Inhibition by Wnt-1 or Wnt-3a of nerve growth factor-induced differentiation of PC12 cells is reversed by bisindolylmaleimide-I but not by several other PKC inhibitors
Wnt-1 and Wnt-3a exhibit redundancy in neural crest development. We have found that they do not produce the same effects on PC12 cells, which were obtained from the adrenal medulla, a neural crest derivative. However, both Wnt-1 or Wnt-3a inhibit nerve growth factor (NGF)-induced neurite outgrowth....
Gespeichert in:
| Veröffentlicht in: | Oncogene 2002-09, Vol.21 (41), p.6348-6355 |
|---|---|
| Hauptverfasser: | , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 6355 |
|---|---|
| container_issue | 41 |
| container_start_page | 6348 |
| container_title | Oncogene |
| container_volume | 21 |
| creator | CHOU, Alice H HOWARD, Bruce D |
| description | Wnt-1 and Wnt-3a exhibit redundancy in neural crest development. We have found that they do not produce the same effects on PC12 cells, which were obtained from the adrenal medulla, a neural crest derivative. However, both Wnt-1 or Wnt-3a inhibit nerve growth factor (NGF)-induced neurite outgrowth. The inhibition is reversed by the protein kinase C (PKC) inhibitor, bisindolylmaleimide-I, but it did not reverse Wnt-1-induced activation of the canonical Wnt pathway. The Wnt-1 inhibitory effect was not reversed by several other PKC inhibitors, by phorbol ester-induced down-regulation of PKC, or by pertussis toxin, which is known to inhibit another Wnt signaling pathway, the Wnt/Ca(2+) pathway. We suggest that bisindolylmaleimide-I acts by affecting either a pathway downstream from Lef-1/Tcf in the canonical pathway or a Wnt signaling pathway other than the canonical pathway. In either case, the bisindolylmaleimide-I sensitivity of this pathway should aid in its identification. |
| doi_str_mv | 10.1038/sj.onc.1205791 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_18602507</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1028540031</sourcerecordid><originalsourceid>FETCH-LOGICAL-c439t-cbc5ea98abaa496ffea29c8fb41e923c7d02eecf37ba970caa9d2a645fe9a613</originalsourceid><addsrcrecordid>eNp10ctq3DAUBmBRGppp2m2XRbS0O0918U3LMPQyJJAsAl2aY_moo8GWUklOmSfqa1aTMQQKWUmL7_wc6SfkHWdrzmT7Je7X3uk1F6xqFH9BVrxs6qKqVPmSrJiqWKGEFOfkdYx7xlijmHhFzrkQvBRNtSJ_t25ne5usd7Q_0J8uFZz68HiRQL2hDsMD0l_B_0k7akAnHwrrhlnjQAdrDAZ0ycJjQua3Gy6oxnGM1EYa8AFDzDJn9zbmOT8exglGtJMdsNjSfk7U-XQE8YhhpD7tMNDbqw21p-V8iG_ImYEx4tvlvCB3377ebX4U1zfft5vL60KXUqVC97pCUC30AKWq83YglG5NX3LMH6GbgQlEbWTTg2qYBlCDgLqsDCqoubwgn0-x98H_njGmbrLx-Bpw6OfY8bZmomJNhh__g3s_B5dX60Rdcika2YqsPjyrshBcqjaj9Qnp4GMMaLr7YCcIh46z7lhyF_ddLrlbSs4D75fUuZ9weOJLqxl8WgBEDaMJ4LSNT04qLpSq5T-oXrJd</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>227321398</pqid></control><display><type>article</type><title>Inhibition by Wnt-1 or Wnt-3a of nerve growth factor-induced differentiation of PC12 cells is reversed by bisindolylmaleimide-I but not by several other PKC inhibitors</title><source>MEDLINE</source><source>Nature Journals Online</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>SpringerLink Journals - AutoHoldings</source><creator>CHOU, Alice H ; HOWARD, Bruce D</creator><creatorcontrib>CHOU, Alice H ; HOWARD, Bruce D</creatorcontrib><description>Wnt-1 and Wnt-3a exhibit redundancy in neural crest development. We have found that they do not produce the same effects on PC12 cells, which were obtained from the adrenal medulla, a neural crest derivative. However, both Wnt-1 or Wnt-3a inhibit nerve growth factor (NGF)-induced neurite outgrowth. The inhibition is reversed by the protein kinase C (PKC) inhibitor, bisindolylmaleimide-I, but it did not reverse Wnt-1-induced activation of the canonical Wnt pathway. The Wnt-1 inhibitory effect was not reversed by several other PKC inhibitors, by phorbol ester-induced down-regulation of PKC, or by pertussis toxin, which is known to inhibit another Wnt signaling pathway, the Wnt/Ca(2+) pathway. We suggest that bisindolylmaleimide-I acts by affecting either a pathway downstream from Lef-1/Tcf in the canonical pathway or a Wnt signaling pathway other than the canonical pathway. In either case, the bisindolylmaleimide-I sensitivity of this pathway should aid in its identification.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1205791</identifier><identifier>PMID: 12214275</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing</publisher><subject>Adrenal medulla ; Animals ; Axonogenesis ; Biological and medical sciences ; Cell differentiation ; Cell Differentiation - drug effects ; Cell Differentiation - genetics ; Cell differentiation, maturation, development, hematopoiesis ; Cell physiology ; Drug Antagonism ; Enzyme inhibitors ; Enzyme Inhibitors - pharmacology ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Growth factors ; Indoles - pharmacology ; Kinases ; Maleimides - pharmacology ; Molecular and cellular biology ; Molecular genetics ; Morphology ; Nerve growth factor ; Nerve Growth Factor - pharmacology ; Neural crest ; PC12 Cells ; Pertussis ; Pertussis toxin ; Pheochromocytoma cells ; Protein Biosynthesis ; Protein kinase C ; Protein Kinase C - antagonists & inhibitors ; Proteins ; Proteins - genetics ; Proto-Oncogene Proteins - biosynthesis ; Proto-Oncogene Proteins - genetics ; Rats ; Signal transduction ; Signal Transduction - drug effects ; Signal Transduction - genetics ; Wnt protein ; Wnt Proteins ; Wnt1 Protein ; Wnt3 Protein ; Zebrafish Proteins</subject><ispartof>Oncogene, 2002-09, Vol.21 (41), p.6348-6355</ispartof><rights>2002 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Sep 12, 2002</rights><rights>Macmillan Publishers Limited 2002.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-cbc5ea98abaa496ffea29c8fb41e923c7d02eecf37ba970caa9d2a645fe9a613</citedby><cites>FETCH-LOGICAL-c439t-cbc5ea98abaa496ffea29c8fb41e923c7d02eecf37ba970caa9d2a645fe9a613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13912996$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12214275$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CHOU, Alice H</creatorcontrib><creatorcontrib>HOWARD, Bruce D</creatorcontrib><title>Inhibition by Wnt-1 or Wnt-3a of nerve growth factor-induced differentiation of PC12 cells is reversed by bisindolylmaleimide-I but not by several other PKC inhibitors</title><title>Oncogene</title><addtitle>Oncogene</addtitle><description>Wnt-1 and Wnt-3a exhibit redundancy in neural crest development. We have found that they do not produce the same effects on PC12 cells, which were obtained from the adrenal medulla, a neural crest derivative. However, both Wnt-1 or Wnt-3a inhibit nerve growth factor (NGF)-induced neurite outgrowth. The inhibition is reversed by the protein kinase C (PKC) inhibitor, bisindolylmaleimide-I, but it did not reverse Wnt-1-induced activation of the canonical Wnt pathway. The Wnt-1 inhibitory effect was not reversed by several other PKC inhibitors, by phorbol ester-induced down-regulation of PKC, or by pertussis toxin, which is known to inhibit another Wnt signaling pathway, the Wnt/Ca(2+) pathway. We suggest that bisindolylmaleimide-I acts by affecting either a pathway downstream from Lef-1/Tcf in the canonical pathway or a Wnt signaling pathway other than the canonical pathway. In either case, the bisindolylmaleimide-I sensitivity of this pathway should aid in its identification.</description><subject>Adrenal medulla</subject><subject>Animals</subject><subject>Axonogenesis</subject><subject>Biological and medical sciences</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Differentiation - genetics</subject><subject>Cell differentiation, maturation, development, hematopoiesis</subject><subject>Cell physiology</subject><subject>Drug Antagonism</subject><subject>Enzyme inhibitors</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Growth factors</subject><subject>Indoles - pharmacology</subject><subject>Kinases</subject><subject>Maleimides - pharmacology</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Morphology</subject><subject>Nerve growth factor</subject><subject>Nerve Growth Factor - pharmacology</subject><subject>Neural crest</subject><subject>PC12 Cells</subject><subject>Pertussis</subject><subject>Pertussis toxin</subject><subject>Pheochromocytoma cells</subject><subject>Protein Biosynthesis</subject><subject>Protein kinase C</subject><subject>Protein Kinase C - antagonists & inhibitors</subject><subject>Proteins</subject><subject>Proteins - genetics</subject><subject>Proto-Oncogene Proteins - biosynthesis</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Rats</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - genetics</subject><subject>Wnt protein</subject><subject>Wnt Proteins</subject><subject>Wnt1 Protein</subject><subject>Wnt3 Protein</subject><subject>Zebrafish Proteins</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp10ctq3DAUBmBRGppp2m2XRbS0O0918U3LMPQyJJAsAl2aY_moo8GWUklOmSfqa1aTMQQKWUmL7_wc6SfkHWdrzmT7Je7X3uk1F6xqFH9BVrxs6qKqVPmSrJiqWKGEFOfkdYx7xlijmHhFzrkQvBRNtSJ_t25ne5usd7Q_0J8uFZz68HiRQL2hDsMD0l_B_0k7akAnHwrrhlnjQAdrDAZ0ycJjQua3Gy6oxnGM1EYa8AFDzDJn9zbmOT8exglGtJMdsNjSfk7U-XQE8YhhpD7tMNDbqw21p-V8iG_ImYEx4tvlvCB3377ebX4U1zfft5vL60KXUqVC97pCUC30AKWq83YglG5NX3LMH6GbgQlEbWTTg2qYBlCDgLqsDCqoubwgn0-x98H_njGmbrLx-Bpw6OfY8bZmomJNhh__g3s_B5dX60Rdcika2YqsPjyrshBcqjaj9Qnp4GMMaLr7YCcIh46z7lhyF_ddLrlbSs4D75fUuZ9weOJLqxl8WgBEDaMJ4LSNT04qLpSq5T-oXrJd</recordid><startdate>20020912</startdate><enddate>20020912</enddate><creator>CHOU, Alice H</creator><creator>HOWARD, Bruce D</creator><general>Nature Publishing</general><general>Nature Publishing Group</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>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</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>8G5</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>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope></search><sort><creationdate>20020912</creationdate><title>Inhibition by Wnt-1 or Wnt-3a of nerve growth factor-induced differentiation of PC12 cells is reversed by bisindolylmaleimide-I but not by several other PKC inhibitors</title><author>CHOU, Alice H ; HOWARD, Bruce D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-cbc5ea98abaa496ffea29c8fb41e923c7d02eecf37ba970caa9d2a645fe9a613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Adrenal medulla</topic><topic>Animals</topic><topic>Axonogenesis</topic><topic>Biological and medical sciences</topic><topic>Cell differentiation</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Differentiation - genetics</topic><topic>Cell differentiation, maturation, development, hematopoiesis</topic><topic>Cell physiology</topic><topic>Drug Antagonism</topic><topic>Enzyme inhibitors</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene expression</topic><topic>Growth factors</topic><topic>Indoles - pharmacology</topic><topic>Kinases</topic><topic>Maleimides - pharmacology</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>Morphology</topic><topic>Nerve growth factor</topic><topic>Nerve Growth Factor - pharmacology</topic><topic>Neural crest</topic><topic>PC12 Cells</topic><topic>Pertussis</topic><topic>Pertussis toxin</topic><topic>Pheochromocytoma cells</topic><topic>Protein Biosynthesis</topic><topic>Protein kinase C</topic><topic>Protein Kinase C - antagonists & inhibitors</topic><topic>Proteins</topic><topic>Proteins - genetics</topic><topic>Proto-Oncogene Proteins - biosynthesis</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Rats</topic><topic>Signal transduction</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - genetics</topic><topic>Wnt protein</topic><topic>Wnt Proteins</topic><topic>Wnt1 Protein</topic><topic>Wnt3 Protein</topic><topic>Zebrafish Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CHOU, Alice H</creatorcontrib><creatorcontrib>HOWARD, Bruce D</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>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & 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>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>Research Library (Alumni Edition)</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>Research Library Prep</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>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</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>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CHOU, Alice H</au><au>HOWARD, Bruce D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition by Wnt-1 or Wnt-3a of nerve growth factor-induced differentiation of PC12 cells is reversed by bisindolylmaleimide-I but not by several other PKC inhibitors</atitle><jtitle>Oncogene</jtitle><addtitle>Oncogene</addtitle><date>2002-09-12</date><risdate>2002</risdate><volume>21</volume><issue>41</issue><spage>6348</spage><epage>6355</epage><pages>6348-6355</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>Wnt-1 and Wnt-3a exhibit redundancy in neural crest development. We have found that they do not produce the same effects on PC12 cells, which were obtained from the adrenal medulla, a neural crest derivative. However, both Wnt-1 or Wnt-3a inhibit nerve growth factor (NGF)-induced neurite outgrowth. The inhibition is reversed by the protein kinase C (PKC) inhibitor, bisindolylmaleimide-I, but it did not reverse Wnt-1-induced activation of the canonical Wnt pathway. The Wnt-1 inhibitory effect was not reversed by several other PKC inhibitors, by phorbol ester-induced down-regulation of PKC, or by pertussis toxin, which is known to inhibit another Wnt signaling pathway, the Wnt/Ca(2+) pathway. We suggest that bisindolylmaleimide-I acts by affecting either a pathway downstream from Lef-1/Tcf in the canonical pathway or a Wnt signaling pathway other than the canonical pathway. In either case, the bisindolylmaleimide-I sensitivity of this pathway should aid in its identification.</abstract><cop>Basingstoke</cop><pub>Nature Publishing</pub><pmid>12214275</pmid><doi>10.1038/sj.onc.1205791</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0950-9232 |
| ispartof | Oncogene, 2002-09, Vol.21 (41), p.6348-6355 |
| issn | 0950-9232 1476-5594 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_18602507 |
| source | MEDLINE; Nature Journals Online; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SpringerLink Journals - AutoHoldings |
| subjects | Adrenal medulla Animals Axonogenesis Biological and medical sciences Cell differentiation Cell Differentiation - drug effects Cell Differentiation - genetics Cell differentiation, maturation, development, hematopoiesis Cell physiology Drug Antagonism Enzyme inhibitors Enzyme Inhibitors - pharmacology Fundamental and applied biological sciences. Psychology Gene expression Growth factors Indoles - pharmacology Kinases Maleimides - pharmacology Molecular and cellular biology Molecular genetics Morphology Nerve growth factor Nerve Growth Factor - pharmacology Neural crest PC12 Cells Pertussis Pertussis toxin Pheochromocytoma cells Protein Biosynthesis Protein kinase C Protein Kinase C - antagonists & inhibitors Proteins Proteins - genetics Proto-Oncogene Proteins - biosynthesis Proto-Oncogene Proteins - genetics Rats Signal transduction Signal Transduction - drug effects Signal Transduction - genetics Wnt protein Wnt Proteins Wnt1 Protein Wnt3 Protein Zebrafish Proteins |
| title | Inhibition by Wnt-1 or Wnt-3a of nerve growth factor-induced differentiation of PC12 cells is reversed by bisindolylmaleimide-I but not by several other PKC inhibitors |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T21%3A00%3A51IST&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=Inhibition%20by%20Wnt-1%20or%20Wnt-3a%20of%20nerve%20growth%20factor-induced%20differentiation%20of%20PC12%20cells%20is%20reversed%20by%20bisindolylmaleimide-I%20but%20not%20by%20several%20other%20PKC%20inhibitors&rft.jtitle=Oncogene&rft.au=CHOU,%20Alice%20H&rft.date=2002-09-12&rft.volume=21&rft.issue=41&rft.spage=6348&rft.epage=6355&rft.pages=6348-6355&rft.issn=0950-9232&rft.eissn=1476-5594&rft.coden=ONCNES&rft_id=info:doi/10.1038/sj.onc.1205791&rft_dat=%3Cproquest_cross%3E1028540031%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=227321398&rft_id=info:pmid/12214275&rfr_iscdi=true |