-689X</identifier><identifier>DOI: 10.1160/TH04-12-0834</identifier><identifier>PMID: 16268479</identifier><identifier>CODEN: THHADQ</identifier><language>eng</language><publisher>Stuttgart: Schattauer Verlag für Medizin und Naturwissenschaften</publisher><subject>Androstadienes - pharmacology ; Animals ; Biological and medical sciences ; Blood coagulation. Blood cells ; Cattle ; Cell Movement - drug effects ; Cells, Cultured ; Chemotaxis - drug effects ; Chromones - pharmacology ; Endothelial Cells - drug effects ; Endothelial Cells - metabolism ; Endothelium and Vascular Development ; Focal Adhesions - drug effects ; Focal Adhesions - metabolism ; Fundamental and applied biological sciences. Psychology ; Glycogen Synthase Kinase 3 - metabolism ; Hematologic and hematopoietic diseases ; Humans ; Kininogen, High-Molecular-Weight - chemistry ; Kininogen, High-Molecular-Weight - pharmacology ; Lysophospholipids - pharmacology ; Medical sciences ; Molecular and cellular biology ; Morpholines - pharmacology ; Peptide Fragments - chemistry ; Peptide Fragments - pharmacology ; Phosphatidylinositol 3-Kinases - antagonists & inhibitors ; Phosphatidylinositol 3-Kinases - metabolism ; Phosphorylation ; Platelet diseases and coagulopathies ; Protein Structure, Tertiary ; Signal Transduction - drug effects ; Sphingosine - analogs & derivatives ; Sphingosine - pharmacology ; Time Factors ; Vascular Endothelial Growth Factor A - pharmacology</subject><ispartof>Thrombosis and haemostasis, 2005-09, Vol.94 (3), p.606-614</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c545t-95b94f88abccf197b6d4131564d768a63276e40814fea6cec3be342aac4607343</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.thieme-connect.de/products/ejournals/pdf/10.1160/TH04-12-0834.pdf$$EPDF$$P50$$Gthieme$$H</linktopdf><linktohtml>$$Uhttps://www.thieme-connect.de/products/ejournals/html/10.1160/TH04-12-0834$$EHTML$$P50$$Gthieme$$H</linktohtml><link.rule.ids>314,776,780,3005,27903,27904,54537,54538</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17058742$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16268479$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Katkade, Vaibhav</creatorcontrib><creatorcontrib>Soyombo, Abigail A.</creatorcontrib><creatorcontrib>Isordia-Salas, Irma</creatorcontrib><creatorcontrib>Bradford, Harlan N.</creatorcontrib><creatorcontrib>Gaughan, John P.</creatorcontrib><creatorcontrib>Colman, Robert W.</creatorcontrib><creatorcontrib>Panetti, Tracee S.</creatorcontrib><title>Domain 5 of cleaved high molecular weight kininogen inhibits endothelial cell migration through Akt</title><title>Thrombosis and haemostasis</title><addtitle>Thromb Haemost</addtitle><description>Summary
Domain 5 (D5) of cleaved high molecular weight kininogen (HKa) inhibits angiogenesis in vivo and endothelial cell migration
in vitro
, but the cell signaling pathways involved in HKa and D5 inhibition of endothelial cell migration are incompletely delineated. This study examines the mechanism of HKa and D5 inhibition of two potent stimulators of endothelial cell migration, sphingosine 1-phosphate (S1P) and vascular endothelial growth factor (VEGF), that act through the PI3-kinase-Akt signaling pathway. HKa and D5 inhibit bovine pulmonary artery endothelial cell (BPAE) or human umbilical vein endothelial cell chemotaxis in the modified-Boyden chamber in response to VEGF or S1P. The inhibition of migration by HKa is reversed by antibodies to urokinase-type plasminogen activator receptor. Both HKa and D5 decrease the speed of BPAE cell migration and alter the morphology in live, time-lapse microscopy after stimulation with S1P or VEGF. HKa and D5 reduce the localization of paxillin to the focal adhesions after S1P and VEGF stimulation. To better understand the intracellular signaling pathways, we examined the effect of HKa on the phosphorylation of Akt and its downstream effector, GSK-3α.HKa and D5 inhibit phosphorylation of Akt and GSK-3α after stimulation withVEGF and S1P. Inhibitors of Akt and PI3-kinase, the upstream activator of Akt, block endothelial cell migration and disrupt paxillin localization to the focal adhesions after stimulation with VEGF and S1P. Therefore we suggest that HKa through its D5 domain alters PI3-kinase- Akt signaling to inhibit endothelial cell migration through alterations in the focal adhesions.</description><subject>Androstadienes - pharmacology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood coagulation. Blood cells</subject><subject>Cattle</subject><subject>Cell Movement - drug effects</subject><subject>Cells, Cultured</subject><subject>Chemotaxis - drug effects</subject><subject>Chromones - pharmacology</subject><subject>Endothelial Cells - drug effects</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelium and Vascular Development</subject><subject>Focal Adhesions - drug effects</subject><subject>Focal Adhesions - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Glycogen Synthase Kinase 3 - metabolism</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Kininogen, High-Molecular-Weight - chemistry</subject><subject>Kininogen, High-Molecular-Weight - pharmacology</subject><subject>Lysophospholipids - pharmacology</subject><subject>Medical sciences</subject><subject>Molecular and cellular biology</subject><subject>Morpholines - pharmacology</subject><subject>Peptide Fragments - chemistry</subject><subject>Peptide Fragments - pharmacology</subject><subject>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Phosphorylation</subject><subject>Platelet diseases and coagulopathies</subject><subject>Protein Structure, Tertiary</subject><subject>Signal Transduction - drug effects</subject><subject>Sphingosine - analogs & derivatives</subject><subject>Sphingosine - pharmacology</subject><subject>Time Factors</subject><subject>Vascular Endothelial Growth Factor A - pharmacology</subject><issn>0340-6245</issn><issn>2567-689X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqtkk1rFTEUhgdRbK3uXEs2utHRZCaTySxL_ahQcFPBXTiTOXOTdpJck0yL_94M92JBcOcqHPLwvoeHU1UvGX3PmKAfri8pr1lTU9nyR9Vp04m-FnL48bg6pS2ntWh4d1I9S-mGUib40D2tTphohOT9cFrpj8GB9aQjYSZ6QbjDiRi7M8SFBfW6QCT3WOZMbq23PuzQE-uNHW1OBP0UssHFwkI0Lgtxdhch2-BJNjGsJeb8Nj-vnsywJHxxfM-q758_XV9c1lffvny9OL-qdce7XA_dOPBZShi1ntnQj2LirGWd4FMvJIi26QVyKhmfEYRG3Y7Y8gZAc0H7lrdn1ZtD7j6GnyumrJxN21rgMaxJCdkLyqUs4LsDqGNIKeKs9tE6iL8Uo2qTqjapijVqk1rwV8fcdXQ4PcBHiwV4fQQgaVjmCF7b9MD1tJM9bwr39sBlY9Ghuglr9MXIv2rtgU7aQM6wYvwTudl1Y0ilBfykDKALKcM26-Az-lw-ojb2DpVNaUVVFCoHfk062n1WvOGNSibcK5PdUrr0f-xKe9TlJP7ua38DeEzeQg</recordid><startdate>20050901</startdate><enddate>20050901</enddate><creator>Katkade, Vaibhav</creator><creator>Soyombo, Abigail A.</creator><creator>Isordia-Salas, Irma</creator><creator>Bradford, Harlan N.</creator><creator>Gaughan, John P.</creator><creator>Colman, Robert W.</creator><creator>Panetti, Tracee S.</creator><general>Schattauer Verlag für Medizin und Naturwissenschaften</general><general>Schattauer GmbH</general><general>Schattauer</general><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>7X8</scope></search><sort><creationdate>20050901</creationdate><title>Domain 5 of cleaved high molecular weight kininogen inhibits endothelial cell migration through Akt</title><author>Katkade, Vaibhav ; Soyombo, Abigail A. ; Isordia-Salas, Irma ; Bradford, Harlan N. ; Gaughan, John P. ; Colman, Robert W. ; Panetti, Tracee S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c545t-95b94f88abccf197b6d4131564d768a63276e40814fea6cec3be342aac4607343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Androstadienes - pharmacology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood coagulation. Blood cells</topic><topic>Cattle</topic><topic>Cell Movement - drug effects</topic><topic>Cells, Cultured</topic><topic>Chemotaxis - drug effects</topic><topic>Chromones - pharmacology</topic><topic>Endothelial Cells - drug effects</topic><topic>Endothelial Cells - metabolism</topic><topic>Endothelium and Vascular Development</topic><topic>Focal Adhesions - drug effects</topic><topic>Focal Adhesions - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Glycogen Synthase Kinase 3 - metabolism</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Kininogen, High-Molecular-Weight - chemistry</topic><topic>Kininogen, High-Molecular-Weight - pharmacology</topic><topic>Lysophospholipids - pharmacology</topic><topic>Medical sciences</topic><topic>Molecular and cellular biology</topic><topic>Morpholines - pharmacology</topic><topic>Peptide Fragments - chemistry</topic><topic>Peptide Fragments - pharmacology</topic><topic>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Phosphorylation</topic><topic>Platelet diseases and coagulopathies</topic><topic>Protein Structure, Tertiary</topic><topic>Signal Transduction - drug effects</topic><topic>Sphingosine - analogs & derivatives</topic><topic>Sphingosine - pharmacology</topic><topic>Time Factors</topic><topic>Vascular Endothelial Growth Factor A - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Katkade, Vaibhav</creatorcontrib><creatorcontrib>Soyombo, Abigail A.</creatorcontrib><creatorcontrib>Isordia-Salas, Irma</creatorcontrib><creatorcontrib>Bradford, Harlan N.</creatorcontrib><creatorcontrib>Gaughan, John P.</creatorcontrib><creatorcontrib>Colman, Robert W.</creatorcontrib><creatorcontrib>Panetti, Tracee S.</creatorcontrib><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>MEDLINE - Academic</collection><jtitle>Thrombosis and haemostasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Katkade, Vaibhav</au><au>Soyombo, Abigail A.</au><au>Isordia-Salas, Irma</au><au>Bradford, Harlan N.</au><au>Gaughan, John P.</au><au>Colman, Robert W.</au><au>Panetti, Tracee S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Domain 5 of cleaved high molecular weight kininogen inhibits endothelial cell migration through Akt</atitle><jtitle>Thrombosis and haemostasis</jtitle><addtitle>Thromb Haemost</addtitle><date>2005-09-01</date><risdate>2005</risdate><volume>94</volume><issue>3</issue><spage>606</spage><epage>614</epage><pages>606-614</pages><issn>0340-6245</issn><eissn>2567-689X</eissn><coden>THHADQ</coden><abstract>Summary
Domain 5 (D5) of cleaved high molecular weight kininogen (HKa) inhibits angiogenesis in vivo and endothelial cell migration
in vitro
, but the cell signaling pathways involved in HKa and D5 inhibition of endothelial cell migration are incompletely delineated. This study examines the mechanism of HKa and D5 inhibition of two potent stimulators of endothelial cell migration, sphingosine 1-phosphate (S1P) and vascular endothelial growth factor (VEGF), that act through the PI3-kinase-Akt signaling pathway. HKa and D5 inhibit bovine pulmonary artery endothelial cell (BPAE) or human umbilical vein endothelial cell chemotaxis in the modified-Boyden chamber in response to VEGF or S1P. The inhibition of migration by HKa is reversed by antibodies to urokinase-type plasminogen activator receptor. Both HKa and D5 decrease the speed of BPAE cell migration and alter the morphology in live, time-lapse microscopy after stimulation with S1P or VEGF. HKa and D5 reduce the localization of paxillin to the focal adhesions after S1P and VEGF stimulation. To better understand the intracellular signaling pathways, we examined the effect of HKa on the phosphorylation of Akt and its downstream effector, GSK-3α.HKa and D5 inhibit phosphorylation of Akt and GSK-3α after stimulation withVEGF and S1P. Inhibitors of Akt and PI3-kinase, the upstream activator of Akt, block endothelial cell migration and disrupt paxillin localization to the focal adhesions after stimulation with VEGF and S1P. Therefore we suggest that HKa through its D5 domain alters PI3-kinase- Akt signaling to inhibit endothelial cell migration through alterations in the focal adhesions.</abstract><cop>Stuttgart</cop><pub>Schattauer Verlag für Medizin und Naturwissenschaften</pub><pmid>16268479</pmid><doi>10.1160/TH04-12-0834</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0340-6245 |
| ispartof | Thrombosis and haemostasis, 2005-09, Vol.94 (3), p.606-614 |
| issn | 0340-6245 2567-689X |
| language | eng |
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| source | MEDLINE; Thieme Connect Journals |
| subjects | Androstadienes - pharmacology Animals Biological and medical sciences Blood coagulation. Blood cells Cattle Cell Movement - drug effects Cells, Cultured Chemotaxis - drug effects Chromones - pharmacology Endothelial Cells - drug effects Endothelial Cells - metabolism Endothelium and Vascular Development Focal Adhesions - drug effects Focal Adhesions - metabolism Fundamental and applied biological sciences. Psychology Glycogen Synthase Kinase 3 - metabolism Hematologic and hematopoietic diseases Humans Kininogen, High-Molecular-Weight - chemistry Kininogen, High-Molecular-Weight - pharmacology Lysophospholipids - pharmacology Medical sciences Molecular and cellular biology Morpholines - pharmacology Peptide Fragments - chemistry Peptide Fragments - pharmacology Phosphatidylinositol 3-Kinases - antagonists & inhibitors Phosphatidylinositol 3-Kinases - metabolism Phosphorylation Platelet diseases and coagulopathies Protein Structure, Tertiary Signal Transduction - drug effects Sphingosine - analogs & derivatives Sphingosine - pharmacology Time Factors Vascular Endothelial Growth Factor A - pharmacology |
| title | Domain 5 of cleaved high molecular weight kininogen inhibits endothelial cell migration through Akt |
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