Stat5a regulates T helper cell differentiation by several distinct mechanisms
We have previously shown that CD4+ T cell–mediated allergic inflammation is diminished in signal transducer and activator of transcription (Stat)5a-deficient (Stat5a−/−) mice. To determine whether Stat5a regulates T helper cell differentiation, we studied T helper (Th)1 and Th2 cell differentiation...
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| Veröffentlicht in: | Blood 2001-04, Vol.97 (8), p.2358-2365 |
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| creator | Kagami, Shin-ichiro Nakajima, Hiroshi Suto, Akira Hirose, Koichi Suzuki, Kotaro Morita, Sumiyo Kato, Ikunoshin Saito, Yasushi Kitamura, Toshio Iwamoto, Itsuo |
| description | We have previously shown that CD4+ T cell–mediated allergic inflammation is diminished in signal transducer and activator of transcription (Stat)5a-deficient (Stat5a−/−) mice. To determine whether Stat5a regulates T helper cell differentiation, we studied T helper (Th)1 and Th2 cell differentiation of Stat5a−/−CD4+ T cells at single-cell levels. First, Th2 cell differentiation from antigen-stimulated splenocytes was significantly decreased in Stat5a−/− mice as compared with that in wild-type mice. Further, Th2 cell differentiation was also impaired in Stat5a−/− mice even when purified CD4+ T cells were stimulated with anti-CD3 plus anti-CD28 antibodies in the presence of interleukin-4. Moreover, the retrovirus-mediated gene expression of Stat5a in Stat5a−/−CD4+ T cells restored the Th2 cell differentiation at the similar levels to that in wild-type CD4+ T cells. In addition, interleukin-4 normally phosphorylated Stat6 in CD4+ T cells from Stat5a−/− mice. Second, the development of CD4+CD25+ immunoregulatory T cells was impaired in Stat5a−/− mice, as indicated by a significant decrease in the number of CD4+CD25+ T cells in Stat5a−/− mice. Furthermore, the depletion of CD4+CD25+ T cells from wild-type splenocytes significantly decreased Th2 cell differentiation but increased Th1 cell differentiation, whereas the depletion of CD4+CD25+ T cells from Stat5a−/−splenocytes had no significant effect on the Th1 and Th2 cell differentiation. Together, these results indicate that the intrinsic expression of Stat5a in CD4+ T cells is required for Th2 cell differentiation and that Stat5a is involved in the development of CD4+CD25+ immunoregulatory T cells that modulate T helper cell differentiation toward Th2 cells. |
| doi_str_mv | 10.1182/blood.V97.8.2358 |
| format | Article |
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To determine whether Stat5a regulates T helper cell differentiation, we studied T helper (Th)1 and Th2 cell differentiation of Stat5a−/−CD4+ T cells at single-cell levels. First, Th2 cell differentiation from antigen-stimulated splenocytes was significantly decreased in Stat5a−/− mice as compared with that in wild-type mice. Further, Th2 cell differentiation was also impaired in Stat5a−/− mice even when purified CD4+ T cells were stimulated with anti-CD3 plus anti-CD28 antibodies in the presence of interleukin-4. Moreover, the retrovirus-mediated gene expression of Stat5a in Stat5a−/−CD4+ T cells restored the Th2 cell differentiation at the similar levels to that in wild-type CD4+ T cells. In addition, interleukin-4 normally phosphorylated Stat6 in CD4+ T cells from Stat5a−/− mice. Second, the development of CD4+CD25+ immunoregulatory T cells was impaired in Stat5a−/− mice, as indicated by a significant decrease in the number of CD4+CD25+ T cells in Stat5a−/− mice. Furthermore, the depletion of CD4+CD25+ T cells from wild-type splenocytes significantly decreased Th2 cell differentiation but increased Th1 cell differentiation, whereas the depletion of CD4+CD25+ T cells from Stat5a−/−splenocytes had no significant effect on the Th1 and Th2 cell differentiation. Together, these results indicate that the intrinsic expression of Stat5a in CD4+ T cells is required for Th2 cell differentiation and that Stat5a is involved in the development of CD4+CD25+ immunoregulatory T cells that modulate T helper cell differentiation toward Th2 cells.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood.V97.8.2358</identifier><identifier>PMID: 11290598</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Allergic diseases ; Animals ; Biological and medical sciences ; CD4 Antigens - analysis ; Cell Cycle ; Cell Differentiation ; DNA-Binding Proteins - deficiency ; DNA-Binding Proteins - physiology ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Gene Expression ; Immunobiology ; Immunopathology ; Interleukin-4 - metabolism ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Milk Proteins ; Modulation of the immune response (stimulation, suppression) ; Receptors, Interleukin-2 - analysis ; Recombinant Fusion Proteins - physiology ; Respiratory and ent allergic diseases ; Specific Pathogen-Free Organisms ; Spleen - cytology ; STAT5 Transcription Factor ; STAT6 Transcription Factor ; Th1 Cells - cytology ; Th1 Cells - metabolism ; Th2 Cells - cytology ; Th2 Cells - metabolism ; Trans-Activators - deficiency ; Trans-Activators - metabolism ; Trans-Activators - physiology</subject><ispartof>Blood, 2001-04, Vol.97 (8), p.2358-2365</ispartof><rights>2001 American Society of Hematology</rights><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-90bde1c71a54739a0e52786af44224313804238c336207db943898054b5c6fff3</citedby><cites>FETCH-LOGICAL-c416t-90bde1c71a54739a0e52786af44224313804238c336207db943898054b5c6fff3</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=950207$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11290598$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kagami, Shin-ichiro</creatorcontrib><creatorcontrib>Nakajima, Hiroshi</creatorcontrib><creatorcontrib>Suto, Akira</creatorcontrib><creatorcontrib>Hirose, Koichi</creatorcontrib><creatorcontrib>Suzuki, Kotaro</creatorcontrib><creatorcontrib>Morita, Sumiyo</creatorcontrib><creatorcontrib>Kato, Ikunoshin</creatorcontrib><creatorcontrib>Saito, Yasushi</creatorcontrib><creatorcontrib>Kitamura, Toshio</creatorcontrib><creatorcontrib>Iwamoto, Itsuo</creatorcontrib><title>Stat5a regulates T helper cell differentiation by several distinct mechanisms</title><title>Blood</title><addtitle>Blood</addtitle><description>We have previously shown that CD4+ T cell–mediated allergic inflammation is diminished in signal transducer and activator of transcription (Stat)5a-deficient (Stat5a−/−) mice. To determine whether Stat5a regulates T helper cell differentiation, we studied T helper (Th)1 and Th2 cell differentiation of Stat5a−/−CD4+ T cells at single-cell levels. First, Th2 cell differentiation from antigen-stimulated splenocytes was significantly decreased in Stat5a−/− mice as compared with that in wild-type mice. Further, Th2 cell differentiation was also impaired in Stat5a−/− mice even when purified CD4+ T cells were stimulated with anti-CD3 plus anti-CD28 antibodies in the presence of interleukin-4. Moreover, the retrovirus-mediated gene expression of Stat5a in Stat5a−/−CD4+ T cells restored the Th2 cell differentiation at the similar levels to that in wild-type CD4+ T cells. In addition, interleukin-4 normally phosphorylated Stat6 in CD4+ T cells from Stat5a−/− mice. Second, the development of CD4+CD25+ immunoregulatory T cells was impaired in Stat5a−/− mice, as indicated by a significant decrease in the number of CD4+CD25+ T cells in Stat5a−/− mice. Furthermore, the depletion of CD4+CD25+ T cells from wild-type splenocytes significantly decreased Th2 cell differentiation but increased Th1 cell differentiation, whereas the depletion of CD4+CD25+ T cells from Stat5a−/−splenocytes had no significant effect on the Th1 and Th2 cell differentiation. Together, these results indicate that the intrinsic expression of Stat5a in CD4+ T cells is required for Th2 cell differentiation and that Stat5a is involved in the development of CD4+CD25+ immunoregulatory T cells that modulate T helper cell differentiation toward Th2 cells.</description><subject>Allergic diseases</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>CD4 Antigens - analysis</subject><subject>Cell Cycle</subject><subject>Cell Differentiation</subject><subject>DNA-Binding Proteins - deficiency</subject><subject>DNA-Binding Proteins - physiology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Gene Expression</subject><subject>Immunobiology</subject><subject>Immunopathology</subject><subject>Interleukin-4 - metabolism</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mice, Transgenic</subject><subject>Milk Proteins</subject><subject>Modulation of the immune response (stimulation, suppression)</subject><subject>Receptors, Interleukin-2 - analysis</subject><subject>Recombinant Fusion Proteins - physiology</subject><subject>Respiratory and ent allergic diseases</subject><subject>Specific Pathogen-Free Organisms</subject><subject>Spleen - cytology</subject><subject>STAT5 Transcription Factor</subject><subject>STAT6 Transcription Factor</subject><subject>Th1 Cells - cytology</subject><subject>Th1 Cells - metabolism</subject><subject>Th2 Cells - cytology</subject><subject>Th2 Cells - metabolism</subject><subject>Trans-Activators - deficiency</subject><subject>Trans-Activators - metabolism</subject><subject>Trans-Activators - physiology</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kDtPHDEUhS0UBAukTxWNFCndLNevsZ0uQgkggShY0loez3XW0Tw2theJf89sdhUqqlvc7xwdfYR8orCkVLPLtp-mbvnLqKVeMi71EVlQyXQNwOADWQBAUwuj6Ck5y_kPABWcyRNySikzII1ekPvH4op0VcLf294VzNWqWmO_wVR57PuqiyFgwrFEV-I0Vu1LlfEZk9u9comjL9WAfu3GmId8QY6D6zN-PNxz8vTzx-rqpr57uL69-n5Xe0GbUhtoO6ReUSeF4sYBSqZ044IQjAlOuQbBuPacNwxU1xrBtdEgRSt9E0Lg5-TrvneTpr9bzMUOMe_2uhGnbbZKAacgYAZhD_o05Zww2E2Kg0svloLdKbT_FNpZodV2p3COfD50b9sBu7fAwdkMfDkALnvXh-RGH_N_zshZvpqpb3sKZw_PEZPNPuLosYsJfbHdFN_f8AqlbY17</recordid><startdate>20010415</startdate><enddate>20010415</enddate><creator>Kagami, Shin-ichiro</creator><creator>Nakajima, Hiroshi</creator><creator>Suto, Akira</creator><creator>Hirose, Koichi</creator><creator>Suzuki, Kotaro</creator><creator>Morita, Sumiyo</creator><creator>Kato, Ikunoshin</creator><creator>Saito, Yasushi</creator><creator>Kitamura, Toshio</creator><creator>Iwamoto, Itsuo</creator><general>Elsevier Inc</general><general>The Americain Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><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>20010415</creationdate><title>Stat5a regulates T helper cell differentiation by several distinct mechanisms</title><author>Kagami, Shin-ichiro ; Nakajima, Hiroshi ; Suto, Akira ; Hirose, Koichi ; Suzuki, Kotaro ; Morita, Sumiyo ; Kato, Ikunoshin ; Saito, Yasushi ; Kitamura, Toshio ; Iwamoto, Itsuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-90bde1c71a54739a0e52786af44224313804238c336207db943898054b5c6fff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Allergic diseases</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>CD4 Antigens - analysis</topic><topic>Cell Cycle</topic><topic>Cell Differentiation</topic><topic>DNA-Binding Proteins - deficiency</topic><topic>DNA-Binding Proteins - physiology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Gene Expression</topic><topic>Immunobiology</topic><topic>Immunopathology</topic><topic>Interleukin-4 - metabolism</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Mice, Transgenic</topic><topic>Milk Proteins</topic><topic>Modulation of the immune response (stimulation, suppression)</topic><topic>Receptors, Interleukin-2 - analysis</topic><topic>Recombinant Fusion Proteins - physiology</topic><topic>Respiratory and ent allergic diseases</topic><topic>Specific Pathogen-Free Organisms</topic><topic>Spleen - cytology</topic><topic>STAT5 Transcription Factor</topic><topic>STAT6 Transcription Factor</topic><topic>Th1 Cells - cytology</topic><topic>Th1 Cells - metabolism</topic><topic>Th2 Cells - cytology</topic><topic>Th2 Cells - metabolism</topic><topic>Trans-Activators - deficiency</topic><topic>Trans-Activators - metabolism</topic><topic>Trans-Activators - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kagami, Shin-ichiro</creatorcontrib><creatorcontrib>Nakajima, Hiroshi</creatorcontrib><creatorcontrib>Suto, Akira</creatorcontrib><creatorcontrib>Hirose, Koichi</creatorcontrib><creatorcontrib>Suzuki, Kotaro</creatorcontrib><creatorcontrib>Morita, Sumiyo</creatorcontrib><creatorcontrib>Kato, Ikunoshin</creatorcontrib><creatorcontrib>Saito, Yasushi</creatorcontrib><creatorcontrib>Kitamura, Toshio</creatorcontrib><creatorcontrib>Iwamoto, Itsuo</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kagami, Shin-ichiro</au><au>Nakajima, Hiroshi</au><au>Suto, Akira</au><au>Hirose, Koichi</au><au>Suzuki, Kotaro</au><au>Morita, Sumiyo</au><au>Kato, Ikunoshin</au><au>Saito, Yasushi</au><au>Kitamura, Toshio</au><au>Iwamoto, Itsuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stat5a regulates T helper cell differentiation by several distinct mechanisms</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2001-04-15</date><risdate>2001</risdate><volume>97</volume><issue>8</issue><spage>2358</spage><epage>2365</epage><pages>2358-2365</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>We have previously shown that CD4+ T cell–mediated allergic inflammation is diminished in signal transducer and activator of transcription (Stat)5a-deficient (Stat5a−/−) mice. To determine whether Stat5a regulates T helper cell differentiation, we studied T helper (Th)1 and Th2 cell differentiation of Stat5a−/−CD4+ T cells at single-cell levels. First, Th2 cell differentiation from antigen-stimulated splenocytes was significantly decreased in Stat5a−/− mice as compared with that in wild-type mice. Further, Th2 cell differentiation was also impaired in Stat5a−/− mice even when purified CD4+ T cells were stimulated with anti-CD3 plus anti-CD28 antibodies in the presence of interleukin-4. Moreover, the retrovirus-mediated gene expression of Stat5a in Stat5a−/−CD4+ T cells restored the Th2 cell differentiation at the similar levels to that in wild-type CD4+ T cells. In addition, interleukin-4 normally phosphorylated Stat6 in CD4+ T cells from Stat5a−/− mice. Second, the development of CD4+CD25+ immunoregulatory T cells was impaired in Stat5a−/− mice, as indicated by a significant decrease in the number of CD4+CD25+ T cells in Stat5a−/− mice. Furthermore, the depletion of CD4+CD25+ T cells from wild-type splenocytes significantly decreased Th2 cell differentiation but increased Th1 cell differentiation, whereas the depletion of CD4+CD25+ T cells from Stat5a−/−splenocytes had no significant effect on the Th1 and Th2 cell differentiation. Together, these results indicate that the intrinsic expression of Stat5a in CD4+ T cells is required for Th2 cell differentiation and that Stat5a is involved in the development of CD4+CD25+ immunoregulatory T cells that modulate T helper cell differentiation toward Th2 cells.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>11290598</pmid><doi>10.1182/blood.V97.8.2358</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Blood, 2001-04, Vol.97 (8), p.2358-2365 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Allergic diseases Animals Biological and medical sciences CD4 Antigens - analysis Cell Cycle Cell Differentiation DNA-Binding Proteins - deficiency DNA-Binding Proteins - physiology Fundamental and applied biological sciences. Psychology Fundamental immunology Gene Expression Immunobiology Immunopathology Interleukin-4 - metabolism Medical sciences Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Milk Proteins Modulation of the immune response (stimulation, suppression) Receptors, Interleukin-2 - analysis Recombinant Fusion Proteins - physiology Respiratory and ent allergic diseases Specific Pathogen-Free Organisms Spleen - cytology STAT5 Transcription Factor STAT6 Transcription Factor Th1 Cells - cytology Th1 Cells - metabolism Th2 Cells - cytology Th2 Cells - metabolism Trans-Activators - deficiency Trans-Activators - metabolism Trans-Activators - physiology |
| title | Stat5a regulates T helper cell differentiation by several distinct mechanisms |
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