Nuclear expression of maspin is associated with a lower recurrence rate and a longer disease-free interval after surgery for squamous cell carcinoma of the larynx
Aims : Maspin, a protein belonging to the serpin superfamily, is the product of a tumour suppressor gene. Tissue distribution studies have shown maspin expression in normal mammary epithelial cells, in the placenta, prostate, thymus, testis, oral cavity, small intestine, skin, and cornea. Maspin is...
Gespeichert in:
Veröffentlicht in: | Histopathology 2005-05, Vol.46 (5), p.576-582 |
---|---|
Hauptverfasser: | , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 582 |
---|---|
container_issue | 5 |
container_start_page | 576 |
container_title | Histopathology |
container_volume | 46 |
creator | Marioni, G Blandamura, S Giacomelli, L Calgaro, N Segato, P Leo, G Fischetto, D Staffieri, A De Filippis, C |
description | Aims : Maspin, a protein belonging to the serpin superfamily, is the product of a tumour suppressor gene. Tissue distribution studies have shown maspin expression in normal mammary epithelial cells, in the placenta, prostate, thymus, testis, oral cavity, small intestine, skin, and cornea. Maspin is expressed but down‐regulated in human breast, prostatic, and colonic cancers but apparently up‐regulated in pancreatic, ovarian, and gastric cancers. Only two studies concerning maspin expression in head and neck carcinomas are available. The present study is the first attempt to determine maspin expression in laryngeal carcinoma.
Methods and results : Maspin expression was evaluated in 21 cases of laryngeal carcinoma consecutively treated with an exclusively surgical approach with a follow‐up period longer than 24 months. The expression of p53, p27 and MIB‐1 was also studied. Two patterns of distribution of maspin in laryngeal neoplastic cells were found. Cytoplasmic expression of maspin was identified in 47.6% of the cases. Nuclear maspin positivity was determined in 47.6% of the cases. A statistically significant difference in nuclear maspin expression between the group of patients without carcinoma recurrence and the group with evidence of recurrence was demonstrated (P = 0.039). Log rank test analysis showed a statistically significant direct correlation between nuclear maspin expression and disease‐free intervals after surgical treatment calculated in months (P = 0.028). A significant inverse correlation was disclosed between nuclear maspin staining and MIB‐1 (P = 0.028). A trend of increasing p27 expression was noted in cases with positive nuclear maspin expression. Nuclear maspin expression was not statistically correlated with p53 expression. A trend towards direct correlation between cytoplasmic maspin expression and squamous cell carcinoma histological grade (G) was apparent. Cytoplasmic maspin expression did not correlate with p53, MIB‐1 or p27 expression.
Conclusions : These preliminary results suggest that nuclear location of maspin is a good prognostic factor in laryngeal carcinoma. |
doi_str_mv | 10.1111/j.1365-2559.2005.02141.x |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67760798</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>67760798</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4351-81937bde6883ba3a7715f735b676239741032c11b85bb55c670802bc945e9b653</originalsourceid><addsrcrecordid>eNqNkc1u1DAUhS0EokPhFZA3sEtqx7GdLFjAqPSHqiwoQurGuvHcUA_5mdoJk3kdnrROZ9Ru8cZXOt_xPdYhhHKW8nhO1ikXSiaZlGWaMSZTlvGcp9MLsngSXpIFE6xMGFf6iLwJYc0Y1yLLXpMjLos8UzlbkH_Xo20QPMVp4zEE13e0r2kLYeM66gKFEHrrYMAV3brhjgJt-i166tGO3mNnkfqoUuhWj1r3O4orFxACJrVHpK4b0P-FhkIdBxpGH5Edrfs434_Q9mOgFpuGWvDWdX0Lc4LhDmkDftdNb8mrGpqA7w73Mfn59fRmeZ5cfT-7WH6-SmwuJE8KXgpdrVAVhahAgNZc1lrISmmViVLnnInMcl4VsqqktEqzgmWVLXOJZaWkOCYf9-9ufH8_YhhM68IcDDqMGY3SWjFdFhEs9qD1fQgea7Pxro1ZDWdm7seszVyDmWswcz_msR8zRev7w46xanH1bDwUEoEPBwCChab20FkXnjmlucgLHblPe27rGtz9dwBzfvFjnqI_2ftdGHB68oP_E_8ptDS_rs_M5e235aX6cmtuxAPT4bzg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>67760798</pqid></control><display><type>article</type><title>Nuclear expression of maspin is associated with a lower recurrence rate and a longer disease-free interval after surgery for squamous cell carcinoma of the larynx</title><source>MEDLINE</source><source>Wiley Journals</source><creator>Marioni, G ; Blandamura, S ; Giacomelli, L ; Calgaro, N ; Segato, P ; Leo, G ; Fischetto, D ; Staffieri, A ; De Filippis, C</creator><creatorcontrib>Marioni, G ; Blandamura, S ; Giacomelli, L ; Calgaro, N ; Segato, P ; Leo, G ; Fischetto, D ; Staffieri, A ; De Filippis, C</creatorcontrib><description>Aims : Maspin, a protein belonging to the serpin superfamily, is the product of a tumour suppressor gene. Tissue distribution studies have shown maspin expression in normal mammary epithelial cells, in the placenta, prostate, thymus, testis, oral cavity, small intestine, skin, and cornea. Maspin is expressed but down‐regulated in human breast, prostatic, and colonic cancers but apparently up‐regulated in pancreatic, ovarian, and gastric cancers. Only two studies concerning maspin expression in head and neck carcinomas are available. The present study is the first attempt to determine maspin expression in laryngeal carcinoma.
Methods and results : Maspin expression was evaluated in 21 cases of laryngeal carcinoma consecutively treated with an exclusively surgical approach with a follow‐up period longer than 24 months. The expression of p53, p27 and MIB‐1 was also studied. Two patterns of distribution of maspin in laryngeal neoplastic cells were found. Cytoplasmic expression of maspin was identified in 47.6% of the cases. Nuclear maspin positivity was determined in 47.6% of the cases. A statistically significant difference in nuclear maspin expression between the group of patients without carcinoma recurrence and the group with evidence of recurrence was demonstrated (P = 0.039). Log rank test analysis showed a statistically significant direct correlation between nuclear maspin expression and disease‐free intervals after surgical treatment calculated in months (P = 0.028). A significant inverse correlation was disclosed between nuclear maspin staining and MIB‐1 (P = 0.028). A trend of increasing p27 expression was noted in cases with positive nuclear maspin expression. Nuclear maspin expression was not statistically correlated with p53 expression. A trend towards direct correlation between cytoplasmic maspin expression and squamous cell carcinoma histological grade (G) was apparent. Cytoplasmic maspin expression did not correlate with p53, MIB‐1 or p27 expression.
Conclusions : These preliminary results suggest that nuclear location of maspin is a good prognostic factor in laryngeal carcinoma.</description><identifier>ISSN: 0309-0167</identifier><identifier>EISSN: 1365-2559</identifier><identifier>DOI: 10.1111/j.1365-2559.2005.02141.x</identifier><identifier>PMID: 15842640</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Adult ; Aged ; Biological and medical sciences ; carcinoma ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Carcinoma, Squamous Cell - surgery ; Cell Nucleus - chemistry ; Disease-Free Survival ; Female ; Genes, Tumor Suppressor ; Humans ; Immunohistochemistry ; Investigative techniques, diagnostic techniques (general aspects) ; Laryngeal Neoplasms - metabolism ; Laryngeal Neoplasms - pathology ; Laryngeal Neoplasms - surgery ; larynx ; Male ; maspin ; Medical sciences ; Middle Aged ; Neoplasm Recurrence, Local ; nuclear ; Otorhinolaryngology. Stomatology ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; prognosis ; Serpins - biosynthesis ; Time Factors ; Tumors ; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</subject><ispartof>Histopathology, 2005-05, Vol.46 (5), p.576-582</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4351-81937bde6883ba3a7715f735b676239741032c11b85bb55c670802bc945e9b653</citedby><cites>FETCH-LOGICAL-c4351-81937bde6883ba3a7715f735b676239741032c11b85bb55c670802bc945e9b653</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-2559.2005.02141.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2559.2005.02141.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16713487$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15842640$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Marioni, G</creatorcontrib><creatorcontrib>Blandamura, S</creatorcontrib><creatorcontrib>Giacomelli, L</creatorcontrib><creatorcontrib>Calgaro, N</creatorcontrib><creatorcontrib>Segato, P</creatorcontrib><creatorcontrib>Leo, G</creatorcontrib><creatorcontrib>Fischetto, D</creatorcontrib><creatorcontrib>Staffieri, A</creatorcontrib><creatorcontrib>De Filippis, C</creatorcontrib><title>Nuclear expression of maspin is associated with a lower recurrence rate and a longer disease-free interval after surgery for squamous cell carcinoma of the larynx</title><title>Histopathology</title><addtitle>Histopathology</addtitle><description>Aims : Maspin, a protein belonging to the serpin superfamily, is the product of a tumour suppressor gene. Tissue distribution studies have shown maspin expression in normal mammary epithelial cells, in the placenta, prostate, thymus, testis, oral cavity, small intestine, skin, and cornea. Maspin is expressed but down‐regulated in human breast, prostatic, and colonic cancers but apparently up‐regulated in pancreatic, ovarian, and gastric cancers. Only two studies concerning maspin expression in head and neck carcinomas are available. The present study is the first attempt to determine maspin expression in laryngeal carcinoma.
Methods and results : Maspin expression was evaluated in 21 cases of laryngeal carcinoma consecutively treated with an exclusively surgical approach with a follow‐up period longer than 24 months. The expression of p53, p27 and MIB‐1 was also studied. Two patterns of distribution of maspin in laryngeal neoplastic cells were found. Cytoplasmic expression of maspin was identified in 47.6% of the cases. Nuclear maspin positivity was determined in 47.6% of the cases. A statistically significant difference in nuclear maspin expression between the group of patients without carcinoma recurrence and the group with evidence of recurrence was demonstrated (P = 0.039). Log rank test analysis showed a statistically significant direct correlation between nuclear maspin expression and disease‐free intervals after surgical treatment calculated in months (P = 0.028). A significant inverse correlation was disclosed between nuclear maspin staining and MIB‐1 (P = 0.028). A trend of increasing p27 expression was noted in cases with positive nuclear maspin expression. Nuclear maspin expression was not statistically correlated with p53 expression. A trend towards direct correlation between cytoplasmic maspin expression and squamous cell carcinoma histological grade (G) was apparent. Cytoplasmic maspin expression did not correlate with p53, MIB‐1 or p27 expression.
Conclusions : These preliminary results suggest that nuclear location of maspin is a good prognostic factor in laryngeal carcinoma.</description><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>carcinoma</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Carcinoma, Squamous Cell - surgery</subject><subject>Cell Nucleus - chemistry</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Genes, Tumor Suppressor</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Laryngeal Neoplasms - metabolism</subject><subject>Laryngeal Neoplasms - pathology</subject><subject>Laryngeal Neoplasms - surgery</subject><subject>larynx</subject><subject>Male</subject><subject>maspin</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoplasm Recurrence, Local</subject><subject>nuclear</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>prognosis</subject><subject>Serpins - biosynthesis</subject><subject>Time Factors</subject><subject>Tumors</subject><subject>Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</subject><issn>0309-0167</issn><issn>1365-2559</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1u1DAUhS0EokPhFZA3sEtqx7GdLFjAqPSHqiwoQurGuvHcUA_5mdoJk3kdnrROZ9Ru8cZXOt_xPdYhhHKW8nhO1ikXSiaZlGWaMSZTlvGcp9MLsngSXpIFE6xMGFf6iLwJYc0Y1yLLXpMjLos8UzlbkH_Xo20QPMVp4zEE13e0r2kLYeM66gKFEHrrYMAV3brhjgJt-i166tGO3mNnkfqoUuhWj1r3O4orFxACJrVHpK4b0P-FhkIdBxpGH5Edrfs434_Q9mOgFpuGWvDWdX0Lc4LhDmkDftdNb8mrGpqA7w73Mfn59fRmeZ5cfT-7WH6-SmwuJE8KXgpdrVAVhahAgNZc1lrISmmViVLnnInMcl4VsqqktEqzgmWVLXOJZaWkOCYf9-9ufH8_YhhM68IcDDqMGY3SWjFdFhEs9qD1fQgea7Pxro1ZDWdm7seszVyDmWswcz_msR8zRev7w46xanH1bDwUEoEPBwCChab20FkXnjmlucgLHblPe27rGtz9dwBzfvFjnqI_2ftdGHB68oP_E_8ptDS_rs_M5e235aX6cmtuxAPT4bzg</recordid><startdate>200505</startdate><enddate>200505</enddate><creator>Marioni, G</creator><creator>Blandamura, S</creator><creator>Giacomelli, L</creator><creator>Calgaro, N</creator><creator>Segato, P</creator><creator>Leo, G</creator><creator>Fischetto, D</creator><creator>Staffieri, A</creator><creator>De Filippis, C</creator><general>Blackwell Science Ltd</general><general>Blackwell</general><scope>BSCLL</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>200505</creationdate><title>Nuclear expression of maspin is associated with a lower recurrence rate and a longer disease-free interval after surgery for squamous cell carcinoma of the larynx</title><author>Marioni, G ; Blandamura, S ; Giacomelli, L ; Calgaro, N ; Segato, P ; Leo, G ; Fischetto, D ; Staffieri, A ; De Filippis, C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4351-81937bde6883ba3a7715f735b676239741032c11b85bb55c670802bc945e9b653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>carcinoma</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Carcinoma, Squamous Cell - surgery</topic><topic>Cell Nucleus - chemistry</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Genes, Tumor Suppressor</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Laryngeal Neoplasms - metabolism</topic><topic>Laryngeal Neoplasms - pathology</topic><topic>Laryngeal Neoplasms - surgery</topic><topic>larynx</topic><topic>Male</topic><topic>maspin</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoplasm Recurrence, Local</topic><topic>nuclear</topic><topic>Otorhinolaryngology. Stomatology</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>prognosis</topic><topic>Serpins - biosynthesis</topic><topic>Time Factors</topic><topic>Tumors</topic><topic>Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Marioni, G</creatorcontrib><creatorcontrib>Blandamura, S</creatorcontrib><creatorcontrib>Giacomelli, L</creatorcontrib><creatorcontrib>Calgaro, N</creatorcontrib><creatorcontrib>Segato, P</creatorcontrib><creatorcontrib>Leo, G</creatorcontrib><creatorcontrib>Fischetto, D</creatorcontrib><creatorcontrib>Staffieri, A</creatorcontrib><creatorcontrib>De Filippis, C</creatorcontrib><collection>Istex</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>Histopathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Marioni, G</au><au>Blandamura, S</au><au>Giacomelli, L</au><au>Calgaro, N</au><au>Segato, P</au><au>Leo, G</au><au>Fischetto, D</au><au>Staffieri, A</au><au>De Filippis, C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nuclear expression of maspin is associated with a lower recurrence rate and a longer disease-free interval after surgery for squamous cell carcinoma of the larynx</atitle><jtitle>Histopathology</jtitle><addtitle>Histopathology</addtitle><date>2005-05</date><risdate>2005</risdate><volume>46</volume><issue>5</issue><spage>576</spage><epage>582</epage><pages>576-582</pages><issn>0309-0167</issn><eissn>1365-2559</eissn><abstract>Aims : Maspin, a protein belonging to the serpin superfamily, is the product of a tumour suppressor gene. Tissue distribution studies have shown maspin expression in normal mammary epithelial cells, in the placenta, prostate, thymus, testis, oral cavity, small intestine, skin, and cornea. Maspin is expressed but down‐regulated in human breast, prostatic, and colonic cancers but apparently up‐regulated in pancreatic, ovarian, and gastric cancers. Only two studies concerning maspin expression in head and neck carcinomas are available. The present study is the first attempt to determine maspin expression in laryngeal carcinoma.
Methods and results : Maspin expression was evaluated in 21 cases of laryngeal carcinoma consecutively treated with an exclusively surgical approach with a follow‐up period longer than 24 months. The expression of p53, p27 and MIB‐1 was also studied. Two patterns of distribution of maspin in laryngeal neoplastic cells were found. Cytoplasmic expression of maspin was identified in 47.6% of the cases. Nuclear maspin positivity was determined in 47.6% of the cases. A statistically significant difference in nuclear maspin expression between the group of patients without carcinoma recurrence and the group with evidence of recurrence was demonstrated (P = 0.039). Log rank test analysis showed a statistically significant direct correlation between nuclear maspin expression and disease‐free intervals after surgical treatment calculated in months (P = 0.028). A significant inverse correlation was disclosed between nuclear maspin staining and MIB‐1 (P = 0.028). A trend of increasing p27 expression was noted in cases with positive nuclear maspin expression. Nuclear maspin expression was not statistically correlated with p53 expression. A trend towards direct correlation between cytoplasmic maspin expression and squamous cell carcinoma histological grade (G) was apparent. Cytoplasmic maspin expression did not correlate with p53, MIB‐1 or p27 expression.
Conclusions : These preliminary results suggest that nuclear location of maspin is a good prognostic factor in laryngeal carcinoma.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>15842640</pmid><doi>10.1111/j.1365-2559.2005.02141.x</doi><tpages>7</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0309-0167 |
ispartof | Histopathology, 2005-05, Vol.46 (5), p.576-582 |
issn | 0309-0167 1365-2559 |
language | eng |
recordid | cdi_proquest_miscellaneous_67760798 |
source | MEDLINE; Wiley Journals |
subjects | Adult Aged Biological and medical sciences carcinoma Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Carcinoma, Squamous Cell - surgery Cell Nucleus - chemistry Disease-Free Survival Female Genes, Tumor Suppressor Humans Immunohistochemistry Investigative techniques, diagnostic techniques (general aspects) Laryngeal Neoplasms - metabolism Laryngeal Neoplasms - pathology Laryngeal Neoplasms - surgery larynx Male maspin Medical sciences Middle Aged Neoplasm Recurrence, Local nuclear Otorhinolaryngology. Stomatology Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques prognosis Serpins - biosynthesis Time Factors Tumors Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology |
title | Nuclear expression of maspin is associated with a lower recurrence rate and a longer disease-free interval after surgery for squamous cell carcinoma of the larynx |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-03T04%3A19%3A25IST&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=Nuclear%20expression%20of%20maspin%20is%20associated%20with%20a%20lower%20recurrence%20rate%20and%20a%20longer%20disease-free%20interval%20after%20surgery%20for%20squamous%20cell%20carcinoma%20of%20the%20larynx&rft.jtitle=Histopathology&rft.au=Marioni,%20G&rft.date=2005-05&rft.volume=46&rft.issue=5&rft.spage=576&rft.epage=582&rft.pages=576-582&rft.issn=0309-0167&rft.eissn=1365-2559&rft_id=info:doi/10.1111/j.1365-2559.2005.02141.x&rft_dat=%3Cproquest_cross%3E67760798%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=67760798&rft_id=info:pmid/15842640&rfr_iscdi=true |