Loading…

Decreased mucosal expression of intestinal alkaline phosphatase in children with coeliac disease

A major function of the enzyme intestinal alkaline phosphatase (iAP) is the detoxification of lipopolysaccharide (LPS), the ligand of Toll-like receptor 4 (TLR4). Hence, iAP has a role in the defence of maintaining intestinal barrier integrity. As intestinal barrier integrity is impaired in coeliac...

Full description

Saved in:
Bibliographic Details
Published in:Virchows Archiv : an international journal of pathology 2012-02, Vol.460 (2), p.157-161
Main Authors: Molnár, Kriszta, Vannay, Ádám, Sziksz, Erna, Bánki, Nóra Fanni, Győrffy, Hajnalka, Arató, András, Dezsőfi, Antal, Veres, Gabor
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c401t-2ab3598986987e31a804441f5a3b41ab4b47e7f7262b1f40468f8bd0a4a213503
cites cdi_FETCH-LOGICAL-c401t-2ab3598986987e31a804441f5a3b41ab4b47e7f7262b1f40468f8bd0a4a213503
container_end_page 161
container_issue 2
container_start_page 157
container_title Virchows Archiv : an international journal of pathology
container_volume 460
creator Molnár, Kriszta
Vannay, Ádám
Sziksz, Erna
Bánki, Nóra Fanni
Győrffy, Hajnalka
Arató, András
Dezsőfi, Antal
Veres, Gabor
description A major function of the enzyme intestinal alkaline phosphatase (iAP) is the detoxification of lipopolysaccharide (LPS), the ligand of Toll-like receptor 4 (TLR4). Hence, iAP has a role in the defence of maintaining intestinal barrier integrity. As intestinal barrier integrity is impaired in coeliac disease (CD), we tested the expression and localization of iAP in duodenal mucosa specimens from children with newly diagnosed CD ( n  = 10), with CD on gluten-free diet (GFD) ( n  = 5) and compared to those from ten healthy children. The mRNA and protein expression was determined by RT-PCR and Western blot analysis, respectively. Tissue localization of iAP and TLR4 was determined by immunofluorescence staining. iAP protein expression level was significantly lower than normal in newly diagnosed CD, while it was normalised in children on GFD. iAP and TLR4 colocalized at the epithelial surface of duodenal mucosa in each group of subjects enrolled. The finding of decreased iAP protein levels in newly diagnosed CD is consistent with its role in decreased intestinal barrier integrity. The latter may be the result of decreased LPS-detoxifying ability.
doi_str_mv 10.1007/s00428-011-1188-5
format article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1002793510</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1002793510</sourcerecordid><originalsourceid>FETCH-LOGICAL-c401t-2ab3598986987e31a804441f5a3b41ab4b47e7f7262b1f40468f8bd0a4a213503</originalsourceid><addsrcrecordid>eNp1kEuP1DAQhC0EYoeFH8AFWUhIXAJuP2LniJantBIXOIeO4zBePHFwJwL-PR7NwEpInHyor8rVxdhjEC9ACPuShNDSNQKgAXCuMXfYDrSSjVTC3mU70WnTtArsBXtAdCOEBAftfXYhpWylULBjX14HXwJSGPlh85kw8fBzKYEo5pnnicd5DbTGuQqYvmGKc-DLPtOyx7Xaqs79PqaxhJn_iOue-xxSRM_HSMfch-zehInCo_N7yT6_ffPp6n1z_fHdh6tX143XAtZG4qBM5zrXds4GBeiE1homg2rQgIMetA12srX3AJMWunWTG0aBGiUoI9Qle37KXUr-vtXK_SGSDynhHPJGfR1M2k4ZOKJP_0Fv8lbqhdR30jpjoNUVghPkSyYqYeqXEg9YftWkY5jtT-v3df3-uH5vqufJOXgbDmH86_gzdwWenQEkj2kqOPtIt5xpjXHOVU6eOKrS_DWU24b___038TWbng</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>927855164</pqid></control><display><type>article</type><title>Decreased mucosal expression of intestinal alkaline phosphatase in children with coeliac disease</title><source>Springer Link</source><creator>Molnár, Kriszta ; Vannay, Ádám ; Sziksz, Erna ; Bánki, Nóra Fanni ; Győrffy, Hajnalka ; Arató, András ; Dezsőfi, Antal ; Veres, Gabor</creator><creatorcontrib>Molnár, Kriszta ; Vannay, Ádám ; Sziksz, Erna ; Bánki, Nóra Fanni ; Győrffy, Hajnalka ; Arató, András ; Dezsőfi, Antal ; Veres, Gabor</creatorcontrib><description>A major function of the enzyme intestinal alkaline phosphatase (iAP) is the detoxification of lipopolysaccharide (LPS), the ligand of Toll-like receptor 4 (TLR4). Hence, iAP has a role in the defence of maintaining intestinal barrier integrity. As intestinal barrier integrity is impaired in coeliac disease (CD), we tested the expression and localization of iAP in duodenal mucosa specimens from children with newly diagnosed CD ( n  = 10), with CD on gluten-free diet (GFD) ( n  = 5) and compared to those from ten healthy children. The mRNA and protein expression was determined by RT-PCR and Western blot analysis, respectively. Tissue localization of iAP and TLR4 was determined by immunofluorescence staining. iAP protein expression level was significantly lower than normal in newly diagnosed CD, while it was normalised in children on GFD. iAP and TLR4 colocalized at the epithelial surface of duodenal mucosa in each group of subjects enrolled. The finding of decreased iAP protein levels in newly diagnosed CD is consistent with its role in decreased intestinal barrier integrity. The latter may be the result of decreased LPS-detoxifying ability.</description><identifier>ISSN: 0945-6317</identifier><identifier>EISSN: 1432-2307</identifier><identifier>DOI: 10.1007/s00428-011-1188-5</identifier><identifier>PMID: 22262031</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Adolescent ; Alkaline Phosphatase - biosynthesis ; Biological and medical sciences ; Blotting, Western ; Celiac Disease - enzymology ; Child ; Child, Preschool ; Detoxification ; Female ; Fluorescent Antibody Technique ; Gastroenterology. Liver. Pancreas. Abdomen ; Gluten ; Humans ; Infant ; Intestinal Mucosa - enzymology ; Investigative techniques, diagnostic techniques (general aspects) ; Male ; Medical sciences ; Medicine ; Medicine &amp; Public Health ; Original Article ; Other diseases. Semiology ; Pathology ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Real-Time Polymerase Chain Reaction ; RNA, Messenger - analysis ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Toll-Like Receptor 4 - biosynthesis</subject><ispartof>Virchows Archiv : an international journal of pathology, 2012-02, Vol.460 (2), p.157-161</ispartof><rights>Springer-Verlag 2012</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c401t-2ab3598986987e31a804441f5a3b41ab4b47e7f7262b1f40468f8bd0a4a213503</citedby><cites>FETCH-LOGICAL-c401t-2ab3598986987e31a804441f5a3b41ab4b47e7f7262b1f40468f8bd0a4a213503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=25655888$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22262031$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Molnár, Kriszta</creatorcontrib><creatorcontrib>Vannay, Ádám</creatorcontrib><creatorcontrib>Sziksz, Erna</creatorcontrib><creatorcontrib>Bánki, Nóra Fanni</creatorcontrib><creatorcontrib>Győrffy, Hajnalka</creatorcontrib><creatorcontrib>Arató, András</creatorcontrib><creatorcontrib>Dezsőfi, Antal</creatorcontrib><creatorcontrib>Veres, Gabor</creatorcontrib><title>Decreased mucosal expression of intestinal alkaline phosphatase in children with coeliac disease</title><title>Virchows Archiv : an international journal of pathology</title><addtitle>Virchows Arch</addtitle><addtitle>Virchows Arch</addtitle><description>A major function of the enzyme intestinal alkaline phosphatase (iAP) is the detoxification of lipopolysaccharide (LPS), the ligand of Toll-like receptor 4 (TLR4). Hence, iAP has a role in the defence of maintaining intestinal barrier integrity. As intestinal barrier integrity is impaired in coeliac disease (CD), we tested the expression and localization of iAP in duodenal mucosa specimens from children with newly diagnosed CD ( n  = 10), with CD on gluten-free diet (GFD) ( n  = 5) and compared to those from ten healthy children. The mRNA and protein expression was determined by RT-PCR and Western blot analysis, respectively. Tissue localization of iAP and TLR4 was determined by immunofluorescence staining. iAP protein expression level was significantly lower than normal in newly diagnosed CD, while it was normalised in children on GFD. iAP and TLR4 colocalized at the epithelial surface of duodenal mucosa in each group of subjects enrolled. The finding of decreased iAP protein levels in newly diagnosed CD is consistent with its role in decreased intestinal barrier integrity. The latter may be the result of decreased LPS-detoxifying ability.</description><subject>Adolescent</subject><subject>Alkaline Phosphatase - biosynthesis</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Celiac Disease - enzymology</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Detoxification</subject><subject>Female</subject><subject>Fluorescent Antibody Technique</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gluten</subject><subject>Humans</subject><subject>Infant</subject><subject>Intestinal Mucosa - enzymology</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Original Article</subject><subject>Other diseases. Semiology</subject><subject>Pathology</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>RNA, Messenger - analysis</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Toll-Like Receptor 4 - biosynthesis</subject><issn>0945-6317</issn><issn>1432-2307</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNp1kEuP1DAQhC0EYoeFH8AFWUhIXAJuP2LniJantBIXOIeO4zBePHFwJwL-PR7NwEpInHyor8rVxdhjEC9ACPuShNDSNQKgAXCuMXfYDrSSjVTC3mU70WnTtArsBXtAdCOEBAftfXYhpWylULBjX14HXwJSGPlh85kw8fBzKYEo5pnnicd5DbTGuQqYvmGKc-DLPtOyx7Xaqs79PqaxhJn_iOue-xxSRM_HSMfch-zehInCo_N7yT6_ffPp6n1z_fHdh6tX143XAtZG4qBM5zrXds4GBeiE1homg2rQgIMetA12srX3AJMWunWTG0aBGiUoI9Qle37KXUr-vtXK_SGSDynhHPJGfR1M2k4ZOKJP_0Fv8lbqhdR30jpjoNUVghPkSyYqYeqXEg9YftWkY5jtT-v3df3-uH5vqufJOXgbDmH86_gzdwWenQEkj2kqOPtIt5xpjXHOVU6eOKrS_DWU24b___038TWbng</recordid><startdate>20120201</startdate><enddate>20120201</enddate><creator>Molnár, Kriszta</creator><creator>Vannay, Ádám</creator><creator>Sziksz, Erna</creator><creator>Bánki, Nóra Fanni</creator><creator>Győrffy, Hajnalka</creator><creator>Arató, András</creator><creator>Dezsőfi, Antal</creator><creator>Veres, Gabor</creator><general>Springer-Verlag</general><general>Springer</general><general>Springer Nature B.V</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>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</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>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>20120201</creationdate><title>Decreased mucosal expression of intestinal alkaline phosphatase in children with coeliac disease</title><author>Molnár, Kriszta ; Vannay, Ádám ; Sziksz, Erna ; Bánki, Nóra Fanni ; Győrffy, Hajnalka ; Arató, András ; Dezsőfi, Antal ; Veres, Gabor</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c401t-2ab3598986987e31a804441f5a3b41ab4b47e7f7262b1f40468f8bd0a4a213503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adolescent</topic><topic>Alkaline Phosphatase - biosynthesis</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Celiac Disease - enzymology</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Detoxification</topic><topic>Female</topic><topic>Fluorescent Antibody Technique</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gluten</topic><topic>Humans</topic><topic>Infant</topic><topic>Intestinal Mucosa - enzymology</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Original Article</topic><topic>Other diseases. Semiology</topic><topic>Pathology</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>RNA, Messenger - analysis</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Toll-Like Receptor 4 - biosynthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Molnár, Kriszta</creatorcontrib><creatorcontrib>Vannay, Ádám</creatorcontrib><creatorcontrib>Sziksz, Erna</creatorcontrib><creatorcontrib>Bánki, Nóra Fanni</creatorcontrib><creatorcontrib>Győrffy, Hajnalka</creatorcontrib><creatorcontrib>Arató, András</creatorcontrib><creatorcontrib>Dezsőfi, Antal</creatorcontrib><creatorcontrib>Veres, Gabor</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>ProQuest Central (Corporate)</collection><collection>ProQuest Nursing &amp; Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</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)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</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 &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Biological Science Journals</collection><collection>Nursing &amp; Allied Health Premium</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>MEDLINE - Academic</collection><jtitle>Virchows Archiv : an international journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Molnár, Kriszta</au><au>Vannay, Ádám</au><au>Sziksz, Erna</au><au>Bánki, Nóra Fanni</au><au>Győrffy, Hajnalka</au><au>Arató, András</au><au>Dezsőfi, Antal</au><au>Veres, Gabor</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Decreased mucosal expression of intestinal alkaline phosphatase in children with coeliac disease</atitle><jtitle>Virchows Archiv : an international journal of pathology</jtitle><stitle>Virchows Arch</stitle><addtitle>Virchows Arch</addtitle><date>2012-02-01</date><risdate>2012</risdate><volume>460</volume><issue>2</issue><spage>157</spage><epage>161</epage><pages>157-161</pages><issn>0945-6317</issn><eissn>1432-2307</eissn><abstract>A major function of the enzyme intestinal alkaline phosphatase (iAP) is the detoxification of lipopolysaccharide (LPS), the ligand of Toll-like receptor 4 (TLR4). Hence, iAP has a role in the defence of maintaining intestinal barrier integrity. As intestinal barrier integrity is impaired in coeliac disease (CD), we tested the expression and localization of iAP in duodenal mucosa specimens from children with newly diagnosed CD ( n  = 10), with CD on gluten-free diet (GFD) ( n  = 5) and compared to those from ten healthy children. The mRNA and protein expression was determined by RT-PCR and Western blot analysis, respectively. Tissue localization of iAP and TLR4 was determined by immunofluorescence staining. iAP protein expression level was significantly lower than normal in newly diagnosed CD, while it was normalised in children on GFD. iAP and TLR4 colocalized at the epithelial surface of duodenal mucosa in each group of subjects enrolled. The finding of decreased iAP protein levels in newly diagnosed CD is consistent with its role in decreased intestinal barrier integrity. The latter may be the result of decreased LPS-detoxifying ability.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>22262031</pmid><doi>10.1007/s00428-011-1188-5</doi><tpages>5</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0945-6317
ispartof Virchows Archiv : an international journal of pathology, 2012-02, Vol.460 (2), p.157-161
issn 0945-6317
1432-2307
language eng
recordid cdi_proquest_miscellaneous_1002793510
source Springer Link
subjects Adolescent
Alkaline Phosphatase - biosynthesis
Biological and medical sciences
Blotting, Western
Celiac Disease - enzymology
Child
Child, Preschool
Detoxification
Female
Fluorescent Antibody Technique
Gastroenterology. Liver. Pancreas. Abdomen
Gluten
Humans
Infant
Intestinal Mucosa - enzymology
Investigative techniques, diagnostic techniques (general aspects)
Male
Medical sciences
Medicine
Medicine & Public Health
Original Article
Other diseases. Semiology
Pathology
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
Real-Time Polymerase Chain Reaction
RNA, Messenger - analysis
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Toll-Like Receptor 4 - biosynthesis
title Decreased mucosal expression of intestinal alkaline phosphatase in children with coeliac disease
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-17T20%3A19%3A42IST&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=Decreased%20mucosal%20expression%20of%20intestinal%20alkaline%20phosphatase%20in%20children%20with%20coeliac%20disease&rft.jtitle=Virchows%20Archiv%20:%20an%20international%20journal%20of%20pathology&rft.au=Moln%C3%A1r,%20Kriszta&rft.date=2012-02-01&rft.volume=460&rft.issue=2&rft.spage=157&rft.epage=161&rft.pages=157-161&rft.issn=0945-6317&rft.eissn=1432-2307&rft_id=info:doi/10.1007/s00428-011-1188-5&rft_dat=%3Cproquest_cross%3E1002793510%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c401t-2ab3598986987e31a804441f5a3b41ab4b47e7f7262b1f40468f8bd0a4a213503%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=927855164&rft_id=info:pmid/22262031&rfr_iscdi=true