The effect of hydroxylation of linoleoyl amides on their cannabinomimetic properties
As yet, the physiological significance of hydroxylation of anandamide and linoleoyl amides is unknown. Therefore, we investigated whether hydroxylation of ODNHEtOH and ODNH 2 influences their binding abilities to the CB-1 receptor and whether it alters their reactivity towards a fatty acid amide hyd...
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| Veröffentlicht in: | FEBS letters 1997-10, Vol.415 (3), p.313-316 |
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| creator | van der Stelt, Marcelis Paoletti, Anna Maria Maccarrone, Mauro Nieuwenhuizen, Willem F Bagetta, Giacinto Veldink, Gerrit A Finazzi Agrò, Alessandro Vliegenthart, Johannes F.G |
| description | As yet, the physiological significance of hydroxylation of anandamide and linoleoyl amides is unknown. Therefore, we investigated whether hydroxylation of ODNHEtOH and ODNH
2 influences their binding abilities to the CB-1 receptor and whether it alters their reactivity towards a fatty acid amide hydrolase (FAAH) from rat brain. Neither the fatty acid amides nor their hydroxylated derivatives were able to displace the potent cannabinoid [
3H]CP 55.940 from the CB-1 receptor (
K
i>1 μM). Hydroxylation of ODNHEtOH resulted in a strong reduction of the maximum rate of hydrolysis by a FAAH, but the affinity of FAAH for the substrate remained of the same order of magnitude. Hydroxylation of ODNH
2 led to a decrease in the affinity of FAAH for the substrate, but its maximum rate of conversion was unaffected. Furthermore, hydroxylation of ODNHEtOH enhanced its capacity to inhibit competitively the hydrolysis of anandamide. The resulting prolonged lifetime of anandamide and other fatty acid amide derivatives may have a considerable impact on cellular signal transduction. |
| doi_str_mv | 10.1016/S0014-5793(97)01148-4 |
| format | Article |
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2 influences their binding abilities to the CB-1 receptor and whether it alters their reactivity towards a fatty acid amide hydrolase (FAAH) from rat brain. Neither the fatty acid amides nor their hydroxylated derivatives were able to displace the potent cannabinoid [
3H]CP 55.940 from the CB-1 receptor (
K
i>1 μM). Hydroxylation of ODNHEtOH resulted in a strong reduction of the maximum rate of hydrolysis by a FAAH, but the affinity of FAAH for the substrate remained of the same order of magnitude. Hydroxylation of ODNH
2 led to a decrease in the affinity of FAAH for the substrate, but its maximum rate of conversion was unaffected. Furthermore, hydroxylation of ODNHEtOH enhanced its capacity to inhibit competitively the hydrolysis of anandamide. The resulting prolonged lifetime of anandamide and other fatty acid amide derivatives may have a considerable impact on cellular signal transduction.</description><identifier>ISSN: 0014-5793</identifier><identifier>EISSN: 1873-3468</identifier><identifier>DOI: 10.1016/S0014-5793(97)01148-4</identifier><identifier>PMID: 9357990</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>12/15-HETE ; 12/15-hydroxyeicosatetraenoic acid ; 13-(S)-hydroxy-9Z,11E-octadeca-9,11-dienoyl amide ; 13-(S)-hydroxy-9Z,11E-octadeca-9,11-dienoyl ethanolamide ; 13-HODNH2 ; 13-HODNHEtOH ; 9Z,12Z-octadeca-9,12-dienoyl amide ; 9Z,12Z-octadeca-9,12-dienoyl ethanolamide ; Amidohydrolases - antagonists & inhibitors ; Amidohydrolases - metabolism ; Anandamide ; Animals ; Arachidonic Acids - metabolism ; Binding, Competitive ; bovine serum albumin ; Brain - enzymology ; BSA ; cannabinoid binding receptor-1/2 ; Cannabinoid receptor ; Cannabinoids - metabolism ; CB-1/2 ; Cyclohexanols - metabolism ; Endocannabinoids ; Enzyme Inhibitors - pharmacology ; FAAH ; Fatty acid amide hydrolase ; Hydroxylation ; Kinetics ; LCS ; Linoleic Acids - metabolism ; Linoleic Acids - pharmacology ; Lipoxygenase ; liquid scintillation cocktail ; Male ; ODNH2 ; ODNHEtOH ; PEI ; phenylmethylsulfonyl fluoride ; PMSF ; polyethylene imine ; Polyunsaturated Alkamides ; Rats ; Rats, Wistar ; Receptors, Cannabinoid ; Receptors, Drug - metabolism ; reversed phase high performance liquid chromatography ; RP-HPLC ; Substrate Specificity ; thin layer chromatography ; TLC</subject><ispartof>FEBS letters, 1997-10, Vol.415 (3), p.313-316</ispartof><rights>1997 Federation of European Biochemical Societies</rights><rights>FEBS Letters 415 (1997) 1873-3468 © 2015 Federation of European Biochemical Societies</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4254-3de10c714c3746852bf938b9af1c34f7b0604865294234473a15aac1d23dc4643</citedby><cites>FETCH-LOGICAL-c4254-3de10c714c3746852bf938b9af1c34f7b0604865294234473a15aac1d23dc4643</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1016%2FS0014-5793%2897%2901148-4$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014579397011484$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,1427,3536,27903,27904,45553,45554,46387,46811,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9357990$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van der Stelt, Marcelis</creatorcontrib><creatorcontrib>Paoletti, Anna Maria</creatorcontrib><creatorcontrib>Maccarrone, Mauro</creatorcontrib><creatorcontrib>Nieuwenhuizen, Willem F</creatorcontrib><creatorcontrib>Bagetta, Giacinto</creatorcontrib><creatorcontrib>Veldink, Gerrit A</creatorcontrib><creatorcontrib>Finazzi Agrò, Alessandro</creatorcontrib><creatorcontrib>Vliegenthart, Johannes F.G</creatorcontrib><title>The effect of hydroxylation of linoleoyl amides on their cannabinomimetic properties</title><title>FEBS letters</title><addtitle>FEBS Lett</addtitle><description>As yet, the physiological significance of hydroxylation of anandamide and linoleoyl amides is unknown. Therefore, we investigated whether hydroxylation of ODNHEtOH and ODNH
2 influences their binding abilities to the CB-1 receptor and whether it alters their reactivity towards a fatty acid amide hydrolase (FAAH) from rat brain. Neither the fatty acid amides nor their hydroxylated derivatives were able to displace the potent cannabinoid [
3H]CP 55.940 from the CB-1 receptor (
K
i>1 μM). Hydroxylation of ODNHEtOH resulted in a strong reduction of the maximum rate of hydrolysis by a FAAH, but the affinity of FAAH for the substrate remained of the same order of magnitude. Hydroxylation of ODNH
2 led to a decrease in the affinity of FAAH for the substrate, but its maximum rate of conversion was unaffected. Furthermore, hydroxylation of ODNHEtOH enhanced its capacity to inhibit competitively the hydrolysis of anandamide. The resulting prolonged lifetime of anandamide and other fatty acid amide derivatives may have a considerable impact on cellular signal transduction.</description><subject>12/15-HETE</subject><subject>12/15-hydroxyeicosatetraenoic acid</subject><subject>13-(S)-hydroxy-9Z,11E-octadeca-9,11-dienoyl amide</subject><subject>13-(S)-hydroxy-9Z,11E-octadeca-9,11-dienoyl ethanolamide</subject><subject>13-HODNH2</subject><subject>13-HODNHEtOH</subject><subject>9Z,12Z-octadeca-9,12-dienoyl amide</subject><subject>9Z,12Z-octadeca-9,12-dienoyl ethanolamide</subject><subject>Amidohydrolases - antagonists & inhibitors</subject><subject>Amidohydrolases - metabolism</subject><subject>Anandamide</subject><subject>Animals</subject><subject>Arachidonic Acids - metabolism</subject><subject>Binding, Competitive</subject><subject>bovine serum albumin</subject><subject>Brain - enzymology</subject><subject>BSA</subject><subject>cannabinoid binding receptor-1/2</subject><subject>Cannabinoid receptor</subject><subject>Cannabinoids - metabolism</subject><subject>CB-1/2</subject><subject>Cyclohexanols - metabolism</subject><subject>Endocannabinoids</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>FAAH</subject><subject>Fatty acid amide hydrolase</subject><subject>Hydroxylation</subject><subject>Kinetics</subject><subject>LCS</subject><subject>Linoleic Acids - metabolism</subject><subject>Linoleic Acids - pharmacology</subject><subject>Lipoxygenase</subject><subject>liquid scintillation cocktail</subject><subject>Male</subject><subject>ODNH2</subject><subject>ODNHEtOH</subject><subject>PEI</subject><subject>phenylmethylsulfonyl fluoride</subject><subject>PMSF</subject><subject>polyethylene imine</subject><subject>Polyunsaturated Alkamides</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors, Cannabinoid</subject><subject>Receptors, Drug - metabolism</subject><subject>reversed phase high performance liquid chromatography</subject><subject>RP-HPLC</subject><subject>Substrate Specificity</subject><subject>thin layer chromatography</subject><subject>TLC</subject><issn>0014-5793</issn><issn>1873-3468</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcFPwyAUxonRzDn9E5b0ZPRQhUJLORk1zpks8eA8E0pfM0xbJnRq_3vptuyqJ8L3Pd733g-EpgTfEEyy2zeMCYtTLuiV4NeYEJbH7AiNSc5pTFmWH6PxoeQUnXn_gcM9J2KERoIGVeAxWi5XEEFVge4iW0WrvnT2p69VZ2w7CLVpbQ22ryPVmBJ8FORuBcZFWrWtKoLdmAY6o6O1s2twnQF_jk4qVXu42J8T9D57Wj7O48Xr88vj_SLWLElZTEsgWHPCNOVh3jQpKkHzQqiKaMoqXuAMszxLE8ESyhiniqRKaVImtNQsY3SCLnd9Q_TnBnwnG-M11LVqwW68DIvnOQ48JijdFWpnvXdQybUzjXK9JFgONOWWphxQScHllqYcAqb7gE3RQHl4tccX_PnO_zY19P9rKmdPD8nWGQzBt_IQdbdrBQHYlwEnvTbQaiiNC58jS2v-GPYXV3qYJA</recordid><startdate>19971006</startdate><enddate>19971006</enddate><creator>van der Stelt, Marcelis</creator><creator>Paoletti, Anna Maria</creator><creator>Maccarrone, Mauro</creator><creator>Nieuwenhuizen, Willem F</creator><creator>Bagetta, Giacinto</creator><creator>Veldink, Gerrit A</creator><creator>Finazzi Agrò, Alessandro</creator><creator>Vliegenthart, Johannes F.G</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</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>19971006</creationdate><title>The effect of hydroxylation of linoleoyl amides on their cannabinomimetic properties</title><author>van der Stelt, Marcelis ; Paoletti, Anna Maria ; Maccarrone, Mauro ; Nieuwenhuizen, Willem F ; Bagetta, Giacinto ; Veldink, Gerrit A ; Finazzi Agrò, Alessandro ; Vliegenthart, Johannes F.G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4254-3de10c714c3746852bf938b9af1c34f7b0604865294234473a15aac1d23dc4643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>12/15-HETE</topic><topic>12/15-hydroxyeicosatetraenoic acid</topic><topic>13-(S)-hydroxy-9Z,11E-octadeca-9,11-dienoyl amide</topic><topic>13-(S)-hydroxy-9Z,11E-octadeca-9,11-dienoyl ethanolamide</topic><topic>13-HODNH2</topic><topic>13-HODNHEtOH</topic><topic>9Z,12Z-octadeca-9,12-dienoyl amide</topic><topic>9Z,12Z-octadeca-9,12-dienoyl ethanolamide</topic><topic>Amidohydrolases - antagonists & inhibitors</topic><topic>Amidohydrolases - metabolism</topic><topic>Anandamide</topic><topic>Animals</topic><topic>Arachidonic Acids - metabolism</topic><topic>Binding, Competitive</topic><topic>bovine serum albumin</topic><topic>Brain - enzymology</topic><topic>BSA</topic><topic>cannabinoid binding receptor-1/2</topic><topic>Cannabinoid receptor</topic><topic>Cannabinoids - metabolism</topic><topic>CB-1/2</topic><topic>Cyclohexanols - metabolism</topic><topic>Endocannabinoids</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>FAAH</topic><topic>Fatty acid amide hydrolase</topic><topic>Hydroxylation</topic><topic>Kinetics</topic><topic>LCS</topic><topic>Linoleic Acids - metabolism</topic><topic>Linoleic Acids - pharmacology</topic><topic>Lipoxygenase</topic><topic>liquid scintillation cocktail</topic><topic>Male</topic><topic>ODNH2</topic><topic>ODNHEtOH</topic><topic>PEI</topic><topic>phenylmethylsulfonyl fluoride</topic><topic>PMSF</topic><topic>polyethylene imine</topic><topic>Polyunsaturated Alkamides</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptors, Cannabinoid</topic><topic>Receptors, Drug - metabolism</topic><topic>reversed phase high performance liquid chromatography</topic><topic>RP-HPLC</topic><topic>Substrate Specificity</topic><topic>thin layer chromatography</topic><topic>TLC</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van der Stelt, Marcelis</creatorcontrib><creatorcontrib>Paoletti, Anna Maria</creatorcontrib><creatorcontrib>Maccarrone, Mauro</creatorcontrib><creatorcontrib>Nieuwenhuizen, Willem F</creatorcontrib><creatorcontrib>Bagetta, Giacinto</creatorcontrib><creatorcontrib>Veldink, Gerrit A</creatorcontrib><creatorcontrib>Finazzi Agrò, Alessandro</creatorcontrib><creatorcontrib>Vliegenthart, Johannes F.G</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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>FEBS letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van der Stelt, Marcelis</au><au>Paoletti, Anna Maria</au><au>Maccarrone, Mauro</au><au>Nieuwenhuizen, Willem F</au><au>Bagetta, Giacinto</au><au>Veldink, Gerrit A</au><au>Finazzi Agrò, Alessandro</au><au>Vliegenthart, Johannes F.G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effect of hydroxylation of linoleoyl amides on their cannabinomimetic properties</atitle><jtitle>FEBS letters</jtitle><addtitle>FEBS Lett</addtitle><date>1997-10-06</date><risdate>1997</risdate><volume>415</volume><issue>3</issue><spage>313</spage><epage>316</epage><pages>313-316</pages><issn>0014-5793</issn><eissn>1873-3468</eissn><abstract>As yet, the physiological significance of hydroxylation of anandamide and linoleoyl amides is unknown. Therefore, we investigated whether hydroxylation of ODNHEtOH and ODNH
2 influences their binding abilities to the CB-1 receptor and whether it alters their reactivity towards a fatty acid amide hydrolase (FAAH) from rat brain. Neither the fatty acid amides nor their hydroxylated derivatives were able to displace the potent cannabinoid [
3H]CP 55.940 from the CB-1 receptor (
K
i>1 μM). Hydroxylation of ODNHEtOH resulted in a strong reduction of the maximum rate of hydrolysis by a FAAH, but the affinity of FAAH for the substrate remained of the same order of magnitude. Hydroxylation of ODNH
2 led to a decrease in the affinity of FAAH for the substrate, but its maximum rate of conversion was unaffected. Furthermore, hydroxylation of ODNHEtOH enhanced its capacity to inhibit competitively the hydrolysis of anandamide. The resulting prolonged lifetime of anandamide and other fatty acid amide derivatives may have a considerable impact on cellular signal transduction.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>9357990</pmid><doi>10.1016/S0014-5793(97)01148-4</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0014-5793 |
| ispartof | FEBS letters, 1997-10, Vol.415 (3), p.313-316 |
| issn | 0014-5793 1873-3468 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_79388087 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Wiley Free Content; Alma/SFX Local Collection |
| subjects | 12/15-HETE 12/15-hydroxyeicosatetraenoic acid 13-(S)-hydroxy-9Z,11E-octadeca-9,11-dienoyl amide 13-(S)-hydroxy-9Z,11E-octadeca-9,11-dienoyl ethanolamide 13-HODNH2 13-HODNHEtOH 9Z,12Z-octadeca-9,12-dienoyl amide 9Z,12Z-octadeca-9,12-dienoyl ethanolamide Amidohydrolases - antagonists & inhibitors Amidohydrolases - metabolism Anandamide Animals Arachidonic Acids - metabolism Binding, Competitive bovine serum albumin Brain - enzymology BSA cannabinoid binding receptor-1/2 Cannabinoid receptor Cannabinoids - metabolism CB-1/2 Cyclohexanols - metabolism Endocannabinoids Enzyme Inhibitors - pharmacology FAAH Fatty acid amide hydrolase Hydroxylation Kinetics LCS Linoleic Acids - metabolism Linoleic Acids - pharmacology Lipoxygenase liquid scintillation cocktail Male ODNH2 ODNHEtOH PEI phenylmethylsulfonyl fluoride PMSF polyethylene imine Polyunsaturated Alkamides Rats Rats, Wistar Receptors, Cannabinoid Receptors, Drug - metabolism reversed phase high performance liquid chromatography RP-HPLC Substrate Specificity thin layer chromatography TLC |
| title | The effect of hydroxylation of linoleoyl amides on their cannabinomimetic properties |
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