The pro-inflammatory effects of low-toxicity low-solubility particles, nanoparticles and fine particles, on epithelial cells in vitro: the role of surface area

Objective: Rats exposed to high airborne mass concentrations of low-solubility low-toxicity particles (LSLTP) have been reported to develop lung disease such as fibrosis and lung cancer. These particles are regulated on a mass basis in occupational settings, but mass might not be the appropriate met...

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Veröffentlicht in:Occupational and environmental medicine (London, England) England), 2007-09, Vol.64 (9), p.609-615
Hauptverfasser: Monteiller, Claire, Tran, Lang, MacNee, William, Faux, Steve, Jones, Alan, Miller, Brian, Donaldson, Ken
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container_end_page 615
container_issue 9
container_start_page 609
container_title Occupational and environmental medicine (London, England)
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creator Monteiller, Claire
Tran, Lang
MacNee, William
Faux, Steve
Jones, Alan
Miller, Brian
Donaldson, Ken
description Objective: Rats exposed to high airborne mass concentrations of low-solubility low-toxicity particles (LSLTP) have been reported to develop lung disease such as fibrosis and lung cancer. These particles are regulated on a mass basis in occupational settings, but mass might not be the appropriate metric as animal studies have shown that nanoparticles (ultrafine particles) produce a stronger adverse effect than fine particles when delivered on an equal mass basis. Methods: This study investigated whether the surface area is a better descriptor than mass of LSLTP of their ability to stimulate pro-inflammatory responses in vitro. In a human alveolar epithelial type II-like cell line, A549, we measured interleukin (IL)-8 mRNA, IL8 protein release and glutathione (GSH) depletion as markers of pro-inflammatory effects and oxidative stress after treatment with a range of LSLTP (fine and nanoparticles) and DQ12 quartz, a particle with a highly reactive surface. Results: In all the assays, nanoparticle preparations of titanium dioxide (TiO2-np) and of carbon black (CB-np) produced much stronger pro-inflammatory responses than the same mass dose of fine TiO2 and CB. The results of the GSH assay confirmed that oxidative stress was involved in the response to all the particles, and two ultra-fine metal dusts (cobalt and nickel) produced GSH depletion similar to TiO2-np, for similar surface-area dose. As expected, DQ12 quartz was more inflammatory than the low toxicity dusts, on both a mass and surface-area basis. Conclusion: Dose–response relationships observed in the in vitro assays appeared to be directly comparable with dose–response relationships in vivo when the doses were similarly standardised. Both sets of data suggested a threshold in dose measured as surface area of particles relative to the surface area of the exposed cells, at around 1–10 cm2/cm2. These findings are consistent with the hypothesis that surface area is a more appropriate dose metric than mass for the pro-inflammatory effects of LSLTP in vitro and in vivo, and consequently that the high surface area of nanoparticles is a key factor in their inflammogenicity.
doi_str_mv 10.1136/oem.2005.024802
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The results of the GSH assay confirmed that oxidative stress was involved in the response to all the particles, and two ultra-fine metal dusts (cobalt and nickel) produced GSH depletion similar to TiO2-np, for similar surface-area dose. As expected, DQ12 quartz was more inflammatory than the low toxicity dusts, on both a mass and surface-area basis. Conclusion: Dose–response relationships observed in the in vitro assays appeared to be directly comparable with dose–response relationships in vivo when the doses were similarly standardised. Both sets of data suggested a threshold in dose measured as surface area of particles relative to the surface area of the exposed cells, at around 1–10 cm2/cm2. 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Toxic occupational diseases ; Cobalt ; DMEM ; Dosage ; Dose-Response Relationship, Drug ; Dulbecco’s modified Eagle’s medium ; Environmental pollutants toxicology ; Epithelial Cells ; FCS ; fetal calf serum ; GAPDH ; glutathione ; Glutathione - metabolism ; glyceraldehyde-3-phosphate ; GSH ; Humans ; IL8 ; Inflammation ; Inhalation Exposure - adverse effects ; Inhalation Exposure - analysis ; Inorganic dusts (pneumoconiosises) and organic dusts (byssinosis etc.) ; interleukin ; Interleukin-8 - metabolism ; Laboratories ; lactate dehydrogenase ; LDH ; low-solubility low-toxicity particles ; LSLTP ; Lung cancer ; Lung Neoplasms - etiology ; Lungs ; Medical sciences ; Messenger RNA ; nanoparticle ; Nanoparticles ; Nanoparticles - toxicity ; Nickel ; nuclear factor ; Original ; Oxidative Stress ; Particle mass ; Particle Size ; Particulate Matter - toxicity ; Proteins ; Pulmonary Fibrosis - etiology ; Quartz ; Quartz - analysis ; reactive oxygen species ; Respiratory Mucosa - drug effects ; RNA, Messenger - metabolism ; ROS ; Solubility ; Surface area ; Surface areas ; TiO2 ; Titanium ; Titanium - toxicity ; Titanium dioxide ; Toxicity ; Toxicology</subject><ispartof>Occupational and environmental medicine (London, England), 2007-09, Vol.64 (9), p.609-615</ispartof><rights>Occupational and Environmental Medicine</rights><rights>Copyright 2007 BMJ Publishing Group Ltd.</rights><rights>2007 INIST-CNRS</rights><rights>Copyright: 2007 (c) Occupational and Environmental Medicine</rights><rights>Copyright © 2007 BMJ Publishing Group</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b641t-8c93fca0edfe75afedcdc5122ed6c00370f2e246adc4152698b43fc6f48bccbd3</citedby><cites>FETCH-LOGICAL-b641t-8c93fca0edfe75afedcdc5122ed6c00370f2e246adc4152698b43fc6f48bccbd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://oem.bmj.com/content/64/9/609.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttps://oem.bmj.com/content/64/9/609.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,230,314,725,778,782,801,883,3185,23558,27911,27912,53778,53780,58004,58237,77355,77386</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=18986686$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17409182$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Monteiller, Claire</creatorcontrib><creatorcontrib>Tran, Lang</creatorcontrib><creatorcontrib>MacNee, William</creatorcontrib><creatorcontrib>Faux, Steve</creatorcontrib><creatorcontrib>Jones, Alan</creatorcontrib><creatorcontrib>Miller, Brian</creatorcontrib><creatorcontrib>Donaldson, Ken</creatorcontrib><title>The pro-inflammatory effects of low-toxicity low-solubility particles, nanoparticles and fine particles, on epithelial cells in vitro: the role of surface area</title><title>Occupational and environmental medicine (London, England)</title><addtitle>Occup Environ Med</addtitle><description>Objective: Rats exposed to high airborne mass concentrations of low-solubility low-toxicity particles (LSLTP) have been reported to develop lung disease such as fibrosis and lung cancer. These particles are regulated on a mass basis in occupational settings, but mass might not be the appropriate metric as animal studies have shown that nanoparticles (ultrafine particles) produce a stronger adverse effect than fine particles when delivered on an equal mass basis. Methods: This study investigated whether the surface area is a better descriptor than mass of LSLTP of their ability to stimulate pro-inflammatory responses in vitro. In a human alveolar epithelial type II-like cell line, A549, we measured interleukin (IL)-8 mRNA, IL8 protein release and glutathione (GSH) depletion as markers of pro-inflammatory effects and oxidative stress after treatment with a range of LSLTP (fine and nanoparticles) and DQ12 quartz, a particle with a highly reactive surface. Results: In all the assays, nanoparticle preparations of titanium dioxide (TiO2-np) and of carbon black (CB-np) produced much stronger pro-inflammatory responses than the same mass dose of fine TiO2 and CB. The results of the GSH assay confirmed that oxidative stress was involved in the response to all the particles, and two ultra-fine metal dusts (cobalt and nickel) produced GSH depletion similar to TiO2-np, for similar surface-area dose. As expected, DQ12 quartz was more inflammatory than the low toxicity dusts, on both a mass and surface-area basis. Conclusion: Dose–response relationships observed in the in vitro assays appeared to be directly comparable with dose–response relationships in vivo when the doses were similarly standardised. Both sets of data suggested a threshold in dose measured as surface area of particles relative to the surface area of the exposed cells, at around 1–10 cm2/cm2. 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Toxic occupational diseases</subject><subject>Cobalt</subject><subject>DMEM</subject><subject>Dosage</subject><subject>Dose-Response Relationship, Drug</subject><subject>Dulbecco’s modified Eagle’s medium</subject><subject>Environmental pollutants toxicology</subject><subject>Epithelial Cells</subject><subject>FCS</subject><subject>fetal calf serum</subject><subject>GAPDH</subject><subject>glutathione</subject><subject>Glutathione - metabolism</subject><subject>glyceraldehyde-3-phosphate</subject><subject>GSH</subject><subject>Humans</subject><subject>IL8</subject><subject>Inflammation</subject><subject>Inhalation Exposure - adverse effects</subject><subject>Inhalation Exposure - analysis</subject><subject>Inorganic dusts (pneumoconiosises) and organic dusts (byssinosis etc.)</subject><subject>interleukin</subject><subject>Interleukin-8 - metabolism</subject><subject>Laboratories</subject><subject>lactate dehydrogenase</subject><subject>LDH</subject><subject>low-solubility low-toxicity particles</subject><subject>LSLTP</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - etiology</subject><subject>Lungs</subject><subject>Medical sciences</subject><subject>Messenger RNA</subject><subject>nanoparticle</subject><subject>Nanoparticles</subject><subject>Nanoparticles - toxicity</subject><subject>Nickel</subject><subject>nuclear factor</subject><subject>Original</subject><subject>Oxidative Stress</subject><subject>Particle mass</subject><subject>Particle Size</subject><subject>Particulate Matter - toxicity</subject><subject>Proteins</subject><subject>Pulmonary Fibrosis - etiology</subject><subject>Quartz</subject><subject>Quartz - analysis</subject><subject>reactive oxygen species</subject><subject>Respiratory Mucosa - drug effects</subject><subject>RNA, Messenger - metabolism</subject><subject>ROS</subject><subject>Solubility</subject><subject>Surface area</subject><subject>Surface areas</subject><subject>TiO2</subject><subject>Titanium</subject><subject>Titanium - toxicity</subject><subject>Titanium dioxide</subject><subject>Toxicity</subject><subject>Toxicology</subject><issn>1351-0711</issn><issn>1470-7926</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFksFvFCEUxidGY2v17ElDYvRgnC0wMzB4MDGrVZNV06R6JQzzcFkZWGGmdv8a_1VZd7OtXjzB4_u9B18-iuIhwTNCKnYaYJhRjJsZpnWL6a3imNQcl1xQdjvvq4aUmBNyVNxLaYUxqXhF7xZHhNdYkJYeF78uloDWMZTWG6eGQY0hbhAYA3pMKBjkws9yDFdW23Hzp0jBTZ1123Kt4mi1g_QCeeXDoUTK98hYDzeJ4BGs7bgEZ5VDGpxLyHp0accYXqJ8jmJwsL0yTdEoDUhFUPeLO0a5BA_260nx5eztxfx9ufj87sP89aLsWE3GstWiMlph6A3wRhnoda8bQin0TGNccWwo0JqpXtekoUy0XZ0bmKnbTuuur06KV7u566kbcjf4MSon19EOKm5kUFb-rXi7lN_CpaRY0IaRPODZfkAMPyZIoxxs2rpUHsKUMkcF51hk8Mk_4CpM0WdzkvCW0LYVAmfqdEfpGFKKYA5PIVhuo5c5ermNXu6izx2Pbzq45vdZZ-DpHlBJK2ei8tqma64VLWMty9yjHbdK-TMcdMrz3xGiyXq5020a4eqgq_hdMl7xRn76OpdnH8_PmzcYy0Xmn-_4blj918VvMhfiBA</recordid><startdate>20070901</startdate><enddate>20070901</enddate><creator>Monteiller, Claire</creator><creator>Tran, Lang</creator><creator>MacNee, William</creator><creator>Faux, Steve</creator><creator>Jones, Alan</creator><creator>Miller, Brian</creator><creator>Donaldson, Ken</creator><general>BMJ Publishing Group Ltd</general><general>BMJ Publishing Group</general><general>BMJ</general><general>BMJ Publishing Group LTD</general><general>BMJ Group</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>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FE</scope><scope>8FG</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>L6V</scope><scope>M0S</scope><scope>M1P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>PATMY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>7T2</scope><scope>7U2</scope><scope>7U7</scope><scope>C1K</scope><scope>5PM</scope></search><sort><creationdate>20070901</creationdate><title>The pro-inflammatory effects of low-toxicity low-solubility particles, nanoparticles and fine particles, on epithelial cells in vitro: the role of surface area</title><author>Monteiller, Claire ; Tran, Lang ; MacNee, William ; Faux, Steve ; Jones, Alan ; Miller, Brian ; Donaldson, Ken</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b641t-8c93fca0edfe75afedcdc5122ed6c00370f2e246adc4152698b43fc6f48bccbd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>activator protein-1</topic><topic>Air</topic><topic>alveolar macrophage</topic><topic>AP-1</topic><topic>barium sulphate</topic><topic>BaSO4</topic><topic>Biological and medical sciences</topic><topic>Black carbon</topic><topic>Carbon black</topic><topic>Cell lines</topic><topic>Cells, Cultured</topic><topic>Chemical and industrial products toxicology. Toxic occupational diseases</topic><topic>Cobalt</topic><topic>DMEM</topic><topic>Dosage</topic><topic>Dose-Response Relationship, Drug</topic><topic>Dulbecco’s modified Eagle’s medium</topic><topic>Environmental pollutants toxicology</topic><topic>Epithelial Cells</topic><topic>FCS</topic><topic>fetal calf serum</topic><topic>GAPDH</topic><topic>glutathione</topic><topic>Glutathione - metabolism</topic><topic>glyceraldehyde-3-phosphate</topic><topic>GSH</topic><topic>Humans</topic><topic>IL8</topic><topic>Inflammation</topic><topic>Inhalation Exposure - adverse effects</topic><topic>Inhalation Exposure - analysis</topic><topic>Inorganic dusts (pneumoconiosises) and organic dusts (byssinosis etc.)</topic><topic>interleukin</topic><topic>Interleukin-8 - metabolism</topic><topic>Laboratories</topic><topic>lactate dehydrogenase</topic><topic>LDH</topic><topic>low-solubility low-toxicity particles</topic><topic>LSLTP</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - etiology</topic><topic>Lungs</topic><topic>Medical sciences</topic><topic>Messenger RNA</topic><topic>nanoparticle</topic><topic>Nanoparticles</topic><topic>Nanoparticles - toxicity</topic><topic>Nickel</topic><topic>nuclear factor</topic><topic>Original</topic><topic>Oxidative Stress</topic><topic>Particle mass</topic><topic>Particle Size</topic><topic>Particulate Matter - toxicity</topic><topic>Proteins</topic><topic>Pulmonary Fibrosis - etiology</topic><topic>Quartz</topic><topic>Quartz - analysis</topic><topic>reactive oxygen species</topic><topic>Respiratory Mucosa - drug effects</topic><topic>RNA, Messenger - metabolism</topic><topic>ROS</topic><topic>Solubility</topic><topic>Surface area</topic><topic>Surface areas</topic><topic>TiO2</topic><topic>Titanium</topic><topic>Titanium - toxicity</topic><topic>Titanium dioxide</topic><topic>Toxicity</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Monteiller, Claire</creatorcontrib><creatorcontrib>Tran, Lang</creatorcontrib><creatorcontrib>MacNee, William</creatorcontrib><creatorcontrib>Faux, Steve</creatorcontrib><creatorcontrib>Jones, Alan</creatorcontrib><creatorcontrib>Miller, Brian</creatorcontrib><creatorcontrib>Donaldson, Ken</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>ProQuest Central (Corporate)</collection><collection>Nursing &amp; 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These particles are regulated on a mass basis in occupational settings, but mass might not be the appropriate metric as animal studies have shown that nanoparticles (ultrafine particles) produce a stronger adverse effect than fine particles when delivered on an equal mass basis. Methods: This study investigated whether the surface area is a better descriptor than mass of LSLTP of their ability to stimulate pro-inflammatory responses in vitro. In a human alveolar epithelial type II-like cell line, A549, we measured interleukin (IL)-8 mRNA, IL8 protein release and glutathione (GSH) depletion as markers of pro-inflammatory effects and oxidative stress after treatment with a range of LSLTP (fine and nanoparticles) and DQ12 quartz, a particle with a highly reactive surface. Results: In all the assays, nanoparticle preparations of titanium dioxide (TiO2-np) and of carbon black (CB-np) produced much stronger pro-inflammatory responses than the same mass dose of fine TiO2 and CB. The results of the GSH assay confirmed that oxidative stress was involved in the response to all the particles, and two ultra-fine metal dusts (cobalt and nickel) produced GSH depletion similar to TiO2-np, for similar surface-area dose. As expected, DQ12 quartz was more inflammatory than the low toxicity dusts, on both a mass and surface-area basis. Conclusion: Dose–response relationships observed in the in vitro assays appeared to be directly comparable with dose–response relationships in vivo when the doses were similarly standardised. Both sets of data suggested a threshold in dose measured as surface area of particles relative to the surface area of the exposed cells, at around 1–10 cm2/cm2. These findings are consistent with the hypothesis that surface area is a more appropriate dose metric than mass for the pro-inflammatory effects of LSLTP in vitro and in vivo, and consequently that the high surface area of nanoparticles is a key factor in their inflammogenicity.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd</pub><pmid>17409182</pmid><doi>10.1136/oem.2005.024802</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; BMJ Journals - NESLi2; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Jstor Complete Legacy; PubMed Central
subjects activator protein-1
Air
alveolar macrophage
AP-1
barium sulphate
BaSO4
Biological and medical sciences
Black carbon
Carbon black
Cell lines
Cells, Cultured
Chemical and industrial products toxicology. Toxic occupational diseases
Cobalt
DMEM
Dosage
Dose-Response Relationship, Drug
Dulbecco’s modified Eagle’s medium
Environmental pollutants toxicology
Epithelial Cells
FCS
fetal calf serum
GAPDH
glutathione
Glutathione - metabolism
glyceraldehyde-3-phosphate
GSH
Humans
IL8
Inflammation
Inhalation Exposure - adverse effects
Inhalation Exposure - analysis
Inorganic dusts (pneumoconiosises) and organic dusts (byssinosis etc.)
interleukin
Interleukin-8 - metabolism
Laboratories
lactate dehydrogenase
LDH
low-solubility low-toxicity particles
LSLTP
Lung cancer
Lung Neoplasms - etiology
Lungs
Medical sciences
Messenger RNA
nanoparticle
Nanoparticles
Nanoparticles - toxicity
Nickel
nuclear factor
Original
Oxidative Stress
Particle mass
Particle Size
Particulate Matter - toxicity
Proteins
Pulmonary Fibrosis - etiology
Quartz
Quartz - analysis
reactive oxygen species
Respiratory Mucosa - drug effects
RNA, Messenger - metabolism
ROS
Solubility
Surface area
Surface areas
TiO2
Titanium
Titanium - toxicity
Titanium dioxide
Toxicity
Toxicology
title The pro-inflammatory effects of low-toxicity low-solubility particles, nanoparticles and fine particles, on epithelial cells in vitro: the role of surface area
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T00%3A29%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20pro-inflammatory%20effects%20of%20low-toxicity%20low-solubility%20particles,%20nanoparticles%20and%20fine%20particles,%20on%20epithelial%20cells%20in%20vitro:%20the%20role%20of%20surface%20area&rft.jtitle=Occupational%20and%20environmental%20medicine%20(London,%20England)&rft.au=Monteiller,%20Claire&rft.date=2007-09-01&rft.volume=64&rft.issue=9&rft.spage=609&rft.epage=615&rft.pages=609-615&rft.issn=1351-0711&rft.eissn=1470-7926&rft_id=info:doi/10.1136/oem.2005.024802&rft_dat=%3Cjstor_pubme%3E27732995%3C/jstor_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1781288990&rft_id=info:pmid/17409182&rft_jstor_id=27732995&rfr_iscdi=true