Absence of Lymph Nodes in NOD Mice Treated With Lymphotoxin-β Receptor Immunoglobulin Protects From Diabetes
Absence of Lymph Nodes in NOD Mice Treated With Lymphotoxin-β Receptor Immunoglobulin Protects From Diabetes Matteo G. Levisetti 1 2 , Anish Suri 2 , Katherine Frederick 2 and Emil R. Unanue 2 1 Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 2 Department of Pat...
Gespeichert in:
| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2004-12, Vol.53 (12), p.3115-3119 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 3119 |
|---|---|
| container_issue | 12 |
| container_start_page | 3115 |
| container_title | Diabetes (New York, N.Y.) |
| container_volume | 53 |
| creator | LEVISETTI, Matteo G SURI, Anish FREDERICK, Katherine UNANUE, Emil R |
| description | Absence of Lymph Nodes in NOD Mice Treated With Lymphotoxin-β Receptor Immunoglobulin Protects From Diabetes
Matteo G. Levisetti 1 2 ,
Anish Suri 2 ,
Katherine Frederick 2 and
Emil R. Unanue 2
1 Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
2 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri
Address correspondencereprint requests to Emil R. Unanue, MD, Campus Box 8118, 660 S. Euclid Av., St. Louis, MO 63110. E-mail:
unanue{at}pathology.wustl.edu
Abstract
Pregnant nonobese diabetic (NOD) mice were treated with lymphotoxin-β receptor immunoglobulin fusion protein (LTβR-Ig) or
control human immunoglobulin on days embryonic day 11 (E11) and E14, and offspring were followed for the development of anti–β-cell
antibodies, islet pathology, and hyperglycemia. The development of anti–β-cell surface antibodies was abrogated in treated
mice compared with controls. Autopsy examination of the mice at 30 weeks of age revealed normal development of secondary lymphoid
structures in the control animals; however, mice treated with LTβR-Ig had no axillary, inguinal, popliteal, or peripancreatic
lymph nodes. Histological examination of the pancreata of the control mice revealed a severe and destructive mononuclear cellular
infiltrate in the islets, whereas the islets of the LTβR-Ig–treated mice were devoid of any insulitis. None of the LTβR-Ig–treated
mice ( n = 22) developed diabetes; in contrast, 80% of the control mice ( n = 46) developed diabetes at 1 year of age. The LTβR-Ig–treated mice did not contain diabetogenic T-cells. However, the treated
mice developed diabetes upon inoculation with diabetogenic T-cells. In this model of spontaneous autoimmune diabetes, secondary
lymphoid structures, most likely the peripancreatic lymph nodes, were essential for the development of pathologic anti–β-cell
autoimmunity.
Footnotes
LTβR-Ig, lymphotoxin-β receptor immunoglobulin fusion protein.
Accepted September 1, 2004.
Received March 29, 2004.
DIABETES |
| doi_str_mv | 10.2337/diabetes.53.12.3115 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_highw</sourceid><recordid>TN_cdi_highwire_diabetes_diabetes_53_12_3115</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A126124900</galeid><sourcerecordid>A126124900</sourcerecordid><originalsourceid>FETCH-LOGICAL-c510t-dcc3e215aeb0c106c599df482da9fbc659108d59f5e89e3362c37f6ee0f8b89b3</originalsourceid><addsrcrecordid>eNqF0t2K1DAUB_AiijuuPoEguVEQbM3HJG0uh113XRh3RVb0LqTpyUykbcYkxd3X8kF8Jju0MiwMyLkIJL9_TgIny14SXFDGyveN0zUkiAVnBaEFI4Q_yhZEMpkzWn5_nC0wJjQnpSxPsmcx_sAYi7GeZieEc0HkkiyyblVH6A0gb9H6vttt0bVvICLXo-ubc_TJjUe3AXSCBn1zaTshn_yd6_M_v9EXMLBLPqCrrht6v2l9PbRj-HPwCUyK6CL4Dp3PT32ePbG6jfBiXk-zrxcfbs8-5uuby6uz1To3nOCUN8YwoIRrqLEhWBguZWOXFW20tLURXBJcNVxaDpUExgQ1rLQCANuqrmTNTrM307274H8OEJPqXDTQtroHP0QlSizLCtP_QlJWfInFHuYT3OgWlOutT0GbDfQQdOt7sG7cXhEqCF1KjEdfHPFjNdA5czTw9kFgNAnu0kYPMarqcv3Qssma4GMMYNUuuE6He0Ww2s-G-jcbijNFqNrPxph6Nf91qDtoDpl5GEbwegY6Gt3aoHvj4sEJhiUW5ejeTW7rNttfLsCh3bG-fwELGdLC</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17854062</pqid></control><display><type>article</type><title>Absence of Lymph Nodes in NOD Mice Treated With Lymphotoxin-β Receptor Immunoglobulin Protects From Diabetes</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>LEVISETTI, Matteo G ; SURI, Anish ; FREDERICK, Katherine ; UNANUE, Emil R</creator><creatorcontrib>LEVISETTI, Matteo G ; SURI, Anish ; FREDERICK, Katherine ; UNANUE, Emil R</creatorcontrib><description>Absence of Lymph Nodes in NOD Mice Treated With Lymphotoxin-β Receptor Immunoglobulin Protects From Diabetes
Matteo G. Levisetti 1 2 ,
Anish Suri 2 ,
Katherine Frederick 2 and
Emil R. Unanue 2
1 Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
2 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri
Address correspondencereprint requests to Emil R. Unanue, MD, Campus Box 8118, 660 S. Euclid Av., St. Louis, MO 63110. E-mail:
unanue{at}pathology.wustl.edu
Abstract
Pregnant nonobese diabetic (NOD) mice were treated with lymphotoxin-β receptor immunoglobulin fusion protein (LTβR-Ig) or
control human immunoglobulin on days embryonic day 11 (E11) and E14, and offspring were followed for the development of anti–β-cell
antibodies, islet pathology, and hyperglycemia. The development of anti–β-cell surface antibodies was abrogated in treated
mice compared with controls. Autopsy examination of the mice at 30 weeks of age revealed normal development of secondary lymphoid
structures in the control animals; however, mice treated with LTβR-Ig had no axillary, inguinal, popliteal, or peripancreatic
lymph nodes. Histological examination of the pancreata of the control mice revealed a severe and destructive mononuclear cellular
infiltrate in the islets, whereas the islets of the LTβR-Ig–treated mice were devoid of any insulitis. None of the LTβR-Ig–treated
mice ( n = 22) developed diabetes; in contrast, 80% of the control mice ( n = 46) developed diabetes at 1 year of age. The LTβR-Ig–treated mice did not contain diabetogenic T-cells. However, the treated
mice developed diabetes upon inoculation with diabetogenic T-cells. In this model of spontaneous autoimmune diabetes, secondary
lymphoid structures, most likely the peripancreatic lymph nodes, were essential for the development of pathologic anti–β-cell
autoimmunity.
Footnotes
LTβR-Ig, lymphotoxin-β receptor immunoglobulin fusion protein.
Accepted September 1, 2004.
Received March 29, 2004.
DIABETES</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/diabetes.53.12.3115</identifier><identifier>PMID: 15561941</identifier><identifier>CODEN: DIAEAZ</identifier><language>eng</language><publisher>Alexandria, VA: American Diabetes Association</publisher><subject>Animals ; Autoimmune diseases ; Biological and medical sciences ; Care and treatment ; Diabetes ; Diabetes Mellitus, Type 1 - prevention & control ; Diabetes. Impaired glucose tolerance ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Female ; Humans ; Immunoglobulin G - therapeutic use ; Immunoglobulins - therapeutic use ; Lymph nodes ; Lymph Nodes - immunology ; Lymphotoxin beta Receptor ; Medical sciences ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Pregnancy ; Receptors, Tumor Necrosis Factor - immunology ; Receptors, Tumor Necrosis Factor - therapeutic use ; Recombinant Fusion Proteins - therapeutic use</subject><ispartof>Diabetes (New York, N.Y.), 2004-12, Vol.53 (12), p.3115-3119</ispartof><rights>2005 INIST-CNRS</rights><rights>COPYRIGHT 2004 American Diabetes Association</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c510t-dcc3e215aeb0c106c599df482da9fbc659108d59f5e89e3362c37f6ee0f8b89b3</citedby><cites>FETCH-LOGICAL-c510t-dcc3e215aeb0c106c599df482da9fbc659108d59f5e89e3362c37f6ee0f8b89b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16309067$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15561941$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>LEVISETTI, Matteo G</creatorcontrib><creatorcontrib>SURI, Anish</creatorcontrib><creatorcontrib>FREDERICK, Katherine</creatorcontrib><creatorcontrib>UNANUE, Emil R</creatorcontrib><title>Absence of Lymph Nodes in NOD Mice Treated With Lymphotoxin-β Receptor Immunoglobulin Protects From Diabetes</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>Absence of Lymph Nodes in NOD Mice Treated With Lymphotoxin-β Receptor Immunoglobulin Protects From Diabetes
Matteo G. Levisetti 1 2 ,
Anish Suri 2 ,
Katherine Frederick 2 and
Emil R. Unanue 2
1 Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
2 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri
Address correspondencereprint requests to Emil R. Unanue, MD, Campus Box 8118, 660 S. Euclid Av., St. Louis, MO 63110. E-mail:
unanue{at}pathology.wustl.edu
Abstract
Pregnant nonobese diabetic (NOD) mice were treated with lymphotoxin-β receptor immunoglobulin fusion protein (LTβR-Ig) or
control human immunoglobulin on days embryonic day 11 (E11) and E14, and offspring were followed for the development of anti–β-cell
antibodies, islet pathology, and hyperglycemia. The development of anti–β-cell surface antibodies was abrogated in treated
mice compared with controls. Autopsy examination of the mice at 30 weeks of age revealed normal development of secondary lymphoid
structures in the control animals; however, mice treated with LTβR-Ig had no axillary, inguinal, popliteal, or peripancreatic
lymph nodes. Histological examination of the pancreata of the control mice revealed a severe and destructive mononuclear cellular
infiltrate in the islets, whereas the islets of the LTβR-Ig–treated mice were devoid of any insulitis. None of the LTβR-Ig–treated
mice ( n = 22) developed diabetes; in contrast, 80% of the control mice ( n = 46) developed diabetes at 1 year of age. The LTβR-Ig–treated mice did not contain diabetogenic T-cells. However, the treated
mice developed diabetes upon inoculation with diabetogenic T-cells. In this model of spontaneous autoimmune diabetes, secondary
lymphoid structures, most likely the peripancreatic lymph nodes, were essential for the development of pathologic anti–β-cell
autoimmunity.
Footnotes
LTβR-Ig, lymphotoxin-β receptor immunoglobulin fusion protein.
Accepted September 1, 2004.
Received March 29, 2004.
DIABETES</description><subject>Animals</subject><subject>Autoimmune diseases</subject><subject>Biological and medical sciences</subject><subject>Care and treatment</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 1 - prevention & control</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoglobulin G - therapeutic use</subject><subject>Immunoglobulins - therapeutic use</subject><subject>Lymph nodes</subject><subject>Lymph Nodes - immunology</subject><subject>Lymphotoxin beta Receptor</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Pregnancy</subject><subject>Receptors, Tumor Necrosis Factor - immunology</subject><subject>Receptors, Tumor Necrosis Factor - therapeutic use</subject><subject>Recombinant Fusion Proteins - therapeutic use</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0t2K1DAUB_AiijuuPoEguVEQbM3HJG0uh113XRh3RVb0LqTpyUykbcYkxd3X8kF8Jju0MiwMyLkIJL9_TgIny14SXFDGyveN0zUkiAVnBaEFI4Q_yhZEMpkzWn5_nC0wJjQnpSxPsmcx_sAYi7GeZieEc0HkkiyyblVH6A0gb9H6vttt0bVvICLXo-ubc_TJjUe3AXSCBn1zaTshn_yd6_M_v9EXMLBLPqCrrht6v2l9PbRj-HPwCUyK6CL4Dp3PT32ePbG6jfBiXk-zrxcfbs8-5uuby6uz1To3nOCUN8YwoIRrqLEhWBguZWOXFW20tLURXBJcNVxaDpUExgQ1rLQCANuqrmTNTrM307274H8OEJPqXDTQtroHP0QlSizLCtP_QlJWfInFHuYT3OgWlOutT0GbDfQQdOt7sG7cXhEqCF1KjEdfHPFjNdA5czTw9kFgNAnu0kYPMarqcv3Qssma4GMMYNUuuE6He0Ww2s-G-jcbijNFqNrPxph6Nf91qDtoDpl5GEbwegY6Gt3aoHvj4sEJhiUW5ejeTW7rNttfLsCh3bG-fwELGdLC</recordid><startdate>20041201</startdate><enddate>20041201</enddate><creator>LEVISETTI, Matteo G</creator><creator>SURI, Anish</creator><creator>FREDERICK, Katherine</creator><creator>UNANUE, Emil R</creator><general>American Diabetes Association</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>8GL</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20041201</creationdate><title>Absence of Lymph Nodes in NOD Mice Treated With Lymphotoxin-β Receptor Immunoglobulin Protects From Diabetes</title><author>LEVISETTI, Matteo G ; SURI, Anish ; FREDERICK, Katherine ; UNANUE, Emil R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c510t-dcc3e215aeb0c106c599df482da9fbc659108d59f5e89e3362c37f6ee0f8b89b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Autoimmune diseases</topic><topic>Biological and medical sciences</topic><topic>Care and treatment</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 1 - prevention & control</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Female</topic><topic>Humans</topic><topic>Immunoglobulin G - therapeutic use</topic><topic>Immunoglobulins - therapeutic use</topic><topic>Lymph nodes</topic><topic>Lymph Nodes - immunology</topic><topic>Lymphotoxin beta Receptor</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>Pregnancy</topic><topic>Receptors, Tumor Necrosis Factor - immunology</topic><topic>Receptors, Tumor Necrosis Factor - therapeutic use</topic><topic>Recombinant Fusion Proteins - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>LEVISETTI, Matteo G</creatorcontrib><creatorcontrib>SURI, Anish</creatorcontrib><creatorcontrib>FREDERICK, Katherine</creatorcontrib><creatorcontrib>UNANUE, Emil R</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>Gale In Context: High School</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>LEVISETTI, Matteo G</au><au>SURI, Anish</au><au>FREDERICK, Katherine</au><au>UNANUE, Emil R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Absence of Lymph Nodes in NOD Mice Treated With Lymphotoxin-β Receptor Immunoglobulin Protects From Diabetes</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2004-12-01</date><risdate>2004</risdate><volume>53</volume><issue>12</issue><spage>3115</spage><epage>3119</epage><pages>3115-3119</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><coden>DIAEAZ</coden><abstract>Absence of Lymph Nodes in NOD Mice Treated With Lymphotoxin-β Receptor Immunoglobulin Protects From Diabetes
Matteo G. Levisetti 1 2 ,
Anish Suri 2 ,
Katherine Frederick 2 and
Emil R. Unanue 2
1 Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
2 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri
Address correspondencereprint requests to Emil R. Unanue, MD, Campus Box 8118, 660 S. Euclid Av., St. Louis, MO 63110. E-mail:
unanue{at}pathology.wustl.edu
Abstract
Pregnant nonobese diabetic (NOD) mice were treated with lymphotoxin-β receptor immunoglobulin fusion protein (LTβR-Ig) or
control human immunoglobulin on days embryonic day 11 (E11) and E14, and offspring were followed for the development of anti–β-cell
antibodies, islet pathology, and hyperglycemia. The development of anti–β-cell surface antibodies was abrogated in treated
mice compared with controls. Autopsy examination of the mice at 30 weeks of age revealed normal development of secondary lymphoid
structures in the control animals; however, mice treated with LTβR-Ig had no axillary, inguinal, popliteal, or peripancreatic
lymph nodes. Histological examination of the pancreata of the control mice revealed a severe and destructive mononuclear cellular
infiltrate in the islets, whereas the islets of the LTβR-Ig–treated mice were devoid of any insulitis. None of the LTβR-Ig–treated
mice ( n = 22) developed diabetes; in contrast, 80% of the control mice ( n = 46) developed diabetes at 1 year of age. The LTβR-Ig–treated mice did not contain diabetogenic T-cells. However, the treated
mice developed diabetes upon inoculation with diabetogenic T-cells. In this model of spontaneous autoimmune diabetes, secondary
lymphoid structures, most likely the peripancreatic lymph nodes, were essential for the development of pathologic anti–β-cell
autoimmunity.
Footnotes
LTβR-Ig, lymphotoxin-β receptor immunoglobulin fusion protein.
Accepted September 1, 2004.
Received March 29, 2004.
DIABETES</abstract><cop>Alexandria, VA</cop><pub>American Diabetes Association</pub><pmid>15561941</pmid><doi>10.2337/diabetes.53.12.3115</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0012-1797 |
| ispartof | Diabetes (New York, N.Y.), 2004-12, Vol.53 (12), p.3115-3119 |
| issn | 0012-1797 1939-327X |
| language | eng |
| recordid | cdi_highwire_diabetes_diabetes_53_12_3115 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Autoimmune diseases Biological and medical sciences Care and treatment Diabetes Diabetes Mellitus, Type 1 - prevention & control Diabetes. Impaired glucose tolerance Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Female Humans Immunoglobulin G - therapeutic use Immunoglobulins - therapeutic use Lymph nodes Lymph Nodes - immunology Lymphotoxin beta Receptor Medical sciences Mice Mice, Inbred NOD Mice, SCID Pregnancy Receptors, Tumor Necrosis Factor - immunology Receptors, Tumor Necrosis Factor - therapeutic use Recombinant Fusion Proteins - therapeutic use |
| title | Absence of Lymph Nodes in NOD Mice Treated With Lymphotoxin-β Receptor Immunoglobulin Protects From Diabetes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-22T22%3A59%3A29IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_highw&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Absence%20of%20Lymph%20Nodes%20in%20NOD%20Mice%20Treated%20With%20Lymphotoxin-%CE%B2%20Receptor%20Immunoglobulin%20Protects%20From%20Diabetes&rft.jtitle=Diabetes%20(New%20York,%20N.Y.)&rft.au=LEVISETTI,%20Matteo%20G&rft.date=2004-12-01&rft.volume=53&rft.issue=12&rft.spage=3115&rft.epage=3119&rft.pages=3115-3119&rft.issn=0012-1797&rft.eissn=1939-327X&rft.coden=DIAEAZ&rft_id=info:doi/10.2337/diabetes.53.12.3115&rft_dat=%3Cgale_highw%3EA126124900%3C/gale_highw%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=17854062&rft_id=info:pmid/15561941&rft_galeid=A126124900&rfr_iscdi=true |