Stress deprivation from the patellar tendon induces apoptosis of fibroblasts in vivo with activation of mitogen-activated protein kinases
Abstract The effect of stress deprivation on the tendon tissue has been an important focus in the field of biomechanics. However, less is known about the in vivo effect of stress deprivation on fibroblast apoptosis as of yet. This study was conducted to test a hypothesis that complete stress depriva...
Gespeichert in:
| Veröffentlicht in: | Journal of biomechanics 2009-11, Vol.42 (15), p.2611-2615 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2615 |
|---|---|
| container_issue | 15 |
| container_start_page | 2611 |
| container_title | Journal of biomechanics |
| container_volume | 42 |
| creator | Kawabata, Hideyuki Katsura, Taro Kondo, Eiji Kitamura, Nobuto Miyatake, Shin Tanabe, Yoshie Setoguchi, Takao Komiya, Setsuro Yasuda, Kazunori |
| description | Abstract The effect of stress deprivation on the tendon tissue has been an important focus in the field of biomechanics. However, less is known about the in vivo effect of stress deprivation on fibroblast apoptosis as of yet. This study was conducted to test a hypothesis that complete stress deprivation of the patellar tendon induces fibroblast apoptosis in vivo with activation of Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) within 24 h after treatment. A total of 35 mature rabbits were divided into stress-shielded ( n =15), sham-operated ( n =15), and control ( n =5) groups. To completely shield the patellar tendon from stress, we used an established surgical method. Animals were sacrificed at 24 h, and 2, 4, 7, and 14 days after the treatment. Tendon specimens underwent TUNEL assay and immunohistological examinations of active caspase-3, JNK, and p38. Both the number and the ratio of TUNEL-positive and caspase-3-positive cells were significantly greater ( p |
| doi_str_mv | 10.1016/j.jbiomech.2009.07.027 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_734119565</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S002192900900428X</els_id><sourcerecordid>2744240981</sourcerecordid><originalsourceid>FETCH-LOGICAL-c481t-f95091829c3ab15a32ef4046e00e2e9e4bf864de1c897e78810f6c36cd055e603</originalsourceid><addsrcrecordid>eNqFkl2L1DAUhoso7rj6F5aAoFcdTz6aNjeiLH7Bgher4F1I01Mn3bapSWZkf4L_2pSZZWEvFAKB5Dnv4T3vKYoLClsKVL4ZtkPr_IR2t2UAagv1Flj9qNjQpuYl4w08LjYAjJaKKTgrnsU4AEAtavW0OKNKyopy2BR_rlPAGEmHS3AHk5yfSR_8RNIOyWISjqMJJOHc5Q83d3uLkZjFL8lHF4nvSe_a4NvRxBQzQA7u4Mlvl3bE2HSnmLHJJf8T5_L0ih1Zgk-YK27cbCLG58WT3owRX5zu8-L7xw_fLj-XV18_fbl8f1Va0dBU9qoCRRumLDctrQxn2AsQEgGQoULR9o0UHVLbqBrrpqHQS8ul7aCqUAI_L14fdXP_X3uMSU8u2tXnjH4fdc0FpaqSVSZf_ZPkklVcSJHBlw_Awe_DnF1oClwoISVf5eSRssHHGLDXeeSTCbcZ0muoetB3oeo1VA21zqHmwouT_L6dsLsvO6WYgXdHAPPcDg6DjtbhbLFzAW3SnXf_7_H2gYQd3eysGW_wFuO9Hx2ZBn29rta6WZCPYM0P_hcgvs2P</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1034946635</pqid></control><display><type>article</type><title>Stress deprivation from the patellar tendon induces apoptosis of fibroblasts in vivo with activation of mitogen-activated protein kinases</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><source>ProQuest Central UK/Ireland</source><creator>Kawabata, Hideyuki ; Katsura, Taro ; Kondo, Eiji ; Kitamura, Nobuto ; Miyatake, Shin ; Tanabe, Yoshie ; Setoguchi, Takao ; Komiya, Setsuro ; Yasuda, Kazunori</creator><creatorcontrib>Kawabata, Hideyuki ; Katsura, Taro ; Kondo, Eiji ; Kitamura, Nobuto ; Miyatake, Shin ; Tanabe, Yoshie ; Setoguchi, Takao ; Komiya, Setsuro ; Yasuda, Kazunori</creatorcontrib><description>Abstract The effect of stress deprivation on the tendon tissue has been an important focus in the field of biomechanics. However, less is known about the in vivo effect of stress deprivation on fibroblast apoptosis as of yet. This study was conducted to test a hypothesis that complete stress deprivation of the patellar tendon induces fibroblast apoptosis in vivo with activation of Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) within 24 h after treatment. A total of 35 mature rabbits were divided into stress-shielded ( n =15), sham-operated ( n =15), and control ( n =5) groups. To completely shield the patellar tendon from stress, we used an established surgical method. Animals were sacrificed at 24 h, and 2, 4, 7, and 14 days after the treatment. Tendon specimens underwent TUNEL assay and immunohistological examinations of active caspase-3, JNK, and p38. Both the number and the ratio of TUNEL-positive and caspase-3-positive cells were significantly greater ( p <0.0001) in the stress-shielded group than in the sham group at 24 h, 2, 4, and 7 days. Concerning JNK and p38, both the number and the ratio were significantly greater ( p <0.0001) in the stress-shielded group than in the sham group at 24 h, 2, and 4 days. This study demonstrated that complete stress deprivation induces fibroblast apoptosis in vivo with activation of JNK and p38 within 24 h. This fact suggested that the fibroblast apoptosis caused by stress deprivation is induced via the mitogen-activated protein kinase signaling pathway.</description><identifier>ISSN: 0021-9290</identifier><identifier>EISSN: 1873-2380</identifier><identifier>DOI: 10.1016/j.jbiomech.2009.07.027</identifier><identifier>PMID: 19665130</identifier><language>eng</language><publisher>United States: Elsevier Ltd</publisher><subject>Animals ; Apoptosis ; Apoptosis - physiology ; Cells, Cultured ; Enzyme Activation ; Female ; Fibroblast ; Fibroblasts - cytology ; Fibroblasts - physiology ; Hindlimb Suspension ; Kinases ; Knee ; Mechanotransduction, Cellular - physiology ; Mitogen-activated protein kinase ; Mitogen-Activated Protein Kinases - metabolism ; Patellar Ligament - cytology ; Patellar Ligament - physiology ; Physical Medicine and Rehabilitation ; Proteins ; Rabbits ; Stress deprivation ; Stress, Mechanical ; Tendon ; Tendons</subject><ispartof>Journal of biomechanics, 2009-11, Vol.42 (15), p.2611-2615</ispartof><rights>Elsevier Ltd</rights><rights>2009 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-f95091829c3ab15a32ef4046e00e2e9e4bf864de1c897e78810f6c36cd055e603</citedby><cites>FETCH-LOGICAL-c481t-f95091829c3ab15a32ef4046e00e2e9e4bf864de1c897e78810f6c36cd055e603</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1034946635?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19665130$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kawabata, Hideyuki</creatorcontrib><creatorcontrib>Katsura, Taro</creatorcontrib><creatorcontrib>Kondo, Eiji</creatorcontrib><creatorcontrib>Kitamura, Nobuto</creatorcontrib><creatorcontrib>Miyatake, Shin</creatorcontrib><creatorcontrib>Tanabe, Yoshie</creatorcontrib><creatorcontrib>Setoguchi, Takao</creatorcontrib><creatorcontrib>Komiya, Setsuro</creatorcontrib><creatorcontrib>Yasuda, Kazunori</creatorcontrib><title>Stress deprivation from the patellar tendon induces apoptosis of fibroblasts in vivo with activation of mitogen-activated protein kinases</title><title>Journal of biomechanics</title><addtitle>J Biomech</addtitle><description>Abstract The effect of stress deprivation on the tendon tissue has been an important focus in the field of biomechanics. However, less is known about the in vivo effect of stress deprivation on fibroblast apoptosis as of yet. This study was conducted to test a hypothesis that complete stress deprivation of the patellar tendon induces fibroblast apoptosis in vivo with activation of Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) within 24 h after treatment. A total of 35 mature rabbits were divided into stress-shielded ( n =15), sham-operated ( n =15), and control ( n =5) groups. To completely shield the patellar tendon from stress, we used an established surgical method. Animals were sacrificed at 24 h, and 2, 4, 7, and 14 days after the treatment. Tendon specimens underwent TUNEL assay and immunohistological examinations of active caspase-3, JNK, and p38. Both the number and the ratio of TUNEL-positive and caspase-3-positive cells were significantly greater ( p <0.0001) in the stress-shielded group than in the sham group at 24 h, 2, 4, and 7 days. Concerning JNK and p38, both the number and the ratio were significantly greater ( p <0.0001) in the stress-shielded group than in the sham group at 24 h, 2, and 4 days. This study demonstrated that complete stress deprivation induces fibroblast apoptosis in vivo with activation of JNK and p38 within 24 h. This fact suggested that the fibroblast apoptosis caused by stress deprivation is induced via the mitogen-activated protein kinase signaling pathway.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - physiology</subject><subject>Cells, Cultured</subject><subject>Enzyme Activation</subject><subject>Female</subject><subject>Fibroblast</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - physiology</subject><subject>Hindlimb Suspension</subject><subject>Kinases</subject><subject>Knee</subject><subject>Mechanotransduction, Cellular - physiology</subject><subject>Mitogen-activated protein kinase</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Patellar Ligament - cytology</subject><subject>Patellar Ligament - physiology</subject><subject>Physical Medicine and Rehabilitation</subject><subject>Proteins</subject><subject>Rabbits</subject><subject>Stress deprivation</subject><subject>Stress, Mechanical</subject><subject>Tendon</subject><subject>Tendons</subject><issn>0021-9290</issn><issn>1873-2380</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkl2L1DAUhoso7rj6F5aAoFcdTz6aNjeiLH7Bgher4F1I01Mn3bapSWZkf4L_2pSZZWEvFAKB5Dnv4T3vKYoLClsKVL4ZtkPr_IR2t2UAagv1Flj9qNjQpuYl4w08LjYAjJaKKTgrnsU4AEAtavW0OKNKyopy2BR_rlPAGEmHS3AHk5yfSR_8RNIOyWISjqMJJOHc5Q83d3uLkZjFL8lHF4nvSe_a4NvRxBQzQA7u4Mlvl3bE2HSnmLHJJf8T5_L0ih1Zgk-YK27cbCLG58WT3owRX5zu8-L7xw_fLj-XV18_fbl8f1Va0dBU9qoCRRumLDctrQxn2AsQEgGQoULR9o0UHVLbqBrrpqHQS8ul7aCqUAI_L14fdXP_X3uMSU8u2tXnjH4fdc0FpaqSVSZf_ZPkklVcSJHBlw_Awe_DnF1oClwoISVf5eSRssHHGLDXeeSTCbcZ0muoetB3oeo1VA21zqHmwouT_L6dsLsvO6WYgXdHAPPcDg6DjtbhbLFzAW3SnXf_7_H2gYQd3eysGW_wFuO9Hx2ZBn29rta6WZCPYM0P_hcgvs2P</recordid><startdate>20091113</startdate><enddate>20091113</enddate><creator>Kawabata, Hideyuki</creator><creator>Katsura, Taro</creator><creator>Kondo, Eiji</creator><creator>Kitamura, Nobuto</creator><creator>Miyatake, Shin</creator><creator>Tanabe, Yoshie</creator><creator>Setoguchi, Takao</creator><creator>Komiya, Setsuro</creator><creator>Yasuda, Kazunori</creator><general>Elsevier Ltd</general><general>Elsevier Limited</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>7QP</scope><scope>7TB</scope><scope>7TS</scope><scope>7X7</scope><scope>7XB</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>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>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20091113</creationdate><title>Stress deprivation from the patellar tendon induces apoptosis of fibroblasts in vivo with activation of mitogen-activated protein kinases</title><author>Kawabata, Hideyuki ; Katsura, Taro ; Kondo, Eiji ; Kitamura, Nobuto ; Miyatake, Shin ; Tanabe, Yoshie ; Setoguchi, Takao ; Komiya, Setsuro ; Yasuda, Kazunori</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c481t-f95091829c3ab15a32ef4046e00e2e9e4bf864de1c897e78810f6c36cd055e603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - physiology</topic><topic>Cells, Cultured</topic><topic>Enzyme Activation</topic><topic>Female</topic><topic>Fibroblast</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - physiology</topic><topic>Hindlimb Suspension</topic><topic>Kinases</topic><topic>Knee</topic><topic>Mechanotransduction, Cellular - physiology</topic><topic>Mitogen-activated protein kinase</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Patellar Ligament - cytology</topic><topic>Patellar Ligament - physiology</topic><topic>Physical Medicine and Rehabilitation</topic><topic>Proteins</topic><topic>Rabbits</topic><topic>Stress deprivation</topic><topic>Stress, Mechanical</topic><topic>Tendon</topic><topic>Tendons</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kawabata, Hideyuki</creatorcontrib><creatorcontrib>Katsura, Taro</creatorcontrib><creatorcontrib>Kondo, Eiji</creatorcontrib><creatorcontrib>Kitamura, Nobuto</creatorcontrib><creatorcontrib>Miyatake, Shin</creatorcontrib><creatorcontrib>Tanabe, Yoshie</creatorcontrib><creatorcontrib>Setoguchi, Takao</creatorcontrib><creatorcontrib>Komiya, Setsuro</creatorcontrib><creatorcontrib>Yasuda, Kazunori</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>Calcium & Calcified Tissue Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Physical Education Index</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>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>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>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>MEDLINE - Academic</collection><jtitle>Journal of biomechanics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kawabata, Hideyuki</au><au>Katsura, Taro</au><au>Kondo, Eiji</au><au>Kitamura, Nobuto</au><au>Miyatake, Shin</au><au>Tanabe, Yoshie</au><au>Setoguchi, Takao</au><au>Komiya, Setsuro</au><au>Yasuda, Kazunori</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stress deprivation from the patellar tendon induces apoptosis of fibroblasts in vivo with activation of mitogen-activated protein kinases</atitle><jtitle>Journal of biomechanics</jtitle><addtitle>J Biomech</addtitle><date>2009-11-13</date><risdate>2009</risdate><volume>42</volume><issue>15</issue><spage>2611</spage><epage>2615</epage><pages>2611-2615</pages><issn>0021-9290</issn><eissn>1873-2380</eissn><abstract>Abstract The effect of stress deprivation on the tendon tissue has been an important focus in the field of biomechanics. However, less is known about the in vivo effect of stress deprivation on fibroblast apoptosis as of yet. This study was conducted to test a hypothesis that complete stress deprivation of the patellar tendon induces fibroblast apoptosis in vivo with activation of Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) within 24 h after treatment. A total of 35 mature rabbits were divided into stress-shielded ( n =15), sham-operated ( n =15), and control ( n =5) groups. To completely shield the patellar tendon from stress, we used an established surgical method. Animals were sacrificed at 24 h, and 2, 4, 7, and 14 days after the treatment. Tendon specimens underwent TUNEL assay and immunohistological examinations of active caspase-3, JNK, and p38. Both the number and the ratio of TUNEL-positive and caspase-3-positive cells were significantly greater ( p <0.0001) in the stress-shielded group than in the sham group at 24 h, 2, 4, and 7 days. Concerning JNK and p38, both the number and the ratio were significantly greater ( p <0.0001) in the stress-shielded group than in the sham group at 24 h, 2, and 4 days. This study demonstrated that complete stress deprivation induces fibroblast apoptosis in vivo with activation of JNK and p38 within 24 h. This fact suggested that the fibroblast apoptosis caused by stress deprivation is induced via the mitogen-activated protein kinase signaling pathway.</abstract><cop>United States</cop><pub>Elsevier Ltd</pub><pmid>19665130</pmid><doi>10.1016/j.jbiomech.2009.07.027</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9290 |
| ispartof | Journal of biomechanics, 2009-11, Vol.42 (15), p.2611-2615 |
| issn | 0021-9290 1873-2380 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_734119565 |
| source | MEDLINE; Access via ScienceDirect (Elsevier); ProQuest Central UK/Ireland |
| subjects | Animals Apoptosis Apoptosis - physiology Cells, Cultured Enzyme Activation Female Fibroblast Fibroblasts - cytology Fibroblasts - physiology Hindlimb Suspension Kinases Knee Mechanotransduction, Cellular - physiology Mitogen-activated protein kinase Mitogen-Activated Protein Kinases - metabolism Patellar Ligament - cytology Patellar Ligament - physiology Physical Medicine and Rehabilitation Proteins Rabbits Stress deprivation Stress, Mechanical Tendon Tendons |
| title | Stress deprivation from the patellar tendon induces apoptosis of fibroblasts in vivo with activation of mitogen-activated protein kinases |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T17%3A55%3A36IST&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=Stress%20deprivation%20from%20the%20patellar%20tendon%20induces%20apoptosis%20of%20fibroblasts%20in%20vivo%20with%20activation%20of%20mitogen-activated%20protein%20kinases&rft.jtitle=Journal%20of%20biomechanics&rft.au=Kawabata,%20Hideyuki&rft.date=2009-11-13&rft.volume=42&rft.issue=15&rft.spage=2611&rft.epage=2615&rft.pages=2611-2615&rft.issn=0021-9290&rft.eissn=1873-2380&rft_id=info:doi/10.1016/j.jbiomech.2009.07.027&rft_dat=%3Cproquest_cross%3E2744240981%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=1034946635&rft_id=info:pmid/19665130&rft_els_id=1_s2_0_S002192900900428X&rfr_iscdi=true |