Abnormal enteric innervation identified without histopathologic staining in aganglionic colorectum from a mouse model of Hirschsprung's disease
Abstract Purpose The piebald lethal mouse with a deletion of endothelin-B receptor gene (EDNRB) is a model for Hirschsprung's disease (HD), whereas the SOX10 gene is vital for the development of intestinal neural crest–derived cells. Recently, we created a SOX10 transgenic mouse with intestinal...
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| Veröffentlicht in: | Journal of pediatric surgery 2010-12, Vol.45 (12), p.2403-2407 |
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| creator | Miyahara, Katsumi Kato, Yoshifumi Koga, Hiroyuki Lane, Geoffrey J Inoue, Takayoshi Akazawa, Chihiro Yamataka, Atsuyuki |
| description | Abstract Purpose The piebald lethal mouse with a deletion of endothelin-B receptor gene (EDNRB) is a model for Hirschsprung's disease (HD), whereas the SOX10 gene is vital for the development of intestinal neural crest–derived cells. Recently, we created a SOX10 transgenic mouse with intestinal neural crest–derived cells visible with enhanced green fluorescent protein (VENUS), that is, SOX10-VENUS+ /EDNRBsl/sl to investigate intestinal innervation in HD. Methods SOX10-VENUS+ /EDNRBsl/sl (n = 30) were compared with wild-type littermates as controls (EDNRBs/s , n = 30). Mice were killed on days 3, 7, or 12 of age. The entire colorectum was excised, fixed with 4% paraformaldehyde, and examined using fluorescence microscopy alone without staining. Results In normoganglionic colorectum from controls, a grid network of nerve fibers/glial cells was visualized that connected smoothly with extrinsic nerve fibers running along the colorectal wall. In aganglionic colorectum from SOX10-VENUS+ /EDNRBsl/sl mice, there was no grid network and more extrinsic nerve fibers than controls that invaded the colon wall becoming elongated with branching fibers. Normoganglionic colon from controls and SOX10-VENUS+ /EDNRBsl/sl mice appeared the same. Innervation patterns did not change over time. Conclusion This is the first time for abnormal enteric innervation in aganglionic colon in a model for HD to be visualized without staining. |
| doi_str_mv | 10.1016/j.jpedsurg.2010.08.039 |
| format | Article |
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Recently, we created a SOX10 transgenic mouse with intestinal neural crest–derived cells visible with enhanced green fluorescent protein (VENUS), that is, SOX10-VENUS+ /EDNRBsl/sl to investigate intestinal innervation in HD. Methods SOX10-VENUS+ /EDNRBsl/sl (n = 30) were compared with wild-type littermates as controls (EDNRBs/s , n = 30). Mice were killed on days 3, 7, or 12 of age. The entire colorectum was excised, fixed with 4% paraformaldehyde, and examined using fluorescence microscopy alone without staining. Results In normoganglionic colorectum from controls, a grid network of nerve fibers/glial cells was visualized that connected smoothly with extrinsic nerve fibers running along the colorectal wall. In aganglionic colorectum from SOX10-VENUS+ /EDNRBsl/sl mice, there was no grid network and more extrinsic nerve fibers than controls that invaded the colon wall becoming elongated with branching fibers. Normoganglionic colon from controls and SOX10-VENUS+ /EDNRBsl/sl mice appeared the same. Innervation patterns did not change over time. Conclusion This is the first time for abnormal enteric innervation in aganglionic colon in a model for HD to be visualized without staining.</description><identifier>ISSN: 0022-3468</identifier><identifier>EISSN: 1531-5037</identifier><identifier>DOI: 10.1016/j.jpedsurg.2010.08.039</identifier><identifier>PMID: 21129555</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animal model ; Animals ; Bacterial Proteins - analysis ; Bacterial Proteins - genetics ; Bacterial Proteins - radiation effects ; Cell Lineage ; Colon - innervation ; Colon - pathology ; Disease Models, Animal ; Endothelin-B receptor ; Enteric Nervous System - abnormalities ; Enteric Nervous System - pathology ; Fluorescent Antibody Technique ; Fluorescent Dyes - analysis ; Fluorescent Dyes - radiation effects ; Ganglia, Parasympathetic - ultrastructure ; Hirschsprung Disease - pathology ; Hirschsprung's disease ; Luminescent Proteins - analysis ; Luminescent Proteins - genetics ; Luminescent Proteins - radiation effects ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Mice, Transgenic ; Microscopy, Confocal ; Microscopy, Fluorescence ; Nerve Fibers - ultrastructure ; Neural Crest - pathology ; Neural crest cell ; Pediatrics ; Receptor, Endothelin B - biosynthesis ; Receptor, Endothelin B - deficiency ; Receptor, Endothelin B - genetics ; Rectum - innervation ; Rectum - pathology ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - analysis ; RNA, Messenger - biosynthesis ; RNA, Messenger - genetics ; SOX10 ; SOXE Transcription Factors - genetics ; Surgery ; Ultraviolet Rays</subject><ispartof>Journal of pediatric surgery, 2010-12, Vol.45 (12), p.2403-2407</ispartof><rights>Elsevier Inc.</rights><rights>2010 Elsevier Inc.</rights><rights>Copyright © 2010 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c488t-b01e74c8f98c4edbb5b859f92644b1817e6683b4b1f388b56ac25cc2c15ea27b3</citedby><cites>FETCH-LOGICAL-c488t-b01e74c8f98c4edbb5b859f92644b1817e6683b4b1f388b56ac25cc2c15ea27b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0022346810007141$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21129555$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miyahara, Katsumi</creatorcontrib><creatorcontrib>Kato, Yoshifumi</creatorcontrib><creatorcontrib>Koga, Hiroyuki</creatorcontrib><creatorcontrib>Lane, Geoffrey J</creatorcontrib><creatorcontrib>Inoue, Takayoshi</creatorcontrib><creatorcontrib>Akazawa, Chihiro</creatorcontrib><creatorcontrib>Yamataka, Atsuyuki</creatorcontrib><title>Abnormal enteric innervation identified without histopathologic staining in aganglionic colorectum from a mouse model of Hirschsprung's disease</title><title>Journal of pediatric surgery</title><addtitle>J Pediatr Surg</addtitle><description>Abstract Purpose The piebald lethal mouse with a deletion of endothelin-B receptor gene (EDNRB) is a model for Hirschsprung's disease (HD), whereas the SOX10 gene is vital for the development of intestinal neural crest–derived cells. Recently, we created a SOX10 transgenic mouse with intestinal neural crest–derived cells visible with enhanced green fluorescent protein (VENUS), that is, SOX10-VENUS+ /EDNRBsl/sl to investigate intestinal innervation in HD. Methods SOX10-VENUS+ /EDNRBsl/sl (n = 30) were compared with wild-type littermates as controls (EDNRBs/s , n = 30). Mice were killed on days 3, 7, or 12 of age. The entire colorectum was excised, fixed with 4% paraformaldehyde, and examined using fluorescence microscopy alone without staining. Results In normoganglionic colorectum from controls, a grid network of nerve fibers/glial cells was visualized that connected smoothly with extrinsic nerve fibers running along the colorectal wall. In aganglionic colorectum from SOX10-VENUS+ /EDNRBsl/sl mice, there was no grid network and more extrinsic nerve fibers than controls that invaded the colon wall becoming elongated with branching fibers. Normoganglionic colon from controls and SOX10-VENUS+ /EDNRBsl/sl mice appeared the same. Innervation patterns did not change over time. Conclusion This is the first time for abnormal enteric innervation in aganglionic colon in a model for HD to be visualized without staining.</description><subject>Animal model</subject><subject>Animals</subject><subject>Bacterial Proteins - analysis</subject><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Proteins - radiation effects</subject><subject>Cell Lineage</subject><subject>Colon - innervation</subject><subject>Colon - pathology</subject><subject>Disease Models, Animal</subject><subject>Endothelin-B receptor</subject><subject>Enteric Nervous System - abnormalities</subject><subject>Enteric Nervous System - pathology</subject><subject>Fluorescent Antibody Technique</subject><subject>Fluorescent Dyes - analysis</subject><subject>Fluorescent Dyes - radiation effects</subject><subject>Ganglia, Parasympathetic - ultrastructure</subject><subject>Hirschsprung Disease - pathology</subject><subject>Hirschsprung's disease</subject><subject>Luminescent Proteins - analysis</subject><subject>Luminescent Proteins - genetics</subject><subject>Luminescent Proteins - radiation effects</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Mutant Strains</subject><subject>Mice, Transgenic</subject><subject>Microscopy, Confocal</subject><subject>Microscopy, Fluorescence</subject><subject>Nerve Fibers - ultrastructure</subject><subject>Neural Crest - pathology</subject><subject>Neural crest cell</subject><subject>Pediatrics</subject><subject>Receptor, Endothelin B - biosynthesis</subject><subject>Receptor, Endothelin B - deficiency</subject><subject>Receptor, Endothelin B - genetics</subject><subject>Rectum - innervation</subject><subject>Rectum - pathology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - analysis</subject><subject>RNA, Messenger - biosynthesis</subject><subject>RNA, Messenger - genetics</subject><subject>SOX10</subject><subject>SOXE Transcription Factors - genetics</subject><subject>Surgery</subject><subject>Ultraviolet Rays</subject><issn>0022-3468</issn><issn>1531-5037</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUstu1TAQtRCIXgq_UHnX1b34kYezQVQVpUiVWABry3YmuQ6JHeykqF_RX2ai27Jgw8b2HJ8zY88ZQi44O3DGq_fDYZihzWvqD4IhyNSByeYF2fFS8n3JZP2S7BgTYi-LSp2RNzkPjCHM-GtyJjgXTVmWO_J4ZUNMkxkphAWSd9SHAOneLD4G6ltEfeehpb_9cozrQo8-L3E2GIyxR3pejA8-9KijpjehH1GIuMP7BG5ZJ9qlOFFDp7hmwLWFkcaO3vqU3THPaQ39Zaatz2AyvCWvOjNmePe0n5MfN5--X9_u775-_nJ9dbd3hVLL3jIOdeFU1yhXQGttaVXZdI2oisJyxWuoKiUtnjuplC0r40TpnHC8BCNqK8_J5SnvnOKvFfKiJ58djKMJgO_UilcSM0qGzOrEdCnmnKDTc_KTSQ-aM715oQf97IXevNBMafQChRdPJVY7QftX9tx8JHw8EQA_eu8h6ew8BAet3zqn2-j_X-PDPynciHY4M_6EB8hDXFPANmqus9BMf9smYhsIjrNQ84LLP5wzt44</recordid><startdate>20101201</startdate><enddate>20101201</enddate><creator>Miyahara, Katsumi</creator><creator>Kato, Yoshifumi</creator><creator>Koga, Hiroyuki</creator><creator>Lane, Geoffrey J</creator><creator>Inoue, Takayoshi</creator><creator>Akazawa, Chihiro</creator><creator>Yamataka, Atsuyuki</creator><general>Elsevier Inc</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>7X8</scope></search><sort><creationdate>20101201</creationdate><title>Abnormal enteric innervation identified without histopathologic staining in aganglionic colorectum from a mouse model of Hirschsprung's disease</title><author>Miyahara, Katsumi ; Kato, Yoshifumi ; Koga, Hiroyuki ; Lane, Geoffrey J ; Inoue, Takayoshi ; Akazawa, Chihiro ; Yamataka, Atsuyuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c488t-b01e74c8f98c4edbb5b859f92644b1817e6683b4b1f388b56ac25cc2c15ea27b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animal model</topic><topic>Animals</topic><topic>Bacterial Proteins - analysis</topic><topic>Bacterial Proteins - genetics</topic><topic>Bacterial Proteins - radiation effects</topic><topic>Cell Lineage</topic><topic>Colon - innervation</topic><topic>Colon - pathology</topic><topic>Disease Models, Animal</topic><topic>Endothelin-B receptor</topic><topic>Enteric Nervous System - abnormalities</topic><topic>Enteric Nervous System - pathology</topic><topic>Fluorescent Antibody Technique</topic><topic>Fluorescent Dyes - analysis</topic><topic>Fluorescent Dyes - radiation effects</topic><topic>Ganglia, Parasympathetic - ultrastructure</topic><topic>Hirschsprung Disease - pathology</topic><topic>Hirschsprung's disease</topic><topic>Luminescent Proteins - analysis</topic><topic>Luminescent Proteins - genetics</topic><topic>Luminescent Proteins - radiation effects</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Mutant Strains</topic><topic>Mice, Transgenic</topic><topic>Microscopy, Confocal</topic><topic>Microscopy, Fluorescence</topic><topic>Nerve Fibers - ultrastructure</topic><topic>Neural Crest - pathology</topic><topic>Neural crest cell</topic><topic>Pediatrics</topic><topic>Receptor, Endothelin B - biosynthesis</topic><topic>Receptor, Endothelin B - deficiency</topic><topic>Receptor, Endothelin B - genetics</topic><topic>Rectum - innervation</topic><topic>Rectum - pathology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - analysis</topic><topic>RNA, Messenger - biosynthesis</topic><topic>RNA, Messenger - genetics</topic><topic>SOX10</topic><topic>SOXE Transcription Factors - genetics</topic><topic>Surgery</topic><topic>Ultraviolet Rays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miyahara, Katsumi</creatorcontrib><creatorcontrib>Kato, Yoshifumi</creatorcontrib><creatorcontrib>Koga, Hiroyuki</creatorcontrib><creatorcontrib>Lane, Geoffrey J</creatorcontrib><creatorcontrib>Inoue, Takayoshi</creatorcontrib><creatorcontrib>Akazawa, Chihiro</creatorcontrib><creatorcontrib>Yamataka, Atsuyuki</creatorcontrib><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>Journal of pediatric surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miyahara, Katsumi</au><au>Kato, Yoshifumi</au><au>Koga, Hiroyuki</au><au>Lane, Geoffrey J</au><au>Inoue, Takayoshi</au><au>Akazawa, Chihiro</au><au>Yamataka, Atsuyuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Abnormal enteric innervation identified without histopathologic staining in aganglionic colorectum from a mouse model of Hirschsprung's disease</atitle><jtitle>Journal of pediatric surgery</jtitle><addtitle>J Pediatr Surg</addtitle><date>2010-12-01</date><risdate>2010</risdate><volume>45</volume><issue>12</issue><spage>2403</spage><epage>2407</epage><pages>2403-2407</pages><issn>0022-3468</issn><eissn>1531-5037</eissn><abstract>Abstract Purpose The piebald lethal mouse with a deletion of endothelin-B receptor gene (EDNRB) is a model for Hirschsprung's disease (HD), whereas the SOX10 gene is vital for the development of intestinal neural crest–derived cells. Recently, we created a SOX10 transgenic mouse with intestinal neural crest–derived cells visible with enhanced green fluorescent protein (VENUS), that is, SOX10-VENUS+ /EDNRBsl/sl to investigate intestinal innervation in HD. Methods SOX10-VENUS+ /EDNRBsl/sl (n = 30) were compared with wild-type littermates as controls (EDNRBs/s , n = 30). Mice were killed on days 3, 7, or 12 of age. The entire colorectum was excised, fixed with 4% paraformaldehyde, and examined using fluorescence microscopy alone without staining. Results In normoganglionic colorectum from controls, a grid network of nerve fibers/glial cells was visualized that connected smoothly with extrinsic nerve fibers running along the colorectal wall. In aganglionic colorectum from SOX10-VENUS+ /EDNRBsl/sl mice, there was no grid network and more extrinsic nerve fibers than controls that invaded the colon wall becoming elongated with branching fibers. Normoganglionic colon from controls and SOX10-VENUS+ /EDNRBsl/sl mice appeared the same. Innervation patterns did not change over time. Conclusion This is the first time for abnormal enteric innervation in aganglionic colon in a model for HD to be visualized without staining.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>21129555</pmid><doi>10.1016/j.jpedsurg.2010.08.039</doi><tpages>5</tpages></addata></record> |
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| subjects | Animal model Animals Bacterial Proteins - analysis Bacterial Proteins - genetics Bacterial Proteins - radiation effects Cell Lineage Colon - innervation Colon - pathology Disease Models, Animal Endothelin-B receptor Enteric Nervous System - abnormalities Enteric Nervous System - pathology Fluorescent Antibody Technique Fluorescent Dyes - analysis Fluorescent Dyes - radiation effects Ganglia, Parasympathetic - ultrastructure Hirschsprung Disease - pathology Hirschsprung's disease Luminescent Proteins - analysis Luminescent Proteins - genetics Luminescent Proteins - radiation effects Mice Mice, Inbred C57BL Mice, Mutant Strains Mice, Transgenic Microscopy, Confocal Microscopy, Fluorescence Nerve Fibers - ultrastructure Neural Crest - pathology Neural crest cell Pediatrics Receptor, Endothelin B - biosynthesis Receptor, Endothelin B - deficiency Receptor, Endothelin B - genetics Rectum - innervation Rectum - pathology Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - analysis RNA, Messenger - biosynthesis RNA, Messenger - genetics SOX10 SOXE Transcription Factors - genetics Surgery Ultraviolet Rays |
| title | Abnormal enteric innervation identified without histopathologic staining in aganglionic colorectum from a mouse model of Hirschsprung's disease |
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