Isolation of human lymphatic malformation endothelial cells, their in vitro characterization and in vivo survival in a mouse xenograft model
Human lymphatic vascular malformations (LMs), also known as cystic hygromas or lymphangioma, consist of multiple lymphatic endothelial cell-lined lymph-containing cysts. No animal model of this disease exists. To develop a mouse xenograft model of human LM, CD34 Neg CD31 Pos LM lymphatic endothelial...
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| Veröffentlicht in: | Angiogenesis (London) 2014-01, Vol.17 (1), p.1-15 |
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| creator | Lokmic, Zerina Mitchell, Geraldine M. Koh Wee Chong, Nicholas Bastiaanse, Jacqueline Gerrand, Yi-Wen Zeng, Yiping Williams, Elizabeth D. Penington, Anthony J. |
| description | Human lymphatic vascular malformations (LMs), also known as cystic hygromas or lymphangioma, consist of multiple lymphatic endothelial cell-lined lymph-containing cysts. No animal model of this disease exists. To develop a mouse xenograft model of human LM, CD34
Neg
CD31
Pos
LM lymphatic endothelial cells (LM-LEC) were isolated from surgical specimens and compared to foreskin CD34
Neg
CD31
Pos
lymphatic endothelial cells (LECs). Cells were implanted into a mouse tissue engineering model for 1, 2 and 4 weeks. In vitro LM-LECs showed increased proliferation and survival under starvation conditions (
P
|
| doi_str_mv | 10.1007/s10456-013-9371-8 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1490751350</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3173032101</sourcerecordid><originalsourceid>FETCH-LOGICAL-c415t-4d772738d6be699801670b06392e0c4194f5fbc202408f1e237a4b0f6c31a1733</originalsourceid><addsrcrecordid>eNp1kc1q3TAQhUVoaG6TPEA2RdBNF3U6smTJWpbQn0Agm3QtZFvKdZClW8kOTZ4hD925OA2h0NUwc74zGnEIOWNwzgDU58JANLICxivNFavaA7JhjeKVqkG_IRvQUldSKzgi70q5A8BBK96So5q3rVBabsjTZUnBzmOKNHm6XSYbaXiYdluc9XSywac8rbqLQ5q3Low20N6FUD5RbMdMx0jvxzkn2m9ttv3s8vi4WmwcVvU-0bJkrOjFgaVTWoqjv11Mt9n6GfvBhRNy6G0o7vS5HpOf377eXPyorq6_X158uap6wZq5EoNSteLtIDsntW6BSQUdSK5rB4ho4Rvf9TXUAlrPXM2VFR142XNmmeL8mHxc9-5y-rW4MptpLPsv2ejwLsOEBtUw3gCiH_5B79KSI16HlBIgGTQCKbZSfU6lZOfNLo-TzQ-GgdlHZdaoDEZl9lGZFj3vnzcv3eSGF8ffbBCoV6CgFG9dfvX0f7f-AUMCn9E</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1474061054</pqid></control><display><type>article</type><title>Isolation of human lymphatic malformation endothelial cells, their in vitro characterization and in vivo survival in a mouse xenograft model</title><source>MEDLINE</source><source>SpringerLink</source><creator>Lokmic, Zerina ; Mitchell, Geraldine M. ; Koh Wee Chong, Nicholas ; Bastiaanse, Jacqueline ; Gerrand, Yi-Wen ; Zeng, Yiping ; Williams, Elizabeth D. ; Penington, Anthony J.</creator><creatorcontrib>Lokmic, Zerina ; Mitchell, Geraldine M. ; Koh Wee Chong, Nicholas ; Bastiaanse, Jacqueline ; Gerrand, Yi-Wen ; Zeng, Yiping ; Williams, Elizabeth D. ; Penington, Anthony J.</creatorcontrib><description>Human lymphatic vascular malformations (LMs), also known as cystic hygromas or lymphangioma, consist of multiple lymphatic endothelial cell-lined lymph-containing cysts. No animal model of this disease exists. To develop a mouse xenograft model of human LM, CD34
Neg
CD31
Pos
LM lymphatic endothelial cells (LM-LEC) were isolated from surgical specimens and compared to foreskin CD34
Neg
CD31
Pos
lymphatic endothelial cells (LECs). Cells were implanted into a mouse tissue engineering model for 1, 2 and 4 weeks. In vitro LM-LECs showed increased proliferation and survival under starvation conditions (
P
< 0.0005 at 48 h, two-way ANOVA), increased migration (
P
< 0.001, two-way ANOVA) and formed fewer (
P
= 0.029, independent samples
t
test), shorter tubes (
P
= 0.029, independent samples
t
test) than foreskin LECs. In vivo LM-LECs implanted into a Matrigel™-containing mouse chamber model assembled to develop vessels with dilated cystic lumens lined with flat endothelium, morphology similar to that of clinical LMs. Human foreskin LECs failed to survive implantation. In LM-LEC implanted chambers the percent volume of podoplanin
Pos
vessels was 1.18 ± 2.24 % at 1 week, 6.34 ± 2.68 % at 2 weeks and increasing to 7.67 ± 3.60 % at 4 weeks. In conclusion, the significantly increased proliferation, migration, resistance to apoptosis and decreased tubulogenesis of LM-LECs observed in vitro is likely to account for their survival and assembly into stable LM-like structures when implanted into a mouse vascularised chamber model. This in vivo xenograft model will provide the basis of future studies of LM biology and testing of potential pharmacological interventions for patients with lymphatic malformations.</description><identifier>ISSN: 0969-6970</identifier><identifier>EISSN: 1573-7209</identifier><identifier>DOI: 10.1007/s10456-013-9371-8</identifier><identifier>PMID: 23884796</identifier><identifier>CODEN: AGIOFT</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Animals ; Antigens, CD34 - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Cardiology ; Cell Biology ; Cell Proliferation ; Cell Separation ; Cell Survival ; Child ; Child, Preschool ; Endothelial Cells - metabolism ; Endothelial Cells - pathology ; Endothelial Cells - transplantation ; Female ; Graft Survival ; Heterografts ; Humans ; Infant ; Lymphatic Vessels - abnormalities ; Lymphatic Vessels - metabolism ; Lymphatic Vessels - pathology ; Male ; Mice ; Mice, SCID ; Oncology ; Ophthalmology ; Original Paper ; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism ; Time Factors ; Tissue Engineering - methods</subject><ispartof>Angiogenesis (London), 2014-01, Vol.17 (1), p.1-15</ispartof><rights>Springer Science+Business Media Dordrecht 2013</rights><rights>Springer Science+Business Media Dordrecht 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-4d772738d6be699801670b06392e0c4194f5fbc202408f1e237a4b0f6c31a1733</citedby><cites>FETCH-LOGICAL-c415t-4d772738d6be699801670b06392e0c4194f5fbc202408f1e237a4b0f6c31a1733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10456-013-9371-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10456-013-9371-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23884796$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lokmic, Zerina</creatorcontrib><creatorcontrib>Mitchell, Geraldine M.</creatorcontrib><creatorcontrib>Koh Wee Chong, Nicholas</creatorcontrib><creatorcontrib>Bastiaanse, Jacqueline</creatorcontrib><creatorcontrib>Gerrand, Yi-Wen</creatorcontrib><creatorcontrib>Zeng, Yiping</creatorcontrib><creatorcontrib>Williams, Elizabeth D.</creatorcontrib><creatorcontrib>Penington, Anthony J.</creatorcontrib><title>Isolation of human lymphatic malformation endothelial cells, their in vitro characterization and in vivo survival in a mouse xenograft model</title><title>Angiogenesis (London)</title><addtitle>Angiogenesis</addtitle><addtitle>Angiogenesis</addtitle><description>Human lymphatic vascular malformations (LMs), also known as cystic hygromas or lymphangioma, consist of multiple lymphatic endothelial cell-lined lymph-containing cysts. No animal model of this disease exists. To develop a mouse xenograft model of human LM, CD34
Neg
CD31
Pos
LM lymphatic endothelial cells (LM-LEC) were isolated from surgical specimens and compared to foreskin CD34
Neg
CD31
Pos
lymphatic endothelial cells (LECs). Cells were implanted into a mouse tissue engineering model for 1, 2 and 4 weeks. In vitro LM-LECs showed increased proliferation and survival under starvation conditions (
P
< 0.0005 at 48 h, two-way ANOVA), increased migration (
P
< 0.001, two-way ANOVA) and formed fewer (
P
= 0.029, independent samples
t
test), shorter tubes (
P
= 0.029, independent samples
t
test) than foreskin LECs. In vivo LM-LECs implanted into a Matrigel™-containing mouse chamber model assembled to develop vessels with dilated cystic lumens lined with flat endothelium, morphology similar to that of clinical LMs. Human foreskin LECs failed to survive implantation. In LM-LEC implanted chambers the percent volume of podoplanin
Pos
vessels was 1.18 ± 2.24 % at 1 week, 6.34 ± 2.68 % at 2 weeks and increasing to 7.67 ± 3.60 % at 4 weeks. In conclusion, the significantly increased proliferation, migration, resistance to apoptosis and decreased tubulogenesis of LM-LECs observed in vitro is likely to account for their survival and assembly into stable LM-like structures when implanted into a mouse vascularised chamber model. This in vivo xenograft model will provide the basis of future studies of LM biology and testing of potential pharmacological interventions for patients with lymphatic malformations.</description><subject>Animals</subject><subject>Antigens, CD34 - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Cardiology</subject><subject>Cell Biology</subject><subject>Cell Proliferation</subject><subject>Cell Separation</subject><subject>Cell Survival</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelial Cells - pathology</subject><subject>Endothelial Cells - transplantation</subject><subject>Female</subject><subject>Graft Survival</subject><subject>Heterografts</subject><subject>Humans</subject><subject>Infant</subject><subject>Lymphatic Vessels - abnormalities</subject><subject>Lymphatic Vessels - metabolism</subject><subject>Lymphatic Vessels - pathology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>Oncology</subject><subject>Ophthalmology</subject><subject>Original Paper</subject><subject>Platelet Endothelial Cell Adhesion Molecule-1 - metabolism</subject><subject>Time Factors</subject><subject>Tissue Engineering - methods</subject><issn>0969-6970</issn><issn>1573-7209</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kc1q3TAQhUVoaG6TPEA2RdBNF3U6smTJWpbQn0Agm3QtZFvKdZClW8kOTZ4hD925OA2h0NUwc74zGnEIOWNwzgDU58JANLICxivNFavaA7JhjeKVqkG_IRvQUldSKzgi70q5A8BBK96So5q3rVBabsjTZUnBzmOKNHm6XSYbaXiYdluc9XSywac8rbqLQ5q3Low20N6FUD5RbMdMx0jvxzkn2m9ttv3s8vi4WmwcVvU-0bJkrOjFgaVTWoqjv11Mt9n6GfvBhRNy6G0o7vS5HpOf377eXPyorq6_X158uap6wZq5EoNSteLtIDsntW6BSQUdSK5rB4ho4Rvf9TXUAlrPXM2VFR142XNmmeL8mHxc9-5y-rW4MptpLPsv2ejwLsOEBtUw3gCiH_5B79KSI16HlBIgGTQCKbZSfU6lZOfNLo-TzQ-GgdlHZdaoDEZl9lGZFj3vnzcv3eSGF8ffbBCoV6CgFG9dfvX0f7f-AUMCn9E</recordid><startdate>20140101</startdate><enddate>20140101</enddate><creator>Lokmic, Zerina</creator><creator>Mitchell, Geraldine M.</creator><creator>Koh Wee Chong, Nicholas</creator><creator>Bastiaanse, Jacqueline</creator><creator>Gerrand, Yi-Wen</creator><creator>Zeng, Yiping</creator><creator>Williams, Elizabeth D.</creator><creator>Penington, Anthony J.</creator><general>Springer Netherlands</general><general>Springer Nature B.V</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>7QO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20140101</creationdate><title>Isolation of human lymphatic malformation endothelial cells, their in vitro characterization and in vivo survival in a mouse xenograft model</title><author>Lokmic, Zerina ; Mitchell, Geraldine M. ; Koh Wee Chong, Nicholas ; Bastiaanse, Jacqueline ; Gerrand, Yi-Wen ; Zeng, Yiping ; Williams, Elizabeth D. ; Penington, Anthony J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-4d772738d6be699801670b06392e0c4194f5fbc202408f1e237a4b0f6c31a1733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Antigens, CD34 - metabolism</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Cardiology</topic><topic>Cell Biology</topic><topic>Cell Proliferation</topic><topic>Cell Separation</topic><topic>Cell Survival</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Endothelial Cells - metabolism</topic><topic>Endothelial Cells - pathology</topic><topic>Endothelial Cells - transplantation</topic><topic>Female</topic><topic>Graft Survival</topic><topic>Heterografts</topic><topic>Humans</topic><topic>Infant</topic><topic>Lymphatic Vessels - abnormalities</topic><topic>Lymphatic Vessels - metabolism</topic><topic>Lymphatic Vessels - pathology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, SCID</topic><topic>Oncology</topic><topic>Ophthalmology</topic><topic>Original Paper</topic><topic>Platelet Endothelial Cell Adhesion Molecule-1 - metabolism</topic><topic>Time Factors</topic><topic>Tissue Engineering - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lokmic, Zerina</creatorcontrib><creatorcontrib>Mitchell, Geraldine M.</creatorcontrib><creatorcontrib>Koh Wee Chong, Nicholas</creatorcontrib><creatorcontrib>Bastiaanse, Jacqueline</creatorcontrib><creatorcontrib>Gerrand, Yi-Wen</creatorcontrib><creatorcontrib>Zeng, Yiping</creatorcontrib><creatorcontrib>Williams, Elizabeth D.</creatorcontrib><creatorcontrib>Penington, Anthony J.</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>Biotechnology Research 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>Technology Research Database</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</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Angiogenesis (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lokmic, Zerina</au><au>Mitchell, Geraldine M.</au><au>Koh Wee Chong, Nicholas</au><au>Bastiaanse, Jacqueline</au><au>Gerrand, Yi-Wen</au><au>Zeng, Yiping</au><au>Williams, Elizabeth D.</au><au>Penington, Anthony J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Isolation of human lymphatic malformation endothelial cells, their in vitro characterization and in vivo survival in a mouse xenograft model</atitle><jtitle>Angiogenesis (London)</jtitle><stitle>Angiogenesis</stitle><addtitle>Angiogenesis</addtitle><date>2014-01-01</date><risdate>2014</risdate><volume>17</volume><issue>1</issue><spage>1</spage><epage>15</epage><pages>1-15</pages><issn>0969-6970</issn><eissn>1573-7209</eissn><coden>AGIOFT</coden><abstract>Human lymphatic vascular malformations (LMs), also known as cystic hygromas or lymphangioma, consist of multiple lymphatic endothelial cell-lined lymph-containing cysts. No animal model of this disease exists. To develop a mouse xenograft model of human LM, CD34
Neg
CD31
Pos
LM lymphatic endothelial cells (LM-LEC) were isolated from surgical specimens and compared to foreskin CD34
Neg
CD31
Pos
lymphatic endothelial cells (LECs). Cells were implanted into a mouse tissue engineering model for 1, 2 and 4 weeks. In vitro LM-LECs showed increased proliferation and survival under starvation conditions (
P
< 0.0005 at 48 h, two-way ANOVA), increased migration (
P
< 0.001, two-way ANOVA) and formed fewer (
P
= 0.029, independent samples
t
test), shorter tubes (
P
= 0.029, independent samples
t
test) than foreskin LECs. In vivo LM-LECs implanted into a Matrigel™-containing mouse chamber model assembled to develop vessels with dilated cystic lumens lined with flat endothelium, morphology similar to that of clinical LMs. Human foreskin LECs failed to survive implantation. In LM-LEC implanted chambers the percent volume of podoplanin
Pos
vessels was 1.18 ± 2.24 % at 1 week, 6.34 ± 2.68 % at 2 weeks and increasing to 7.67 ± 3.60 % at 4 weeks. In conclusion, the significantly increased proliferation, migration, resistance to apoptosis and decreased tubulogenesis of LM-LECs observed in vitro is likely to account for their survival and assembly into stable LM-like structures when implanted into a mouse vascularised chamber model. This in vivo xenograft model will provide the basis of future studies of LM biology and testing of potential pharmacological interventions for patients with lymphatic malformations.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>23884796</pmid><doi>10.1007/s10456-013-9371-8</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antigens, CD34 - metabolism Biomedical and Life Sciences Biomedicine Cancer Research Cardiology Cell Biology Cell Proliferation Cell Separation Cell Survival Child Child, Preschool Endothelial Cells - metabolism Endothelial Cells - pathology Endothelial Cells - transplantation Female Graft Survival Heterografts Humans Infant Lymphatic Vessels - abnormalities Lymphatic Vessels - metabolism Lymphatic Vessels - pathology Male Mice Mice, SCID Oncology Ophthalmology Original Paper Platelet Endothelial Cell Adhesion Molecule-1 - metabolism Time Factors Tissue Engineering - methods |
| title | Isolation of human lymphatic malformation endothelial cells, their in vitro characterization and in vivo survival in a mouse xenograft model |
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