TY - CPAPER T1 - FLT3 ligand: A potential new immunorestorative agent? AN - 39640478; 3673986 AU - Sinha, M AU - Fry, T AU - Mackall, CL Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39640478?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=FLT3+ligand%3A+A+potential+new+immunorestorative+agent%3F&rft.au=Sinha%2C+M%3BFry%2C+T%3BMackall%2C+CL&rft.aulast=Sinha&rft.aufirst=M&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Biological Therapy, 611 East Wells Street, Milwaukee, Wisconsin, USA; phone: 414-271-2456; fax: 414-276-3349; email: info@socbiother.com; URL: www.socbiother.com. Poster Paper No. 63 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Signal and transcriptional activation of proinflammatory and proangiogenic factor expression by cancer cells as a target for biological therapy AN - 39640014; 3673908 AU - Van Waes, C Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39640014?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Signal+and+transcriptional+activation+of+proinflammatory+and+proangiogenic+factor+expression+by+cancer+cells+as+a+target+for+biological+therapy&rft.au=Van+Waes%2C+C&rft.aulast=Van+Waes&rft.aufirst=C&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Biological Therapy, 611 East Wells Street, Milwaukee, Wisconsin, USA; phone: 414-271-2456; fax: 414-276-3349; email: info@socbiother.com; URL: www.socbiother.com N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Emergence and selection of viral immune escape following antiretroviral therapy and IL-2 suspension in primary and chronic SIVmac251 infection of Rhesus macaques AN - 39621098; 3672796 AU - Nacsa, J AU - Stanton, J AU - Hel, Z AU - Kunstman, K AU - Tryniszewska, E AU - Tsai, W-P AU - Giuliani, L AU - Altman, J AU - Watkins, DI AU - Lewis, M G Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39621098?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Emergence+and+selection+of+viral+immune+escape+following+antiretroviral+therapy+and+IL-2+suspension+in+primary+and+chronic+SIVmac251+infection+of+Rhesus+macaques&rft.au=Nacsa%2C+J%3BStanton%2C+J%3BHel%2C+Z%3BKunstman%2C+K%3BTryniszewska%2C+E%3BTsai%2C+W-P%3BGiuliani%2C+L%3BAltman%2C+J%3BWatkins%2C+DI%3BLewis%2C+M+G&rft.aulast=Nacsa&rft.aufirst=J&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 520-M N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Containment of viral rebound after antiretroviral therapy suspension in macaques chronically infected with SIV following vaccination with NYVAC-SIV recombinant vaccines AN - 39619982; 3672567 AU - Tryniszewska, E AU - Lewis, M G AU - Hel, Z AU - Nacsa, J AU - Tsai, W-P AU - Stevceva, L AU - Parks, R W AU - Moniuszko, M AU - Cairns, S AU - Smith, KA Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39619982?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft.genre=dissertations+%26+theses&rft.jtitle=&rft.atitle=&rft.au=Lewis%2C+Denise&rft.aulast=Lewis&rft.aufirst=Denise&rft.date=2016-01-01&rft.volume=&rft.issue=&rft.spage=&rft.isbn=9781339647357&rft.btitle=&rft.title=Perceptions+of+School+Administrators+and+Teachers+of+Students+with+Disabilities+Regarding+Special+Education+Teacher+Attrition&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 313-W N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Viremia containment following mucosal challenge with SIVmac251 correlates with SIV-specific CTL and lymphoproliferative responses induced by a DNA-SIV and NYVAC-SIV prime/boost regimen AN - 39544456; 3673040 AU - Hel, Z AU - Nacsa, J AU - Tryniszewska, E AU - Tsai, W-P AU - Montefiori, D AU - Felber, B K AU - Pavlakis, G N AU - Tartaglia, J AU - Franchini, G Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39544456?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Sleep%3A+Journal+of+Sleep+and+Sleep+Disorders+Research&rft.atitle=A+randomized+controlled+trial+of+problem-solving+therapy+compared+to+cognitive+therapy+for+the+treatment+of+insomnia+in+adults&rft.au=Pech%2C+Melissa%3BO%E2%80%99Kearney%2C+Richard&rft.aulast=Pech&rft.aufirst=Melissa&rft.date=2013-05-01&rft.volume=36&rft.issue=5&rft.spage=739&rft.isbn=&rft.btitle=&rft.title=Sleep%3A+Journal+of+Sleep+and+Sleep+Disorders+Research&rft.issn=01618105&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 74 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Novel approach to the analysis of specificity, clonality, and frequency of HIV-specific T-cell responses reveals a mechanism for lack of escape within an immunodominant epitope AN - 39534198; 3672340 AU - Douek, D AU - Betts, M AU - Brenchley, J AU - Hill, B AU - Ambrozak, D AU - Ngai, K L AU - Casazza, J AU - Koup, R Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39534198?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Novel+approach+to+the+analysis+of+specificity%2C+clonality%2C+and+frequency+of+HIV-specific+T-cell+responses+reveals+a+mechanism+for+lack+of+escape+within+an+immunodominant+epitope&rft.au=Douek%2C+D%3BBetts%2C+M%3BBrenchley%2C+J%3BHill%2C+B%3BAmbrozak%2C+D%3BNgai%2C+K+L%3BCasazza%2C+J%3BKoup%2C+R&rft.aulast=Douek&rft.aufirst=D&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 106 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Imagery of famous faces: Effects of memory and attention revealed by fMRI AN - 39533387; 3678266 AU - Ishai, A AU - Haxby, J AU - Ungerleider, L Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39533387?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Imagery+of+famous+faces%3A+Effects+of+memory+and+attention+revealed+by+fMRI&rft.au=Ishai%2C+A%3BHaxby%2C+J%3BUngerleider%2C+L&rft.aulast=Ishai&rft.aufirst=A&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Cognitive Neuroscience Society, Center for Cognitive Neuroscience, Box 90999, Duke University, Durham, North Carolina 27708, USA; phone: 978-749-0021; fax: 978-749-0025. Poster Paper No. D113 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Dose-dependent reduction in infarct growth with citicoline treatment: Evidence of neuroprotection in human stroke? AN - 39532027; 3676623 AU - Warach, S AU - Harnett, K Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39532027?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Dose-dependent+reduction+in+infarct+growth+with+citicoline+treatment%3A+Evidence+of+neuroprotection+in+human+stroke%3F&rft.au=Warach%2C+S%3BHarnett%2C+K&rft.aulast=Warach&rft.aufirst=S&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Stroke Association, National Center, 7272 Greeenville Ave., Dallas, TX 75231, USA; phone: 1-888-4STROKE; email: strokeconference@heart.org; URL: www.strokeconference.org. Paper No. 69 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Phylogenetic aspects of the renin-angiotensin system AN - 39528049; 3682424 AU - Schneermann, J Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39528049?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Phylogenetic+aspects+of+the+renin-angiotensin+system&rft.au=Schneermann%2C+J&rft.aulast=Schneermann&rft.aufirst=J&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Gordon Research Conferences, P.O. Box 984, West Kingston, RI 02892-0984, USA; phone: 401-783-4011; fax: 401-783-7644; email: grc@grc.org; URL: www.grc.uri.edu N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Effect of maxipost on ischemic lesions in patients with acute stroke: The post-010 MRI substudy AN - 39527076; 3676845 AU - Warach, S AU - Hacke, W AU - Hsu, C AU - Luby, M AU - Sullivan, M AU - Noonan, T AU - Lin, C-Y AU - Fernandes, L AU - Brunell, R AU - Bozik, M Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39527076?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Effect+of+maxipost+on+ischemic+lesions+in+patients+with+acute+stroke%3A+The+post-010+MRI+substudy&rft.au=Warach%2C+S%3BHacke%2C+W%3BHsu%2C+C%3BLuby%2C+M%3BSullivan%2C+M%3BNoonan%2C+T%3BLin%2C+C-Y%3BFernandes%2C+L%3BBrunell%2C+R%3BBozik%2C+M&rft.aulast=Warach&rft.aufirst=S&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Stroke Association, National Center, 7272 Greeenville Ave., Dallas, TX 75231, USA; phone: 1-888-4STROKE; email: strokeconference@heart.org; URL: www.strokeconference.org. Poster Paper No. P117 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Defects in CD4+ T-cell-mediated B cell help in HIV-infected patients AN - 39524880; 3672458 AU - Moir, S AU - Ogwaro, K AU - Malaspina, A AU - Ehler, L AU - Liu, S AU - McLaughlin, M AU - Dybul, M AU - Chun, T W AU - Fauci, A S Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39524880?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Defects+in+CD4%2B+T-cell-mediated+B+cell+help+in+HIV-infected+patients&rft.au=Moir%2C+S%3BOgwaro%2C+K%3BMalaspina%2C+A%3BEhler%2C+L%3BLiu%2C+S%3BMcLaughlin%2C+M%3BDybul%2C+M%3BChun%2C+T+W%3BFauci%2C+A+S&rft.aulast=Moir&rft.aufirst=S&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 214-T N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Risk of grade IV events and death in HIV patients co-infected with Hepatitis B and/or Hepatitis C receiving HAART AN - 39524410; 3672947 AU - Reisler, R AU - Han, C AU - Burman, W AU - Tedaldi, E AU - Neaton, J Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39524410?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Risk+of+grade+IV+events+and+death+in+HIV+patients+co-infected+with+Hepatitis+B+and%2For+Hepatitis+C+receiving+HAART&rft.au=Reisler%2C+R%3BHan%2C+C%3BBurman%2C+W%3BTedaldi%2C+E%3BNeaton%2C+J&rft.aulast=Reisler&rft.aufirst=R&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 657-M N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - CCR5 promoter polymorphism P1 is associated with enhanced expression of HIV-1 entry co-receptors CCR5, CXCR4, and CCR3 on primary T cells AN - 39522664; 3672552 AU - Carrington, M AU - Perfetto, S AU - Lamoreaux, L AU - Wang, C AU - Larrimore, K AU - Ehrenberg, P AU - Michael, N Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39522664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=CCR5+promoter+polymorphism+P1+is+associated+with+enhanced+expression+of+HIV-1+entry+co-receptors+CCR5%2C+CXCR4%2C+and+CCR3+on+primary+T+cells&rft.au=Carrington%2C+M%3BPerfetto%2C+S%3BLamoreaux%2C+L%3BWang%2C+C%3BLarrimore%2C+K%3BEhrenberg%2C+P%3BMichael%2C+N&rft.aulast=Carrington&rft.aufirst=M&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 30 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Productive HIV infection of CD4+ T cells lacking markers of classic T-cell activation: The role of the lymphoid tissue microenvironment AN - 39522576; 3672518 AU - Kinter, A AU - Moorthy, A AU - Jackson, R AU - Fauci, A S Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39522576?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Productive+HIV+infection+of+CD4%2B+T+cells+lacking+markers+of+classic+T-cell+activation%3A+The+role+of+the+lymphoid+tissue+microenvironment&rft.au=Kinter%2C+A%3BMoorthy%2C+A%3BJackson%2C+R%3BFauci%2C+A+S&rft.aulast=Kinter&rft.aufirst=A&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 269-T N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Innate immune defense mechanisms involved in the control of HIV replication: Inverse correlation of HIV viremia with NK cell function AN - 39522467; 3672497 AU - Kottilil, S AU - Chun, T W AU - Moir, S AU - Liu, S AU - McLaughlin, M AU - Maldarelli, F AU - Fauci, A S Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39522467?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Innate+immune+defense+mechanisms+involved+in+the+control+of+HIV+replication%3A+Inverse+correlation+of+HIV+viremia+with+NK+cell+function&rft.au=Kottilil%2C+S%3BChun%2C+T+W%3BMoir%2C+S%3BLiu%2C+S%3BMcLaughlin%2C+M%3BMaldarelli%2C+F%3BFauci%2C+A+S&rft.aulast=Kottilil&rft.aufirst=S&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 25 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Viral CTL escape mutations do not explain HIV progression in HLA B*5701+ patients AN - 39522372; 3672477 AU - Migueles, S AU - Laborico, A AU - Imamichi, H AU - Connors, M Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39522372?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Viral+CTL+escape+mutations+do+not+explain+HIV+progression+in+HLA+B*5701%2B+patients&rft.au=Migueles%2C+S%3BLaborico%2C+A%3BImamichi%2C+H%3BConnors%2C+M&rft.aulast=Migueles&rft.aufirst=S&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 231-T N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Delayed in vivo growth of Lewis lung carcinoma cells that have been genetically engineered to secrete the kringle 5 domain of plasminogen AN - 39521952; 3673999 AU - Yazawa, H AU - Roessler, P G AU - Wiltrout, R H AU - Watanabe, M Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39521952?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:book&rft.genre=book&rft.jtitle=&rft.atitle=&rft.au=Gauthier%2C+Marni&rft.aulast=Gauthier&rft.aufirst=Marni&rft.date=2011-01-01&rft.volume=&rft.issue=&rft.spage=&rft.isbn=9780230115774&rft.btitle=Amnesia+and+Redress+in+Contemporary+American+Fiction%3A+Counterhistory&rft.title=Amnesia+and+Redress+in+Contemporary+American+Fiction%3A+Counterhistory&rft.issn=&rft_id=info:doi/10.1057%2F9780230337824 LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Biological Therapy, 611 East Wells Street, Milwaukee, Wisconsin, USA; phone: 414-271-2456; fax: 414-276-3349; email: info@socbiother.com; URL: www.socbiother.com. Poster Paper No. 76 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Involvement of HIV Vpr protein in G2/M arrest through interaction with 14-3-3 AN - 39519001; 3672379 AU - Tsopanomichalou, M AU - Kino, T AU - Gragerov, A AU - Ilyina-Gragerova, G AU - Chrousos, G P AU - Pavlakis, G N Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39519001?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Involvement+of+HIV+Vpr+protein+in+G2%2FM+arrest+through+interaction+with+14-3-3&rft.au=Tsopanomichalou%2C+M%3BKino%2C+T%3BGragerov%2C+A%3BIlyina-Gragerova%2C+G%3BChrousos%2C+G+P%3BPavlakis%2C+G+N&rft.aulast=Tsopanomichalou&rft.aufirst=M&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 141-M N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Dissociating the roles of the ventrolateral prefrontal and anterior cingulate cortex in cognitive control AN - 39513620; 3678069 AU - Dreher, J-C AU - Berman, K Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39513620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Dissociating+the+roles+of+the+ventrolateral+prefrontal+and+anterior+cingulate+cortex+in+cognitive+control&rft.au=Dreher%2C+J-C%3BBerman%2C+K&rft.aulast=Dreher&rft.aufirst=J-C&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Cognitive Neuroscience Society, Center for Cognitive Neuroscience, Box 90999, Duke University, Durham, North Carolina 27708, USA; phone: 978-749-0021; fax: 978-749-0025. Poster Paper No. C35 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Induction of MIG and IP-10 gene expression by LPS and IL-12/pulse IL-2 in kidney messangial cells can use IFN-g dependent and independent pathways AN - 39508696; 3673987 AU - Subleski, J AU - Park, J-W AU - Wallace, C AU - Wigginton, J AU - Wiltrout, R H Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39508696?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Induction+of+MIG+and+IP-10+gene+expression+by+LPS+and+IL-12%2Fpulse+IL-2+in+kidney+messangial+cells+can+use+IFN-g+dependent+and+independent+pathways&rft.au=Subleski%2C+J%3BPark%2C+J-W%3BWallace%2C+C%3BWigginton%2C+J%3BWiltrout%2C+R+H&rft.aulast=Subleski&rft.aufirst=J&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Biological Therapy, 611 East Wells Street, Milwaukee, Wisconsin, USA; phone: 414-271-2456; fax: 414-276-3349; email: info@socbiother.com; URL: www.socbiother.com. Poster Paper No. 64 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Incidence of grade IV events, AIDS, and mortality in a large multicenter cohort receiving HAART AN - 39508591; 3672618 AU - Reisler, R AU - Han, C AU - Burman, W AU - Tedaldi, E AU - Neaton, J Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39508591?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Incidence+of+grade+IV+events%2C+AIDS%2C+and+mortality+in+a+large+multicenter+cohort+receiving+HAART&rft.au=Reisler%2C+R%3BHan%2C+C%3BBurman%2C+W%3BTedaldi%2C+E%3BNeaton%2C+J&rft.aulast=Reisler&rft.aufirst=R&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 36 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Poly(ADP-ribose) polymerase role in the repair of topoisomerase L - Induced DNA damage AN - 39508542; 3673928 AU - Barcelo, J M AU - Kholhagen, G AU - Van Hattum, A AU - Simbulan-Rosenthal, C M AU - Smulson, ME AU - Pommier, Y Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39508542?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Poly%28ADP-ribose%29+polymerase+role+in+the+repair+of+topoisomerase+L+-+Induced+DNA+damage&rft.au=Barcelo%2C+J+M%3BKholhagen%2C+G%3BVan+Hattum%2C+A%3BSimbulan-Rosenthal%2C+C+M%3BSmulson%2C+ME%3BPommier%2C+Y&rft.aulast=Barcelo&rft.aufirst=J&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Biological Therapy, 611 East Wells Street, Milwaukee, Wisconsin, USA; phone: 414-271-2456; fax: 414-276-3349; email: info@socbiother.com; URL: www.socbiother.com. Poster Paper No. 3 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Reversible parenchymal injury associated with clinical recovery following standard intravenous rt-PA therapy AN - 39507976; 3676739 AU - Warach, S AU - Chalela, J AU - Ezzeddine, M AU - Baird, A AU - Luby, M AU - Latour, L Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39507976?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Reversible+parenchymal+injury+associated+with+clinical+recovery+following+standard+intravenous+rt-PA+therapy&rft.au=Warach%2C+S%3BChalela%2C+J%3BEzzeddine%2C+M%3BBaird%2C+A%3BLuby%2C+M%3BLatour%2C+L&rft.aulast=Warach&rft.aufirst=S&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Stroke Association, National Center, 7272 Greeenville Ave., Dallas, TX 75231, USA; phone: 1-888-4STROKE; email: strokeconference@heart.org; URL: www.strokeconference.org. Poster Paper No. P10 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Frequency of HIV-specific CD8+ T cells is not a predictor of the breadth of the HIV-specific CD8+ T-cell response AN - 39505382; 3672462 AU - Betts, M AU - Ambrozak, D AU - Brenchley, J AU - Douek, D AU - Koup, R Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39505382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Frequency+of+HIV-specific+CD8%2B+T+cells+is+not+a+predictor+of+the+breadth+of+the+HIV-specific+CD8%2B+T-cell+response&rft.au=Betts%2C+M%3BAmbrozak%2C+D%3BBrenchley%2C+J%3BDouek%2C+D%3BKoup%2C+R&rft.aulast=Betts&rft.aufirst=M&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 218-T N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - HIV preferentially infects HIV-specific CD4 T cells AN - 39503968; 3673162 AU - Douek, D AU - Brenchley, J AU - Betts, M AU - Ambrozak, D AU - Hill, B AU - Okamoto, Y AU - Casazza, J AU - Kuruppu, J AU - Kunstman, K AU - Dybul, M Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39503968?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=HIV+preferentially+infects+HIV-specific+CD4+T+cells&rft.au=Douek%2C+D%3BBrenchley%2C+J%3BBetts%2C+M%3BAmbrozak%2C+D%3BHill%2C+B%3BOkamoto%2C+Y%3BCasazza%2C+J%3BKuruppu%2C+J%3BKunstman%2C+K%3BDybul%2C+M&rft.aulast=Douek&rft.aufirst=D&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. LB7 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Parallel visual motion processing streams in lateral temporal cortex for manipulable objects and human movements AN - 39497923; 3678140 AU - Beauchamp, M AU - Lee, K AU - Haxby, J AU - Martin, A Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39497923?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Parallel+visual+motion+processing+streams+in+lateral+temporal+cortex+for+manipulable+objects+and+human+movements&rft.au=Beauchamp%2C+M%3BLee%2C+K%3BHaxby%2C+J%3BMartin%2C+A&rft.aulast=Beauchamp&rft.aufirst=M&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Cognitive Neuroscience Society, Center for Cognitive Neuroscience, Box 90999, Duke University, Durham, North Carolina 27708, USA; phone: 978-749-0021; fax: 978-749-0025. Poster Paper No. C106 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Initial CD4+ T-cell counts in patients with newly diagnosed HIV infection indicate that a substantial proportion of these patients have advanced disease regardless of gender, race, or socio-economic status AN - 39495432; 3672745 AU - Dybul, M AU - Bolan, R AU - Condoluci, D AU - Cox-Iyamu, R AU - Redfield, R AU - Hallahan, C AU - Sathasivam, K AU - Folino, M AU - Weisberg, M AU - Andrews, M Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39495432?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Initial+CD4%2B+T-cell+counts+in+patients+with+newly+diagnosed+HIV+infection+indicate+that+a+substantial+proportion+of+these+patients+have+advanced+disease+regardless+of+gender%2C+race%2C+or+socio-economic+status&rft.au=Dybul%2C+M%3BBolan%2C+R%3BCondoluci%2C+D%3BCox-Iyamu%2C+R%3BRedfield%2C+R%3BHallahan%2C+C%3BSathasivam%2C+K%3BFolino%2C+M%3BWeisberg%2C+M%3BAndrews%2C+M&rft.aulast=Dybul&rft.aufirst=M&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 475-M N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Molecular and functional characterization of Tg.AC zeta-globin promoter AN - 39479115; 3678525 AU - Humble, M AU - Faircloth, R AU - Tennant, R AU - Cannon, R Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 4300:Environmental Science KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39479115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Molecular+and+functional+characterization+of+Tg.AC+zeta-globin+promoter&rft.au=Humble%2C+M%3BFaircloth%2C+R%3BTennant%2C+R%3BCannon%2C+R&rft.aulast=Humble&rft.aufirst=M&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: The Society of Toxicology, 1767 Business Center Drive, Suite 302, Resont, VA 20190-5332, USA; URL: www.toxicology.org. Paper No. LB12 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Accumulation of DC-SIGN+ CD40+ dendritic cells with reduced CD80 and CD86 expression in lymphoid tissue during acute HIV-1 infection AN - 39471303; 3673139 AU - Lore, K AU - Sonnerborg, A AU - Brostrom, C AU - Goh, L AU - Perrin, L AU - McDade, H AU - Stellbrink, HJ AU - Gazzard, B AU - Weber, R AU - Napolitano, LA Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39471303?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Accumulation+of+DC-SIGN%2B+CD40%2B+dendritic+cells+with+reduced+CD80+and+CD86+expression+in+lymphoid+tissue+during+acute+HIV-1+infection&rft.au=Lore%2C+K%3BSonnerborg%2C+A%3BBrostrom%2C+C%3BGoh%2C+L%3BPerrin%2C+L%3BMcDade%2C+H%3BStellbrink%2C+HJ%3BGazzard%2C+B%3BWeber%2C+R%3BNapolitano%2C+LA&rft.aulast=Lore&rft.aufirst=K&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 99 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Molecular epidemiology of HIV-1 circulating recombinant forms CRF01_AE and CRF08_BC in Guangxi province, China AN - 39471193; 3673064 AU - Laeyendecker, O AU - Yu, X F AU - Zhang, G W AU - Garten, R AU - Lai, S AU - Liu, W AU - Chen, J AU - Zhang, C AU - Quinn, T Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39471193?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Molecular+epidemiology+of+HIV-1+circulating+recombinant+forms+CRF01_AE+and+CRF08_BC+in+Guangxi+province%2C+China&rft.au=Laeyendecker%2C+O%3BYu%2C+X+F%3BZhang%2C+G+W%3BGarten%2C+R%3BLai%2C+S%3BLiu%2C+W%3BChen%2C+J%3BZhang%2C+C%3BQuinn%2C+T&rft.aulast=Laeyendecker&rft.aufirst=O&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 761-W N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - IFN-g responsiveness of mouse renal cell carcinoma cells contributes to host-mediated antimetastatic effects AN - 39460725; 3673985 AU - Shorts, L H AU - Gruys, ME AU - Back, T C AU - Wigginton, J M AU - Subleski, J AU - Wiltrout, R H Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39460725?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=IFN-g+responsiveness+of+mouse+renal+cell+carcinoma+cells+contributes+to+host-mediated+antimetastatic+effects&rft.au=Shorts%2C+L+H%3BGruys%2C+ME%3BBack%2C+T+C%3BWigginton%2C+J+M%3BSubleski%2C+J%3BWiltrout%2C+R+H&rft.aulast=Shorts&rft.aufirst=L&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Biological Therapy, 611 East Wells Street, Milwaukee, Wisconsin, USA; phone: 414-271-2456; fax: 414-276-3349; email: info@socbiother.com; URL: www.socbiother.com. Poster Paper No. 62 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Acute and long-term regulation of synaptic transmission and plasticity by neurotrophins AN - 39457534; 3678691 AU - Lu, B Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39457534?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Acute+and+long-term+regulation+of+synaptic+transmission+and+plasticity+by+neurotrophins&rft.au=Lu%2C+B&rft.aulast=Lu&rft.aufirst=B&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Elsevier Science Ltd., Pergamon, P.O. Box 800, Kidlington, Oxford OX5 1DX, UK; URL: www.elsevier.nl. Paper No. S3.3 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Predictive validity of MRI as a surrogate end point in stroke trials: Change in lesion volume predicts clinical outcome AN - 39456244; 3676634 AU - Warach, S AU - Harnett, K Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39456244?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Predictive+validity+of+MRI+as+a+surrogate+end+point+in+stroke+trials%3A+Change+in+lesion+volume+predicts+clinical+outcome&rft.au=Warach%2C+S%3BHarnett%2C+K&rft.aulast=Warach&rft.aufirst=S&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Stroke Association, National Center, 7272 Greeenville Ave., Dallas, TX 75231, USA; phone: 1-888-4STROKE; email: strokeconference@heart.org; URL: www.strokeconference.org. Paper No. 80 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Increased T-cell turnover with HIV infection correlates strongly with immune activation and does not normalize after 52 weeks of HAART AN - 39450439; 3672755 AU - Anthony, K AU - Sereti, I AU - Herpin, B AU - Metcalf, JA AU - Lane, H C AU - Polis, MA Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39450439?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Increased+T-cell+turnover+with+HIV+infection+correlates+strongly+with+immune+activation+and+does+not+normalize+after+52+weeks+of+HAART&rft.au=Anthony%2C+K%3BSereti%2C+I%3BHerpin%2C+B%3BMetcalf%2C+JA%3BLane%2C+H+C%3BPolis%2C+MA&rft.aulast=Anthony&rft.aufirst=K&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 484-M N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Replicative senescence of HIV-specific CD8+ T cells defined by CD57 AN - 39450144; 3672461 AU - Brenchley, J AU - Ambrozak, D AU - Karandikar, N AU - Betts, M AU - Kuruppu, J AU - Douek, D AU - Koup, R Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39450144?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Replicative+senescence+of+HIV-specific+CD8%2B+T+cells+defined+by+CD57&rft.au=Brenchley%2C+J%3BAmbrozak%2C+D%3BKarandikar%2C+N%3BBetts%2C+M%3BKuruppu%2C+J%3BDouek%2C+D%3BKoup%2C+R&rft.aulast=Brenchley&rft.aufirst=J&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 217-T N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Complete supression of proliferation despite persistence of virus specific CD4+ T cells during HIV viremia AN - 39450103; 3672460 AU - Iyasere, CA AU - Tilton, J C AU - Migueles, S AU - Laborico, A AU - Connors, M Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39450103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Complete+supression+of+proliferation+despite+persistence+of+virus+specific+CD4%2B+T+cells+during+HIV+viremia&rft.au=Iyasere%2C+CA%3BTilton%2C+J+C%3BMigueles%2C+S%3BLaborico%2C+A%3BConnors%2C+M&rft.aulast=Iyasere&rft.aufirst=CA&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 216-T N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Rev-independent SIV as model to study pathogenic mechanisms in neonatal and juvenile rhesus macaques AN - 39449779; 3672589 AU - Von Gegerfelt, A AU - Liska, V AU - Marthas, M AU - McClure, H AU - Montefiori, D AU - Li, P AU - Markham, P AU - Miller, N AU - Ruprecht, R AU - Felber, B K Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39449779?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Rev-independent+SIV+as+model+to+study+pathogenic+mechanisms+in+neonatal+and+juvenile+rhesus+macaques&rft.au=Von+Gegerfelt%2C+A%3BLiska%2C+V%3BMarthas%2C+M%3BMcClure%2C+H%3BMontefiori%2C+D%3BLi%2C+P%3BMarkham%2C+P%3BMiller%2C+N%3BRuprecht%2C+R%3BFelber%2C+B+K&rft.aulast=Von+Gegerfelt&rft.aufirst=A&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 333-W N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Nonmonotonic coherence tuning of bold fMRI signal to random dot kinematograms in human area MT AN - 39439694; 3678504 AU - Heekeren, H AU - Marrett, S AU - Bandettini, P AU - Ungerleider, L Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39439694?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+chemistry&rft.atitle=DNA+binding+properties+of+the+yeast+Msh2-Msh6+and+Mlh1-Pms1+heterodimers.&rft.au=Drotschmann%2C+Karin%3BHall%2C+Mark+C%3BShcherbakova%2C+Polina+V%3BWang%2C+Hong%3BErie%2C+Dorothy+A%3BBrownewell%2C+Floyd+R%3BKool%2C+Eric+T%3BKunkel%2C+Thomas+A&rft.aulast=Drotschmann&rft.aufirst=Karin&rft.date=2002-06-01&rft.volume=383&rft.issue=6&rft.spage=969&rft.isbn=&rft.btitle=&rft.title=Biological+chemistry&rft.issn=14316730&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Cognitive Neuroscience Society, Center for Cognitive Neuroscience, Box 90999, Duke University, Durham, North Carolina 27708, USA; phone: 978-749-0021; fax: 978-749-0025. Poster Paper No. F113 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - CD8+ T cells in the murine renal cancer renca: Cytotoxic activity and anti-tumor effects in vivo AN - 39433499; 3673983 AU - Seki, N AU - Brooks, AD AU - Mason, A T AU - Wine, J W AU - Back, T C AU - Parsoneault, E M AU - Wiltrout, R H AU - Sayers, T J Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39433499?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=CD8%2B+T+cells+in+the+murine+renal+cancer+renca%3A+Cytotoxic+activity+and+anti-tumor+effects+in+vivo&rft.au=Seki%2C+N%3BBrooks%2C+AD%3BMason%2C+A+T%3BWine%2C+J+W%3BBack%2C+T+C%3BParsoneault%2C+E+M%3BWiltrout%2C+R+H%3BSayers%2C+T+J&rft.aulast=Seki&rft.aufirst=N&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Biological Therapy, 611 East Wells Street, Milwaukee, Wisconsin, USA; phone: 414-271-2456; fax: 414-276-3349; email: info@socbiother.com; URL: www.socbiother.com. Poster Paper No. 60 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Randomized, controlled trial of pegylated interferon alpha-2a with ribavirin vs. interferon alpha-2a with ribavirin for the treatment of chronic HCV in HIV co-infection: ACTG A5071 AN - 39425609; 3673155 AU - Chung, R AU - Andersen, J AU - Alston, B AU - Vallee, M AU - Robbins, G AU - Nevin, T AU - Colquhoun, D AU - Sherman, K AU - Peters, M AU - Harb, G Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39425609?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Randomized%2C+controlled+trial+of+pegylated+interferon+alpha-2a+with+ribavirin+vs.+interferon+alpha-2a+with+ribavirin+for+the+treatment+of+chronic+HCV+in+HIV+co-infection%3A+ACTG+A5071&rft.au=Chung%2C+R%3BAndersen%2C+J%3BAlston%2C+B%3BVallee%2C+M%3BRobbins%2C+G%3BNevin%2C+T%3BColquhoun%2C+D%3BSherman%2C+K%3BPeters%2C+M%3BHarb%2C+G&rft.aulast=Chung&rft.aufirst=R&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. LB15 N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - Kinematic strategies for hyoid movement in rapid sequential swallowing. AN - 85372528; pmid-12068999 AB - Past videofluoroscopic and EMG evidence has shown that rapid sequential swallowing differs from discrete swallows, but our knowledge of the control strategies remains incomplete. This study examined in detail the interrelationships among kinematic variables to discern the strategies for deglutitive hyoid motion during discrete (5 cc, 10 cc, 20 cc, 30 cc) and rapid sequential (120 cc) swallowing tasks. Submental ultrasound was conducted with head and transducer stabilization on 30 healthy subjects (15 males, 15 females) in three age groups (20-39, 40-59, 60-79 yrs). Frame-by-frame changes in hyoid position were tracked from digitized images of 236 discrete and 318 rapid sequential swallows. Repeated-measures analyses of variance were conducted on a number of kinematic variables with corrections for multiple tests and comparisons. The main effect of task was significant for all variables except forward peak velocity. Per post hoc contrasts, rapid sequential swallows had significantly reduced maximal amplitude (maximal displacement), total distance, backward peak velocity, at-max and total durations, and time to backward peak velocity in comparison with discrete swallows of any volume. Amplitude "down-scaling" was the prominent kinematic strategy used to accomplish rapid sequential swallows in a shorter time while keeping forward peak velocity essentially unchanged. In contrast, amplitude "up-scaling" was the strategy for accommodating larger-volume discrete swallows. Our results confirm built-in flexibility in the functional range of deglutitive hyoid motion. JF - Journal of speech, language, and hearing research : JSLHR AU - Chi-Fishman, Gloria AU - Sonies, Barbara C AD - Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. gcf@nih.gov Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 457 EP - 468 VL - 45 IS - 3 SN - 1092-4388, 1092-4388 KW - Index Medicus KW - National Library of Medicine KW - Adult KW - Age Factors KW - Aged KW - Biomechanics KW - *Deglutition: physiology KW - Female KW - Humans KW - *Hyoid Bone: physiology KW - Hyoid Bone: ultrasonography KW - Male KW - Middle Aged KW - *Movement: physiology KW - Sex Factors KW - Time Factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85372528?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+speech%2C+language%2C+and+hearing+research+%3A+JSLHR&rft.atitle=Kinematic+strategies+for+hyoid+movement+in+rapid+sequential+swallowing.&rft.au=Chi-Fishman%2C+Gloria%3BSonies%2C+Barbara+C&rft.aulast=Chi-Fishman&rft.aufirst=Gloria&rft.date=2002-06-01&rft.volume=45&rft.issue=3&rft.spage=457&rft.isbn=&rft.btitle=&rft.title=Journal+of+speech%2C+language%2C+and+hearing+research+%3A+JSLHR&rft.issn=10924388&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Design of a SENSE-optimized high-sensitivity MRI receive coil for brain imaging. AN - 85272067; pmid-12111969 AB - An 8-channel receive-only detector array was developed for SENSE MRI of human brain. The coil geometry was based on a gapped element design and used ultra-high impedance preamplifiers for mutual decoupling of the elements. Computer simulations of the electric and magnetic fields showed that excellent signal-to-noise ratio (SNR) and SENSE performance could be achieved by placing the coil elements close to the head and maintaining a substantial gap between the elements. Measurements with a 1.5 T prototype coil showed a 2.7-fold improvement of the SNR averaged over the brain compared to a conventional quadrature birdcage receive coil and an average geometrical noise amplification factor (g-value) of 1.06 and 1.38 for rate-2 and rate-3 SENSE, respectively. JF - Magnetic Resonance in Medicine AU - de Zwart Jacco A AU - Ledden, Patrick J AU - Kellman, Peter AU - van Gelderen Peter AU - Duyn, Jeff H AD - Advanced MRI, Laboratory of Functional and Molecular Imaging, NINDS, National Institutes of Health, Bethesda, Maryland 20892-1065, USA. PY - 2002 SP - 1218 EP - 1227 VL - 47 IS - 6 SN - 0740-3194, 0740-3194 KW - Magnetic Resonance Imaging KW - Computer Simulation KW - Human KW - Brain KW - Image Processing, Computer-Assisted UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85272067?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+Resonance+in+Medicine&rft.atitle=Design+of+a+SENSE-optimized+high-sensitivity+MRI+receive+coil+for+brain+imaging.&rft.au=de+Zwart+Jacco+A%3BLedden%2C+Patrick+J%3BKellman%2C+Peter%3Bvan+Gelderen+Peter%3BDuyn%2C+Jeff+H&rft.aulast=de+Zwart+Jacco+A&rft.aufirst=&rft.date=2002-06-01&rft.volume=47&rft.issue=6&rft.spage=1218&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Antibody Penetration into a Spherical Prevascular Tumor Nodule Embedded in Normal Tissue AN - 831170892; 13866495 AB - A finite-element (FE) method is used to numerically solve a pharmacokinetic model that describes the uptake of systemically administered antibody (mAb) in a prevascular spherical tumor nodule embedded in normal tissue. The model incorporates plasma kinetics, transcapillary transport, lymphatic clearance, interstitial diffusion in both the normal tissue and tumor, and binding reactions. We use results from the FE analysis to assess previous predictions that employed either a Dirichlet boundary condition (b.c.), or an approximate, composite (Dirichlet and Neumann) b.c. at the tumor surface. We find that the Dirichlet b.c. significantly overpredicted the mean total tumor mAb concentration. In contrast, the composite b.c. yielded good agreement with FE predictions, except at early times. We also used the FE model to investigate the influence of the approximately 30-fold difference in the values of mAb diffusion coefficient measured by Clauss and Jain (Cancer Res. 50:3487-3492, 1990) and Berk [et_al.] (Proc. Natl. Acad. Sci. U.S.A. 94:1785-1790, 1997). For low diffusivity, diffusional resistance slows both mAb uptake by and efflux from the tumor. For high diffusivity at the same mAb dose, more rapid uptake produces earlier and higher peak mAb levels in the tumor, while the efflux rate is limited by the dissociation of the mAb-tumor antigen complex. The differences in spatial and temporal variation in mAb concentration between low and high diffusivities are of sufficient magnitude to be experimentally observable, particularly at short times after antibody administration. [copy 2002 Biomedical Engineering Society. PAC2002: 8715Vv, 8710+e, 8719Xx JF - Annals of Biomedical Engineering AU - Banerjee, Rupak K AU - Sung, Cynthia AU - Bungay, Peter M AU - Dedrick, Robert L AU - van Osdol, William W AD - Drug Delivery and Kinetics Resource, Division of Bioengineering and Physical Science, Office of Research Services, National Institutes of Health, Bethesda, MD Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 828 EP - 839 PB - Springer-Verlag, Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 30 IS - 6 SN - 0090-6964, 0090-6964 KW - Biotechnology and Bioengineering Abstracts KW - Mathematical models KW - Monoclonal antibodies KW - Temporal variations KW - Kinetics KW - Boundaries KW - Tumors KW - Diffusion coefficient KW - Nodules KW - Cancer KW - Pharmacokinetics KW - Models KW - W 30940:Products UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/831170892?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+Biomedical+Engineering&rft.atitle=Antibody+Penetration+into+a+Spherical+Prevascular+Tumor+Nodule+Embedded+in+Normal+Tissue&rft.au=Banerjee%2C+Rupak+K%3BSung%2C+Cynthia%3BBungay%2C+Peter+M%3BDedrick%2C+Robert+L%3Bvan+Osdol%2C+William+W&rft.aulast=Banerjee&rft.aufirst=Rupak&rft.date=2002-06-01&rft.volume=30&rft.issue=6&rft.spage=828&rft.isbn=&rft.btitle=&rft.title=Annals+of+Biomedical+Engineering&rft.issn=00906964&rft_id=info:doi/10.1114%2F1.1496087 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-03-01 N1 - Last updated - 2015-03-19 N1 - SubjectsTermNotLitGenreText - Mathematical models; Temporal variations; Monoclonal antibodies; Kinetics; Boundaries; Diffusion coefficient; Tumors; Pharmacokinetics; Cancer; Nodules; Models DO - http://dx.doi.org/10.1114/1.1496087 ER - TY - JOUR T1 - Bone formation by human postnatal bone marrow stromal stem cells is enhanced by telomerase expression AN - 762280305; 13744554 AB - Human postnatal bone marrow stromal stem cells (BMSSCs) have a limited life-span and progressively lose their stem cell properties during ex vivo expansion. Here we report that ectopic expression of human telomerase reverse transcriptase (hTERT) in BMSSCs extended their life-span and maintained their osteogenic potential. In xenogenic transplants, hTERT-expressing BMSSCs (BMSSC-Ts) generated more bone tissue, with a mineralized lamellar bone structure and associated marrow, than did control BMSSCs. The enhanced bone-forming ability of BMSSC-Ts was correlated with a higher and sustained expression of the early pre-osteogenic stem cell marker STRO-1, indicating that telomerase expression helped to maintain the osteogenic stem cell pool during ex vivo expansion. These results show that telomerase expression can overcome critical technical barriers to the ex vivo expansion of BMSSCs, and suggest that telomerase therapy may be a useful strategy for bone regeneration and repair. JF - Nature Biotechnology AU - Shi, Songtao AU - Gronthos, Stan AU - Chen, Shaoqiong AU - Reddi, Anand AU - Counter, Christopher M AU - Robey, Pamela G AU - Wang, Cun-Yu AD - [1] Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892. [2] These authors contributed equally to this work. Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 587 EP - 591 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 20 IS - 6 SN - 1087-0156, 1087-0156 KW - Biochemistry Abstracts 2: Nucleic Acids; Calcium & Calcified Tissue Abstracts; Biotechnology and Bioengineering Abstracts KW - Bone healing KW - Stem cells KW - Regeneration KW - Bone marrow KW - Bone growth KW - telomerase reverse transcriptase KW - Bone (lamellar) KW - Osteogenesis KW - N 14820:DNA Metabolism & Structure KW - W 30920:Tissue Engineering KW - T 2040:Ectopic Calcification and Ossification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/762280305?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Adenomatous+polyp+recurrence+and+physical+activity+in+the+Polyp+Prevention+Trial+%28United+States%29&rft.au=Colbert%2C+L+H%3BLanza%2C+E%3BBallard-Barbash%2C+R%3BSlattery%2C+M+L%3BTangrea%2C+JA%3BCaan%2C+B%3BPaskett%2C+ED%3BIber%2C+F%3BKikendall%2C+W%3BLance%2C+P%3BShike%2C+M%3BSchoen%2C+R+E%3BDaston%2C+C%3BSchatzkin%2C+A&rft.aulast=Colbert&rft.aufirst=L&rft.date=2002-06-01&rft.volume=13&rft.issue=5&rft.spage=445&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Bone healing; Stem cells; Regeneration; Bone growth; Bone marrow; telomerase reverse transcriptase; Bone (lamellar); Osteogenesis DO - http://dx.doi.org/10.1038/nbt0602-587 ER - TY - JOUR T1 - DNA binding properties of the yeast Msh2-Msh6 and Mlh1-Pms1 heterodimers. AN - 72075141; 12222686 AB - We describe here our recent studies of the DNA binding properties of Msh2-Msh6 and Mlh1-Pms1, two protein complexes required to repair mismatches generated during DNA replication. Mismatched DNA binding by Msh2-Msh6 was probed by mutagenesis based on the crystal structure of the homologous bacterial MutS homodimer bound to DNA. The results suggest that several amino acid side chains inferred to interact with the DNA backbone near the mismatch are critical for repair activity. These contacts, which are different in Msh2 and Msh6, likely facilitate stacking and hydrogen bonding interactions between side chains in Msh6 and the mismatched base, thus stabilizing a kinked DNA conformation that permits subsequent repair steps coordinated by the Mlh1-Pms1 heterodimer. Mlh1-Pms1 also binds to DNA, but independently of a mismatch. Mlh1-Pms1 binds short DNA substrates with low affinity and with a slight preference for single-stranded DNA. It also binds longer duplex DNA molecules, but with a higher affinity indicative of cooperative binding. Indeed, imaging by atomic force microscopy reveals cooperative DNA binding and simultaneous interaction with two DNA duplexes. The novel DNA binding properties of Mlh1-Pms1 may be relevant to signal transduction during DNA mismatch repair and to recombination, meiosis and cellular responses to DNA damage. JF - Biological chemistry AU - Drotschmann, Karin AU - Hall, Mark C AU - Shcherbakova, Polina V AU - Wang, Hong AU - Erie, Dorothy A AU - Brownewell, Floyd R AU - Kool, Eric T AU - Kunkel, Thomas A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2002/06// PY - 2002 DA - June 2002 SP - 969 EP - 975 VL - 383 IS - 6 SN - 1431-6730, 1431-6730 KW - Carrier Proteins KW - 0 KW - DNA-Binding Proteins KW - Fungal Proteins KW - MSH6 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - DNA KW - 9007-49-2 KW - MSH2 protein, S cerevisiae KW - EC 3.6.1.3 KW - MutS Homolog 2 Protein KW - Index Medicus KW - Models, Molecular KW - Molecular Conformation KW - Saccharomyces cerevisiae Proteins -- metabolism KW - Fungal Proteins -- metabolism KW - Carrier Proteins -- metabolism KW - DNA -- metabolism KW - Base Pair Mismatch -- genetics KW - Yeasts -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72075141?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+nursing&rft.atitle=The+role+of+the+nurse+in+cancer+genetics.&rft.au=Middelton%2C+Lindsay%3BDimond%2C+Eileen%3BCalzone%2C+Kathleen%3BDavis%2C+Joie%3BJenkins%2C+Jean&rft.aulast=Middelton&rft.aufirst=Lindsay&rft.date=2002-06-01&rft.volume=25&rft.issue=3&rft.spage=196&rft.isbn=&rft.btitle=&rft.title=Cancer+nursing&rft.issn=0162220X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-11 N1 - Date created - 2002-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tyrosine phosphatase CD45 regulates hydrogen peroxide-induced calcium mobilization in B cells. AN - 72066659; 12215216 AB - By taking advantage of established CD45-deficient DT40 cells, the roles of CD45 in oxidative stress signaling were investigated. Using p-nitrophenyl phosphate as substrate, it was found that CD45 constituted nearly 40% of the total protein-tyrosine phosphatase activity. Almost 90% of the phosphatase activity was rapidly inactivated upon hydrogen peroxide treatment. Hydrogen peroxide-induced tyrosine phosphorylation of cellular proteins and c-Jun N-terminal kinase activation were markedly enhanced in CD45-deficient cells relative to that in its parental cells. In comparison, hydrogen peroxide-induced inositol 1,4,5-trisphosphate production and Ca(2+) mobilization were impaired in CD45-deficient DT40 cells. However, hydrogen peroxide-induced tyrosine phosphorylation of phospholipase Cgamma2 (PLCgamma2), phosphatidylinositol 3-kinase activity precipitated by anti-phosphotyrosine antibody, and activation of Bruton's tyrosine kinase appeared intact in CD45-deficient DT40 cells. This suggests that CD45 mediates the ability of hydrogen peroxide-activated PLCgamma2 to hydrolyze its substrate via a mechanism independent of both tyrosine phosphorylation of PLCgamma2 and phosphatidylinositol 3-kinase, as well as activation of Bruton's tyrosine kinase. Taken together, our observations demonstrated that, in addition to its negative regulatory or phosphatase activity, CD45 has a positive role in oxidative stress signaling. JF - Antioxidants & redox signaling AU - Qin, Suofu AU - Chock, P Boon AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-8012, USA. Y1 - 2002/06// PY - 2002 DA - June 2002 SP - 481 EP - 490 VL - 4 IS - 3 SN - 1523-0864, 1523-0864 KW - Androstadienes KW - 0 KW - Isoenzymes KW - Oxidants KW - Tyrosine KW - 42HK56048U KW - Inositol 1,4,5-Trisphosphate KW - 85166-31-0 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Agammaglobulinaemia tyrosine kinase KW - EC 2.7.10.1 KW - Protein-Tyrosine Kinases KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - Antigens, CD45 KW - EC 3.1.3.48 KW - Type C Phospholipases KW - EC 3.1.4.- KW - Phospholipase C gamma KW - EC 3.1.4.3 KW - Calcium KW - SY7Q814VUP KW - wortmannin KW - XVA4O219QW KW - Index Medicus KW - Animals KW - Androstadienes -- metabolism KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Enzyme Activation KW - Mitogen-Activated Protein Kinases -- metabolism KW - Protein-Tyrosine Kinases -- metabolism KW - Isoenzymes -- metabolism KW - Type C Phospholipases -- metabolism KW - Inositol 1,4,5-Trisphosphate -- metabolism KW - Chickens KW - Phosphorylation KW - Oxidative Stress KW - Tyrosine -- metabolism KW - Cell Line KW - Phosphatidylinositol 3-Kinases -- antagonists & inhibitors KW - Calcium -- metabolism KW - B-Lymphocytes -- drug effects KW - Oxidants -- pharmacology KW - Calcium Signaling -- physiology KW - Antigens, CD45 -- genetics KW - Hydrogen Peroxide -- pharmacology KW - B-Lymphocytes -- metabolism KW - B-Lymphocytes -- enzymology KW - Antigens, CD45 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72066659?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antioxidants+%26+redox+signaling&rft.atitle=Tyrosine+phosphatase+CD45+regulates+hydrogen+peroxide-induced+calcium+mobilization+in+B+cells.&rft.au=Qin%2C+Suofu%3BChock%2C+P+Boon&rft.aulast=Qin&rft.aufirst=Suofu&rft.date=2002-06-01&rft.volume=4&rft.issue=3&rft.spage=481&rft.isbn=&rft.btitle=&rft.title=Antioxidants+%26+redox+signaling&rft.issn=15230864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-27 N1 - Date created - 2002-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The use of methadone for cancer pain. AN - 71993181; 12170567 AB - Methadone is not a new analgesic drug [69]. Several studies have demonstrated that methadone is a valid alternative to morphine, hydromorphone, and fentanyl for the treatment of cancer-related pain, and extensive reviews on the subject have been published in recent years [10,23,25,64,70,71]. Most people involved in pain therapy, however, are not well informed about the properties of methadone. The authors believe that the low cost of methadone paradoxically contributes to the limited knowledge of its characteristics and to the restricted therapeutic use of this drug. The low cost of methadone means there is little financial incentive for pharmaceutical companies to invest in research or to disseminate scientific information. Unfortunately, the lack of scientific information from pharmaceutical companies frequently results in a lack of knowledge on the part of physicians. Unless the existing approach changes, both culturally and politically, ignorance about methadone will persist among medical experts. The low cost of methadone, rather than being an advantage, will result in the limited exploitation of an effective drug. JF - Hematology/oncology clinics of North America AU - Ripamonti, Carla AU - Bianchi, Mauro AD - Rehabilitation and Palliative Care Operative Unit, National Cancer Institute, Via Venezian, 1-20133 Milan, Italy. ripamonti@istitutotumori.mi.it Y1 - 2002/06// PY - 2002 DA - June 2002 SP - 543 EP - 555 VL - 16 IS - 3 SN - 0889-8588, 0889-8588 KW - Analgesics, Opioid KW - 0 KW - Morphine KW - 76I7G6D29C KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Drug Administration Schedule KW - Drug Interactions KW - Attitude of Health Personnel KW - Dose-Response Relationship, Drug KW - Humans KW - Information Dissemination KW - Metabolic Clearance Rate KW - Child KW - Patient Selection KW - Palliative Care -- methods KW - Morphine -- pharmacology KW - Biological Availability KW - Drug Costs KW - Drug Industry -- economics KW - Morphine -- therapeutic use KW - Treatment Outcome KW - Drug Information Services KW - Health Knowledge, Attitudes, Practice KW - Clinical Protocols KW - Pain -- etiology KW - Pain -- drug therapy KW - Analgesics, Opioid -- economics KW - Analgesics, Opioid -- chemistry KW - Neoplasms -- complications KW - Methadone -- therapeutic use KW - Analgesics, Opioid -- pharmacology KW - Methadone -- chemistry KW - Methadone -- economics KW - Analgesics, Opioid -- therapeutic use KW - Pain -- diagnosis KW - Methadone -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71993181?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hematology%2Foncology+clinics+of+North+America&rft.atitle=The+use+of+methadone+for+cancer+pain.&rft.au=Ripamonti%2C+Carla%3BBianchi%2C+Mauro&rft.aulast=Ripamonti&rft.aufirst=Carla&rft.date=2002-06-01&rft.volume=16&rft.issue=3&rft.spage=543&rft.isbn=&rft.btitle=&rft.title=Hematology%2Foncology+clinics+of+North+America&rft.issn=08898588&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-07 N1 - Date created - 2002-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Do the epilepsies, pain syndromes, and affective disorders share common kindling-like mechanisms? AN - 71989462; 12151130 AB - Kindling, in the classical sense, involves progressively increasing responsivity to the intermittent repetition of the same 1-s subthreshold electrical stimulation over time, with the amygdala being the area most frequently studied. Such repeated subthreshold stimulation is associated with: lowering of the after-discharge (AD) threshold; lengthening and spread of the AD; marked seizure stage progression culminating in full-blown tonic-clonic forelimb convulsions with rearing and falling; and evolution from triggered to spontaneous seizures. This evolving process concomitantly involves changes in the spatio-temporal expression of immediate early genes (IEGs), neurotrophic factors, and late effector genes (LEGs), and an associated changing pattern of effectiveness of different pharmacological interventions. Since seizures are the paradigmatic behavioral manifestation of kindling, some types of pharmacological seizures, such as those induced by the local anesthetics cocaine and lidocaine, and some epileptic syndromes, are most likely homologously modeled by kindling. However, since non-epileptiform syndromes, such as recurrent episodes of affective illness and some pain syndromes possess non-homogenous elements of kindling-like evolution, some of the principles involved in kindling progression may, nonetheless, be pertinent to the understanding and treatment of these syndromes. For example, one could attempt to distinguish between the genes involved in the primary pathological processes of syndrome evolution versus those that are secondary and adaptive; such a differentiation could have important implications for the development of therapeutic approaches targeted to suppressing or enhancing these alterations, respectively. In these instances, inferences drawn from the kindling model are necessarily indirect and circumscribed because different neuroanatomical and biochemical processes are likely involved in the evolution of each neuropsychiatric syndrome. Given these recognized limitations of non-homologous models, kindling may still provide insights into the longitudinal course, progression, and treatment of some neuropsychiatric syndromes that can then be directly tested in the clinic. JF - Epilepsy research AU - Post, Robert M AD - Biological Psychiatry Branch, National Institute of Mental Health, NIH Building 10, Bethesda, MD 20892-1272, USA. Y1 - 2002/06// PY - 2002 DA - June 2002 SP - 203 EP - 219 VL - 50 IS - 1-2 SN - 0920-1211, 0920-1211 KW - Index Medicus KW - Animals KW - Humans KW - Amygdala -- physiology KW - Kindling, Neurologic -- drug effects KW - Epilepsy -- physiopathology KW - Epilepsy -- chemically induced KW - Pain -- physiopathology KW - Pain -- chemically induced KW - Pain -- psychology KW - Epilepsy -- psychology KW - Mood Disorders -- physiopathology KW - Mood Disorders -- chemically induced KW - Kindling, Neurologic -- physiology KW - Mood Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71989462?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsy+research&rft.atitle=Do+the+epilepsies%2C+pain+syndromes%2C+and+affective+disorders+share+common+kindling-like+mechanisms%3F&rft.au=Post%2C+Robert+M&rft.aulast=Post&rft.aufirst=Robert&rft.date=2002-06-01&rft.volume=50&rft.issue=1-2&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=Epilepsy+research&rft.issn=09201211&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-16 N1 - Date created - 2002-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The potential for bias in Cohen's ecological analysis of lung cancer and residential radon. AN - 71987756; 12148789 AB - Cohen's ecological analysis of US lung cancer mortality rates and mean county radon concentration shows decreasing mortality rates with increasing radon concentration (Cohen 1995 Health Phys. 68 157-74). The results prompted his rejection of the linear-no-threshold (LNT) model for radon and lung cancer. Although several authors have demonstrated that risk patterns in ecological analyses provide no inferential value for assessment of risk to individuals, Cohen advances two arguments in a recent response to Darby and Doll (2000 J. Radiol. Prot. 20 221-2) who suggest Cohen's results are and will always be burdened by the ecological fallacy. Cohen asserts that the ecological fallacy does not apply when testing the LNT model, for which average exposure determines average risk, and that the influence of confounding factors is obviated by the use of large numbers of stratification variables. These assertions are erroneous. Average dose determines average risk only for models which are linear in all covariates, in which case ecological analyses are valid. However, lung cancer risk and radon exposure, while linear in the relative risk, are not linearly related to the scale of absolute risk, and thus Cohen's rejection of the LNT model is based on a false premise of linearity. In addition, it is demonstrated that the deleterious association for radon and lung cancer observed in residential and miner studies is consistent with negative trends from ecological studies, of the type described by Cohen. JF - Journal of radiological protection : official journal of the Society for Radiological Protection AU - Lubin, Jay H AD - Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20892-7244, USA. lubinj@mail.nih.gov Y1 - 2002/06// PY - 2002 DA - June 2002 SP - 141 EP - 148 VL - 22 IS - 2 SN - 0952-4746, 0952-4746 KW - Air Pollutants, Radioactive KW - 0 KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Humans KW - Confounding Factors (Epidemiology) KW - Models, Statistical KW - Bias (Epidemiology) KW - United States -- epidemiology KW - Risk Assessment KW - Lung Neoplasms -- etiology KW - Neoplasms, Radiation-Induced -- etiology KW - Neoplasms, Radiation-Induced -- mortality KW - Lung Neoplasms -- mortality KW - Air Pollutants, Radioactive -- adverse effects KW - Radon -- adverse effects KW - Environmental Exposure -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71987756?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+radiological+protection+%3A+official+journal+of+the+Society+for+Radiological+Protection&rft.atitle=The+potential+for+bias+in+Cohen%27s+ecological+analysis+of+lung+cancer+and+residential+radon.&rft.au=Lubin%2C+Jay+H&rft.aulast=Lubin&rft.aufirst=Jay&rft.date=2002-06-01&rft.volume=22&rft.issue=2&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Journal+of+radiological+protection+%3A+official+journal+of+the+Society+for+Radiological+Protection&rft.issn=09524746&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-06 N1 - Date created - 2002-07-31 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Radiol Prot. 2002 Sep;22(3):305-7; author reply 307-9 [12375791] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mixing during intravertebral arterial infusions in an in vitro model. AN - 71986901; 12164691 AB - Regional delivery of drugs can offer a pharmacokinetic advantage in the treatment of localized tumors. One method of regional delivery is by intra-arterial infusion into the basilar/vertebral artery network that provides local access to infratentorial tumors, which are frequent locations of childhood brain cancers. Proper delivery of drug by infused solutions requires adequate mixing of the infusate at the site of infusion within the artery lumen. Our mixing studies with an in vitro model of the vertebral artery network indicate that streaming of drug solution is likely to occur at low, steady infusion rates of 2 ml/min. Streaming leads to maldistribution of drug to distal perfused brain regions and may result in toxic levels in some regions while concurrently yielding subtherapeutic levels in adjacent regions. According to our model findings, distribution to both brain hemispheres is not likely following infusion into a single vertebral artery even if the infusate is well-mixed at the infusion site. This outcome results from the unique fluid flow properties of two converging channels, which are represented by the left and right vertebral branches converging into the basilar. Fluid in the model remains stratified on the side of the basilar artery served by the infused vertebral artery. Careful thought and planning of the methods of intravertebral drug infusions for treating posterior fossa tumors are required to assure proper distribution of the drug to the desired tissue regions. Improper delivery may be responsible for some noted toxicities or for failure of the treatments. JF - Journal of neuro-oncology AU - Lutz, Robert J AU - Warren, Kathy AU - Balis, Frank AU - Patronas, Nicholas AU - Dedrick, Robert L AD - Division of Bioengineering and Physical Science, National Institutes of Health, Bethesda, MD 20892-5766, USA. rjlutz@mail.nih.gov Y1 - 2002/06// PY - 2002 DA - June 2002 SP - 95 EP - 106 VL - 58 IS - 2 SN - 0167-594X, 0167-594X KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Humans KW - Cranial Fossa, Posterior KW - Brain -- metabolism KW - Models, Cardiovascular KW - Infusions, Intra-Arterial KW - Brain Neoplasms -- drug therapy KW - Antineoplastic Agents -- administration & dosage KW - Antineoplastic Agents -- pharmacokinetics KW - Vertebral Artery KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71986901?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuro-oncology&rft.atitle=Mixing+during+intravertebral+arterial+infusions+in+an+in+vitro+model.&rft.au=Lutz%2C+Robert+J%3BWarren%2C+Kathy%3BBalis%2C+Frank%3BPatronas%2C+Nicholas%3BDedrick%2C+Robert+L&rft.aulast=Lutz&rft.aufirst=Robert&rft.date=2002-06-01&rft.volume=58&rft.issue=2&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuro-oncology&rft.issn=0167594X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-15 N1 - Date created - 2002-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Psychoactive substance-induced sexual dysfunction in men]. AN - 71973404; 12166192 JF - Nihon rinsho. Japanese journal of clinical medicine AU - Ozaki, Shigeru AD - Division of Drug Dependence Research, National Institute of Mental Health, National Center of Neurology and Psychiatry. Y1 - 2002/06// PY - 2002 DA - June 2002 SP - 421 EP - 425 VL - 60 Suppl 6 SN - 0047-1852, 0047-1852 KW - Psychotropic Drugs KW - 0 KW - Index Medicus KW - Erectile Dysfunction -- chemically induced KW - Humans KW - Prognosis KW - Substance-Related Disorders -- complications KW - Erectile Dysfunction -- etiology KW - Male KW - Female KW - Sexual Dysfunction, Physiological -- etiology KW - Sexual Dysfunction, Physiological -- chemically induced KW - Psychotropic Drugs -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71973404?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nihon+rinsho.+Japanese+journal+of+clinical+medicine&rft.atitle=%5BPsychoactive+substance-induced+sexual+dysfunction+in+men%5D.&rft.au=Ozaki%2C+Shigeru&rft.aulast=Ozaki&rft.aufirst=Shigeru&rft.date=2002-06-01&rft.volume=60+Suppl+6&rft.issue=&rft.spage=421&rft.isbn=&rft.btitle=&rft.title=Nihon+rinsho.+Japanese+journal+of+clinical+medicine&rft.issn=00471852&rft_id=info:doi/ LA - Japanese DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-27 N1 - Date created - 2002-08-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antisense DNAs as targeted therapeutics for cancer: no longer a dream. AN - 71941412; 12137417 AB - Progress in antisense technology has been rapid, and the traditional antisense inhibition of gene expression has now been viewed at a genomic scale. This global view has led to a deeper understanding of the mechanism of action, the elimination of non-specific and undesirable side effects and, ultimately, greater efficacy and reduced toxicity for nucleic acid medicines. Several antisense oligonucleotides are in clinical trials; these are well tolerated and have therapeutic potential. Antisense oligonucleotides are promising molecular medicines with potential to treat human cancer in the foreseeable future. JF - Current opinion in investigational drugs (London, England : 2000) AU - Cho-Chung, Yoon S AD - Cellular Biochemistry Section, BRL, CCR, National Cancer Institute, NIH, Bethesda, MD 20892-1750, USA. ChoChung@helix.nih.gov Y1 - 2002/06// PY - 2002 DA - June 2002 SP - 934 EP - 939 VL - 3 IS - 6 SN - 1472-4472, 1472-4472 KW - DNA, Antisense KW - 0 KW - Oligodeoxyribonucleotides, Antisense KW - Index Medicus KW - Clinical Trials, Phase II as Topic KW - Clinical Trials, Phase III as Topic KW - Humans KW - Clinical Trials, Phase I as Topic KW - Oligodeoxyribonucleotides, Antisense -- therapeutic use KW - Oligodeoxyribonucleotides, Antisense -- chemistry KW - Gene Expression -- drug effects KW - Neoplasms -- drug therapy KW - DNA, Antisense -- therapeutic use KW - DNA, Antisense -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71941412?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+investigational+drugs+%28London%2C+England+%3A+2000%29&rft.atitle=Antisense+DNAs+as+targeted+therapeutics+for+cancer%3A+no+longer+a+dream.&rft.au=Cho-Chung%2C+Yoon+S&rft.aulast=Cho-Chung&rft.aufirst=Yoon&rft.date=2002-06-01&rft.volume=3&rft.issue=6&rft.spage=934&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+investigational+drugs+%28London%2C+England+%3A+2000%29&rft.issn=14724472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-26 N1 - Date created - 2002-07-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of phospholipase D and secretion in mast cells by protein kinase A and other protein kinases. AN - 71907445; 12119277 AB - Functions attributed to phospholipase (PL) D include the regulation of intracellular trafficking of Golgi-derived vesicles and secretion of granules from mast cells. We have reported that activation of PLD and secretion in a rat mast cell (RBL-2H3) line is substantially enhanced by cholera toxin, a known activator of protein kinase (PK) A. Here we review the evidence that (1) the synergistic interactions of cholera toxin and other pharmacological agents on mast cell secretion are attributable to the synergistic activation of PLD via PKA, CaM kinase II, and PKC and (2) both PLD1 and PLD2 participate in this process. For example, treatment with cholera toxin, thapsigargin, and phorbol 12-myristate 13-acetate (which activate PKA, CaM kinase II, and PKC, respectively) exhibit synergy in the stimulation of both PLD and secretion. These kinases and PLD are likely confined to membrane components, as similar synergistic interactions could be demonstrated in permeabilized cells. The regulation of PLD and secretion by these kinases is also apparent from studies of inhibitors of PKA and other kinases. Also, by overexpression of either PLD1 or PLD2 it is apparent that both isoforms respond to the same stimuli as endogenous PLD, although PLD1 is largely associated with secretory granules and PLD2 with plasma membrane. The studies reveal interesting differences in the regulation of the translocation of granules (regulated by PKA) and the fusion of these granules with the plasma membrane (regulated by Ca(2+) and PKC). The pathological/physiological implications of the regulation of PLD by PKA require further evaluation in other cell systems. JF - Annals of the New York Academy of Sciences AU - Choi, Wahn Soo AU - Chahdi, Ahmed AU - Kim, Young Mi AU - Fraundorfer, Paul F AU - Beaven, Michael A AD - Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1760, USA. Y1 - 2002/06// PY - 2002 DA - June 2002 SP - 198 EP - 212 VL - 968 SN - 0077-8923, 0077-8923 KW - Isoenzymes KW - 0 KW - Cholera Toxin KW - 9012-63-9 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2 KW - EC 2.7.11.17 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - Phospholipase D KW - EC 3.1.4.4 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Protein Kinase C -- metabolism KW - Calcium -- metabolism KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Animals KW - Transport Vesicles -- physiology KW - Cholera Toxin -- pharmacology KW - Exocytosis -- physiology KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Phospholipase D -- metabolism KW - Phospholipase D -- genetics KW - Mast Cells -- metabolism KW - Cyclic AMP-Dependent Protein Kinases -- antagonists & inhibitors KW - Mast Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71907445?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Regulation+of+phospholipase+D+and+secretion+in+mast+cells+by+protein+kinase+A+and+other+protein+kinases.&rft.au=Choi%2C+Wahn+Soo%3BChahdi%2C+Ahmed%3BKim%2C+Young+Mi%3BFraundorfer%2C+Paul+F%3BBeaven%2C+Michael+A&rft.aulast=Choi&rft.aufirst=Wahn&rft.date=2002-06-01&rft.volume=968&rft.issue=&rft.spage=198&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-20 N1 - Date created - 2002-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thalidomide, an antiangiogenic agent with clinical activity in cancer. AN - 71903016; 12109812 AB - Despite the teratogenic past of thalidomide, there is recent evidence indicating the drug's efficacy in the management of various diseases from immune disorders to cancers. The history, pharmacodynamic and pharmacokinetic properties of thalidomide in the clinic are discussed in this review article. JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie AU - Ng, S S W AU - Brown, M AU - Figg, W D AD - Molecular Pharmacology Section, Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/06// PY - 2002 DA - June 2002 SP - 194 EP - 199 VL - 56 IS - 4 SN - 0753-3322, 0753-3322 KW - Angiogenesis Inhibitors KW - 0 KW - Thalidomide KW - 4Z8R6ORS6L KW - Index Medicus KW - Animals KW - Neovascularization, Pathologic -- drug therapy KW - Humans KW - Neovascularization, Pathologic -- metabolism KW - Clinical Trials as Topic -- statistics & numerical data KW - Angiogenesis Inhibitors -- therapeutic use KW - Neoplasms -- drug therapy KW - Thalidomide -- pharmacokinetics KW - Angiogenesis Inhibitors -- pharmacokinetics KW - Thalidomide -- therapeutic use KW - Thalidomide -- chemistry KW - Angiogenesis Inhibitors -- chemistry KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71903016?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biomedicine+%26+pharmacotherapy+%3D+Biomedecine+%26+pharmacotherapie&rft.atitle=Thalidomide%2C+an+antiangiogenic+agent+with+clinical+activity+in+cancer.&rft.au=Ng%2C+S+S+W%3BBrown%2C+M%3BFigg%2C+W+D&rft.aulast=Ng&rft.aufirst=S+S&rft.date=2002-06-01&rft.volume=56&rft.issue=4&rft.spage=194&rft.isbn=&rft.btitle=&rft.title=Biomedicine+%26+pharmacotherapy+%3D+Biomedecine+%26+pharmacotherapie&rft.issn=07533322&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-31 N1 - Date created - 2002-07-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relationship of the delta-opioid receptor gene to heroin abuse in a large Chinese case/control sample. AN - 71896077; 12116270 AB - Pharmacological and electrophysiological evidence has shown that opioid receptors are involved in the mechanism of heroin dependence. Thus, opioid receptors are appropriate candidate genes for case-control association studies of heroin dependence. Previously, two single nucleotide polymorphisms (SNPs), OPRD1 921T > C and 80G > T, of the human delta opioid receptor gene were used in population-based studies of heroin dependence. One study in a German population found that OPRD1 921T > C was associated with heroin dependence. This finding, however, was not replicated in a different German sample. To test the hypothesis that OPRD1 or a closely linked gene is associated with heroin dependence, we used 5' nuclease assays to genotype both OPRD1 SNPs in 450 Chinese heroin dependent patients and 304 unaffected controls from the same population. In addition, five SNPs distributed in four other genes: ADH2, ALDH2, OPRM1, and DRD1, were used as genomic control loci to test the case and control populations for stratification bias. Genotype and allele frequencies at OPRD1 921T > C were not significantly different, and the OPRD1 80G was absent from both Chinese opioid dependence patients and controls. Based on the genotype and allele frequencies of the genomic control loci, there was no evidence for stratification bias capable of masking an association of OPRD1 to heroin dependence in this large and homogenous Chinese sample. Therefore, these data do not support an association between the OPRD1 gene and heroin dependence in the Chinese population. Published 2002 Wiley-Liss, Inc. JF - American journal of medical genetics AU - Xu, Ke AU - Liu, Xie-he AU - Nagarajan, Saumya AU - Gu, Xiao-Yong AU - Goldman, David AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, Maryland 20852, USA. Y1 - 2002/06/01/ PY - 2002 DA - 2002 Jun 01 SP - 45 EP - 50 VL - 110 IS - 1 SN - 0148-7299, 0148-7299 KW - Receptors, Opioid, delta KW - 0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Polymorphism, Single Nucleotide KW - Gene Frequency KW - DNA Mutational Analysis KW - Humans KW - Genotype KW - Alleles KW - Adult KW - DNA -- genetics KW - Case-Control Studies KW - DNA -- chemistry KW - China KW - Female KW - Male KW - Receptors, Opioid, delta -- genetics KW - Heroin Dependence -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71896077?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+medical+genetics&rft.atitle=Relationship+of+the+delta-opioid+receptor+gene+to+heroin+abuse+in+a+large+Chinese+case%2Fcontrol+sample.&rft.au=Xu%2C+Ke%3BLiu%2C+Xie-he%3BNagarajan%2C+Saumya%3BGu%2C+Xiao-Yong%3BGoldman%2C+David&rft.aulast=Xu&rft.aufirst=Ke&rft.date=2002-06-01&rft.volume=110&rft.issue=1&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=American+journal+of+medical+genetics&rft.issn=01487299&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-01 N1 - Date created - 2002-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preclinical evaluation of GBR12909 decanoate as a long-acting medication for methamphetamine dependence. AN - 71893609; 12105088 AB - Methamphetamine (METH) abuse is a growing health problem, and no treatments for METH dependence have been identified. The powerful addictive properties of METH are mediated by release of dopamine (DA) from nerve terminals in mesolimbic reward pathways. METH stimulates DA release by acting as a substrate for DA transporter (DAT) proteins, thereby triggering efflux of DA from cells into the synapse. We have shown that blocking DAT activity with high-affinity DA uptake inhibitors, like GBR12909, can substantially reduce METH-evoked DA release in vitro, suggesting GBR12909 may have potential as a pharmacotherapy for METH dependence. The purpose of the present study was to examine the neurobiological effects of a long-acting oil-soluble preparation of GBR12909 (1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-hydroxy-3-phenylpropyl) piperazinyl decanoate, or GBR-decanoate). Male rats received GBR-decanoate (480 mg/kg, i.m.) or its oil vehicle, and were tested using a variety of methods one and two weeks later. Ex vivo autoradiography showed that GBR-decanoate decreases DAT binding in DA-rich brain regions. In vivo microdialysis in the nucleus accumbens revealed that GBR-decanoate elevates baseline levels of extracellular DA and antagonizes the ability of METH to evoke DA release. The dopaminergic effects of GBR-decanoate were sustained, lasting for at least two weeks. Rats pretreated with GBR-decanoate displayed enhanced locomotor responses to novelty at one week, but not two weeks, postinjection. Administration of the D(2)/D(3) receptor agonist quinpirole (10 and 100 microg/kg, s.c.) decreased locomotor activity and suppressed plasma prolactin levels; quinpirole-induced responses were not altered by GBR-decanoate. Thus, GBR-decanoate is able to elevate basal synaptic DA levels and block METH-evoked DA release in a persistent manner, without significant perturbation of DA receptor function. The findings suggest that GBR-decanoate, or similar long-acting agents, should be evaluated further as potential treatment adjuncts in the management of METH addiction in humans. JF - Annals of the New York Academy of Sciences AU - Baumann, Michael H AU - Phillips, Jennifer M AU - Ayestas, Mario A AU - Ali, Syed F AU - Rice, Kenner C AU - Rothman, Richard B AD - Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. mbaumann@intra.nida.nih.gov Y1 - 2002/06// PY - 2002 DA - June 2002 SP - 92 EP - 108 VL - 965 SN - 0077-8923, 0077-8923 KW - (1-(2-(bis(4-fluorophenyl)methoxy)ethyl)-4-(3-hydroxy-3-phenylpropyl) piperazinyl decanoate) KW - 0 KW - Carrier Proteins KW - Dopamine Plasma Membrane Transport Proteins KW - Dopamine Uptake Inhibitors KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Piperazines KW - Serotonin Plasma Membrane Transport Proteins KW - Slc6a3 protein, rat KW - Slc6a4 protein, rat KW - Quinpirole KW - 20OP60125T KW - Serotonin KW - 333DO1RDJY KW - Methamphetamine KW - 44RAL3456C KW - vanoxerine KW - 90X28IKH43 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Membrane Glycoproteins -- chemistry KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry KW - Membrane Transport Proteins -- chemistry KW - Dopamine Uptake Inhibitors -- therapeutic use KW - Binding Sites KW - Rats KW - Rats, Sprague-Dawley KW - Quinpirole -- pharmacology KW - Exploratory Behavior -- drug effects KW - Exploratory Behavior -- physiology KW - Time Factors KW - Membrane Transport Proteins -- metabolism KW - Male KW - Membrane Glycoproteins -- metabolism KW - Piperazines -- therapeutic use KW - Dopamine -- metabolism KW - Motor Activity -- physiology KW - Motor Activity -- drug effects KW - Serotonin -- metabolism KW - Piperazines -- pharmacology KW - Amphetamine-Related Disorders -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71893609?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Preclinical+evaluation+of+GBR12909+decanoate+as+a+long-acting+medication+for+methamphetamine+dependence.&rft.au=Baumann%2C+Michael+H%3BPhillips%2C+Jennifer+M%3BAyestas%2C+Mario+A%3BAli%2C+Syed+F%3BRice%2C+Kenner+C%3BRothman%2C+Richard+B&rft.aulast=Baumann&rft.aufirst=Michael&rft.date=2002-06-01&rft.volume=965&rft.issue=&rft.spage=92&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-02 N1 - Date created - 2002-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Appetite suppressants as agonist substitution therapies for stimulant dependence. AN - 71890654; 12105089 AB - Several lines of evidence support a dual-deficit model of stimulant withdrawal in which decreases in synaptic dopamine (DA) and serotonin (5-HT) contribute to withdrawal symptoms, drug craving, and relapse. According to the dual-deficit model, DA dysfunction during withdrawal underlies anhedonia and psychomotor disturbances, whereas 5-HT dysfunction gives rise to depressed mood, obsessive thoughts, and lack of impulse control. The model suggests that medications capable of normalizing stimulant-induced DA and 5-HT deficits should be effective treatment adjuncts. Furthermore, the model may explain why medications targeting only one neurotransmitter system (i.e., DA) have failed to treat cocaine dependence. Amphetamine-type appetite suppressants are logical choices for neurochemical normalization therapy of stimulant dependence, yet few clinical studies have tested anorectics in this regard. The chief purpose of the present work is to profile the activity of various anorectic agents at DA, 5-HT, and NE transporters, in order to identify possible medications for stimulant dependence. Compounds were tested in vitro for their ability to stimulate release and inhibit uptake of [(3)H]DA, [(3)H]NE, and [(3)H]5-HT. Selected compounds were tested in vivo for their ability to elevate extracellular levels of DA and 5-HT in rat nucleus accumbens. The results show that clinically available appetite suppressants display a wide range of activities at monoamine transporters. However, no single medication possesses equal potency at DA and 5-HT transporters, suggesting that none of the anorectics is ideally suited for treatment of stimulant addictions. Future efforts should focus on developing new medications that possess the desired therapeutic activity but lack the adverse effects associated with older amphetamine-type anorectics. JF - Annals of the New York Academy of Sciences AU - Rothman, Richard B AU - Blough, Bruce E AU - Baumann, Michael H AD - Clinical Psychopharmacology Section, NIDA, NIH, Baltimore, Maryland 21224, USA. rrothmna@intra.nida.nih.gov Y1 - 2002/06// PY - 2002 DA - June 2002 SP - 109 EP - 126 VL - 965 SN - 0077-8923, 0077-8923 KW - Appetite Depressants KW - 0 KW - Serotonin Uptake Inhibitors KW - Fenfluramine KW - 2DS058H2CF KW - Aminorex KW - 2SH16612I9 KW - Serotonin KW - 333DO1RDJY KW - Methamphetamine KW - 44RAL3456C KW - Dopamine KW - VTD58H1Z2X KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Rats KW - Microdialysis KW - Animals KW - Rats, Sprague-Dawley KW - Aminorex -- pharmacology KW - Norepinephrine -- metabolism KW - Methamphetamine -- pharmacology KW - Dopamine -- metabolism KW - Fenfluramine -- pharmacology KW - Serotonin -- metabolism KW - Male KW - Synaptosomes -- drug effects KW - Serotonin Uptake Inhibitors -- therapeutic use KW - Substance-Related Disorders -- drug therapy KW - Appetite Depressants -- pharmacology KW - Synaptosomes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71890654?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Appetite+suppressants+as+agonist+substitution+therapies+for+stimulant+dependence.&rft.au=Rothman%2C+Richard+B%3BBlough%2C+Bruce+E%3BBaumann%2C+Michael+H&rft.aulast=Rothman&rft.aufirst=Richard&rft.date=2002-06-01&rft.volume=965&rft.issue=&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-02 N1 - Date created - 2002-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicogenomics: the new frontier in risk analysis. AN - 71856432; 12082011 AB - Risk assessment involves the identification of potential human health hazards, the assessment of the level of exposure by humans to these hazards and the evaluation of the relationship between exposure and response in humans. Research is currently underway to improve the scientific basis of risk assessment through the incorporation of new technologies such as transgenic animals, molecular epidemiology, toxicogenomics, alternative models to animals and mechanism-based mathematical modeling into the estimation of risk in a quantitative manner. This paper briefly discusses these technologies and how each is being employed for more scientifically sound risk assessments. JF - Carcinogenesis AU - Simmons, P Trinia AU - Portier, Christopher J AD - National Institute of Environmental Health Sciences, Laboratory of Computational Biology and Risk Analysis, MD A3-06, Research Triangle Park, NC 27709, USA. simmons4@niehs.nih.gov Y1 - 2002/06// PY - 2002 DA - June 2002 SP - 903 EP - 905 VL - 23 IS - 6 SN - 0143-3334, 0143-3334 KW - Index Medicus KW - Animals KW - Public Health KW - Animals, Genetically Modified KW - Risk Assessment KW - Toxicology -- trends KW - Genomics -- trends UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71856432?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Toxicogenomics%3A+the+new+frontier+in+risk+analysis.&rft.au=Simmons%2C+P+Trinia%3BPortier%2C+Christopher+J&rft.aulast=Simmons&rft.aufirst=P&rft.date=2002-06-01&rft.volume=23&rft.issue=6&rft.spage=903&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-31 N1 - Date created - 2002-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bauxite manufacturing residues from Gardanne (France) and Portovesme (Italy) exert different patterns of pollution and toxicity to sea urchin embryos. AN - 71829339; 12069314 AB - This study was designed to investigate the composition and toxicity of solid residues from bauxite manufacturing plants. Soil and dust samples were collected in the proximity of two bauxite plants (Gardanne, France, and Portovesme, Italy). Samples were analyzed for their content of some selected inorganic contaminants by means of inductively coupled plasma optical emission spectroscopy (ICP-OES) either following acid digestion procedures or by seawater release of soluble components. Toxicity was tested by sea urchin bioassays to evaluate a set of toxicity endpoints including acute embryotoxicity, developmental defects, changes in sperm fertilization success, transmissible damage from sperm to the offspring, and cytogenetic abnormalities. Inorganic analysis showed two distinct sets of inorganic contaminants in Gardanne versus Portovesme, including Al, Cr, Cu, Fe, Mn, Pb, Ti, and Zn; sample composition (seawater-soluble contaminants) and toxicity showed a noteworthy association. The most severe toxicity to embryogenesis and to sperm fertilization success was exerted by some Portovesme samples (0.03-0.5% w/v), with a significant association between toxicity and dose-related seawater release of Zn, Pb, and Mn. Seawater extraction of a toxic dust sample (G20) from the Gardanne factory showed increasing seawater release of Al, Fe, and Mn; the G20 sample, at the level of 0.5%, affected both developing sea urchin embryos and sperm (offspring quality). Soil samples around the Gardanne factory showed the highest frequency of toxic soil sites eastward from the factory. The present data point to solid deposition from bauxite plants as a potential subject of environmental health concern. The results suggest that extraction methods for evaluating the toxicity of complex mixtures should be based on the environmental availability of mixture components. The differences in sample toxicity among the tested sites, however, suggest possible site-to-site variability in geochemical and/or technological parameters. JF - Environmental toxicology and chemistry AU - Pagano, Giovanni AU - de Biase, Antonella AU - Iaccarino, Mario AU - Meriç, Süreyya AU - Petruzzelli, Domenico AU - Tünay, Olcay AU - Warnau, Michel AU - Trieff, Norman M AD - Italian National Cancer Institute, G. Pascale Foundation, Naples, Italy. gbpagano@tin.it Y1 - 2002/06// PY - 2002 DA - June 2002 SP - 1272 EP - 1278 VL - 21 IS - 6 SN - 0730-7268, 0730-7268 KW - Industrial Waste KW - 0 KW - Metals, Heavy KW - Soil Pollutants KW - Aluminum Oxide KW - LMI26O6933 KW - Index Medicus KW - France KW - Animals KW - Manufactured Materials KW - Fertilization -- drug effects KW - Italy KW - Metals, Heavy -- adverse effects KW - Embryonic and Fetal Development -- drug effects KW - Aluminum Oxide -- chemistry KW - Sea Urchins -- drug effects KW - Industrial Waste -- adverse effects KW - Sea Urchins -- embryology KW - Soil Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71829339?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+toxicology+and+chemistry&rft.atitle=Bauxite+manufacturing+residues+from+Gardanne+%28France%29+and+Portovesme+%28Italy%29+exert+different+patterns+of+pollution+and+toxicity+to+sea+urchin+embryos.&rft.au=Pagano%2C+Giovanni%3Bde+Biase%2C+Antonella%3BIaccarino%2C+Mario%3BMeri%C3%A7%2C+S%C3%BCreyya%3BPetruzzelli%2C+Domenico%3BT%C3%BCnay%2C+Olcay%3BWarnau%2C+Michel%3BTrieff%2C+Norman+M&rft.aulast=Pagano&rft.aufirst=Giovanni&rft.date=2002-06-01&rft.volume=21&rft.issue=6&rft.spage=1272&rft.isbn=&rft.btitle=&rft.title=Environmental+toxicology+and+chemistry&rft.issn=07307268&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-19 N1 - Date created - 2002-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lifetime exposure to a soluble TGF-beta antagonist protects mice against metastasis without adverse side effects. AN - 71828849; 12070308 AB - TGF-betas play diverse and complex roles in many biological processes. In tumorigenesis, they can function either as tumor suppressors or as pro-oncogenic factors, depending on the stage of the disease. We have developed transgenic mice expressing a TGF-beta antagonist of the soluble type II TGF-beta receptor:Fc fusion protein class, under the regulation of the mammary-selective MMTV-LTR promoter/enhancer. Biologically significant levels of antagonist were detectable in the serum and most tissues of this mouse line. The mice were resistant to the development of metastases at multiple organ sites when compared with wild-type controls, both in a tail vein metastasis assay using isogenic melanoma cells and in crosses with the MMTV-neu transgenic mouse model of metastatic breast cancer. Importantly, metastasis from endogenous mammary tumors was suppressed without any enhancement of primary tumorigenesis. Furthermore, aged transgenic mice did not exhibit the severe pathology characteristic of TGF-beta null mice, despite lifetime exposure to the antagonist. The data suggest that in vivo the antagonist may selectively neutralize the undesirable TGF-beta associated with metastasis, while sparing the regulatory roles of TGF-betas in normal tissues. Thus this soluble TGF-beta antagonist has potential for long-term clinical use in the prevention of metastasis. JF - The Journal of clinical investigation AU - Yang, Yu-An AU - Dukhanina, Oksana AU - Tang, Binwu AU - Mamura, Mizuko AU - Letterio, John J AU - MacGregor, Jennifer AU - Patel, Sejal C AU - Khozin, Shahram AU - Liu, Zi-Yao AU - Green, Jeffrey AU - Anver, Miriam R AU - Merlino, Glenn AU - Wakefield, Lalage M AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2002/06// PY - 2002 DA - June 2002 SP - 1607 EP - 1615 VL - 109 IS - 12 SN - 0021-9738, 0021-9738 KW - Immunoglobulin Fc Fragments KW - 0 KW - Immunoglobulin G KW - Receptors, Transforming Growth Factor beta KW - Recombinant Fusion Proteins KW - Transforming Growth Factor beta KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Solubility KW - Tumor Cells, Cultured KW - Humans KW - Genetic Vectors KW - Recombinant Fusion Proteins -- genetics KW - Mammary Tumor Virus, Mouse KW - Mice KW - Neoplasm Metastasis -- prevention & control KW - Mice, Transgenic KW - Female KW - Recombinant Fusion Proteins -- physiology KW - Immunoglobulin Fc Fragments -- physiology KW - Receptors, Transforming Growth Factor beta -- genetics KW - Mammary Neoplasms, Animal -- pathology KW - Immunoglobulin G -- genetics KW - Receptors, Transforming Growth Factor beta -- physiology KW - Receptors, Transforming Growth Factor beta -- immunology KW - Melanoma, Experimental -- prevention & control KW - Mammary Neoplasms, Animal -- prevention & control KW - Immunoglobulin Fc Fragments -- genetics KW - Liver Neoplasms -- secondary KW - Immunoglobulin G -- physiology KW - Transforming Growth Factor beta -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71828849?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+investigation&rft.atitle=Lifetime+exposure+to+a+soluble+TGF-beta+antagonist+protects+mice+against+metastasis+without+adverse+side+effects.&rft.au=Yang%2C+Yu-An%3BDukhanina%2C+Oksana%3BTang%2C+Binwu%3BMamura%2C+Mizuko%3BLetterio%2C+John+J%3BMacGregor%2C+Jennifer%3BPatel%2C+Sejal+C%3BKhozin%2C+Shahram%3BLiu%2C+Zi-Yao%3BGreen%2C+Jeffrey%3BAnver%2C+Miriam+R%3BMerlino%2C+Glenn%3BWakefield%2C+Lalage+M&rft.aulast=Yang&rft.aufirst=Yu-An&rft.date=2002-06-01&rft.volume=109&rft.issue=12&rft.spage=1607&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-12 N1 - Date created - 2002-06-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nat Genet. 2001 Oct;29(2):117-29 [11586292] Trends Cardiovasc Med. 2000 Apr;10(3):132-7 [11428000] J Cell Biol. 1987 Aug;105(2):965-75 [2887577] J Cell Physiol. 1989 Jan;138(1):79-86 [2910889] Nature. 1990 Jul 26;346(6282):371-4 [2374609] Growth Factors. 1990;3(2):115-27 [2169772] Nature. 1992 Oct 22;359(6397):693-9 [1436033] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10578-82 [1359541] Nature. 1992 Nov 26;360(6402):361-4 [1280332] Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):770-4 [8421714] Am J Pathol. 1993 Aug;143(2):381-9 [8393616] J Clin Invest. 1993 Dec;92(6):2569-76 [7504687] Nature. 1994 Jun 23;369(6482):669-71 [8208295] Ann Surg. 1995 Aug;222(2):155-62 [7543740] J Immunol. 1995 Sep 15;155(6):3205-12 [7673733] Cancer Immunol Immunother. 1995 Nov;41(5):302-8 [8536276] J Immunother Emphasis Tumor Immunol. 1996 May;19(3):169-75 [8811491] J Clin Invest. 1996 Nov 1;98(9):2109-19 [8903331] Kidney Int. 1997 May;51(5):1376-82 [9150447] Cancer Res. 1997 Dec 15;57(24):5564-70 [9407968] Mol Carcinog. 1998 May;22(1):46-56 [9609100] Nat Med. 1998 Jun;4(6):685-90 [9623977] Nat Med. 1998 Jul;4(7):802-7 [9662371] Oncogene. 1998 Jul 9;17(1):25-34 [9671311] Eur J Biochem. 1998 Jun 15;254(3):505-13 [9688260] Kidney Int. 1999 Feb;55(2):465-75 [9987071] Cancer Res. 1999 Jul 15;59(14):3379-86 [10416598] Thorax. 1999 Sep;54(9):805-12 [10456973] Nat Med. 2001 Oct;7(10):1118-22 [11590434] Microbes Infect. 1999 Dec;1(15):1327-47 [10611761] Microbes Infect. 1999 Dec;1(15):1349-65 [10611762] Microbes Infect. 1999 Dec;1(15):1367-80 [10611763] Hum Gene Ther. 2000 Jan 1;11(1):33-42 [10646637] Crit Rev Oncog. 1999;10(4):303-60 [10654929] Mol Cell Biol. 2000 Mar;20(6):2055-65 [10688652] Immunity. 2000 Feb;12(2):171-81 [10714683] J Exp Med. 2000 Apr 3;191(7):1187-96 [10748236] J Natl Cancer Inst. 2000 Sep 6;92(17):1388-402 [10974075] Cell. 2000 Oct 13;103(2):295-309 [11057902] Gastroenterology. 2000 Nov;119(5):1286-96 [11054386] Expert Opin Investig Drugs. 2000 Mar;9(3):497-514 [11060691] Breast Cancer Res. 2000;2(2):92-9 [11250698] Microbes Infect. 1999 Dec;1(15):1313-25 [10611760] Surg Oncol Clin N Am. 2001 Apr;10(2):243-55, vii [11382585] Comment In: J Clin Invest. 2002 Jun;109(12):1533-6 [12070299] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson's disease. AN - 71824748; 12068076 AB - The etiology of sporadic Parkinson's disease (PD) remains unknown. Increasing evidence has suggested a role for inflammation in the brain in the pathogenesis of PD. However, it has not been clearly demonstrated whether microglial activation, the most integral part of the brain inflammatory process, will result in a delayed and progressive degeneration of dopaminergic neurons in substantia nigra, a hallmark of PD. We report here that chronic infusion of an inflammagen lipopolysaccharide at 5 ng/h for 2 weeks into rat brain triggered a rapid activation of microglia that reached a plateau in 2 weeks, followed by a delayed and gradual loss of nigral dopaminergic neurons that began at between 4 and 6 weeks and reached 70% by 10 weeks. Further investigation of the underlying mechanism of action of microglia-mediated neurotoxicity using rat mesencephalic neuron-glia cultures demonstrated that low concentrations of lipopolysaccharide (0.1-10 ng/mL)-induced microglial activation and production of neurotoxic factors preceded the progressive and selective degeneration of dopaminergic neurons. Among the factors produced by activated microglia, the NADPH oxidase-mediated release of superoxide appeared to be a predominant effector of neurodegeneration, consistent with the notion that dopaminergic neurons are particularly vulnerable to oxidative insults. This is the first report that microglial activation induced by chronic exposure to inflammagen was capable of inducing a delayed and selective degeneration of nigral dopaminergic neurons and that microglia-originated free radicals play a pivotal role in dopaminergic neurotoxicity in this inflammation-mediated model of PD. JF - Journal of neurochemistry AU - Gao, Hui-Ming AU - Jiang, Janwei AU - Wilson, Belinda AU - Zhang, Wanqin AU - Hong, Jau-Shyong AU - Liu, Bin AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences/National Institutes of Health, North Carolina, USA. Y1 - 2002/06// PY - 2002 DA - June 2002 SP - 1285 EP - 1297 VL - 81 IS - 6 SN - 0022-3042, 0022-3042 KW - Lipopolysaccharides KW - 0 KW - Multienzyme Complexes KW - Neurotoxins KW - Superoxides KW - 11062-77-4 KW - NADH oxidase KW - EC 1.6.- KW - NADH, NADPH Oxidoreductases KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Coculture Techniques KW - Neurotoxins -- metabolism KW - Lipopolysaccharides -- pharmacology KW - Parkinson Disease -- physiopathology KW - Neuroglia -- drug effects KW - Mesencephalon -- cytology KW - Neuroglia -- physiology KW - Rats KW - Superoxides -- metabolism KW - Rats, Inbred F344 KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Multienzyme Complexes -- physiology KW - Time Factors KW - NADH, NADPH Oxidoreductases -- physiology KW - Male KW - Substantia Nigra -- physiopathology KW - Microglia -- physiology KW - Neurons -- drug effects KW - Nerve Degeneration -- physiopathology KW - Neurons -- physiology KW - Dopamine -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71824748?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Microglial+activation-mediated+delayed+and+progressive+degeneration+of+rat+nigral+dopaminergic+neurons%3A+relevance+to+Parkinson%27s+disease.&rft.au=Gao%2C+Hui-Ming%3BJiang%2C+Janwei%3BWilson%2C+Belinda%3BZhang%2C+Wanqin%3BHong%2C+Jau-Shyong%3BLiu%2C+Bin&rft.aulast=Gao&rft.aufirst=Hui-Ming&rft.date=2002-06-01&rft.volume=81&rft.issue=6&rft.spage=1285&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-12 N1 - Date created - 2002-06-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Matrix metalloproteinase inhibitors: do they have a place in anticancer therapy? AN - 71819202; 12066962 AB - Matrix metalloproteinases (MMPs) are a family of enzymes involved in degradation of extracellular matrix. An imbalance between MMPs and naturally occurring MMP inhibitors may cause excess extracellular matrix destruction, allowing cancer cells to invade surrounding tissues and metastasize, and permitting angiogenesis to occur. Inhibition of certain key MMPs may prevent angiogenesis, tumor growth, invasion, and metastasis. Gelatinases MMP-2 and MMP-9 are expressed during carcinogenesis and angiogenesis. Synthetic MMP inhibitors were designed to target these enzymes and potentially prevent the tumor growth and metastases associated with cancer. JF - Pharmacotherapy AU - Rudek, Michelle A AU - Venitz, Jürgen AU - Figg, William D AD - Clinical Pharmacology Research Core, Medical Oncology Clinical Research Unit Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/06// PY - 2002 DA - June 2002 SP - 705 EP - 720 VL - 22 IS - 6 SN - 0277-0008, 0277-0008 KW - Antineoplastic Agents KW - 0 KW - Matrix Metalloproteinase Inhibitors KW - Protease Inhibitors KW - Index Medicus KW - Humans KW - Protease Inhibitors -- therapeutic use KW - Neoplasms -- drug therapy KW - Neoplasms -- pathology KW - Neoplasms -- enzymology KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71819202?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacotherapy&rft.atitle=Matrix+metalloproteinase+inhibitors%3A+do+they+have+a+place+in+anticancer+therapy%3F&rft.au=Rudek%2C+Michelle+A%3BVenitz%2C+J%C3%BCrgen%3BFigg%2C+William+D&rft.aulast=Rudek&rft.aufirst=Michelle&rft.date=2002-06-01&rft.volume=22&rft.issue=6&rft.spage=705&rft.isbn=&rft.btitle=&rft.title=Pharmacotherapy&rft.issn=02770008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-11 N1 - Date created - 2002-06-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recruitment of dioxin receptor to active transcription sites. AN - 71810244; 12058065 AB - The aryl hydrocarbon receptor (AhR or dioxin receptor) is a ligand-activated transcription factor that heterodimerizes with the AhR nuclear translocator (ARNT/HIF-1beta) to form an AhR/ARNT transcription factor complex. This complex binds to specific DNA sites in the regulatory domains of numerous target genes and mediates the biological effects of exogenous ligands. Herein, we have investigated the subcellular distribution of the AhR/ARNT complex in response to ligand stimulation, by using live-cell confocal and high-resolution deconvolution microscopy. We found that unliganded AhR shows a predominantly cytoplasmic diffuse distribution in mouse hepatoma cells. On addition of ligand, AhR rapidly translocates to the nucleus and accumulates in multiple bright foci. Inhibition of transcription prevented the formation of AhR foci. Dual- and triple-immunolabeling experiments, combined with labeling of nascent RNA, showed that the foci are transcription sites, indicating that upon ligand stimulation, AhR is recruited to active transcription sites. The interaction of AhR with ARNT was both necessary and sufficient for the recruitment of AhR to transcription sites. These results indicate that AhR/ARNT complexes are recruited to specific subnuclear compartments in a ligand-dependent manner and that these foci represent the sites of AhR target genes. JF - Molecular biology of the cell AU - Elbi, Cem AU - Misteli, Tom AU - Hager, Gordon L AD - Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-5055, USA. Y1 - 2002/06// PY - 2002 DA - June 2002 SP - 2001 EP - 2015 VL - 13 IS - 6 SN - 1059-1524, 1059-1524 KW - Amanitins KW - 0 KW - Arnt protein, mouse KW - DNA-Binding Proteins KW - Luminescent Proteins KW - Receptors, Aryl Hydrocarbon KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - Transcription Factors KW - Aryl Hydrocarbon Receptor Nuclear Translocator KW - 138391-32-9 KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Index Medicus KW - Animals KW - Luminescent Proteins -- metabolism KW - Mice KW - Mutagenesis KW - Recombinant Fusion Proteins -- metabolism KW - Liver Neoplasms, Experimental KW - Tumor Cells, Cultured KW - Transfection KW - Recombinant Proteins -- metabolism KW - Amanitins -- pharmacology KW - Genes, Reporter KW - Luminescent Proteins -- genetics KW - Protein Transport KW - Transcription, Genetic -- drug effects KW - Transcription Factors -- metabolism KW - Receptors, Aryl Hydrocarbon -- metabolism KW - Receptors, Aryl Hydrocarbon -- genetics KW - Receptors, Aryl Hydrocarbon -- deficiency KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71810244?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+biology+of+the+cell&rft.atitle=Recruitment+of+dioxin+receptor+to+active+transcription+sites.&rft.au=Elbi%2C+Cem%3BMisteli%2C+Tom%3BHager%2C+Gordon+L&rft.aulast=Elbi&rft.aufirst=Cem&rft.date=2002-06-01&rft.volume=13&rft.issue=6&rft.spage=2001&rft.isbn=&rft.btitle=&rft.title=Molecular+biology+of+the+cell&rft.issn=10591524&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-13 N1 - Date created - 2002-06-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):779-82 [10639156] Mol Pharmacol. 1994 Oct;46(4):618-26 [7526149] Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5510-4 [7539918] Annu Rev Pharmacol Toxicol. 1995;35:307-40 [7598497] J Cell Sci. 1995 Sep;108 ( Pt 9):3003-11 [8537440] Mol Cell Biol. 1996 Jan;16(1):430-6 [8524325] Genes Dev. 1996 Jan 1;10(1):93-102 [8557198] Genes Dev. 1996 Jan 1;10(1):103-17 [8557189] Mol Cell Biol. 1996 May;16(5):2144-50 [8628281] Cell. 1996 May 3;85(3):403-14 [8616895] Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6731-6 [8692887] J Cell Sci. 1996 Apr;109 ( Pt 4):787-92 [8718670] EMBO J. 1996 Jul 15;15(14):3667-75 [8670870] J Cell Sci. 1996 Jun;109 ( Pt 6):1427-36 [8799830] Mol Biol Cell. 1996 Oct;7(10):1559-72 [8898362] Exp Cell Res. 1996 Dec 15;229(2):201-3 [8986598] Dev Biol. 1997 Jan 15;181(2):296-307 [9013938] Exp Cell Res. 1997 Feb 25;231(1):27-37 [9056409] Nature. 1997 Mar 27;386(6623):403-7 [9121557] Crit Rev Toxicol. 1997 Mar;27(2):109-34 [9099515] J Biol Chem. 1997 Apr 25;272(17):11452-6 [9111057] Cell. 1997 May 16;89(4):641-53 [9160755] J Cell Sci. 1997 Aug;110 ( Pt 15):1781-91 [9264465] Cell. 1997 Sep 19;90(6):1003-11 [9323128] Nature. 1997 Oct 2;389(6650):512-6 [9333243] Mol Cell Biol. 1998 Feb;18(2):978-88 [9447995] Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1585-9 [9465059] Genes Dev. 1998 Mar 1;12(5):607-20 [9499397] Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2973-8 [9501200] Arch Biochem Biophys. 1998 Oct 1;358(1):149-56 [9750175] J Cell Biol. 1998 Oct 5;143(1):35-47 [9763419] Mol Endocrinol. 1999 Mar;13(3):366-75 [10076994] Annu Rev Pharmacol Toxicol. 1999;39:103-25 [10331078] Genes Dev. 1999 Jul 1;13(13):1742-53 [10398686] J Cell Biol. 1999 Aug 9;146(3):543-58 [10444064] Science. 1991 May 17;252(5008):954-8 [1852076] Oncogene. 2000 Jan 6;19(1):85-96 [10644983] Annu Rev Pharmacol Toxicol. 2000;40:519-61 [10836146] J Cell Biol. 2000 Jul 10;150(1):265-73 [10893273] J Steroid Biochem Mol Biol. 2000 Nov 30;74(5):249-54 [11162932] J Biol Chem. 1982 Jun 10;257(11):6402-7 [6896205] Cell. 1991 Dec 20;67(6):1157-67 [1760843] Biochem Biophys Res Commun. 1992 Apr 15;184(1):246-53 [1314586] Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8185-9 [1325649] EMBO J. 1993 Mar;12(3):1059-65 [8458323] J Cell Biol. 1993 Jul;122(2):283-93 [8320255] Mol Pharmacol. 1993 Sep;44(3):511-8 [8396713] Mol Pharmacol. 1994 Mar;45(3):428-38 [8145729] J Cell Sci. 1994 Feb;107 ( Pt 2):639-48 [8207086] Mol Cell Biol. 1994 Sep;14(9):6075-86 [8065341] J Biol Chem. 1994 Nov 11;269(45):28098-105 [7961746] Science. 1995 May 5;268(5211):722-6 [7732381] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thalidomide metabolism by the CYP2C subfamily. AN - 71805648; 12060642 AB - This research investigated the biotransformation of thalidomide by cytochrome P-450 (CYP). We used liver microsomes from humans and/or animals and the recombinant specific CYP isozymes to investigate CYP-mediated metabolism of thalidomide. Thalidomide was biotransformed into 5-hydroxythalidomide (5-OH) and diastereomeric 5'-hydroxythalidomide (5'-OH) by liver microsomes. The human liver microsomes with higher CYP2C19 activity formed more metabolites than those with lower CYP2C19 activity and had less activity in metabolite formations than those from rats. Recombinant human CYP2C19 and rat CYP2C6 isozymes were primarily responsible for forming these metabolites, and the male rat-specific CYP2C11 formed only 5'-OH. 5-OH was subsequently hydroxylated to 5,6-dihydroxythalidomide by CYP2C19, CYP2C9, and CYP1A1 in humans and by CYP2C11, CYP1A1, CYP2C6, and CYP2C12 in rats. Incubations with S-mephenytoin and omeprazole, substrates of CYP2C19, inhibited metabolism by human liver microsomes, supporting the involvement of CYP2C19. alpha-Naphthoflavone, an inhibitor of CYP1A, simultaneously stimulated the 5-OH formation and inhibited cis-5'-OH formation catalyzed by human liver microsomes. The contribution of the CYP2C subfamily was supported by the immunoinhibition study using human liver microsomes. When we used the microsomes from treated rats, the metabolite formations did not increase by inducers for CYP1A, CYP2B, CYP2E, CYP3A, or CYP4A, suggesting that these could not be involved in the main metabolic pathway in rats. We discovered that the polymorphic enzyme CYP2C19 is responsible for 5- and 5'-hydroxylation of thalidomide in humans. In rats, thalidomide was hydroxylated extensively by CYP2C6 as well as the sex-specific enzyme CYP2C11. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Ando, Yuichi AU - Fuse, Eiichi AU - Figg, William D AD - Molecular Pharmacology Section, Cancer Therapeutic Branch, Center for Cancer Research, National Cancer Institute/NIH, Building 10 Room 5A01, 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 2002/06// PY - 2002 DA - June 2002 SP - 1964 EP - 1973 VL - 8 IS - 6 SN - 1078-0432, 1078-0432 KW - Isoenzymes KW - 0 KW - Recombinant Proteins KW - Teratogens KW - cytochrome P-450 CYP2C subfamily KW - Thalidomide KW - 4Z8R6ORS6L KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Animals KW - Stereoisomerism KW - Humans KW - Mice KW - Rabbits KW - Chromatography, High Pressure Liquid KW - Isoenzymes -- metabolism KW - Rats KW - Rats, Sprague-Dawley KW - Rats, Inbred F344 KW - Recombinant Proteins -- metabolism KW - Biotransformation KW - Dogs KW - Female KW - Male KW - Teratogens -- metabolism KW - Microsomes, Liver -- enzymology KW - Thalidomide -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71805648?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Thalidomide+metabolism+by+the+CYP2C+subfamily.&rft.au=Ando%2C+Yuichi%3BFuse%2C+Eiichi%3BFigg%2C+William+D&rft.aulast=Ando&rft.aufirst=Yuichi&rft.date=2002-06-01&rft.volume=8&rft.issue=6&rft.spage=1964&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-27 N1 - Date created - 2002-06-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preoperative chemoradiation in patients with resectable rectal cancer: results on tumor response. AN - 71799803; 12052754 AB - There is no consensus about the role of preoperative radiotherapy (RT) and chemotherapy (CT) in patients with resectable cancer of the distal rectum. This study analyzed the local clinical and pathologic response in patients receiving preoperative RT/CT for rectal cancer. Thirty-two consecutive patients with a palpable adenocarcinoma of the rectum received preoperative RT (45 Gy in 25 fractions over 5 weeks) plus continuous chemotherapy with doxifluridine and leucovorin or 5-fluorouracil by continuous intravenous infusion during RT. Surgery was performed 8 weeks later. The Wilcoxon and chi(2) tests were used for data analysis. Twelve patients had mild gastrointestinal toxicity, only one of whom required interruption of therapy. The tumor shrank to 57.8% of its original size, and at the echoendoscopy (u) there was a 58.7% decrease of the maximum diameter (P <.001). Downstaging from uT3 and uT2 to 2 people [OR = 2.3, 95% CI: 1.3-4.2]), washing/bathing in a pond or ditch (OR = 1.5, 95% CI: 1.0-2.4), and medium (OR = 1.6, 95% CI: 1.3-2.0) and low (OR = 2.3, 95% CI: 1.9-2.9) compared to high village education level, and reduced for never being married or divorced (OR = 0.4, 95% CI: 0.2-1.0). There was also a suggestion that source of drinking water, especially water from a shallow village well might be related to H. pylori seropositivity. There was no evidence of an association between H. pylori prevalence and alcohol or tobacco use, raw fruit and vegetable intake, or individual social class measures. Conclusions The results of this study suggest that person-to-person transmission is the most plausible route of H. pylori infection in this rural Chinese population, but waterborne exposures deserve further investigation. JF - International Journal of Epidemiology AU - Brown, L M AU - Thomas, T L AU - Ma, J-L AU - Chang, Y S AU - You, W-C AU - Liu, W-D AU - Zhang, L AU - Pee, D AU - Gail, M H AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Executive Plaza South, Room 8026, 6120 Executive Blvd. MSC 7244, Bethesda, MD 20892-7244, USA, BrownL@mail.nih.gov Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 638 EP - 645 VL - 31 IS - 3 SN - 0300-5771, 0300-5771 KW - alcohol use KW - life style KW - Microbiology Abstracts B: Bacteriology KW - J 02846:Gastrointestinal tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18679303?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Epidemiology&rft.atitle=Helicobacter+pylori+infection+in+rural+China%3A+demographic%2C+lifestyle+and+environmental+factors&rft.au=Brown%2C+L+M%3BThomas%2C+T+L%3BMa%2C+J-L%3BChang%2C+Y+S%3BYou%2C+W-C%3BLiu%2C+W-D%3BZhang%2C+L%3BPee%2C+D%3BGail%2C+M+H&rft.aulast=Brown&rft.aufirst=L&rft.date=2002-06-01&rft.volume=31&rft.issue=3&rft.spage=638&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Epidemiology&rft.issn=03005771&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Computational selection of distinct class- and subclass-specific gene expression signatures AN - 18675592; 5568465 AB - In this investigation we used statistical methods to select genes with expression profiles that partition classes and subclasses of biological samples. Gene expression data corresponding to liver samples from rats treated for 24 h with an enzyme inducer (phenobarbital) or a peroxisome proliferator (clofibrate, gemfibrozil or Wyeth 14,643) were subjected to a modified Z-score test to identify gene outliers and a binomial distribution to reduce the probability of detecting genes as differentially expressed by chance. Hierarchical clustering of 238 statistically valid differentially expressed genes partitioned class- specific gene expression signatures into groups that clustered samples exposed to the enzyme inducer or to peroxisome proliferators. Using analysis of variance (ANOVA) and linear discriminant analysis methods we identified single genes as well as coupled gene expression profiles that separated the phenobarbital from the peroxisome proliferator treated samples and discerned the fibrate (gemfibrozil and clofibrate) subclass of peroxisome proliferators. A comparison of genes ranked by ANOVA with genes assessed as significant by mixed linear models analysis [J. Comput. Biol. 8 (2001) 625] or ranked by information gain revealed good congruence with the top 10 genes from each statistical method in the contrast between phenobarbital and peroxisome proliferators expression profiles. We propose building upon a classification regimen comprised of analysis of replicate data, outlier diagnostics and gene selection procedures to utilize cDNA microarray data to categorize subclasses of samples exposed to pharmacologic agents. JF - Journal of Biomedical Informatics AU - Bushel, PR AU - Hamadeh, H K AU - Bennett, L AU - Green, J AU - Ableson, A AU - Misener, S AU - Afshari, CA AU - Paules, R S AD - National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA, bushel@niehs.nih.gov Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 160 EP - 170 VL - 35 IS - 3 SN - 1532-0464, 1532-0464 KW - DNA microarrays KW - cDNA KW - gemfibrozil KW - gene expression KW - peroxisome proliferators KW - phenobarbital KW - rats KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18675592?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biomedical+Informatics&rft.atitle=Computational+selection+of+distinct+class-+and+subclass-specific+gene+expression+signatures&rft.au=Bushel%2C+PR%3BHamadeh%2C+H+K%3BBennett%2C+L%3BGreen%2C+J%3BAbleson%2C+A%3BMisener%2C+S%3BAfshari%2C+CA%3BPaules%2C+R+S&rft.aulast=Bushel&rft.aufirst=PR&rft.date=2002-06-01&rft.volume=35&rft.issue=3&rft.spage=160&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomedical+Informatics&rft.issn=15320464&rft_id=info:doi/10.1016%2FS1532-0464%2802%2900525-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S1532-0464(02)00525-7 ER - TY - JOUR T1 - Transfer of super(131)I into human breast milk and transfer coefficients for radiological dose assessments AN - 18599504; 5451626 AB - Data on transfer of radioiodine into human milk are rare in the literature. Data from sixteen publications were reviewed and analyzed to estimate the transfer coefficient (f sub(hm)*, having units of d L super(-1)). The data on the radioiodine concentration in breast milk were analyzed by two methods: direct numerical integration and integration of a fitted exponential model. In general, the integrated fitted functions were greater. The fitted functions likely better describe the transfer into milk since few data sets sampled mothers' milk near the time of maximum excretion. The derived transfer coefficient values seem to represent two populations. The first group was those individuals who had very low excretions, including those where thyroid and mammary uptake was impaired by the administration of stable iodine or iodinated compounds. The second group included those with much higher excretions. The second group, termed the "normal-excretion" group, had transfers of iodine to milk that were more than ten-fold higher than in the "low-excretion" group. The derived milk transfer coefficient data for the low- and normal-excretion groups fitted to lognormal distributions gave geometric means, (geometric standard deviations), of 0.043 d L super(-1) (2.1, n = 14) and 0.37 d L super(-1) (1.5, n = 12), respectively. Estimates of the effective half-time (time from maximum concentration to half the value) were determined for the low- and normal-excretion groups separately. There was evidence that the effective half-time was longer for the normal- than for the low-excretion group; the geometric mean (and geometric standard deviation) were 12 (1.7) and 8.5 (2.6) h, respectively, though the difference was not statistically significant. The geometric mean times to maximum milk concentration in the low- and normal-excretion groups were nearly identical, 9.4 (3.1) and 9.0 (1.6) h, respectively. The data show that administration of large doses of stable iodine (commonly used to block uptake of iodine into the thyroid) is also an effective means to block radioiodine transfer into milk. Thus, protecting the mother's thyroid also protects the nursing infant. Despite inadequacies of available data describing the transfer of radioiodine to human milk within a healthy population of women, the values of f sub(hm)* provided here are believed to be the best available for use in radiological assessments. These values are particularly applicable to lactating women having normal diets and availability to stable iodine, as in the United States. JF - Health Physics AU - Simon, S L AU - Luckyanov, N AU - Bouville, A AU - VanMiddlesworth, L AU - Weinstock, R M AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA, ssimon@mail.nih.gov Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 796 EP - 806 VL - 82 IS - 6 SN - 0017-9078, 0017-9078 KW - man KW - transfer KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - X 24210:Radiation & radioactive materials KW - H 8000:Radiation Safety/Electrical Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18599504?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+Physics&rft.atitle=Transfer+of+super%28131%29I+into+human+breast+milk+and+transfer+coefficients+for+radiological+dose+assessments&rft.au=Simon%2C+S+L%3BLuckyanov%2C+N%3BBouville%2C+A%3BVanMiddlesworth%2C+L%3BWeinstock%2C+R+M&rft.aulast=Simon&rft.aufirst=S&rft.date=2002-06-01&rft.volume=82&rft.issue=6&rft.spage=796&rft.isbn=&rft.btitle=&rft.title=Health+Physics&rft.issn=00179078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Boning up on telomerase AN - 18556558; 5522977 AB - The expression of telomerase is bone marrow stromal cells brings cell-based bone tissue engineering one step closer to reality. JF - Nature Biotechnology AU - Tuan, R AD - Cartilage Biology and Orthopaedics Branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-8022, USA, Tuanr@mail.nih.gov Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 560 EP - 561 VL - 20 IS - 6 SN - 1087-0156, 1087-0156 KW - stromal cells KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts KW - N 14740:Miscellaneous KW - W 30965:Miscellaneous, Reviews KW - W3 33000:General topics and reviews KW - W4 110:Biomedical Materials & Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18556558?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=Boning+up+on+telomerase&rft.au=Tuan%2C+R&rft.aulast=Tuan&rft.aufirst=R&rft.date=2002-06-01&rft.volume=20&rft.issue=6&rft.spage=560&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Adenomatous polyp recurrence and physical activity in the Polyp Prevention Trial (United States) AN - 18476940; 5438070 AB - To examine prospectively the association between physical activity and adenomatous polyp recurrence. Information on past year total physical activity was collected annually through an interview-administered questionnaire from the 1905 men and women enrolled in a randomized dietary intervention study, the Polyp Prevention Trial. Multiple logistic regression analysis was used to examine the association between physical activity and polyp recurrence in up to three years of follow-up from baseline colonoscopy. There were no significant associations between moderate, vigorous, or total physical activity at the start of the trial and overall polyp recurrence in either men or women. Participants who reported consistent vigorous activity throughout the trial period had no significantly reduced risk of polyp recurrence compared to those who reported consistent sedentary activity (OR = 0.8, CI=0.5-1.1). Consistent vigorous activity was also not significantly associated with either advanced or multiple polyps, nor with polyp recurrence at any specific anatomical location in the large bowel. These prospective data suggest that recent physical activity is not associated with polyp recurrence in a three-year period. JF - Cancer Causes & Control AU - Colbert, L H AU - Lanza, E AU - Ballard-Barbash, R AU - Slattery, M L AU - Tangrea, JA AU - Caan, B AU - Paskett, ED AU - Iber, F AU - Kikendall, W AU - Lance, P AU - Shike, M AU - Schoen, R E AU - Daston, C AU - Schatzkin, A AD - Gateway Building, Suite 3C-309, 7201 Wisconsin Ave., MSC 9205, Bethesda, MD 20892-9205, USA, colbertl@mail.nih.gov Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 445 EP - 453 VL - 13 IS - 5 SN - 0957-5243, 0957-5243 KW - Physical Education Index KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18476940?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Adenomatous+polyp+recurrence+and+physical+activity+in+the+Polyp+Prevention+Trial+%28United+States%29&rft.au=Colbert%2C+L+H%3BLanza%2C+E%3BBallard-Barbash%2C+R%3BSlattery%2C+M+L%3BTangrea%2C+JA%3BCaan%2C+B%3BPaskett%2C+ED%3BIber%2C+F%3BKikendall%2C+W%3BLance%2C+P%3BShike%2C+M%3BSchoen%2C+R+E%3BDaston%2C+C%3BSchatzkin%2C+A&rft.aulast=Colbert&rft.aufirst=L&rft.date=2002-06-01&rft.volume=13&rft.issue=5&rft.spage=445&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - A prospective study of medical conditions, anthropometry, physical activity, and pancreatic cancer in male smokers (Finland) AN - 18476266; 5438068 AB - To examine the association between several medical conditions, anthropometric measurements, occupational and leisure physical activity, and pancreatic cancer in a cohort of male Finnish smokers. We performed a cohort analysis of the 172 subjects who developed pancreatic cancer between 1985 and 1997 (median 10.2 years follow-up) among the 29,048 male smokers, 50-69 years old, who had complete baseline data and participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Cox proportional hazards models were used to estimate multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CI). We observed positive associations between pancreatic cancer risk and self-reported history of diabetes mellitus (HR=2.02, 95% CI 1.17-3.50) and bronchial asthma (HR=2.16, 95% CI 1.17-3.98). Men having combined occupational and leisure activity greater than at sedentary levels had reduced risk for the cancer; for example those with moderate/heavy activity in both settings showed a HR of 0.42 (95% CI 0.22-0.83). There were no significant associations with other self-reported illnesses, total or HDL (high-density lipoprotein) cholesterol, height, weight, or body mass index. Our data suggest that diabetes mellitus and bronchial asthma predict the subsequent risk of developing pancreatic cancer in male smokers, and that greater physical activity may reduce the risk. JF - Cancer Causes & Control AU - Stolzenberg-Solomon, R Z AU - Pietinen, P AU - Taylor, PR AU - Virtamo, J AU - Albanes, D AD - Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda MD 6120 Executive Blvd. MSC 7026, Rockville, MD 20852-7026, USA, rs221z@nih.gov Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 417 EP - 426 VL - 13 IS - 5 SN - 0957-5243, 0957-5243 KW - man KW - Physical Education Index; Toxicology Abstracts KW - PE 090:Sports Medicine & Exercise Sport Science KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18476266?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=A+prospective+study+of+medical+conditions%2C+anthropometry%2C+physical+activity%2C+and+pancreatic+cancer+in+male+smokers+%28Finland%29&rft.au=Stolzenberg-Solomon%2C+R+Z%3BPietinen%2C+P%3BTaylor%2C+PR%3BVirtamo%2C+J%3BAlbanes%2C+D&rft.aulast=Stolzenberg-Solomon&rft.aufirst=R&rft.date=2002-06-01&rft.volume=13&rft.issue=5&rft.spage=417&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - Physical Education Index; ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Microevolutionary Genomics of Bacteria AN - 18456470; 5429874 AB - The availability of multiple complete genome sequences from the same species can facilitate attempts to systematically address basic questions in genome evolution. We refer to such efforts as 'microevolutionary genomics'. We report the results of comparative analyses of complete intraspecific genome (and proteome) sequences from four bacterial species-Chlamydophila pneumoniae, Escherichia coli, Helicobacter pylori and Neisseria meningitidis. Comparisons of average synonymous (K sub(s)) and nonsynonymous (K sub(a)) substitution rates were used to assess the influence of various biological factors on the rate of protein evolution. For example, E. coli experiences the most intense purifying selection of the species analyzed, and this may be due to the relatively larger population size of this species. In addition, essential genes were shown to be more evolutionarily conserved than nonessential genes in E. coli and duplicated genes have higher rates of evolution than unique genes for all species studied except C. pneumoniae. Different functional categories of genes were shown to evolve at significantly different rates emphasizing the role of category-specific functional constraints in determining evolutionary rates. Finally, functionally characterized genes tend to be conserved between strains, while uncharacterized genes are over-represented among the unique, strain-specific genes. This suggests the possibility that nonessential genes are responsible for driving the evolutionary diversification between strains. [copy ] 2002 Elsevier Science (USA). JF - Theoretical Population Biology AU - Jordan, I K AU - Rogozin, IB AU - Wolf, YI AU - Koonin, E V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Building. 38A, 8600 Rockville Pike, Bethesda, Maryland, 20894, koonin@ncbi.nlm.nih.gov Y1 - 2002/06/01/ PY - 2002 DA - 2002 Jun 01 SP - 435 EP - 447 PB - Academic Press VL - 61 IS - 4 SN - 0040-5809, 0040-5809 KW - microevolutionary genomics KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02740:Genetics and evolution KW - G 07260:Taxonomy, systematics and evolutionary genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18456470?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Theoretical+Population+Biology&rft.atitle=Microevolutionary+Genomics+of+Bacteria&rft.au=Jordan%2C+I+K%3BRogozin%2C+IB%3BWolf%2C+YI%3BKoonin%2C+E+V&rft.aulast=Jordan&rft.aufirst=I&rft.date=2002-06-01&rft.volume=61&rft.issue=4&rft.spage=435&rft.isbn=&rft.btitle=&rft.title=Theoretical+Population+Biology&rft.issn=00405809&rft_id=info:doi/10.1006%2Ftpbi.2002.1588 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1006/tpbi.2002.1588 ER - TY - JOUR T1 - Gene Expression Analysis Reveals Chemical-Specific Profiles AN - 18443227; 5419964 AB - The application of gene expression profiling technology to examine multiple genes and signaling pathways simultaneously promises a significant advance in understanding toxic mechanisms to ultimately aid in protection of public health. Public and private efforts in the new field of toxicogenomics are focused on populating databases with gene expression profiles of compounds where toxicological and pathological endpoints are well characterized. The validity and utility of a toxicogenomics is dependent on whether gene expression profiles that correspond to different chemicals can be distinguished. The principal hypothesis underlying a toxicogenomic or pharmacogenomic strategy is that chemical-specific patterns of altered gene expression will be revealed using high-density microarray analysis of tissues from exposed organisms. Analyses of these patterns should allow classification of toxicants and provide important mechanistic insights. This report provides a verification of this hypothesis. Patterns of gene expression corresponding to liver tissue derived from chemically exposed rats revealed similarity in gene expression profiles between animals treated with different agents from a common class of compounds, peroxisome proliferators [clofibrate (ethyl-p-chlorophenoxyisobutyrate), Wyeth 14,643 ([4-chloro-6(2,3-xylidino)-2-pyrimidinylthio]acetic acid), and gemfibrozil (5-2[2,5-dimethylphenoxy]2-2-dimethylpentanoic acid)], but a very distinct gene expression profile was produced using a compound from another class, enzyme inducers (phenobarbital). JF - Toxicological Sciences AU - Hamadeh, H K AU - Bushel, PR AU - Jayadev, S AU - Martin, K AU - DiSorbo, O AU - Sieber, S AU - Bennett, L AU - Tennant, R AU - Stoll, R AU - Barrett, J C AU - Blanchard, K AU - Paules, R S AU - Afshari, CA AD - National Institute of Environmental Health Sciences, P.O. Box 12233, MD2-04, Research Triangle Park, North Carolina 27709, USA Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 219 EP - 231 VL - 67 IS - 2 SN - 1096-6080, 1096-6080 KW - peroxisome proliferators KW - rats KW - Toxicology Abstracts KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18443227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Gene+Expression+Analysis+Reveals+Chemical-Specific+Profiles&rft.au=Hamadeh%2C+H+K%3BBushel%2C+PR%3BJayadev%2C+S%3BMartin%2C+K%3BDiSorbo%2C+O%3BSieber%2C+S%3BBennett%2C+L%3BTennant%2C+R%3BStoll%2C+R%3BBarrett%2C+J+C%3BBlanchard%2C+K%3BPaules%2C+R+S%3BAfshari%2C+CA&rft.aulast=Hamadeh&rft.aufirst=H&rft.date=2002-06-01&rft.volume=67&rft.issue=2&rft.spage=219&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Prediction of Compound Signature Using High Density Gene Expression Profiling AN - 18441847; 5419965 AB - DNA microarrays, used to measure the gene expression of thousands of genes simultaneously, hold promise for future application in efficient screening of therapeutic drugs. This will be aided by the development and population of a database with gene expression profiles corresponding to biological responses to exposures to known compounds whose toxicological and pathological endpoints are well characterized. Such databases could then be interrogated, using profiles corresponding to biological responses to drugs after developmental or environmental exposures. A positive correlation with an archived profile could lead to some knowledge regarding the potential effects of the tested compound or exposure. We have previously shown that cDNA microarrays can be used to generate chemical-specific gene expression profiles that can be distinguished across and within compound classes, using clustering, simple correlation, or principal component analyses. In this report, we test the hypothesis that knowledge can be gained regarding the nature of blinded samples, using an initial training set comprised of gene expression profiles derived from rat liver exposed to clofibrate, Wyeth 14,643, gemfibrozil, or phenobarbital for 24 h or 2 weeks of exposure. Highly discriminant genes were derived from our database training set using approaches including linear discriminant analysis (LDA) and genetic algorithm/K-nearest neighbors (GA/KNN). Using these genes in the analysis of coded liver RNA samples derived from 24-h, 3-day, or 2-week exposures to phenytoin, diethylhexylpthalate, or hexobarbital led to successful prediction of whether these samples were derived from livers of rats exposed to enzyme inducers or to peroxisome proliferators. This validates our initial hypothesis and lends credibility to the concept that the further development of a gene expression database for chemical effects will greatly enhance the hazard identification processes. JF - Toxicological Sciences AU - Hamadeh, H K AU - Bushel, PR AU - Jayadev, S AU - DiSorbo, O AU - Bennett, L AU - Li, L AU - Tennant, R AU - Stoll, R AU - Barrett, J C AU - Paules, R S AU - Blanchard, K AU - Afshari, CA AD - National Institute of Environmental Health Sciences, P.O. Box 12233, MD2-04, Research Triangle Park, North Carolina 27709, USA Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 232 EP - 240 VL - 67 IS - 2 SN - 1096-6080, 1096-6080 KW - DNA microarrays KW - Wyeth 14 KW - clofibrate KW - peroxisome proliferators KW - rats KW - Toxicology Abstracts KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18441847?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Prediction+of+Compound+Signature+Using+High+Density+Gene+Expression+Profiling&rft.au=Hamadeh%2C+H+K%3BBushel%2C+PR%3BJayadev%2C+S%3BDiSorbo%2C+O%3BBennett%2C+L%3BLi%2C+L%3BTennant%2C+R%3BStoll%2C+R%3BBarrett%2C+J+C%3BPaules%2C+R+S%3BBlanchard%2C+K%3BAfshari%2C+CA&rft.aulast=Hamadeh&rft.aufirst=H&rft.date=2002-06-01&rft.volume=67&rft.issue=2&rft.spage=232&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Research on tobacco use among teenagers: ethical challenges AN - 18433829; 5411019 AB - Recent increases in adolescent smoking portend upcoming public health challenges as the majority of smokers initiate long-term addiction during youth, but experience major health consequences later in life. To effectively address this important teenage and adult health issue, critical research information and early interventions are needed, yet conducting tobacco research with teen smokers poses substantial challenges, including several ethical dilemmas. This paper reviews some of the ethical issues presented in etiologic and clinical treatment research addressing adolescent smoking. Common problems and possible solutions are presented. Issues of parent/guardian involvement, decision-making ability of teens, the need to maintain confidentiality are discussed, along with the specific problems of recruitment, compensation, and ethical challenges that arise in group treatment settings. Context-specific ethical adjustments and alternative perspectives are likely to be needed if we are to overcome procedural difficulties in conducting teen smoking studies. JF - Journal of Adolescent Health AU - Moolchan, E T AU - Mermelstein, R AD - National Institutes of Health, National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland, USA Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 409 EP - 417 VL - 30 IS - 6 SN - 1054-139X, 1054-139X KW - Physical Education Index KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18433829?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Adolescent+Health&rft.atitle=Research+on+tobacco+use+among+teenagers%3A+ethical+challenges&rft.au=Moolchan%2C+E+T%3BMermelstein%2C+R&rft.aulast=Moolchan&rft.aufirst=E&rft.date=2002-06-01&rft.volume=30&rft.issue=6&rft.spage=409&rft.isbn=&rft.btitle=&rft.title=Journal+of+Adolescent+Health&rft.issn=1054139X&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Genomics of the marA/soxS/rob regulon of Escherichia coli : identification of directly activated promoters by application of molecular genetics and informatics to microarray data AN - 18428111; 5411814 AB - Microarray analyses are providing a plethora of data concerning transcriptional responses to specific gene regulators and their inducers but do not distinguish between direct and indirect responses. Here, we identify directly activated promoters of the overlapping marA , soxS and rob regulon(s) of Escherichia coli by applying informatics, genomics and molecular genetics to microarray data obtained by others. Those studies found that overexpression of marA , or the treatment of cells with salicylate to derepress marA , or treatment with paraquat to induce soxS , resulted in elevated transcription of 153 genes. However, only 27 out of the promoters showed increased transcription under at least two of the aforementioned conditions and eight of those were previously known to be directly activated. A computer algorithm was used to identify potential activator binding sites located upstream of the remaining 19 promoters of this subset, and conventional genetic and biochemical approaches were applied to test whether these sites are critical for activation by the homologous MarA, SoxS and Rob transcriptional activators. Only seven out of the 19 promoters were found to be activated when fused to lacZ and tested as single lysogens. All seven contained an essential activator binding site. The remaining promoters were insensitive to stimulation by the inducers suggesting that the great majority of elevated microarray transcripts either were misidentified or resulted from indirect effects requiring sequences outside of the promoter region. We estimate that the total number of directly activated promoters in the regulon is less than 40. JF - Molecular Microbiology AU - Martin, R G AU - Rosner, J L AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0560, USA. Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 1611 EP - 1624 PB - Blackwell Science Ltd VL - 44 IS - 6 SN - 0950-382X, 0950-382X KW - DNA microarrays KW - MarA protein KW - Rob protein KW - SoxS protein KW - marA/soxS/rob regulon KW - microarrays KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - N 14555:Miscellaneous KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18428111?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Genomics+of+the+marA%2FsoxS%2Frob+regulon+of+Escherichia+coli+%3A+identification+of+directly+activated+promoters+by+application+of+molecular+genetics+and+informatics+to+microarray+data&rft.au=Martin%2C+R+G%3BRosner%2C+J+L&rft.aulast=Martin&rft.aufirst=R&rft.date=2002-06-01&rft.volume=44&rft.issue=6&rft.spage=1611&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2002.02985.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1046/j.1365-2958.2002.02985.x ER - TY - JOUR T1 - The Immunotherapy of Patients With Ovarian Cancer AN - 18414006; 5395099 AB - Ovarian cancer is a leading cause of cancer mortality. Chemotherapy is effective in reducing tumor burden in a majority of patients, however, only approximately 20% of advanced disease patients will ultimately survive tumor free, and further treatment options are needed. Continuing advances in immunology make immunotherapy a promising area for future research. The design of immunotherapy strategies for ovarian cancer requires an understanding of the immune microenvironment of the peritoneal cavity, which is frequently involved with ovarian cancer metastases and is the site of its most devastating effects. Immunotherapy approaches for ovarian cancer include locoregional and systemic cytokine therapies, prophylactic and therapeutic vaccines, and adoptive immunotherapy strategies. This review will summarize previous clinical trials as well as future directions for research. Further progress in T-cell specific immune responses will require the identification of specific ovarian cancer antigens that are processed and presented on the surface of tumor cells in the context of specific HLA molecules. In addition, a more detailed understanding of functional relations between the peritoneal microenvironment and the metastatic process is required. JF - Journal of Immunotherapy AU - Hwu, P AU - Freedman, R S AD - National Cancer Institute, Bethesda, Maryland; and The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 189 EP - 201 VL - 25 IS - 3 SN - 1067-5582, 1067-5582 KW - histocompatibility antigen HLA KW - man KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Immunology Abstracts KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - F 06818:Cancer immunotherapy KW - F 06838:Human KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18414006?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunotherapy&rft.atitle=The+Immunotherapy+of+Patients+With+Ovarian+Cancer&rft.au=Hwu%2C+P%3BFreedman%2C+R+S&rft.aulast=Hwu&rft.aufirst=P&rft.date=2002-06-01&rft.volume=25&rft.issue=3&rft.spage=189&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunotherapy&rft.issn=10675582&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Frequency of MART-1/MelanA and gp100/PMel17-Specific T Cells in Tumor Metastases and Cultured Tumor-Infiltrating Lymphocytes AN - 18410513; 5395106 AB - Melanoma differentiation antigens, such as MART-1/MelanA and gp100/PMel17, frequently are observed as targets of tumor infiltrating lymphocytes (TIL) originated from HLA-A*0201-expressing patients with melanoma. Furthermore, particular clinical relevance was attributed to gp100/pMel17 based on the impression that the adoptive transfer of gp100-recognizing TIL was associated with clinical responses in a small group of patients. However, the actual frequency of specific T cells for these melanoma differentiation antigens has never been directly enumerated in ex vivo or in vitro expanded TIL cultures. Here, we enumerated melanoma differentiation antigen-specific T-cell precursor frequency in TIL using tetrameric HLA/epitope complexes, functionally characterizing their responsiveness to cognate epitope by cytokine release assay. T-cell precursor frequencies were enumerated in 11 fresh-tumor preparations and 17 TIL adoptively transferred into patients bearing HLA-A*0201. MART-1 or gp100-specific T cells could be detected respectively in 5 and 2 of the 11 fresh preparations and in 5 and 2 of the 17 adoptively transferred TIL. With one exception, melanoma differentiation antigen-specific T-cell precursor frequency in fresh material and TIL ranged between 5,000 to 21,000/10 super(6) CD8 super(+) T cells. T-cell precursor frequency was not significantly higher in TIL whose administration was associated with clinical response. These data provide direct enumeration of MART-1/MelanA and gp100/pMel17 reactivity ex vivo and in vitro in the context of HLA-A*0201. JF - Journal of Immunotherapy AU - Seiter, S AU - Monsurro, V AU - Nielsen, M-B AU - Wang, E AU - Provenzano, M AU - Wunderlich, R AU - Rosenberg, SA AU - Marincola, F M AD - Department of Transfusion Medicine, Clinical Center, Surgery Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 252 EP - 263 VL - 25 IS - 3 SN - 1067-5582, 1067-5582 KW - A determinant KW - Melan-A antigen KW - PMel17 antigen KW - histocompatibility antigen HLA KW - man KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Immunology Abstracts KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - F 06818:Cancer immunotherapy KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18410513?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunotherapy&rft.atitle=Frequency+of+MART-1%2FMelanA+and+gp100%2FPMel17-Specific+T+Cells+in+Tumor+Metastases+and+Cultured+Tumor-Infiltrating+Lymphocytes&rft.au=Seiter%2C+S%3BMonsurro%2C+V%3BNielsen%2C+M-B%3BWang%2C+E%3BProvenzano%2C+M%3BWunderlich%2C+R%3BRosenberg%2C+SA%3BMarincola%2C+F+M&rft.aulast=Seiter&rft.aufirst=S&rft.date=2002-06-01&rft.volume=25&rft.issue=3&rft.spage=252&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunotherapy&rft.issn=10675582&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Mobilization of Dendritic Cell Precursors in Patients With Cancer by Flt3 Ligand Allows the Generation of Higher Yields of Cultured Dendritic Cells AN - 18407912; 5395109 AB - Flt3 ligand (Flt3L) stimulates the proliferation and differentiation of hematopoietic cells. Subcutaneous Flt3L administration has been shown to effectively manage some murine cancers and in humans, to lead to an increase in peripheral blood monocyte and dendritic cell (DC) counts. In the current study, we determined the effects of Flt3L therapy on patients with melanoma and renal cancer, and in particular, if Flt3L could be used either by enhancing the immunization of patients with melanoma to tumor antigen peptides in vivo, or by mobilizing DC precursors to allow the production of larger numbers of cultured DC. Flt3 ligand administration resulted in a 19-fold increase in DC counts in the peripheral blood of patients. The DC generated in vivo appeared only partially activated, expressing increased levels of CD86, CD33, and major histocompatibility complex class II, but no or low levels of CD80 and CD83. This partial activation may account for the lack of enhanced immune responses to melanoma antigens and absence of clinical responses in the patients even in combination with antigen immunization. Flt3 ligand administration did result, however, in a 7-fold increased yield of monocytes per liter of blood from leukapheresed patients. Dendritic cells were as readily generated from monocytes collected before and after Flt3L therapy, and they stimulated allogeneic T-cell proliferation in a mixed leukocyte reaction to a similar magnitude. Thus, the use of Flt3L may be an important method to mobilize DC precursors to allow patient therapy with larger numbers of cultured DC. JF - Journal of Immunotherapy AU - Marroquin, CE AU - Westwood, JA AU - Lapointe, R AU - Mixon, A AU - Wunderlich, J R AU - Caron, D AU - Rosenberg, SA AU - Hwu, P AD - National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 278 EP - 288 VL - 25 IS - 3 SN - 1067-5582, 1067-5582 KW - Flt3L protein KW - man KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Immunology Abstracts KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - F 06818:Cancer immunotherapy KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18407912?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunotherapy&rft.atitle=Mobilization+of+Dendritic+Cell+Precursors+in+Patients+With+Cancer+by+Flt3+Ligand+Allows+the+Generation+of+Higher+Yields+of+Cultured+Dendritic+Cells&rft.au=Marroquin%2C+CE%3BWestwood%2C+JA%3BLapointe%2C+R%3BMixon%2C+A%3BWunderlich%2C+J+R%3BCaron%2C+D%3BRosenberg%2C+SA%3BHwu%2C+P&rft.aulast=Marroquin&rft.aufirst=CE&rft.date=2002-06-01&rft.volume=25&rft.issue=3&rft.spage=278&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunotherapy&rft.issn=10675582&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Malignant Neoplasms after Radiation Therapy for Peptic Ulcer AN - 18391206; 5374024 AB - Most information on radiation-related cancer risk comes from the Life Span Study (LSS) of the Japanese atomic bomb survivors. Stomach cancer mortality rates are much higher in Japan than in the U.S., making the applicability of LSS findings to the U.S. population uncertain. A unique cohort of U.S. patients who were irradiated for peptic ulcer to control gastric secretion provides a different perspective on risk. Cancer mortality data were analyzed and relative risks estimated for 3719 subjects treated by radiotherapy (mean stomach dose 14.8 Gy) and/or by surgery and medication during the period 1936-1965 and followed through 1997 (average 25 years). Compared to the U.S. rates, stomach cancer mortality was significantly increased for irradiated and nonirradiated patients (observed/expected = 3.20 and 1.52, respectively). We observed strong evidence of exposure-related excess mortality from cancer of the stomach (RR 2.6, 95% CI 1.3, 5.1), pancreas (RR 2.7, 95% CI 1.5, 5.1), and lung (RR 1.5, 95% CI 1.1, 2.1), with commensurate radiation dose responses in analyses that included nonexposed patients. However, the dose responses for these cancers were not significant when restricted to exposed patients. Our excess relative risk per gray estimate of 0.20 at doses ,10 Gy (95% CI 0, 0.73) is consistent with the estimate of 0.24 (95% CI 0.10, 0.40) obtained from the LSS study with the linear model. JF - Radiation Research AU - Carr, Z A AU - Kleinerman, R A AU - Stovall, M AU - Weinstock, R M AU - Griem, M L AU - Land, CE AD - Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, abylkasz@mail.nih.gov Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 668 EP - 677 PB - The Radiation Research Society VL - 157 IS - 6 SN - 0033-7587, 0033-7587 KW - Toxicology Abstracts KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18391206?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+Research&rft.atitle=Malignant+Neoplasms+after+Radiation+Therapy+for+Peptic+Ulcer&rft.au=Carr%2C+Z+A%3BKleinerman%2C+R+A%3BStovall%2C+M%3BWeinstock%2C+R+M%3BGriem%2C+M+L%3BLand%2C+CE&rft.aulast=Carr&rft.aufirst=Z&rft.date=2002-06-01&rft.volume=157&rft.issue=6&rft.spage=668&rft.isbn=&rft.btitle=&rft.title=Radiation+Research&rft.issn=00337587&rft_id=info:doi/10.1043%2F0033-7587%282002%29157%280668%3AMNARTF%292.0.CO%3B2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1043/0033-7587(2002)157(0668:MNARTF)2.0.CO;2 ER - TY - JOUR T1 - Acute Methamphetamine Administration Upregulates NGFI-B mRNA Expression in the Striatum: Co-localization with C-FOS Immunoreactivity AN - 18390709; 5376113 AB - In this study, the effects of acute methamphetamine administration on expression of the nuclear transcription factor NGFI-B mRNA and its co-localization with c-Fos immunoreactivity in the striatum were evaluated in animals receiving a single dose of methamphetamine (4 mg/kg) given at 2 or 6 h prior to perfusion. All animals received a daily saline injection for 6 days prior to methamphetamine treatment. We have found that, similar to c-fos activation, NGFI-B mRNA levels were significantly increased 2 h after methamphetamine treatment and returned to basal levels 6 h later. Induction of NGFI-B mRNA levels by methamphetamine was highest in central striatum as compared to the dorsomedial distribution pattern observed in control animals. After acute methamphetamine treatment, the distribution pattern of NGFI-B mRNA upregulation was very similar to that of methamphetamine induced c-Fos immunoreactivity. However, co-localization studies with c-Fos immunoreactivity showed that not all NGFI-B-positive cells contained c-Fos after methamphetamine treatment. Forty-five percent of all NGFI-B mRNA expressing neurons contained c-Fos immunoreactivity in the dorsomedial striatum as compared to 60% in central and 35% in ventrolateral striatum. This study provides a detailed description of the differential spatial and temporal modulation of NGFI-B and c-Fos expression in the striatum by acute methamphetamine treatment over time. JF - Synapse AU - Baeckman, C AU - Morales, M AD - Cellular Neurobiology Department, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, cbackman@intra.nida.nih.gov Y1 - 2002/06/01/ PY - 2002 DA - 2002 Jun 01 SP - 158 EP - 165 VL - 44 IS - 3 SN - 0887-4476, 0887-4476 KW - NGFI-B KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - N3 11104:Mammals (except primates) KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18390709?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Synapse&rft.atitle=Acute+Methamphetamine+Administration+Upregulates+NGFI-B+mRNA+Expression+in+the+Striatum%3A+Co-localization+with+C-FOS+Immunoreactivity&rft.au=Baeckman%2C+C%3BMorales%2C+M&rft.aulast=Baeckman&rft.aufirst=C&rft.date=2002-06-01&rft.volume=44&rft.issue=3&rft.spage=158&rft.isbn=&rft.btitle=&rft.title=Synapse&rft.issn=08874476&rft_id=info:doi/10.1002%2Fsyn.10065 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/syn.10065 ER - TY - JOUR T1 - Intramolecular Regulation of the Opposing (p)ppGpp Catalytic Activities of Rel sub(Seq), the Rel/Spo Enzyme from Streptococcus equisimilis AN - 18379843; 5367429 AB - Catalytic and regulatory domains of the Rel/Spo homolog of Streptococcus equisimilis affecting (p)ppGpp synthesis and degradation activities have been defined, and opposing activities of the purified protein and its fragments have been compared. Two major domains of the 739-residue Rel sub(Seq) protein are defined by limited proteolytic digestion. In vitro assays of the purified N- terminal half-protein reveal synthesis of (p)ppGpp by an ATP-GTP 3'- pyrophosphotransferase as well as an ability to degrade (p)ppGpp by a Mn super(2+)- dependent 3'-pyrophosphohydrolase. Removal of the C-terminal half-protein has reciprocal regulatory effects on the activities of the N-terminal half-protein. Compared to the full-length protein, deletion activates (p)ppGpp synthesis specific activity about 12-fold and simultaneously inhibits (p)ppGpp degradation specific activity about 150-fold to shift the balance of the two activities in favor of synthesis. Cellular (p)ppGpp accumulation behavior is consistent with these changes. The bifunctional N-terminal half-protein can be further dissected into overlapping monofunctional subdomains, since purified peptides display either degradation activity (residues 1 to 224) or synthetic activity (residues 79 to 385) in vitro. These assignments can also apply to RelA and SpoT. The ability of Rel sub(Seq) to mediate (p)ppGpp accumulation during amino acid starvation in S. equisimilis is absent when the protein is expressed ectopically in Escherichia coli. Fusing the N-terminal half of Rel sub(Seq) with the C-terminal domain of RelA creates a chimeric protein that restores the stringent response in E. coli by inhibiting unregulated degradation and restoring regulated synthetic activity. Reciprocal intramolecular regulation of the dual activities may be a general intrinsic feature of Rel/Spo homolog proteins. JF - Journal of Bacteriology AU - Mechold, U AU - Murphy, H AU - Brown, L AU - Cashel, M AD - Building 6B, Room 3B-314, National Institutes of Health, Bethesda, MD 20892- 2785., mcashel@nih.gov Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 2878 EP - 2888 VL - 184 IS - 11 SN - 0021-9193, 0021-9193 KW - Rel protein KW - Spo protein KW - Microbiology Abstracts B: Bacteriology KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18379843?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Intramolecular+Regulation+of+the+Opposing+%28p%29ppGpp+Catalytic+Activities+of+Rel+sub%28Seq%29%2C+the+Rel%2FSpo+Enzyme+from+Streptococcus+equisimilis&rft.au=Mechold%2C+U%3BMurphy%2C+H%3BBrown%2C+L%3BCashel%2C+M&rft.aulast=Mechold&rft.aufirst=U&rft.date=2002-06-01&rft.volume=184&rft.issue=11&rft.spage=2878&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.184.11.2878-2888.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JB.184.11.2878-2888.2002 ER - TY - JOUR T1 - Modifications of the Human Immunodeficiency Virus Envelope Glycoprotein Enhance Immunogenicity for Genetic Immunization AN - 18314161; 5366929 AB - In this study, we have investigated the effect of specific mutations in human immunodeficiency virus type 1 (HIV-1) envelope (Env) on antibody production in an effort to improve humoral immune responses to this glycoprotein by DNA vaccination. Mice were injected with plasmid expression vectors encoding HIV Env with modifications in regions that might affect this response. Elimination of conserved glycosylation sites did not substantially enhance humoral or cytotoxic-T-lymphocyte (CTL) immunity. In contrast, a modified gp140 with different COOH-terminal mutations intended to mimic a fusion intermediate and stabilize trimer formation enhanced humoral immunity without reducing the efficacy of the CTL response. This mutant, with deletions in the cleavage site, fusogenic domain, and spacing of heptad repeats 1 and 2, retained native antigenic conformational determinants as defined by binding to known monoclonal antibodies or CD4, oligomer formation, and virus neutralization in vitro. Importantly, this modified Env, gp140[Delta]CFI, stimulated the antibody response to native gp160 while it retained its ability to induce a CTL response, a desirable feature for an AIDS vaccine. JF - Journal of Virology AU - Chakrabarti, B K AU - Kong, W AU - Wu, B AU - Yang, Z AU - Friborg, J AU - Ling, X AU - King AU - Montefiori, D C AU - Nabel, G J AD - Vaccine Research Center, NIAID, National Institutes of Health, 40 Convent Dr., Bethesda, MD 20892-3005., gnabel@mail.nih.gov Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 5357 EP - 5368 PB - American Society for Microbiology VL - 76 IS - 11 SN - 0022-538X, 0022-538X KW - mice KW - HIV-1 KW - HIV KW - env protein KW - glycoprotein gp140 KW - glycoprotein gp160 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Acquired immune deficiency syndrome KW - Glycosylation KW - Envelopes KW - DNA vaccines KW - Envelope protein KW - Human immunodeficiency virus 1 KW - Glycoproteins KW - Immune response (humoral) KW - Immunity KW - Human immunodeficiency virus KW - Vaccines KW - F 06807:Active immunization KW - W3 33345:DNA vaccines KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews KW - F 06856:Animal KW - N 14800:Immunological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18314161?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=Modifications+of+the+Human+Immunodeficiency+Virus+Envelope+Glycoprotein+Enhance+Immunogenicity+for+Genetic+Immunization&rft.au=Chakrabarti%2C+B+K%3BKong%2C+W%3BWu%2C+B%3BYang%2C+Z%3BFriborg%2C+J%3BLing%2C+X%3BKing%3BMontefiori%2C+D+C%3BNabel%2C+G+J&rft.aulast=Chakrabarti&rft.aufirst=B&rft.date=2002-06-01&rft.volume=76&rft.issue=11&rft.spage=5357&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/10.1128%2FJVI.76.11.5357-5368.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; Human immunodeficiency virus 1; Acquired immune deficiency syndrome; DNA vaccines; Glycoproteins; Vaccines; Envelopes; Glycosylation; Immune response (humoral); Immunity; Envelope protein DO - http://dx.doi.org/10.1128/JVI.76.11.5357-5368.2002 ER - TY - JOUR T1 - A Qualitative Evaluation of Questions and Responses from Five Occupational Questionnaires Developed to Assess Exposures AN - 17760436; 6095611 AB - Questionnaires are increasingly being used in the workplace to assess exposures to chemicals and other agents. Although the literature contains much information on questionnaire design in general, little information is available on the challenges related to questionnaires applied to the occupational setting. Questionnaires on dry cleaning workers, nurses, farmers, car mechanics, and truck drivers were administered to a total of 25 people currently performing one of these jobs. After asking each question, the interviewer probed to identify the difficulties the respondents had in answering the questions. Overall, the respondents were able to answer the questions. Problems were found, however, with particular questions that reduced the effectiveness of the questionnaire. These included the use of unclear terms, questions open to multiple interpretations, difficult computational requirements (e.g., asking for averages for highly variable tasks), ineffective transitions between topics, and overlapping response categories. This type of testing is a crucial part of questionnaire development and can be used to effectively identify potential problems with questions and, therefore, improve them to enhance collection of higher-quality data for assessments of occupational exposures. JF - Applied Occupational & Environmental Hygiene AU - Stewart, P AU - Rice, C AU - Beatty, P AU - Wilson, B AU - Stewart, W AU - Blair, A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 444 EP - 453 PB - Elsevier Science Inc., Box 882 New York NY 10159 USA, [mailto:usinfo-f@elsevier.com] VL - 17 IS - 6 SN - 1047-322X, 1047-322X KW - Health & Safety Science Abstracts KW - Chemicals KW - Data collection KW - Hazardous materials KW - Occupational exposure KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17760436?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+Occupational+%26+Environmental+Hygiene&rft.atitle=A+Qualitative+Evaluation+of+Questions+and+Responses+from+Five+Occupational+Questionnaires+Developed+to+Assess+Exposures&rft.au=Stewart%2C+P%3BRice%2C+C%3BBeatty%2C+P%3BWilson%2C+B%3BStewart%2C+W%3BBlair%2C+A&rft.aulast=Stewart&rft.aufirst=P&rft.date=2002-06-01&rft.volume=17&rft.issue=6&rft.spage=444&rft.isbn=&rft.btitle=&rft.title=Applied+Occupational+%26+Environmental+Hygiene&rft.issn=1047322X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Data collection; Occupational exposure; Hazardous materials; Chemicals ER - TY - JOUR T1 - Differential effects of supplementary affinity tags on the solubility of MBP fusion proteins AN - 1034816159; 17027032 AB - It is difficult to imagine any strategy for high-throughput protein expression and purification that does not involve genetically engineered affinity tags. Because of its ability to enhance the solubility and promote the proper folding of its fusion partners, Escherichia coli maltose-binding protein (MBP) is a particularly useful affinity tag. However, not all MBP fusion proteins bind efficiently to amylose resin, and even when they do it is usually not possible to obtain a sample of adequate purity after a single affinity step. To address this problem, we endeavored to incorporate supplemental affinity tags within the framework of an MBP fusion protein. We show that both the nature of the supplemental tags and their location can influence the ability of MBP to promote the solubility of its fusion partners. The most promising configurations for high-throughput protein expression and purification appear to be a fusion protein with a biotin acceptor peptide (BAP) on the N-terminus of MBP and/or a hexahistidine tag (His-tag) on the C-terminus of the passenger protein. Abbreviatoins: BAP, biotin acceptor peptide; EDTA, ethelenediaminetetraacetic acid; IPTG, isopropyl- beta -d-thiogalactopyranoside; MBP, E. coli maltose-binding protein; GFP; green fluorescent protein; Ni-NTA, nickel-nitrilotriacetic acid; ORF, open reading frame; PCR; polymerase chain reaction; R5, polyarginine tag; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; TEV, tobacco etch virus; WT, wild-type JF - Journal of Structural and Functional Genomics AU - Routzahn, Karen M AU - Waugh, David S AD - Protein Engineering Section, Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, P.O. Box B, Frederick, Maryland, 21702, USA Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 83 EP - 92 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 2 IS - 2 SN - 1345-711X, 1345-711X KW - Genetics Abstracts; Virology & AIDS Abstracts; Biotechnology and Bioengineering Abstracts KW - Amylose KW - Escherichia coli KW - protein purification KW - V:22310 KW - W 30900:Methods KW - G:07770 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1034816159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Structural+and+Functional+Genomics&rft.atitle=Differential+effects+of+supplementary+affinity+tags+on+the+solubility+of+MBP+fusion+proteins&rft.au=Routzahn%2C+Karen+M%3BWaugh%2C+David+S&rft.aulast=Routzahn&rft.aufirst=Karen&rft.date=2002-06-01&rft.volume=2&rft.issue=2&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Journal+of+Structural+and+Functional+Genomics&rft.issn=1345711X&rft_id=info:doi/10.1023%2FA%3A1020424023207 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-08-01 N1 - Last updated - 2014-02-21 N1 - SubjectsTermNotLitGenreText - protein purification; Escherichia coli DO - http://dx.doi.org/10.1023/A:1020424023207 ER - TY - JOUR T1 - Attenuation of protein kinase C and cAMP-dependent protein kinase signal transduction in the neurogranin knockout mouse. AN - 71720208; 11912190 AB - Neurogranin (Ng) is a brain-specific, postsynaptically located protein kinase C (PKC) substrate, highly expressed in the cortex, hippocampus, striatum, and amygdala. This protein is a Ca(2+)-sensitive calmodulin (CaM)-binding protein whose CaM-binding affinity is modulated by phosphorylation and oxidation. To investigate the role of Ng in neural function, a strain of Ng knockout mouse (KO) was generated. Previously we reported (Pak, J. H., Huang, F. L., Li, J., Balschun, D., Reymann, K. G., Chiang, C., Westphal, H., and Huang, K.-P. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 11232-11237) that these KO mice displayed no obvious neuroanatomical abnormality, but exhibited deficits in learning and memory and activation of Ca(2+)/CaM-dependent protein kinase II. In this report, we analyzed several downstream phosphorylation targets in phorbol 12-myristate 13-acetate- and forskolin-treated hippocampal slices from wild type (WT) and KO mice. Phorbol 12-myristate 13-acetate caused phosphorylation of Ng in WT mice and promoted the translocation of PKC from the cytosolic to the particulate fractions of both the WT and KO mice, albeit to a lesser extent in the latter. Phosphorylation of downstream targets, including mitogen-activated protein kinases, 90-kDa ribosomal S6 kinase, and the cAMP response element binding protein (CREB) was significantly attenuated in KO mice. Stimulation of hippocampal slices with forskolin also caused greater stimulation of protein kinase A (PKA) in the WT as compared with those of the KO mice. Again, phosphorylation of the downstream targets of PKA was attenuated in the KO mice. These results suggest that Ng plays a pivotal role in regulating both PKC- and PKA-mediated signaling pathways, and that the deficits in learning and memory of spatial tasks detected in the KO mice may be the result of defects in the signaling pathways leading to the phosphorylation of CREB. JF - The Journal of biological chemistry AU - Wu, Junfang AU - Li, Junfa AU - Huang, Kuo-Ping AU - Huang, Freesia L AD - Section on Metabolic Regulation, Endocrinology and Reproduction Research Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892-4510, USA. Y1 - 2002/05/31/ PY - 2002 DA - 2002 May 31 SP - 19498 EP - 19505 VL - 277 IS - 22 SN - 0021-9258, 0021-9258 KW - Calmodulin-Binding Proteins KW - 0 KW - Nerve Tissue Proteins KW - Nrgn protein, mouse KW - Neurogranin KW - 132654-77-4 KW - Colforsin KW - 1F7A44V6OU KW - Cyclic AMP KW - E0399OZS9N KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Cytosol -- metabolism KW - Immunoblotting KW - Hippocampus -- metabolism KW - Temperature KW - Mice KW - Protein Binding KW - Mice, Knockout KW - Colforsin -- pharmacology KW - Phosphorylation KW - Kinetics KW - Cyclic AMP -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Time Factors KW - Protein Kinase C -- metabolism KW - Nerve Tissue Proteins -- physiology KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Calmodulin-Binding Proteins -- physiology KW - Calmodulin-Binding Proteins -- genetics KW - Nerve Tissue Proteins -- genetics KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71720208?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=Boning+up+on+telomerase&rft.au=Tuan%2C+R&rft.aulast=Tuan&rft.aufirst=R&rft.date=2002-06-01&rft.volume=20&rft.issue=6&rft.spage=560&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-02 N1 - Date created - 2002-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Low Fidelity DNA Synthesis by a Y Family DNA Polymerase Due to Misalignment in the Active Site AN - 18332800; 5380956 AB - Sulfolobus solfataricus DNA polymerase IV (Dpo4) is a member of the Y family of DNA polymerases whose crystal structure has recently been solved. As a model for other evolutionarily conserved Y family members that perform translesion DNA synthesis and have low fidelity, we describe here the base substitution and frameshift fidelity of DNA synthesis by Dpo4. Dpo4 generates all 12 base- base mismatches at high rates, 11 of which are similar to those of its human homolog, DNA polymerase Kappa . This result is consistent with the Dpo4 structure, implying lower geometric selection for correct base pairs. Surprisingly, Dpo4 generates C super(.)dCMP mismatches at an unusually high average rate and preferentially at cytosine flanked by 5'-template guanine. Dpo4 also has very low frameshift fidelity and frequently generates deletions of even noniterated nucleotides, especially cytosine flanked by a 5'-template guanine. Both unusual features of error specificity suggest that Dpo4 can incorporate dNTP precursors when two template nucleotides are present in the active site binding pocket. These results have implications for mutagenesis resulting from DNA synthesis by Y family polymerases. JF - Journal of Biological Chemistry AU - Kokoska, R J AU - Bebenek, K AU - Boudsocq, F AU - Woodgate, R AU - Kunkel, T A AD - Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA, kunkel@niehs.nih.gov Y1 - 2002/05/31/ PY - 2002 DA - 2002 May 31 SP - 19633 EP - 19638 VL - 277 IS - 22 SN - 0021-9258, 0021-9258 KW - Dpo4 protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Sulfolobus solfataricus KW - Fidelity KW - DNA-directed DNA polymerase KW - Crystal structure KW - Mutagenesis KW - N 14640:Structure & sequence KW - J 02725:DNA UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18332800?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Low+Fidelity+DNA+Synthesis+by+a+Y+Family+DNA+Polymerase+Due+to+Misalignment+in+the+Active+Site&rft.au=Kokoska%2C+R+J%3BBebenek%2C+K%3BBoudsocq%2C+F%3BWoodgate%2C+R%3BKunkel%2C+T+A&rft.aulast=Kokoska&rft.aufirst=R&rft.date=2002-05-31&rft.volume=277&rft.issue=22&rft.spage=19633&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Sulfolobus solfataricus; DNA-directed DNA polymerase; Crystal structure; Mutagenesis; Fidelity ER - TY - JOUR T1 - Structure-based interpretation of missense mutations in Y-family DNA polymerases and their implications for polymerase function and lesion bypass. AN - 72799502; 12509239 AB - Our understanding of the molecular mechanisms of error-prone lesion bypass has changed dramatically in the past few years. The concept that the key participants in the mutagenic process were accessory proteins that somehow modified the ability of the cell's main replicase to facilitate bypass of normally blocking lesions has been replaced with one in which the replicase is displaced by a polymerase specialized in lesion bypass. The participants in this process remain the same, only their function has been reassigned. What was once known as the UmuC/DinB/Rev1/Rad30 superfamily of mutagenesis proteins, is now known as the Y-family of DNA polymerases. Quite remarkably, within the space of 3 years, the field has advanced from the initial discovery of intrinsic polymerase function, to the determination of the tertiary structures of several Y-family DNA polymerases.A key to determining the biochemical properties of each DNA polymerase is through structure-function studies that result in the site-specific substitution of particular amino acids at critical sites within each DNA polymerase. However, we should not forget the power of genetic selection that allows us to identify residues within each polymerase that are generated by "random mutagenesis" and which are important for both a gain or loss of function in vivo. In this review, we discuss the structural ramifications of several missense mutations previously identified in various Y-family DNA polymerase and speculate on how each amino acid substitution might modify the enzymatic activity of the respective polymerase or possibly perturb protein-protein interactions necessary for efficient translesion replication in vivo. JF - DNA repair AU - Boudsocq, François AU - Ling, Hong AU - Yang, Wei AU - Woodgate, Roger AD - Section on DNA Replication, Repair and Mutagenesis, Building 6, Room 1A13, National Institute of Child Health and Human Development, National Institutes of Health, 9000 Rockville Pike, Bethesda MD 20892-2725, USA. Y1 - 2002/05/30/ PY - 2002 DA - 2002 May 30 SP - 343 EP - 358 VL - 1 IS - 5 SN - 1568-7864, 1568-7864 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Animals KW - DNA Repair KW - DNA Damage KW - Humans KW - Multigene Family KW - Escherichia coli -- genetics KW - Amino Acid Sequence KW - Escherichia coli -- enzymology KW - Structure-Activity Relationship KW - Models, Genetic KW - Protein Folding KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Amino Acid Substitution KW - DNA Replication KW - Protein Conformation KW - Mutation, Missense KW - DNA-Directed DNA Polymerase -- genetics KW - DNA-Directed DNA Polymerase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72799502?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=DNA+repair&rft.atitle=Structure-based+interpretation+of+missense+mutations+in+Y-family+DNA+polymerases+and+their+implications+for+polymerase+function+and+lesion+bypass.&rft.au=Boudsocq%2C+Fran%C3%A7ois%3BLing%2C+Hong%3BYang%2C+Wei%3BWoodgate%2C+Roger&rft.aulast=Boudsocq&rft.aufirst=Fran%C3%A7ois&rft.date=2002-05-30&rft.volume=1&rft.issue=5&rft.spage=343&rft.isbn=&rft.btitle=&rft.title=DNA+repair&rft.issn=15687864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-05 N1 - Date created - 2003-01-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adenoviral vectors can impair adrenocortical steroidogenesis: Clinical implications for natural infections and gene therapy AN - 18580214; 5383088 AB - Recombinant adenoviral vectors are effective in transferring foreign genes to a variety of cells and tissue types, both in vitro and in vivo. However, during the gene transfer, they may alter the principal function and local environment of transfected cells. Increasing evidence exists for a selective adrenotropism of adenovirus during infections and gene transfer. Therefore, using bovine adrenocortical cells in primary culture, we analyzed the influence of different adenoviral deletion mutants on cell morphology and physiology. Transfection of cells with an E1/E3-deleted adenoviral vector, engineered to express a modified form of the Aequorea victoria green fluorescent protein, was highly efficient, as documented by fluorescent microscopy. Ultrastructural analysis, however, demonstrated nuclear fragmentation and mitochondrial alterations in addition to intranuclear viral particles. Basal secretion of 17-OH-progesterone, 11-deoxycortisol cortisol was significantly increased by E1/E3-deleted vectors; yet, the corticotropin-stimulated release of these steroids was decreased. Interestingly, neither purified viral capsids nor E3/E4-deleted adenoviral mutants altered basal and stimulated steroidogenesis of adrenocortical cells. An intact adrenal response is crucial for adaptation to stress and survival. Therefore, the implications of our findings need to be considered in patients with adenoviral infections and those undergoing clinical studies using adenoviral gene transfer. At the same time, the high level of transfection in adrenocortical cells might make appropriately modified adenoviral vectors suitable for gene therapy of adrenocortical carcinomas with poor prognosis. JF - Proceedings of the National Academy of Sciences, USA AU - Alesci, S AU - Ramsey, W J AU - Bornstein AU - Chrousos, G P AU - Hornsby, P J AU - Benvenga, S AU - Trimarchi, F AU - Ehrhart-Bornstein, M AD - Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1583, USA, alescis@mail.nih.gov Y1 - 2002/05/28/ PY - 2002 DA - 2002 May 28 SP - 7484 EP - 7489 VL - 99 IS - 11 SN - 0027-8424, 0027-8424 KW - cattle KW - Water jellyfish KW - green fluorescent protein KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Deletion mutant KW - Gene therapy KW - Adenovirus KW - Steroidogenesis KW - Carcinoma KW - Expression vectors KW - Transfection KW - Adrenal cortex KW - Aequorea victoria KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18580214?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Adenoviral+vectors+can+impair+adrenocortical+steroidogenesis%3A+Clinical+implications+for+natural+infections+and+gene+therapy&rft.au=Alesci%2C+S%3BRamsey%2C+W+J%3BBornstein%3BChrousos%2C+G+P%3BHornsby%2C+P+J%3BBenvenga%2C+S%3BTrimarchi%2C+F%3BEhrhart-Bornstein%2C+M&rft.aulast=Alesci&rft.aufirst=S&rft.date=2002-05-28&rft.volume=99&rft.issue=11&rft.spage=7484&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.062170099 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adenovirus; Aequorea victoria; Expression vectors; Carcinoma; Gene therapy; Adrenal cortex; Steroidogenesis; Deletion mutant; Transfection DO - http://dx.doi.org/10.1073/pnas.062170099 ER - TY - JOUR T1 - Insight into the molecular basis of pathogen abundance: Group A Streptococcus inhibitor of complement inhibits bacterial adherence and internalization into human cells AN - 18395740; 5383117 AB - Streptococcal inhibitor of complement (Sic) is a secreted protein made predominantly by serotype M1 Group A Streptococcus (GAS), which contributes to persistence in the mammalian upper respiratory tract and epidemics of human disease. Unexpectedly, an isogenic sic-negative mutant adhered to human epithelial cells significantly better than the wild-type parental strain. Purified Sic inhibited the adherence of a sic negative serotype M1 mutant and of non-Sic-producing GAS strains to human epithelial cells. Sic was rapidly internalized by human epithelial cells, inducing cell flattening and loss of microvilli. Ezrin and moesin, human proteins that functionally link the cytoskeleton to the plasma membrane, were identified as Sic-binding proteins by affinity chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis. Sic colocalized with ezrin inside epithelial cells and bound to the F-actin-binding site region located in the carboxyl terminus of ezrin and moesin. Synthetic peptides corresponding to two regions of Sic had GAS adherence-inhibitory activity equivalent to mature Sic and inhibited binding of Sic to ezrin. In addition, the sic mutant was phagocytosed and killed by human polymorphonuclear leukocytes significantly better than the wild-type strain, and Sic colocalized with ezrin in discrete regions of polymorphonuclear leukocytes. The data suggest that binding of Sic to ezrin alters cellular processes critical for efficient GAS contact, internalization, and killing. Sic enhances bacterial survival by enabling the pathogen to avoid the intracellular environment. This process contributes to the abundance of M1 GAS in human infections and their ability to cause epidemics. JF - Proceedings of the National Academy of Sciences, USA AU - Hoe, N P AU - Ireland, R M AU - DeLeo AU - Gowen, B B AU - Dorward, D W AU - Voyich, J M AU - Liu, M AU - Burns, EH Jr AU - Culnan, D M AU - Bretscher, A AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA, jmusser@niaid.nih.gov Y1 - 2002/05/28/ PY - 2002 DA - 2002 May 28 SP - 7646 EP - 7651 VL - 99 IS - 11 SN - 0027-8424, 0027-8424 KW - Sic protein KW - ezrin KW - moesin KW - streptococci KW - Microbiology Abstracts B: Bacteriology KW - J 02721:Cell cycle, morphology and motility UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18395740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Insight+into+the+molecular+basis+of+pathogen+abundance%3A+Group+A+Streptococcus+inhibitor+of+complement+inhibits+bacterial+adherence+and+internalization+into+human+cells&rft.au=Hoe%2C+N+P%3BIreland%2C+R+M%3BDeLeo%3BGowen%2C+B+B%3BDorward%2C+D+W%3BVoyich%2C+J+M%3BLiu%2C+M%3BBurns%2C+EH+Jr%3BCulnan%2C+D+M%3BBretscher%2C+A%3BMusser%2C+J+M&rft.aulast=Hoe&rft.aufirst=N&rft.date=2002-05-28&rft.volume=99&rft.issue=11&rft.spage=7646&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.112039899 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1073/pnas.112039899 ER - TY - JOUR T1 - Evidence for distinct cation and calcimimetic compound (NPS 568) recognition domains in the transmembrane regions of the human Ca2+ receptor. AN - 71704951; 11880385 AB - The Ca(2+) receptor, a member of the family 3 of G protein-coupled receptors (GPCR), responds not only to its primary physiological ligand Ca(2+) but also to other di- and trivalent metals (Mg(2+), Gd(3+)) and the organic polycations spermine and poly-l-Arginine. As has been found for other family 3 GPCRs, the large amino-terminal extracellular domain (ECD) of the Ca(2+) receptor is the primary Ca(2+) binding domain. To examine how the signal is propagated from the ECD to the seven-transmembrane core domain (7TM) we constructed a Ca(2+) receptor mutant (T903-Rhoc) lacking the entire ECD but containing the 7TM. We have found that this structure initiates signaling in human embryonic kidney (HEK) 293 cells stably expressing the construct. One or more cation recognition sites are also located within the 7TM. Not only Ca(2+), but also several other Ca(2+) receptor-specific agonists, Mg(2+), Gd(3+), spermine, and poly-l-Arginine, can activate T903-Rhoc truncated receptor-initiated phosphoinositide hydrolysis in HEK 293 cells. The phenylalkylamine compound, NPS 568, identified as a positive allosteric modulator of the Ca(2+) receptor can selectively potentiate the actions of Ca(2+) and other polycationic agonists on the T903-Rhoc receptor. Similarly, organic polycations synergistically activate T903-Rhoc with di- and trivalent metals. Alanine substitution of all the acidic residues in the second extracellular loop of the T903-Rhoc receptor significantly impairs activation by metal ions and organic polycations in the presence of NPS 568 but not the synergistic activation of Ca(2+) with poly-l-Arginine. These data indicate that although the ECD has been thought to be the main determinant for Ca(2+) recognition, the 7TM core of the Ca(2+) receptor contains activating site(s) recognizing Ca(2+) and Gd(3+) as well as the allosteric modulators NPS 568 and organic polycations that may play important roles in the regulation of receptor activation. JF - The Journal of biological chemistry AU - Ray, Kausik AU - Northup, John AD - Laboratory of Cellular Biology, NIDCD, National Institutes of Health, Bethesda, Maryland 20892, USA. rayk@nidcd.nih.gov Y1 - 2002/05/24/ PY - 2002 DA - 2002 May 24 SP - 18908 EP - 18913 VL - 277 IS - 21 SN - 0021-9258, 0021-9258 KW - Aniline Compounds KW - 0 KW - Calcium-Binding Proteins KW - Cations KW - N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine KW - Phenethylamines KW - Propylamines KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Cell Membrane -- metabolism KW - Signal Transduction KW - Cell Line KW - Aniline Compounds -- pharmacology KW - Molecular Mimicry KW - Calcium -- pharmacology KW - Calcium-Binding Proteins -- genetics KW - Calcium-Binding Proteins -- metabolism KW - Calcium-Binding Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71704951?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Evidence+for+distinct+cation+and+calcimimetic+compound+%28NPS+568%29+recognition+domains+in+the+transmembrane+regions+of+the+human+Ca2%2B+receptor.&rft.au=Ray%2C+Kausik%3BNorthup%2C+John&rft.aulast=Ray&rft.aufirst=Kausik&rft.date=2002-05-24&rft.volume=277&rft.issue=21&rft.spage=18908&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-24 N1 - Date created - 2002-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification by site-directed mutagenesis of residues involved in ligand recognition and activation of the human A3 adenosine receptor. AN - 71696771; 11891221 AB - Ligand recognition has been extensively explored in G protein-coupled A(1), A(2A), and A(2B) adenosine receptors but not in the A(3) receptor, which is cerebroprotective and cardioprotective. We mutated several residues of the human A(3) adenosine receptor within transmembrane domains 3 and 6 and the second extracellular loop, which have been predicted by previous molecular modeling to be involved in the ligand recognition, including His(95), Trp(243), Leu(244), Ser(247), Asn(250), and Lys(152). The N250A mutant receptor lost the ability to bind both radiolabeled agonist and antagonist. The H95A mutation significantly reduced affinity of both agonists and antagonists. In contrast, the K152A (EL2), W243A (6.48), and W243F (6.48) mutations did not significantly affect the agonist binding but decreased antagonist affinity by approximately 3-38-fold, suggesting that these residues were critical for the high affinity of A(3) adenosine receptor antagonists. Activation of phospholipase C by wild type (WT) and mutant receptors was measured. The A(3) agonist 2-chloro-N(6)-(3-iodobenzyl)-5'-N-methylcarbamoyladenosine stimulated phosphoinositide turnover in the WT but failed to evoke a response in cells expressing W243A and W243F mutant receptors, in which agonist binding was less sensitive to guanosine 5'-gamma-thiotriphosphate than in WT. Thus, although not important for agonist binding, Trp(243) was critical for receptor activation. The results were interpreted using a rhodopsin-based model of ligand-A(3) receptor interactions. JF - The Journal of biological chemistry AU - Gao, Zhan-Guo AU - Chen, Aishe AU - Barak, Dov AU - Kim, Soo-Kyung AU - Müller, Christa E AU - Jacobson, Kenneth A AD - Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/05/24/ PY - 2002 DA - 2002 May 24 SP - 19056 EP - 19063 VL - 277 IS - 21 SN - 0021-9258, 0021-9258 KW - Ligands KW - 0 KW - Phosphatidylinositols KW - Purinergic P1 Receptor Agonists KW - Receptor, Adenosine A3 KW - Receptors, Purinergic P1 KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Phosphatidylinositols -- metabolism KW - Animals KW - COS Cells KW - Models, Molecular KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Guanosine 5'-O-(3-Thiotriphosphate) -- pharmacology KW - Receptors, Purinergic P1 -- chemistry KW - Receptors, Purinergic P1 -- genetics KW - Receptors, Purinergic P1 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71696771?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Identification+by+site-directed+mutagenesis+of+residues+involved+in+ligand+recognition+and+activation+of+the+human+A3+adenosine+receptor.&rft.au=Gao%2C+Zhan-Guo%3BChen%2C+Aishe%3BBarak%2C+Dov%3BKim%2C+Soo-Kyung%3BM%C3%BCller%2C+Christa+E%3BJacobson%2C+Kenneth+A&rft.aulast=Gao&rft.aufirst=Zhan-Guo&rft.date=2002-05-24&rft.volume=277&rft.issue=21&rft.spage=19056&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-24 N1 - Date created - 2002-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rabies DNA vaccination of non-human primates: post-exposure studies using gene gun methodology that accelerates induction of neutralizing antibody and enhances neutralizing antibody titers AN - 18437324; 5411428 AB - Pre-exposure DNA vaccination protects non-human primates against rabies virus. Post-exposure protection of monkeys against rabies virus by DNA vaccination has not been attempted. Presumably, post-exposure experiments have not been undertaken because neutralizing antibody is usually slow to be induced after DNA vaccination. In this study, we initially attempted to accelerate the induction of neutralizing antibody by varying the route and site of DNA vaccination and booster frequency. Gene gun (GG) vaccinations above axillary and inguinal lymph nodes or in ear pinnae generated higher levels of neutralizing antibody than intradermal (ID) needle vaccinations in the pinnae. Concurrent GG booster vaccinations above axillary and inguinal lymph nodes and in ear pinnae, 3 days after primary vaccination, accelerated detectable neutralizing antibody. GG booster vaccinations also resulted in higher neutralizing antibody levels and increased the durability of this response. Post-exposure vaccination with DNA or the human diploid cell vaccine (HDCV), in combination with an one-time treatment with human rabies immune globulin (HRIG), protected 50 and 75% of the monkeys, respectively, as compared to 75% mortality of the controls. These data will be useful for the refinement, development, and implementation of future pre- and post-exposure rabies DNA vaccination studies. JF - Vaccine AU - Lodmell, D L AU - Parnell, MJ AU - Bailey, J R AU - Ewalt, L C AU - Hanlon, CA AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, 903 South Fourth Street, Hamilton, MT 59840, USA, dlodmell@nih.gov Y1 - 2002/05/22/ PY - 2002 DA - 2002 May 22 SP - 2221 EP - 2228 VL - 20 IS - 17-18 SN - 0264-410X, 0264-410X KW - Primates KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts; Immunology Abstracts KW - F 06807:Active immunization KW - V 22097:Immunization: Vaccines & vaccination: Human KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18437324?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Rabies+DNA+vaccination+of+non-human+primates%3A+post-exposure+studies+using+gene+gun+methodology+that+accelerates+induction+of+neutralizing+antibody+and+enhances+neutralizing+antibody+titers&rft.au=Lodmell%2C+D+L%3BParnell%2C+MJ%3BBailey%2C+J+R%3BEwalt%2C+L+C%3BHanlon%2C+CA&rft.aulast=Lodmell&rft.aufirst=D&rft.date=2002-05-22&rft.volume=22&rft.issue=6&rft.spage=705&rft.isbn=&rft.btitle=&rft.title=Pharmacotherapy&rft.issn=02770008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - A new intra-NALT route elicits mucosal and systemic immunity against Moraxella catarrhalis in a mouse challenge model AN - 18431093; 5411446 AB - Mucosally administered antigens are often poorly immunogenic due to the difficulty of transporting antigens through the mucosal epithelium. We investigated a new route of intranasal-associated lymphoid tissue (intra-NALT) administration of antigens to circumvent the antigen transportation barrier. A comparative study was carried out on mice administered with killed whole cells of Moraxella catarrhalis strain 25238 plus cholera toxin (CT) by intra-NALT injection and nasal inoculation. Both routes induced significant elevations of several isotype antibodies against strain 25238 in saliva, lung lavage, and serum as measured by an enzyme-linked immunosorbent assay (ELISA). Most of these antibodies were paralleled by the numbers of their corresponding antibody forming cells in mucosal or systemic lymphoid tissues. However, intra-NALT injection elicited higher levels of immunoglobulin (Ig) A and IgG in saliva, IgA and IgG in lung lavage, and IgG and IgM in sera than nasal inoculation (P less than or equal to 0.05). In addition, both routes generated significant reductions of bacteria in lungs following an aerosol challenge with strain 25238 in a mouse model of pulmonary clearance. Once again, intra-NALT route showed better bacterial clearance in mouse lungs than nasal inoculation (P < 0.01). These results demonstrate that intra-NALT administration of antigens is a convenient and effective route for mucosal immunization that elicits improved mucosal and systemic immunity. This new route can be used as a model to study mucosal antigens or vaccine candidates for antigen activation and interaction with the NALT that is one of major inductive sites for common mucosal immune system. JF - Vaccine AU - Hou, Y AU - Hu, W-G AU - Hirano, T AU - Gu, X-X AD - National Institute for Deafness and Other Communication Disorders, National Institute of Health, 5 Research Court, Rockville, MD 20850, USA, guxx@nidcd.nih.gov Y1 - 2002/05/22/ PY - 2002 DA - 2002 May 22 SP - 2375 EP - 2381 VL - 20 IS - 17-18 SN - 0264-410X, 0264-410X KW - man KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18431093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=A+new+intra-NALT+route+elicits+mucosal+and+systemic+immunity+against+Moraxella+catarrhalis+in+a+mouse+challenge+model&rft.au=Hou%2C+Y%3BHu%2C+W-G%3BHirano%2C+T%3BGu%2C+X-X&rft.aulast=Hou&rft.aufirst=Y&rft.date=2002-05-22&rft.volume=20&rft.issue=17-18&rft.spage=2375&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Adenovirus HSV-TK construct with thyroid-specific promoter: enhancement of activity and specificity with histone deacetylase inhibitors and agents modulating the camp pathway. AN - 71712795; 11992417 AB - The successful use of tissue- or tumor-selective promoters in targeted gene therapy for cancer depends on high and selective activity. Tg is a thyroid-specific protein that is expressed in the normal thyroid and a majority of thyroid tumors. In the present study, we show, using a luciferase reporter assay, that a construct containing the putative Tg promoter and enhancer is active in 4 thyroid carcinoma cell lines (including 2 anaplastic thyroid carcinoma cell lines) and not in 5 cancer cell lines arising from nonthyroid tissues. Furthermore, both the activity and the specificity of this construct were increased by pretreatment with 8-Br-cAMP and the histone deacetylase inhibitor depsipeptide (FR901228). Expression of thymidine kinase in thyroid cancer cells infected with a recombinant adenovirus (Ad) carrying a Tg enhancer/promoter-thymidine kinase expression cassette (AdTg enhancer/promoter-TK) correlated with the level of Tg enhancer/promoter activity in these cells. Under similar conditions, TK expression was not observed in cancer cell lines arising from nonthyroid tissues. Cells infected with AdTg enhancer/promoter-TK demonstrated preferential GCV sensitivity, with up to a 100,000-fold increase in GCV sensitivity in thyroid cancer cell lines compared to cancer cell lines of nonthyroid origin. The construct described herein can be used to selectively target thyroid cancer cells, and its expression can be modulated to further increase its specificity and selectivity, especially in anaplastic thyroid carcinoma cells, using 8-Br-cAMP and depsipeptide. JF - International journal of cancer AU - Kitazono, Masaki AU - Chuman, Yutaka AU - Aikou, Takashi AU - Fojo, Tito AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/05/20/ PY - 2002 DA - 2002 May 20 SP - 453 EP - 459 VL - 99 IS - 3 SN - 0020-7136, 0020-7136 KW - DNA-Binding Proteins KW - 0 KW - Histone Deacetylase Inhibitors KW - Nuclear Proteins KW - PAX8 Transcription Factor KW - PAX8 protein, human KW - Paired Box Transcription Factors KW - Trans-Activators KW - Transcription Factors KW - thyroid nuclear factor 1 KW - Thyroglobulin KW - 9010-34-8 KW - Cyclic AMP KW - E0399OZS9N KW - Luciferases KW - EC 1.13.12.- KW - Thymidine Kinase KW - EC 2.7.1.21 KW - Histone Deacetylases KW - EC 3.5.1.98 KW - Index Medicus KW - Immunoblotting KW - Thyroglobulin -- biosynthesis KW - Plasmids -- metabolism KW - Thyroid Neoplasms -- genetics KW - Dose-Response Relationship, Drug KW - Electrophoresis, Polyacrylamide Gel KW - Thyroid Neoplasms -- metabolism KW - Humans KW - DNA-Binding Proteins -- biosynthesis KW - Luciferases -- metabolism KW - Transcription Factors -- biosynthesis KW - Adenoviridae -- genetics KW - Cell Survival KW - Polymerase Chain Reaction KW - Tumor Cells, Cultured KW - Trans-Activators -- biosynthesis KW - Transfection KW - Cyclic AMP -- metabolism KW - Nuclear Proteins -- biosynthesis KW - Genetic Therapy -- methods KW - Inhibitory Concentration 50 KW - Promoter Regions, Genetic KW - Histone Deacetylases -- metabolism KW - Simplexvirus -- enzymology KW - Thymidine Kinase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71712795?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Adenovirus+HSV-TK+construct+with+thyroid-specific+promoter%3A+enhancement+of+activity+and+specificity+with+histone+deacetylase+inhibitors+and+agents+modulating+the+camp+pathway.&rft.au=Kitazono%2C+Masaki%3BChuman%2C+Yutaka%3BAikou%2C+Takashi%3BFojo%2C+Tito&rft.aulast=Kitazono&rft.aufirst=Masaki&rft.date=2002-05-20&rft.volume=99&rft.issue=3&rft.spage=453&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-19 N1 - Date created - 2002-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disruption of transforming growth factor beta signaling by a novel ligand-dependent mechanism. AN - 71705790; 12021305 AB - Transforming growth factor (TGF)-beta is the prototype in a family of secreted proteins that act in autocrine and paracrine pathways to regulate cell development and function. Normal cells typically coexpress TGF-beta receptors and one or more isoforms of TGF-beta, thus the synthesis and secretion of TGF-beta as an inactive latent complex is considered an essential step in regula-ting the activity of this pathway. To determine whether intracellular activation of TGF-beta results in TGF-beta ligand-receptor interactions within the cell, we studied pristane-induced plasma cell tumors (PCTs). We now demonstrate that active TGF-beta1 in the PCT binds to intracellular TGF-beta type II receptor (TbetaRII). Disruption of the expression of TGF-beta1 by antisense TGF-beta1 mRNA restores localization of TbetaRII at the PCT cell surface, indicating a ligand-induced impediment in receptor trafficking. We also show that retroviral expression of a truncated, dominant-negative TbetaRII (dnTbetaRII) effectively competes for intracellular binding of active ligand in the PCT and restores cell surface expression of the endogenous TbetaRII. Analysis of TGF-beta receptor-activated Smad2 suggests the intracellular ligand-receptor complex is not capable of signaling. These data are the first to demonstrate the formation of an intracellular TGF-beta-receptor complex, and define a novel mechanism for modulating the TGF-beta signaling pathway. JF - The Journal of experimental medicine AU - Fernandez, Tania AU - Amoroso, Stephanie AU - Sharpe, Shellyann AU - Jones, Gary M AU - Bliskovski, Valery AU - Kovalchuk, Alexander AU - Wakefield, Lalage M AU - Kim, Seong-Jin AU - Potter, Michael AU - Letterio, John J AD - Laboratory of Cell Regulation and Carcinogenesis, The National Cancer Institute, The National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/05/20/ PY - 2002 DA - 2002 May 20 SP - 1247 EP - 1255 VL - 195 IS - 10 SN - 0022-1007, 0022-1007 KW - DNA-Binding Proteins KW - 0 KW - Ligands KW - RNA, Antisense KW - Receptors, Transforming Growth Factor beta KW - Smad2 Protein KW - Smad2 protein, mouse KW - Terpenes KW - Trans-Activators KW - Transforming Growth Factor beta KW - pristane KW - 26HZV48DT1 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - Trans-Activators -- metabolism KW - Animals KW - Plasmacytoma -- metabolism KW - Plasmacytoma -- chemically induced KW - Autocrine Communication KW - Mice KW - RNA, Antisense -- genetics KW - Protein Binding KW - Blotting, Western KW - Plasmacytoma -- enzymology KW - Terpenes -- pharmacology KW - Cell Membrane -- metabolism KW - DNA-Binding Proteins -- metabolism KW - Protein Transport KW - Signal Transduction -- drug effects KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Transforming Growth Factor beta -- genetics KW - Transforming Growth Factor beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71705790?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+experimental+medicine&rft.atitle=Disruption+of+transforming+growth+factor+beta+signaling+by+a+novel+ligand-dependent+mechanism.&rft.au=Fernandez%2C+Tania%3BAmoroso%2C+Stephanie%3BSharpe%2C+Shellyann%3BJones%2C+Gary+M%3BBliskovski%2C+Valery%3BKovalchuk%2C+Alexander%3BWakefield%2C+Lalage+M%3BKim%2C+Seong-Jin%3BPotter%2C+Michael%3BLetterio%2C+John+J&rft.aulast=Fernandez&rft.aufirst=Tania&rft.date=2002-05-20&rft.volume=195&rft.issue=10&rft.spage=1247&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-19 N1 - Date created - 2002-05-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Exp Med. 1994 Nov 1;180(5):1693-703 [7964455] Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11576-80 [7972105] J Clin Invest. 1996 Jan 15;97(2):388-95 [8567959] Cytokine Growth Factor Rev. 1996 Jun;7(1):93-102 [8864357] Cancer Res. 1996 Nov 1;56(21):4831-5 [8895728] J Clin Invest. 1996 Dec 1;98(11):2496-506 [8958212] Cancer Res. 1997 Mar 1;57(5):970-7 [9041203] J Biol Chem. 1997 Apr 25;272(17):11444-51 [9111056] Nature. 1997 Jul 3;388(6637):28-9 [9214496] Blood. 1997 Aug 15;90(4):1649-55 [9269785] Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):189-94 [9419351] J Cell Biol. 1998 Feb 23;140(4):767-77 [9472030] J Biol Chem. 1998 Jun 26;273(26):16527-34 [9632722] Transplantation. 1998 Oct 27;66(8):1014-20 [9808485] Cell. 1998 Dec 11;95(6):779-91 [9865696] Cancer Res. 1999 Jan 15;59(2):320-4 [9927040] Am J Med. 1999 Apr;106(4):477-9 [10225252] Nat Genet. 1999 Oct;23(2):222-7 [10508522] Cancer Res. 1999 Oct 1;59(19):4834-42 [10519393] Exp Cell Res. 1999 Nov 1;252(2):352-62 [10527625] Genes Dev. 2000 Jan 15;14(2):163-76 [10652271] N Engl J Med. 2000 May 4;342(18):1350-8 [10793168] J Natl Cancer Inst. 2000 Sep 6;92(17):1388-402 [10974075] Nat Rev Mol Cell Biol. 2000 Dec;1(3):169-78 [11252892] Nat Cell Biol. 2001 Apr;3(4):392-9 [11283613] J Biol Chem. 2001 Apr 13;276(15):11469-72 [11278244] J Immunol. 2001 Jun 15;166(12):7238-43 [11390472] Gene Expr. 2001;9(4-5):157-71 [11444526] J Exp Med. 2001 Sep 17;194(6):809-21 [11560996] Nat Med. 2001 Oct;7(10):1118-22 [11590434] J Cell Biol. 1987 Aug;105(2):965-75 [2887577] Science. 1988 Apr 8;240(4849):196-9 [2895499] Princess Takamatsu Symp. 1986;17:95-108 [3332023] Science. 1989 Sep 29;245(4925):1496-9 [2551043] Proc Natl Acad Sci U S A. 1989 Oct;86(20):8063-7 [2813378] Cancer Cells. 1989 Sep;1(1):9-17 [2701363] Cancer Commun. 1990;2(11):363-9 [2173622] J Immunol. 1991 Apr 15;146(8):2865-72 [1826699] Carcinogenesis. 1992 Oct;13(10):1681-97 [1423827] Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11332-6 [1454816] Cell Growth Differ. 1993 Mar;4(3):193-201 [8466857] Science. 1993 May 28;260(5112):1335-8 [8388126] Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5359-63 [8389483] Crit Rev Oncog. 1993;4(5):493-540 [8241322] Development. 1994 Jan;120(1):165-75 [8119124] Cancer Immunol Immunother. 1994 Apr;38(4):215-24 [8168116] Br J Cancer. 1994 May;69(5):802-8 [8180008] Nature. 1994 Aug 4;370(6488):341-7 [8047140] Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8772-6 [8090721] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Guidelines for using antiretroviral agents among HIV-infected adults and adolescents. Recommendations of the Panel on Clinical Practices for Treatment of HIV. AN - 71713138; 12027060 AB - The availability of an increasing number of antiretroviral agents and the rapid evolution of new information has introduced substantial complexity into treatment regimens for persons infected with human immunodeficiency virus (HIV). In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for clinical management of HIV-infected adults and adolescents (CDC. Report of the NIH Panel To Define Principles of Therapy of HIV Infection and Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR 1998;47[RR-5]:1-41). This report, which updates the 1998 guidelines, addresses 1) using testing for plasma HIV ribonucleic acid levels (i.e., viral load) and CD4+ T cell count; 2) using testing for antiretroviral drug resistance; 3) considerations for when to initiate therapy; 4) adherence to antiretroviral therapy; 5) considerations for therapy among patients with advanced disease; 6) therapy-related adverse events; 7) interruption of therapy; 8) considerations for changing therapy and available therapeutic options; 9) treatment for acute HIV infection; 10) considerations for antiretroviral therapy among adolescents; 11) considerations for antiretroviral therapy among pregnant women; and 12) concerns related to transmission of HIV to others. Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions is critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. Treatment should be offered to persons who have 55,000 copies/mL (by b-deoxyribonucleic acid [bDNA] or reverse transcriptase-polymerase chain reaction [RT-PCR] assays). The recommendation to treat asymptomatic patients should be based on the willingness and readiness of the person to begin therapy; the degree of existing immunodeficiency as determined by the CD4+ T cell count; the risk for disease progression as determined by the CD4+ T cell count and level of plasma HIV RNA; the potential benefits and risks of initiating therapy in an asymptomatic person; and the likelihood, after counseling and education, of adherence to the prescribed treatment regimen. Treatment goals should be maximal and durable suppression of viral load, restoration and preservation of immunologic function, improvement of quality of life, and reduction of HIV-related morbidity and mortality. Results of therapy are evaluated through plasma HIV RNA levels, which are expected to indicate a 1.0 log10 decrease at 2-8 weeks and no detectable virus (<50 copies/mL) at 4-6 months after treatment initiation. Failure of therapy at 4-6 months might be ascribed to nonadherence, inadequate potency of drugs or suboptimal levels of antiretroviral agents, viral resistance, and other factors that are poorly understood. Patients whose therapy fails in spite of a high level of adherence to the regimen should have their regimen changed; this change should be guided by a thorough drug treatment history and the results of drug-resistance testing. Because of limitations in the available alternative antiretroviral regimens that have documented efficacy, optimal changes in therapy might be difficult to achieve for patients in whom the preferred regimen has failed. These decisions are further confounded by problems with adherence, toxicity, and resistance. For certain patients, participating in a clinical trial with or without access to new drugs or using a regimen that might not achieve complete suppression of viral replication might be preferable. Because concepts regarding HIV management are evolving rapidly, readers should check regularly for additional information and updates at the HIV/AIDS Treatment Information Service website (http://www.hivatis.org). JF - MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports AU - Dybul, Mark AU - Fauci, Anthony S AU - Bartlett, John G AU - Kaplan, Jonathan E AU - Pau, Alice K AU - Panel on Clinical Practices for the Treatment of HIV AD - National Institutes of Health, Bethesda, Maryland, USA. ; Panel on Clinical Practices for the Treatment of HIV Y1 - 2002/05/17/ PY - 2002 DA - 2002 May 17 SP - 1 EP - 55 VL - 51 SN - 1057-5987, 1057-5987 KW - Anti-HIV Agents KW - 0 KW - Index Medicus KW - Viral Load KW - Drug Resistance, Viral KW - Patient Compliance KW - Humans KW - Adult KW - Counseling KW - CD4 Lymphocyte Count KW - Adolescent KW - Pregnancy Complications, Infectious -- drug therapy KW - Male KW - Female KW - Pregnancy KW - Antiretroviral Therapy, Highly Active -- adverse effects KW - Antiretroviral Therapy, Highly Active -- standards KW - Anti-HIV Agents -- therapeutic use KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy KW - Anti-HIV Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71713138?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=MMWR.+Recommendations+and+reports+%3A+Morbidity+and+mortality+weekly+report.+Recommendations+and+reports&rft.atitle=Guidelines+for+using+antiretroviral+agents+among+HIV-infected+adults+and+adolescents.+Recommendations+of+the+Panel+on+Clinical+Practices+for+Treatment+of+HIV.&rft.au=Dybul%2C+Mark%3BFauci%2C+Anthony+S%3BBartlett%2C+John+G%3BKaplan%2C+Jonathan+E%3BPau%2C+Alice+K%3BPanel+on+Clinical+Practices+for+the+Treatment+of+HIV&rft.aulast=Dybul&rft.aufirst=Mark&rft.date=2002-05-17&rft.volume=51&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=MMWR.+Recommendations+and+reports+%3A+Morbidity+and+mortality+weekly+report.+Recommendations+and+reports&rft.issn=10575987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-29 N1 - Date created - 2002-05-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of the peroxisome proliferation-activated receptor gamma (PPARgamma ) does not affect mammary development and propensity for tumor formation but leads to reduced fertility. AN - 71681860; 11884400 AB - The peroxisome proliferation-activated receptor gamma (PPARgamma) is expressed in many cell types including mammary epithelium, ovary, macrophages, and B- and T-cells. PPARgamma has an anti-proliferative effect in pre-adipocytes and mammary epithelial cells, and treatment with its ligands reduced the progression of carcinogen-induced mammary tumors in mice. Because PPARgamma-null mice die in utero it has not been possible to study its role in development and tumorigenesis in vivo. To investigate whether PPARgamma is required for the establishment and physiology of different cell types, a cell-specific deletion of the gene was carried out in mice using the Cre-loxP recombination system. We deleted the PPARgamma gene in mammary epithelium using WAP-Cre transgenic mice and in epithelial cells, B- and T-cells, and ovary cells using MMTV-Cre mice. The presence of PPARgamma was not required for functional development of the mammary gland during pregnancy and for the establishment of B- and T-cells. In addition, no increase in mammary tumors was observed. However, loss of the PPARgamma gene in oocytes and granulosa cells resulted in impaired fertility. These mice have normal populations of follicles, they ovulate and develop corpora lutea. Although progesterone levels are decreased and implantation rates are reduced, the exact cause of the impaired fertility remains to be determined. JF - The Journal of biological chemistry AU - Cui, Yongzhi AU - Miyoshi, Keiko AU - Claudio, Estefania AU - Siebenlist, Ulrich K AU - Gonzalez, Frank J AU - Flaws, Jodi AU - Wagner, Kay-Uwe AU - Hennighausen, Lothar AD - Laboratory of Genetics and Physiology, NIDDK, the Laboratory of Immunoregulation, Immune Activation Section, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA. Yongzhic@intra.niddk.nih.gov Y1 - 2002/05/17/ PY - 2002 DA - 2002 May 17 SP - 17830 EP - 17835 VL - 277 IS - 20 SN - 0021-9258, 0021-9258 KW - Receptors, Cytoplasmic and Nuclear KW - 0 KW - Transcription Factors KW - Progesterone KW - 4G7DS2Q64Y KW - Index Medicus KW - Animals KW - Embryo Implantation KW - T-Lymphocytes -- physiology KW - Mice KW - Flow Cytometry KW - Radioimmunoassay KW - Progesterone -- blood KW - B-Lymphocytes -- physiology KW - Female KW - Pregnancy KW - Mice, Knockout KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Mammary Neoplasms, Animal -- etiology KW - Transcription Factors -- physiology KW - Mammary Neoplasms, Animal -- pathology KW - Infertility, Female -- etiology KW - Infertility, Female -- complications KW - Mammary Glands, Animal -- growth & development KW - Receptors, Cytoplasmic and Nuclear -- genetics KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71681860?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Loss+of+the+peroxisome+proliferation-activated+receptor+gamma+%28PPARgamma+%29+does+not+affect+mammary+development+and+propensity+for+tumor+formation+but+leads+to+reduced+fertility.&rft.au=Cui%2C+Yongzhi%3BMiyoshi%2C+Keiko%3BClaudio%2C+Estefania%3BSiebenlist%2C+Ulrich+K%3BGonzalez%2C+Frank+J%3BFlaws%2C+Jodi%3BWagner%2C+Kay-Uwe%3BHennighausen%2C+Lothar&rft.aulast=Cui&rft.aufirst=Seung&rft.date=2002-06-01&rft.volume=301&rft.issue=3&rft.spage=1126&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-16 N1 - Date created - 2002-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Signaling events in amyloid beta-peptide-induced neuronal death and insulin-like growth factor I protection. AN - 71680892; 11882652 AB - Amyloid beta-peptide (Abeta) is implicated as the toxic agent in Alzheimer's disease and is the major component of brain amyloid plaques. In vitro, Abeta causes cell death, but the molecular mechanisms are unclear. We analyzed the early signaling mechanisms involved in Abeta toxicity using the SH-SY5Y neuroblastoma cell line. Abeta caused cell death and induced a 2- to 3-fold activation of JNK. JNK activation and cell death were inhibited by overexpression of a dominant-negative SEK1 (SEK1-AL) construct. Butyrolactone I, a cdk5 inhibitor, had an additional protective effect against Abeta toxicity in these SEK1-AL-expressing cells suggesting that cdk5 and JNK activation independently contributed to this toxicity. Abeta also weakly activated ERK and Akt but had no effect on p38 kinase. Inhibitors of ERK and phosphoinositide 3-kinase (PI3K) pathways did not affect Abeta-induced cell death, suggesting that these pathways were not important in Abeta toxicity. Insulin-like growth factor I protected against Abeta toxicity by strongly activating ERK and Akt and blocking JNK activation in a PI3K-dependent manner. Pertussis toxin also blocked Abeta-induced cell death and JNK activation suggesting that G(i/o) proteins were upstream activators of JNK. The results suggest that activation of the JNK pathway and cdk5 may be initial signaling cascades in Abeta-induced cell death. JF - The Journal of biological chemistry AU - Wei, Wanli AU - Wang, Xiantao AU - Kusiak, John W AD - Molecular Neurobiology Unit, Laboratory of Cellular and Molecular Biology, NIA, Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA. weiwa@grc.nia.nih.gov Y1 - 2002/05/17/ PY - 2002 DA - 2002 May 17 SP - 17649 EP - 17656 VL - 277 IS - 20 SN - 0021-9258, 0021-9258 KW - Amyloid beta-Peptides KW - 0 KW - Virulence Factors, Bordetella KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - butyrolactone I KW - 87414-49-1 KW - Pertussis Toxin KW - EC 2.4.2.31 KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Cyclin-Dependent Kinase 5 KW - EC 2.7.11.1 KW - CDK5 protein, human KW - EC 2.7.11.22 KW - Cyclin-Dependent Kinases KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - p38 Mitogen-Activated Protein Kinases KW - MAP Kinase Kinase 4 KW - EC 2.7.12.2 KW - MAP2K4 protein, human KW - Mitogen-Activated Protein Kinase Kinases KW - 4-Butyrolactone KW - OL659KIY4X KW - Index Medicus KW - Cyclin-Dependent Kinases -- metabolism KW - Neuroblastoma -- pathology KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Enzyme Activation KW - Mitogen-Activated Protein Kinases -- metabolism KW - Humans KW - Insulin-Like Growth Factor I -- metabolism KW - Mitogen-Activated Protein Kinase Kinases -- metabolism KW - Virulence Factors, Bordetella -- pharmacology KW - Tumor Cells, Cultured KW - Signal Transduction -- physiology KW - Amyloid beta-Peptides -- toxicity KW - Cell Death KW - 4-Butyrolactone -- pharmacology KW - Neurons -- pathology KW - 4-Butyrolactone -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71680892?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Signaling+events+in+amyloid+beta-peptide-induced+neuronal+death+and+insulin-like+growth+factor+I+protection.&rft.au=Wei%2C+Wanli%3BWang%2C+Xiantao%3BKusiak%2C+John+W&rft.aulast=Wei&rft.aufirst=Wanli&rft.date=2002-05-17&rft.volume=277&rft.issue=20&rft.spage=17649&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-16 N1 - Date created - 2002-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Crystal structure of the human estrogen sulfotransferase-PAPS complex: evidence for catalytic role of Ser137 in the sulfuryl transfer reaction. AN - 71680708; 11884392 AB - Estrogen sulfotransferase (EST) transfers the sulfate group from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to estrogenic steroids. Here we report the crystal structure of human EST (hEST) in the context of the V269E mutant-PAPS complex, which is the first structure containing the active sulfate donor for any sulfotransferase. Superimposing this structure with the crystal structure of hEST in complex with the donor product 3'-phosphoadenosine 5'-phosphate (PAP) and the acceptor substrate 17beta-estradiol, the ternary structure with the PAPS and estradiol molecule, is modeled. These structures have now provided a more complete view of the S(N)2-like in-line displacement reaction catalyzed by sulfotransferases. In the PAPS-bound structure, the side chain nitrogen of the catalytic Lys(47) interacts with the side chain hydroxyl of Ser(137) and not with the bridging oxygen between the 5'-phosphate and sulfate groups of the PAPS molecule as is seen in the PAP-bound structures. This conformational change of the side chain nitrogen indicates that the interaction of Lys(47) with Ser(137) may regulate PAPS hydrolysis in the absences of an acceptor substrate. Supporting the structural data, the mutations of Ser(137) to cysteine and alanine decrease gradually k(cat) for PAPS hydrolysis and transfer activity. Thus, Ser(137) appears to play an important role in regulating the side chain interaction of Lys(47) with the bridging oxygen between the 5'-phosphate and the sulfate of PAPS. JF - The Journal of biological chemistry AU - Pedersen, Lars C AU - Petrotchenko, Evgeniy AU - Shevtsov, Sergei AU - Negishi, Masahiko AD - Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/05/17/ PY - 2002 DA - 2002 May 17 SP - 17928 EP - 17932 VL - 277 IS - 20 SN - 0021-9258, 0021-9258 KW - Macromolecular Substances KW - 0 KW - Sulfates KW - Serine KW - 452VLY9402 KW - Phosphoadenosine Phosphosulfate KW - 482-67-7 KW - Estradiol KW - 4TI98Z838E KW - Sulfotransferases KW - EC 2.8.2.- KW - estrone sulfotransferase KW - EC 2.8.2.4 KW - Lysine KW - K3Z4F929H6 KW - Cysteine KW - K848JZ4886 KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Cysteine -- metabolism KW - Models, Molecular KW - Protein Binding KW - Serine -- metabolism KW - Lysine -- metabolism KW - Binding Sites KW - Estradiol -- metabolism KW - Sulfates -- metabolism KW - Mutagenesis, Site-Directed KW - Alanine -- metabolism KW - Crystallography, X-Ray KW - Models, Chemical KW - Amino Acid Substitution KW - Protein Conformation KW - Catalysis KW - Sulfotransferases -- chemistry KW - Phosphoadenosine Phosphosulfate -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71680708?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Crystal+structure+of+the+human+estrogen+sulfotransferase-PAPS+complex%3A+evidence+for+catalytic+role+of+Ser137+in+the+sulfuryl+transfer+reaction.&rft.au=Pedersen%2C+Lars+C%3BPetrotchenko%2C+Evgeniy%3BShevtsov%2C+Sergei%3BNegishi%2C+Masahiko&rft.aulast=Pedersen&rft.aufirst=Lars&rft.date=2002-05-17&rft.volume=277&rft.issue=20&rft.spage=17928&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-16 N1 - Date created - 2002-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Further evidence for distinct reactive intermediates from nitroxyl and peroxynitrite: effects of buffer composition on the chemistry of Angeli's salt and synthetic peroxynitrite. AN - 71798697; 12054463 AB - The nitroxyl (HNO) donor Angeli's salt (Na(2)N(2)O(3); AS) is cytotoxic in vitro, inducing double strand DNA breaks and base oxidation, yet may have pharmacological application in the treatment of cardiovascular disease. The chemical profiles of AS and synthetic peroxynitrite (ONOO(-)) in aerobic solution were recently compared, and AS was found to form a distinct reactive intermediate. However, similarities in the chemical behavior of the reactive nitrogen oxide species (RNOS) were apparent under certain conditions. Buffer composition was found to have a significant and unexpected impact on the observed chemistry of RNOS, and varied buffer conditions were utilized to further distinguish the chemical profiles elicited by the RNOS donors AS and synthetic ONOO(-). Addition of HEPES to the assay buffer significantly quenched oxidation of dihydrorhodamine (DHR), hydroxylation of benzoic acid (BA), and DNA damage by both AS and ONOO(-), and oxidation and nitration of hydroxyphenylacetic acid by ONOO(-). Additionally, H(2)O(2) was produced in a concentration-dependent manner from the interaction of HEPES with both the donor intermediates. Interestingly, clonogenic survival was not affected by HEPES, indicating that H(2)O(2) is not a contributing factor to in vitro cytotoxicity of AS. Variation in RNOS reactivity was dramatic with significantly higher relative affinity for the AS intermediate toward DHR, BA, DNA, and HEPES and increased production of H(2)O(2). Further, AS reacted to a significantly greater extent with the unprotonated amine form of HEPES while the interaction of ONOO(-) with HEPES was pH-independent. Addition of bicarbonate only altered ONOO(-) chemistry. This study emphasizes the importance of buffer composition on chemical outcome and thus on interpretation and provides further evidence that ONOO(-) is not an intermediate formed between the reaction of O(2) and HNO produced by AS. (c) 2002 Elsevier Science (USA). JF - Archives of biochemistry and biophysics AU - Miranda, Katrina M AU - Yamada, Ken-ichi AU - Espey, Michael G AU - Thomas, Douglas D AU - DeGraff, William AU - Mitchell, James B AU - Krishna, Murali C AU - Colton, Carol A AU - Wink, David A AD - Radiation Biology Branch, National Cancer Institute/NIH, Building 10, Room B3-B69, Bethesda, MD 20892, USA. kmiranda@box-k.nih.gov Y1 - 2002/05/15/ PY - 2002 DA - 2002 May 15 SP - 134 EP - 144 VL - 401 IS - 2 SN - 0003-9861, 0003-9861 KW - Buffers KW - 0 KW - Nitric Oxide Donors KW - Nitrites KW - Nitrogen Oxides KW - Phenylacetates KW - Reactive Nitrogen Species KW - Rhodamines KW - dihydrorhodamine 123 KW - 109244-58-8 KW - Peroxynitrous Acid KW - 14691-52-2 KW - 4-hydroxyphenylacetic acid KW - 156-38-7 KW - oxyhyponitrite KW - 18550-55-5 KW - Benzoic Acid KW - 8SKN0B0MIM KW - nitroxyl KW - GFQ4MMS07W KW - Index Medicus KW - Animals KW - DNA Damage KW - Benzoic Acid -- chemistry KW - Hydroxylation KW - Nitric Oxide Donors -- pharmacology KW - Oxidation-Reduction KW - Reactive Nitrogen Species -- chemistry KW - Cell Line KW - Phenylacetates -- chemistry KW - Rhodamines -- chemistry KW - Cricetinae KW - Nitric Oxide Donors -- chemistry KW - Nitrites -- chemistry KW - Nitrites -- pharmacology KW - Peroxynitrous Acid -- chemistry KW - Nitrogen Oxides -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71798697?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+biochemistry+and+biophysics&rft.atitle=Further+evidence+for+distinct+reactive+intermediates+from+nitroxyl+and+peroxynitrite%3A+effects+of+buffer+composition+on+the+chemistry+of+Angeli%27s+salt+and+synthetic+peroxynitrite.&rft.au=Miranda%2C+Katrina+M%3BYamada%2C+Ken-ichi%3BEspey%2C+Michael+G%3BThomas%2C+Douglas+D%3BDeGraff%2C+William%3BMitchell%2C+James+B%3BKrishna%2C+Murali+C%3BColton%2C+Carol+A%3BWink%2C+David+A&rft.aulast=Miranda&rft.aufirst=Katrina&rft.date=2002-05-15&rft.volume=401&rft.issue=2&rft.spage=134&rft.isbn=&rft.btitle=&rft.title=Archives+of+biochemistry+and+biophysics&rft.issn=00039861&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-01 N1 - Date created - 2002-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations that bypass tRNA binding activate the intrinsically defective kinase domain in GCN2. AN - 71745651; 12023305 AB - The protein kinase GCN2 is activated in amino acid-starved cells on binding of uncharged tRNA to a histidyl-tRNA synthetase (HisRS)-related domain. We isolated two point mutations in the protein kinase (PK) domain, R794G and F842L, that permit strong kinase activity in the absence of tRNA binding. These mutations also bypass the requirement for ribosome binding, dimerization, and association with the GCN1/GCN20 regulatory complex, suggesting that all of these functions facilitate tRNA binding to wild-type GCN2. While the isolated wild-type PK domain was completely inert, the mutant PK was highly active in vivo and in vitro. These results identify an inhibitory structure intrinsic to the PK domain that must be overcome on tRNA binding by interactions with a regulatory region, most likely the N terminus of the HisRS segment. As Arg 794 and Phe 842 are predicted to lie close to one another and to the active site, they may participate directly in misaligning active site residues. Autophosphorylation of the activation loop was stimulated by R794G and F842L, and the autophosphorylation sites remained critical for GCN2 function in the presence of these mutations. Our results imply a two-step activation mechanism involving distinct conformational changes in the PK domain. JF - Genes & development AU - Qiu, Hongfang AU - Hu, Cuihua AU - Dong, Jinsheng AU - Hinnebusch, Alan G AD - Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. Y1 - 2002/05/15/ PY - 2002 DA - 2002 May 15 SP - 1271 EP - 1280 VL - 16 IS - 10 SN - 0890-9369, 0890-9369 KW - RNA, Transfer KW - 9014-25-9 KW - Protein Kinases KW - EC 2.7.- KW - Histidine-tRNA Ligase KW - EC 6.1.1.21 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Phosphorylation KW - Enzyme Activation KW - Dimerization KW - Histidine-tRNA Ligase -- genetics KW - Gene Expression Regulation KW - Protein Structure, Tertiary KW - Binding Sites KW - Protein Kinases -- metabolism KW - RNA, Transfer -- metabolism KW - Protein Kinases -- genetics KW - Mutation -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71745651?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Containment+of+viral+rebound+after+antiretroviral+therapy+suspension+in+macaques+chronically+infected+with+SIV+following+vaccination+with+NYVAC-SIV+recombinant+vaccines&rft.au=Tryniszewska%2C+E%3BLewis%2C+M+G%3BHel%2C+Z%3BNacsa%2C+J%3BTsai%2C+W-P%3BStevceva%2C+L%3BParks%2C+R+W%3BMoniuszko%2C+M%3BCairns%2C+S%3BSmith%2C+KA&rft.aulast=Tryniszewska&rft.aufirst=E&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-26 N1 - Date created - 2002-05-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: EMBO J. 2000 Apr 17;19(8):1887-99 [10775272] Mol Cell Biol. 1998 May;18(5):2697-711 [9566889] EMBO J. 2000 Dec 1;19(23):6622-33 [11101534] EMBO J. 2001 Mar 15;20(6):1425-38 [11250908] Mol Cell. 2000 Nov;6(5):1099-108 [11106749] Mol Cell Biol. 1984 Jul;4(7):1326-33 [6095062] Proc Natl Acad Sci U S A. 1989 Jun;86(12):4579-83 [2660141] Mol Cell Biol. 1990 Jun;10(6):2820-31 [2188100] Science. 1991 Jul 26;253(5018):407-14 [1862342] Mol Cell Biol. 1992 Dec;12(12):5801-15 [1448107] FASEB J. 1995 May;9(8):576-96 [7768349] Mol Cell Biol. 1995 Aug;15(8):4497-506 [7623840] Nature. 1995 Jul 27;376(6538):313-20 [7630397] Cell. 1996 Apr 19;85(2):149-58 [8612268] Mol Cell Biol. 1997 Mar;17(3):1298-313 [9032257] Mol Cell Biol. 1997 Aug;17(8):4474-89 [9234705] J Biol Chem. 1998 Jan 16;273(3):1808-14 [9430731] Mol Cell Biol. 1998 Apr;18(4):2282-97 [9528799] Mol Cell. 2000 Aug;6(2):269-79 [10983975] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidative DNA and protein damage in metal-induced toxicity and carcinogenesis. AN - 71685347; 12008111 AB - This review discusses the relevance of oxidative damage to metal-induced toxicity and carcinogenesis. Presented are important facts and mechanistic concepts on the capacity of selected transition metals, mainly Ni, but also Cu, Co, Cr, and briefly several others, to generate active oxygen species and other reactive intermediates under physiological conditions. These metals are known to be toxic and/or carcinogenic contaminants of the occupational and general environments. Their redox activity may underlay the mechanism of mediation of oxidative damage to cell constituents. The presentation is focused on selected issues relative to genetic and epigenetic toxicity and illustrated with examples of metal-mediated oxidative damage to the principal components of chromatin, i.e., DNA, histones, and protamines. JF - Free radical biology & medicine AU - Kasprzak, Kazimierz S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD 21701-1201, USA. kasprkaz@mail.ncifcrf.gov Y1 - 2002/05/15/ PY - 2002 DA - 2002 May 15 SP - 958 EP - 967 VL - 32 IS - 10 SN - 0891-5849, 0891-5849 KW - Carcinogens KW - 0 KW - Free Radicals KW - Metals KW - Proteins KW - Reactive Oxygen Species KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Oxidation-Reduction KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Humans KW - Proteins -- drug effects KW - DNA -- metabolism KW - Oxidative Stress -- drug effects KW - Carcinogens -- toxicity KW - Proteins -- metabolism KW - Metals -- toxicity KW - DNA Damage -- drug effects KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71685347?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Oxidative+DNA+and+protein+damage+in+metal-induced+toxicity+and+carcinogenesis.&rft.au=Kasprzak%2C+Kazimierz+S&rft.aulast=Kasprzak&rft.aufirst=Kazimierz&rft.date=2002-05-15&rft.volume=32&rft.issue=10&rft.spage=958&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-19 N1 - Date created - 2002-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Changes in T-cell receptor VB repertoire in aplastic anemia: effects of different immunosuppressive regimens. AN - 71641491; 11986222 AB - We studied the degree and the pattern of skewing of the variable region of beta-chain (VB) T-cell receptor (TCR) repertoire in aplastic anemia (AA) at initial presentation and after immunosuppression using a high-resolution analysis of the TCR VB complementarity-determining region 3 (CDR3). Age-matched healthy individuals and multitransfused patients with non-immune-mediated hematologic diseases were used as controls. In newly diagnosed AA, the average frequency of CDR3 size distribution deviation indicative of oligoclonal T-cell proliferation was increased (44% +/- 33% vs 9% +/- 9%; P =.0001); AA patients with human leukocyte antigen (HLA)-DR2 and those with expanded paroxysmal nocturnal hemoglobinuria clones showed more skewed VB repertoires. Nonrandom oligoclonal patterns were found for VB6, VB14-16, VB21, VB23, and VB24 subfamilies in more than 50%, and for VB15, VB21, and VB24 in more than 70% of AA patients with HLA-DR2. Patients received immunosuppression with antithymocyte globulin (ATG)/cyclosporine (CsA) or cyclophosphamide (CTX) with CsA in combination, and their VB repertoire was reanalyzed after treatment. Whereas no significant change in the degree of VB skewing in patients who had received ATG was seen, patients treated with CTX showed a much higher extent of oligoclonality within all VB families, consistent with a profound and long-lasting contraction of the T-cell repertoire. VB analysis did not correlate with the lymphocyte count prior to lymphocytotoxic therapy; however, after therapy the degree of VB skewing was highly reflective of the decrease in lymphocyte numbers, suggesting iatrogenic gaps in the VB repertoire rather than the emergence of clonal dominance. Our data indicate that multiple specific clones mediate the immune process in AA. JF - Blood AU - Kook, Hoon AU - Risitano, Antonio M AU - Zeng, Weihua AU - Wlodarski, Marcin AU - Lottemann, Craig AU - Nakamura, Ryotaro AU - Barrett, John AU - Young, Neal S AU - Maciejewski, Jaroslaw P AD - Hematology Branch of the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2002/05/15/ PY - 2002 DA - 2002 May 15 SP - 3668 EP - 3675 VL - 99 IS - 10 SN - 0006-4971, 0006-4971 KW - Antilymphocyte Serum KW - 0 KW - Complementarity Determining Regions KW - Immunosuppressive Agents KW - Receptors, Antigen, T-Cell, alpha-beta KW - Cyclosporine KW - 83HN0GTJ6D KW - Cyclophosphamide KW - 8N3DW7272P KW - Abridged Index Medicus KW - Index Medicus KW - Lymphocyte Count KW - Cyclophosphamide -- therapeutic use KW - Humans KW - Cyclosporine -- therapeutic use KW - Complementarity Determining Regions -- genetics KW - Adult KW - Middle Aged KW - Child KW - Adolescent KW - Antilymphocyte Serum -- therapeutic use KW - Anemia, Aplastic -- genetics KW - Anemia, Aplastic -- drug therapy KW - Gene Rearrangement, beta-Chain T-Cell Antigen Receptor KW - Anemia, Aplastic -- diagnosis KW - Receptors, Antigen, T-Cell, alpha-beta -- genetics KW - Immunosuppressive Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71641491?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Changes+in+T-cell+receptor+VB+repertoire+in+aplastic+anemia%3A+effects+of+different+immunosuppressive+regimens.&rft.au=Kook%2C+Hoon%3BRisitano%2C+Antonio+M%3BZeng%2C+Weihua%3BWlodarski%2C+Marcin%3BLottemann%2C+Craig%3BNakamura%2C+Ryotaro%3BBarrett%2C+John%3BYoung%2C+Neal+S%3BMaciejewski%2C+Jaroslaw+P&rft.aulast=Kook&rft.aufirst=Hoon&rft.date=2002-05-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-10 N1 - Date created - 2002-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Controversies in Clostridium difficile Testing AN - 18435031; 5412582 AB - Recent reports of two nosocomial outbreaks of Clostridium difficile-associated disease caused by toxin A-deficient strains emphasize that these strains can cause disease. Laboratories using an assay that detects only toxin A as their primary diagnostic test risk misdiagnosis of cases or outbreaks in the institutions they serve. Repeat testing can account for a significant portion of a laboratory's C. difficile testing workload. Published data are available to support laboratory rules for rejection of repeat stood specimens within 7 days of an initial specimen. There are also substantial published data to support laboratory rejection of formed stools sent to the laboratory for C. difficile testing. JF - Clinical Microbiology Newsletter AU - Fedorko, D P AD - Senior Staff Microbiologist, Microbiology Service, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, USA, dfedorko@nih.gov Y1 - 2002/05/15/ PY - 2002 DA - 2002 May 15 SP - 76 EP - 79 VL - 24 IS - 10 SN - 0196-4399, 0196-4399 KW - misdiagnosis KW - Microbiology Abstracts B: Bacteriology KW - J 02710:Identification, taxonomy and typing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18435031?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Microbiology+Newsletter&rft.atitle=Controversies+in+Clostridium+difficile+Testing&rft.au=Fedorko%2C+D+P&rft.aulast=Fedorko&rft.aufirst=D&rft.date=2002-05-15&rft.volume=24&rft.issue=10&rft.spage=76&rft.isbn=&rft.btitle=&rft.title=Clinical+Microbiology+Newsletter&rft.issn=01964399&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Connected gene neighborhoods in prokaryotic genomes AN - 18333717; 5385000 AB - A computational method was developed for delineating connected gene neighborhoods in bacterial and archaeal genomes. These gene neighborhoods are not typically present, in their entirety, in any single genome, but are held together by overlapping, partially conserved gene arrays. The procedure was applied to comparing the orders of orthologous genes, which were extracted from the database of Clusters of Orthologous Groups of proteins (COGs), in 31 prokaryotic genomes and resulted in the identification of 188 clusters of gene arrays, which included 1001 of 2890 COGs. These clusters were projected onto actual genomes to produce extended neighborhoods including additional genes, which are adjacent to the genes from the clusters and are transcribed in the same direction, which resulted in a total of 2387 COGs being included in the neighborhoods. Most of the neighborhoods consist predominantly of genes united by a coherent functional theme, but also include a minority of genes without an obvious functional connection to the main theme. We hypothesize that although some of the latter genes might have unsuspected roles, others are maintained within gene arrays because of the advantage of expression at a level that is typical of the given neighborhood. We designate this phenomenon `genomic hitchhiking'. The largest neighborhood includes 79 genes (COGs) and consists of overlapping, rearranged ribosomal protein superoperons; apparent genome hitchhiking is particularly typical of this neighborhood and other neighborhoods that consist of genes coding for translation machinery components. Several neighborhoods involve previously undetected connections between genes, allowing new functional predictions. Gene neighborhoods appear to evolve via complex rearrangement, with different combinations of genes from a neighborhood fixed in different lineages. JF - Nucleic Acids Research AU - Rogozin, IB AU - Makarova, K S AU - Murvai, J AU - Czabarka, E AU - Wolf, YI AU - Tatusov, R L AU - Szekely, LA AU - Koonin, E V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA, koonin@ncbi.nlm.nih.gov Y1 - 2002/05/15/ PY - 2002 DA - 2002 May 15 SP - 2212 EP - 2223 VL - 30 IS - 10 SN - 0305-1048, 0305-1048 KW - gene neighborhoods KW - gene arrays KW - genomic hitchhiking KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Gene expression KW - Genomes KW - Bacteria KW - Archaea KW - N 14510:Occurrence, isolation & assay KW - J 02725:DNA UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18333717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=Connected+gene+neighborhoods+in+prokaryotic+genomes&rft.au=Rogozin%2C+IB%3BMakarova%2C+K+S%3BMurvai%2C+J%3BCzabarka%2C+E%3BWolf%2C+YI%3BTatusov%2C+R+L%3BSzekely%2C+LA%3BKoonin%2C+E+V&rft.aulast=Rogozin&rft.aufirst=IB&rft.date=2002-05-15&rft.volume=30&rft.issue=10&rft.spage=2212&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Archaea; Genomes; Gene expression; Bacteria ER - TY - JOUR T1 - Mutations associated with base excision repair deficiency and methylation-induced genotoxic stress. AN - 71694867; 11983862 AB - The long-term effect of exposure to DNA alkylating agents is entwined with the cell's genetic capacity for DNA repair and appropriate DNA damage responses. A unique combination of environmental exposure and deficiency in these responses can lead to genomic instability; this "gene-environment interaction" paradigm is a theme for research on chronic disease etiology. In the present study, we used mouse embryonic fibroblasts with a gene deletion in the base excision repair (BER) enzymes DNA beta-polymerase (beta-pol) and alkyladenine DNA glycosylase (AAG), along with exposure to methyl methanesulfonate (MMS) to study mutagenesis as a function of a particular gene-environment interaction. The beta-pol null cells, defective in BER, exhibit a modest increase in spontaneous mutagenesis compared with wild-type cells. MMS exposure increases mutant frequency in beta-pol null cells, but not in isogenic wild-type cells; UV light exposure or N-methyl-N'-nitro-N-nitrosoguanidine exposure increases mutant frequency similarly in both cell lines. The MMS-induced increase in mutant frequency in beta-pol null cells appears to be caused by DNA lesions that are AAG substrates, because overexpression of AAG in beta-pol null cells eliminates the effect. In contrast, beta-pol/AAG double null cells are slightly more mutable than the beta-pol null cells after MMS exposure. These results illustrate that BER plays a role in protecting mouse embryonic fibroblast cells against methylation-induced mutations and characterize the effect of a particular combination of BER gene defect and environmental exposure. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Sobol, Robert W AU - Watson, David E AU - Nakamura, Jun AU - Yakes, F Michael AU - Hou, Esther AU - Horton, Julie K AU - Ladapo, Joseph AU - Van Houten, Bennett AU - Swenberg, James A AU - Tindall, Kenneth R AU - Samson, Leona D AU - Wilson, Samuel H AD - Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2002/05/14/ PY - 2002 DA - 2002 May 14 SP - 6860 EP - 6865 VL - 99 IS - 10 SN - 0027-8424, 0027-8424 KW - Alkylating Agents KW - 0 KW - Mesylates KW - Mutagens KW - Transcription Factors KW - Viral Proteins KW - cII protein, bacteriophage lambda KW - methanesulfonic acid KW - 12EH9M7279 KW - Methylnitronitrosoguanidine KW - 12H3O2UGSF KW - DNA Polymerase beta KW - EC 2.7.7.- KW - 3-methyladenine-DNA glycosylase KW - EC 3.2.2.- KW - DNA Glycosylases KW - N-Glycosyl Hydrolases KW - Carbon-Oxygen Lyases KW - EC 4.2.- KW - DNA-(Apurinic or Apyrimidinic Site) Lyase KW - EC 4.2.99.18 KW - Index Medicus KW - Animals KW - Bacteriophage lambda -- genetics KW - Alkylating Agents -- pharmacology KW - Mice KW - Mutagens -- pharmacology KW - Transcription Factors -- genetics KW - Mutagenesis KW - Binding Sites KW - Mice, Knockout KW - Carbon-Oxygen Lyases -- metabolism KW - Cells, Cultured KW - Methylnitronitrosoguanidine -- pharmacology KW - Genes, Viral KW - Mesylates -- pharmacology KW - Base Pairing KW - DNA Repair KW - N-Glycosyl Hydrolases -- genetics KW - DNA Polymerase beta -- genetics KW - DNA Methylation KW - N-Glycosyl Hydrolases -- metabolism KW - DNA Damage KW - DNA Polymerase beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71694867?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Mutations+associated+with+base+excision+repair+deficiency+and+methylation-induced+genotoxic+stress.&rft.au=Sobol%2C+Robert+W%3BWatson%2C+David+E%3BNakamura%2C+Jun%3BYakes%2C+F+Michael%3BHou%2C+Esther%3BHorton%2C+Julie+K%3BLadapo%2C+Joseph%3BVan+Houten%2C+Bennett%3BSwenberg%2C+James+A%3BTindall%2C+Kenneth+R%3BSamson%2C+Leona+D%3BWilson%2C+Samuel+H&rft.aulast=Sobol&rft.aufirst=Robert&rft.date=2002-05-14&rft.volume=99&rft.issue=10&rft.spage=6860&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-18 N1 - Date created - 2002-05-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1999 Jun 1;59(11):2522-6 [10363965] Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13087-92 [9371804] Mutat Res. 1999 Jun 30;427(2):67-78 [10393261] Exp Neurol. 1999 Sep;159(1):309-18 [10486199] Science. 1999 Dec 3;286(5446):1897-905 [10583946] J Biol Chem. 2000 Jan 21;275(3):2211-8 [10636928] Nat Struct Biol. 2000 Mar;7(3):176-8 [10700268] Nature. 2000 Jun 15;405(6788):807-10 [10866204] J Biol Chem. 2000 Sep 15;275(37):28433-8 [10854423] Prog Nucleic Acid Res Mol Biol. 2001;68:57-74 [11554313] J Biol Chem. 1998 Jan 9;273(2):898-902 [9422747] Cancer Res. 1998 Jan 15;58(2):222-5 [9443396] Nucleic Acids Res. 1998 Apr 15;26(8):2001-7 [9518496] Biochemistry. 1998 Mar 17;37(11):3575-80 [9530283] J Biol Chem. 1998 May 1;273(18):11121-6 [9556598] J Biol Chem. 1998 Jun 12;273(24):15263-70 [9614142] Mutat Res. 1998 Feb 26;398(1-2):83-92 [9626968] Cold Spring Harb Symp Quant Biol. 2000;65:143-55 [12760029] Mutat Res. 1990 Jul;231(1):11-30 [2195323] Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9127-31 [1924375] Mutat Res. 1992 Apr;271(2):101-13 [1372680] Nucleic Acids Res. 1992 Jul 11;20(13):3485-94 [1630919] Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5695-9 [8202550] J Biol Chem. 1995 Jan 13;270(2):949-57 [7822335] Mutat Res. 1995 May;336(3):307-16 [7739617] Science. 1995 Aug 4;269(5224):699-702 [7624801] Trends Biochem Sci. 1995 Oct;20(10):391-7 [8533150] Nature. 1996 Jan 11;379(6561):183-6 [8538772] Mutat Res. 1998 Jun;407(3):203-15 [9653447] J Biol Chem. 1998 Aug 14;273(33):21203-9 [9694877] Mutat Res. 1998 Jul 17;403(1-2):171-5 [9726017] Mol Cell Biol. 1998 Oct;18(10):5828-37 [9742100] Environ Mol Mutagen. 1998;32(2):163-72 [9776179] Carcinogenesis. 1998 Nov;19(11):1931-7 [9855005] Environ Mol Mutagen. 1999;33(1):21-7 [10037320] Cancer Res. 1999 Apr 1;59(7):1544-51 [10197627] Mutat Res. 1996 May 15;363(1):57-66 [8632778] J Biol Chem. 1996 Jul 26;271(30):17811-5 [8663612] Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9073-8 [8799156] EMBO J. 1996 Dec 2;15(23):6662-70 [8978692] Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):514-9 [9012815] Mutat Res. 1997 Feb 14;388(2-3):155-63 [9057876] Mutat Res. 1997 Feb 14;388(2-3):219-22 [9057883] Biochemistry. 1997 Jun 17;36(24):7557-66 [9200707] Photochem Photobiol. 1997 Sep;66(3):356-62 [9297978] Mutat Res. 1997 Sep 18;393(1-2):99-106 [9357566] Exp Eye Res. 1999 Jun;68(6):765-72 [10375440] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Initiating oncogenic event determines gene-expression patterns of human breast cancer models. AN - 71686029; 12011455 AB - Molecular expression profiling of tumors initiated by transgenic overexpression of c-myc, c-neu, c-ha-ras, polyoma middle T antigen (PyMT) or simian virus 40 T/t antigen (T-ag) targeted to the mouse mammary gland have identified both common and oncogene-specific events associated with tumor formation and progression. The tumors shared great similarities in their gene-expression profiles as compared with the normal mammary gland with an induction of cell-cycle regulators, metabolic regulators, zinc finger proteins, and protein tyrosine phosphatases, along with the suppression of some protein tyrosine kinases. Selection and hierarchical clustering of the most variant genes, however, resulted in separating the mouse models into three groups with distinct oncogene-specific patterns of gene expression. Such an identification of targets specified by particular oncogenes may facilitate development of lesion-specific therapeutics and preclinical testing. Moreover, similarities in gene expression between human breast cancers and the mouse models have been identified, thus providing an important component for the validation of transgenic mammary cancer models. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Desai, Kartiki V AU - Xiao, Nianqing AU - Wang, Weili AU - Gangi, Lisa AU - Greene, John AU - Powell, John I AU - Dickson, Robert AU - Furth, Priscilla AU - Hunter, Kent AU - Kucherlapati, Raju AU - Simon, Richard AU - Liu, Edison T AU - Green, Jeffrey E AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2002/05/14/ PY - 2002 DA - 2002 May 14 SP - 6967 EP - 6972 VL - 99 IS - 10 SN - 0027-8424, 0027-8424 KW - Antigens, Polyomavirus Transforming KW - 0 KW - Index Medicus KW - Genes, ras KW - Gene Expression Profiling KW - Animals KW - Oligonucleotide Array Sequence Analysis KW - Genes, myc KW - Genes, erbB-2 KW - Multigene Family KW - Humans KW - Disease Models, Animal KW - Mice KW - Mice, Transgenic KW - Antigens, Polyomavirus Transforming -- genetics KW - Female KW - Breast Neoplasms -- genetics KW - Gene Expression KW - Proto-Oncogenes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71686029?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Initiating+oncogenic+event+determines+gene-expression+patterns+of+human+breast+cancer+models.&rft.au=Desai%2C+Kartiki+V%3BXiao%2C+Nianqing%3BWang%2C+Weili%3BGangi%2C+Lisa%3BGreene%2C+John%3BPowell%2C+John+I%3BDickson%2C+Robert%3BFurth%2C+Priscilla%3BHunter%2C+Kent%3BKucherlapati%2C+Raju%3BSimon%2C+Richard%3BLiu%2C+Edison+T%3BGreen%2C+Jeffrey+E&rft.aulast=Desai&rft.aufirst=Kartiki&rft.date=2002-05-14&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-18 N1 - Date created - 2002-05-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Steroid Biochem Mol Biol. 2000 May;73(1-2):29-38 [10822022] Anticancer Drugs. 2000 Feb;11(2):63-8 [10789587] Biotechniques. 2000 Sep;29(3):548-50, 552-4, 556 passim [10997270] Genes Dev. 2000 Oct 1;14(19):2393-409 [11018009] Annu Rev Cell Dev Biol. 2000;16:653-99 [11031250] Cancer Res. 2000 Nov 1;60(21):5922-8 [11085504] Cancer Res. 2000 Dec 15;60(24):6901-10 [11156389] N Engl J Med. 2001 Feb 22;344(8):539-48 [11207349] Nature. 2000 Aug 17;406(6797):747-52 [10963602] Oncologist. 2001;6(2):133-46 [11306725] Oncogene. 2001 Apr 5;20(15):1803-15 [11313928] Nat Med. 2001 May;7(5):548-52 [11329054] Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991-5 [6326095] Cell. 1986 May 23;45(4):485-95 [3011271] Science. 1987 Jan 9;235(4785):177-82 [3798106] Anal Biochem. 1987 Apr;162(1):156-9 [2440339] Cell. 1988 Jul 15;54(2):275-83 [2839300] Cancer Res. 1989 Apr 15;49(8):2087-90 [2564806] Mol Cell Biol. 1989 Feb;9(2):854-9 [2540427] Cell. 1989 Jun 16;57(6):931-6 [2567634] Mol Cell Biol. 1992 Mar;12(3):954-61 [1312220] EMBO J. 1992 Dec;11(13):5013-20 [1464323] Oncogene. 1993 Jul;8(7):1965-71 [8390039] Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11236-40 [7972041] Breast Cancer Res Treat. 1994;31(1):5-9 [7981456] Genes Chromosomes Cancer. 1995 Dec;14(4):227-51 [8605112] Cancer Res. 1998 Nov 15;58(22):5009-13 [9823299] Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8 [9843981] Mamm Genome. 1999 Mar;10(3):311-4 [10051331] Genes Chromosomes Cancer. 1999 Jul;25(3):251-60 [10379871] Mech Dev. 1999 Jul;85(1-2):173-7 [10415358] J Cell Biol. 1999 Jul 26;146(2):477-92 [10427099] Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9212-7 [10430922] Nat Rev Mol Cell Biol. 2001 Feb;2(2):127-37 [11252954] Mol Cell Biol. 2000 Jan;20(2):672-83 [10611246] J Cell Biol. 2000 Feb 7;148(3):591-602 [10662783] Curr Opin Genet Dev. 2000 Feb;10(1):106-13 [10679397] Oncogene. 2000 Feb 21;19(8):968-88 [10713680] Oncogene. 2000 Feb 21;19(8):1038-44 [10713687] Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3260-5 [10737792] J Biol Chem. 2000 Apr 14;275(15):11141-6 [10753920] Erratum In: Proc Natl Acad Sci U S A 2002 Jul 23;99(15):10227 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - JAKs, STATs and Src kinases in hematopoiesis. AN - 71722025; 12032773 AB - Hematopoiesis is the cumulative result of intricately regulated signal transduction cascades that are mediated by cytokines and their cognate receptors. Proper culmination of these diverse signaling pathways forms the basis for an orderly generation of different cell types and aberrations in these pathways is an underlying cause for diseases such as leukemias and other myeloproliferative and lymphoproliferative disorders. Over the past decade, downstream signal transduction events initiated upon cytokine/growth factor stimulation have been a major focus of basic and applied biomedical research. As a result, several key concepts have emerged allowing a better understanding of the complex signaling processes. A group of transcription factors, termed signal transducers and activators of transcription (STATs) appear to orchestrate the downstream events propagated by cytokine/growth factor interactions with their cognate receptors. Similarly, cytoplasmic Janus protein tyrosine kinases (JAKs) and Src family of kinases seem to play a critical role in diverse signal transduction pathways that govern cellular survival, proliferation, differentiation and apoptosis. Accumulating evidence suggests that STAT protein activation may be mediated by members of both JAK and Src family members following cytokine/growth factor stimulation. In addition, JAK kinases appear to be essential for the phosphorylation of the cytokine receptors which results in the creation of docking sites on the receptors for binding of SH2-containing proteins such as STATs, Src-kinases and other signaling intermediates. Cell and tissue-specificity of cytokine action appears to be determined by the nature of signal transduction pathways activated by cytokine/receptor interactions. The integration of these diverse signaling cues from active JAK kinases, members of the Src-family kinases and STAT proteins, leads to cell proliferation, cell survival and differentiation, the end-point of the cytokine/growth factor stimulus. JF - Oncogene AU - Rane, Sushil G AU - Reddy, E Premkumar AD - Laboratory of Cell Regulation & Carcinogenesis, NCI, NIH, Bldg. 41, C629, 41 Library Drive, Bethesda, Maryland, MD 20892, USA. Y1 - 2002/05/13/ PY - 2002 DA - 2002 May 13 SP - 3334 EP - 3358 VL - 21 IS - 21 SN - 0950-9232, 0950-9232 KW - Cytokines KW - 0 KW - DNA-Binding Proteins KW - STAT1 Transcription Factor KW - STAT1 protein, human KW - Trans-Activators KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - JAK1 protein, human KW - EC 2.7.10.2 KW - Janus Kinase 1 KW - src-Family Kinases KW - Index Medicus KW - Animals KW - Apoptosis KW - Phosphorylation KW - Humans KW - Cytokines -- metabolism KW - Models, Biological KW - Signal Transduction KW - Cloning, Molecular KW - Cell Division KW - Hematopoiesis -- physiology KW - DNA-Binding Proteins -- physiology KW - Trans-Activators -- physiology KW - src-Family Kinases -- physiology KW - Protein-Tyrosine Kinases -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71722025?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=JAKs%2C+STATs+and+Src+kinases+in+hematopoiesis.&rft.au=Rane%2C+Sushil+G%3BReddy%2C+E+Premkumar&rft.aulast=Rane&rft.aufirst=Sushil&rft.date=2002-05-13&rft.volume=21&rft.issue=21&rft.spage=3334&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-17 N1 - Date created - 2002-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional regulation of cyclooxygenase-1 by histone deacetylase inhibitors in normal human astrocyte cells. AN - 71655143; 11877441 AB - While cyclooxygenase (COX)-2 is a highly inducible gene, COX-1 is widely known as a noninducible gene and is constitutively expressed in a variety of cell lines and human tissues. Recently, several reports have indicated that COX-1 is also regulated at the transcriptional level by various stimuli. We present evidence that histone deacetylase (HDAC) inhibitors induce COX-1 transcription and translation in normal human astrocyte (NHA) cells and glioma cell lines. HDAC inhibitors increased acetylated histone H4 protein expression in NHA cells. The levels of COX-1 mRNA and protein were maximal at 24 and 48 h, respectively, after treatment with the specific HDAC inhibitor, trichostatin A (TSA). In addition, TSA-treated NHA cells produced prostaglandin E(2) as determined by enzyme-linked immunosorbent assay after incubation with 10 microm exogenous arachidonic acid, indicating that the induced COX-1 is functionally active. In addition to NHA cells, this up-regulation of COX-1 after treatment with HDAC inhibitors was observed in 5 different glioma cell lines. The nucleotide sequence of the inducible COX-1 cDNA was confirmed identical to human COX-1 that was previously reported. HDAC inhibitors stimulated COX-1 promoter activity as measured by luciferase reporter assays, suggesting that the induction of COX-1 is regulated at the transcriptional level. Furthermore, mutation analysis of the COX-1 promoter suggests that TSA-responsive element exists in the proximal Sp1-binding site at +25 to +31. In conclusion, COX-1 is an inducible gene in glial-derived cells including immortalized cells, and appears to be transcriptionally regulated by a unique mechanism associated with histone acetylation. JF - The Journal of biological chemistry AU - Taniura, Seijiro AU - Kamitani, Hideki AU - Watanabe, Takashi AU - Eling, Thomas E AD - Laboratory of Molecular Carcinogenesis, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/05/10/ PY - 2002 DA - 2002 May 10 SP - 16823 EP - 16830 VL - 277 IS - 19 SN - 0021-9258, 0021-9258 KW - DNA, Complementary KW - 0 KW - Enzyme Inhibitors KW - Histone Deacetylase Inhibitors KW - Histones KW - Hydroxamic Acids KW - Isoenzymes KW - Membrane Proteins KW - Oligonucleotides KW - RNA, Messenger KW - Sp1 Transcription Factor KW - Arachidonic Acid KW - 27YG812J1I KW - trichostatin A KW - 3X2S926L3Z KW - Cyclooxygenase 1 KW - EC 1.14.99.1 KW - PTGS1 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Dinoprostone KW - K7Q1JQR04M KW - Index Medicus KW - Blotting, Northern KW - Cell Nucleus -- metabolism KW - Oligonucleotides -- pharmacology KW - Humans KW - Promoter Regions, Genetic KW - Tumor Cells, Cultured KW - Sp1 Transcription Factor -- metabolism KW - Enzyme-Linked Immunosorbent Assay KW - Glioma -- metabolism KW - Time Factors KW - Hydroxamic Acids -- pharmacology KW - Immunoblotting KW - Dose-Response Relationship, Drug KW - DNA Mutational Analysis KW - Arachidonic Acid -- pharmacology KW - Reverse Transcriptase Polymerase Chain Reaction KW - Binding Sites KW - Neuroglia -- metabolism KW - Acetylation KW - RNA, Messenger -- metabolism KW - Dinoprostone -- metabolism KW - DNA, Complementary -- metabolism KW - Histones -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Up-Regulation KW - Mutation KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Transcription, Genetic KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism KW - Astrocytes -- enzymology KW - Astrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71655143?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Transcriptional+regulation+of+cyclooxygenase-1+by+histone+deacetylase+inhibitors+in+normal+human+astrocyte+cells.&rft.au=Taniura%2C+Seijiro%3BKamitani%2C+Hideki%3BWatanabe%2C+Takashi%3BEling%2C+Thomas+E&rft.aulast=Taniura&rft.aufirst=Seijiro&rft.date=2002-05-10&rft.volume=277&rft.issue=19&rft.spage=16823&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-13 N1 - Date created - 2002-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Down-regulation of von Hippel-Lindau protein in N-nitroso compound-induced rat non-clear cell renal tumors. AN - 71490157; 11880179 AB - Non-clear cell rat kidney tumors, inducible by N-nitroso compounds but lacking mutations in the von Hippel--Lindau (VHL) coding sequence, were examined for other VHL alterations. Neither mutations nor DNA methylation was detected in a putative promoter region. By immunohistochemistry, however, VHL protein level was evidently reduced in six of the eight eosinophilic renal epithelial tumors and in all the ten nephroblastomas. Immunoblotting of normal kidney detected two VHL proteins of 20 and 22kDa in a 16-day-old fetal rat but only 20kDa protein in an adult rat. This is the first demonstration of VHL alteration at the protein level. JF - Cancer letters AU - Shiao, Yih Horng AU - Ramakrishna, Gayatri AU - Anderson, Lucy M AU - Perantoni, Alan O AU - Rice, Jerry M AU - Diwan, Bhalchandra A AD - Laboratory of Comparative Carcinogenesis, Building 538, Room 205, National Cancer Institute at Frederick, Frederick, MD 21702, USA. shiao@mail.ncifcrf.gov Y1 - 2002/05/08/ PY - 2002 DA - 2002 May 08 SP - 33 EP - 38 VL - 179 IS - 1 SN - 0304-3835, 0304-3835 KW - Carcinogens KW - 0 KW - DNA Primers KW - DNA, Neoplasm KW - Tumor Suppressor Proteins KW - N-ethyl-N-hydroxyethylnitrosamine KW - 13147-25-6 KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Ubiquitin-Protein Ligases KW - EC 2.3.2.27 KW - Von Hippel-Lindau Tumor Suppressor Protein KW - Ligases KW - EC 6.- KW - Index Medicus KW - Animals KW - DNA Mutational Analysis KW - Wilms Tumor -- chemically induced KW - Wilms Tumor -- pathology KW - Rats KW - Polymerase Chain Reaction KW - Wilms Tumor -- metabolism KW - Blotting, Western KW - Rats, Inbred F344 KW - Down-Regulation KW - Immunoenzyme Techniques KW - Male KW - Ligases -- genetics KW - Adenocarcinoma -- metabolism KW - Kidney Neoplasms -- pathology KW - von Hippel-Lindau Disease -- metabolism KW - Adenocarcinoma -- chemically induced KW - Kidney Neoplasms -- chemically induced KW - Adenocarcinoma -- pathology KW - Diethylnitrosamine -- analogs & derivatives KW - Kidney Neoplasms -- metabolism KW - von Hippel-Lindau Disease -- genetics KW - Ligases -- metabolism KW - DNA, Neoplasm -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71490157?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Down-regulation+of+von+Hippel-Lindau+protein+in+N-nitroso+compound-induced+rat+non-clear+cell+renal+tumors.&rft.au=Shiao%2C+Yih+Horng%3BRamakrishna%2C+Gayatri%3BAnderson%2C+Lucy+M%3BPerantoni%2C+Alan+O%3BRice%2C+Jerry+M%3BDiwan%2C+Bhalchandra+A&rft.aulast=Shiao&rft.aufirst=Yih&rft.date=2002-05-08&rft.volume=179&rft.issue=1&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-15 N1 - Date created - 2002-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor growth enhancing effects of vascular endothelial growth factor are associated with increased nitric oxide synthase activity and inhibition of apoptosis in human breast carcinoma xenografts. AN - 71489645; 11880187 AB - Previously, we demonstrated the significance of vascular endothelial growth factor (VEGF) in promoting the growth of tetracycline-regulated human VEGF165 retroviral vector transduced T47-D breast carcinoma cells, particularly at the early stages of tumor development (Cancer Res. 57 (1997) 3924). Here, we showed histologically that the VEGF overexpressing (VEGF (+)) T47-D cells formed a distinct tumor nodule at day 11, while control cells showed no evidence of replication. The VEGF (+) tumors contained large avascular cavities at days 11 and 21, which were replaced by basement membrane-lined channels at day 30. The number of proliferating tumor cells was not significantly different between the VEGF (+) and control tumors, but the number of apoptotic cells was significantly decreased in the VEGF (+) tumors. Increased nitric oxide synthase (NOS) activity was also observed in the VEGF (+) tumors. These findings indicate that VEGF contributes to tumor growth through inhibition of apoptosis and increased NOS activity, which may be critical during pre-vascular stages of tumor development. JF - Cancer letters AU - Harris, Steven R AU - Schoeffner, Daniel J AU - Yoshiji, Hitoshi AU - Thorgeirsson, Unnur P AD - Tumor Biology and Carcinogenesis Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/05/08/ PY - 2002 DA - 2002 May 08 SP - 95 EP - 101 VL - 179 IS - 1 SN - 0304-3835, 0304-3835 KW - Endothelial Growth Factors KW - 0 KW - Lymphokines KW - VEGFA protein, human KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - Nitric Oxide KW - 31C4KY9ESH KW - NOS2 protein, human KW - EC 1.14.13.39 KW - NOS3 protein, human KW - Nitric Oxide Synthase KW - Nitric Oxide Synthase Type II KW - Nitric Oxide Synthase Type III KW - Nos2 protein, mouse KW - Nos3 protein, mouse KW - Index Medicus KW - Animals KW - Humans KW - Neoplasms, Experimental -- genetics KW - Nitric Oxide -- metabolism KW - Mice KW - Mice, Nude KW - Neoplasms, Experimental -- pathology KW - Blotting, Western KW - Neoplasms, Experimental -- enzymology KW - Tumor Cells, Cultured KW - Transplantation, Heterologous KW - Enzyme Induction KW - Retroviridae -- genetics KW - Female KW - Immunoenzyme Techniques KW - Cell Division KW - Breast Neoplasms -- genetics KW - Apoptosis KW - Breast Neoplasms -- pathology KW - Nitric Oxide Synthase -- genetics KW - Endothelial Growth Factors -- physiology KW - Nitric Oxide Synthase -- metabolism KW - Lymphokines -- physiology KW - Breast Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71489645?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Tumor+growth+enhancing+effects+of+vascular+endothelial+growth+factor+are+associated+with+increased+nitric+oxide+synthase+activity+and+inhibition+of+apoptosis+in+human+breast+carcinoma+xenografts.&rft.au=Harris%2C+Steven+R%3BSchoeffner%2C+Daniel+J%3BYoshiji%2C+Hitoshi%3BThorgeirsson%2C+Unnur+P&rft.aulast=Harris&rft.aufirst=Steven&rft.date=2002-05-08&rft.volume=179&rft.issue=1&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-15 N1 - Date created - 2002-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of Shuanghuanglian and Qingkailing, two multi-components of traditional Chinese medicinal preparations, on human leukocyte function. AN - 72117754; 12269401 AB - Qingkailing (QKL) and Shuanghuanglian (SHHL) are two commonly used Chinese herbal preparations with reported antiinflammatory activity. The effects of these two preparations on the capacity of staphylococcal toxic shock syndrome toxin 1 (TSST-1) to stimulate the production of cytokines (IL-1beta, IL-6, TNF-alpha, IFN-gamma) and chemokines (MIP-1alpha, MIP-1beta and MCP-1) by peripheral blood mononuclear cell (PBMC) was tested. We also evaluated their effect on LPS-stimulated NF-kappaB transcriptional activity in a THP-1 cell line, and on human monocyte chemotactic response to chemoattractants. Non-cytotoxic concentrations of QKL (0.1 to approximately 2%) and SHHL (6 to approximately 120 microg) significantly inhibited production of cytokines and chemokines in a dose-dependent manner (P < 0.05). Both, QKL at 1:100 and SHHL at 60 microg/ml, markedly inhibited RANTES, MIP-1alpha, SDF-1alpha and fMLP induced human monocyte migration (P < 0.05 or 0.01). QKL (1%) did not inhibit monocyte chemotaxis induced by super-or sub-optimal concentrations of fMLP (10(-5), 10(-6) and 10(-10) M), but only inhibited chemotaxis induced by optimal concentrations of fMLP at 10(-7), 10(-8) and 10(-9) M. QKL (0.1% or 1%) and SHHL (6 or 60 microg/ml) markedly inhibited LPS-induced NF-kappaB activity in THP-1 cells. The results suggested that the pharmacological basis for the antiinflammatory effects of QKL and SHHL is the result of suppression of NF-kappaB regulated gene transcription, leading to suppressed production of proinflammatory cytokine and chemokine. Interference with leukocyte chemotaxis also contributes to the antiinflammatory and immunomodulating effects of these medicinals. Identification of the responsible components in these two herbal preparations may yield compounds suitable for structural modification into potent novel drugs. JF - Life sciences AU - Chen, Xin AU - Howard, O M Zack AU - Yang, Xiaoyi AU - Wang, Lihua AU - Oppenheim, Joost J AU - Krakauer, Teresa AD - Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute-Frederick, Fort Detrick, MD, 21702-1201, USA. xinc@mail.ncifcrf.gov Y1 - 2002/05/03/ PY - 2002 DA - 2002 May 03 SP - 2897 EP - 2913 VL - 70 IS - 24 SN - 0024-3205, 0024-3205 KW - Bacterial Toxins KW - 0 KW - Chemokine CCL2 KW - Cytokines KW - Drugs, Chinese Herbal KW - Enterotoxins KW - Lipopolysaccharides KW - NF-kappa B KW - Superantigens KW - enterotoxin F, Staphylococcal KW - Luciferases KW - EC 1.13.12.- KW - Index Medicus KW - Humans KW - Lipopolysaccharides -- pharmacology KW - Luciferases -- metabolism KW - Cytokines -- metabolism KW - Macrophages -- drug effects KW - Cell Survival -- drug effects KW - Transfection KW - Cell Movement -- drug effects KW - Chemokine CCL2 -- pharmacology KW - Monocytes -- drug effects KW - Chemotaxis -- drug effects KW - Enterotoxins -- toxicity KW - Staphylococcus aureus KW - Cell Line KW - NF-kappa B -- metabolism KW - Leukocytes, Mononuclear -- physiology KW - Leukocytes, Mononuclear -- drug effects KW - Drugs, Chinese Herbal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72117754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Life+sciences&rft.atitle=Effects+of+Shuanghuanglian+and+Qingkailing%2C+two+multi-components+of+traditional+Chinese+medicinal+preparations%2C+on+human+leukocyte+function.&rft.au=Chen%2C+Xin%3BHoward%2C+O+M+Zack%3BYang%2C+Xiaoyi%3BWang%2C+Lihua%3BOppenheim%2C+Joost+J%3BKrakauer%2C+Teresa&rft.aulast=Chen&rft.aufirst=Xin&rft.date=2002-05-03&rft.volume=70&rft.issue=24&rft.spage=2897&rft.isbn=&rft.btitle=&rft.title=Life+sciences&rft.issn=00243205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-04 N1 - Date created - 2002-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thapsigargin binds to and inhibits the cloned vanilloid receptor-1. AN - 71806440; 12054538 AB - We investigated the effect of thapsigargin, a well-known sarcoplasmic reticulum ATPase (SERCA) inhibitor, on the non-specific Ca2+ channel vanilloid receptor-1 (VR1) in CHO-VR1 cells. We found that thapsigargin inhibited the VR-1 mediated (45)Ca2+ uptake of CHO-VR1 cells (IC50=6.4+/-1.9 microM) and the [3H]RTX binding to VR1 (IC50=4.0+/-1.3 microM). Further analysis revealed that thapsigargin is a mixed-type inhibitor, suggesting both direct and indirect interactions between thapsigargin and the capsaicin binding site of VR1. Thapsigargin alone transiently elevated the [Ca2+]i in CHO-VR1 cells (EC50=44 nM). However, 45Ca2+ uptake was not detected after thapsigargin treatment, indicating that the emptying of the thapsigargin sensitive intracellular pools of Ca2+ was responsible for the elevated [Ca2+]i level rather than the activation of VR-1. We conclude that thapsigargin represents a new prototype of a VR1 inhibitor and that caution should be exercised in interpreting the effects of thapsigargin, especially when it is used in the micromolar range to inhibit SERCA activity. Copyright 2002 Elsevier Science (USA). JF - Biochemical and biophysical research communications AU - Tóth, Attila AU - Kedei, Noémi AU - Szabó, Tamás AU - Wang, Yun AU - Blumberg, Peter M AD - Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Building 37, Room 3A01, 37 Convent Drive, MSC 4255, Bethesda, MD 20892, USA. Y1 - 2002/05/03/ PY - 2002 DA - 2002 May 03 SP - 777 EP - 782 VL - 293 IS - 2 SN - 0006-291X, 0006-291X KW - Diterpenes KW - 0 KW - Enzyme Inhibitors KW - Receptors, Drug KW - TRPV Cation Channels KW - TRPV1 receptor KW - Thapsigargin KW - 67526-95-8 KW - resiniferatoxin KW - A5O6P1UL4I KW - Calcium-Transporting ATPases KW - EC 3.6.3.8 KW - Sarcoplasmic Reticulum Calcium-Transporting ATPases KW - Capsaicin KW - S07O44R1ZM KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Calcium-Transporting ATPases -- antagonists & inhibitors KW - Diterpenes -- metabolism KW - Cloning, Molecular KW - Diterpenes -- chemistry KW - Calcium -- metabolism KW - Kinetics KW - CHO Cells KW - Capsaicin -- antagonists & inhibitors KW - Cricetinae KW - Thapsigargin -- pharmacology KW - Receptors, Drug -- genetics KW - Thapsigargin -- metabolism KW - Thapsigargin -- chemistry KW - Enzyme Inhibitors -- chemistry KW - Enzyme Inhibitors -- pharmacology KW - Enzyme Inhibitors -- metabolism KW - Receptors, Drug -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71806440?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Thapsigargin+binds+to+and+inhibits+the+cloned+vanilloid+receptor-1.&rft.au=T%C3%B3th%2C+Attila%3BKedei%2C+No%C3%A9mi%3BSzab%C3%B3%2C+Tam%C3%A1s%3BWang%2C+Yun%3BBlumberg%2C+Peter+M&rft.aulast=T%C3%B3th&rft.aufirst=Attila&rft.date=2002-05-03&rft.volume=293&rft.issue=2&rft.spage=777&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-12 N1 - Date created - 2002-06-10 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Challenges for computer-aided diagnosis for CT colonography AN - 954652641; 16389536 AB - Computer-aided diagnosis for computed tomographic colonography is in its infancy but has the potential to improve sensitivity and decrease costs for colonic polyp detection. This article reviews the current state of research in this nascent field and explores major challenges and avenues for future work. JF - Abdominal Imaging AU - Summers, R M AD - Diagnostic Radiology Department, National Institutes of Health, Building 10, Room 1C660, 10 Center Drive, MSC 1182, Bethesda, MD 20892-1182, USA, US Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 268 EP - 274 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 27 IS - 3 SN - 0942-8925, 0942-8925 KW - Biotechnology and Bioengineering Abstracts KW - Computed tomography KW - Polyps KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/954652641?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Abdominal+Imaging&rft.atitle=Challenges+for+computer-aided+diagnosis+for+CT+colonography&rft.au=Summers%2C+R+M&rft.aulast=Summers&rft.aufirst=R&rft.date=2002-05-01&rft.volume=27&rft.issue=3&rft.spage=268&rft.isbn=&rft.btitle=&rft.title=Abdominal+Imaging&rft.issn=09428925&rft_id=info:doi/10.1007%2Fs00261-001-0168-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-03-01 N1 - Last updated - 2012-05-18 N1 - SubjectsTermNotLitGenreText - Computed tomography; Polyps DO - http://dx.doi.org/10.1007/s00261-001-0168-7 ER - TY - JOUR T1 - A more astonishing hypothesis AN - 864953480; 13744505 JF - Nature Biotechnology AU - McKay, Ron AD - Ron McKay is a senior investigator at the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892mckayr[AT]ninds.nih.gov. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 426 EP - 427 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 20 IS - 5 SN - 1087-0156, 1087-0156 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/864953480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=A+more+astonishing+hypothesis&rft.au=McKay%2C+Ron&rft.aulast=McKay&rft.aufirst=Ron&rft.date=2002-05-01&rft.volume=20&rft.issue=5&rft.spage=426&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2Fnbt0502-426 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-05-01 N1 - Last updated - 2012-03-29 DO - http://dx.doi.org/10.1038/nbt0502-426 ER - TY - JOUR T1 - The role of AP-1, NF-B and ROS/NOS in skin carcinogenesis: The JB6 model is predictive AN - 856761709; 13862170 AB - Generation of reactive oxygen species (ROS) stimulates transcription by activating transcription factors activator protein 1 (AP-1) and nuclear factor B (NF-B). The mouse epidermal JB6 cells constitute a model system that has significantly contributed to the understanding of these events. Clonal variants of JB6 cells are differentially responsive to transformation induced by tumor promoters such as phorbol esters (TPA), epidermal growth factor (EGF) and tumor necrosis factor alpha (TNF-a), as well as oxidative stress. TPA and EGF, acting through the MAP kinase pathway, activate AP-1 and subsequently NF-B proteins and downstream transcription processes that are involved in the transformation response in transformation-sensitive (P+) JB6 cells. The effect of TNF-a is primarily on the NF-B pathway. ROS and other free radicals can activate AP-1 and NF-B transcription coordinately. In JB6 cells, both ERK/Fra-1 and NF-B activity is essential for the transformation response. Inhibition of NF-B and AP-1 activity abrogates transformation in JB6 cells as well as in transgenic mice and human keratinocytes. A similar effect is seen with antioxidants, which inhibit NF-B and AP-1 activity as well as transformation in JB6 cells. The JB6 model is therefore valuable for monitoring early events in oxidative stress related signaling leading to carcinogenesis, and for identifying molecular targets for cancer chemoprevention. JF - Molecular and Cellular Biochemistry AU - Dhar, Arindam AU - Young, Mathew R AU - Colburn, Nancy H AD - Gene Regulation Section, National Cancer Institute at Frederick, Frederick, MD, 21702, USA, adhar@ncifcrf.gov Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 185 EP - 193 PB - Springer-Verlag, Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 234-235 IS - 1 SN - 0300-8177, 0300-8177 KW - Toxicology Abstracts KW - Transformation KW - Molecular modelling KW - Fra1 protein KW - Antioxidants KW - Phorbol esters KW - Animal models KW - TPA KW - Extracellular signal-regulated kinase KW - Promoters KW - Reactive oxygen species KW - Oxidative stress KW - Keratinocytes KW - MAP kinase KW - Skin KW - Free radicals KW - Activator protein 1 KW - Transgenic mice KW - Tumor necrosis factor-a KW - Cancer KW - Nitric-oxide synthase KW - Transcription factors KW - NF-B protein KW - Carcinogenesis KW - Epidermal growth factor KW - Signal transduction KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/856761709?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+Cellular+Biochemistry&rft.atitle=The+role+of+AP-1%2C+NF-B+and+ROS%2FNOS+in+skin+carcinogenesis%3A+The+JB6+model+is+predictive&rft.au=Dhar%2C+Arindam%3BYoung%2C+Mathew+R%3BColburn%2C+Nancy+H&rft.aulast=Dhar&rft.aufirst=Arindam&rft.date=2002-05-01&rft.volume=234-235&rft.issue=1&rft.spage=185&rft.isbn=&rft.btitle=&rft.title=Molecular+and+Cellular+Biochemistry&rft.issn=03008177&rft_id=info:doi/10.1023%2FA%3A1015948505117 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-03-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - Transformation; Molecular modelling; Fra1 protein; Phorbol esters; Antioxidants; Animal models; TPA; Promoters; Extracellular signal-regulated kinase; Reactive oxygen species; Oxidative stress; Keratinocytes; MAP kinase; Skin; Free radicals; Activator protein 1; Tumor necrosis factor-a; Transgenic mice; Cancer; Nitric-oxide synthase; Transcription factors; Carcinogenesis; NF-B protein; Epidermal growth factor; Signal transduction DO - http://dx.doi.org/10.1023/A:1015948505117 ER - TY - JOUR T1 - Cooperative interaction as the physical basis of the negative stiffness in hair cell stereocilia. AN - 85372753; pmid-12051440 AB - A recent report confirmed that stiffness of the stereocilia can be negative, as predicted by the Howard-Hudspeth model. According to this model, the mechanotransducer channel's gating not only reduces the stereociliary stiffness, but can alter its sign as well. The basic assumptions of this model do not include cooperativity in channel gating. Here we consider two possible explanations for the observed negative stiffness. If the stereocilia have a special structure so that microscopic displacement can be imposed on each channel by controlling the bending of the bundle, negative stiffness can occur without channel cooperativity. If such a microscopic condition cannot be imposed by a macroscopic manipulation, an additional physical process, such as cooperativity in channel gating, is required to explain negative stiffness. JF - The Journal of the Acoustical Society of America AU - Iwasa, K H AU - Ehrenstein, G AD - National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA. iwasa@nih.gov Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 2208 EP - 2212 VL - 111 IS - 5 Pt 1 SN - 0001-4966, 0001-4966 KW - Index Medicus KW - National Library of Medicine KW - *Hair Cells, Auditory: physiology KW - Humans KW - *Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85372753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+the+Acoustical+Society+of+America&rft.atitle=Cooperative+interaction+as+the+physical+basis+of+the+negative+stiffness+in+hair+cell+stereocilia.&rft.au=Iwasa%2C+K+H%3BEhrenstein%2C+G&rft.aulast=Iwasa&rft.aufirst=K&rft.date=2002-05-01&rft.volume=111&rft.issue=5+Pt+1&rft.spage=2208&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+the+Acoustical+Society+of+America&rft.issn=00014966&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - SuppNotes - Erratum In: J Acoust Soc Am 2002 Nov;112(5 Pt 1):2193 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Effect of attention on central auditory processing: an fMRI study. AN - 85253370; pmid-12325392 AB - Functional magnetic resonance imaging was used to investigate preattentive and attentional processing of auditory stimuli in 18 right-handed normal volunteers. Responses to trains of 1000-Hz pure tones and infrequent (15%) deviant 1300-Hz tones were characterized while subjects ignored all tones; listened for deviants in the left ear; or listened for deviants in the right ear. Preattentive detection of deviants, associated with the mismatch negativity in electrophysiology, was associated with bilateral temporal lobe activation, with a rightward predominance. Processing of deviant stimuli while attending to either ear produced a more robust and widespread activation of these temporal regions, again with a rightward predominance. Thus, preattentive tone processing appears to be linked to asymmetric activation of a core set of temporal regions in which activity is significantly amplified by selective attention. Extratemporal regions activated by attending to targets in either ear included the anterior cingulate cortex, supramarginal gyrus, and dorsolateral prefrontal cortex. JF - The International Journal of Neuroscience AU - Sevostianov Andrei AU - Fromm, Stephen AU - Nechaev Vladimir AU - Horwitz, Barry AU - Braun, Allen AD - National Institute on Deafness and Other Communication Disorders, Bethesda, Maryland, USA.; National Institute on Deafness and Other Communication Disorders PY - 2002 SP - 587 EP - 606 VL - 112 IS - 5 SN - 0020-7454, 0020-7454 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85253370?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+International+Journal+of+Neuroscience&rft.atitle=Effect+of+attention+on+central+auditory+processing%3A+an+fMRI+study.&rft.au=Sevostianov+Andrei%3BFromm%2C+Stephen%3BNechaev+Vladimir%3BHorwitz%2C+Barry%3BBraun%2C+Allen&rft.aulast=Sevostianov+Andrei&rft.aufirst=&rft.date=2002-05-01&rft.volume=112&rft.issue=5&rft.spage=587&rft.isbn=&rft.btitle=&rft.title=The+International+Journal+of+Neuroscience&rft.issn=00207454&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Benzodiazepines have no effect on fear-potentiated startle in humans. AN - 85248411; pmid-12021826 AB - RATIONALE: Pre-clinical and clinical investigations have provided a great deal of evidence that the fear-potentiated startle paradigm represents a valid model for the objective assessment of emotional states of anxiety and fear. OBJECTIVE: The four studies presented in this report sought to further validate the "threat of shock" paradigm as a human analogue to fear-potentiated startle in rats, by examining the effect of benzodiazepine administration on both baseline and fear-potentiated startle. METHODS: Three studies, conducted at Utrecht University, evaluated the effects of oxazepam and of diazepam on baseline and fear-potentiated startle, whereas a fourth study, conducted at Yale University, evaluated the effect of diazepam on baseline, contextual and cue-specific fear-potentiated startle. The threat of shock paradigm consisted of verbal instruction about two visual cues (the threat cue predicted the possible administration of electric shock, the other predicted a safe period), followed by a series of presentations of these cues. During these conditions, acoustic startle stimuli were presented in order to elicit startle responses. The magnitude of the startle response was used to index the degree of fear or alarm experienced during the periods of threat and safety. The fourth study examined the effect of IV administration of diazepam in a similar threat of shock paradigm except that there were two additional context manipulations: electrode placement and darkness. RESULTS: None of the drug manipulations affected specific threat-cue potentiation of startle. However, reductions in baseline startle were observed. Further, startle potentiation by darkness was inhibited by diazepam. CONCLUSIONS: At least one type of fear-potentiated startle, i.e. potentiation by a cue-specific fear manipulation, is not susceptible to benzodiazepine treatment. In contrast, effects of manipulations more akin to anxiety (darkness, context) appear sensitive to benzodiazepines. Human experimental models differentiating between these cue specific and contextual responses are needed to shed more light on differences in the anatomy and pharmacology of anxiety disorders. JF - Psychopharmacology AU - Baas Johanna M P AU - Grillon, Christian AU - Böcker Koen B E AU - Brack, Anouk A AU - Morgan, Charles A AU - Leon, Kenemans J AU - Verbaten, Marinus N AD - Mood and Anxiety Disorder Program, NIMH, NIH, 15k North Drive MSC 2670, Bethesda, MD 20892, USA. PY - 2002 SP - 233 EP - 247 VL - 161 IS - 3 SN - 0033-3158, 0033-3158 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85248411?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Benzodiazepines+have+no+effect+on+fear-potentiated+startle+in+humans.&rft.au=Baas+Johanna+M+P%3BGrillon%2C+Christian%3BB%C3%B6cker+Koen+B+E%3BBrack%2C+Anouk+A%3BMorgan%2C+Charles+A%3BLeon%2C+Kenemans+J%3BVerbaten%2C+Marinus+N&rft.aulast=Baas+Johanna+M+P&rft.aufirst=&rft.date=2002-05-01&rft.volume=161&rft.issue=3&rft.spage=233&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Childhood cancer incidence and arsenic exposure in drinking water in Nevada. AN - 72800312; 12507173 AB - Inorganic arsenic exposure through drinking water causes cancer in adults; however, the carcinogenic potential in children remains unknown. A recent leukemia cluster in Churchill County, Nevada, where arsenic levels in water supplies are relatively high, has prompted concern. The authors investigated the incidence of childhood cancer between 1979 and 1999 in all 17 Nevada counties, grouped by low (i.e., < 10 microg/l), medium (10-25 microg/l), and high (35-90 microg/l) population-weighted arsenic levels in public drinking water supplies. The standardized incidence ratios (SIRs) for all childhood cancers combined were 1.00 (95% confidence interval [CI] = 0.94, 1.06), 0.72 (95% CI = 0.43, 1.12), and 1.25 (95% CI = 0.91, 1.69) for low-, medium-, and high-exposure counties, respectively. There was no relationship between arsenic levels in water and childhood leukemia (SIRs = 1.02, 0.61, and 0.86, respectively [95% CIIs = 0.90, 1.15; 0.12, 1.79; and 0.37, 1.70, respectively]). For all childhood cancers, excluding leukemias, the SIRs were 0.99 (95% CI = 0.92, 1.07), 0.82 (95% CI = 0.42, 1.22), and 1.37 (0.92, 1.83), respectively. The excess in 5- to 9-yr-old children and 10- to 14-yr-old children was in bone cancers, and the excess in 15- to 19-yr-old young adults was primarily in lymphomas. The findings in this study are reassuring in that leukemia risks were not increased at the concentrations of arsenic in water found in this study. Nonetheless, the results raise the possibility that there are increased risks for nonleukemic childhood cancers that require confirmation in other studies, particularly those in which higher exposures are addressed. JF - Archives of environmental health AU - Moore, Lee E AU - Lu, Meng AU - Smith, Allan H AD - School of Public Health University of California at Berkeley, Berkeley, California, USA. moorele@mail.nih.gov PY - 2002 SP - 201 EP - 206 VL - 57 IS - 3 SN - 0003-9896, 0003-9896 KW - Water Pollutants, Chemical KW - 0 KW - Arsenic KW - N712M78A8G KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Water Supply KW - Neoplasms -- epidemiology KW - Child KW - Child, Preschool KW - Infant KW - Risk Factors KW - Adult KW - Neoplasms -- chemically induced KW - Incidence KW - Nevada -- epidemiology KW - Adolescent KW - Female KW - Male KW - Arsenic -- adverse effects KW - Leukemia -- chemically induced KW - Water Pollutants, Chemical -- adverse effects KW - Leukemia -- epidemiology KW - Environmental Exposure -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72800312?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+environmental+health&rft.atitle=Childhood+cancer+incidence+and+arsenic+exposure+in+drinking+water+in+Nevada.&rft.au=Moore%2C+Lee+E%3BLu%2C+Meng%3BSmith%2C+Allan+H&rft.aulast=Moore&rft.aufirst=Lee&rft.date=2002-05-01&rft.volume=57&rft.issue=3&rft.spage=201&rft.isbn=&rft.btitle=&rft.title=Archives+of+environmental+health&rft.issn=00039896&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-14 N1 - Date created - 2002-12-31 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Expression and promoter activation of the Rpe65 gene in retinal pigment epithelium cell lines. AN - 72698371; 12434305 AB - To examine the expression and promoter activation of the retinal pigment epithelium (RPE)-preferentially expressed Rpe65 gene in the commonly available RPE cell lines. Reverse transcription coupled to polymerase chain reaction (RT-PCR) was performed after total RNA extraction from different RPE (ARPE-19, monkey, hTERT-RP1 and D407) and non-RPE (COS-7, HeLa, HepG2 and HS27) cell lines. Promoter activity was assayed by transient transfection of luciferase reporter constructs containing nested deletions of the 5' flanking region of the mouse Rpe65 gene. The involvement of a putative TATA box in the basal promoter expression was studied by site-directed mutagenesis in D407 cells and binding of TATA box-related transcription factors to that region was demonstrated by Electrophoretic Mobility Shift Assays (EMSA). Expression of the human RPE65 cDNA was observed in all the RPE cell lines tested, and in COS-7 cells (monkey RPE65 cDNA). Transient transfections of the mouse Rpe65 promoter/luciferase transgene containing nested deletions of the Rpe65 5' flanking region showed that fragments containing bases -655 to +48 and -1240 to +48 generated specific promoter activity only in the D407 cell line. A promoter fragment from -49 to +48 directed basal promoter activity in all the cell lines tested. Part of this basal activity was due to a putative TATA box that specifically binds transcription factors contained in a D407 nuclear extract. Although transcription of the Rpe65 gene occurs in all the tested cell lines, we find that the D407 cell line is the only one capable of directing specific mouse Rpe65 promoter activity. This limits the study of the transcriptional regulation of the mouse Rpe65 gene in vitro to this particular cell line. JF - Current eye research AU - Boulanger, Ana AU - Redmond, T Michael AD - Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 368 EP - 375 VL - 24 IS - 5 SN - 0271-3683, 0271-3683 KW - Carrier Proteins KW - 0 KW - DNA, Complementary KW - Eye Proteins KW - Proteins KW - Luciferases KW - EC 1.13.12.- KW - retinoid isomerohydrolase KW - EC 3.1.1.64 KW - cis-trans-Isomerases KW - EC 5.2.- KW - Index Medicus KW - Animals KW - DNA, Complementary -- genetics KW - Humans KW - TATA Box -- genetics KW - Luciferases -- metabolism KW - Mice KW - Haplorhini KW - Gene Deletion KW - TATA Box -- physiology KW - Mutation -- physiology KW - Cell Line KW - Promoter Regions, Genetic -- physiology KW - Pigment Epithelium of Eye -- physiology KW - Gene Expression KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72698371?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+eye+research&rft.atitle=Expression+and+promoter+activation+of+the+Rpe65+gene+in+retinal+pigment+epithelium+cell+lines.&rft.au=Boulanger%2C+Ana%3BRedmond%2C+T+Michael&rft.aulast=Boulanger&rft.aufirst=Ana&rft.date=2002-05-01&rft.volume=24&rft.issue=5&rft.spage=368&rft.isbn=&rft.btitle=&rft.title=Current+eye+research&rft.issn=02713683&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-13 N1 - Date created - 2002-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential induction of early response genes by adrenomedullin and transforming growth factor-beta1 in human lung cancer cells. AN - 71989134; 12168820 AB - Adrenomedullin (AM) is a hypotensive polypeptide that has been shown to stimulate cyclic AMP and intracellular free Ca2+ agents that are known to induce expression of proto-oncogenes, in various cell types. Transforming growth factor-beta 1 (TGF-beta1) is a multifunctional polypeptide that regulates proliferation, differentiation and cell cycle progression in both normal and malignant epithelial cells. The diverse biological actions of AM and TGF-beta1 may be related to their capacities to initiate different genomic programs in target cells via the induction of expression of multiple genes including early response genes and proto-oncogenes. AM, TGF-beta1 and phorbol-12-myristate-13-acetate (PMA) exert both positive and negative effects on mitogenesis. The effects of AM, TGF-beta1 and PMA were examined in human non-small cell lung cancer (NSCLC) cells. AM caused an increase in its mRNA transcript that peaked by 6 hours and persisted to 24 hours. While expression of TGF-beta1 mRNA was not affected by AM in these cells, the mRNAs for TGF-beta1 and TGF-beta3 decreased by 3 hours. In contrast, TGF-beta1 had no effect on expression of AM mRNA. Interestingly, PMA caused an increase in AM and TGF-beta1 mRNAs in NSCLC cells. While both TGF-beta1 and PMA caused a transient increase in expression of the mRNAs for early response genes including c-fos, c-jun and egr-1 that peaked by 1 hour following treatment, the increase in expression of these mRNAs following treatment with AM peaked only after 3-6 hours. Western blotting analysis showed increases in the levels of c-jun protein following treatment with AM, TGF-beta1 and PMA. The increase in c-jun protein from treatment with AM occurred 10 hours after that from TGF-beta1 and PMA. Activator protein 1 (AP-1) DNA binding activity was also demonstrated to increase following treatment with AM, TGF-beta1 and PMA, with the increase in AP-1 DNA binding activity following AM treatment occurring 10 hours later than that from TGF-beta1 and PMA treatment. These data show that AM can regulate expression of its mRNA transcript in NSCLC cells. Our study suggests that NSCLC cells are important targets of AM and TGF-beta1 and that AM and TGF-beta1 may regulate activities in these malignant lung cells through differential induction of various early response genes. JF - Anticancer research AU - Kane, Stephanie AU - Prentice, Margaret A AU - Mariano, Jennifer M AU - Cuttitta, Frank AU - Jakowlew, Sonia B AD - National Cancer Institute, Cell and Cancer Biology Branch, Rockville, Maryland 20850, USA. PY - 2002 SP - 1433 EP - 1444 VL - 22 IS - 3 SN - 0250-7005, 0250-7005 KW - Peptides KW - 0 KW - RNA, Messenger KW - TGFB1 protein, human KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - Adrenomedullin KW - 148498-78-6 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Tumor Cells, Cultured KW - Humans KW - Tetradecanoylphorbol Acetate -- pharmacology KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Transforming Growth Factor beta -- biosynthesis KW - Transforming Growth Factor beta -- pharmacology KW - Carcinoma, Non-Small-Cell Lung -- metabolism KW - Carcinoma, Non-Small-Cell Lung -- genetics KW - Lung Neoplasms -- drug therapy KW - Peptides -- metabolism KW - Peptides -- pharmacology KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Genes, Immediate-Early -- drug effects KW - Genes, Immediate-Early -- genetics KW - Lung Neoplasms -- genetics KW - Peptides -- genetics KW - Transforming Growth Factor beta -- genetics KW - Carcinoma, Non-Small-Cell Lung -- drug therapy KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71989134?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Parallel+visual+motion+processing+streams+in+lateral+temporal+cortex+for+manipulable+objects+and+human+movements&rft.au=Beauchamp%2C+M%3BLee%2C+K%3BHaxby%2C+J%3BMartin%2C+A&rft.aulast=Beauchamp&rft.aufirst=M&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-13 N1 - Date created - 2002-08-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitroxides as antioxidants: Tempol protects against EO9 cytotoxicity. AN - 71984577; 12162451 AB - Nitroxide free radicals have been shown to be potent antioxidants in a variety of experimental models using diverse means of insults. Among other insults, nitroxides have been shown effective in inhibiting cytotoxicity of quinone-based drugs such as streptonigrin and mitomycin C. These drugs and other chemotherapeutic agents have the potential to undergo bioreductive activation by the normal reducing enzymes within a cell. In the present work we studied the effect of the nitroxide Tempol on the cytotoxicity induced by EO9, a mitomycin C analogue, in HT29 cells under aerobic and hypoxic conditions. The study was aimed to better understand the mechanism of EO9 cytotoxicity and the molecular level of the nitroxide's mode of protection. The reactions of Tempol with activated EO9, and the reactive species formed during EO9 activation were studied in a cell-free solution, using spin-trapping, and electron paramagnetic resonance (EPR) spectrometry. Our results indicate that EO9 induced similar cytotoxicity in HT29 cells under aerobic and hypoxic conditions while Tempol provided similar and almost complete protection to both aerobic and hypoxic cells. The results indicate that EO9 cytotoxicity is due to both 1- and 2-electron reductive activation processes, with aerobic toxicity caused by back-oxidation of the hydroquinone to the semiquinone, EO9.-. Tempol serves both as a useful tool in the study of the mechanisms of quinone-mediated cytotoxicity and as a potent antioxidant against the damaging effects of redox cycling quinones and semiquinones by scavenging of EO9.- or detoxification of O2.- and H2O2. JF - Molecular and cellular biochemistry AU - Samuni, Ayelet M AU - DeGraff, William AU - Krishna, Murali C AU - Mitchell, James B AD - Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892-1002, USA. PY - 2002 SP - 327 EP - 333 VL - 234-235 IS - 1-2 SN - 0300-8177, 0300-8177 KW - Aziridines KW - 0 KW - Cyclic N-Oxides KW - Indolequinones KW - Indoles KW - Spin Labels KW - apaziquone KW - H464ZO600O KW - tempol KW - U78ZX2F65X KW - Index Medicus KW - Tumor Cells, Cultured KW - Oxidation-Reduction -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Electron Spin Resonance Spectroscopy KW - Cell Death -- drug effects KW - Time Factors KW - Indoles -- antagonists & inhibitors KW - Aziridines -- metabolism KW - Aziridines -- toxicity KW - Aziridines -- antagonists & inhibitors KW - Indoles -- toxicity KW - Cyclic N-Oxides -- pharmacology KW - Indoles -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71984577?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biochemistry&rft.atitle=Nitroxides+as+antioxidants%3A+Tempol+protects+against+EO9+cytotoxicity.&rft.au=Samuni%2C+Ayelet+M%3BDeGraff%2C+William%3BKrishna%2C+Murali+C%3BMitchell%2C+James+B&rft.aulast=Samuni&rft.aufirst=Ayelet&rft.date=2002-05-01&rft.volume=234-235&rft.issue=1-2&rft.spage=327&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biochemistry&rft.issn=03008177&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-14 N1 - Date created - 2002-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specifically targeting the CD22 receptor of human B-cell lymphomas with RNA damaging agents: a new generation of therapeutics. AN - 71945814; 12148905 AB - Targeting CD22 on human B-cells with a monoclonal antibody conjugated to a cytotoxic RNAse causes potent and specific killing of the lymphoma cells in vitro. This translates to anti-tumor effects in human lymphoma models in SCID mice. RNA damage caused by RNAses could be an important alternative to standard DNA-damaging chemotherapeutics. A second generation construct with an improved recombinant cytotoxic RNAse is described. Targeted RNAses may overcome problems of toxicity and immunogenicity associated with plant or bacterial toxin-containing immunoconjugates. JF - Leukemia & lymphoma AU - Hursey, Miriam AU - Newton, Dianne L AU - Hansen, Hans J AU - Ruby, Dale AU - Goldenberg, David M AU - Rybak, Susanna M AD - Division of Cancer Treatment and Diagnosis, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 953 EP - 959 VL - 43 IS - 5 SN - 1042-8194, 1042-8194 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD KW - Antigens, Differentiation, B-Lymphocyte KW - CD22 protein, human KW - Cd22 protein, mouse KW - Cell Adhesion Molecules KW - Immunotoxins KW - Lectins KW - Sialic Acid Binding Ig-like Lectin 2 KW - Ribonucleases KW - EC 3.1.- KW - rapLR1 enzyme KW - Index Medicus KW - Animals KW - Humans KW - Mice KW - Mice, SCID KW - Antibodies, Monoclonal -- therapeutic use KW - Lymphoma, B-Cell -- drug therapy KW - Ribonucleases -- therapeutic use KW - Immunotoxins -- therapeutic use KW - Lectins -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71945814?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia+%26+lymphoma&rft.atitle=Specifically+targeting+the+CD22+receptor+of+human+B-cell+lymphomas+with+RNA+damaging+agents%3A+a+new+generation+of+therapeutics.&rft.au=Hursey%2C+Miriam%3BNewton%2C+Dianne+L%3BHansen%2C+Hans+J%3BRuby%2C+Dale%3BGoldenberg%2C+David+M%3BRybak%2C+Susanna+M&rft.aulast=Hursey&rft.aufirst=Miriam&rft.date=2002-05-01&rft.volume=43&rft.issue=5&rft.spage=953&rft.isbn=&rft.btitle=&rft.title=Leukemia+%26+lymphoma&rft.issn=10428194&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-07 N1 - Date created - 2002-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of genomics in identifying new targets for cancer therapy. AN - 71892411; 12102580 AB - The detailed map of the human genome can potentially transform future cancer therapy by merging genomics with pharmacology, thereby identifying which patients will benefit from specific therapeutic agents. Single-nucleotide polymorphisms (SNPs) provide a valuable tool for this pharmacogenetic approach to cancer therapy. The discovery of SNPs as disease markers may facilitate identification of populations at increased risk for certain cancers. In addition, SNP genetic screening may facilitate administration of appropriate treatment modalities or reveal specific genetic profiles that have importance in drug efficacy and toxicity. In addition to SNP analysis, DNA and tissue microarray analyses have the potential to transform the future of cancer therapy. For example, DNA microarrays may improve tumor classification systems as well as provide a molecular level dissection of global gene expression changes that occur in carcinogenesis. Tissue microarrays would allow one to verify candidate genes, identified from DNA microarrays, against archival tumor specimens with known clinical outcome. In addition, both microarray technologies may be combined to rapidly validate gene targets. We will review and discuss these state-of-the-art technologies including data suggesting that the combined use of these high throughput technologies will facilitate our understanding of the genetic complexities inherent in cancer and will revolutionize cancer therapy. JF - Oncology (Williston Park, N.Y.) AU - Anzick, Sarah L AU - Trent, Jeffrey M AD - Division of Intramural Research, Cancer Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-8002, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 7 EP - 13 VL - 16 IS - 5 Suppl 4 SN - 0890-9091, 0890-9091 KW - Index Medicus KW - Genetic Variation KW - Gene Expression Profiling KW - Humans KW - Drug Design KW - Genome, Human KW - Genomics -- methods KW - Neoplasms -- therapy KW - Polymorphism, Single Nucleotide -- genetics KW - Pharmacogenetics KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71892411?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncology+%28Williston+Park%2C+N.Y.%29&rft.atitle=Role+of+genomics+in+identifying+new+targets+for+cancer+therapy.&rft.au=Anzick%2C+Sarah+L%3BTrent%2C+Jeffrey+M&rft.aulast=Anzick&rft.aufirst=Sarah&rft.date=2002-05-01&rft.volume=16&rft.issue=5+Suppl+4&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Oncology+%28Williston+Park%2C+N.Y.%29&rft.issn=08909091&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-19 N1 - Date created - 2002-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suramin's development: what did we learn? AN - 71877415; 12099581 AB - Suramin, a polysulphonated napthylurea, has been extensively evaluated over the past 10 years as an anticancer agent, with the most interest in the treatment of prostate cancer. Early clinical results were promising with response rates of up to 70% being reported. However, a recent double-blind study showed only modest palliative effect in patients with androgen independent prostate cancer. In retrospect, it appears those initial reports failed to control for confounding variables such as antiandrogen withdrawal and hydrocortisone. Suramin causes numerous reversible toxicities (lethargy, rash, fatigue, anemia, hyperglycemia, hypocalcemia, coagulopathies, neutropenia, renal and hepatic complications). Neurotoxicity has been the most significant complication and appears to be related to the intensity of the dosing regimen. An optimal therapeutic dose has not been determined, but it is clear that adaptive controls add little benefit. Aside from moderate toxicities and the low therapeutic index in patients with prostate cancer, suramin's development has taught us some valuable lessons (i.e., anti-androgen withdrawal was noted during suramin's development, the use of PSA as an indicator of tumor burden was initiated during the evaluation of suramin). These lessons can be applied to all clinical trials in hormone refractory prostate cancer. Suramin has significantly enhanced the evolution of our knowledge in several areas of prostate cancer biology and treatment. JF - Investigational new drugs AU - Kaur, Maninderjeet AU - Reed, Eddie AU - Sartor, Oliver AU - Dahut, William AU - Figg, William D AD - Molecular Pharmacology Section, Cancer Therapeutic Branch, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 209 EP - 219 VL - 20 IS - 2 SN - 0167-6997, 0167-6997 KW - Antineoplastic Agents KW - 0 KW - Suramin KW - 6032D45BEM KW - Prostate-Specific Antigen KW - EC 3.4.21.77 KW - Index Medicus KW - Half-Life KW - Humans KW - Treatment Outcome KW - Clinical Trials as Topic KW - Metabolic Clearance Rate KW - Tissue Distribution KW - Male KW - Survival Analysis KW - Suramin -- adverse effects KW - Prostatic Neoplasms -- mortality KW - Antineoplastic Agents -- pharmacokinetics KW - Prostate-Specific Antigen -- blood KW - Suramin -- pharmacokinetics KW - Prostatic Neoplasms -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Prostate-Specific Antigen -- drug effects KW - Suramin -- therapeutic use KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71877415?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Effect+of+maxipost+on+ischemic+lesions+in+patients+with+acute+stroke%3A+The+post-010+MRI+substudy&rft.au=Warach%2C+S%3BHacke%2C+W%3BHsu%2C+C%3BLuby%2C+M%3BSullivan%2C+M%3BNoonan%2C+T%3BLin%2C+C-Y%3BFernandes%2C+L%3BBrunell%2C+R%3BBozik%2C+M&rft.aulast=Warach&rft.aufirst=S&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-10 N1 - Date created - 2002-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicology and carcinogenesis studies of o-nitrotoluene sulfone (CAS no. 88-72-2) in F344/N rats and B6C3F(1) mice (feed studies). AN - 71857027; 12087420 AB - [structure: see text] o-Nitrotoluene is used to synthesize agricultural and rubber chemicals, azo and sulfur dyes, and dyes for cotton, wool, silk, leather, and paper. o-Nitrotoluene was nominated for study by NIOSH and the NTP based on its considerable human exposure as well as the absence of long-term studies of carcinogenicity in rodents. Male and female F344/N rats and B6C3F1 mice were exposed to o-nitrotoluene (greater than 99% pure) in feed for 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, rat and mouse bone marrow cells, and mouse peripheral blood erythrocytes. 2-YEAR STUDY IN RATS: In the core study, groups of 60 male and 60 female rats were fed diets containing 625, 1,250, or 2,000 ppm o-nitrotoluene (equivalent to average daily doses of approximately 25, 50, or 90 mg o-nitrotoluene/kg body weight to males and 30, 60, or 100 mg/kg to females) for 105 weeks. In a 3-month stop-exposure study, groups of 70 male rats were fed diets containing 2,000 or 5,000 ppm o-nitrotoluene (equivalent to average daily doses of approximately 125 or 315 mg/kg) for 13 weeks followed by undosed feed for the remainder of the study. A group of 70 male rats receiving undosed feed served as a control group for both male rat studies; 60 female rats receiving undosed feed were the control group for the female core study. Ten control males and 10 males from each stop-exposure group were sacrificed at 3 months. Survival, Body Weights, and Feed Consumption: All 2,000 ppm core study, all 5,000 ppm stop-exposure, and all but three core study 1,250 ppm male rats died before the end of the studies. Survival of 625 ppm core study and 2,000 ppm stop-exposure males and of 2,000 ppm females was significantly less than that of the controls. Mean body weights of all exposed groups of males except the 625 ppm group were generally less than those of the controls throughout the study. Mean body weights of 2,000 ppm females were less than those of the controls during year 2 of the study. Feed consumption by exposed groups of rats was similar to that by the controls. Biomarkers of Exposure: Three urinary metabolites were followed during the study as biomarkers of exposure. The ratios of o-nitrobenzoic acid to creatinine and of o-nitrobenzylmercapturic acid to creatinine determined at 2 weeks and at 3, 12, and 18 months were linearly related to exposure concentration in males and females. The ratio of o-aminobenzoic acid to creatinine was not related to exposure concentration. Pathology Findings: The incidences of malignant mesothelioma in male rats occurred with positive trends in both the core and stop-exposure studies and were significantly greater in exposed groups than in the controls. Incidences of subcutaneous skin neoplasms (fibroma, fibrosarcoma, and lipoma) were increased in exposed groups of males, while the incidences of fibroma or fibrosarcoma (combined) were increased in exposed females. In all exposed groups of males and females except 2,000 ppm core study males, the incidences of mammary gland fibroadenoma were significantly increased. The incidences of mammary gland hyperplasia were significantly increased in 625 and 1,250 ppm females. Increased incidences of mesothelioma, skin neoplasms, and mammary gland fibroadenoma in the stop-exposure males indicated that 3 months of dosing were sufficient to produce a carcinogenic effect. Liver weights of 5,000 ppm stop-exposure males were significantly greater than those of the controls at 3 months. The incidences of hepatocellular adenoma in 2,000 ppm core study males and females and of hepatocellular adenoma or carcinoma (combined) in 2,000 ppm core study and 5,000 ppm stop-exposure males were significantly increased. Cholangiocarcinoma occurred in three 5,000 ppm stop-exposure males, and a single hepatocholangiocarcinoma occurred in a 625 ppm male and in a 2,000 ppm core study male. Nonneoplastic lesions of the liver included eosinophilic, mixed cell, and clear cell foci in exposed groups of males and females and mixed cell infiltrate in exposed males and basophilic focus in exposed females. The incidences of alveolar/bronchiolar adenoma and alveolar/bronchiolar adenoma or carcinoma (combined) were significantly increased in 5,000 ppm stop-exposure males, as were alveolar/bronchiolar hyperplasia in most exposed groups of males and females. The incidences of hematopoietic cell proliferation of the spleen and of hyperplasia of the mandibular lymph node (females) and bone marrow were increased in exposed groups of males at 3 months and/or 2 years and in exposed groups of females at 2 years. The incidences of mononuclear cell leukemia were significantly decreased in all groups of males exposed to 1,250 ppm or greater and in all exposed groups of females; the incidence of testicular interstitial cell adenoma was significantly decreased in 5,000 ppm stop-exposure males. 2-YEAR STUDY IN MICE: Groups of 60 male and 60 female mice were fed diets containing 0, 1,250, 2,500, or 5,000 ppm o-nitrotoluene (equivalent to average daily doses of approximately 165, 360, or 700 mg/kg to males and 150, 320, or 710 mg/kg to females) for 105 weeks. Survival, Body Weights, and Feed Consumption: All 2,500 and 5,000 ppm males died before the end of the study. Survival of 1,250 ppm males and 5,000 ppm females was significantly less than that of the controls. Mean body weights of exposed males and 5,000 ppm females were generally less than those of the controls throughout the study, and those of 2,500 ppm females were less during the second year of the study. Feed consumption by 5,000 ppm males was less than that by the controls. Biomarkers of Exposure: Three urinary metabolites were followed during the study as biomarkers of exposure. The ratios of o-nitrobenzoic acid to creatinine determined at 2 weeks and at 3, 12, and 18 months were linearly related to exposure concentration in males and females. The concentrations of o-nitrobenzylmercapturic acid and o-aminobenzoic acid were below the limit of quantitation at most time points. Pathology Findings: The incidences of hemangiosarcoma in all exposed groups of males and in 5,000 ppm females were significantly greater than those in the controls. Large intestine (cecum) carcinomas were observed in all exposed groups except 5,000 ppm males. The incidences of hepatocellular neoplasms were significantly increased in 2,500 and 5,000 ppm females. Nonneoplastic liver lesions including eosinophilic and basophilic foci and minimal to mild necrosis were enhanced in exposed males and females. Also present were focal hepatocyte syncytial alteration in exposed males and hepatocyte necrosis and focal hepatocyte cytoplasmic vacuolization in 5,000 ppm females. Renal tubule pigmentation occurred more frequently in exposed groups of males and in 5,000 ppm females than in the controls. Olfactory epithelial degeneration occurred in every male and female mouse exposed to 2,500 or 5,000 ppm, and the severity of this lesion increased with increasing exposure concentration. o-Nitrotoluene was not mutagenic in any of several strains of S. typhimurium, with or without metabolic activation enzymes (S9). Sister chromatid exchanges were significantly increased in cultured Chinese hamster ovary cells following exposure to o-nitrotoluene in the presence of S9; an equivocal response was seen without S9. o-Nitrotoluene did not induce chromosomal aberrations in cultured Chinese hamster ovary cells, with or without S9. o-Nitrotoluene did not induce a significant increase in the frequency of micronuclei in bone marrow polychromatic erythrocytes of male rats or male mice when administered by intraperitoneal injection. Results of a peripheral blood micronucleus test were equivocal for male mice and negative for female mice administered o-nitrotoluene in feed for 13 weeks. Under the conditions of these studies, there was clear evidence of carcinogenic activity* of o-nitrotoluene in male rats based on increased incidences of malignant mesothelioma, subcutaneous skin neoplasms, mammary gland fibroadenoma, and liver neoplasms. The increased incidences of lung neoplasms in male rats were also considered to be exposure related. There was clear evidence of carcinogenic activity of o-nitrotoluene in female rats based on increased incidences of subcutaneous skin neoplasms and mammary gland fibroadenoma. The increased incidence of hepatocellular adenoma in female rats was also considered to be exposure related. There was clear evidence of carcinogenic activity of -o-nitrotoluene in male and female mice based on increased incidences of hemangiosarcoma, carcinoma of the large intestine (cecum), and hepatocellular neoplasms (females only). Exposure to o--nitrotoluene caused increased incidences of nonneoplastic lesions of the mammary gland (females only), liver, bone marrow, spleen, lung, and mandibular lymph node (females only) in male and female rats and of the liver, kidney, and nose in male and female mice. Decreased incidences of mononuclear cell leukemia occurred in exposed groups of rats; the incidence of testicular interstitial cell adenoma was decreased in exposed male rats. [tables: see text] JF - National Toxicology Program technical report series AU - National Toxicology Program, Public Health Service, National Institutes of Health, US Department of Health and Human Services AD - National Toxicology Program, Public Health Service, National Institutes of Health, US Department of Health and Human Services Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 1 EP - 357 IS - 504 SN - 0888-8051, 0888-8051 KW - Carcinogens KW - 0 KW - Mutagens KW - Toluene KW - 3FPU23BG52 KW - 2-nitrotoluene KW - 6Q9N88YIAY KW - Index Medicus KW - Administration, Oral KW - Injections, Intraperitoneal KW - Animals KW - Dose-Response Relationship, Drug KW - Longevity -- drug effects KW - Mice KW - Rats KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Mutagenicity Tests KW - In Vitro Techniques KW - Carcinogenicity Tests KW - CHO Cells KW - Diet KW - Female KW - Male KW - Cricetinae KW - Toluene -- analogs & derivatives KW - Toluene -- administration & dosage KW - Carcinogens -- metabolism KW - Carcinogens -- administration & dosage KW - Neoplasms, Experimental -- chemically induced KW - Mutagens -- metabolism KW - Carcinogens -- toxicity KW - Toluene -- metabolism KW - Mutagens -- toxicity KW - Toluene -- toxicity KW - Mutagens -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71857027?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Emergence+and+selection+of+viral+immune+escape+following+antiretroviral+therapy+and+IL-2+suspension+in+primary+and+chronic+SIVmac251+infection+of+Rhesus+macaques&rft.au=Nacsa%2C+J%3BStanton%2C+J%3BHel%2C+Z%3BKunstman%2C+K%3BTryniszewska%2C+E%3BTsai%2C+W-P%3BGiuliani%2C+L%3BAltman%2C+J%3BWatkins%2C+DI%3BLewis%2C+M+G&rft.aulast=Nacsa&rft.aufirst=J&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-26 N1 - Date created - 2002-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Kinetics of G-CSF-induced granulocyte mobilization in healthy subjects: effects of route of administration and addition of dexamethasone. AN - 71854944; 12084168 AB - Granulocyte donors are frequently given G-CSF with or without dexamethasone approximately 18 hours before apheresis to increase cell yields. The purpose of this study was to assess the kinetics of G-CSF plus dexamethasone neutrophil mobilization to determine whether the neutrophils can be mobilized and collected the same day. Sixteen subjects were given four separate mobilization regimens: IV G-CSF (5 microg/kg), subcutaneous G-CSF (5 microg/kg), IV G-CSF (5 microg/kg) plus oral dexamethasone (8 mg), and subcutaneous G-CSF (5 microg/kg) plus oral dexamethasone (8 mg). Blood cell counts were measured before and after G-CSF administration. Following all four mobilization regimens, neutrophil counts fell 0.5 hour after the mobilizing agents were given, rose above baseline levels at Hour 2, and increased further with each time interval to Hour 8. In the absence of dexamethasone at Hours 2 through 8, there was no difference in neutrophil counts by subcutaneous or IV G-CSF administration routes. The addition of dexamethasone enhanced mobilization of neutrophils from Hours 3 through 24. Through Hour 8, there was no difference in the degree of mobilization among the subcutaneous G-CSF plus dexamethasone and the IV G-CSF plus dexamethasone regimens. However, at Hour 24, neutrophil counts were sustained at higher levels with subcutaneous G-CSF plus dexamethasone than with IV G-CSF plus dexamethasone. Granulocyte mobilization response to subcutaneous G-CSF plus dexamethasone is sustained at peak levels for 8 to 24 hours after coadministration of the two drugs. There was no advantage to giving G-CSF intravenously. JF - Transfusion AU - Stroncek, David F AU - Matthews, Cynthia L AU - Follmann, Dean AU - Leitman, Susan F AD - Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1184, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 597 EP - 602 VL - 42 IS - 5 SN - 0041-1132, 0041-1132 KW - Hemoglobins KW - 0 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Dexamethasone KW - 7S5I7G3JQL KW - Index Medicus KW - Administration, Oral KW - Drug Administration Schedule KW - Injections, Intravenous KW - Humans KW - Leukocyte Count KW - Neutrophils -- drug effects KW - Lymphocyte Count KW - Hemoglobins -- analysis KW - Prospective Studies KW - Kinetics KW - Adult KW - Injections, Subcutaneous KW - Monocytes -- drug effects KW - Drug Synergism KW - Male KW - Female KW - Platelet Count KW - Dexamethasone -- pharmacology KW - Hematopoietic Stem Cell Mobilization KW - Dexamethasone -- administration & dosage KW - Granulocytes -- drug effects KW - Granulocyte Colony-Stimulating Factor -- administration & dosage KW - Granulocyte Colony-Stimulating Factor -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71854944?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Transfusion&rft.atitle=Kinetics+of+G-CSF-induced+granulocyte+mobilization+in+healthy+subjects%3A+effects+of+route+of+administration+and+addition+of+dexamethasone.&rft.au=Stroncek%2C+David+F%3BMatthews%2C+Cynthia+L%3BFollmann%2C+Dean%3BLeitman%2C+Susan+F&rft.aulast=Stroncek&rft.aufirst=David&rft.date=2002-05-01&rft.volume=42&rft.issue=5&rft.spage=597&rft.isbn=&rft.btitle=&rft.title=Transfusion&rft.issn=00411132&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-15 N1 - Date created - 2002-06-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thymosin alpha1 inhibits mammary carcinogenesis in Fisher rats. AN - 71850465; 12084534 AB - The effects of thymosin alpha1 (Talpha1) on mammary carcinogenesis was investigated in Fisher rats. Mammary carcinomas were observed 3 months after N-nitrosomethylurea (NMU) injection (10mg, i.p.) into Fisher rats. Daily administration of Talpha1 (10 microg, s.c.) reduced mammary carcinoma incidence and prolonged survival time. Animals treated with exogenous Talpha1 had a significantly greater blood white cell density than control Fisher rats. These results suggest that Talpha1 prevents mammary carcinoma incidence as a result of stimulation of the immune system. JF - Peptides AU - Moody, Terry W AU - Tuthill, Cynthia AU - Badamchian, Mahnaz AU - Goldstein, Allan L AD - Cell and Cancer Biology Branch, National Cancer Institute, 9610 Medical Center Drive, Building KWC, Rockville, MD 20850, USA. moodyt@bprb.nci.nih.gov Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 1011 EP - 1014 VL - 23 IS - 5 SN - 0196-9781, 0196-9781 KW - Thymosin KW - 61512-21-8 KW - Methylnitrosourea KW - 684-93-5 KW - thymalfasin KW - W0B22ISQ1C KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Blood Chemical Analysis KW - Methylnitrosourea -- pharmacology KW - Cell Transformation, Neoplastic -- drug effects KW - Cell Transformation, Neoplastic -- immunology KW - Leukocyte Count KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Thymosin -- analogs & derivatives KW - Mammary Neoplasms, Experimental -- prevention & control KW - Mammary Neoplasms, Experimental -- immunology KW - Thymosin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71850465?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Peptides&rft.atitle=Thymosin+alpha1+inhibits+mammary+carcinogenesis+in+Fisher+rats.&rft.au=Moody%2C+Terry+W%3BTuthill%2C+Cynthia%3BBadamchian%2C+Mahnaz%3BGoldstein%2C+Allan+L&rft.aulast=Moody&rft.aufirst=Terry&rft.date=2002-05-01&rft.volume=23&rft.issue=5&rft.spage=1011&rft.isbn=&rft.btitle=&rft.title=Peptides&rft.issn=01969781&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-21 N1 - Date created - 2002-06-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Surgical approaches to liver metastases. AN - 71847974; 12075704 AB - Metastases confined to the liver from tumors arising in the gastrointestinal tract or other sites represent a significant clinical problem. Although the majority of patients present with disease that is not amenable to resection based on the size, number, or anatomic distribution of tumors, for selected patients with limited extent of disease surgical resection can result in long-term survival. In patients with colorectal cancer, a number of adverse prognostic factors have been identified that are associated with shortened survival following hepatic resection. The role of adjuvant hepatic artery infusion and systemic chemotherapyfollowing resection in this patient population has been the topic of several prospective random assignment trials. For patients with unresectable metastases confined to liver, a number of regional therapies are in clinical development and share the advantages of intensifying therapy at the site of tumor while minimizing or eliminating unnecessary systemic exposure and toxicity. One such approach is vascular isolation and perfusion, also known as isolated hepatic perfusion or IHP, in which the liver is treated with high dose chemotherapy and/or biological agents under hyperthermic conditions. Although only a limited number of centers have reported substantial experience with this procedure, it appears to have significant efficacy even in patients with advanced tumor burden orthose with tumors refractory to other types of therapy. The status of IHP is presented. JF - Cancer journal (Sudbury, Mass.) AU - Alexander, H Richard AD - Surgical Metabolism Section, Surgery, Branch, National Cancer Institute/National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 2002 SP - S68 EP - S81 VL - 8 Suppl 1 SN - 1528-9117, 1528-9117 KW - Tumor Necrosis Factor-alpha KW - 0 KW - Index Medicus KW - Neoplasm Staging KW - Humans KW - Chemotherapy, Cancer, Regional Perfusion KW - Prognosis KW - Tumor Necrosis Factor-alpha -- therapeutic use KW - Chemotherapy, Adjuvant KW - Survival Analysis KW - Colorectal Neoplasms -- pathology KW - Liver Neoplasms -- drug therapy KW - Hepatectomy -- methods KW - Liver Neoplasms -- surgery KW - Liver Neoplasms -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71847974?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+journal+%28Sudbury%2C+Mass.%29&rft.atitle=Surgical+approaches+to+liver+metastases.&rft.au=Alexander%2C+H+Richard&rft.aulast=Alexander&rft.aufirst=H&rft.date=2002-05-01&rft.volume=8+Suppl+1&rft.issue=&rft.spage=S68&rft.isbn=&rft.btitle=&rft.title=Cancer+journal+%28Sudbury%2C+Mass.%29&rft.issn=15289117&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-10 N1 - Date created - 2002-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p38 MAP kinase is involved in lipopolysaccharide-induced dopaminergic neuronal cell death in rat mesencephalic neuron-glia cultures. AN - 71847920; 12076985 AB - Immune stimulants, such as the bacterial endotoxin, lipopolysaccharide (LPS), the human immunodeficiency virus-1 coat protein gp120, or beta-amyloid peptides, lead to glial activation and production of various immune mediators, such as nitric oxide (NO) and proinflammatory cytokines in the brain. These mediators appear to contribute to neuronal cell death in neurodegenerative diseases. However, the signaling pathways, which mediate the neurotoxic effect by the endotoxin, are not understood. The purpose of this study was to determine the role of mitogen-activated protein kinase (MAPK) in LPS-induced neurodegeneration using mesencephalic dopaminergic neuron/glia cultures. We have found that the p38 MAPK is important in LPS-induced death of mesencephalic neurons in rat neuron-glia mixed cultures. Upon treatment with 10 ng/ml LPS, the number of dopaminergic neurons decreased by 80% within 48 h, preceded by a significant production of NO by glia. Neuroprotection by selective inhibition of p38 MAPK activity paralleled a decrease in LPS-induced inducible nitric oxide synthase (iNOS) expression. These events were significantly reduced by the selective p38 MAPK inhibitor, SB202190, but not by the inactive analogue SB202474. Inhibition of iNOS activity and NO production by treatment with GW274150 was also neuroprotective. Although the p38 MAPK inhibitor afforded significant neuroprotection from LPS toxicity in the neuron-glia mixed culture, it failed to protect dopaminergic neurons from 6-hydroxy-dopamine-induced toxicity, which acts directly on dopaminergic neurons by inducing hydroxyl radical formation from the mitochondria. The results suggest that p38 MAPK in glia plays a significant role in the LPS-induced death of mesencephalic neurons through induction of nitric oxide synthase and resulting NO production. JF - Annals of the New York Academy of Sciences AU - Jeohn, Gwang-Ho AU - Cooper, Cynthia L AU - Wilson, Belinda AU - Chang, Raymond C C AU - Jang, Kyung-Jin AU - Kim, Hyoung-Chun AU - Liu, Bin AU - Hong, Jau-Shyong AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 332 EP - 346 VL - 962 SN - 0077-8923, 0077-8923 KW - Enzyme Inhibitors KW - 0 KW - Lipopolysaccharides KW - Neuroprotective Agents KW - Sympatholytics KW - Nitric Oxide KW - 31C4KY9ESH KW - Oxidopamine KW - 8HW4YBZ748 KW - NOS2 protein, human KW - EC 1.14.13.39 KW - Nitric Oxide Synthase KW - Nitric Oxide Synthase Type II KW - Nos2 protein, rat KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Neuroglia -- cytology KW - Animals KW - Humans KW - Nitric Oxide -- metabolism KW - Neuroglia -- drug effects KW - Mesencephalon -- cytology KW - Oxidopamine -- pharmacology KW - Neuroprotective Agents -- pharmacology KW - Sympatholytics -- pharmacology KW - Rats KW - Neuroglia -- metabolism KW - Rats, Inbred F344 KW - Cells, Cultured KW - Nitric Oxide Synthase -- genetics KW - Enzyme Inhibitors -- pharmacology KW - Nitric Oxide Synthase -- metabolism KW - Neurons -- metabolism KW - Mitogen-Activated Protein Kinases -- metabolism KW - Neurons -- drug effects KW - Lipopolysaccharides -- pharmacology KW - Neurons -- cytology KW - Cell Death KW - Mitogen-Activated Protein Kinases -- antagonists & inhibitors KW - Dopamine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71847920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=p38+MAP+kinase+is+involved+in+lipopolysaccharide-induced+dopaminergic+neuronal+cell+death+in+rat+mesencephalic+neuron-glia+cultures.&rft.au=Jeohn%2C+Gwang-Ho%3BCooper%2C+Cynthia+L%3BWilson%2C+Belinda%3BChang%2C+Raymond+C+C%3BJang%2C+Kyung-Jin%3BKim%2C+Hyoung-Chun%3BLiu%2C+Bin%3BHong%2C+Jau-Shyong&rft.aulast=Jeohn&rft.aufirst=Gwang-Ho&rft.date=2002-05-01&rft.volume=962&rft.issue=&rft.spage=332&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-26 N1 - Date created - 2002-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gö6976 protects mesencephalic neurons from lipopolysaccharide-elicited death by inhibiting p38 MAP kinase phosphorylation. AN - 71844769; 12076986 AB - Glial activation is associated with inflammation-related neuron degeneration in the brain. A variety of protein kinases are assumed to contribute to the expression of inflammation-related products, such as nitric oxide (NO) and proinflammatory cytokines, however, the mechanisms of glial activation and glia-mediated neurotoxicity remain unclear. We found that the indolocarbazole, Gö6976, originally known as a selective protein kinase C (PKC) inhibitor, protects neurons from glia-mediated damage and suppresses lipopolysaccharide (LPS)-induced microglial production of inflammatory factors. The purpose of the study we report here was to determine the mechanism underlying the neuroprotective effect of Gö6976 in mesencephalic neuron/glia cultures. Gö6976 suppressed LPS-induced neurotoxicity in mesencephalic neuron/glia cultures and the protective effect of Gö6976 paralleled the suppression of p38 mitogen activated protein kinase (MAPK) activation and inhibition of NO production. Gö6976 did not directly inhibit the activity of p38 MAPK; rather, the inhibitor suppressed the phosphorylation of p38 MAPK, suggesting that the target of Gö6976 is a signaling event upstream of p38 MAPK. Although Gö6976 was originally known to be a selective PKC inhibitor, the neuroprotection was not mediated through its reputed effects on PKC activity. This paper demonstrates that the neuroprotective effect of Gö6976 against LPS-induced damage is mediated through the inhibition of proinflammatory factors, such as NO from microglia, by inhibiting the phosphorylation of p38 MAPK. JF - Annals of the New York Academy of Sciences AU - Jeohn, Gwang-Ho AU - Cooper, Cynthia L AU - Jang, Kyung-Jin AU - Kim, Hyoung-Chun AU - Hong, Jau-Shyong AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 347 EP - 359 VL - 962 SN - 0077-8923, 0077-8923 KW - Carbazoles KW - 0 KW - Enzyme Inhibitors KW - Indoles KW - Lipopolysaccharides KW - Neuroprotective Agents KW - Tumor Necrosis Factor-alpha KW - Go 6976 KW - 136194-77-9 KW - Nitric Oxide KW - 31C4KY9ESH KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - Index Medicus KW - Neuroglia -- cytology KW - Animals KW - Nitric Oxide -- metabolism KW - Mesencephalon -- cytology KW - Models, Biological KW - Neuroprotective Agents -- pharmacology KW - Neuroglia -- metabolism KW - Rats KW - Rats, Inbred F344 KW - Phosphorylation KW - Cells, Cultured KW - Cell Death KW - Enzyme Inhibitors -- pharmacology KW - Tumor Necrosis Factor-alpha -- metabolism KW - Neurons -- metabolism KW - Mitogen-Activated Protein Kinases -- metabolism KW - Neurons -- drug effects KW - Lipopolysaccharides -- pharmacology KW - Neurons -- cytology KW - Carbazoles -- pharmacology KW - Indoles -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71844769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=G%C3%B66976+protects+mesencephalic+neurons+from+lipopolysaccharide-elicited+death+by+inhibiting+p38+MAP+kinase+phosphorylation.&rft.au=Jeohn%2C+Gwang-Ho%3BCooper%2C+Cynthia+L%3BJang%2C+Kyung-Jin%3BKim%2C+Hyoung-Chun%3BHong%2C+Jau-Shyong&rft.aulast=Jeohn&rft.aufirst=Gwang-Ho&rft.date=2002-05-01&rft.volume=962&rft.issue=&rft.spage=347&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-26 N1 - Date created - 2002-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of nitric oxide in inflammation-mediated neurodegeneration. AN - 71835882; 12076984 AB - Increasing evidence has suggested that inflammation in the brain is closely associated with the pathogenesis of several degenerative neurologic disorders, including Parkinson's disease, Alzheimer's diseases, multiple sclerosis, amyotrophic lateral sclerosis, and AIDS dementia. The hallmark of brain inflammation is the activation of glial cells, especially that of microglia that produce a variety of proinflammatory and neurotoxic factors, including cytokines, fatty acid metabolites, free radicals--such as nitric oxide (NO) and superoxide. Excessive production of NO, as a consequence of nitric oxide synthase induction in activated glia, has been attributed to participate in neurodegeneration. Using primary mixed neuron-glia cultures and glia-enriched cultures prepared from embryonic rodent brain tissues, we have systemically studied the relationship between the production of NO and neurodegeneration in response to stimulation by the inflammagen lipopolysaccharide. This review summarizes our recent findings on the kinetics of NO generation, the relative contribution of microglia and astrocytes to NO accumulation, the relationship between NO production and neurodegeneration, and points of intervention along the pathways associated with NO generation to achieve neuroprotection. We also describe our results relating to the effect of several opioid-related agents on microglial activation and neuroprotection. Among these agents, the opioid receptor antagonist naloxone, especially its non-opioid enantiomer (+)-naloxone, promises to be of potential therapeutic value for the treatment of inflammation-related diseases. JF - Annals of the New York Academy of Sciences AU - Liu, Bin AU - Gao, Hui-Ming AU - Wang, Jiz-Yuh AU - Jeohn, Gwang-Ho AU - Cooper, Cynthia L AU - Hong, Jau-Shyong AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, North Carolina 27710, USA. liu3@niehs.nih.gov Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 318 EP - 331 VL - 962 SN - 0077-8923, 0077-8923 KW - Cytokines KW - 0 KW - Lipopolysaccharides KW - Narcotics KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Neuroglia -- metabolism KW - Animals KW - Cells, Cultured KW - Lipopolysaccharides -- metabolism KW - Humans KW - Narcotics -- metabolism KW - Cytokines -- metabolism KW - Nerve Degeneration KW - Inflammation -- physiopathology KW - Neurons -- metabolism KW - Neurodegenerative Diseases -- metabolism KW - Nitric Oxide -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71835882?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Role+of+nitric+oxide+in+inflammation-mediated+neurodegeneration.&rft.au=Liu%2C+Bin%3BGao%2C+Hui-Ming%3BWang%2C+Jiz-Yuh%3BJeohn%2C+Gwang-Ho%3BCooper%2C+Cynthia+L%3BHong%2C+Jau-Shyong&rft.aulast=Liu&rft.aufirst=Bin&rft.date=2002-05-01&rft.volume=962&rft.issue=&rft.spage=318&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-26 N1 - Date created - 2002-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Detection of alcohol and drug problems in an urban gynecology clinic. AN - 71824327; 12063880 AB - To compare screening instruments for their utility to detect substance use problems in women seeking gynecologic care, to assess the likelihood that alcohol/drug problems will be detected by physicians during a routine office visit and to examine the relationship between regular alcohol and/or drug use and the patient's presenting gynecologic complaints. Women (N = 360) attending a hospital-based gynecology clinic were screened prior to physician visit using the Michigan Alcoholism Screening Test, CAGE and T-ACE. After the visit, information on presenting complaint and physician's documentation of the patient's tobacco, alcohol and other drug use was abstracted from the medical record. The rates of alcohol and illicit drug use varied across assessment instruments; physician documentation, however, yielded the lowest prevalence estimates. Regular alcohol and drug users were more likely to present with chronic and acute medical problems than patients who were not regular users of these substances. The gynecology clinic offers an opportunity for early identification of women with substance problems, and alternative strategies are needed to encourage gynecologists to routinely screen for such problems at each medical visit. JF - The Journal of reproductive medicine AU - Gupman, Anne E AU - Svikis, Dace AU - McCaul, Mary E AU - Anderson, Jean AU - Santora, Patricia B AD - National Institute on Drug Abuse, Intramural Research Program, Departments of Psychiatry and Behavioral Sciences and of Obstetrics and Gynecology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. agupman@intra.nida.nih.gov Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 404 EP - 410 VL - 47 IS - 5 SN - 0024-7758, 0024-7758 KW - Index Medicus KW - Urban Health KW - Humans KW - Adult KW - Surveys and Questionnaires KW - Baltimore -- epidemiology KW - Mass Screening -- methods KW - Female KW - Prevalence KW - Pregnancy KW - Outpatient Clinics, Hospital KW - Pregnancy Complications -- prevention & control KW - Substance-Related Disorders -- prevention & control KW - Substance-Related Disorders -- epidemiology KW - Pregnancy Complications -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71824327?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+reproductive+medicine&rft.atitle=Detection+of+alcohol+and+drug+problems+in+an+urban+gynecology+clinic.&rft.au=Gupman%2C+Anne+E%3BSvikis%2C+Dace%3BMcCaul%2C+Mary+E%3BAnderson%2C+Jean%3BSantora%2C+Patricia+B&rft.aulast=Gupman&rft.aufirst=Anne&rft.date=2002-05-01&rft.volume=47&rft.issue=5&rft.spage=404&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+reproductive+medicine&rft.issn=00247758&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-26 N1 - Date created - 2002-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Contribution of substance abuse and HIV infection to psychiatric distress in an inner-city African-American population. AN - 71821455; 12069213 AB - We used Symptom Checklist 90-Revised (SCL90-R) to investigate psychiatric symptom severity in African-American drug-abusing individuals. Three hundred and seventeen African-American volunteers (52 control subjects; 265 drug users) were recruited, 19.2% of whom were HIV-positive. The impact of drug of choice or HIV status on mental distress was assessed. Symptomatic HIV-positive participants were excluded. The intake SCL90-R, Addiction Severity Index, and demographic data were subjected to regression analyses. Drug-abusing African Americans reported increased global distress, a finding that remained robust after we adjusted for HIV status, gender, age, and education. Drug of choice had no influence on the severity of global mental distress in our sample. Asymptomatic HIV-positive African Americans who abused drugs reported more distress than the HIV-negative drug users. Levels of global distress were similar in the HIV-negative and the HIV-positive controls. Subscales of the SCL90-R showed more symptom severity among drug-using, compared with nonusing, African Americans. Except for paranoia, anxiety, and obsessive-compulsive subscales, other symptom dimensions were significantly elevated in HIV-positive, compared with HIV-negative, drug abusers. When taken together, these findings suggest that drug abuse can exacerbate the severity of mental distress in HIV-positive patients. Treatment of these patients may be more successful if both sets of needs are addressed with matched interventions. JF - Journal of the National Medical Association AU - Nnadi, C U AU - Better, W AU - Tate, K AU - Herning, R I AU - Cadet, Jean Lud AD - Molecular Neuropsychiatry Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 336 EP - 343 VL - 94 IS - 5 SN - 1943-4693, 1943-4693 KW - Index Medicus KW - Severity of Illness Index KW - Regression Analysis KW - Chi-Square Distribution KW - Humans KW - Comorbidity KW - Risk Assessment KW - Age Distribution KW - Risk Factors KW - Adult KW - Health Surveys KW - Case-Control Studies KW - Incidence KW - Middle Aged KW - Adolescent KW - Urban Population KW - United States -- epidemiology KW - Sex Distribution KW - Female KW - Male KW - Poverty KW - Mental Disorders -- epidemiology KW - HIV Infections -- epidemiology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71821455?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Medical+Association&rft.atitle=Contribution+of+substance+abuse+and+HIV+infection+to+psychiatric+distress+in+an+inner-city+African-American+population.&rft.au=Nnadi%2C+C+U%3BBetter%2C+W%3BTate%2C+K%3BHerning%2C+R+I%3BCadet%2C+Jean+Lud&rft.aulast=Nnadi&rft.aufirst=C&rft.date=2002-05-01&rft.volume=94&rft.issue=5&rft.spage=336&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Medical+Association&rft.issn=19434693&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-18 N1 - Date created - 2002-06-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am Fam Physician. 2000 Mar 1;61(5):1423-8, 1431-2 [10735347] Psychiatr Clin North Am. 1993 Mar;16(1):127-40 [8456039] Psychopharmacol Bull. 1973 Jan;9(1):13-28 [4682398] Compr Psychiatry. 1993 May-Jun;34(3):150-8 [8339532] J Nerv Ment Dis. 1994 Oct;182(10):564-9 [7931204] Psychol Med. 1994 Nov;24(4):897-904 [7892357] AIDS. 1995 Jan;9(1):73-9 [7893444] Addiction. 1995 Mar;90(3):351-9 [7735020] J Subst Abuse. 1995;7(2):165-74 [7580227] AIDS. 1996 Aug;10(9):1033-9 [8853738] Psychiatry Res. 1996 Jan 31;59(3):245-9 [8930030] JAMA. 1997 May 7;277(17):1362-8 [9134941] J Subst Abuse Treat. 1997 Jan-Feb;14(1):71-80 [9218240] West J Nurs Res. 1997 Aug;19(4):442-60; discussion 460-5 [9260525] Am J Drug Alcohol Abuse. 1997 Nov;23(4):569-80 [9366974] Exp Clin Psychopharmacol. 1997 Nov;5(4):353-64 [9386962] Am J Addict. 1997 Fall;6(4):293-303 [9398927] J Subst Abuse Treat. 1998 May-Jun;15(3):213-20 [9633033] J Stud Alcohol. 1998 Nov;59(6):640-6 [9811085] J Natl Med Assoc. 1999 Jan;91(1):17-24 [10063784] Child Abuse Negl. 1999 May;23(5):421-33 [10348379] Addict Behav. 1999 Jul-Aug;24(4):481-96 [10466844] Mod Probl Pharmacopsychiatry. 1974;7(0):79-110 [4607278] Br J Psychiatry. 1976 Mar;128:280-9 [1252693] J Nerv Ment Dis. 1980 Jan;168(1):26-33 [7351540] Int J Addict. 1983 Dec;18(8):1109-14 [6671843] J Clin Psychol. 1988 Jan;44(1):82-6 [3343370] Br J Addict. 1989 Jun;84(6):673-9 [2752198] J Clin Psychol. 1990 Mar;46(2):230-7 [2324307] AIDS. 1990 Feb;4(2):145-52 [2328097] Arch Gen Psychiatry. 1991 Feb;48(2):143-7 [1989570] Res Nurs Health. 1991 Aug;14(4):269-77 [1891612] J Health Soc Behav. 1991 Sep;32(3):288-301 [1940211] J Subst Abuse Treat. 1993 Jan-Feb;10(1):53-7 [8450574] Psychiatr Serv. 2000 Sep;51(9):1126-9 [10970914] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cellular and molecular mechanisms of alcoholic hepatitis: introduction and summary of the symposium. AN - 71809779; 12062629 AB - The National Institute on Alcohol Abuse and Alcoholism and the Office of Rare Diseases, National Institutes of Health, sponsored a satellite symposium on "Cellular and Molecular Mechanisms of Alcoholic Hepatitis" at the 24th Annual Scientific Meeting of the Research Society on Alcoholism, Montreal, Quebec, Canada, June 2001. Alcohol intake is a major cause of hepatitis that may lead to alcoholic cirrhosis-a major cause of death in the United States. In up to one third of heavy drinkers alcoholic hepatitis develops, which is characterized by liver cell death and infiltration of leukocytes in hepatic parenchyma. Although leukocytes have been implicated in the pathogenesis of alcoholic hepatitis, the underlying cellular and molecular mechanisms by which leukocytes migrate to hepatic parenchyma and initiate tissue injury are not clear. For this symposium, 10 speakers were invited to address the following aspects of the mechanisms of alcoholic hepatitis: role of Kupffer cells in initiating the process of alcoholic hepatitis; types of leukocytes involved in the pathogenesis of alcoholic hepatitis; chemokines that are responsible for the attraction of leukocytes; adhesion molecules that promote the attachment of leukocytes to the endothelial cells and hepatocytes; mechanisms of leukocyte transmigration to hepatic parenchyma; mechanisms by which leukocytes initiate tissue injury; and interactive effects of alcohol and hepatitis viral proteins on liver injury. This article provides an introduction to the problem and a summary of the 10 scientific presentations delivered at the symposium. JF - Alcohol (Fayetteville, N.Y.) AU - Purohit, Vishnudutt AU - Russo, Denise AD - Biomedical Research Branch/Division of Basic Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 6000 Executive Boulevard, Suite 402, Bethesda, MD 20892-7003, USA. vpurohit@willco.niaaa.nih.gov Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 3 EP - 6 VL - 27 IS - 1 SN - 0741-8329, 0741-8329 KW - Index Medicus KW - United States KW - Leukocytes -- metabolism KW - Animals KW - Leukocytes -- pathology KW - Humans KW - National Institutes of Health (U.S.) KW - Kupffer Cells -- pathology KW - Hepatitis, Alcoholic -- pathology KW - Hepatitis, Alcoholic -- metabolism KW - Hepatitis, Alcoholic -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71809779?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.atitle=Cellular+and+molecular+mechanisms+of+alcoholic+hepatitis%3A+introduction+and+summary+of+the+symposium.&rft.au=Purohit%2C+Vishnudutt%3BRusso%2C+Denise&rft.aulast=Purohit&rft.aufirst=Vishnudutt&rft.date=2002-05-01&rft.volume=27&rft.issue=1&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.issn=07418329&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-20 N1 - Date created - 2002-06-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction of alcohol and hepatitis viral proteins: implication in synergistic effect of alcohol drinking and viral hepatitis on liver injury. AN - 71809204; 12062640 AB - Alcohol drinking and viral hepatitis are both recognized as major causes of liver disease worldwide, and they frequently coexist and synergistically cause liver injury in patients with chronic liver disease. Several mechanisms have been implicated in exacerbation of liver injury in patients with alcohol drinking and viral hepatitis. These include impairment of host defense and liver regeneration by alcohol consumption. The findings obtained from my laboratory have demonstrated that alcohol potentiates cooperatively several signals activated by hepatitis B virus X protein (HBX) or hepatitis C virus core protein, and HBX sensitizes hepatocytes to tumor necrosis factor-alpha (TNF-alpha)- and ethanol-induced apoptosis by a caspase-3-dependent mechanism, which may also contribute to the synergistic effect of alcohol drinking and viral hepatitis on liver injury. JF - Alcohol (Fayetteville, N.Y.) AU - Gao, Bin AD - Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Park Building Room 120, 12420 Parklawn Drive, MSC 8115, Bethesda, MD 20892, USA. bgao@mail.nih.gov Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 69 EP - 72 VL - 27 IS - 1 SN - 0741-8329, 0741-8329 KW - Hepatitis Antigens KW - 0 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Ethanol -- adverse effects KW - Animals KW - Humans KW - Hepatitis B -- metabolism KW - Hepatitis B -- chemically induced KW - Hepatitis C -- chemically induced KW - Ethanol -- metabolism KW - Hepatitis C -- metabolism KW - Liver -- virology KW - Liver -- pathology KW - Alcohol Drinking -- metabolism KW - Liver -- metabolism KW - Hepatitis, Alcoholic -- metabolism KW - Hepatitis Antigens -- metabolism KW - Hepatitis, Alcoholic -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71809204?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.atitle=Interaction+of+alcohol+and+hepatitis+viral+proteins%3A+implication+in+synergistic+effect+of+alcohol+drinking+and+viral+hepatitis+on+liver+injury.&rft.au=Gao%2C+Bin&rft.aulast=Gao&rft.aufirst=Bin&rft.date=2002-05-01&rft.volume=27&rft.issue=1&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.issn=07418329&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-20 N1 - Date created - 2002-06-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neutrophilic infiltration in alcoholic hepatitis. AN - 71804652; 12062632 AB - Leukocyte infiltration in the liver is one of the most important features of alcoholic liver disease. However, in alcoholic hepatitis, the role of polymorphonuclear neutrophils (PMNs) in liver injury still remains to be fully elucidated. Furthermore, the migration of PMNs and their presence in the liver during alcoholic hepatitis have not been fully investigated. Up-regulation of chemokine secretion and adhesion molecule expression on effector cells (i.e., PMNs) and target cells (i.e., hepatocytes) are important factors in neutrophilic infiltration of the liver. The CXC chemokines--that is, interleukin (IL)-8 (in human beings), cytokine-induced neutrophil chemoattractant (CINC) (in rats), and KC (in mice)--are proneutrophilic agents. They are up-regulated during chronic--that is, several years of--alcohol use in human beings and in up to 30 weeks in experimental models of ethanol intoxication in mice and rats. Up-regulation of these chemokines in the circulation and tissues is also associated with enhanced neutrophilic infiltration in the liver. In the rat, the up-regulation of CXC chemokine production is time dependent. For example, after 16 weeks of feeding, up-regulation of CXC chemokine is observed, whereas after 32 weeks, CC chemokines are enhanced. Concomitantly, selective migration of PMNs and mononuclear cells is observed. In another model, in which both CXC and CC chemokines were enhanced after chronic ethanol use for 12 weeks in mice, neutrophilic and mononuclear/lymphocytic infiltrations were also seen. This model correlates closely with alcoholic hepatitis in human beings, characterized by increased IL-8, RANTES (regulated upon activation, normal T cell expressed and secreted), and macrophage inflammatory protein-1 (MIP-1) and profound increases in neutrophils and lymphocytes in the liver. JF - Alcohol (Fayetteville, N.Y.) AU - Bautista, Abraham P AD - Department of Physiology and NIAAA-Sponsored Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. abauti123@cs.com Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 17 EP - 21 VL - 27 IS - 1 SN - 0741-8329, 0741-8329 KW - Index Medicus KW - Animals KW - Alcoholism -- pathology KW - Humans KW - Alcoholism -- metabolism KW - Hepatitis, Alcoholic -- pathology KW - Hepatitis, Alcoholic -- metabolism KW - Neutrophil Infiltration UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71804652?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.atitle=Neutrophilic+infiltration+in+alcoholic+hepatitis.&rft.au=Bautista%2C+Abraham+P&rft.aulast=Bautista&rft.aufirst=Abraham&rft.date=2002-05-01&rft.volume=27&rft.issue=1&rft.spage=17&rft.isbn=&rft.btitle=&rft.title=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.issn=07418329&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-20 N1 - Date created - 2002-06-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analyzing array data using supervised methods. AN - 71799099; 12052147 AB - Pharmacogenomics is the application of genomic technologies to drug discovery and development, as well as for the elucidation of the mechanisms of drug action on cells and organisms. DNA microarrays measure genome-wide gene expression patterns and are an important tool for pharmacogenomic applications, such as the identification of molecular targets for drugs, toxicological studies and molecular diagnostics. Genome-wide investigations generate vast amounts of data and there is a need for computational methods to manage and analyze this information. Recently, several supervised methods, in which other information is utilized together with gene expression data, have been used to characterize genes and samples. The choice of analysis methods will influence the results and their interpretation, therefore it is important to be familiar with each method, its scope and limitations. Here, methods with special reference to applications for pharmacogenomics are reviewed. JF - Pharmacogenomics AU - Ringnér, Markus AU - Peterson, Carsten AU - Khan, Javed AD - Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Building 50, Room 5142,50 South Drive MSC 8000, Bethesda, MD 20892, USA. mringner@nhgri.nih.gov. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 403 EP - 415 VL - 3 IS - 3 SN - 1462-2416, 1462-2416 KW - Proteins KW - 0 KW - Index Medicus KW - Proteins -- classification KW - Neural Networks (Computer) KW - Proteins -- genetics KW - Artificial Intelligence KW - Data Interpretation, Statistical KW - Oligonucleotide Array Sequence Analysis -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71799099?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenomics&rft.atitle=Analyzing+array+data+using+supervised+methods.&rft.au=Ringn%C3%A9r%2C+Markus%3BPeterson%2C+Carsten%3BKhan%2C+Javed&rft.aulast=Ringn%C3%A9r&rft.aufirst=Markus&rft.date=2002-05-01&rft.volume=3&rft.issue=3&rft.spage=403&rft.isbn=&rft.btitle=&rft.title=Pharmacogenomics&rft.issn=14622416&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-13 N1 - Date created - 2002-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Function of cytokines within the TGF-beta superfamily as determined from transgenic and gene knockout studies in mice. AN - 71769262; 12041733 AB - Several major conceptual problems regarding specific in vivo functions of the TGF-beta family members remain the key focus of many researchers studying the biology of these secreted signaling molecules. More than 45 members of this family of growth factors have been identified and partially characterized for their molecular roles in numerous processes such as cell proliferation and differentiation, embryonic development, carcinogenesis, immune dysfunction, inflammation and wound healing. The high degree of similarity that exists at the structural level among the isoforms of these growth factors is accompanied by a significant overlap in function, as defined by many in vitro model systems and in vivo systems involving administration of exogenous ligand or of ligand-specific blocking antibodies. The ability to discern the critical functions of these molecules based on patterns of expression has also often been quite difficult. The evolution of more sophisticated functional genomics approaches has been recently instrumental in generating unique perspectives into the mechanisms governing the activity of the members of the TGF-beta family. The studies outlined in this review are significant in that they not only support working hypotheses regarding the activities of TGF-beta generated through extensive in vitro studies but also raise new questions regarding the role of each isoform in numerous processes. With the rapid advances in these approaches to probe activity in a more cell and time-dependent fashion, we will gain valuable insights for designing approaches for targeting the complex cellular pathways mediating their responses and will also help us develop novel therapies to treat disease processes. JF - Current molecular medicine AU - Kulkarni, Ashok B AU - Thyagarajan, Tamizchelvi AU - Letterio, John J AD - Functional Genomics Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA. ak40m@.nih.gov Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 303 EP - 327 VL - 2 IS - 3 SN - 1566-5240, 1566-5240 KW - DNA-Binding Proteins KW - 0 KW - Ligands KW - Receptors, Transforming Growth Factor beta KW - Smad Proteins KW - Trans-Activators KW - Transforming Growth Factor beta KW - Index Medicus KW - Leukocytes -- metabolism KW - Phylogeny KW - Trans-Activators -- metabolism KW - Receptors, Transforming Growth Factor beta -- genetics KW - Animals KW - Cell Transformation, Neoplastic -- metabolism KW - Receptors, Transforming Growth Factor beta -- metabolism KW - DNA-Binding Proteins -- genetics KW - Mice KW - Wound Healing -- physiology KW - Homeostasis -- physiology KW - Mice, Transgenic KW - Mice, Knockout KW - Phenotype KW - Trans-Activators -- genetics KW - DNA-Binding Proteins -- metabolism KW - Transforming Growth Factor beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71769262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+molecular+medicine&rft.atitle=Function+of+cytokines+within+the+TGF-beta+superfamily+as+determined+from+transgenic+and+gene+knockout+studies+in+mice.&rft.au=Kulkarni%2C+Ashok+B%3BThyagarajan%2C+Tamizchelvi%3BLetterio%2C+John+J&rft.aulast=Kulkarni&rft.aufirst=Ashok&rft.date=2002-05-01&rft.volume=2&rft.issue=3&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=Current+molecular+medicine&rft.issn=15665240&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-29 N1 - Date created - 2002-06-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase II trial of combination chemotherapy and surgical resection for the treatment of metastatic adrenocortical carcinoma: continuous infusion doxorubicin, vincristine, and etoposide with daily mitotane as a P-glycoprotein antagonist. AN - 71711257; 12015757 AB - Adrenocortical carcinoma (ACC) is rare, nearly always fatal, and to the authors' knowledge has few nonsurgical treatment options. Based on in vitro studies demonstrating the efficacy of mitotane as a P-glycoprotein (Pgp) antagonist, and expression of high levels of Pgp in ACC, the authors conducted a study of infusional doxorubicin, vincristine, and etoposide with oral mitotane +/- surgical resection in patients with metastatic ACC. Thirty-six patients with metastatic ACC received daily oral mitotane (mean, 4.6 g/day) and 96-hour infusional doxorubicin (10 mg/m(2)/day), etoposide (75 mg/m(2)/day), and vincristine (0.4 mg/m(2)/day). Four responding patients (11%) underwent surgery. Thirty-five patients were evaluable; all had metastatic disease. Eleven patients had not undergone resection of the primary tumor. Approximately 53% of patients had functional tumors. A total of 190 cycles were administered to 36 patients. Responses were observed in 8 patients (22%): 1 complete, 4 partial, and 3 minor responses. The mean duration of response was 12.4 months. Using a landmark method, the median survival of patients who did not respond to chemotherapy was 11.6 months from a point 4 months after the initiation of therapy, whereas that of 8 patients who demonstrated a response to chemotherapy was 34.3 months from that same landmark. High levels of Pgp expression were documented in nine of nine tumors. Mitotane levels > 10 microg/mL, previously shown to antagonize Pgp in vitro, were achieved in 25 of 36 patients (69%). However, rhodamine efflux from CD56-positive cells was not impaired, suggesting poor in vivo Pgp inhibition. The predominant Grade 3/4 toxicity (according to the Common Toxicity Criteria of the National Cancer Institute) was neutropenia in 66% of cycles; however, fever occurred in only 3% of cycles. Daily mitotane was associated with Grade 1/2 nausea, diarrhea, fatigue, and neuropsychiatric changes in 31 of 36 patients (86%). Using a combination regimen of daily mitotane with infusional doxorubicin, vincristine, and etoposide in patients with metastatic ACC, responses were observed in 22% of patients. The superiority of this combination over single-agent mitotane is uncertain. The side effects of mitotane made treatment difficult. More effective Pgp antagonists are needed. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10487 JF - Cancer AU - Abraham, Jame AU - Bakke, Susan AU - Rutt, Ann AU - Meadows, Beverly AU - Merino, Maria AU - Alexander, Richard AU - Schrump, David AU - Bartlett, David AU - Choyke, Peter AU - Robey, Rob AU - Hung, Elizabeth AU - Steinberg, Seth M AU - Bates, Susan AU - Fojo, Tito AD - Medicine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/05/01/ PY - 2002 DA - 2002 May 01 SP - 2333 EP - 2343 VL - 94 IS - 9 SN - 0008-543X, 0008-543X KW - Antigens, CD56 KW - 0 KW - Antineoplastic Agents, Phytogenic KW - P-Glycoprotein KW - Rhodamines KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Mitotane KW - 78E4J5IB5J KW - Doxorubicin KW - 80168379AG KW - Abridged Index Medicus KW - Index Medicus KW - Administration, Oral KW - Rhodamines -- metabolism KW - Combined Modality Therapy KW - Humans KW - Vincristine -- administration & dosage KW - Aged KW - Doxorubicin -- administration & dosage KW - Antigens, CD56 -- analysis KW - Survival Rate KW - Etoposide -- administration & dosage KW - Adult KW - Treatment Outcome KW - Neoplasm Metastasis KW - Middle Aged KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - Female KW - Male KW - Mitotane -- administration & dosage KW - Adrenocortical Carcinoma -- surgery KW - Adrenocortical Carcinoma -- mortality KW - P-Glycoprotein -- blood KW - Adrenal Cortex Neoplasms -- surgery KW - Adrenal Cortex Neoplasms -- mortality KW - Adrenal Cortex Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Mitotane -- adverse effects KW - P-Glycoprotein -- antagonists & inhibitors KW - Adrenocortical Carcinoma -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71711257?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=A+phase+II+trial+of+combination+chemotherapy+and+surgical+resection+for+the+treatment+of+metastatic+adrenocortical+carcinoma%3A+continuous+infusion+doxorubicin%2C+vincristine%2C+and+etoposide+with+daily+mitotane+as+a+P-glycoprotein+antagonist.&rft.au=Abraham%2C+Jame%3BBakke%2C+Susan%3BRutt%2C+Ann%3BMeadows%2C+Beverly%3BMerino%2C+Maria%3BAlexander%2C+Richard%3BSchrump%2C+David%3BBartlett%2C+David%3BChoyke%2C+Peter%3BRobey%2C+Rob%3BHung%2C+Elizabeth%3BSteinberg%2C+Seth+M%3BBates%2C+Susan%3BFojo%2C+Tito&rft.aulast=Abraham&rft.aufirst=Jame&rft.date=2002-05-01&rft.volume=94&rft.issue=9&rft.spage=2333&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-13 N1 - Date created - 2002-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methamphetamine induces apoptosis in an immortalized rat striatal cell line by activating the mitochondrial cell death pathway. AN - 71710365; 12015210 AB - Methamphetamine is a neurotoxic drug of abuse known to cause cell death both in vitro and in vivo. Nevertheless, the molecular and cellular mechanisms involved in this process remain to be clarified. Herein, we show that methamphetamine-induced apoptosis is associated with early (2 h) overexpression of bax, decreases of mitochondrial membrane potential and oxygen consumption as well as release of cytochrome c from mitochondria. In addition, activated caspase-9 was detected at 4 h post-METH exposure. Cell death was detectable by annexin V and propidium iodide staining after 8 h of methamphetamine exposure. At that time, the majority of the cells were stained by annexin V alone, with some cells being stained for both annexin V and propidium iodide. Moreover, cleavage of caspase-3, poly (ADP-ribose) polymerase and DNA fragmentation-related factor 45 was detected at 8 h post drug treatment. These results indicate that methamphetamine-induced apoptotic cell death results from early overexpression of bax, reduction of mitochondrial respiration and membrane potential and release of mitochondrial cytochrome c with subsequent activation of the caspase cascade. JF - Neuropharmacology AU - Deng, Xiaolin AU - Cai, Ning-Sheng AU - McCoy, Michael T AU - Chen, Weiguo AU - Trush, Michael A AU - Cadet, Jean Lud AD - Molecular Neuropsychiatry Section, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 837 EP - 845 VL - 42 IS - 6 SN - 0028-3908, 0028-3908 KW - Dopamine Uptake Inhibitors KW - 0 KW - Methamphetamine KW - 44RAL3456C KW - Index Medicus KW - Rats KW - Cell Death -- physiology KW - Animals KW - Cell Death -- drug effects KW - Dopamine Uptake Inhibitors -- pharmacology KW - Cell Line, Transformed -- cytology KW - Corpus Striatum -- cytology KW - Apoptosis -- physiology KW - Mitochondria -- enzymology KW - Corpus Striatum -- enzymology KW - Signal Transduction -- physiology KW - Cell Line, Transformed -- drug effects KW - Apoptosis -- drug effects KW - Mitochondria -- drug effects KW - Signal Transduction -- drug effects KW - Methamphetamine -- pharmacology KW - Corpus Striatum -- drug effects KW - Cell Line, Transformed -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71710365?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropharmacology&rft.atitle=Methamphetamine+induces+apoptosis+in+an+immortalized+rat+striatal+cell+line+by+activating+the+mitochondrial+cell+death+pathway.&rft.au=Deng%2C+Xiaolin%3BCai%2C+Ning-Sheng%3BMcCoy%2C+Michael+T%3BChen%2C+Weiguo%3BTrush%2C+Michael+A%3BCadet%2C+Jean+Lud&rft.aulast=Deng&rft.aufirst=Xiaolin&rft.date=2002-05-01&rft.volume=42&rft.issue=6&rft.spage=837&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=00283908&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-25 N1 - Date created - 2002-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - State trends in health risk factors and receipt of clinical preventive services among US adults during the 1990s. AN - 71702517; 12020301 AB - Monitoring trends is essential for evaluating past activities and guiding current preventive health program and policy efforts. Although tracking progress toward national health goals is helpful, use of national estimates is limited because most preventive health care activities, policies, and other efforts occur at the state or community level. There may be important state trends that are obscured by national data. To estimate state-specific trends for 5 health risk factors and 6 clinical preventive services. Telephone surveys were conducted from 1991 through 2000 as part of the Behavioral Risk Factor Surveillance System. Randomly selected adults aged 18 years or older from 49 US states. Annual state sample sizes ranged from 1188 to 7543. Statistically significant changes (P<.01) in state prevalences of cigarette smoking, binge alcohol use, physical inactivity, obesity, safety belt use, and mammography; screening for cervical cancer, colorectal cancer, and cholesterol levels; and receipt of influenza and pneumococcal disease vaccination. There were statistically significant increases in safety belt use for 39 of 47 states and receipt of mammography in the past 2 years for women aged 40 years or older for 43 of 47 states. For persons aged 65 years or older, there were increases in receipt of influenza vaccination for 44 of 49 states and ever receiving pneumococcal vaccination for 48 of 49 states. State trends were mixed for binge alcohol use (increasing in 19 of 47 states and declining in 3), physical inactivity (increasing in 3 of 48 states and declining in 11), and cholesterol screening (increasing in 13 of 47 states and decreasing in 5). Obesity increased in all states and smoking increased in 14 of 47 states (declining only in Minnesota). Cervical cancer screening increased in 8 of 48 states and colorectal cancer screening increased in 13 of 49 states. New York experienced improvements for 8 of 11 measures, while 7 of 11 measures improved in Delaware, Kentucky, and Maryland; in contrast, Alaska experienced improvements for no measures and at least 4 of 11 measures worsened in Iowa, North Dakota, and South Dakota. Most states experienced increases in safety belt use, mammography, and adult vaccinations. Trends for smoking and binge alcohol use are disturbing, and obesity data support previous findings. Trend data are useful for targeting state preventive health efforts. JF - JAMA AU - Nelson, David E AU - Bland, Shayne AU - Powell-Griner, Eve AU - Klein, Richard AU - Wells, Henry E AU - Hogelin, Gary AU - Marks, James S AD - National Cancer Institute, Division of Cancer Control and Population Sciences, 6130 Executive Blvd, MSC 7365, EPN 4068, Bethesda, MD 20892-7365, USA. nelsond@mail.nih.gov PY - 2002 SP - 2659 EP - 2667 VL - 287 IS - 20 SN - 0098-7484, 0098-7484 KW - Influenza Vaccines KW - 0 KW - Pneumococcal Vaccines KW - Ethanol KW - 3K9958V90M KW - Abridged Index Medicus KW - Index Medicus KW - Uterine Cervical Neoplasms -- prevention & control KW - Mammography -- utilization KW - Vaccination -- utilization KW - Alcoholic Intoxication -- epidemiology KW - Humans KW - Pneumococcal Infections -- prevention & control KW - Models, Statistical KW - Exercise KW - Obesity -- epidemiology KW - Hypercholesterolemia -- prevention & control KW - Smoking -- epidemiology KW - Mass Screening -- trends KW - Seat Belts -- utilization KW - Influenza, Human -- prevention & control KW - Ethanol -- poisoning KW - Adult KW - Data Collection KW - United States -- epidemiology KW - Colorectal Neoplasms -- prevention & control KW - Female KW - Male KW - Preventive Medicine -- trends KW - Health Behavior KW - Preventive Medicine -- statistics & numerical data KW - Population Surveillance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71702517?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA&rft.atitle=State+trends+in+health+risk+factors+and+receipt+of+clinical+preventive+services+among+US+adults+during+the+1990s.&rft.au=Nelson%2C+David+E%3BBland%2C+Shayne%3BPowell-Griner%2C+Eve%3BKlein%2C+Richard%3BWells%2C+Henry+E%3BHogelin%2C+Gary%3BMarks%2C+James+S&rft.aulast=Nelson&rft.aufirst=David&rft.date=2002-05-01&rft.volume=287&rft.issue=20&rft.spage=2659&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-04 N1 - Date created - 2002-05-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 2002 Sep 11;288(10):1233 [12215128] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adult-onset calorie restriction and fasting delay spontaneous tumorigenesis in p53-deficient mice. AN - 71695649; 12016155 AB - Heterozygous p53-deficient (p53(+/-)) mice, a potential model for human Li-Fraumeni Syndrome, have one functional allele of the p53 tumor suppressor gene. These mice are prone to spontaneous neoplasms, most commonly sarcoma and lymphoma; the median time to death of p53+/- mice is 18 months. We have shown previously that juvenile-onset calorie restriction (CR) to 60% of ad libitum (AL) intake delays tumor development in young p53-null (-/-) mice by a p53-independent and insulin-like growth factor 1 (IGF-1)-related mechanism. To determine whether CR is effective when started in adult p53-deficient mice, and to compare chronic CR with an intermittent fasting regimen, male p53+/- mice (7-10 months old, 31-32 mice/group) were randomly assigned to the following regimens: (i) AL (AIN-76A diet), (ii) CR to 60% of AL intake or (iii) 1 day/week fast. Food availability on non-fasting days was controlled to prevent compensatory over feeding. Relative to the AL group, CR significantly delayed (P = 0.001) the onset of tumors in adult mice, whereas the 1 day/week fast caused a moderate delay (P = 0.039). Substantial variation in longevity and maximum body weight within treatments was not correlated with variation in growth characteristics of individual mice. In a separate group of p53+/- mice treated for 4 weeks (n = five mice per treatment), plasma IGF-1 levels in CR versus AL mice were reduced by 20% (P < 0.01) and leptin levels were reduced by 71% (P < 0.01); fasted mice had intermediate levels of leptin and IGF-1. Our findings that CR or a 1 day/week fast suppressed carcinogenesis-even when started late in life in mice predestined to develop tumors due to decreased p53 gene dosage-support efforts to identify suitable interventions influencing energy balance in humans as a tool for cancer prevention. JF - Carcinogenesis AU - Berrigan, David AU - Perkins, Susan N AU - Haines, Diana C AU - Hursting, Stephen D AD - Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892-7105, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 817 EP - 822 VL - 23 IS - 5 SN - 0143-3334, 0143-3334 KW - Tumor Suppressor Protein p53 KW - 0 KW - Index Medicus KW - Animals KW - Mice KW - Longevity KW - Tumor Suppressor Protein p53 -- physiology KW - Energy Intake KW - Neoplasms, Experimental -- prevention & control KW - Tumor Suppressor Protein p53 -- genetics KW - Neoplasms, Experimental -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71695649?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Adult-onset+calorie+restriction+and+fasting+delay+spontaneous+tumorigenesis+in+p53-deficient+mice.&rft.au=Berrigan%2C+David%3BPerkins%2C+Susan+N%3BHaines%2C+Diana+C%3BHursting%2C+Stephen+D&rft.aulast=Berrigan&rft.aufirst=David&rft.date=2002-05-01&rft.volume=23&rft.issue=5&rft.spage=817&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-21 N1 - Date created - 2002-05-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A major human arsenic metabolite, dimethylarsinic acid, requires reduced glutathione to induce apoptosis. AN - 71695227; 12018983 AB - Inorganic arsenicals are important environmental toxicants and carcinogens in humans. In mammals, including humans, inorganic arsenicals often undergo methylation, forming compounds such as dimethyarsinic acid (DMA). Recent evidence indicates DMA is a complete carcinogen in rodents while evidence for inorganic arsenicals as carcinogens in rodents remains equivocal. Thus, we studied the molecular mechanisms of in vitro cytolethality of DMA compared to that of the trivalent inorganic arsenical, sodium arsenite, using a rat liver epithelial cell line (TRL 1215). Arsenite was very cytotoxic in these cells (LC(50) = 35 microM after 48 h of exposure). With arsenite exposure, most dead cells showed histological and biochemical evidence of necrosis. Arsenite cytotoxicity increased markedly when cellular GSH was depleted with the glutathione synthase inhibitor, L-buthionine-[S,R]-sulfoximine (BSO). In contrast, DMA was nearly 3 orders of magnitude less cytotoxic (LC(50) = 1.5 mM) although evidence showed the predominating form of death was apoptosis. Surprisingly, GSH depletion actually decreased DMA-induced apoptosis. A glutathione scavenger, diethyl maleate (DEM), and a glutathione reductase inhibitor, carmustine, also prevented DMA-induced apoptosis. These data indicate that DMA requires intracellular GSH to induce apoptosis. Ethacrynic acid (EA), an inhibitor of glutathione S-transferase (GST) that catalyzes GSH-substrate conjugation, acivicin, an inhibitor of gamma-glutamyltranspeptidase (GGT) which catalyzes the initial breakdown of GSH-substrate conjugates, and aminooxyacetic acid (AOAA), an inhibitor of beta-lyase which catalyzes the final breakdown of GSH-substrate conjugates, all were effective in suppressing DMA-induced apoptosis. These findings indicate that DMA likely is conjugated in some form with GSH, and that it is this conjugate that induces apoptosis during subsequent metabolic reactions. JF - Chemical research in toxicology AU - Sakurai, Teruaki AU - Qu, Wei AU - Sakurai, Masumi H AU - Waalkes, Michael P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 629 EP - 637 VL - 15 IS - 5 SN - 0893-228X, 0893-228X KW - Arsenites KW - 0 KW - Herbicides KW - Cacodylic Acid KW - AJ2HL7EU8K KW - Glutathione KW - GAN16C9B8O KW - arsenite KW - N5509X556J KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Drug Interactions KW - Humans KW - Flow Cytometry KW - Chromatography, Thin Layer KW - Cell Line KW - Liver -- pathology KW - Herbicides -- metabolism KW - Liver -- drug effects KW - Glutathione -- metabolism KW - Arsenites -- toxicity KW - Arsenites -- metabolism KW - Apoptosis -- drug effects KW - Herbicides -- toxicity KW - Cacodylic Acid -- toxicity KW - Cacodylic Acid -- metabolism KW - Glutathione -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71695227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=A+major+human+arsenic+metabolite%2C+dimethylarsinic+acid%2C+requires+reduced+glutathione+to+induce+apoptosis.&rft.au=Sakurai%2C+Teruaki%3BQu%2C+Wei%3BSakurai%2C+Masumi+H%3BWaalkes%2C+Michael+P&rft.aulast=Sakurai&rft.aufirst=Teruaki&rft.date=2002-05-01&rft.volume=15&rft.issue=5&rft.spage=629&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-05 N1 - Date created - 2002-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the mammary gland of Big Blue rats on high-and low-fat diets. AN - 71691197; 12016163 AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a food-borne mutagen and mammary gland carcinogen in female rats. A high-fat diet has been shown to increase the incidence of PhIP-induced mammary gland tumors. The current study used Big Blue rats harboring the lambda lacI mutational reporter transgene, to address whether the promotional effect of a high-fat diet is mediated via modulation in mammary gland mutagenesis. Big Blue rats were given 10 doses of PhIP (75 mg/kg, p.o.) and placed on defined low-fat (5% corn oil) or high-fat (23.5% corn oil) diet for 6 weeks prior to collecting mammary glands. The lacI mutant frequency (mean +/- standard error, n = 3 rats) was 231 +/- 15 (x10(-6)) and 193 +/- 12 (x10(-6)) in the low-and high-fat group, respectively. Values were increased 12-fold over control but were not significantly different between the two diets. In a parallel study, diet did not alter the mutant frequency induced by 7,12-dimethylbenz[a]anthracene (DMBA) (125 mg/kg, p.o.) in the mammary gland. The findings suggest that the promotion by the high-fat diet is not mediated via an increase in mutations. Consistent with the high potency of DMBA as a mammary carcinogen, the mutant frequency was 20-30% higher with DMBA than with PhIP. Sixty-nine and 56 PhIP-induced lacI mutants were sequenced from the low-and high-fat diet groups, respectively. While the percentage of various types of mutations was identical between the diet groups, some difference in the distribution of mutations along the lacI gene was observed. The mutation spectrum in the mammary gland from rats on both diets was consistent with the formation of PhIP-guanine adducts which were detected by a (32)P-post-labeling assay. Guanine base substitutions accounted for approximately 85% of all mutations irrespective of diet. Single base pair deletions at guanine occurred in 11-17% of mutants. G:C to T:A transversions were the predominant base substitution mutation accounting for 35-43% of all mutations. The majority of all guanine mutations (74%) occurred at guanine bases adjacent to another G:C pair. Five out of 125 (4%) mutations involved a guanine deletion in the 5'-GGGA-3' sequence, a PhIP signature mutation reported previously. Twelve out of 125 (10%) mutations involved the guanine base in the sequence 5'-CAG(Purine)-3' (Pu). The findings from these studies suggest that 5'-CAG(Pu)-3' is an additional characteristic target site for PhIP-guanine adduct-induced mutations in vivo in the mammary gland. JF - Carcinogenesis AU - Yu, Minshu AU - Jones, Marion Lisa AU - Gong, Min AU - Sinha, Ranjana AU - Schut, Herman A J AU - Snyderwine, Elizabeth G AD - Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, MSC-425, Bethesda, MD 20892-425, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 877 EP - 884 VL - 23 IS - 5 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - DNA Primers KW - Imidazoles KW - Mutagens KW - DNA KW - 9007-49-2 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Rats KW - Animals KW - Mutagenicity Tests KW - Base Sequence KW - Rats, Mutant Strains KW - Female KW - DNA -- drug effects KW - Imidazoles -- toxicity KW - Mammary Glands, Animal -- drug effects KW - Carcinogens -- toxicity KW - Mutagens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71691197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Mutagenicity+of+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine+%28PhIP%29+in+the+mammary+gland+of+Big+Blue+rats+on+high-and+low-fat+diets.&rft.au=Yu%2C+Minshu%3BJones%2C+Marion+Lisa%3BGong%2C+Min%3BSinha%2C+Ranjana%3BSchut%2C+Herman+A+J%3BSnyderwine%2C+Elizabeth+G&rft.aulast=Yu&rft.aufirst=Minshu&rft.date=2002-05-01&rft.volume=23&rft.issue=5&rft.spage=877&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-21 N1 - Date created - 2002-05-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers. AN - 71684585; 12013352 AB - To characterize the pharmacokinetics of indinavir in the presence and absence of milk thistle and to determine the offset of any effect of milk thistle on indinavir disposition. Prospective open-label drug interaction study. Outpatient clinic. Ten healthy volunteers. Intervention. Blood samples were collected over 8 hours after the volunteers took four doses of indinavir 800 mg every 8 hours on an empty stomach for baseline pharmacokinetics. This dosing and sampling were repeated after the subjects took milk thistle 175 mg (confirmed to contain silymarin 153 mg, the active ingredient) 3 times/day for 3 weeks. After an 11-day washout, indinavir dosing and blood sampling were repeated to evaluate the offset of any potential interaction. Indinavir concentrations were measured by using a validated high-performance liquid chromatography method. The following pharmacokinetic parameters were determined: highest concentration (Cmax), hour-0 concentration, hour-8 concentration (C8), time to reach Cmax, and area under the plasma concentration-time curve over the 8-hour dosing interval (AUC8). Milk thistle did not alter significantly the overall exposure of indinavir, as evidenced by a 9% reduction in the indinavir AUC8 after 3 weeks of dosing with milk thistle, although the least squares mean trough level (C8) was significantly decreased by 25%. Milk thistle in commonly administered dosages should not interfere with indinavir therapy in patients infected with the human immunodeficiency virus. JF - Pharmacotherapy AU - Piscitelli, Stephen C AU - Formentini, Elizabeth AU - Burstein, Aaron H AU - Alfaro, Raul AU - Jagannatha, Shyla AU - Falloon, Judith AD - Department of Pharmacy, National Institutes of Health, Bethesda, Maryland 20892-1880, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 551 EP - 556 VL - 22 IS - 5 SN - 0277-0008, 0277-0008 KW - Anti-HIV Agents KW - 0 KW - Antioxidants KW - Silymarin KW - Indinavir KW - 5W6YA9PKKH KW - Index Medicus KW - Antioxidants -- analysis KW - Antioxidants -- adverse effects KW - Area Under Curve KW - Silymarin -- adverse effects KW - Silymarin -- analysis KW - Humans KW - Adult KW - Spectrophotometry, Ultraviolet KW - Middle Aged KW - Male KW - Female KW - Chromatography, High Pressure Liquid KW - Anti-HIV Agents -- pharmacokinetics KW - Indinavir -- pharmacokinetics KW - Milk Thistle -- chemistry KW - Milk Thistle -- adverse effects KW - Phytotherapy -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71684585?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacotherapy&rft.atitle=Effect+of+milk+thistle+on+the+pharmacokinetics+of+indinavir+in+healthy+volunteers.&rft.au=Piscitelli%2C+Stephen+C%3BFormentini%2C+Elizabeth%3BBurstein%2C+Aaron+H%3BAlfaro%2C+Raul%3BJagannatha%2C+Shyla%3BFalloon%2C+Judith&rft.aulast=Piscitelli&rft.aufirst=Stephen&rft.date=2002-05-01&rft.volume=22&rft.issue=5&rft.spage=551&rft.isbn=&rft.btitle=&rft.title=Pharmacotherapy&rft.issn=02770008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-05 N1 - Date created - 2002-05-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phenformin suppresses calcium responses to glutamate and protects hippocampal neurons against excitotoxicity. AN - 71684285; 12009768 AB - Phenformin is a biguanide compound that can modulate glucose metabolism and promote weight loss and is therefore used to treat patients with type-2 diabetes. While phenformin may indirectly affect neurons by changing peripheral energy metabolism, the possibility that it directly affects neurons has not been examined. We now report that phenformin suppresses responses of hippocampal neurons to glutamate and decreases their vulnerability to excitotoxicity. Pretreatment of embryonic rat hippocampal cell cultures with phenformin protected neurons against glutamate-induced death, which was correlated with reduced calcium responses to glutamate. Immunoblot analyses showed that levels of the N-methyl-d-aspartate (NMDA) subunits NR1 and NR2A were significantly decreased in neurons exposed to phenformin, whereas levels of the AMPA receptor subunit GluR1 were unchanged. Whole-cell patch clamp analyses revealed that NMDA-induced currents were decreased, and AMPA-induced currents were unchanged in neurons pretreated with phenformin. Our data demonstrate that phenformin can protect neurons against excitotoxicity by differentially modulating levels of NMDA receptor subunits in a manner that decreases glutamate-induced calcium influx. These findings show that phenformin can modulate neuronal responses to glutamate, and suggest possible use of phenformin and related compounds in the prevention and/or treatment of neurodegenerative conditions. Copyright 2002 Elsevier Science (USA). JF - Experimental neurology AU - Lee, Jaewon AU - Chan, Sic L AU - Lu, Chengbiao AU - Lane, Mark A AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 161 EP - 167 VL - 175 IS - 1 SN - 0014-4886, 0014-4886 KW - Hypoglycemic Agents KW - 0 KW - NR1 NMDA receptor KW - NR2A NMDA receptor KW - Neuroprotective Agents KW - Receptors, AMPA KW - Receptors, N-Methyl-D-Aspartate KW - glutamate receptor ionotropic, AMPA 1 KW - Glutamic Acid KW - 3KX376GY7L KW - N-Methylaspartate KW - 6384-92-5 KW - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid KW - 77521-29-0 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Phenformin KW - DD5K7529CE KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Immunoblotting KW - Dose-Response Relationship, Drug KW - Cytoprotection KW - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Receptors, AMPA -- metabolism KW - Hippocampus -- embryology KW - Neuroprotective Agents -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Patch-Clamp Techniques KW - Cells, Cultured KW - N-Methylaspartate -- pharmacology KW - Adenosine Triphosphate -- metabolism KW - Hippocampus -- cytology KW - Calcium -- metabolism KW - Glutamic Acid -- toxicity KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Neurons -- cytology KW - Hypoglycemic Agents -- pharmacology KW - Phenformin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71684285?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+neurology&rft.atitle=Phenformin+suppresses+calcium+responses+to+glutamate+and+protects+hippocampal+neurons+against+excitotoxicity.&rft.au=Lee%2C+Jaewon%3BChan%2C+Sic+L%3BLu%2C+Chengbiao%3BLane%2C+Mark+A%3BMattson%2C+Mark+P&rft.aulast=Lee&rft.aufirst=Jaewon&rft.date=2002-05-01&rft.volume=175&rft.issue=1&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Experimental+neurology&rft.issn=00144886&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-23 N1 - Date created - 2002-05-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reproducibility of urinary phthalate metabolites in first morning urine samples. AN - 71678056; 12003755 AB - Phthalates are ubiquitous in our modern environment because of their use in plastics and cosmetic products. Phthalate monoesters--primarily monoethylhexyl phthalate and monobutyl phthalate--are reproductive and developmental toxicants in animals. Accurate measures of phthalate exposure are needed to assess their human health effects. Phthalate monoesters have a biologic half-life of approximately 12 hr, and little is known about the temporal variability and daily reproducibility of urinary measures in humans. To explore these aspects, we measured seven phthalate monoesters and creatinine concentration in two consecutive first-morning urine specimens from 46 African-American women, ages 35-49 years, residing in the Washington, DC, area in 1996-1997. We measured phthalate monoesters using high-pressure liquid chromatography followed by tandem mass spectrometry on a triple quadrupole instrument using atmospheric pressure chemical ionization. We detected four phthalate monoesters in all subjects, with median levels of 31 ng/mL for monobenzyl phthalate (mBzP), 53 ng/mL for monobutyl phthalate (mBP), 211 ng/mL for monoethyl phthalate (mEP), and 7.3 ng/mL for monoethylhexyl phthalate (mEHP). These were similar to concentrations reported for other populations using spot urine specimens. Phthalate levels did not differ between the two sampling days. The Pearson correlation coefficient between the concentrations on the 2 days was 0.8 for mBP, 0.7 for mEHP, 0.6 for mEP, and 0.5 for mBzP. These results suggest that even with the short half-lives of phthalates, women's patterns of exposure may be sufficiently stable to assign an exposure level based on a single first morning void urine measurement. JF - Environmental health perspectives AU - Hoppin, Jane A AU - Brock, John W AU - Davis, Barbara J AU - Baird, Donna D AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709-2233, USA. hoppin1@niehs.nih.gov Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 515 EP - 518 VL - 110 IS - 5 SN - 0091-6765, 0091-6765 KW - Biomarkers KW - 0 KW - Phthalic Acids KW - Index Medicus KW - Sensitivity and Specificity KW - Reproducibility of Results KW - Half-Life KW - Humans KW - Biomarkers -- analysis KW - Adult KW - Specimen Handling KW - Middle Aged KW - Urinalysis KW - Female KW - Chromatography, High Pressure Liquid KW - Environmental Exposure KW - Phthalic Acids -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71678056?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Reproducibility+of+urinary+phthalate+metabolites+in+first+morning+urine+samples.&rft.au=Hoppin%2C+Jane+A%3BBrock%2C+John+W%3BDavis%2C+Barbara+J%3BBaird%2C+Donna+D&rft.aulast=Hoppin&rft.aufirst=Jane&rft.date=2002-05-01&rft.volume=110&rft.issue=5&rft.spage=515&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-25 N1 - Date created - 2002-05-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Reprod Toxicol. 2000 Jan-Feb;14(1):13-9 [10689199] Reprod Toxicol. 2000 Jul-Aug;14(4):293-301 [10908832] Anal Chem. 2000 Sep 1;72(17):4127-34 [10994974] Environ Health Perspect. 2000 Oct;108(10):979-82 [11049818] Am J Ind Med. 2001 Jan;39(1):100-11 [11148020] Toxicology. 2001 Feb 21;159(1-2):55-68 [11250055] Food Chem Toxicol. 2001 Feb;39(2):97-108 [11267702] Am J Epidemiol. 1985 Jul;122(1):51-65 [4014201] Scand J Work Environ Health. 1985 Oct;11(5):381-7 [4071004] Environ Health Perspect. 1986 Mar;65:293-8 [3086077] Toxicol Appl Pharmacol. 1987 Apr;88(2):255-69 [3564043] J Appl Toxicol. 1992 Jun;12(3):179-83 [1629513] Toxicol Appl Pharmacol. 1992 Jul;115(1):116-23 [1321518] Int Arch Occup Environ Health. 1993;64(8):549-54 [8314612] Toxicol Appl Pharmacol. 1994 Oct;128(2):216-23 [7940536] Cancer Epidemiol Biomarkers Prev. 1995 Sep;4(6):649-54 [8547832] Cancer Epidemiol Biomarkers Prev. 1997 May;6(5):327-32 [9149892] Toxicol Sci. 1998 Dec;46(2):282-93 [10048131] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Safety, tolerability, and pharmacokinetic effects of thalidomide in patients infected with human immunodeficiency virus: AIDS Clinical Trials Group 267. AN - 71670105; 12001058 AB - Thalidomide is used to treat human immunodeficiency virus (HIV)-associated conditions, including aphthous ulcers and wasting syndrome. The safety, tolerability, and pharmacokinetics of a formulation of thalidomide with improved bioavailability in HIV-infected persons was examined in a placebo-controlled, dose-escalating phase 1 study. Subjects with CD4 cell counts of 200-500 cells/mm(3) were enrolled and randomized 3:1 in groups of 12 to receive 50, 100, or 150 mg of thalidomide or matching placebo. Two subjects who received 150 mg of drug and 2 subjects assigned placebo experienced dose-limiting toxicity. Concentrations of thalidomide in the blood increased with escalating dose, but the time to maximum concentration and clearance did not differ across dose cohorts. Previous suggestions of autoinduction of drug metabolism were not confirmed by this study. At the doses studied, thalidomide was tolerated well and had linear pharmacokinetics. JF - The Journal of infectious diseases AU - Wohl, David A AU - Aweeka, Francesca T AU - Schmitz, John AU - Pomerantz, Roger AU - Cherng, Deborah Weng AU - Spritzler, John AU - Fox, Lawrence AU - Simpson, David AU - Bell, Dawn AU - Holohan, M K AU - Thomas, Steven AU - Robinson, Wayne AU - Kaplan, Gilla AU - Teppler, Hedy AU - National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group 267 AD - Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC 27599, USA. wohl@med.unc.edu ; National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group 267 Y1 - 2002/05/01/ PY - 2002 DA - 2002 May 01 SP - 1359 EP - 1363 VL - 185 IS - 9 SN - 0022-1899, 0022-1899 KW - Anti-HIV Agents KW - 0 KW - Thalidomide KW - 4Z8R6ORS6L KW - Abridged Index Medicus KW - Index Medicus KW - Randomized Controlled Trials as Topic KW - Double-Blind Method KW - Humans KW - Adult KW - CD4 Lymphocyte Count KW - Male KW - Female KW - Thalidomide -- pharmacokinetics KW - Thalidomide -- adverse effects KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy KW - Anti-HIV Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71670105?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=Safety%2C+tolerability%2C+and+pharmacokinetic+effects+of+thalidomide+in+patients+infected+with+human+immunodeficiency+virus%3A+AIDS+Clinical+Trials+Group+267.&rft.au=Wohl%2C+David+A%3BAweeka%2C+Francesca+T%3BSchmitz%2C+John%3BPomerantz%2C+Roger%3BCherng%2C+Deborah+Weng%3BSpritzler%2C+John%3BFox%2C+Lawrence%3BSimpson%2C+David%3BBell%2C+Dawn%3BHolohan%2C+M+K%3BThomas%2C+Steven%3BRobinson%2C+Wayne%3BKaplan%2C+Gilla%3BTeppler%2C+Hedy%3BNational+Institute+of+Allergy+and+Infectious+Diseases+AIDS+Clinical+Trials+Group+267&rft.aulast=Wohl&rft.aufirst=David&rft.date=2002-05-01&rft.volume=185&rft.issue=9&rft.spage=1359&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-23 N1 - Date created - 2002-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Flavopiridol, a novel cyclin-dependent kinase inhibitor, in clinical development. AN - 71669753; 11978170 AB - To review preclinical and clinical information on flavopiridol, an inhibitor of cyclin-dependent kinases (CDKs), tested as an antitumor agent. Primary and review articles were identified by MEDLINE search (1990-June 2001). Abstracts from recent meetings were also used as source materials. Flavopiridol was reviewed with regard to its mechanisms, preclinical and clinical results, pharmacokinetics, and metabolism. Flavopiridol is an inhibitor of several CDKs and displays unique anticancer properties. In addition to direct CDK inhibition, flavopiridol also exhibited other features such as inducing apoptosis in many cancer cell lines, decreasing cyclin D1 concentration, and inhibiting angiogenesis. Preclinical xenograft models showed significant antitumor activity for flavopiridol. The regimen using 72-hour continuous infusion every 2 weeks has been most extensively applied in clinical trials, with a 1-hour infusion currently being explored to achieve higher peak concentrations. Several Phase I and II trials have been reported, with some evidence of antitumor activity noted. Further Phase I and II trials using flavopiridol as a single agent and in combination with standard chemotherapeutic regimens and various tumor types are ongoing. Flavopiridol is the first CDK inhibitor to enter clinical trials. Several Phase I and Phase II clinical trials with different regimens (72-h or 1-h infusion) have been completed. Initial clinical trials have been intriguing, but many questions remain: What is the best regimen (< or =72-h infusion)? Does optimal future development of this drug depend on the combination with other chemotherapy? What is the best combination of flavopiridol with other chemotherapy? JF - The Annals of pharmacotherapy AU - Zhai, Suoping AU - Senderowicz, Adrian M AU - Sausville, Edward A AU - Figg, William D AD - Center for Cancer Research, National Cancer Institute, Building 10 Room 5A01, 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 905 EP - 911 VL - 36 IS - 5 SN - 1060-0280, 1060-0280 KW - Antineoplastic Agents KW - 0 KW - Flavonoids KW - Piperidines KW - alvocidib KW - 45AD6X575G KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Index Medicus KW - Drug Therapy, Combination KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Kidney Neoplasms -- drug therapy KW - Infusion Pumps KW - Diarrhea -- chemically induced KW - Clinical Trials, Phase II as Topic KW - Humans KW - Clinical Trials, Phase I as Topic KW - Fatigue -- chemically induced KW - Colonic Neoplasms -- drug therapy KW - Neutropenia -- chemically induced KW - Drug Evaluation, Preclinical KW - Neoplasms -- drug therapy KW - Piperidines -- therapeutic use KW - Antineoplastic Agents -- pharmacokinetics KW - Piperidines -- pharmacokinetics KW - Flavonoids -- adverse effects KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Flavonoids -- pharmacokinetics KW - Antineoplastic Agents -- therapeutic use KW - Piperidines -- adverse effects KW - Flavonoids -- therapeutic use KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71669753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Annals+of+pharmacotherapy&rft.atitle=Flavopiridol%2C+a+novel+cyclin-dependent+kinase+inhibitor%2C+in+clinical+development.&rft.au=Zhai%2C+Suoping%3BSenderowicz%2C+Adrian+M%3BSausville%2C+Edward+A%3BFigg%2C+William+D&rft.aulast=Zhai&rft.aufirst=Suoping&rft.date=2002-05-01&rft.volume=36&rft.issue=5&rft.spage=905&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+pharmacotherapy&rft.issn=10600280&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-18 N1 - Date created - 2002-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I study of nonmyeloablative chemotherapy and adoptive transfer of autologous tumor antigen-specific T lymphocytes in patients with metastatic melanoma. AN - 71667893; 12000866 AB - This report describes a phase I clinical trial using nonmyeloablative, lympho-depleting chemotherapy in combination with adoptive immunotherapy in patients with metastatic melanoma. The chemotherapy-conditioning schedule that induced transient lymphopenia consisted of cyclophosphamide (30 or 60 mg/kg per day for 2 days) followed by fludarabine (25 mg/m(2) per day for 5 days). Immunotherapy for all patients consisted of in vitro expanded, tumor-reactive, autologous T-cell clones selected for high avidity recognition of melanoma antigens. Cohorts of three to six patients each received either no interleukin (IL)-2, low-dose IL-2 (72,000 IU/kg intravenously three times a day to a maximum of 15 doses), or high-dose IL-2 (720,000 IU/kg intravenously three times a day for a maximum of 12 doses). The toxicities associated with this treatment were transient and included neutropenia and thrombocytopenia that resolved in all patients. High dose intravenous IL-2 was better tolerated by patients after chemotherapy than during previous immunotherapy cycles without chemotherapy. No patient exhibited an objective clinical response to treatment, although five patients demonstrated mixed responses or transient shrinkage of metastatic deposits. This study established a nonmyeloablative-conditioning regimen that could be safely administered in conjunction with adoptive T-cell transfer and IL-2 in patients with metastatic melanoma. JF - Journal of immunotherapy (Hagerstown, Md. : 1997) AU - Dudley, Mark E AU - Wunderlich, John R AU - Yang, James C AU - Hwu, Patrick AU - Schwartzentruber, Douglas J AU - Topalian, Suzanne L AU - Sherry, Richard M AU - Marincola, Francesco M AU - Leitman, Susan F AU - Seipp, Claudia A AU - Rogers-Freezer, Linda AU - Morton, Kathleen E AU - Nahvi, Azam AU - Mavroukakis, Sharon A AU - White, Donald E AU - Rosenberg, Steven A AD - Surgery Branch, National Cancer Institute, Building 10, Room 2B08, 9000 Rockville Pike, Bethesda, MD 20892, USA. Mark_Dudley@nih.gov PY - 2002 SP - 243 EP - 251 VL - 25 IS - 3 SN - 1524-9557, 1524-9557 KW - Antigens, Neoplasm KW - 0 KW - Interleukin-2 KW - Index Medicus KW - Interleukin-2 -- therapeutic use KW - Humans KW - Adult KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Melanoma -- secondary KW - Immunotherapy, Adoptive KW - Melanoma -- therapy KW - Antigens, Neoplasm -- immunology KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71667893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.atitle=A+phase+I+study+of+nonmyeloablative+chemotherapy+and+adoptive+transfer+of+autologous+tumor+antigen-specific+T+lymphocytes+in+patients+with+metastatic+melanoma.&rft.au=Dudley%2C+Mark+E%3BWunderlich%2C+John+R%3BYang%2C+James+C%3BHwu%2C+Patrick%3BSchwartzentruber%2C+Douglas+J%3BTopalian%2C+Suzanne+L%3BSherry%2C+Richard+M%3BMarincola%2C+Francesco+M%3BLeitman%2C+Susan+F%3BSeipp%2C+Claudia+A%3BRogers-Freezer%2C+Linda%3BMorton%2C+Kathleen+E%3BNahvi%2C+Azam%3BMavroukakis%2C+Sharon+A%3BWhite%2C+Donald+E%3BRosenberg%2C+Steven+A&rft.aulast=Dudley&rft.aufirst=Mark&rft.date=2002-05-01&rft.volume=25&rft.issue=3&rft.spage=243&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.issn=15249557&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-03 N1 - Date created - 2002-05-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Trends Immunol. 2001 Oct;22(10):564-71 [11574281] J Immunother. 2001 Jul-Aug;24(4):363-73 [11565838] J Immunol. 1975 Jul;115(1):234-8 [1080165] N Engl J Med. 1979 May 10;300(19):1068-73 [34792] J Exp Med. 1982 Apr 1;155(4):1063-74 [6460831] Science. 1986 Sep 19;233(4770):1318-21 [3489291] J Immunol Methods. 1987 Aug 24;102(1):127-41 [3305708] J Exp Med. 1990 Jan 1;171(1):249-63 [2295878] J Immunol Methods. 1990 Apr 17;128(2):189-201 [1691237] Cancer. 1994 Mar 15;73(6):1731-7 [8156501] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9 [8170938] J Natl Cancer Inst. 1994 Aug 3;86(15):1159-66 [8028037] J Immunol. 1995 Apr 15;154(8):3961-8 [7706734] N Engl J Med. 1995 Oct 19;333(16):1038-44 [7675046] J Immunol. 1996 Nov 1;157(9):4079-86 [8892642] Curr Opin Immunol. 1996 Oct;8(5):674-80 [8902393] Immunol Rev. 1997 Dec;160:91-102 [9476668] Nat Med. 1998 Mar;4(3):321-7 [9500606] Blood. 1998 Apr 15;91(8):2925-34 [9531603] Blood. 1998 Sep 1;92(5):1549-55 [9716582] Cancer J Sci Am. 2000 Feb;6 Suppl 1:S2-7 [10685650] J Immunol. 1999 Dec 1;163(11):6292-300 [10570323] J Immunother. 1999 Jul;22(4):288-98 [10404430] Cancer J Sci Am. 2000 Feb;6 Suppl 1:S11-4 [10685652] J Immunother. 2000 May-Jun;23(3):387-92 [10838668] N Engl J Med. 2000 Sep 14;343(11):750-8 [10984562] Cancer J. 2000 Mar-Apr;6(2):69-77 [11069222] Cancer Immunol Immunother. 2001 Mar;50(1):3-15 [11315507] J Exp Med. 2001 Jun 4;193(11):1285-94 [11390435] J Exp Med. 2001 Jun 4;193(11):1295-302 [11390436] J Exp Med. 2001 Jun 4;193(11):1303-10 [11390437] Blood. 2001 Nov 1;98(9):2736-44 [11675346] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insulin-like growth factor-1 inscribes a gene expression profile for angiogenic factors and cancer progression in breast epithelial cells. AN - 71650104; 11988840 AB - Activation of the insulin-like growth factor-1 receptor (IGF-1R) by IGF-1 is associated with the risk and progression of many types of cancer, although despite this it remains unclear how activated IGF-1R contributes to cancer progression. In this study, gene expression changes elicited by IGF-1 were profiled in breast epithelial cells. We noted that many genes are functionally linked to cancer progression and angiogenesis. To validate some of the changes observed, the RNA and/or protein was confirmed for c-fos, cytochrome P450 1A1, cytochrome P450 1B1, interleukin-1 beta, fas ligand, vascular endothelial growth factor, and urokinase plasminogen activator. Nuclear proteins were also temporally monitored to address how gene expression changes were regulated. We found that IGF-1 stimulated the nuclear translocation of phosphorylated AKT, hypoxic-inducible factor-1 alpha, and phosphorylated cAMP-responsive element-binding protein, which correlated with temporal changes in gene expression. Next, the promoter regions of IGF-1-regulated genes were searched in silico. The promoters of genes that clustered together had similar regulatory regions. In summary, IGF-1 inscribes a gene expression profile relevant to cancer progression, and this study provides insight into the mechanism(s) whereby some of these changes occur. JF - Neoplasia (New York, N.Y.) AU - Oh, J S AU - Kucab, J E AU - Bushel, P R AU - Martin, K AU - Bennett, L AU - Collins, J AU - DiAugustine, R P AU - Barrett, J C AU - Afshari, C A AU - Dunn, S E AD - Laboratory of Molecular Carcinogenesis, Hormones and Cancer Group, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, USA. PY - 2002 SP - 204 EP - 217 VL - 4 IS - 3 SN - 1522-8002, 1522-8002 KW - Cyclic AMP Response Element-Binding Protein KW - 0 KW - Endothelial Growth Factors KW - FASLG protein, human KW - Fas Ligand Protein KW - Lymphokines KW - Membrane Glycoproteins KW - RNA, Messenger KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Urokinase-Type Plasminogen Activator KW - EC 3.4.21.73 KW - Index Medicus KW - Lymphokines -- metabolism KW - Oligonucleotide Array Sequence Analysis KW - Cell Nucleus -- metabolism KW - Humans KW - Disease Progression KW - Reverse Transcriptase Polymerase Chain Reaction KW - Models, Biological KW - Urokinase-Type Plasminogen Activator -- metabolism KW - Promoter Regions, Genetic KW - Blotting, Western KW - Cyclic AMP Response Element-Binding Protein -- metabolism KW - RNA, Messenger -- metabolism KW - Phosphorylation KW - Endothelial Growth Factors -- metabolism KW - Time Factors KW - Signal Transduction KW - Cell Line KW - Membrane Glycoproteins -- metabolism KW - Insulin-Like Growth Factor I -- genetics KW - Insulin-Like Growth Factor I -- biosynthesis KW - Gene Expression Regulation, Neoplastic KW - Neovascularization, Pathologic KW - Epithelium -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71650104?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neoplasia+%28New+York%2C+N.Y.%29&rft.atitle=Insulin-like+growth+factor-1+inscribes+a+gene+expression+profile+for+angiogenic+factors+and+cancer+progression+in+breast+epithelial+cells.&rft.au=Oh%2C+J+S%3BKucab%2C+J+E%3BBushel%2C+P+R%3BMartin%2C+K%3BBennett%2C+L%3BCollins%2C+J%3BDiAugustine%2C+R+P%3BBarrett%2C+J+C%3BAfshari%2C+C+A%3BDunn%2C+S+E&rft.aulast=Oh&rft.aufirst=J&rft.date=2002-05-01&rft.volume=4&rft.issue=3&rft.spage=204&rft.isbn=&rft.btitle=&rft.title=Neoplasia+%28New+York%2C+N.Y.%29&rft.issn=15228002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-08 N1 - Date created - 2002-05-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Clin Invest. 1994 Sep;94(3):1235-42 [8083365] J Natl Cancer Inst. 1995 Feb 1;87(3):213-9 [7535859] Biochem Biophys Res Commun. 1995 Sep 14;214(2):475-81 [7677754] Am J Pathol. 1995 Dec;147(6):1823-39 [7495306] Nucleic Acids Res. 1995 Nov 25;23(22):4542-50 [8524640] Nature. 1995 Dec 21-28;378(6559):785-9 [8524413] Cancer Res. 1996 Apr 1;56(7):1509-11 [8603394] Cell. 1996 Aug 9;86(3):353-64 [8756718] Science. 1997 Jan 31;275(5300):661-5 [9005851] Science. 1997 Jan 31;275(5300):628-30 [9019819] Oncogene. 1997 Jun 12;14(23):2825-34 [9190899] Cancer Res. 1997 Nov 1;57(21):4667-72 [9354418] Science. 1997 Oct 24;278(5338):680-6 [9381177] Cancer. 1997 Nov 15;80(10):1945-53 [9366297] Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12886-91 [9371770] J Biol Chem. 1997 Dec 12;272(50):31515-24 [9395488] Science. 1998 Jan 23;279(5350):563-6 [9438850] J Biol Chem. 1998 Mar 13;273(11):5997-6000 [9497311] Gene. 1998 Mar 27;210(1):1-7 [9524203] Lancet. 1998 May 9;351(9113):1393-6 [9593409] Curr Biol. 1998 Jun 4;8(12):684-91 [9637919] Cancer Res. 1999 Nov 1;59(21):5464-70 [10554019] Circ Res. 2000 Jan 7-21;86(1):4-5 [10625297] Mol Carcinog. 2000 Jan;27(1):10-7 [10642432] Gene. 2000 Mar 7;245(1):49-57 [10713444] Cancer Res. 2000 Mar 15;60(6):1541-5 [10749120] Mol Cell Biol. 2000 Jun;20(12):4320-7 [10825195] FEBS Lett. 2000 Jul 14;477(1-2):27-32 [10899305] Cancer Res. 2000 Jul 15;60(14):3744-8 [10919644] Nature. 2000 Aug 17;406(6797):747-52 [10963602] Br J Cancer. 2000 Dec;83(11):1473-9 [11076656] J Biol Chem. 2000 Dec 8;275(49):38139-50 [10973960] Brain Res Mol Brain Res. 2000 Dec 8;84(1-2):150-7 [11113543] Cancer Res. 2000 Dec 15;60(24):6890-4 [11156387] Biochem Pharmacol. 2001 Mar 1;61(5):605-12 [11239504] Cancer Res. 2001 Feb 15;61(4):1367-74 [11245436] Cell Signal. 2001 Jan;13(1):23-7 [11257444] J Clin Oncol. 2001 Apr 15;19(8):2189-200 [11304771] J Biol Chem. 2001 May 4;276(18):15519-26 [11278455] Bioinformatics. 2001 Jun;17(6):564-5 [11395436] Cancer Res. 2001 Aug 1;61(15):5885-94 [11479230] Oncogene. 2001 Aug 30;20(38):5331-40 [11536045] Gene. 1989 Jan 30;75(1):3-11 [2542132] Mol Cell Biol. 1990 Feb;10(2):464-73 [2153917] Proc Natl Acad Sci U S A. 1991 May 1;88(9):3720-4 [1827203] Breast Cancer Res Treat. 1992;22(1):101-6 [1421419] Mol Pharmacol. 1993 Sep;44(3):560-8 [8396716] Cancer Res. 1994 May 15;54(10):2552-5 [8168078] Cancer Res. 1994 Apr 15;54(8):2218-22 [8174129] Cancer Epidemiol Biomarkers Prev. 2001 Mar;10(3):243-8 [11303594] J Biol Chem. 1998 Jul 31;273(31):19834-9 [9677418] Cancer Res. 1998 Aug 1;58(15):3353-61 [9699666] EMBO J. 1998 Sep 1;17(17):5085-94 [9724644] Epidemiology. 1998 Sep;9(5):570-3 [9730040] Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11211-6 [9736715] J Biol Chem. 1998 Oct 2;273(40):26130-7 [9748294] J Biol Chem. 1998 Dec 4;273(49):32377-9 [9829964] Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8 [9843981] FASEB J. 1999 Jan;13(1):9-22 [9872925] Clin Cancer Res. 1997 Nov;3(11):2025-32 [9815593] J Biol Chem. 1999 Jan 29;274(5):2829-37 [9915817] J Natl Cancer Inst. 1999 Jan 20;91(2):151-6 [9923856] Cell. 1999 Mar 19;96(6):857-68 [10102273] J Natl Cancer Inst. 1999 Apr 7;91(7):620-5 [10203281] Mol Carcinog. 1999 Mar;24(3):153-9 [10204799] Nature. 1999 Apr 15;398(6728):630-4 [10217147] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol, breastfeeding, and development at 18 months. AN - 71645934; 11986478 AB - We aimed to replicate a previous study of 1-year-olds that reported a deficit in motor development associated with moderate alcohol use during lactation, using a different but comparable population. The mental development of 915 18-month-old toddlers from a random sample of a longitudinal population-based study in the United Kingdom was measured using the Griffiths Developmental Scales. Frequent self-administered questionnaires during and after pregnancy provided maternal data. The dose of alcohol available to the lactating infant was obtained by multiplying the alcohol intake of the mother by the proportion of breast milk in the infant's diet. We compared this dose with the Griffiths Scales of Mental Development, taking into account potentially confounding variables. Three of the Griffiths scales increased slightly but significantly with increasing infant alcohol exposure; there was no association in the remaining 2 or average of the scales. We were unable to replicate the earlier deficit in motor skills associated with lactation alcohol use. One reason may be that the dose of alcohol reaching the lactating infant is small, and tests of infants and toddlers have limited ability to pick up small effects. Studies of older children may resolve the question of the safety of drinking while nursing. JF - Pediatrics AU - Little, Ruth E AU - Northstone, Kate AU - Golding, Jean AU - ALSPAC Study Team AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. little1@niehs.nih.gov ; ALSPAC Study Team Y1 - 2002/05// PY - 2002 DA - May 2002 SP - E72 VL - 109 IS - 5 KW - Ethanol KW - 3K9958V90M KW - Abridged Index Medicus KW - Index Medicus KW - Maternal Behavior KW - Infant KW - Motor Skills Disorders -- etiology KW - United Kingdom -- epidemiology KW - Humans KW - Infant, Newborn KW - Motor Skills Disorders -- epidemiology KW - Female KW - Lactation -- physiology KW - Lactation -- drug effects KW - Ethanol -- adverse effects KW - Breast Feeding -- adverse effects KW - Alcohol Drinking -- adverse effects KW - Child Development -- drug effects KW - Child Development -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71645934?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=Alcohol%2C+breastfeeding%2C+and+development+at+18+months.&rft.au=Little%2C+Ruth+E%3BNorthstone%2C+Kate%3BGolding%2C+Jean%3BALSPAC+Study+Team&rft.aulast=Little&rft.aufirst=Ruth&rft.date=2002-05-01&rft.volume=109&rft.issue=5&rft.spage=E72&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=1098-4275&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-22 N1 - Date created - 2002-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MCP-1 expression in endotoxin-induced uveitis. AN - 71640167; 11980865 AB - Monocyte chemoattractant protein (MCP)-1 (CCL-2) is a chemokine with chemoattractant properties for monocytes, memory T cells, natural killer cells, mast cells, and basophils. To delineate the role played by MCP-1 in acute anterior uveitis, a common ocular inflammation, MCP-1(-/-) mice and wild-type matched control mice were analyzed for the development of endotoxin-induced uveitis (EIU) in response to subcutaneous injection of a sublethal dose of lipopolysaccharide (LPS). EIU was induced in MCP-1(-/-) and wild-type control mice by a single subcutaneous injection of Salmonella typhimurium LPS endotoxin at day 0. Alternatively, MCP-1(-/-) mice were injected subcutaneously with LPS plus recombinant MCP-1 at day 0 and with recombinant MCP-1 6 hours later. Mice were killed at day 1 or 3 after injection. Serum levels of IL-1alpha, IL-1beta, IL-6, IFN-gamma, TNF-alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage inflammatory protein (MIP)-1alpha, MIP-2, regulated on activation normal T-cell expressed and secreted (RANTES), and MCP-1 were determined by ELISA. Eyes were collected and analyzed histologically and by RT-PCR for MCP-1, IFN-gamma, IL-6, TNF-alpha, beta-actin, MCP-5, RANTES, KC, inflammatory protein (IP)-10, and toll-like receptor (TLR)-4. EIU was strongly reduced in MCP-1(-/-) mice compared with wild-type control mice. The number of ocular inflammatory cells was significantly reduced. Moreover, intraocular IFN-gamma transcription was increased. EIU was induced in MCP-1(-/-) mice by co-administration of recombinant rat MCP-1 and LPS. Data indicate that MCP-1 plays a crucial role in the induction of EIU. MCP-1 may be a new therapeutic strategy for acute anterior uveitis. JF - Investigative ophthalmology & visual science AU - Tuaillon, Nadine AU - Shen, De Fen AU - Berger, Ravi B AU - Lu, Bao AU - Rollins, Barrett J AU - Chan, Chi-Chao AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bldg. 10 Room 10-N-103, 10 Center Drive, Bethesda, MD 20892-1857, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 1493 EP - 1498 VL - 43 IS - 5 SN - 0146-0404, 0146-0404 KW - Chemokine CCL2 KW - 0 KW - Cytokines KW - Lipopolysaccharides KW - RNA, Messenger KW - Index Medicus KW - Cytokines -- blood KW - Animals KW - Cytokines -- genetics KW - RNA, Messenger -- metabolism KW - Mice, Inbred C57BL KW - Enzyme-Linked Immunosorbent Assay KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Male KW - Female KW - Mice, Knockout KW - Chemokine CCL2 -- genetics KW - Uveitis, Anterior -- chemically induced KW - Uveitis, Anterior -- pathology KW - Lipopolysaccharides -- toxicity KW - Salmonella typhimurium KW - Chemokine CCL2 -- physiology KW - Uveitis, Anterior -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71640167?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigative+ophthalmology+%26+visual+science&rft.atitle=MCP-1+expression+in+endotoxin-induced+uveitis.&rft.au=Tuaillon%2C+Nadine%3BShen%2C+De+Fen%3BBerger%2C+Ravi+B%3BLu%2C+Bao%3BRollins%2C+Barrett+J%3BChan%2C+Chi-Chao&rft.aulast=Tuaillon&rft.aufirst=Nadine&rft.date=2002-05-01&rft.volume=43&rft.issue=5&rft.spage=1493&rft.isbn=&rft.btitle=&rft.title=Investigative+ophthalmology+%26+visual+science&rft.issn=01460404&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-03 N1 - Date created - 2002-04-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dextromethorphan and memantine in painful diabetic neuropathy and postherpetic neuralgia: efficacy and dose-response trials. AN - 71639683; 11981142 AB - There are few repeated dose-controlled trials of N-methyl-d-aspartate glutamate receptor antagonists in patients with neuropathic pain. The authors sought to evaluate two low-affinity N-methyl-d-aspartate antagonists using a novel two-stage design. The authors studied patients with painful diabetic neuropathy (DN) and postherpetic neuralgia (PHN) in two crossover trials: (1) efficacy trial (dextromethorphan vs. memantine vs. active placebo [lorazepam]) and (2) dose-response trial of the preferred active drug in responders from the first study (0% vs. 25% vs. 50% vs. 100% of each patient's maximally tolerated dose). Pain intensity was measured on a 20-point scale. Nineteen of 23 DN patients and 17 of 21 PHN patients completed the efficacy trial. Median doses for DN and PHN were 400 and 400 mg/day dextromethorphan, 55 and 35 mg/day memantine, and 1.8 and 1.2 mg/day lorazepam. In the efficacy trial, among patients with DN, dextromethorphan reduced pain intensity by a mean of 33% from baseline, memantine reduced pain intensity by a mean of 17%, and lorazepam reduced pain intensity by a mean of 16%; the proportions of subjects achieving greater than moderate pain relief were 68% with dextromethorphan, 47% with memantine, and 37% with lorazepam. Mean reductions in pain intensity in patients with PHN were 6% with dextromethorphan, 2% with memantine, and 0% with lorazepam. No comparison with placebo reached statistical significance in the efficacy trial. In the 10 DN subjects who responded to dextromethorphan, there was a significant dose-response effect on pain intensity (P = 0.035), with the highest dose significantly better than that of lorazepam (P = 0.03). Dextromethorphan is effective in a dose-related fashion in selected patients with DN. This was not true of PHN, suggesting a difference in pain mechanisms. Selective approaches to pain-relevant N-methyl-d-aspartate receptors are warranted. JF - Anesthesiology AU - Sang, Christine N AU - Booher, Susan AU - Gilron, Ian AU - Parada, Suzan AU - Max, Mitchell B AD - Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. csang@partners.org Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 1053 EP - 1061 VL - 96 IS - 5 SN - 0003-3022, 0003-3022 KW - Excitatory Amino Acid Antagonists KW - 0 KW - Receptors, N-Methyl-D-Aspartate KW - Dextromethorphan KW - 7355X3ROTS KW - Memantine KW - W8O17SJF3T KW - Abridged Index Medicus KW - Index Medicus KW - Endpoint Determination KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Treatment Outcome KW - Quality of Life KW - Pain Measurement -- drug effects KW - Aged KW - Middle Aged KW - Male KW - Female KW - Pain -- drug therapy KW - Dextromethorphan -- administration & dosage KW - Diabetic Neuropathies -- complications KW - Neuralgia -- psychology KW - Memantine -- therapeutic use KW - Pain -- psychology KW - Excitatory Amino Acid Antagonists -- administration & dosage KW - Memantine -- adverse effects KW - Dextromethorphan -- therapeutic use KW - Herpesviridae Infections -- complications KW - Pain -- etiology KW - Neuralgia -- drug therapy KW - Neuralgia -- etiology KW - Memantine -- administration & dosage KW - Dextromethorphan -- adverse effects KW - Excitatory Amino Acid Antagonists -- therapeutic use KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Excitatory Amino Acid Antagonists -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71639683?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anesthesiology&rft.atitle=Dextromethorphan+and+memantine+in+painful+diabetic+neuropathy+and+postherpetic+neuralgia%3A+efficacy+and+dose-response+trials.&rft.au=Sang%2C+Christine+N%3BBooher%2C+Susan%3BGilron%2C+Ian%3BParada%2C+Suzan%3BMax%2C+Mitchell+B&rft.aulast=Sang&rft.aufirst=Christine&rft.date=2002-05-01&rft.volume=96&rft.issue=5&rft.spage=1053&rft.isbn=&rft.btitle=&rft.title=Anesthesiology&rft.issn=00033022&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-29 N1 - Date created - 2002-04-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression and regulation of nonsteroidal anti-inflammatory drug-activated gene (NAG-1) in human and mouse tissue. AN - 71637001; 11984525 AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) induce NSAID-activated gene 1 (NAG-1), which has proapoptotic and antitumorigenic activities. However, NAG-1 expression and its relationship with apoptosis in human and mouse intestinal tract have not been determined. NAG-1 expression in human and mouse tissue was determined by immunohistochemistry, and apoptosis was estimated by in situ apoptosis detection. Apoptosis in NAG-1 overexpressing HCT-116 cells was examined with flow cytometry after cell sorting by green fluorescence protein. NAG-1 regulation in mouse cells was examined by Northern blot analysis, comparing sulindac-treated and nontreated mice. Apoptosis was higher in NAG-1 overexpressing cells compared with controls. Human NAG-1 protein was localized to the colonic surface epithelium where cells undergo apoptosis, and higher expression was observed in the normal surface epithelium than in most of the tumors. This localization and lower expression in tumors was similar to that in the Min mouse, in which NSAIDs were also shown to regulate the expression of NAG-1 in mouse cells. Sulindac treatment of mice increased the NAG-1 expression in the colon and liver. Based on these results, we propose that NAG-1 acts as a mediator of apoptosis in intestinal cells and may contribute to cancer chemoprevention by NSAIDs. JF - Gastroenterology AU - Kim, Kyung-Su AU - Baek, Seung Joon AU - Flake, Gordon P AU - Loftin, Charles D AU - Calvo, Benjamin F AU - Eling, Thomas E AD - Laboratories of Molecular Carcinogenesis, Experimental Pathology, and Environmental Carcinogenesis/Mutagenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 1388 EP - 1398 VL - 122 IS - 5 SN - 0016-5085, 0016-5085 KW - Cytokines KW - 0 KW - GDF15 protein, human KW - Gdf15 protein, mouse KW - Growth Differentiation Factor 15 KW - Sulindac KW - 184SNS8VUH KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Aged, 80 and over KW - Humans KW - Adult KW - Sulindac -- pharmacology KW - Mice, Inbred C57BL KW - Aged KW - Middle Aged KW - Mice KW - Male KW - Female KW - Cytokines -- analysis KW - Cytokines -- genetics KW - Apoptosis KW - Colon -- chemistry KW - Gene Expression Regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71637001?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gastroenterology&rft.atitle=Expression+and+regulation+of+nonsteroidal+anti-inflammatory+drug-activated+gene+%28NAG-1%29+in+human+and+mouse+tissue.&rft.au=Kim%2C+Kyung-Su%3BBaek%2C+Seung+Joon%3BFlake%2C+Gordon+P%3BLoftin%2C+Charles+D%3BCalvo%2C+Benjamin+F%3BEling%2C+Thomas+E&rft.aulast=Kim&rft.aufirst=Kyung-Su&rft.date=2002-05-01&rft.volume=122&rft.issue=5&rft.spage=1388&rft.isbn=&rft.btitle=&rft.title=Gastroenterology&rft.issn=00165085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-23 N1 - Date created - 2002-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional and genomic implications of global gene expression profiles in cell lines from human hepatocellular cancer. AN - 71635558; 11981763 AB - Global gene expression profiles in cancer have impacted both classification of tumors and definition of molecular pathways in neoplasia. To explore the possibility of employing human tumor cell lines to obtain information on the functional genomics of the early stages of tumorigenesis, we have characterized variation in gene-expression patterns in a cytogenetically well-defined series of cell lines derived from human hepatocellular carcinoma (HCC). Microarrays containing 6,720 sequence-verified human cDNAs were used in this study. Nineteen well-characterized HCC cell lines were analyzed, and a nontumorigenic liver-derived epithelial cell line (Chang) was used as a reference. Each sample was examined at least twice by switching fluorescent dyes, Cy-5 and Cy-3, and average values of 2 experiments on each sample were used for further analysis. Analysis of the clustered data revealed 2 distinctive subtypes of gene-expression patterns among the 19 cell lines, suggesting a degree of heterogeneity among the gene-expression profiles of cell lines. Remarkably, expression of alpha-fetoprotein (AFP) was highly correlated with the molecular subtypes of HCC. Although the 3 most distinctive gene-expression modules represented the signatures of 2 different subgroups of HCC, most of the cell lines shared many coexpressed genes. However, sets of coexpressed genes that are specific for the subtypes of HCC were identified. Furthermore, our results indicate that the comparison between gene-expression patterns and structural alterations in chromosomes is potentially useful in identifying genes critical in early stages of tumorigenesis. In conclusion, these results not only identified unrecognized subtypes of HCC, but also provided potential molecular markers for each subtype that can be useful for diagnostic and/or therapeutic purposes. JF - Hepatology (Baltimore, Md.) AU - Lee, Ju-Seog AU - Thorgeirsson, Snorri S AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4258, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 1134 EP - 1143 VL - 35 IS - 5 SN - 0270-9139, 0270-9139 KW - Index Medicus KW - Tumor Cells, Cultured KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Gene Expression Regulation, Neoplastic KW - Genome, Human KW - Carcinoma, Hepatocellular -- genetics KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71635558?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Functional+and+genomic+implications+of+global+gene+expression+profiles+in+cell+lines+from+human+hepatocellular+cancer.&rft.au=Lee%2C+Ju-Seog%3BThorgeirsson%2C+Snorri+S&rft.aulast=Lee&rft.aufirst=Ju-Seog&rft.date=2002-05-01&rft.volume=35&rft.issue=5&rft.spage=1134&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=02709139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-24 N1 - Date created - 2002-04-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer in Korean war navy technicians: mortality survey after 40 years. AN - 71634338; 11978584 AB - This study reports on over 40 years of mortality follow-up of 40,581 Navy veterans of the Korean War with potential exposure to high-intensity radar. The cohort death rates were compared with mortality rates for White US men using standardized mortality ratios, and the death rates for men in occupations considered a priori to have high radar exposure were compared with the rates for men in low-exposure occupations using Poisson regression. Deaths from all diseases and all cancers were significantly below expectation overall and for the 20,021 sailors with high radar exposure potential. There was no evidence of increased brain cancer in the entire cohort (standardized mortality ratio (SMR) = 0.9, 95% confidence interval (CI): 0.7, 1.1) or in high-exposure occupations (SMR = 0.7, 95% CI: 0.5, 1.0). Testicular cancer deaths also occurred less frequently than expected in the entire cohort and high-exposure occupations. Death rates for several smoking-related diseases were significantly lower in the high-exposure occupations. Nonlymphocytic leukemia was significantly elevated among men in high-exposure occupations but in only one of the three high-exposure occupations, namely, electronics technicians in aviation squadrons (SMR = 2.2, 95% CI: 1.3, 3.7). Radar exposure had little effect on mortality in this cohort of US Navy veterans. JF - American journal of epidemiology AU - Groves, Frank D AU - Page, William F AU - Gridley, Gloria AU - Lisimaque, Laure AU - Stewart, Patricia A AU - Tarone, Robert E AU - Gail, Mitchell H AU - Boice, John D AU - Beebe, Gilbert W AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. grovesf@musc.edu Y1 - 2002/05/01/ PY - 2002 DA - 2002 May 01 SP - 810 EP - 818 VL - 155 IS - 9 SN - 0002-9262, 0002-9262 KW - Index Medicus KW - Warfare KW - Humans KW - Cohort Studies KW - Adult KW - Aged KW - Middle Aged KW - Poisson Distribution KW - Korea KW - United States -- epidemiology KW - Male KW - Cause of Death KW - Veterans KW - Microwaves -- adverse effects KW - Neoplasms -- mortality KW - Occupational Exposure -- adverse effects KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71634338?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+epidemiology&rft.atitle=Cancer+in+Korean+war+navy+technicians%3A+mortality+survey+after+40+years.&rft.au=Groves%2C+Frank+D%3BPage%2C+William+F%3BGridley%2C+Gloria%3BLisimaque%2C+Laure%3BStewart%2C+Patricia+A%3BTarone%2C+Robert+E%3BGail%2C+Mitchell+H%3BBoice%2C+John+D%3BBeebe%2C+Gilbert+W&rft.aulast=Groves&rft.aufirst=Frank&rft.date=2002-05-01&rft.volume=155&rft.issue=9&rft.spage=810&rft.isbn=&rft.btitle=&rft.title=American+journal+of+epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-23 N1 - Date created - 2002-04-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Epidemiol. 2003 Feb 1;157(3):279; author reply 279 [12543630] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - BK virus regulatory region rearrangements in brain and cerebrospinal fluid from a leukemia patient with tubulointerstitial nephritis and meningoencephalitis. AN - 71632911; 11979356 AB - BK virus (BKV) was recovered by polymerase chain reaction (PCR) from brain, kidney, lung, urine, and cerebrospinal fluid (CSF) of a fatal case of BKV tubulointerstitial nephritis with dissemination to lung and brain. Viral regulatory regions in PCR-amplified urine and the lung samples were identical to the archetypal structure, WWT. In the brain and CSF, a rearranged sequence predominated, however. A 94-bp deletion preceded a 71-bp tandem duplication because the same 94-bp segment was deleted from both copies. PCR-amplified regulatory region products were cloned and sequenced to define further the extent of the rearranged structures. Two kidney clones were archetypal, whereas two others were rearranged differently from the brain and from each other. In contrast to the brain clones, the kidney rearrangements seemed to involve deletion after duplication. Three of four brain clones sequenced were identical to the rearrangement found to dominate in the PCR product. A fourth clone showed two short deletions without any duplication. The four CSF clones all showed rearrangements identical to that which was amplified by PCR from CSF and brain. This represents the first molecular analysis of a BKV strain obtained from a central nervous system infection, and it reveals regulatory region rearrangements reminiscent of those described in JC virus from brains with progressive multifocal leukoencephalopathy. We suggest that the presence in the CSF of BKV with a dominant rearranged regulatory region may be useful in the diagnosis of BKV meningoencephalitis secondary to BKV nephritis. Copyright 2002 by the National Kidney Foundation, Inc. JF - American journal of kidney diseases : the official journal of the National Kidney Foundation AU - Stoner, Gerald L AU - Alappan, Raj AU - Jobes, David V AU - Ryschkewitsch, Caroline F AU - Landry, Marie L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4126, USA. stonerg@ninds.nih.gov Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 1102 EP - 1112 VL - 39 IS - 5 KW - Index Medicus KW - Tumor Virus Infections -- cerebrospinal fluid KW - Tumor Virus Infections -- diagnosis KW - Humans KW - Polyomavirus Infections -- cerebrospinal fluid KW - Urine -- virology KW - Tumor Virus Infections -- genetics KW - Lung -- virology KW - Cloning, Molecular KW - Kidney -- virology KW - Base Sequence KW - Molecular Sequence Data KW - Polyomavirus Infections -- diagnosis KW - Middle Aged KW - Male KW - Polyomavirus Infections -- genetics KW - Regulatory Sequences, Nucleic Acid -- genetics KW - BK Virus -- genetics KW - Meningoencephalitis -- virology KW - Gene Rearrangement -- genetics KW - Leukemia -- cerebrospinal fluid KW - Meningoencephalitis -- genetics KW - Meningoencephalitis -- cerebrospinal fluid KW - BK Virus -- isolation & purification KW - Nephritis, Interstitial -- virology KW - Nephritis, Interstitial -- cerebrospinal fluid KW - Brain -- virology KW - Leukemia -- virology KW - Nephritis, Interstitial -- genetics KW - Leukemia -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71632911?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+kidney+diseases+%3A+the+official+journal+of+the+National+Kidney+Foundation&rft.atitle=BK+virus+regulatory+region+rearrangements+in+brain+and+cerebrospinal+fluid+from+a+leukemia+patient+with+tubulointerstitial+nephritis+and+meningoencephalitis.&rft.au=Stoner%2C+Gerald+L%3BAlappan%2C+Raj%3BJobes%2C+David+V%3BRyschkewitsch%2C+Caroline+F%3BLandry%2C+Marie+L&rft.aulast=Stoner&rft.aufirst=Gerald&rft.date=2002-05-01&rft.volume=39&rft.issue=5&rft.spage=1102&rft.isbn=&rft.btitle=&rft.title=American+journal+of+kidney+diseases+%3A+the+official+journal+of+the+National+Kidney+Foundation&rft.issn=1523-6838&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-20 N1 - Date created - 2002-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of mitotic spindle checkpoint protein hsMAD1 correlates with cellular proliferation and is activated by a gain-of-function p53 mutant. AN - 71632801; 11980658 AB - Human mitotic arrest deficiency protein 1, hsMAD1, is a component of the mitotic spindle assembly checkpoint (MSC) that monitors fidelity of chromosomal segregation and guards against emergence of cellular aneuploidy. Because aneuploidy is a pervasive characteristic of human cancers, understanding how MSC genes are regulated is important. Here, we have analyzed human genomic sequences upstream of the 5' most hsMAD1 coding exon and have identified a 1.5-kb fragment with promoter activity. The hsMad1 promoter, consistent with characteristics of housekeeping genes, is highly GC rich and is devoid of a TATA-box. Mutational analyses revealed a core region spanning -73 to -31 as being essential for hsMad1 transcription. Surprisingly, although MSC function, prototypically induced by microtubule inhibitors, is active selectively during mitosis, we found the hsMad1 promoter to be expressed predominantly in G1 and to respond not to microtubule inhibitor but to mitogenic stimulus. In primary, as well as transformed cells, intracellular levels of hsMAD1 correlated with the proliferative status of cells. The hsMad1 promoter was also activated preferentially by a gain-of-function p53 mutant. Taken together, our results suggest that hsMAD1 might link p53 function to the generation of cellular aneuuploidy and that heightened activation of hsMad1 by gain-of-function p53 mutants could contribute to the worse prognosis of certain cancers. JF - Cancer research AU - Iwanaga, Yoichi AU - Jeang, Kuan-Teh AD - Molecular Virology Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892-0460, USA. Y1 - 2002/05/01/ PY - 2002 DA - 2002 May 01 SP - 2618 EP - 2624 VL - 62 IS - 9 SN - 0008-5472, 0008-5472 KW - Cell Cycle Proteins KW - 0 KW - MAD1L1 protein, human KW - Mitogens KW - Nuclear Proteins KW - Phosphoproteins KW - Repressor Proteins KW - Tumor Suppressor Protein p53 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Mitogens -- pharmacology KW - HeLa Cells KW - Cell Cycle -- physiology KW - Humans KW - Cell Division -- physiology KW - Microtubules -- physiology KW - Microtubules -- drug effects KW - Transcriptional Activation KW - Cloning, Molecular KW - Promoter Regions, Genetic KW - Base Sequence KW - Tumor Cells, Cultured KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Up-Regulation KW - Repressor Proteins -- biosynthesis KW - Tumor Suppressor Protein p53 -- physiology KW - Phosphoproteins -- genetics KW - Phosphoproteins -- biosynthesis KW - Tumor Suppressor Protein p53 -- genetics KW - Repressor Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71632801?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Expression+of+mitotic+spindle+checkpoint+protein+hsMAD1+correlates+with+cellular+proliferation+and+is+activated+by+a+gain-of-function+p53+mutant.&rft.au=Iwanaga%2C+Yoichi%3BJeang%2C+Kuan-Teh&rft.aulast=Iwanaga&rft.aufirst=Yoichi&rft.date=2002-05-01&rft.volume=62&rft.issue=9&rft.spage=2618&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-31 N1 - Date created - 2002-04-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Stress-induced deoxycorticosterone-derived neurosteroids modulate GABA(A) receptor function and seizure susceptibility. AN - 71630873; 11978855 AB - Stress affects seizure susceptibility in animals and humans, but the underlying mechanisms are obscure. Here, we provide evidence that GABA(A) receptor-modulating neurosteroids derived from deoxycorticosterone (DOC) play a role in stress-related changes in seizure control. DOC, an adrenal steroid whose synthesis is enhanced during stress, undergoes sequential metabolic reduction by 5alpha-reductase and 3alpha-hydroxysteroid oxidoreductase to form 5alpha-dihydrodeoxycorticosterone (DHDOC) and allotetrahydrodeoxycorticosterone (THDOC), a GABA(A) receptor-modulating neurosteroid with anticonvulsant properties. Acute swim stress in rats significantly elevated plasma THDOC concentrations and raised the pentylenetetrazol (PTZ) seizure threshold. Small systemic doses of DOC produced comparable increases in THDOC and PTZ seizure threshold. Pretreatment with finasteride, a 5alpha-reductase inhibitor that blocks the conversion of DOC to DHDOC, reversed the antiseizure effects of stress. DOC also elevated plasma THDOC levels and protected mice against PTZ, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate, picrotoxin, and amygdala-kindled seizures in mice (ED50 values, 84-97 mg/kg). Finasteride reversed the antiseizure activity of DOC (ED50, 7.2 mg/kg); partial antagonism was also obtained with indomethacin (100 mg/kg), an inhibitor of 3alpha-hydroxysteroid oxidoreductase. Finasteride had no effect on seizure protection by DHDOC and THDOC, whereas indomethacin partially reversed DHDOC but not THDOC. DHDOC, like THDOC, potentiated GABA-activated Cl- currents in cultured hippocampal neurons ( or =1 microm), compatible with a role for DHDOC in the antiseizure activity of DOC. DOC is a mediator of the physiological effects of acute stress that could contribute to stress-induced changes in seizure susceptibility through its conversion to neurosteroids with modulatory actions on GABA(A) receptors including THDOC and possibly also DHDOC. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Reddy, Doodipala S AU - Rogawski, Michael A AD - Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/05/01/ PY - 2002 DA - 2002 May 01 SP - 3795 EP - 3805 VL - 22 IS - 9 KW - 5-alpha Reductase Inhibitors KW - 0 KW - 5-dihydrodeoxycorticosterone KW - Anti-Inflammatory Agents, Non-Steroidal KW - Convulsants KW - Enzyme Inhibitors KW - Receptors, GABA-A KW - Steroids KW - Desoxycorticosterone KW - 40GP35YQ49 KW - tetrahydrodeoxycorticosterone KW - 4AB717DP4A KW - Finasteride KW - 57GNO57U7G KW - Corticosterone KW - W980KJ009P KW - Pentylenetetrazole KW - WM5Z385K7T KW - Indomethacin KW - XXE1CET956 KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Drug Resistance KW - Corticosterone -- antagonists & inhibitors KW - Mice KW - Finasteride -- pharmacology KW - Adrenalectomy KW - Indomethacin -- pharmacology KW - Rats KW - Exercise Test KW - Disease Susceptibility -- physiopathology KW - Corticosterone -- metabolism KW - Rats, Sprague-Dawley KW - Kindling, Neurologic -- drug effects KW - Corticosterone -- analogs & derivatives KW - Enzyme Inhibitors -- pharmacology KW - Motor Activity -- drug effects KW - Corticosterone -- pharmacology KW - Drug Antagonism KW - Male KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology KW - Seizures -- chemically induced KW - Desoxycorticosterone -- metabolism KW - Stress, Physiological -- metabolism KW - Seizures -- physiopathology KW - Steroids -- antagonists & inhibitors KW - Steroids -- pharmacology KW - Receptors, GABA-A -- metabolism KW - Desoxycorticosterone -- pharmacology KW - Receptors, GABA-A -- drug effects KW - Steroids -- metabolism KW - Desoxycorticosterone -- antagonists & inhibitors KW - Desoxycorticosterone -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71630873?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Stress-induced+deoxycorticosterone-derived+neurosteroids+modulate+GABA%28A%29+receptor+function+and+seizure+susceptibility.&rft.au=Reddy%2C+Doodipala+S%3BRogawski%2C+Michael+A&rft.aulast=Reddy&rft.aufirst=Doodipala&rft.date=2002-05-01&rft.volume=22&rft.issue=9&rft.spage=3795&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-20 N1 - Date created - 2002-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recovery from osteoporosis through skeletal growth: early bone mass acquisition has little effect on adult bone density. AN - 71630107; 11923218 AB - It is often assumed that bone mineral accretion should be optimized throughout childhood to maximize peak bone mass. In contrast, we hypothesized that bone mineral acquisition early in life would have little or no effect on adult bone mass because many areas of the juvenile skeleton are replaced in toto through skeletal growth. To test this hypothesis, we induced osteoporosis by administering dexamethasone to 5-week-old rabbits for 5 weeks and then allowed them to recover for 16 weeks. Tibial bone mineral density (ash weight/volume) was decreased in the dexamethasone-treated animals at the end of treatment but recovered completely. Bone structure in the femur was assessed by histomorphometry. Trabecular and cortical bone in the distal metaphysis was made osteoporotic by dexamethasone, but was then replaced through endochondral bone formation and recovered. Periosteal bone formation rate in the diaphysis was decreased during dexamethasone treatment but afterwards rebounded above controls and normalized cortical width. Our data suggest that bone mineral acquisition early in life has little effect on adult bone density because the juvenile bone is largely replaced through growth. If this concept generalizes, then interventions to maximize peak bone mass should be directed at adolescents rather than young children. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Gafni, Rachel I AU - McCarthy, Edward F AU - Hatcher, Tracy AU - Meyers, Jodi L AU - Inoue, Nozomu AU - Reddy, Chitra AU - Weise, Martina AU - Barnes, Kevin M AU - Abad, Veronica AU - Baron, Jeffrey AD - Unit on Growth and Development, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1862, USA. gafnir@mail.nih.gov Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 736 EP - 738 VL - 16 IS - 7 KW - Glucocorticoids KW - 0 KW - Dexamethasone KW - 7S5I7G3JQL KW - Index Medicus KW - Epiphyses -- growth & development KW - Animals KW - Periosteum -- growth & development KW - Kinetics KW - Bone Density KW - Rabbits KW - Calcification, Physiologic KW - Models, Biological KW - Bone Development KW - Osteoporosis -- pathology KW - Osteoporosis -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71630107?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.atitle=Recovery+from+osteoporosis+through+skeletal+growth%3A+early+bone+mass+acquisition+has+little+effect+on+adult+bone+density.&rft.au=Gafni%2C+Rachel+I%3BMcCarthy%2C+Edward+F%3BHatcher%2C+Tracy%3BMeyers%2C+Jodi+L%3BInoue%2C+Nozomu%3BReddy%2C+Chitra%3BWeise%2C+Martina%3BBarnes%2C+Kevin+M%3BAbad%2C+Veronica%3BBaron%2C+Jeffrey&rft.aulast=Gafni&rft.aufirst=Rachel&rft.date=2002-05-01&rft.volume=16&rft.issue=7&rft.spage=736&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=1530-6860&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-06 N1 - Date created - 2002-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective inhibition of cyclooxygenase-2 expression by 15-deoxy-Delta(12,14)(12,14)-prostaglandin J(2) in activated human astrocytes, but not in human brain macrophages. AN - 71627572; 11971025 AB - Overexpression of the inducible cyclooxygenase (COX-2) and inducible NO synthase (iNOS) in activated brain macrophages (microglia) and astrocytes appears central to many neuroinflammatory conditions. 15-Deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) is a ligand for the peroxisome proliferator-activated receptor (PPAR)gamma. It has been proposed as an inhibitor of microglial activation, based on the study of iNOS down-regulation in rodent microglia. Because iNOS induction after cytokine activation remains controversial in human microglia, we examined the effect of 15d-PGJ(2) and other PPAR agonists on human microglia and astrocytes, using COX-2 induction as an index of activation. We found that PPAR alpha ligands (clofibrate and WY14643) enhanced IL-1 beta-induced COX-2 expression in human astrocytes and microglia, while inhibiting IL-1 beta plus IFN-gamma induction of iNOS in astrocytes. This is the first description of an inhibition of iNOS uncoupled from that of COX-2. 15d-PGJ(2) suppressed COX-2 induction in human astrocytes. It prevented NF-kappa B binding to the COX-2 promoter through a new pathway that is the repression of NF-kappa Bp50 induction by IL-1 beta. In contrast, 15d-PGJ(2) increased c-Jun and c-Fos DNA-binding activity in astrocytes, which may result in the activation of other inflammatory pathways. In human microglia, no effect of 15d-PGJ(2) on COX-2 and NF-kappa Bp65/p50 induction was observed. However, the entry of 15d-PGJ(2) occurred in microglia because STAT-1 and c-Jun expression was modulated. Our data suggest the existence of novel pathways mediated by 15d-PGJ(2) in human astrocytes. They also demonstrate that, unlike astrocytes and peripheral macrophages or rodent brain macrophages, human microglia are not subject to the anti-inflammatory effect of 15d-PGJ(2) in terms of COX-2 inhibition. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Janabi, Nazila AD - Laboratory of Molecular Medicine and Neuroscience, National Institutes of Health, Bethesda, MD 20892, USA. n.janabi@envt.fr Y1 - 2002/05/01/ PY - 2002 DA - 2002 May 01 SP - 4747 EP - 4755 VL - 168 IS - 9 SN - 0022-1767, 0022-1767 KW - 15-deoxy-delta(12,14)-prostaglandin J2 KW - 0 KW - Anti-Inflammatory Agents KW - Cytokines KW - Isoenzymes KW - Membrane Proteins KW - NF-kappa B KW - Pyrimidines KW - RNA, Messenger KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - pirinixic acid KW - 86C4MRT55A KW - NOS2 protein, human KW - EC 1.14.13.39 KW - Nitric Oxide Synthase KW - Nitric Oxide Synthase Type II KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Clofibrate KW - HPN91K7FU3 KW - Prostaglandin D2 KW - RXY07S6CZ2 KW - Abridged Index Medicus KW - Index Medicus KW - Cytokines -- pharmacology KW - Transcription Factors -- agonists KW - Transcription Factors -- metabolism KW - Gene Silencing KW - Humans KW - Pyrimidines -- pharmacology KW - RNA, Messenger -- biosynthesis KW - Clofibrate -- pharmacology KW - Receptors, Cytoplasmic and Nuclear -- agonists KW - Promoter Regions, Genetic KW - Cells, Cultured KW - Anti-Inflammatory Agents -- pharmacology KW - NF-kappa B -- metabolism KW - Prostaglandin D2 -- pharmacology KW - Brain -- enzymology KW - Microglia -- enzymology KW - Brain -- cytology KW - Prostaglandin D2 -- analogs & derivatives KW - Isoenzymes -- biosynthesis KW - Astrocytes -- drug effects KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Microglia -- drug effects KW - Isoenzymes -- genetics KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis KW - Astrocytes -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71627572?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Selective+inhibition+of+cyclooxygenase-2+expression+by+15-deoxy-Delta%2812%2C14%29%2812%2C14%29-prostaglandin+J%282%29+in+activated+human+astrocytes%2C+but+not+in+human+brain+macrophages.&rft.au=Janabi%2C+Nazila&rft.aulast=Janabi&rft.aufirst=Nazila&rft.date=2002-05-01&rft.volume=168&rft.issue=9&rft.spage=4747&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-17 N1 - Date created - 2002-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Escherichia coli DNA polymerase III can replicate efficiently past a T-T cis-syn cyclobutane dimer if DNA polymerase V and the 3' to 5' exonuclease proofreading function encoded by dnaQ are inactivated. AN - 71623410; 11976296 AB - Although very little replication past a T-T cis-syn cyclobutane dimer normally takes place in Escherichia coli in the absence of DNA polymerase V (Pol V), we previously observed as much as half of the wild-type bypass frequency in Pol V-deficient (DeltaumuDC) strains if the 3' to 5' exonuclease proofreading activity of the Pol III epsilon subunit was also disabled by mutD5. This observation might be explained in at least two ways. In the absence of Pol V, wild-type Pol III might bind preferentially to the blocked primer terminus but be incapable of bypass, whereas the proofreading-deficient enzyme might dissociate more readily, providing access to bypass polymerases. Alternatively, even though wild-type Pol III is generally regarded as being incapable of lesion bypass, proofreading-impaired Pol III might itself perform this function. We have investigated this issue by examining dimer bypass frequencies in DeltaumuDC mutD5 strains that were also deficient for Pol I, Pol II, and Pol IV, both singly and in all combinations. Dimer bypass frequencies were not decreased in any of these strains and indeed in some were increased to levels approaching those found in strains containing Pol V. Efficient dimer bypass was, however, entirely dependent on the proofreading deficiency imparted by mutD5, indicating the surprising conclusion that bypass was probably performed by the mutD5 Pol III enzyme itself. This mutant polymerase does not replicate past the much more distorted T-T (6-4) photoadduct, however, suggesting that it may only replicate past lesions, like the T-T dimer, that form base pairs normally. JF - Journal of bacteriology AU - Borden, Angela AU - O'Grady, Paul I AU - Vandewiele, Dominique AU - Fernández de Henestrosa, Antonio R AU - Lawrence, Christopher W AU - Woodgate, Roger AD - Section on DNA Replication, Repair, and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2725, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 2674 EP - 2681 VL - 184 IS - 10 SN - 0021-9193, 0021-9193 KW - Escherichia coli Proteins KW - 0 KW - Pyrimidine Dimers KW - DNA Polymerase III KW - EC 2.7.7.- KW - DNA polymerase V, E coli KW - EC 2.7.7.7 KW - DNA-Directed DNA Polymerase KW - dnaQ protein, E coli KW - Exodeoxyribonucleases KW - EC 3.1.- KW - Exodeoxyribonuclease V KW - EC 3.1.11.5 KW - Index Medicus KW - DNA-Directed DNA Polymerase -- physiology KW - Pyrimidine Dimers -- metabolism KW - Exodeoxyribonucleases -- physiology KW - DNA Polymerase III -- physiology KW - Escherichia coli -- genetics KW - Exodeoxyribonucleases -- genetics KW - DNA Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71623410?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+bacteriology&rft.atitle=Escherichia+coli+DNA+polymerase+III+can+replicate+efficiently+past+a+T-T+cis-syn+cyclobutane+dimer+if+DNA+polymerase+V+and+the+3%27+to+5%27+exonuclease+proofreading+function+encoded+by+dnaQ+are+inactivated.&rft.au=Borden%2C+Angela%3BO%27Grady%2C+Paul+I%3BVandewiele%2C+Dominique%3BFern%C3%A1ndez+de+Henestrosa%2C+Antonio+R%3BLawrence%2C+Christopher+W%3BWoodgate%2C+Roger&rft.aulast=Borden&rft.aufirst=Angela&rft.date=2002-05-01&rft.volume=184&rft.issue=10&rft.spage=2674&rft.isbn=&rft.btitle=&rft.title=Journal+of+bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-22 N1 - Date created - 2002-04-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell. 2001 Aug;8(2):417-26 [11545743] Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9224-9 [10430924] Cell. 2001 Oct 5;107(1):91-102 [11595188] Mol Genet Genomics. 2001 Oct;266(2):207-15 [11683261] Nat Struct Biol. 2001 Nov;8(11):984-9 [11685247] Bioessays. 2002 Feb;24(2):141-8 [11835278] Cold Spring Harb Symp Quant Biol. 2000;65:31-40 [12760018] J Biol Chem. 1999 Nov 5;274(45):31763-6 [10542196] J Bacteriol. 2000 Apr;182(8):2285-91 [10735873] Mol Microbiol. 2000 Mar;35(6):1560-72 [10760155] EMBO J. 2000 Oct 2;19(19):5259-66 [11013228] EMBO J. 2000 Nov 15;19(22):6259-65 [11080171] Annu Rev Genet. 2000;34:479-497 [11092836] Genetics. 2001 May;158(1):41-64 [11333217] Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8342-9 [11459973] Mol Cell. 2001 Jul;8(1):7-8 [11515498] Mol Gen Genet. 1977 Nov 14;156(2):121-31 [340898] Proc Natl Acad Sci U S A. 1978 Jul;75(7):3037-41 [356043] Proc Natl Acad Sci U S A. 1980 May;77(5):2819-23 [6771759] J Bacteriol. 1984 May;158(2):636-43 [6233260] Nucleic Acids Res. 1987 Jun 11;15(11):4645-53 [3035498] FEBS Lett. 1988 Mar 28;230(1-2):171-5 [2450783] Proc Natl Acad Sci U S A. 1988 Nov;85(21):8141-5 [3054882] J Bacteriol. 1990 Apr;172(4):2105-12 [2180917] Mol Gen Genet. 1990 Jun;222(1):166-8 [2233676] Biochemistry. 1990 Sep 18;29(37):8858-66 [2271562] Mutat Res. 1992 Mar;281(3):221-5 [1371846] J Bacteriol. 1992 Mar;174(6):1974-82 [1548237] J Bacteriol. 1993 Sep;175(17):5411-9 [8366028] J Bacteriol. 1996 May;178(9):2559-63 [8626322] Mol Cell. 1999 Aug;4(2):281-6 [10488344] J Bacteriol. 1996 Jun;178(12):3550-6 [8655553] Science. 1997 Sep 5;277(5331):1453-62 [9278503] J Bacteriol. 1998 Apr;180(8):2063-71 [9555887] Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13114-9 [9789050] Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15519-24 [9861001] Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8919-24 [10430871] Mol Cell. 2001 Aug;8(2):427-37 [11545744] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lead exposure and amyotrophic lateral sclerosis. AN - 71613919; 11964933 AB - Previous interview-based studies have suggested that exposure to neurotoxicants including metals might be related to ALS. We evaluated the relation of lead exposure to ALS, using both biological measures and interviews, in a case-control study conducted in New England from 1993 to 1996. Cases (N = 109) were recruited at two hospitals in Boston, MA. Population controls (N = 256) identified by random-digit dialing were frequency-matched to cases by age, sex, and region of residence within New England. Risk of ALS was associated with self-reported occupational exposure to lead (odds ratio [OR] = 1.9; 95% confidence interval [CI] = 1.1-3.3), with a dose response for lifetime days of lead exposure. Blood and bone lead levels were measured in most cases (N = 107) and in a subset of controls (N = 41). Risk of ALS was associated with elevations in both blood and bone lead levels. ORs were 1.9 (95% CI = 1.4-2.6) for each microg/dl increase in blood lead, 3.6 (95% CI = 0.6-20.6) for each unit increase in log-transformed patella lead, and 2.3 (95% CI = 0.4-14.5) for each unit increase in log-transformed tibia lead. These results are consistent with previous reports and suggest a potential role for lead exposure in the etiology of ALS. JF - Epidemiology (Cambridge, Mass.) AU - Kamel, Freya AU - Umbach, David M AU - Munsat, Theodore L AU - Shefner, Jeremy M AU - Hu, Howard AU - Sandler, Dale P AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. kamel@niehs.nih.gov Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 311 EP - 319 VL - 13 IS - 3 SN - 1044-3983, 1044-3983 KW - Lead KW - 2P299V784P KW - Index Medicus KW - Aged, 80 and over KW - Humans KW - Linear Models KW - Adult KW - Surveys and Questionnaires KW - Case-Control Studies KW - Aged KW - Middle Aged KW - New England -- epidemiology KW - Environmental Exposure -- adverse effects KW - Male KW - Female KW - Lead -- adverse effects KW - Bone and Bones -- chemistry KW - Occupational Exposure -- adverse effects KW - Lead -- blood KW - Amyotrophic Lateral Sclerosis -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71613919?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiology+%28Cambridge%2C+Mass.%29&rft.atitle=Lead+exposure+and+amyotrophic+lateral+sclerosis.&rft.au=Kamel%2C+Freya%3BUmbach%2C+David+M%3BMunsat%2C+Theodore+L%3BShefner%2C+Jeremy+M%3BHu%2C+Howard%3BSandler%2C+Dale+P&rft.aulast=Kamel&rft.aufirst=Freya&rft.date=2002-05-01&rft.volume=13&rft.issue=3&rft.spage=311&rft.isbn=&rft.btitle=&rft.title=Epidemiology+%28Cambridge%2C+Mass.%29&rft.issn=10443983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-23 N1 - Date created - 2002-04-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MHC class I recognition by Ly49 natural killer cell receptors. AN - 71602860; 11955594 AB - Natural killer (NK) cell function is regulated by NK receptors that bind either classical MHC class I (MHC-I) molecules or their structural relatives (MICA, RAE-1 and H-60). Two distinct families of NK receptors have been identified: the C-type lectin-like family (Ly49, NKG2D and CD94/NKG2) and the immunoglobulin-like family (KIRs and LIRs). Here, we describe the crystal structure of the C-type lectin-like NK receptor (Ly49A), bound to its MHC-I ligand (H-2D(d)). We also discuss results from recent mutagenesis studies of the Ly49A/H-2D(d) interaction in the context of the complex structure. JF - Molecular immunology AU - Natarajan, Kannan AU - Dimasi, Nazzareno AU - Wang, Jian AU - Margulies, David H AU - Mariuzza, Roy A AD - Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 1023 EP - 1027 VL - 38 IS - 14 SN - 0161-5890, 0161-5890 KW - Antigens, Ly KW - 0 KW - Histocompatibility Antigens Class I KW - Klra1 protein, mouse KW - Lectins, C-Type KW - Membrane Glycoproteins KW - NK Cell Lectin-Like Receptor Subfamily A KW - Receptors, Immunologic KW - Receptors, NK Cell Lectin-Like KW - Index Medicus KW - Animals KW - Models, Molecular KW - Humans KW - Mice KW - Protein Structure, Tertiary KW - Membrane Glycoproteins -- chemistry KW - Receptors, Immunologic -- immunology KW - Histocompatibility Antigens Class I -- immunology KW - Receptors, Immunologic -- chemistry KW - Histocompatibility Antigens Class I -- chemistry KW - Membrane Glycoproteins -- immunology KW - Killer Cells, Natural -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71602860?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+immunology&rft.atitle=MHC+class+I+recognition+by+Ly49+natural+killer+cell+receptors.&rft.au=Natarajan%2C+Kannan%3BDimasi%2C+Nazzareno%3BWang%2C+Jian%3BMargulies%2C+David+H%3BMariuzza%2C+Roy+A&rft.aulast=Natarajan&rft.aufirst=Kannan&rft.date=2002-05-01&rft.volume=38&rft.issue=14&rft.spage=1023&rft.isbn=&rft.btitle=&rft.title=Molecular+immunology&rft.issn=01615890&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-23 N1 - Date created - 2002-04-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Feeding melatonin enhances the phase shifting response to triazolam in both young and old golden hamsters. AN - 71599936; 11959680 AB - Aging alters many aspects of circadian rhythmicity, including responsivity to phase-shifting stimuli and the amplitude of the rhythm of melatonin secretion. As melatonin is both an output from and an input to the circadian clock, we hypothesized that the decreased melatonin levels exhibited by old hamsters may adversely impact the circadian system as a whole. We enhanced the diurnal rhythm of melatonin by feeding melatonin to young and old hamsters. Animals of both age groups on the melatonin diet showed larger phase shifts than control-fed animals in response to an injection with the benzodiazepine triazolam at a circadian time known to induce phase advances in the activity rhythm of young animals. Thus melatonin treatment can increase the sensitivity of the circadian timing system of young animals to a nonphotic stimulus, and the ability to increase this sensitivity persists into old age, indicating exogenous melatonin might be useful in reversing at least some age-related changes in circadian clock function. JF - American journal of physiology. Regulatory, integrative and comparative physiology AU - Kolker, Daniel E AU - Losee Olson, Susan AU - Dutton-Boilek, Jeanette AU - Bennett, Katherine M AU - Wallen, Edward P AU - Horton, Teresa H AU - Turek, Fred W AD - Department of Neurobiology and Physiology and Center for Sleep and Circadian Biology, Northwestern University, Evanston, Illinois 60208, USA. kolkerd@mail.nih.gov Y1 - 2002/05// PY - 2002 DA - May 2002 SP - R1382 EP - R1388 VL - 282 IS - 5 SN - 0363-6119, 0363-6119 KW - Triazolam KW - 1HM943223R KW - Melatonin KW - JL5DK93RCL KW - Index Medicus KW - Space life sciences KW - Administration, Oral KW - Animals KW - Reference Values KW - In Vitro Techniques KW - Mesocricetus KW - Drug Synergism KW - Male KW - Cricetinae KW - Aging -- physiology KW - Melatonin -- pharmacology KW - Melatonin -- administration & dosage KW - Circadian Rhythm -- drug effects KW - Triazolam -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71599936?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+physiology.+Regulatory%2C+integrative+and+comparative+physiology&rft.atitle=Feeding+melatonin+enhances+the+phase+shifting+response+to+triazolam+in+both+young+and+old+golden+hamsters.&rft.au=Kolker%2C+Daniel+E%3BLosee+Olson%2C+Susan%3BDutton-Boilek%2C+Jeanette%3BBennett%2C+Katherine+M%3BWallen%2C+Edward+P%3BHorton%2C+Teresa+H%3BTurek%2C+Fred+W&rft.aulast=Kolker&rft.aufirst=Daniel&rft.date=2002-05-01&rft.volume=282&rft.issue=5&rft.spage=R1382&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Regulatory%2C+integrative+and+comparative+physiology&rft.issn=03636119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-28 N1 - Date created - 2002-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conserved furin cleavage site not essential for secretion and integration of ZP3 into the extracellular egg coat of transgenic mice. AN - 71589356; 11940668 AB - The extracellular zona pellucida surrounding mammalian eggs is formed by interactions of the ZP1, ZP2, and ZP3 glycoproteins. Female mice lacking ZP2 or ZP3 do not form a stable zona matrix and are sterile. The three zona proteins are synthesized in growing oocytes and secreted prior to incorporation into the zona pellucida. A well-conserved furin site upstream of a transmembrane domain near the carboxyl terminus of each has been implicated in the release of the zona ectodomains from oocytes. However, mutation of the furin site (RNRR --> ANAA) does not affect the intracellular trafficking or secretion of an enhanced green fluorescent protein (EGFP)-ZP3 fusion protein in heterologous somatic cells. After transient expression in growing oocytes, normal EGFP-ZP3 and mutant EGFP-ZP3 associate with the inner aspect of the zona pellucida, which is distinct from the plasma membrane. These in vitro results are confirmed in transgenic mice expressing EGFP-ZP3 with or without the mutant furin site. In each case, EGFP-ZP3 is incorporated throughout the width of the zona pellucida and the transgenic mice are fertile. These results indicate that the zona matrix accrues from the inside out and, unexpectedly, suggest that cleavage at the furin site is not required for formation of the extracellular zona pellucida surrounding mouse eggs. JF - Molecular and cellular biology AU - Zhao, Ming AU - Gold, Lyn AU - Ginsberg, Ann M AU - Liang, Li-Fang AU - Dean, Jurrien AD - Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-8028, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 3111 EP - 3120 VL - 22 IS - 9 SN - 0270-7306, 0270-7306 KW - Egg Proteins KW - 0 KW - Luminescent Proteins KW - Membrane Glycoproteins KW - Receptors, Cell Surface KW - Zona Pellucida Glycoproteins KW - Zp1 protein, mouse KW - Zp2 protein, mouse KW - Zp3 protein, mouse KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Subtilisins KW - EC 3.4.21.- KW - Furin KW - EC 3.4.21.75 KW - Index Medicus KW - Microscopy, Confocal KW - Animals KW - Amino Acid Sequence KW - Luminescent Proteins -- metabolism KW - Mice KW - Mice, Transgenic KW - Protein Binding KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Blotting, Western KW - Molecular Sequence Data KW - Cell Membrane -- metabolism KW - Immunohistochemistry KW - Female KW - Zona Pellucida -- chemistry KW - Oocytes -- metabolism KW - Conserved Sequence KW - Protein Processing, Post-Translational KW - Egg Proteins -- metabolism KW - Oocytes -- cytology KW - Zona Pellucida -- metabolism KW - Membrane Glycoproteins -- immunology KW - Egg Proteins -- immunology KW - Egg Proteins -- secretion KW - Subtilisins -- metabolism KW - Membrane Glycoproteins -- secretion KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71589356?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Conserved+furin+cleavage+site+not+essential+for+secretion+and+integration+of+ZP3+into+the+extracellular+egg+coat+of+transgenic+mice.&rft.au=Zhao%2C+Ming%3BGold%2C+Lyn%3BGinsberg%2C+Ann+M%3BLiang%2C+Li-Fang%3BDean%2C+Jurrien&rft.aulast=Zhao&rft.aufirst=Ming&rft.date=2002-05-01&rft.volume=22&rft.issue=9&rft.spage=3111&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-16 N1 - Date created - 2002-04-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1996 May 28;93(11):5431-6 [8643592] Annu Rev Biochem. 1995;64:563-91 [7574493] J Biol Chem. 1996 Sep 27;271(39):24236-41 [8798668] J Biol Chem. 1997 Jan 10;272(2):1344-8 [8995442] Biochem J. 1997 Jan 15;321 ( Pt 2):265-79 [9020855] Arch Biochem Biophys. 1998 Jan 1;349(1):192-200 [9439598] Nature. 1998 Apr 30;392(6679):917-20 [9582070] Biochem J. 1997 Nov 1;327 ( Pt 3):625-35 [9599222] Development. 1998 Jul;125(13):2415-24 [9609824] Biol Reprod. 1998 Nov;59(5):1230-9 [9780332] Biochem J. 1998 Dec 1;336 ( Pt 2):311-6 [9820806] Trends Cell Biol. 1999 Jan;9(1):28-35 [10087614] Trends Genet. 2000 Feb;16(2):83-7 [10652535] Rev Reprod. 2000 May;5(2):114-21 [10864856] J Biol Chem. 2000 Sep 15;275(37):28866-72 [10979984] Biochemistry. 2001 Jan 30;40(4):929-37 [11170414] Development. 2001 Apr;128(7):1119-26 [11245577] Int Rev Cytol. 1965;18:29-71 [5337036] J Ultrastruct Res. 1980 Jul;72(1):1-12 [7191010] Anal Biochem. 1981 Apr;112(2):195-203 [6266278] J Biol Chem. 1983 May 10;258(9):5858-63 [6853551] J Biol Chem. 1983 Nov 10;258(21):13243-9 [6630229] J Cell Biol. 1984 Mar;98(3):795-800 [6699085] Dev Biol. 1985 Jun;109(2):268-73 [3996750] Dev Genes Evol. 1999 Jun;209(6):330-9 [10370114] J Biol Chem. 1999 Jul 23;274(30):20745-8 [10409610] Development. 1999 Sep;126(17):3847-55 [10433913] Biochemistry. 1999 Sep 21;38(38):12280-7 [10493795] Am J Anat. 1960 Mar;106:149-69 [13693138] Dev Biol. 1988 Jun;127(2):287-95 [3378665] Science. 1989 Nov 17;246(4932):935-8 [2479101] Nucleic Acids Res. 1990 Oct 11;18(19):5905-6 [2216797] J Cell Biol. 1991 Nov;115(3):655-64 [1655811] Mol Cell Biol. 1991 Dec;11(12):6197-204 [1944285] FEBS Lett. 1992 Apr 6;300(3):237-40 [1313375] Dev Biol. 1992 May;151(1):48-54 [1577197] J Biol Chem. 1993 Apr 25;268(12):8480-90 [8473292] Biochim Biophys Acta. 1993 Aug 19;1174(2):211-4 [8357839] J Biol Chem. 1993 Oct 5;268(28):21351-8 [8407974] J Cell Biol. 1994 Oct;127(2):333-41 [7929579] J Biol Chem. 1994 Dec 23;269(51):32209-13 [7798220] Infect Immun. 1995 Jan;63(1):82-7 [7806387] Dev Biol. 1995 Jan;167(1):9-17 [7851666] Development. 1996 Sep;122(9):2903-10 [8787763] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - alpha-Melanocyte-simulating hormone and interleukin-10 do not protect the kidney against mercuric chloride-induced injury. AN - 71577949; 11934688 AB - The anti-inflammatory cytokines alpha-melanocyte-stimulating hormone (MSH) and interleukin (IL)-10 inhibit acute renal failure (ARF) after ischemia or cisplatin administration; however, these agents have not been tested in a pure nephrotoxic model of ARF. Therefore, we examined the effects of alpha-MSH and IL-10 in HgCl(2)-induced ARF. Mice were injected subcutaneously with HgCl(2) and then given vehicle, alpha-MSH, or IL-10 by intravenous injection. Animals were killed to study serum creatinine, histology, and myeloperoxidase activity. Treatment with either alpha-MSH or IL-10 did not alter the increase in serum creatinine, tubular damage, or leukocyte accumulation at 48 h after HgCl(2) injection. Because alpha-MSH and IL-10 are active in other injury models that involve leukocytes, we studied the time course of tubular damage and leukocyte accumulation to investigate whether leukocytes caused the tubular damage or accumulated in response to the tubular damage. Tubular damage was present in the outer stripe 12 h after HgCl(2) injection. In contrast, the number of leukocytes and renal myleoperoxidase activity were normal at 12 h but were significantly increased at 24 and 48 h after injection. We conclude that neither alpha-MSH nor IL-10 altered the course of HgCl(2)-induced renal injury. Because the tubular damage preceded leukocyte infiltration, the delayed leukocyte accumulation may play a role in the removal of necrotic tissue and/or tissue repair in HgCl(2)-induced ARF. JF - American journal of physiology. Renal physiology AU - Miyaji, Takehiko AU - Hu, Xuzhen AU - Star, Robert A AD - Renal Diagnostics and Therapeutics Unit, National Institutes of Health, Bethesda, Maryland 20892-1268, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - F795 EP - F801 VL - 282 IS - 5 SN - 1931-857X, 1931-857X KW - Interleukin-10 KW - 130068-27-8 KW - Mercuric Chloride KW - 53GH7MZT1R KW - alpha-MSH KW - 581-05-5 KW - Creatinine KW - AYI8EX34EU KW - Peroxidase KW - EC 1.11.1.7 KW - Esterases KW - EC 3.1.- KW - Index Medicus KW - Animals KW - Necrosis KW - Kidney Tubules -- pathology KW - Injections, Intravenous KW - Leukocytes -- pathology KW - Kinetics KW - Peroxidase -- metabolism KW - Esterases -- analysis KW - Mice KW - Mice, Inbred BALB C KW - Creatinine -- blood KW - Male KW - Interleukin-10 -- administration & dosage KW - Interleukin-10 -- therapeutic use KW - Acute Kidney Injury -- pathology KW - Acute Kidney Injury -- chemically induced KW - alpha-MSH -- therapeutic use KW - Kidney Diseases -- prevention & control KW - Acute Kidney Injury -- prevention & control KW - Mercuric Chloride -- toxicity KW - alpha-MSH -- administration & dosage KW - Kidney Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71577949?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+physiology.+Renal+physiology&rft.atitle=alpha-Melanocyte-simulating+hormone+and+interleukin-10+do+not+protect+the+kidney+against+mercuric+chloride-induced+injury.&rft.au=Miyaji%2C+Takehiko%3BHu%2C+Xuzhen%3BStar%2C+Robert+A&rft.aulast=Miyaji&rft.aufirst=Takehiko&rft.date=2002-05-01&rft.volume=282&rft.issue=5&rft.spage=F795&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Renal+physiology&rft.issn=1931857X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-17 N1 - Date created - 2002-04-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Confocal imaging of organic anion transport in intact rat choroid plexus. AN - 71570162; 11934698 AB - We used confocal microscopy and quantitative image analysis to follow the movement of the fluorescent organic anion fluorescein (FL) from bath to cell and cell to blood vessel in intact rat lateral choroid plexus. FL accumulation in epithelial cells and underlying vessels was rapid, concentrative, and reduced by other organic anions. At steady state, cell fluorescence exceeded bath fluorescence by a factor of 3-5, and vessel fluorescence exceeded cell fluorescence by a factor of approximately 2. In cells, FL distributed between diffuse and punctate compartments. Cell and vessel accumulation of FL decreased when metabolism was inhibited by KCN, when bath Na(+) was reduced from 130 to 26 mM, and when the Na(+) gradient was collapsed with ouabain. Cell and vessel accumulation increased by >50% when 1-10 microM glutarate was added to the bath. Finally, transport of FL and carboxyfluorescein (generated intracellularly from carboxyfluorescein diacetate) from cell to blood vessel was greatly diminished when medium K(+) concentration ([K(+)]) was increased 10-fold. These results 1) validate a new approach to the study of choroid plexus function, and 2) indicate a two-step mechanism for transepithelial organic anion transport: indirect coupling of uptake to Na(+) at the apical membrane and electrical potential-driven efflux at the basolateral membrane. JF - American journal of physiology. Renal physiology AU - Breen, Christopher M AU - Sykes, Destiny B AU - Fricker, Gert AU - Miller, David S AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - F877 EP - F885 VL - 282 IS - 5 SN - 1931-857X, 1931-857X KW - Anions KW - 0 KW - Enzyme Inhibitors KW - Fluorescent Dyes KW - 2,4-Dichlorophenoxyacetic Acid KW - 2577AQ9262 KW - Sodium Chloride KW - 451W47IQ8X KW - Ouabain KW - 5ACL011P69 KW - Potassium Chloride KW - 660YQ98I10 KW - Sodium KW - 9NEZ333N27 KW - Sodium-Potassium-Exchanging ATPase KW - EC 3.6.3.9 KW - Potassium Cyanide KW - MQD255M2ZO KW - Potassium KW - RWP5GA015D KW - Fluorescein KW - TPY09G7XIR KW - p-Aminohippuric Acid KW - Y79XT83BJ9 KW - Index Medicus KW - Animals KW - p-Aminohippuric Acid -- pharmacology KW - Potassium Chloride -- administration & dosage KW - Sodium Chloride -- administration & dosage KW - Potassium Cyanide -- pharmacology KW - Sodium -- pharmacology KW - Rats KW - Epithelial Cells -- metabolism KW - Sodium-Potassium-Exchanging ATPase -- antagonists & inhibitors KW - Rats, Sprague-Dawley KW - Kinetics KW - Fluorescein -- metabolism KW - 2,4-Dichlorophenoxyacetic Acid -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Cell Membrane -- metabolism KW - Potassium -- cerebrospinal fluid KW - Ouabain -- pharmacology KW - Male KW - Sodium -- metabolism KW - Microscopy, Confocal KW - Choroid Plexus -- metabolism KW - Choroid Plexus -- blood supply KW - Ion Transport UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71570162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+physiology.+Renal+physiology&rft.atitle=Confocal+imaging+of+organic+anion+transport+in+intact+rat+choroid+plexus.&rft.au=Breen%2C+Christopher+M%3BSykes%2C+Destiny+B%3BFricker%2C+Gert%3BMiller%2C+David+S&rft.aulast=Breen&rft.aufirst=Christopher&rft.date=2002-05-01&rft.volume=282&rft.issue=5&rft.spage=F877&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Renal+physiology&rft.issn=1931857X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-17 N1 - Date created - 2002-04-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fusion-defective gibbon ape leukemia virus vectors can be rescued by homologous but not heterologous soluble envelope proteins. AN - 71568075; 11932392 AB - Murine leukemia virus (MLV)-derived envelope proteins containing alterations in or adjacent to the highly conserved PHQ motif present at the N terminus of the envelope surface subunit (SU) are incorporated into vector particles but are not infectious due to a postbinding block to viral entry. These mutants can be rendered infectious by the addition of soluble receptor-binding domain (RBD) proteins in the culture medium. The RBD proteins that rescue the infectivity of these defective MLV vectors can be derived from the same MLV or from other MLVs that use distinct receptors to mediate entry. We have now constructed functional immunologically reactive gibbon ape leukemia virus (GALV) envelope proteins, tagged with a feline leukemia virus (FeLV)-derived epitope tag, which are efficiently incorporated into infectious particles. Tagged GALV envelope proteins bind specifically to cells expressing the phosphate transporter protein Pit1, demonstrating for the first time that Pit1 is the binding receptor for GALV and not a coreceptor or another type of GALV entry factor. We have also determined that GALV particles bearing SU proteins with an insertion C-terminal to the PHQ motif (GALV I(10)) bind Pit1 but fail to infect cells. Incubation with soluble GALV RBD renders GALV I(10) particles infectious, whereas incubation with soluble RBDs from MLV or FeLV-B does not. This finding is consistent with the results obtained by Lauring et al. using FeLV-T, a virus that employs Pit1 as a receptor but requires soluble FeLV RBD for entry. MLV and GALV RBDs are not able to render FeLV-T infectious (A. S. Lauring, M. M. Anderson, and J. Overbaugh, J. Virol. 75:8888-8898, 2001). Together, these results suggest that fusion-defective FeLV-T and GALV are restricted to homologous RBD rescue of infectivity. JF - Journal of virology AU - Farrell, Karen B AU - Ting, Yuan-Tsang AU - Eiden, Maribeth V AD - Unit on Molecular Virology, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, Maryland 20892, USA. Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 4267 EP - 4274 VL - 76 IS - 9 SN - 0022-538X, 0022-538X KW - Antigens, CD11 KW - 0 KW - Carrier Proteins KW - Epitopes KW - Membrane Proteins KW - Phospholipid Transfer Proteins KW - Viral Envelope Proteins KW - Index Medicus KW - Animals KW - Solubility KW - Carrier Proteins -- metabolism KW - Antigens, CD11 -- chemistry KW - Amino Acid Sequence KW - Antigens, CD11 -- metabolism KW - Cats KW - Molecular Sequence Data KW - Leukemia Virus, Feline -- genetics KW - Species Specificity KW - Cell Line KW - Mutagenesis, Insertional KW - Leukemia Virus, Feline -- metabolism KW - Leukemia Virus, Gibbon Ape -- pathogenicity KW - Membrane Fusion KW - Leukemia Virus, Gibbon Ape -- metabolism KW - Genetic Vectors KW - Defective Viruses KW - Viral Envelope Proteins -- metabolism KW - Leukemia Virus, Gibbon Ape -- genetics KW - Viral Envelope Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71568075?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Fusion-defective+gibbon+ape+leukemia+virus+vectors+can+be+rescued+by+homologous+but+not+heterologous+soluble+envelope+proteins.&rft.au=Farrell%2C+Karen+B%3BTing%2C+Yuan-Tsang%3BEiden%2C+Maribeth+V&rft.aulast=Farrell&rft.aufirst=Karen&rft.date=2002-05-01&rft.volume=76&rft.issue=9&rft.spage=4267&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-10 N1 - Date created - 2002-04-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1996 Oct;70(10):6982-6 [8794342] J Virol. 1996 Jul;70(7):4387-93 [8676462] J Virol. 1997 Oct;71(10):8078-81 [9311908] J Virol. 1997 Nov;71(11):8103-8 [9343159] J Virol. 1997 Nov;71(11):8116-23 [9343161] J Virol. 1997 Dec;71(12):9383-91 [9371598] J Virol. 1998 Jan;72(1):428-35 [9420242] J Virol. 1998 Jul;72(7):5383-91 [9620992] J Virol. 1998 Dec;72(12):9453-8 [9811678] J Virol. 1998 Dec;72(12):9955-65 [9811733] J Virol. 1999 Apr;73(4):2916-20 [10074140] J Virol. 1999 Jun;73(6):5034-42 [10233966] J Virol. 2000 Jan;74(1):237-44 [10590111] J Virol. 2000 Jan;74(1):295-304 [10590117] J Virol. 2000 Jan;74(2):899-913 [10623753] Science. 2000 Mar 10;287(5459):1828-30 [10710311] Virology. 2000 Mar 30;269(1):7-17 [10725193] J Virol. 2001 Apr;75(8):3685-95 [11264358] Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):4113-8 [11274436] J Virol. 2001 May;75(9):4357-66 [11287584] Microbiol Mol Biol Rev. 2001 Sep;65(3):371-89, table of contents [11528001] J Virol. 2001 Oct;75(19):8888-98 [11533152] J Virol. 2001 Oct;75(19):9096-105 [11533173] J Immunol. 1983 Dec;131(6):3042-8 [6196410] J Virol. 1984 Nov;52(2):695-8 [6092693] J Virol. 1987 Jan;61(1):8-15 [2431166] J Virol. 1988 Oct;62(10):3738-46 [2843671] J Virol. 1989 May;63(5):2374-8 [2784836] Cell Growth Differ. 1990 Mar;1(3):119-27 [2078500] J Virol. 1991 May;65(5):2220-4 [1850008] J Virol. 1992 Feb;66(2):1219-22 [1309898] J Virol. 1992 Mar;66(3):1468-75 [1310758] J Virol. 1992 Mar;66(3):1635-40 [1531369] J Virol. 1992 Aug;66(8):4632-8 [1321266] J Virol. 1993 Jun;67(6):3489-96 [7684467] J Virol. 1993 Nov;67(11):6733-6 [8411375] J Virol. 1993 Nov;67(11):6737-41 [8411376] Blood. 1994 Jan 1;83(1):43-50 [8274751] J Virol. 1994 Dec;68(12):7697-703 [7966559] J Virol. 1994 Dec;68(12):8270-6 [7966619] J Virol. 1995 Feb;69(2):713-9 [7815534] J Virol. 1995 Apr;69(4):2401-5 [7884886] J Virol. 1995 Oct;69(10):6314-22 [7666532] J Virol. 1996 Feb;70(2):1080-5 [8551566] J Virol. 1997 Mar;71(3):2092-9 [9032341] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Studies of the biogenic amine transporters. 10. Characterization of a novel cocaine binding site in brain membranes prepared from dopamine transporter knockout mice. AN - 71519246; 11891881 AB - Previous work suggested that the cocaine analog [(125)I]RTI-55 labels a novel binding site in rat brain membranes, which is not associated with the dopamine (DA), serotonin (5-HT), or norepinephrine (NE) transporters [Rothman et al. 1995 J Pharmacol Exp Ther 274:385-395]. Here, we tested whether this site is a product of the DA transporter (DAT) gene. We used a T-antigen knock-in at the DAT gene that results in an effective DAT knock-out (KO) confirmed by Southern blot, DAT immunohistochemistry, and [(125)I]RTI-55 ligand binding. Brain membranes were prepared from frozen whole brain minus caudate of wild-type (WT) B6/Sv129, +/+ and minus sign/minus sign (KO) mice. KO mice were used at approximately 23 days of age. Binding surface analysis of [(125)I]RTI-55 binding to membranes prepared from the brains of WT mice, with 100 nM citalopram to block binding to the 5-HT transporter (SERT), revealed two binding sites: the DAT and a second site, replicating previous studies conducted with rat brains. In the absence of the DAT (minus sign/minus sign mice), binding surface analysis demonstrated that [(125)I]RTI-55 labeled two sites: the NET and a second site called site "X." Structure-activity studies of site "X" demonstrated that high-affinity ligands for the DAT, NET, and SERT have low or negligible affinity for site "X." The relatively high density of site "X" in brain membranes and the fact that the K(i) values of cocaine and cocaethylene for site "X" are in the range achieved in the brain following cocaine administration suggests that site "X" could contribute to the pharmacological or toxicological effects of cocaine. Further progress in delineating the function of site "X" will depend on developing potent and selective agents for this site. JF - Synapse (New York, N.Y.) AU - Rothman, Richard B AU - Carroll, F Ivy AU - Morales, Marisela AU - Rowley, Daniel L AU - Rice, Kenner C AU - Dersch, Christina M AU - Donovan, David M AD - IRP, NIDA, NIH, Baltimore, Maryland 21224, USA. RROTHMAN@INTRA.NIDA.NIH.GOV Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 94 EP - 105 VL - 44 IS - 2 SN - 0887-4476, 0887-4476 KW - Biogenic Amines KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Norepinephrine Plasma Membrane Transport Proteins KW - Slc6a2 protein, mouse KW - Slc6a2 protein, rat KW - Slc6a3 protein, mouse KW - Slc6a3 protein, rat KW - Symporters KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Caudate Nucleus -- metabolism KW - Algorithms KW - Membranes -- metabolism KW - Mice KW - Mice, Knockout KW - Binding Sites KW - Rats KW - Dopamine -- genetics KW - Rats, Sprague-Dawley KW - In Vitro Techniques KW - Immunohistochemistry KW - Membrane Transport Proteins -- genetics KW - Male KW - Biogenic Amines -- metabolism KW - Symporters -- metabolism KW - Brain -- metabolism KW - Biogenic Amines -- pharmacology KW - Cocaine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71519246?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Synapse+%28New+York%2C+N.Y.%29&rft.atitle=Studies+of+the+biogenic+amine+transporters.+10.+Characterization+of+a+novel+cocaine+binding+site+in+brain+membranes+prepared+from+dopamine+transporter+knockout+mice.&rft.au=Rothman%2C+Richard+B%3BCarroll%2C+F+Ivy%3BMorales%2C+Marisela%3BRowley%2C+Daniel+L%3BRice%2C+Kenner+C%3BDersch%2C+Christina+M%3BDonovan%2C+David+M&rft.aulast=Rothman&rft.aufirst=Richard&rft.date=2002-05-01&rft.volume=44&rft.issue=2&rft.spage=94&rft.isbn=&rft.btitle=&rft.title=Synapse+%28New+York%2C+N.Y.%29&rft.issn=08874476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-13 N1 - Date created - 2002-03-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Child-care structure > process > outcome: direct and indirect effects of child-care quality on young children's development AN - 39026262; 2353666 JF - Psychological science Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 199 EP - 206 VL - 13 IS - 3 SN - 0956-7976, 0956-7976 KW - Sociology KW - Early childhood KW - Child psychology KW - Psychology KW - Children KW - Developmental psychology KW - Child development KW - Child care KW - Child welfare UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39026262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aibss&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychological+science&rft.atitle=Child-care+structure+%26gt%3B+process+%26gt%3B+outcome%3A+direct+and+indirect+effects+of+child-care+quality+on+young+children%27s+development&rft.au=&rft.aulast=&rft.aufirst=&rft.date=2002-05-01&rft.volume=13&rft.issue=3&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Psychological+science&rft.issn=09567976&rft_id=info:doi/ LA - English DB - International Bibliography of the Social Sciences (IBSS) N1 - Date revised - 2013-06-12 N1 - SuppNotes - With data from the NICHD Study of Early Child Care, we used structural equation modeling to test paths from structural indicators of child-care quality, specifically caregiver training and child-staff ratio, through a process indicator to child outcomes. There were three main findings: (a) Quality of maternal caregiving was the strongest predictor of cognitive competence, as well as caregivers' ratings of social competence; (b) quality of nonmaternal caregiving was associated with cognitive competence and caregivers' ratings of social competence; and (c) there was a mediated path from both caregiver training and child-staff ratio through quality of nonmaternal caregiving to cognitive competence, as well as to caregivers' ratings of social competence, that was not accounted for entirely by family variables. These findings provide empirical support for policies that improve state regulations for caregiver training and child-staff ratios. N1 - Last updated - 2013-09-16 N1 - SubjectsTermNotLitGenreText - 10404; 2205 2212 10404; 2212; 2192; 2197 2212 6075 3483; 3518 10404; 3827 2211 652 5676 646 6091 2212; 2208 2212 ER - TY - JOUR T1 - Prospective Study of Diet and Pancreatic Cancer Male Smokers AN - 18914030; 5438659 AB - There have been few prospective studies relating diet to pancreatic cancer, with most having fewer than 100 cases and only one examining dietary nutrients. The authors prospectively examined dietary factors hypothesized to be associated with exocrine pancreatic cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort in Finland. Of the 27,111 male smokers aged 50-69 years with complete dietary information, as ascertained from a self-administered dietary history questionnaire given at baseline (1985-1988), 163 developed pancreatic cancer from 1985 through November 1997. Cox proportional hazards models were used to estimate smoking- and age-adjusted hazard ratios and 95% confidence intervals. Energy-adjusted butter consumption and saturated fat intake were positively associated with pancreatic cancer (highest quintile vs. lowest: hazard ratio (HR) = 1.40, 95% confidence interval (CI): 0.87, 2.25 (p trend = 0.04), and HR = 1.60, 95% CI: 0.96, 2.64 (p trend = 0.02), respectively). Energy intake and energy-adjusted carbohydrate intake were inversely associated with the disease (highest quintile vs. lowest: HR = 0.62, 95% CI: 0.36, 1.07 (p trend = 0.05), and HR = 0.62, 95% CI: 0.37, 1.03 (p trend = 0.02), respectively). These results support the hypothesis that a high intake of saturated fat may increase the risk of pancreatic cancer in smokers, while greater intakes of energy and carbohydrate may reduce the risk. JF - American Journal of Epidemiology AU - Stolzenberg-Solomon, R Z AU - Pietinen, P AU - Taylor, PR AU - Virtamo, J AU - Albanes, D AD - Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA Y1 - 2002/05/01/ PY - 2002 DA - 2002 May 01 SP - 783 EP - 792 VL - 155 IS - 9 SN - 0002-9262, 0002-9262 KW - man KW - males KW - pancreas KW - Risk Abstracts; Health & Safety Science Abstracts; Toxicology Abstracts KW - Diets KW - Pancreas KW - Nutrition KW - Cancer KW - Smoking KW - Cigarette smoking KW - Tobacco KW - X 24120:Food, additives & contaminants KW - H 11000:Diseases/Injuries/Trauma KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18914030?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Epidemiology&rft.atitle=Prospective+Study+of+Diet+and+Pancreatic+Cancer+Male+Smokers&rft.au=Stolzenberg-Solomon%2C+R+Z%3BPietinen%2C+P%3BTaylor%2C+PR%3BVirtamo%2C+J%3BAlbanes%2C+D&rft.aulast=Stolzenberg-Solomon&rft.aufirst=R&rft.date=2002-05-01&rft.volume=155&rft.issue=9&rft.spage=783&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Smoking; Diets; Cancer; Nutrition; Pancreas; Cigarette smoking; Tobacco ER - TY - JOUR T1 - Health effects from fallout AN - 18490527; 5459110 AB - This paper primarily discusses health effects that have resulted from exposures received as a result of above-ground nuclear tests, with emphasis on thyroid disease from exposure to super(131)I and leukemia and solid cancers from low dose rate external and internal exposure. Results of epidemiological studies of fallout exposures in the Marshall Islands and from the Nevada Test Site are summarized, and studies of persons with exposures similar to those from fallout are briefly reviewed (including patients exposed to super(131)I for medical reasons and workers exposed externally at low doses and low dose rates). Promising new studies of populations exposed in countries of the former Soviet Union are also discussed and include persons living near the Semipalatinsk Test Site in Kazakhstan, persons exposed as a result of the Chernobyl accident, and persons exposed as a result of operations of the Mayak Nuclear Plant in the Russian Federation. Very preliminary estimates of cancer risks from fallout doses received by the United States population are presented. JF - Health Physics AU - Gilbert, E S AU - Land, CE AU - Simon, S L AD - Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 6120 Executive Boulevard, MS-7238, Rockville, MD 20852, USA, gilberte@mail.nih.gov Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 726 EP - 735 VL - 82 IS - 5 SN - 0017-9078, 0017-9078 KW - Pollution Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - R2 23020:Technological risks KW - H 8000:Radiation Safety/Electrical Safety KW - P 8000:RADIATION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18490527?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+Physics&rft.atitle=Health+effects+from+fallout&rft.au=Gilbert%2C+E+S%3BLand%2C+CE%3BSimon%2C+S+L&rft.aulast=Gilbert&rft.aufirst=E&rft.date=2002-05-01&rft.volume=82&rft.issue=5&rft.spage=726&rft.isbn=&rft.btitle=&rft.title=Health+Physics&rft.issn=00179078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Estimates of doses from global fallout AN - 18489737; 5459113 AB - This paper summarizes information about external and internal doses resulting from global fallout and presents preliminary estimates of doses resulting from intermediate fallout in the contiguous United States. Most of the data on global fallout were extracted from the reports of the United Nations Scientific Committee on the Effects of Atomic Radiation, in which the radiation exposures from fallout have been extensively reviewed at regular intervals. United Nations Scientific Committee on the Effects of Atomic Radiation estimated the average effective doses received by the world's population before 2000 to be about 0.4 mSv from external irradiation and 0.6 mSv from internal irradiation, the main radionuclide contributing to the effective dose being super(137)Cs. Effective doses received beyond 2000 result mainly from the environmentally mobile, long-lived super(14)C and amount to about 2.5 mSv summed over present and future generations. Specific information about the doses from fallout received by the United States population is based on the preliminary results of a study requested by the U.S. Congress and conducted jointly by the Centers for Disease Control and Prevention and the National Cancer Institute. Separate calculations were made for the tests conducted at the Nevada Test Site and for the high-yield tests conducted mainly by the United States and the former Soviet Union at sites far away from the contiguous United States (global tests). The estimated average doses from external irradiation received by the United States population were about 0.5 mGy for Nevada Test Site fallout and about 0.7 mGy for global fallout. These values vary little from one organ or tissue of the body to another. In contrast, the average doses from internal irradiation vary markedly from one organ or tissue to another; estimated average thyroid doses to children born in 1951 were about 30 mGy from Nevada Test Site fallout and about 2 mGy from global fallout. JF - Health Physics AU - Bouville, A AU - Simon, S L AU - Miller, C W AU - Beck, H L AU - Anspaugh, L R AU - Bennett, B G AD - National Cancer Institute, Division of Cancer Epidemiology and Genetics, Radiation Epidemiology Branch, Bethesda, MD 20892, USA, bouvilla@epndce.nci.nih.gov Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 690 EP - 705 VL - 82 IS - 5 SN - 0017-9078, 0017-9078 KW - dose estimates KW - man KW - Toxicology Abstracts KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18489737?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+Physics&rft.atitle=Estimates+of+doses+from+global+fallout&rft.au=Bouville%2C+A%3BSimon%2C+S+L%3BMiller%2C+C+W%3BBeck%2C+H+L%3BAnspaugh%2C+L+R%3BBennett%2C+B+G&rft.aulast=Bouville&rft.aufirst=A&rft.date=2002-05-01&rft.volume=82&rft.issue=5&rft.spage=690&rft.isbn=&rft.btitle=&rft.title=Health+Physics&rft.issn=00179078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Molecular Analysis of Group A Streptococcus Type emm18 Isolates Temporally Associated with Acute Rheumatic Fever Outbreaks in Salt Lake City, Utah AN - 18469214; 5430929 AB - Acute rheumatic fever (ARF) and subsequent rheumatic heart disease are rare but serious sequelae of group A Streptococcus (GAS) infections in most western countries. Salt Lake City (SLC), Utah, and the surrounding intermountain region experienced a resurgence of ARF in 1985 which has persisted. The largest numbers of cases were encountered in 1985-1986 and in 1997-1998. Organisms with a mucoid colony phenotype when grown on blood agar plates were temporally associated with the higher incidence of ARF. To develop an understanding of the molecular population genetic structure of GAS strains associated with ARF in the SLC region, 964 mucoid and nonmucoid pharyngeal isolates recovered in SLC from 1984 to 1999 were studied by sequencing the emm gene. Isolates with an emm18 allele were further characterized by sequencing the spa, covR, and covS genes. Peak periods of ARF were associated with GAS isolates possessing an emm18 allele encoding the protein found in serotype M18 isolates. Among the serotype M18 isolates, the difference in the number of C repeats produced three size variants. Variation was limited in spa, a gene that encodes a streptococcal protective antigen, and covR and covS, genes that encode a two-component regulatory system that, when inactivated, results in a mucoid phenotype and enhanced virulence in mouse infection models. Pulsed-field gel electrophoresis showed a single restriction profile for serotype M18 organisms isolated during both peak periods of ARF. In SLC, the incidence of ARF coresurged with the occurrence of GAS serotype M18 isolates that have very restricted genetic variation. JF - Journal of Clinical Microbiology AU - Smoot, J C AU - Korgenski, E K AU - Daly, JA AU - Veasy, L G AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th St., Hamilton, MT 59840., jmusser@niaid.nih.gov Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 1805 EP - 1810 VL - 40 IS - 5 SN - 0095-1137, 0095-1137 KW - covR gene KW - covS gene KW - emm gene KW - man KW - outbreaks KW - spa gene KW - Microbiology Abstracts B: Bacteriology KW - J 02725:DNA KW - J 02855:Human Bacteriology: Others KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18469214?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Microbiology&rft.atitle=Molecular+Analysis+of+Group+A+Streptococcus+Type+emm18+Isolates+Temporally+Associated+with+Acute+Rheumatic+Fever+Outbreaks+in+Salt+Lake+City%2C+Utah&rft.au=Smoot%2C+J+C%3BKorgenski%2C+E+K%3BDaly%2C+JA%3BVeasy%2C+L+G%3BMusser%2C+J+M&rft.aulast=Smoot&rft.aufirst=J&rft.date=2002-05-01&rft.volume=40&rft.issue=5&rft.spage=1805&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/10.1128%2FJCM.40.5.1805-1810.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JCM.40.5.1805-1810.2002 ER - TY - JOUR T1 - Second Generation Adeno-Associated Virus Type 2-based Gene Therapy Systems with the Potential for Preferential Integration into AAVS1 AN - 18434157; 5410960 AB - Adeno-associated virus type 2 (AAV-2) is a non-pathogenic human parvovirus that is being developed as a gene therapy vector for the treatment of numerous diseases. One property of wild-type AAV-2, that is highly desirable in a gene therapy vector, is its ability to preferentially integrate its DNA into a 4 kilobase region of human chromosome 19, designated AAVS1. One disadvantage of AAV-2 is its relatively small packaging capacity, approximately 4.7 kilobases. Because of this size limitation, the AAV-2 rep and cap genes were removed from first-generation AAV-2-based gene therapy vectors to make room for the therapeutic or marker gene. It was later discovered that the rep gene, or at least one of its products, the Rep68 or Rep78 protein, is required for preferential integration of AAV-2. Recent developments in AAV-2 gene therapy vector construction allow the inclusion of the rep gene into a second generation of AAV-2-based gene therapy systems. These new systems fall into four major categories: plasmid-based systems, co-transduction with multiple AAV-2 vectors, incorporation of the AAV-2 vector into a larger virus, and in vitro packaging. These systems not only allow the inclusion of the rep gene, they also allow the delivery of larger therapeutic genes. JF - Current Gene Therapy AU - Owens, R A AD - Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bldg. 8, Rm. 310, National Institutes of Health, 8 Center Drive MSC 0840, Bethesda, MD 20892-0840, USA, ro6n@nih.gov Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 145 EP - 159 VL - 2 IS - 2 SN - 1566-5232, 1566-5232 KW - AAVS1 gene KW - Rep68 protein KW - Rep78 protein KW - cap gene KW - chromosome 19 KW - rep gene KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33181:Gene therapy vectors KW - G 07313:Viruses KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18434157?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Gene+Therapy&rft.atitle=Second+Generation+Adeno-Associated+Virus+Type+2-based+Gene+Therapy+Systems+with+the+Potential+for+Preferential+Integration+into+AAVS1&rft.au=Owens%2C+R+A&rft.aulast=Owens&rft.aufirst=R&rft.date=2002-05-01&rft.volume=2&rft.issue=2&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Current+Gene+Therapy&rft.issn=15665232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - First National Survey of Lead and Allergens in Housing: Survey Design and Methods for the Allergen and Endotoxin Components AN - 18429970; 5412250 AB - From July 1998 to August 1999, the U.S. Department of Housing and Urban Development and the National Institute of Environmental Health Sciences conducted the first National Survey of Lead and Allergens in Housing. The purpose of the survey was to assess children's potential household exposure to lead, allergens, and bacterial endotoxins. We surveyed a sample of 831 homes, representing 96 million permanently occupied, noninstitutional housing units that permit resident children. We administered questionnaires to household members, made home observations, and took environmental samples. This article provides general background information on the survey, an overview of the survey design, and a description of the data collection and laboratory methods pertaining to the allergen and endotoxin components. We collected dust samples from a bed, the bedroom floor, a sofa or chair, the living room floor, the kitchen floor, and a basement floor and analyzed them for cockroach allergen Bla g 1, the dust mite allergens Der f 1 and Der p 1, the cat allergen Fel d 1, the dog allergen Can f 1, the rodent allergens Rat n 1 and mouse urinary protein, allergens of the fungus Alternaria alternata, and endotoxin. This article provides the essential context for subsequent reports that will describe the prevalence of allergens and endotoxin in U.S. households, their distribution by various housing characteristics, and their associations with allergic diseases such as asthma and rhinitis. JF - Environmental Health Perspectives AU - Vojta, P J AU - Friedman, W AU - Marker, DA AU - Clickner, R AU - Rogers, J W AU - Viet, S M AU - Muilenberg, M L AU - Thorne, P S AU - Arbes, SJ Jr AU - Zeldin, D C AD - NIEHS, 111 Alexander Drive, Mail Drop D2-02, Research Triangle Park, NC 27709 USA, zeldin@niehs.nih.gov Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 527 EP - 532 VL - 110 IS - 5 SN - 0091-6765, 0091-6765 KW - rhinitis KW - Risk Abstracts; Toxicology Abstracts; Health & Safety Science Abstracts; Pollution Abstracts KW - X 24222:Analytical procedures KW - R2 23060:Medical and environmental health KW - H 12000:Epidemiology and Public Health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18429970?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=First+National+Survey+of+Lead+and+Allergens+in+Housing%3A+Survey+Design+and+Methods+for+the+Allergen+and+Endotoxin+Components&rft.au=Vojta%2C+P+J%3BFriedman%2C+W%3BMarker%2C+DA%3BClickner%2C+R%3BRogers%2C+J+W%3BViet%2C+S+M%3BMuilenberg%2C+M+L%3BThorne%2C+P+S%3BArbes%2C+SJ+Jr%3BZeldin%2C+D+C&rft.aulast=Vojta&rft.aufirst=P&rft.date=2002-05-01&rft.volume=110&rft.issue=5&rft.spage=527&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - A comparison of ELISA and flow microsphere-based assays for quantification of immunoglobulins AN - 18393047; 5370856 AB - An automated microsphere-based flow cytometric assay (FlowMetrix system) was compared with a conventional enzyme-linked immunosorbent assay (ELISA) for quantifying Ig classes in serum and stool samples. The reproducibility of the process of coupling capture antibodies to microspheres was tested. The use of independently coupled microspheres did not increase the variation of assay results relative to using the same bead set in repeated assays. However, it is necessary to ensure quality control of the coupling process since slight variations in the coupling procedures can profoundly affect the density of capture reagents coupled to the microspheres and consequently adversely affect assay precision. Although the ELISA was more sensitive and did not have the problems with instrument performance encountered with the FlowMetrix assay, the latter was more reproducible, had a greater dynamic range of measurement, and took considerably less preparation time than the ELISA. Greater reproducibility is especially important for measurement of fecal Ig, which is typically highly variable. Thus, in addition to its multi-analyte capability, the FlowMetrix assay system has definite advantages over a conventional ELISA. Mechanical problems such as microspheres settling to the bottom of wells during analysis by an automated plate reader will likely be overcome, and sensitivity improved as this technology develops. JF - Journal of Immunological Methods AU - Dasso, J AU - Lee, J AU - Bach, H AU - Mage, R G AD - Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 20892-1892 Bethesda, MD USA Y1 - 2002/05/01/ PY - 2002 DA - 2002 May 01 SP - 23 EP - 33 PB - Elsevier Science VL - 263 IS - 1-2 SN - 0022-1759, 0022-1759 KW - microspheres KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33240:Immunology KW - F 06720:ELISA KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18393047?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunological+Methods&rft.atitle=A+comparison+of+ELISA+and+flow+microsphere-based+assays+for+quantification+of+immunoglobulins&rft.au=Dasso%2C+J%3BLee%2C+J%3BBach%2C+H%3BMage%2C+R+G&rft.aulast=Dasso&rft.aufirst=J&rft.date=2002-05-01&rft.volume=263&rft.issue=1-2&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Morphological Alterations and Elevations in Tumor Necrosis Factor- alpha , Interleukin (IL)-1 alpha , and IL-6 in Mixed Glia Cultures Following Exposure to Trimethyltin: Modulation by Proinflammatory Cytokine Recombinant Proteins and Neutralizing Antibodies AN - 18377556; 5371654 AB - Trimethyltin (TMT), is a hippocampal neurotoxicant characterized by neuronal degeneration, astrogliosis, and microglia reactivity with an associated elevation in proinflammatory cytokine mRNA levels. To examine the role of proinflammatory cytokines in the TMT-induced glia response, mixed cortical glia cultures were exposed to TMT and morphological and cytokine responses were examined. Morphological changes in the glia monolayer, enlarged, rounded cell bodies and retraction of the monolayer into distinct GFAP+ dense processes, displayed a dose (1, 5, and 10 mu M TMT) and temporal response (6-48 h), accompanied by clustering of OX-42+ microglia. Tumor necrosis factor- alpha (TNF), interleukin (IL)-1 alpha , and IL-6 mRNA levels were elevated by 3 and 6 h of TMT (10 mu M) and proteins by 24 h. Recombinant proteins for IL-1 alpha (100 pg/ml) and IL-6 (10 ng/ml) exacerbated the morphological response to TMT while those for TNF alpha (150 pg/ml) did not. Neutralizing antibodies (1:100) to IL-1 alpha and IL-6 showed a slight decrease in the severity of the morphological response to TMT while, at 24 h, TNF alpha antibodies (1:100) and an antibody cocktail offered a significant level of protection. At 6 h, the neutralizing antibodies to TNF alpha or IL-1 alpha did not elevate basal cytokine mRNA levels, however, IL-6 and the cocktail of antibodies significantly elevated IL-1 alpha , IL-1 beta , and IL-6 mRNA levels. The specific elevation in IL-1 alpha and IL-6 mRNA levels induced by TMT remained evident only in cells coexposed to anti-TNF alpha . Similar responses in cytokine mRNA levels were seen in cocultures of hippocampal neurons and glia exposed to TMT. These data suggest a relationship between microglia activation, proinflammatory cytokine release, and glia morphological responses, the significance of which remains to be determined, as well as, the impact on neuronal degeneration. JF - Toxicology and Applied Pharmacology AU - Harry, G J AU - Tyler, K AU - D'hellencourt, CL AU - Tilson, HA AU - Maier, W E AD - National Institute for Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, harry@niehs.nih.gov Y1 - 2002/05/01/ PY - 2002 DA - 2002 May 01 SP - 205 EP - 218 PB - Academic Press VL - 180 IS - 3 SN - 0041-008X, 0041-008X KW - Interleukin 1 alpha KW - morphology KW - Toxicology Abstracts KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18377556?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=Morphological+Alterations+and+Elevations+in+Tumor+Necrosis+Factor-+alpha+%2C+Interleukin+%28IL%29-1+alpha+%2C+and+IL-6+in+Mixed+Glia+Cultures+Following+Exposure+to+Trimethyltin%3A+Modulation+by+Proinflammatory+Cytokine+Recombinant+Proteins+and+Neutralizing+Antibodies&rft.au=Harry%2C+G+J%3BTyler%2C+K%3BD%27hellencourt%2C+CL%3BTilson%2C+HA%3BMaier%2C+W+E&rft.aulast=Harry&rft.aufirst=G&rft.date=2002-05-01&rft.volume=180&rft.issue=3&rft.spage=205&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1006%2Ftaap.2002.9390 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1006/taap.2002.9390 ER - TY - JOUR T1 - Transcriptional Interference by a Complex Formed at the Centromere-Like Partition Site of Plasmid P1 AN - 18376104; 5367345 AB - The partition site, parS, promotes accurate segregation of the replicated P1 plasmid to daughter cells when the P1-encoded ParA and ParB proteins are supplied. The parS site was inserted into the Escherichia coli chromosome between the promoter and the structural gene for s- galactosidase, lacZ. There was little interference with lacZ expression when ParA and ParB were supplied in trans. However, when a mutant ParA protein, ParAM314I, was supplied along with ParB, expression of lacZ was shut down. ParAM314I, ParB, and parS appear to form a nucleoprotein complex that blocks transcription. Mutations in parA and parB that relieved the parAM314I-dependent block were found. In addition, new mutations which impose the block were selected. Five of the latter mapped to parA and one to parB; all had a propagation-defective phenotype (Par super(PD)) similar to that of parAM314I. Thus, whereas a null par mutant P1 plasmid segregates its DNA randomly, these mutants prevent even random distribution of the plasmid. We propose that ParA protein normally interacts transiently with the ParB-parS complex for partition to proceed but that the mutations block ParA dissociation. This "permanent" ParA-ParB-parS complex acts as a transcription block. Consistent with this hypothesis, we found that three of the seven blocking mutations lie within regions of ParA and ParB that are known to interact with each other. When the transcription block is imposed, regional silencing of nearby genes occurs. However, the requirement for ParA and a mutant parA or parB allele distinguishes the transcription block from the regional ParB- dependent gene silencing previously described. JF - Journal of Bacteriology AU - Sawitzke, JA AU - Li, Y AU - Sergueev, K AU - Youngren, B AU - Brendler, T AU - Jones, K AU - Austin, S AD - NCI-Frederick, P.O. Box B, Frederick, MD 21702-1201., austin@ncifcrf.gov Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 2447 EP - 2454 VL - 184 IS - 9 SN - 0021-9193, 0021-9193 KW - ParA protein KW - ParB protein KW - plasmid P1 KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02760:Plasmids KW - G 07320:Bacterial genetics KW - G 07203:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18376104?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Transcriptional+Interference+by+a+Complex+Formed+at+the+Centromere-Like+Partition+Site+of+Plasmid+P1&rft.au=Sawitzke%2C+JA%3BLi%2C+Y%3BSergueev%2C+K%3BYoungren%2C+B%3BBrendler%2C+T%3BJones%2C+K%3BAustin%2C+S&rft.aulast=Sawitzke&rft.aufirst=JA&rft.date=2002-05-01&rft.volume=184&rft.issue=9&rft.spage=2447&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.184.9.2447-2454.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JB.184.9.2447-2454.2002 ER - TY - JOUR T1 - Radiation doses to local populations near nuclear weapons test sites worldwide AN - 17661893; 5459111 AB - Nuclear weapons testing was conducted in the atmosphere at numerous sites worldwide between 1946 and 1980, which resulted in exposures to local populations as a consequence of fallout of radioactive debris. The nuclear tests were conducted by five nations (United States, Soviet Union, United Kingdom, France, and China) primarily at 16 sites. The 16 testing sites, located in nine different countries on five continents (plus Oceania) contributed nearly all of the radioactive materials released to the environment by atmospheric testing; only small amounts were released at a few other minor testing sites. The 16 sites discussed here are Nevada Test Site, USA (North American continent), Bikini and Enewetak, Marshall Islands (Oceania); Johnston Island, USA (Oceania), Christmas and Malden Island, Kiribati (Oceania); Emu Field, Maralinga, and Monte Bello Islands, Australia (Australian continent); Mururoa and Fangataufa, French Polynesia (Oceania), Reggane, Algeria (Africa), Novaya Zemlya and Kapustin Yar, Russia (Europe), Semipalatinsk, Kazakhstan (Asia), and Lop Nor, China (Asia). There were large differences in the numbers of tests conducted at each location and in the total explosive yields. Those factors, as well as differences in population density, lifestyle, environment, and climate at each site, led to large differences in the doses received by local populations. In general, the tests conducted earliest led to the highest individual and population exposures, although the amount of information available for a few of these sites is insufficient to provide any detailed evaluation of radiation exposures. The most comprehensive information for any site is for the Nevada Test Site. The disparities in available information and difficulty to determining the radiation exposures of local populations at each site. It is the goal of this paper to summarize the available information on external and internal doses received by the public living in the regions near each of the mentioned nuclear test sites as a consequence of local fallout deposition. JF - Health Physics AU - Simon, S L AU - Bouville, A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, MSC 7238, Bethesda, MD 20892, USA, ssimon@mail.nih.gov Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 706 EP - 725 VL - 82 IS - 5 SN - 0017-9078, 0017-9078 KW - Pollution Abstracts; Health & Safety Science Abstracts KW - H 8000:Radiation Safety/Electrical Safety KW - P 8000:RADIATION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17661893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+Physics&rft.atitle=Radiation+doses+to+local+populations+near+nuclear+weapons+test+sites+worldwide&rft.au=Simon%2C+S+L%3BBouville%2C+A&rft.aulast=Simon&rft.aufirst=S&rft.date=2002-05-01&rft.volume=82&rft.issue=5&rft.spage=706&rft.isbn=&rft.btitle=&rft.title=Health+Physics&rft.issn=00179078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-12-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Regions of Intermolecular Complementarity in Escherichia coli 16S rRNA, mRNA, and tRNA Molecules AN - 1285082584; 13929621 AB - The results of computer analysis of complementarity regions in the sequences of E. coli 16S rRNA, mRNAs and tRNAs are reported in this article. The potential regions of intermolecular RNA-RNA hybridization, or clinger fragments, in 16S rRNA, which are complementary to the sites frequently occurring in mRNAs and tRNAs, were found. Major clinger fragments on 16S rRNA are universal for genes that belong to different functional groups. Our results show there are adaptations of the structural organization of the 16S rRNA molecule to messenger and transport RNA sequences. RNA interaction with clinger fragments may contribute to upregulation of the translation process through increasing the local concentration of mRNAs and tRNAs in the vicinity of the ribosome and their proper positioning, as well as decrease the efficiency of translation through nonspecific mRNA-16SrRNA interactions. JF - Molecular Biology AU - Shabalina, SA AD - National Institutes of Health, NCBI, NLM, Rockville Pike, Bethesda, MD, 20894 Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 359 EP - 364 PB - Springer-Verlag, Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 36 IS - 3 SN - 0026-8933, 0026-8933 KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Adaptations KW - Complementarity KW - Computer applications KW - RNA transport KW - Ribosomes KW - Translation KW - rRNA 16S KW - tRNA KW - Escherichia coli KW - J 02310:Genetics & Taxonomy KW - N 14810:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1285082584?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Biology&rft.atitle=Regions+of+Intermolecular+Complementarity+in+Escherichia+coli+16S+rRNA%2C+mRNA%2C+and+tRNA+Molecules&rft.au=Shabalina%2C+SA&rft.aulast=Shabalina&rft.aufirst=SA&rft.date=2002-05-01&rft.volume=36&rft.issue=3&rft.spage=359&rft.isbn=&rft.btitle=&rft.title=Molecular+Biology&rft.issn=00268933&rft_id=info:doi/10.1023%2FA%3A1016003228275 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2013-02-01 N1 - Last updated - 2013-02-22 N1 - SubjectsTermNotLitGenreText - Translation; Adaptations; tRNA; Ribosomes; Computer applications; rRNA 16S; Complementarity; RNA transport; Escherichia coli DO - http://dx.doi.org/10.1023/A:1016003228275 ER - TY - JOUR T1 - Involvement of DNA polymerase beta in protection against the cytotoxicity of oxidative DNA damage. AN - 72796848; 12509250 AB - We had shown previously that DNA polymerase beta (beta-pol) null mouse fibroblasts, deficient in base excision repair (BER), are hypersensitive to monofunctional methylating agents but not to hydrogen peroxide (H2O2). This is surprising because beta-pol is thought to be involved in BER of oxidative as well as methylated DNA damage. We confirm these findings here in early-passage cells. However, with time in culture, beta-pol null cells become hypersensitive to H2O2 and other reactive oxygen species-generating agents. Analysis of in vitro BER reveals a strong deficiency in single-nucleotide BER of 8-oxoguanine (8-oxoG) by both early- and late-passage beta-pol null cell extracts. Therefore, in early-passage wild-type and beta-pol null cells, the capacity for single-nucleotide BER of 8-oxoG does not correlate with cellular sensitivity to H2O2. Expression of beta-pol protein in the late-passage null cells almost completely reverses the H2O2-hypersensitivity phenotype. Methoxyamine (MX) treatment sensitizes late-passage wild-type cells to H2O2 as expected for beta-pol-mediated single-nucleotide BER; however in beta-pol null cells, MX has no effect. The data indicate a role(s) of beta-pol-dependent repair in protection against the cytotoxicity of oxidative DNA damage in wild-type cells. JF - DNA repair AU - Horton, Julie K AU - Baker, Audrey AU - Berg, Brian J Vande AU - Sobol, Robert W AU - Wilson, Samuel H AD - Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2002/04/29/ PY - 2002 DA - 2002 Apr 29 SP - 317 EP - 333 VL - 1 IS - 4 SN - 1568-7864, 1568-7864 KW - Antineoplastic Agents KW - 0 KW - DNA Primers KW - Hydroxylamines KW - Oxidants KW - Poly(ADP-ribose) Polymerase Inhibitors KW - Guanosine KW - 12133JR80S KW - Peroxynitrous Acid KW - 14691-52-2 KW - 8-hydroxyguanosine KW - 3868-31-3 KW - methoxyamine KW - 9TZH4WY30J KW - Hydrogen Peroxide KW - BBX060AN9V KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - DNA Polymerase beta KW - EC 2.7.7.- KW - N-Glycosyl Hydrolases KW - EC 3.2.2.- KW - DNA-Formamidopyrimidine Glycosylase KW - EC 3.2.2.23 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Animals KW - Poly(ADP-ribose) Polymerases -- drug effects KW - Glutathione -- metabolism KW - Cell Division -- drug effects KW - Mice KW - Glutathione -- deficiency KW - Hydrogen Peroxide -- toxicity KW - Blotting, Western KW - Cell Survival -- drug effects KW - Transfection KW - N-Glycosyl Hydrolases -- metabolism KW - In Vitro Techniques KW - Antineoplastic Agents -- toxicity KW - Hydroxylamines -- toxicity KW - Peroxynitrous Acid -- toxicity KW - Cytoprotection -- physiology KW - DNA Primers -- chemistry KW - Fibroblasts -- drug effects KW - Fibroblasts -- enzymology KW - DNA Repair KW - Guanosine -- analogs & derivatives KW - DNA Polymerase beta -- genetics KW - DNA Polymerase beta -- physiology KW - Oxidants -- toxicity KW - Guanosine -- metabolism KW - DNA Damage -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72796848?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=DNA+repair&rft.atitle=Involvement+of+DNA+polymerase+beta+in+protection+against+the+cytotoxicity+of+oxidative+DNA+damage.&rft.au=Horton%2C+Julie+K%3BBaker%2C+Audrey%3BBerg%2C+Brian+J+Vande%3BSobol%2C+Robert+W%3BWilson%2C+Samuel+H&rft.aulast=Horton&rft.aufirst=Julie&rft.date=2002-04-29&rft.volume=1&rft.issue=4&rft.spage=317&rft.isbn=&rft.btitle=&rft.title=DNA+repair&rft.issn=15687864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-05 N1 - Date created - 2003-01-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of Yersinia murine toxin in survival of Yersinia pestis in the midgut of the flea vector. AN - 71630984; 11976454 AB - Transmission by flea bite is a relatively recent adaptation that distinguishes Yersinia pestis, the plague bacillus, from closely related enteric bacteria. Here, a plasmid-encoded phospholipase D (PLD), previously characterized as Yersinia murine toxin (Ymt), was shown to be required for survival of Y. pestis in the midgut of its principal vector, the rat flea Xenopsylla cheopis. Intracellular PLD activity appeared to protect Y. pestis from a cytotoxic digestion product of blood plasma in the flea gut. By enabling colonization of the flea midgut, acquisition of this PLD may have precipitated the transition of Y. pestis to obligate arthropod-borne transmission. JF - Science (New York, N.Y.) AU - Hinnebusch, B Joseph AU - Rudolph, Amy E AU - Cherepanov, Peter AU - Dixon, Jack E AU - Schwan, Tom G AU - Forsberg, Ake AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. jhinnebusch@niaid.nih.gov Y1 - 2002/04/26/ PY - 2002 DA - 2002 Apr 26 SP - 733 EP - 735 VL - 296 IS - 5568 KW - Bacterial Toxins KW - 0 KW - Recombinant Fusion Proteins KW - Phospholipase D KW - EC 3.1.4.4 KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Animals KW - Spheroplasts -- physiology KW - Fluorescent Antibody Technique, Indirect KW - Plague -- transmission KW - Digestive System -- metabolism KW - Digestive System -- microbiology KW - Recombinant Fusion Proteins -- toxicity KW - Plasmids KW - Mutation KW - Siphonaptera -- metabolism KW - Bacterial Toxins -- genetics KW - Phospholipase D -- metabolism KW - Phospholipase D -- genetics KW - Bacterial Toxins -- metabolism KW - Insect Vectors -- metabolism KW - Yersinia pestis -- physiology KW - Yersinia pestis -- genetics KW - Yersinia pestis -- enzymology KW - Insect Vectors -- microbiology KW - Siphonaptera -- microbiology KW - Yersinia pestis -- pathogenicity KW - Phospholipase D -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71630984?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28New+York%2C+N.Y.%29&rft.atitle=Role+of+Yersinia+murine+toxin+in+survival+of+Yersinia+pestis+in+the+midgut+of+the+flea+vector.&rft.au=Hinnebusch%2C+B+Joseph%3BRudolph%2C+Amy+E%3BCherepanov%2C+Peter%3BDixon%2C+Jack+E%3BSchwan%2C+Tom+G%3BForsberg%2C+Ake&rft.aulast=Hinnebusch&rft.aufirst=B&rft.date=2002-04-26&rft.volume=296&rft.issue=5568&rft.spage=733&rft.isbn=&rft.btitle=&rft.title=Science+%28New+York%2C+N.Y.%29&rft.issn=1095-9203&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-23 N1 - Date created - 2002-04-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Linkage of caspase-mediated degradation of paxillin to apoptosis in Ba/F3 murine pro-B lymphocytes. AN - 71627069; 11825902 AB - We have cloned the complete cDNA from mouse paxillin, a 68-kDa adapter protein found in focal adhesions. We found that paxillin was degraded by caspases in Ba/F3 cell apoptosis induced by withdrawal of interleukin-3 (IL-3), a survival factor for this cell, and by ionizing radiation. Also, paxillin was degraded in vitro by incubation with recombinant caspase-3. Western blot analyses of degradation products of overexpressed green fluorescence protein-tagged paxillin and site-specific mutants demonstrated that Asp-102 and Asp-301 were early caspase cleavage sites, and Asp-5, Asp-146, Asp-165, and Asp-222 were late cleavage sites. Overexpression of paxillin delayed apoptosis of Ba/F3 after IL-3 withdrawal. Furthermore, this anti-apoptotic effect of paxillin was augmented by a triple mutation in aspartic acids at caspase cleavage sites. These results suggest that paxillin plays a critical role in cell survival signaling and that the cleavage of paxillin by caspases might be an important event for focal adhesion disassembly during cell apoptosis, contributing to detachment, rounding, and death. JF - The Journal of biological chemistry AU - Chay, Kee-Oh AU - Park, Sung Sup AU - Mushinski, J Frederic AD - Laboratory of Genetics, NCI, National Institutes of Health, Bethesda, Maryland 20852, USA. Y1 - 2002/04/26/ PY - 2002 DA - 2002 Apr 26 SP - 14521 EP - 14529 VL - 277 IS - 17 SN - 0021-9258, 0021-9258 KW - Cytoskeletal Proteins KW - 0 KW - DNA Primers KW - Interleukin-3 KW - Luminescent Proteins KW - Paxillin KW - Phosphoproteins KW - Pxn protein, mouse KW - Recombinant Fusion Proteins KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Casp3 protein, mouse KW - EC 3.4.22.- KW - Caspase 3 KW - Caspases KW - Index Medicus KW - Animals KW - Gamma Rays KW - Luminescent Proteins -- metabolism KW - Mice KW - Hydrolysis KW - Recombinant Fusion Proteins -- chemistry KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Interleukin-3 -- metabolism KW - Recombinant Fusion Proteins -- genetics KW - Molecular Sequence Data KW - Cell Line KW - Phosphoproteins -- genetics KW - Phosphoproteins -- chemistry KW - Cytoskeletal Proteins -- chemistry KW - Cytoskeletal Proteins -- metabolism KW - Caspases -- metabolism KW - Phosphoproteins -- metabolism KW - Cytoskeletal Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71627069?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Linkage+of+caspase-mediated+degradation+of+paxillin+to+apoptosis+in+Ba%2FF3+murine+pro-B+lymphocytes.&rft.au=Chay%2C+Kee-Oh%3BPark%2C+Sung+Sup%3BMushinski%2C+J+Frederic&rft.aulast=Chay&rft.aufirst=Kee-Oh&rft.date=2002-04-26&rft.volume=277&rft.issue=17&rft.spage=14521&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-31 N1 - Date created - 2002-04-22 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF293882; GENBANK; AF293883 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Entry into Cells and Selective Degradation of tRNAs by a Cytotoxic Member of the RNase A Family AN - 18381431; 5359957 AB - Onconase (P-30 protein), an enzyme in the ribonuclease A superfamily, exerts cytostatic, cytotoxic, and antiviral activity when added to the medium of growing mammalian cells. We find that onconase enters living mammalian cells and selectively cleaves tRNA with no detectable degradation of rRNA. The RNA specificity of onconase in vitro using reticulocyte lysate and purified RNA substrates indicates that proteins associated with rRNA protect the rRNA from the onconase ribonucleolytic action contributing to the cellular tRNA selectivity of onconase. The onconase-mediated tRNA degradation in cells appears to be accompanied by increased levels of tRNA turnover and induction of tRNA synthesis perhaps in response to the selective toxin-induced loss of tRNA. Degradation products of tRNA sub(3) super(Lys), which acts as a primer for HIV-1 replication, were clearly detected in cells infected with HIV-1 and treated with sublethal concentrations of onconase. However, a new synthesis of tRNA sub(3) super(Lys) also seemed to occur in these cells resulting in plateauing of the steady-state levels of this tRNA. We conclude that the degradation of tRNAs may be a primary factor in the cytotoxic activity of onconase. JF - Journal of Biological Chemistry AU - Saxena, S K AU - Sirdeshmukh, R AU - Ardelt, W AU - Mikulski, S M AU - Shogen, K AU - Youle, R J AD - Biochemistry Section, Surgical Neurology Branch, NINDS, National Institutes of Health, Bethesda, Maryland 20892-1414, USA, youle@helix.nih.gov Y1 - 2002/04/26/ PY - 2002 DA - 2002 Apr 26 SP - 15142 EP - 15146 VL - 277 IS - 17 SN - 0021-9258, 0021-9258 KW - HIV-1 KW - Onconase KW - P-30 protein KW - onconase KW - ribonuclease A KW - tRNA Lys KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - X 24240:Miscellaneous KW - N 14711:RNases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18381431?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Entry+into+Cells+and+Selective+Degradation+of+tRNAs+by+a+Cytotoxic+Member+of+the+RNase+A+Family&rft.au=Saxena%2C+S+K%3BSirdeshmukh%2C+R%3BArdelt%2C+W%3BMikulski%2C+S+M%3BShogen%2C+K%3BYoule%2C+R+J&rft.aulast=Saxena&rft.aufirst=S&rft.date=2002-04-26&rft.volume=277&rft.issue=17&rft.spage=15142&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Transcription Termination: Primary Intermediates and Secondary Adducts AN - 18314829; 5359976 AB - In living organisms, stable elongation complexes of RNA polymerase dissociate at specific template positions in a process of transcription termination. It has been suggested that the dissociation is not the immediate cause of termination but is preceded by catalytic inactivation of the elongation complex. In vitro reducing ionic strength can be used to stabilize very unstable and catalytically inactive complex at the point of termination; the previous biochemical characterization of this complex has led to important conclusions regarding termination mechanism. Here we analyze in detail the complexes formed between DNA template, nascent RNA, and Escherichia coli RNA polymerase during transcription through the tR2 terminator of bacteriophage lambda . At low ionic strength, the majority of elongation complexes fall apart upon reaching the terminator. Released RNA and DNA efficiently rebind RNA polymerase (RNAP) and form binary RNAP super(.)RNA and RNAP super(.)DNA complexes, which are indistinguishable from binary complexes obtained by direct mixing of the purified nucleic acids and the enzyme. A small fraction of elongation complexes that reach termination point escapes dissociation because RNA polymerase has backtracked from the terminator to an upstream DNA position. Thus, transcription elongation to a terminator site produces no termination intermediates that withstand dissociation in the time scale appropriate for biochemical studies. JF - Journal of Biological Chemistry AU - Kashlev, M AU - Komissarova, N AD - NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, mkashlev@mail.ncifcrf.gov Y1 - 2002/04/26/ PY - 2002 DA - 2002 Apr 26 SP - 14501 EP - 14508 VL - 277 IS - 17 SN - 0021-9258, 0021-9258 KW - terminator KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - DNA-directed RNA polymerase KW - Transcription termination KW - Escherichia coli KW - Templates KW - J 02726:RNA and ribosomes KW - N 14553:Transcription initiation, elongation & termination UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18314829?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Transcription+Termination%3A+Primary+Intermediates+and+Secondary+Adducts&rft.au=Kashlev%2C+M%3BKomissarova%2C+N&rft.aulast=Kashlev&rft.aufirst=M&rft.date=2002-04-26&rft.volume=277&rft.issue=17&rft.spage=14501&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Templates; Transcription termination; DNA-directed RNA polymerase ER - TY - JOUR T1 - Dose-related effects of smallpox vaccine. AN - 71622356; 11923489 AB - We conducted a double-blind, randomized trial of three dilutions of vaccinia virus vaccine in previously unimmunized adults in order to assess the clinical success rates, humoral responses, and virus-specific activity of cytotoxic T cells and interferon-gamma-producing T cells. Sixty healthy adults were inoculated intradermally by bifurcated needle with undiluted vaccine (dose, 10(7.8) plaque-forming units [pfu] per milliliter), a 1:10 dilution (dose, 10(6.5) pfu per milliliter), or a 1:100 dilution (dose, 10(5.0) pfu per milliliter); there were 20 subjects in each group. The subjects were monitored with respect to vesicle formation (an indicator of successful vaccination), the viral titer at the time of peak lesion formation, antiviral antibodies, and cellular immune responses. A vaccinia vesicle developed in 19 of the 20 subjects who received undiluted vaccine (95 percent), 14 of the 20 who received the 1:10 dilution (70 percent), and 3 of the 20 who received the 1:100 dilution (15 percent). One month after vaccination, 34 of 36 subjects with vesicles had antibody responses, as compared with only 1 of 24 subjects without clinical evidence of vaccinia virus replication. Vigorous cytotoxic T-cell and interferon-gamma responses occurred in 94 percent of subjects with vesicles, and a cytotoxic T-cell response occurred in only one subject without a vesicle. The vaccinia virus vaccine (which was produced in 1982 or earlier) still has substantial potency when administered by a bifurcated needle to previously unvaccinated adults. Diluting the vaccine reduces the rate of successful vaccination. The development of vesicular skin lesions after vaccination correlates with the induction of the antibody and T-cell responses that are considered essential for clearing vaccinia virus infections. JF - The New England journal of medicine AU - Frey, Sharon E AU - Newman, Frances K AU - Cruz, John AU - Shelton, W Brian AU - Tennant, Janice M AU - Polach, Tamara AU - Rothman, Alan L AU - Kennedy, Jeffrey S AU - Wolff, Mark AU - Belshe, Robert B AU - Ennis, Francis A AD - Department of Medicine, National Institute of Allergy and Infectious Diseases Vaccine and Treatment Evaluation Unit, Saint Louis University School of Medicine, St. Louis, USA. Y1 - 2002/04/25/ PY - 2002 DA - 2002 Apr 25 SP - 1275 EP - 1280 VL - 346 IS - 17 KW - Antibodies, Viral KW - 0 KW - Smallpox Vaccine KW - Interferon-gamma KW - 82115-62-6 KW - Abridged Index Medicus KW - Index Medicus KW - Virus Replication KW - Double-Blind Method KW - Humans KW - Variola virus -- isolation & purification KW - Antibodies, Viral -- blood KW - T-Lymphocytes, Cytotoxic -- physiology KW - Variola virus -- growth & development KW - Dose-Response Relationship, Immunologic KW - Adult KW - Cytotoxicity Tests, Immunologic KW - Adolescent KW - Interferon-gamma -- analysis KW - Variola virus -- immunology KW - Smallpox Vaccine -- immunology KW - Smallpox -- immunology KW - Smallpox Vaccine -- adverse effects KW - Smallpox Vaccine -- administration & dosage KW - Smallpox -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71622356?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Dose-related+effects+of+smallpox+vaccine.&rft.au=Frey%2C+Sharon+E%3BNewman%2C+Frances+K%3BCruz%2C+John%3BShelton%2C+W+Brian%3BTennant%2C+Janice+M%3BPolach%2C+Tamara%3BRothman%2C+Alan+L%3BKennedy%2C+Jeffrey+S%3BWolff%2C+Mark%3BBelshe%2C+Robert+B%3BEnnis%2C+Francis+A&rft.aulast=Frey&rft.aufirst=Sharon&rft.date=2002-04-25&rft.volume=346&rft.issue=17&rft.spage=1275&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=1533-4406&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-30 N1 - Date created - 2002-04-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diagnosis and management of smallpox AN - 18390877; 5382395 AB - The last case of endemic smallpox occurred in Somalia in 1977, and eradication of the disease was declared in 1980. With no natural reservoir, variola virus, which causes smallpox, has existed only in laboratories; indeed, the last case of smallpox was due to infection acquired in a laboratory in the United Kingdom in 1978. During the global program of smallpox eradication, the World Health Organization (WHO) made concerted efforts to decrease the number of laboratories retaining variola virus. On the basis of contacts with all countries and a total of 823 microbiology institutions, 76 such laboratories had been identified by 1978. By 1984, only the Centers for Disease Control and Prevention (CDC), in Atlanta, and the Research Institute of Viral Preparations, in Moscow, retained variola virus isolates. In 1994, the Russian isolates were moved to the State Research Center of Virology and Biotechnology (the Vektor Institute), in Novosibirsk, Russia. There is concern that variola virus resides outside these laboratories and could be used as a weapon by terrorists. Possible sources are virus in countries that claim that they destroyed their stocks but did not and virus acquired from laboratories in the former Soviet Union. An accidental or deliberate release of smallpox could cause a major epidemic. Because vaccination against smallpox has not been performed routinely in the United States since 1972 and in the rest of the world since about 1982, there is now a large population of susceptible persons. Thus, if an outbreak occurred, prompt recognition and institution of control measures would be important. JF - New England Journal of Medicine AU - Breman, J G AU - Henderson, DA AD - Fogarty International Center, National Institutes of Health, 16 Center Dr., MSC 6705, Bldg. 16, Rm. 214, Bethesda, MD 20892, USA, jbreman@nih.gov Y1 - 2002/04/25/ PY - 2002 DA - 2002 Apr 25 SP - 1300 EP - 1308 VL - 346 IS - 17 SN - 0028-4793, 0028-4793 KW - bioterrorism KW - man KW - smallpox virus KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Virology & AIDS Abstracts KW - W4 240:Bioterrorism & Biological Warfare KW - W 30965:Miscellaneous, Reviews KW - V 22121:Diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18390877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=New+England+Journal+of+Medicine&rft.atitle=Diagnosis+and+management+of+smallpox&rft.au=Breman%2C+J+G%3BHenderson%2C+DA&rft.aulast=Breman&rft.aufirst=J&rft.date=2002-04-25&rft.volume=346&rft.issue=17&rft.spage=1300&rft.isbn=&rft.btitle=&rft.title=New+England+Journal+of+Medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Placement of 19F into the center of GB1: effects on structure and stability. AN - 71808806; 12062409 AB - A structural and thermodynamic characterization of 5F-Trp-substituted immunoglobulin binding domain B1 of streptococcal protein G (GB1) was carried out by nuclear magnetic resonance and circular dichroism spectroscopy. A single fluorine reporter atom was positioned at the center of the three-dimensional structure, uniquely poised to be exploited for studying interior properties of this protein. We demonstrate that the introduction of 5F-Trp does not affect the global and local architecture of GB1 and has no influence on the thermodynamic stability. The favorable properties of the fluorinated GB1 render this molecule a desirable model system for the development of spectroscopic methodology and theoretical calculations. JF - FEBS letters AU - Campos-Olivas, Ramón AU - Aziz, Rehan AU - Helms, Gregory L AU - Evans, Jeremy N S AU - Gronenborn, Angela M AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 5, Room 130, Bethesda, MD 20892, USA. Y1 - 2002/04/24/ PY - 2002 DA - 2002 Apr 24 SP - 55 EP - 60 VL - 517 IS - 1-3 SN - 0014-5793, 0014-5793 KW - Bacterial Proteins KW - 0 KW - IgG Fc-binding protein, Streptococcus KW - Immunoglobulin G KW - Fluorine KW - 284SYP0193 KW - Tryptophan KW - 8DUH1N11BX KW - Index Medicus KW - Thermodynamics KW - Models, Molecular KW - Streptococcus -- chemistry KW - Protein Denaturation KW - Hemodynamics KW - Circular Dichroism KW - Protein Structure, Tertiary KW - Immunoglobulin G -- metabolism KW - Mutation KW - Protein Conformation KW - Mutagenesis KW - Magnetic Resonance Spectroscopy KW - Bacterial Proteins -- genetics KW - Bacterial Proteins -- chemistry KW - Bacterial Proteins -- metabolism KW - Fluorine -- chemistry KW - Tryptophan -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71808806?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEBS+letters&rft.atitle=Placement+of+19F+into+the+center+of+GB1%3A+effects+on+structure+and+stability.&rft.au=Campos-Olivas%2C+Ram%C3%B3n%3BAziz%2C+Rehan%3BHelms%2C+Gregory+L%3BEvans%2C+Jeremy+N+S%3BGronenborn%2C+Angela+M&rft.aulast=Campos-Olivas&rft.aufirst=Ram%C3%B3n&rft.date=2002-04-24&rft.volume=517&rft.issue=1-3&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=FEBS+letters&rft.issn=00145793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-29 N1 - Date created - 2002-06-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A nitric oxide-releasing polydiazeniumdiolate derived from acetonitrile. AN - 71641441; 11950353 AB - Acetonitrile, frequently used as a solvent in reactions of nitric oxide (NO) with amines and other nucleophiles to introduce the [N(O)NO](-) (diazeniumdiolate) functional group, has itself been shown to react with NO in the presence of strong base to yield methane trisdiazeniumdiolate (1), presumably via an intermediate trisdiazeniumdiolated imidate. Aqueous hydrolysis of 1 does not follow simple first-order kinetics and produces mixtures of NO and nitrous oxide in ratios that vary with solution pH. [reaction: see text] JF - Organic letters AU - Arnold, Ernst V AU - Citro, Michael L AU - Keefer, Larry K AU - Hrabie, Joseph A AD - Chemistry Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD 21702, USA. Y1 - 2002/04/18/ PY - 2002 DA - 2002 Apr 18 SP - 1323 EP - 1325 VL - 4 IS - 8 SN - 1523-7060, 1523-7060 KW - Acetonitriles KW - 0 KW - Azo Compounds KW - Indicators and Reagents KW - Solvents KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Spectrophotometry, Infrared KW - Azo Compounds -- chemistry KW - Kinetics KW - Reference Standards KW - Spectrophotometry, Ultraviolet KW - Magnetic Resonance Spectroscopy KW - Acetonitriles -- chemistry KW - Nitric Oxide -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71641441?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Organic+letters&rft.atitle=A+nitric+oxide-releasing+polydiazeniumdiolate+derived+from+acetonitrile.&rft.au=Arnold%2C+Ernst+V%3BCitro%2C+Michael+L%3BKeefer%2C+Larry+K%3BHrabie%2C+Joseph+A&rft.aulast=Arnold&rft.aufirst=Ernst&rft.date=2002-04-18&rft.volume=4&rft.issue=8&rft.spage=1323&rft.isbn=&rft.btitle=&rft.title=Organic+letters&rft.issn=15237060&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-23 N1 - Date created - 2002-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene structure, tissue expression, and linkage mapping of the mouse DLC-1 gene (Arhgap7). AN - 71728232; 12034501 AB - DLC-1 (deleted in liver cancer 1) is a candidate tumor suppressor gene for hepatocellular carcinoma and other cancers. It is the human homologue of rat p122, which has been shown to function as a GTPase activating protein for RhoA, and it may be involved in signal transduction pathways regulating cell proliferation and adhesion. To establish an animal model for studying the regulation and function of DLC-1, we have undertaken the characterization of the mouse DLC-1 gene. Northern blot analysis shows that the mouse DLC-1 mRNA is widely expressed, with the highest levels in heart, liver, and lung. Mouse genomic clones that contain the entire DLC-1 gene of 47 kb were isolated. The mouse gene consists of 14 exons, and the structural organization is highly similar to that of the human gene. The promoter region of the mouse gene was GC-rich and contained potential binding sites for transcription factors SP1, GCF, and AP-2. A polymorphic microsatellite marker in intron 8 was used for mapping the gene (Arhgap7) to 20 cM on mouse chromosome 8 and for allelotyping of mouse liver tumor DNAs. JF - Gene AU - Durkin, Marian E AU - Yuan, Bao-Zhu AU - Thorgeirsson, Snorri S AU - Popescu, Nicholas C AD - Laboratory of Experimental Carcinogenesis, Building 37, Room 3C28, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. marian_durkin@nih.gov Y1 - 2002/04/17/ PY - 2002 DA - 2002 Apr 17 SP - 119 EP - 127 VL - 288 IS - 1-2 SN - 0378-1119, 0378-1119 KW - DLC-1 (deleted in liver cancer) protein, mouse KW - 0 KW - GTPase-Activating Proteins KW - RNA, Messenger KW - Tumor Suppressor Proteins KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Humans KW - Gene Expression KW - RNA, Messenger -- genetics KW - Mice, Transgenic KW - Chromosome Mapping KW - Genes -- genetics KW - Liver Neoplasms -- pathology KW - Carcinoma, Hepatocellular -- genetics KW - Carcinoma, Hepatocellular -- pathology KW - Molecular Sequence Data KW - DNA -- chemistry KW - Promoter Regions, Genetic -- genetics KW - Male KW - Exons KW - Mice KW - Sequence Analysis, DNA KW - Gene Deletion KW - Mice, Inbred Strains KW - Base Sequence KW - Mice, Inbred CBA KW - RNA, Messenger -- metabolism KW - DNA -- genetics KW - Introns KW - Mice, Inbred C57BL KW - Female KW - Liver Neoplasms -- genetics KW - GTPase-Activating Proteins -- genetics KW - Tumor Suppressor Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71728232?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene&rft.atitle=Gene+structure%2C+tissue+expression%2C+and+linkage+mapping+of+the+mouse+DLC-1+gene+%28Arhgap7%29.&rft.au=Durkin%2C+Marian+E%3BYuan%2C+Bao-Zhu%3BThorgeirsson%2C+Snorri+S%3BPopescu%2C+Nicholas+C&rft.aulast=Durkin&rft.aufirst=Marian&rft.date=2002-04-17&rft.volume=288&rft.issue=1-2&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-12 N1 - Date created - 2002-05-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A nonsense mutation in zebrafish gata1 causes the bloodless phenotype in vlad tepes. AN - 71614883; 11960002 AB - Vlad tepes (vlt(m651)) is one of only five "bloodless" zebrafish mutants isolated through large-scale chemical mutagenesis screening. It is characterized by a severe reduction in blood cell progenitors and few or no blood cells at the onset of circulation. We now report characterization of the mutant phenotype and the identification of the gene mutated in vlt(m651). Embryos homozygous for the vlt(m651) mutation had normal expression of hematopoietic stem cell markers through 24 h postfertilization, as well as normal expression of myeloid and lymphoid markers. Analysis of erythroid development revealed variable expression of erythroid markers. Through positional and candidate gene cloning approaches we identified a nonsense mutation in the gata1 gene, 1015C --> T (Arg-339 --> Stop), in vlt(m651). The nonsense mutation was located C-terminal to the two zinc fingers and resulted in a truncated protein that was unable to bind DNA or mediate GATA-specific transactivation. A BAC clone containing the zebrafish gata1 gene was able to rescue the bloodless phenotype in vlt(m651). These results show that the vlt(m651) mutation is a previously uncharacterized gata1 allele in the zebrafish. The vlt(m651) mutation sheds new light on Gata1 structure and function in vivo, demonstrates that Gata1 plays an essential role in zebrafish hematopoiesis with significant conservation of function between mammals and zebrafish, and offers a powerful tool for future studies of the hematopoietic pathway. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Lyons, Susan E AU - Lawson, Nathan D AU - Lei, Lin AU - Bennett, Paul E AU - Weinstein, Brant M AU - Liu, P Paul AD - National Human Genome Research Institute, National Institutes of Health, Building 49, Room 3A18, Bethesda, MD 20892, USA. Y1 - 2002/04/16/ PY - 2002 DA - 2002 Apr 16 SP - 5454 EP - 5459 VL - 99 IS - 8 SN - 0027-8424, 0027-8424 KW - Codon, Nonsense KW - 0 KW - DNA, Complementary KW - DNA-Binding Proteins KW - Erythroid-Specific DNA-Binding Factors KW - GATA1 Transcription Factor KW - GATA1 protein, human KW - Gata1 protein, mouse KW - Transcription Factors KW - Zebrafish Proteins KW - gata1 protein, zebrafish KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Genetic Linkage KW - 3T3 Cells KW - Animals KW - Centromere KW - Homozygote KW - Humans KW - DNA -- metabolism KW - Mice KW - Protein Binding KW - Zebrafish KW - Transcriptional Activation KW - Phenotype KW - Genotype KW - Polymerase Chain Reaction KW - In Situ Hybridization KW - Alleles KW - DNA, Complementary -- metabolism KW - Mutation KW - Transcription Factors -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71614883?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=A+nonsense+mutation+in+zebrafish+gata1+causes+the+bloodless+phenotype+in+vlad+tepes.&rft.au=Lyons%2C+Susan+E%3BLawson%2C+Nathan+D%3BLei%2C+Lin%3BBennett%2C+Paul+E%3BWeinstein%2C+Brant+M%3BLiu%2C+P+Paul&rft.aulast=Lyons&rft.aufirst=Susan&rft.date=2002-04-16&rft.volume=99&rft.issue=8&rft.spage=5454&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-14 N1 - Date created - 2002-04-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Exp Hematol. 1995 Feb;23(2):99-107 [7828675] Mol Cell Biol. 1995 Feb;15(2):634-41 [7823932] Genetics. 1995 Apr;139(4):1727-35 [7789773] Blood. 1995 Aug 15;86(4):1502-14 [7632958] Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10713-7 [7479870] Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12355-8 [8901585] Development. 1996 Dec;123:303-9 [9007250] Development. 1996 Dec;123:311-9 [9007251] Mol Cell Biol. 1997 Mar;17(3):1535-42 [9032281] Dev Biol. 1997 Feb 15;182(2):331-41 [9070331] Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4487-92 [9114016] Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):7976-81 [9223298] J Biol Chem. 1997 Oct 17;272(42):26585-94 [9334239] Genes Dev. 1998 Mar 1;12(5):621-6 [9499398] Stem Cells. 1998;16(2):89-98 [9554032] J Biol Chem. 1998 Jul 3;273(27):16798-809 [9642238] EMBO J. 1998 Jul 15;17(14):4029-45 [9670018] Nat Genet. 1998 Nov;20(3):244-50 [9806542] Immunol Rev. 1998 Dec;166:199-220 [9914914] J Biol Chem. 1999 Mar 5;274(10):6062-73 [10037687] Ann N Y Acad Sci. 1999 Apr 30;872:256-62; discussion 262-4 [10372128] Development. 1999 Sep;126(17):3735-45 [10433904] Genes Dev. 2000 Apr 1;14(7):755-62 [10766732] Gene. 2000 Apr 18;247(1-2):153-66 [10773455] Genome Res. 2000 Apr;10(4):558-67 [10779498] Mech Dev. 2000 Oct;97(1-2):173-6 [11025220] Development. 2000 Dec;127(23):5123-32 [11060238] Blood. 2000 Dec 15;96(13):4178-84 [11110689] Blood. 2001 May 1;97(9):2611-7 [11313249] Blood Cells Mol Dis. 2001 Jan-Feb;27(1):62-4 [11358361] Development. 2001 Jun;128(12):2341-50 [11493553] Blood. 2001 Sep 15;98(6):1792-801 [11535513] Curr Biol. 2001 Sep 4;11(17):1353-7 [11553329] Cell. 1990 Nov 16;63(4):665-72 [2225071] Nature. 1991 Jan 17;349(6306):257-60 [1987478] Genes Dev. 1990 Nov;4(11):1886-98 [2276623] Nucleic Acids Res. 1992 Sep 11;20(17):4429-36 [1408744] Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1676-80 [8446581] Science. 1993 Jul 23;261(5120):438-46 [8332909] J Cell Physiol. 1994 Sep;160(3):417-26 [8077279] Genes Dev. 1994 May 15;8(10):1184-97 [7926723] Development. 1995 Jan;121(1):163-72 [7867497] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Complementary advantageous substitutions in the evolution of an antiviral RNase of higher primates. AN - 71613200; 11917138 AB - An improved understanding of the evolution of gene function at the molecular level may provide significant insights into the origin of biological novelty and adaptation. With the approach of ancestral protein reconstruction, we here address the question of how a dramatically enhanced ribonucleolytic activity and the related antiviral activity evolved in a recently duplicated ribonuclease (eosinophil-derived neurotoxin) gene of higher primates. We show that the mother gene of the duplicated genes had already possessed a weak antiviral activity before duplication. After duplication, substitutions at two interacting sites (Arg-64-->Ser and Thr-132-->Arg) resulted in a 13-fold enhancement of the ribonucleolytic activity of eosinophil-derived neurotoxin. These substitutions are also necessary for the potent antiviral activity, with contributions from additional amino acid changes at interacting sites. Our observation that a change in eosinophil-derived neurotoxin function occurs only when both interacting sites are altered indicates the importance of complementary substitutions in protein evolution. Thus, neutral substitutions are not simply "noises" in protein evolution, as many have thought. They may play constructive roles by setting the intramolecular microenvironment for further complementary advantageous substitutions, which can lead to improved or altered function. Overall, our study illustrates the power of the "paleomolecular biochemistry" approach in delineating the complex interplays of amino acid substitutions in evolution and in identifying the molecular basis of biological innovation. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Zhang, Jianzhi AU - Rosenberg, Helene F AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. jianzhi@umich.edu Y1 - 2002/04/16/ PY - 2002 DA - 2002 Apr 16 SP - 5486 EP - 5491 VL - 99 IS - 8 SN - 0027-8424, 0027-8424 KW - Antiviral Agents KW - 0 KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Index Medicus KW - Phylogeny KW - Animals KW - Polymorphism, Genetic KW - Biological Evolution KW - Models, Molecular KW - Humans KW - Amino Acid Sequence KW - Aotidae KW - Mutagenesis, Site-Directed KW - Antiviral Agents -- pharmacology KW - Point Mutation KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Mutation KW - Adaptation, Biological KW - Ribonucleases -- genetics KW - Ribonucleases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71613200?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Complementary+advantageous+substitutions+in+the+evolution+of+an+antiviral+RNase+of+higher+primates.&rft.au=Zhang%2C+Jianzhi%3BRosenberg%2C+Helene+F&rft.aulast=Zhang&rft.aufirst=Jianzhi&rft.date=2002-04-16&rft.volume=99&rft.issue=8&rft.spage=5486&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-14 N1 - Date created - 2002-04-17 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF479627; GENBANK; AF479628; AF479629; AF479630; AF479631; AF479634; AF479632; AF479633 N1 - SuppNotes - Cited By: J Mol Evol. 1999 Dec;49(6):721-8 [10594173] Science. 1999 Jan 8;283(5399):220-1 [9880254] Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4701-6 [10758160] Mol Biol Evol. 2000 Jun;17(6):890-6 [10833195] Science. 2000 Nov 10;290(5494):1151-5 [11073452] Genetics. 2000 Dec;156(4):1949-58 [11102386] J Mol Evol. 2001 Feb;52(2):182-92 [11231898] Gene. 2001 Apr 4;267(1):23-30 [11311552] J Leukoc Biol. 2001 Nov;70(5):691-8 [11698487] Nature. 1969 Jan 4;221(5175):40-2 [5782607] Nature. 1973 Aug 3;244(5414):259-62 [4200792] Genetics. 1980 Dec;96(4):801-17 [7021316] Nature. 1986 Jun 5-11;321(6070):613-6 [2423882] J Immunol. 1986 Nov 1;137(9):2913-7 [3760576] Infect Immun. 1987 Apr;55(4):877-81 [3549562] Mol Biol Evol. 1983 Dec;1(1):94-108 [6599963] J Immunol. 1989 Jun 15;142(12):4428-34 [2656865] FEBS Lett. 1989 Aug 28;254(1-2):1-4 [2673839] Genomics. 1990 Aug;7(4):535-46 [2387583] Comput Appl Biosci. 1992 Jun;8(3):275-82 [1633570] Nature. 1995 Mar 2;374(6517):57-9 [7532788] Nat Genet. 1995 Jun;10(2):219-23 [7663519] J Biol Chem. 1995 Sep 15;270(37):21539-44 [7665566] Nature. 1995 Sep 14;377(6545):108-10 [7675077] Trends Biochem Sci. 1995 Sep;20(9):374 [7482707] Science. 1996 Jan 26;271(5248):502-5 [8560264] Genetics. 1995 Dec;141(4):1641-50 [8601501] J Mol Biol. 1996 Jul 26;260(4):540-52 [8759319] Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12370-5 [8901588] J Mol Evol. 1996 Feb;42(2):313-20 [8919883] J Mol Evol. 1997;44 Suppl 1:S139-46 [9071022] Nucleic Acids Res. 1997 Sep 1;25(17):3532-6 [9254715] Electrophoresis. 1997 Dec;18(15):2714-23 [9504803] Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3708-13 [9520431] Mol Biol Evol. 1998 Apr;15(4):355-69 [9549087] J Infect Dis. 1998 Jun;177(6):1458-64 [9607820] Nucleic Acids Res. 1998 Jul 15;26(14):3358-63 [9649619] Mol Phylogenet Evol. 1998 Jun;9(3):585-98 [9668008] Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2678-81 [10077570] Adv Genet. 1951;4:247-65 [14943679] Biotechniques. 1998 Oct;25(4):644, 647 [9793646] Nucleic Acids Res. 1998 Dec 1;26(23):5327-32 [9826755] Comment In: Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):4760-1 [11959927] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bone morphogenetic proteins BMP-6 and BMP-7 have differential effects on survival and neurite outgrowth of cerebellar granule cell neurons. AN - 71588069; 11948661 AB - The bone morphogenetic proteins (BMPs) play an inductive role in the generation of cerebellar granule cells embryonically. Therefore, we chose to look at their effects on cerebellar granule cell survival and differentiation postnatally. The cells express mRNA for both BMP-6 and BMP-7, as well as for the receptors BMPRIA and BMPRII, demonstrating that the postnatal cells have the ability to form the heterodimer receptors needed to respond to BMPs. BMP-7 promotes cell survival, with a maximal effect at 10 ng/ml, whereas tenfold more BMP-6 is needed: Both were active over the course of 8 days in culture. In addition, both BMPs were able to protect the neurons against death from induced apoptosis (exposure to serum-free, low-potassium medium) or exposure to glutamate. However, only BMP-6 could stimulate neurite outgrowth, measured with a neurofilament ELISA, an effect that was seen over the first 6 days in culture. These results, taken together with others in the literature, suggest that the BMPs have strong neurotrophic effects that are both neuron specific and BMP specific. Published 2002 Wiley-Liss, Inc. JF - Journal of neuroscience research AU - Yabe, Takeshi AU - Samuels, Ivy AU - Schwartz, Joan P AD - Neurotrophic Factors Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 36, Room 4A31, Bethesda, MD 20892-4126, USA. Y1 - 2002/04/15/ PY - 2002 DA - 2002 Apr 15 SP - 161 EP - 168 VL - 68 IS - 2 SN - 0360-4012, 0360-4012 KW - Bmp6 protein, rat KW - 0 KW - Bmp7 protein, rat KW - Bone Morphogenetic Protein 6 KW - Bone Morphogenetic Protein 7 KW - Bone Morphogenetic Proteins KW - Protein Isoforms KW - RNA, Messenger KW - Receptors, Cell Surface KW - Receptors, Growth Factor KW - Transforming Growth Factor beta KW - Glutamic Acid KW - 3KX376GY7L KW - Bone Morphogenetic Protein Receptors KW - EC 2.7.11.30 KW - Index Medicus KW - Animals KW - Apoptosis -- physiology KW - Glutamic Acid -- poisoning KW - Rats KW - Rats, Sprague-Dawley KW - RNA, Messenger -- metabolism KW - Cells, Cultured KW - Receptors, Cell Surface -- genetics KW - Protein Isoforms -- genetics KW - Cell Survival -- physiology KW - Cytoprotection -- physiology KW - Cerebellum -- cytology KW - Neurons -- drug effects KW - Bone Morphogenetic Proteins -- physiology KW - Neurons -- physiology KW - Neurites -- physiology KW - Cerebellum -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71588069?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuroscience+research&rft.atitle=Bone+morphogenetic+proteins+BMP-6+and+BMP-7+have+differential+effects+on+survival+and+neurite+outgrowth+of+cerebellar+granule+cell+neurons.&rft.au=Yabe%2C+Takeshi%3BSamuels%2C+Ivy%3BSchwartz%2C+Joan+P&rft.aulast=Yabe&rft.aufirst=Takeshi&rft.date=2002-04-15&rft.volume=68&rft.issue=2&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroscience+research&rft.issn=03604012&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-03 N1 - Date created - 2002-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. AN - 71577886; 11929754 AB - We hypothesized that incremental improvements in the cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) chemotherapy regimen through optimization of drug selection, schedule, and pharmacokinetics would improve outcome in patients with large B-cell lymphomas. A prospective multi-institutional study of administration of etoposide, vincristine, and doxorubicin for 96 hours with bolus doses of cyclophosphamide and oral prednisone (EPOCH therapy) was done in 50 patients with previously untreated large B-cell lymphomas. The doses of etoposide, doxorubicin, and cyclophosphamide were adjusted 20% each cycle to achieve a nadir absolute neutrophil count below 0.5 x 10(9)/L. The median age of the patients was 46 years (range, 20-88 years); 24% were older than 60 years; and 44% were at high-intermediate or high risk according to International Prognostic Index (IPI) criteria. There was a complete response in 92% of patients, and at the median follow-up time of 62 months, the progression-free survival (PFS) and overall survival (OS) rates were 70% and 73%, respectively. Neither IPI risk factors nor the index itself was associated with response, PFS, or OS. Doses were escalated in 58% of cycles, and toxicity levels were tolerable. Significant inverse correlations were observed between dose intensity and age for all adjusted agents, and drug clearance of doxorubicin and free etoposide was also inversely correlated with age (r = -0.54 and P(2) =.08 and r = -0.45 and P(2) =.034, respectively). Free-etoposide clearance increased significantly during successive cycles (P(2) =.015). Lymphomas with proliferation of at least 80% had somewhat lower progression and those expressing bcl-2 had significantly higher progression (P(2) =.04). Expression of bcl-2 may discriminate the recently described activated B-like from germinal-center B-like large-cell lymphomas and provide important pathobiologic and prognostic information. Dose-adjusted EPOCH may produce more cell kill than CHOP-based regimens. Dynamic dose adjustment may overcome inadequate drug concentrations, particularly in younger patients, and compensate for increased drug clearance over time. JF - Blood AU - Wilson, Wyndham H AU - Grossbard, Michael L AU - Pittaluga, Stefania AU - Cole, Diane AU - Pearson, Deborah AU - Drbohlav, Nicole AU - Steinberg, Seth M AU - Little, Richard F AU - Janik, John AU - Gutierrez, Martin AU - Raffeld, Mark AU - Staudt, Louis AU - Cheson, Bruce D AU - Longo, Dan L AU - Harris, Nancy AU - Jaffe, Elaine S AU - Chabner, Bruce A AU - Wittes, Robert AU - Balis, Frank AD - Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2002/04/15/ PY - 2002 DA - 2002 Apr 15 SP - 2685 EP - 2693 VL - 99 IS - 8 SN - 0006-4971, 0006-4971 KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Abridged Index Medicus KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Doxorubicin -- pharmacokinetics KW - Etoposide -- pharmacokinetics KW - Disease-Free Survival KW - Age Factors KW - Humans KW - Aged KW - Neutropenia -- chemically induced KW - Aged, 80 and over KW - Drug Monitoring KW - Adult KW - Treatment Outcome KW - Male KW - Prednisone -- administration & dosage KW - Vincristine -- administration & dosage KW - Prognosis KW - Neutropenia -- prevention & control KW - Doxorubicin -- administration & dosage KW - Prednisone -- pharmacokinetics KW - Longitudinal Studies KW - Survival Rate KW - Etoposide -- administration & dosage KW - Risk Factors KW - Middle Aged KW - Vincristine -- pharmacokinetics KW - Cyclophosphamide -- pharmacokinetics KW - Female KW - Platelet Count KW - Lymphoma, B-Cell -- drug therapy KW - Lymphoma, Large B-Cell, Diffuse -- mortality KW - Lymphoma, Large B-Cell, Diffuse -- drug therapy KW - Lymphoma, B-Cell -- mortality KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacokinetics KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71577886?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Dose-adjusted+EPOCH+chemotherapy+for+untreated+large+B-cell+lymphomas%3A+a+pharmacodynamic+approach+with+high+efficacy.&rft.au=Wilson%2C+Wyndham+H%3BGrossbard%2C+Michael+L%3BPittaluga%2C+Stefania%3BCole%2C+Diane%3BPearson%2C+Deborah%3BDrbohlav%2C+Nicole%3BSteinberg%2C+Seth+M%3BLittle%2C+Richard+F%3BJanik%2C+John%3BGutierrez%2C+Martin%3BRaffeld%2C+Mark%3BStaudt%2C+Louis%3BCheson%2C+Bruce+D%3BLongo%2C+Dan+L%3BHarris%2C+Nancy%3BJaffe%2C+Elaine+S%3BChabner%2C+Bruce+A%3BWittes%2C+Robert%3BBalis%2C+Frank&rft.aulast=Wilson&rft.aufirst=Wyndham&rft.date=2002-04-15&rft.volume=99&rft.issue=8&rft.spage=2685&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-17 N1 - Date created - 2002-04-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional regulation of human 3'-phosphoadenosine 5'-phosphosulphate synthase 2. AN - 71571321; 11931653 AB - Sulphonation is a fundamental process that is essential for normal growth and development as well as maintenance of the internal milieu. The universal sulphonate donor molecule essential for all sulphoconjugation reactions is adenosine 3'-phosphate 5'-phosphosulphate (PAPS), which is produced from ATP and inorganic sulphate by the action of bifunctional PAPS synthase. There are two isozymes encoded by genes located on chromosome 4 (PAPS synthase 1) and chromosome 10 (PAPS synthase 2). The promoter for PAPS synthase 2 contains neither a TATAAA nor a CCAAT box, although a consensus initiator motif is present. Three human cell lines were used to examine promoter activity after transfection with various lengths of the 5'-flanking region of the PAPS synthase 2 gene fused to a reporter gene. Proximal promoter activity was located between bp -84 and bp -124 upstream of the purported transcription start site. This region contains two GC/GT boxes that are essential for full promoter activity, as indicated by deletion analysis and supported further by mutagenesis. A nuclear extract of SW13 cells, which highly express PAPS synthase 2, contained proteins that bound to probes possessing promoter-specific GC/GT boxes. Furthermore, the presence of specificity protein (Sp) 1, Sp2 and Sp3 proteins in the nuclear extract was confirmed by supershift analysis. Co-transfection experiments using SL2 cells yielded additional support for the involvement of Sp1 in transcriptional regulation of the PAPS synthase 2 gene; the involvement of Sp2 and/or Sp3 remains to be clarified further. JF - The Biochemical journal AU - Shimizu, Chikara AU - Fuda, Hirotoshi AU - Lee, Young C AU - Strott, Charles A AD - Section on Steroid Regulation, Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-4510, U.S.A. Y1 - 2002/04/15/ PY - 2002 DA - 2002 Apr 15 SP - 263 EP - 271 VL - 363 SN - 0264-6021, 0264-6021 KW - DNA-Binding Proteins KW - 0 KW - Multienzyme Complexes KW - SP3 protein, human KW - Sp1 Transcription Factor KW - Transcription Factors KW - Sp3 Transcription Factor KW - 148710-94-5 KW - DNA KW - 9007-49-2 KW - Luciferases KW - EC 1.13.12.- KW - PAPS synthetase KW - EC 2.7.7.4 KW - Sulfate Adenylyltransferase KW - Index Medicus KW - Sp1 Transcription Factor -- genetics KW - Transcription Factors -- metabolism KW - DNA -- metabolism KW - Humans KW - DNA-Binding Proteins -- genetics KW - Transcription, Genetic KW - Transcription Factors -- genetics KW - Promoter Regions, Genetic KW - Base Sequence KW - Gene Expression Regulation, Enzymologic KW - Transfection KW - Genetic Vectors KW - DNA -- genetics KW - Sp1 Transcription Factor -- metabolism KW - Molecular Sequence Data KW - Genes, Reporter KW - Binding Sites -- genetics KW - Luciferases -- genetics KW - Mutation KW - Cell Line KW - DNA-Binding Proteins -- metabolism KW - Sulfate Adenylyltransferase -- genetics KW - Multienzyme Complexes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71571321?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Biochemical+journal&rft.atitle=Transcriptional+regulation+of+human+3%27-phosphoadenosine+5%27-phosphosulphate+synthase+2.&rft.au=Shimizu%2C+Chikara%3BFuda%2C+Hirotoshi%3BLee%2C+Young+C%3BStrott%2C+Charles+A&rft.aulast=Shimizu&rft.aufirst=Chikara&rft.date=2002-04-15&rft.volume=363&rft.issue=&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=The+Biochemical+journal&rft.issn=02646021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-16 N1 - Date created - 2002-04-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1999 Nov 19;274(47):33306-12 [10559207] Nucleic Acids Res. 1997 May 15;25(10):2012-9 [9115370] Nucleic Acids Res. 2000 Jan 1;28(1):316-9 [10592259] Biochem Biophys Res Commun. 2000 Feb 16;268(2):437-44 [10679223] Dev Biol. 2000 Nov 15;227(2):358-72 [11071760] Nucleic Acids Res. 2001 Jan 1;29(1):281-3 [11125113] Biochem Biophys Res Commun. 2001 Jun 15;284(3):763-70 [11396968] J Embryol Exp Morphol. 1972 Apr;27(2):353-65 [4625067] Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 [6828386] Cell. 1983 Nov;35(1):79-87 [6313230] Cell. 1988 Oct 7;55(1):125-33 [3139301] Cell. 1988 Dec 2;55(5):887-98 [3142690] Cell. 1989 Dec 1;59(5):827-36 [2512012] Cell. 1990 Oct 5;63(1):155-65 [2170018] Genes Dev. 1991 Nov;5(11):1935-45 [1657708] Nature. 1993 Dec 16;366(6456):690-4 [8259212] Biochemistry. 1994 May 17;33(19):5920-5 [8180221] EMBO J. 1994 Aug 15;13(16):3843-51 [8070411] Nucleic Acids Res. 1997 Aug 1;25(15):3110-7 [9224612] Int J Biochem Cell Biol. 1997 Dec;29(12):1313-23 [9570130] J Biol Chem. 1998 Jul 24;273(30):19311-20 [9668121] Nat Genet. 1998 Oct;20(2):157-62 [9771708] J Biol Chem. 1999 Jan 1;274(1):20-8 [9867805] Nature. 1999 Feb 4;397(6718):446-50 [9989412] Trends Biochem Sci. 1999 Jun;24(6):236-40 [10366853] Int J Biochem Cell Biol. 1999 May;31(5):613-26 [10399321] Gene. 1996 Dec 5;182(1-2):13-22 [8982062] Biochim Biophys Acta. 1997 Mar 20;1351(1-2):73-88 [9116046] Gene. 1999 Oct 1;238(2):291-300 [10570957] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adrenomedullin functions as an important tumor survival factor in human carcinogenesis. AN - 71556966; 11921362 AB - Adrenomedullin (AM) is a pluripotent regulatory peptide initially isolated from a human pheochromocytoma (adrenal tumor) and subsequently shown to play a critical role in cancer cell division, tumor neovascularization, and circumvention of programmed cell death, thus it is an important tumor cell survival factor underlying human carcinogenesis. A variety of neural and epithelial cancers have been shown to produce abundant amounts of AM. Recent findings have implicated elevation of serum AM with the onset of malignant expression. In addition, patients with tumors producing high levels of this peptide have a poor prognostic clinical outcome. Given that most human epithelial cancers display a microenvironment of reduced oxygen tension, it is interesting to note that AM and several of its receptors are upregulated during hypoxic insult. The existence of such a regulatory pathway has been implicated as the basis for the overexpression of AM/AM-R in human malignancies, thereby generating a subsequent autocrine/paracrine growth advantage for the tumor cell. Furthermore, AM has been implicated as a potential immune suppressor substance, inhibiting macrophage function and acting as a newly identified negative regulator of the complement cascade, protective properties which may help cancer cells to circumvent immune surveillance. Hence, AM's traditional participation in normal physiology (cited elsewhere in this issue) can be extended to a primary player in human carcinogenesis and may have clinical relevance as a biological target for the intervention of tumor progression. JF - Microscopy research and technique AU - Cuttitta, Frank AU - Pío, Rubén AU - Garayoa, Mercedes AU - Zudaire, Enrique AU - Julián, Miguel AU - Elsasser, Ted H AU - Montuenga, Luis M AU - Martínez, Alfredo AD - Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. cuttittf@mail.nih.gov Y1 - 2002/04/15/ PY - 2002 DA - 2002 Apr 15 SP - 110 EP - 119 VL - 57 IS - 2 SN - 1059-910X, 1059-910X KW - Peptides KW - 0 KW - Adrenomedullin KW - 148498-78-6 KW - Index Medicus KW - Rats KW - Animals KW - Apoptosis KW - Tumor Cells, Cultured KW - Humans KW - Disease Progression KW - Neovascularization, Pathologic KW - Neoplasms -- blood supply KW - Neoplasms -- physiopathology KW - Peptides -- metabolism KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71556966?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Microscopy+research+and+technique&rft.atitle=Adrenomedullin+functions+as+an+important+tumor+survival+factor+in+human+carcinogenesis.&rft.au=Cuttitta%2C+Frank%3BP%C3%ADo%2C+Rub%C3%A9n%3BGarayoa%2C+Mercedes%3BZudaire%2C+Enrique%3BJuli%C3%A1n%2C+Miguel%3BElsasser%2C+Ted+H%3BMontuenga%2C+Luis+M%3BMart%C3%ADnez%2C+Alfredo&rft.aulast=Cuttitta&rft.aufirst=Frank&rft.date=2002-04-15&rft.volume=57&rft.issue=2&rft.spage=110&rft.isbn=&rft.btitle=&rft.title=Microscopy+research+and+technique&rft.issn=1059910X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-16 N1 - Date created - 2002-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Indinavir-associated interstitial nephritis and urothelial inflammation: clinical and cytologic findings. AN - 71550467; 11915002 AB - The objective of the present study was to characterize the genitourinary syndromes that accompany indinavir-associated pyuria. Of 23 indinavir-treated patients with persistent pyuria, 4 had isolated interstitial nephritis, 10 had both interstitial nephritis and urothelial inflammation, 7 had isolated urothelial inflammation, and 2 had pyuria with nonspecific urinary tract inflammation. A total of 21 patients had multinucleated histiocytes identified by cytologic testing of urine specimens. Urine abnormalities resolved in all 20 patients who stopped receiving indinavir therapy. Pyuria continued in the 3 patients who continued receiving indinavir. Six patients had elevated serum creatinine levels, which returned to baseline levels when indinavir was discontinued. In conclusion, indinavir-associated pyuria was frequently associated with evidence of interstitial nephritis and/or urothelial inflammation, multinucleated histiocytes were commonly present in urine specimens, and cessation of indinavir therapy was associated with prompt resolution of urine abnormalities. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Kopp, Jeffrey B AU - Falloon, Judith AU - Filie, Armando AU - Abati, Andrea AU - King, Christine AU - Hortin, Glen L AU - Mican, JoAnn M AU - Vaughan, Ellen AU - Miller, Kirk D AD - Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA. jbkopp@nih.gov Y1 - 2002/04/15/ PY - 2002 DA - 2002 Apr 15 SP - 1122 EP - 1128 VL - 34 IS - 8 KW - HIV Protease Inhibitors KW - 0 KW - Indinavir KW - 5W6YA9PKKH KW - Index Medicus KW - Humans KW - Inflammation -- chemically induced KW - Adult KW - Middle Aged KW - Male KW - Female KW - Urothelium -- drug effects KW - Urothelium -- pathology KW - Pyuria -- chemically induced KW - Nephritis, Interstitial -- chemically induced KW - HIV Protease Inhibitors -- adverse effects KW - Indinavir -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71550467?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.atitle=Indinavir-associated+interstitial+nephritis+and+urothelial+inflammation%3A+clinical+and+cytologic+findings.&rft.au=Kopp%2C+Jeffrey+B%3BFalloon%2C+Judith%3BFilie%2C+Armando%3BAbati%2C+Andrea%3BKing%2C+Christine%3BHortin%2C+Glen+L%3BMican%2C+JoAnn+M%3BVaughan%2C+Ellen%3BMiller%2C+Kirk+D&rft.aulast=Kopp&rft.aufirst=Jeffrey&rft.date=2002-04-15&rft.volume=34&rft.issue=8&rft.spage=1122&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=1537-6591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-28 N1 - Date created - 2002-03-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of methacrylonitrile on cytochrome P-450 2E1 (CYP2E1) expression in male F344 rats. AN - 71589014; 11939710 AB - Tissue-specific induction of cytochrome P-450s (CYP) followed by increased in situ bioactivation may contribute to chemical-induced site-specific toxicity. In rats, methacrylonitrile (MAN) is metabolized by cytochrome P-450 2E1 (CYP2E1) to acetone, which is eliminated along with parent MAN in breath. Gavage administration of MAN to rats causes olfactory epithelial damage and liver enlargement. It was hypothesized that treatment of rats with MAN may result in differential expression of CYP2E1 in tissues leading to tissue-specific toxicity via increased in situ formation of cytotoxic MAN metabolites. In this study, male F344 rats received 60 mg MAN/kg and were sacrificed 6, 12, or 24 h after a single dose, or 24 h after 7 consecutive daily doses. Liver, lung, and nasal tissues were collected. Reverse-transcription polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical staining were used to assess CYP2E1 expression and localization, and chlorzoxazone hydroxylation was used as a measure of CYP2E1 catalytic activity. Present results showed that CYP2E1 mRNA was increased in lung and nasal tissues with minimal effects in liver of MAN-treated rats. Induction of CYP2E1 protein expression was detected in lung. CYP2E1 activity was higher in liver and lung microsomes from MAN-treated rats when compared to control animals. To compare the effects of MAN and acetone, male F344 rats received a single acetone dose (5 ml/kg) by gavage. After 12 h, acetone treatment resulted in a significant increase in the levels of CYP2E1 mRNA and protein in lung and nasal tissues, with no obvious change noted in the liver. Overall, these data suggest that administration of MAN to rats causes increased expression of CYP2E1 in lung, liver, and nasal tissues. These results also show that acetone induces the expression of CYP2E1 at both the mRNA and protein levels in rat nasal and lung tissues. In conclusion, MAN increased the expression of CYP2E1, and this effect varied as a function of time, length of exposure, and tissue examined. While the damage in the olfactory mucosa due to MAN treatment may not be explained by the observed induction of CYP2E1, it is possible that other CYPs may play a role in the in situ bioactivation of MAN. JF - Journal of toxicology and environmental health. Part A AU - Wang, Hongbing AU - Chanas, Brian AU - Ghanayem, Burhan I AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/04/12/ PY - 2002 DA - 2002 Apr 12 SP - 523 EP - 537 VL - 65 IS - 7 SN - 1528-7394, 1528-7394 KW - Methacrylates KW - 0 KW - Nitriles KW - RNA primers KW - RNA, Messenger KW - methacrylonitrile KW - 04S4K38612 KW - RNA KW - 63231-63-0 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Blotting, Western KW - RNA, Messenger -- analysis KW - Gene Expression KW - Tissue Distribution KW - Reverse Transcriptase Polymerase Chain Reaction KW - Immunohistochemistry KW - Male KW - Nitriles -- pharmacokinetics KW - Methacrylates -- pharmacokinetics KW - Methacrylates -- toxicity KW - Cytochrome P-450 CYP2E1 -- metabolism KW - Nitriles -- toxicity KW - Cytochrome P-450 CYP2E1 -- genetics KW - Cytochrome P-450 CYP2E1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71589014?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health.+Part+A&rft.atitle=Effect+of+methacrylonitrile+on+cytochrome+P-450+2E1+%28CYP2E1%29+expression+in+male+F344+rats.&rft.au=Wang%2C+Hongbing%3BChanas%2C+Brian%3BGhanayem%2C+Burhan+I&rft.aulast=Wang&rft.aufirst=Hongbing&rft.date=2002-04-12&rft.volume=65&rft.issue=7&rft.spage=523&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health.+Part+A&rft.issn=15287394&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-18 N1 - Date created - 2002-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ubc9 is a novel modulator of the induction properties of glucocorticoid receptors. AN - 71581058; 11812797 AB - The EC(50) of agonists and the partial agonist activity of antagonists are crucial parameters for steroid hormone control of gene expression and endocrine therapies. These parameters have been shown to be modulated by a naturally occurring cis-acting element, called the glucocorticoid modulatory element (GME) that binds two proteins, GMEB-1 and -2. We now present evidence that the GMEBs contact Ubc9, which is the mammalian homolog of a yeast E2 ubiquitin-conjugating enzyme. Ubc9 also binds to glucocorticoid receptors (GRs). Ubc9 displays no intrinsic transactivation activity but modifies both the absolute amount of induced gene product and the fold induction by GR. With high concentrations of GR, added Ubc9 also reduces the EC(50) of agonists and increases the partial agonist activity of antagonists in a manner that is independent of the ability of Ubc9 to transfer SUMO-1 (small ubiquitin-like modifier-1) to proteins. This new activity of Ubc9 requires only the ligand binding domain of GR and part of the hinge region. Interestingly, Ubc9 modulation of full-length GR transcriptional properties can be seen in the absence of a GME. This, though, is consistent with the GME acting by increasing the local concentration of Ubc9, which then activates a previously unobserved target in the transcriptional machinery. With high concentrations of Ubc9 and GR, Ubc9 binding to GR appears to be sufficient to permit Ubc9 to act independently of the GME. JF - The Journal of biological chemistry AU - Kaul, Sunil AU - Blackford, John A AU - Cho, Sehyung AU - Simons, S Stoney AD - Steroid Hormones Section, NIDDK/Laboratory of Molecular and Cellular Biology, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/04/12/ PY - 2002 DA - 2002 Apr 12 SP - 12541 EP - 12549 VL - 277 IS - 15 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Receptors, Glucocorticoid KW - SUMO-1 Protein KW - Thymus Hormones KW - suppressin KW - Ubiquitin-Conjugating Enzymes KW - EC 2.3.2.23 KW - Ligases KW - EC 6.- KW - ubiquitin-conjugating enzyme UBC9 KW - EC 6.3.2.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Thymus Hormones -- physiology KW - Base Sequence KW - COS Cells KW - Two-Hybrid System Techniques KW - SUMO-1 Protein -- metabolism KW - Transcriptional Activation -- physiology KW - Receptors, Glucocorticoid -- physiology KW - Ligases -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71581058?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Ubc9+is+a+novel+modulator+of+the+induction+properties+of+glucocorticoid+receptors.&rft.au=Kaul%2C+Sunil%3BBlackford%2C+John+A%3BCho%2C+Sehyung%3BSimons%2C+S+Stoney&rft.aulast=Kaul&rft.aufirst=Sunil&rft.date=2002-04-12&rft.volume=277&rft.issue=15&rft.spage=12541&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-16 N1 - Date created - 2002-04-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Discovery of a Stable Dimeric Mutant of Cyanovirin-N (CV-N) from a T7 Phage-Displayed CV-N Mutant Library AN - 19765709; 5352769 AB - Mutant proteins with altered properties can be useful probes for investigating structure, ligand binding sites, mechanisms of action, and physicochemical attributes of the corresponding wild-type proteins of interest. In this report, we illuminate properties of mutants of the potent HIV-inactivating protein, cyanovirin-N (CV-N), selected by construction of a mutant library by error-prone polymerase chain reaction and affinity-based screening using T7 phage display technology. After three rounds of biopanning, two phage-displayed, one-point mutants of CV-N, Ser52Pro and Ala77Thr, were isolated. After the elucidation of biological activities of the mutants displayed on phage as well as the Escherichia coli-expressed, purified mutant proteins, we subsequently subjected the mutants to analyses by native PAGE and size-exclusion chromatography. We found that the Ser52Pro mutant not only was active against HIV but also existed exclusively as a dimer in solution. This was in marked contrast to the wild-type CV-N, which exists in solution predominantly as the monomer. The Ser52Pro mutant provides a novel model for further investigations of the folding mechanism as well as structure-activity requirements for CV-N's antiviral properties. [copy ]2002 Elsevier Science (USA). JF - Biochemical and Biophysical Research Communications AU - Han, Z AU - Xiong, C AU - Mori, T AU - Boyd, M R AD - Molecular Targets Drug Discovery Program, NCI Center for Cancer Research, National Cancer Institute, NCI-Frederick, Frederick, Maryland, 21702-1201, boyd@dtpax2.ncifcrf.gov Y1 - 2002/04/12/ PY - 2002 DA - 2002 Apr 12 SP - 1036 EP - 1043 PB - Academic Press VL - 292 IS - 4 SN - 0006-291X, 0006-291X KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts KW - Monomers KW - cyanovirin-N KW - Human immunodeficiency virus KW - Chromatography KW - Phage display KW - Probes KW - Polymerase chain reaction KW - Escherichia KW - Antiviral activity KW - Models KW - V 22360:AIDS and HIV KW - J 02430:Symbiosis, Antibiosis & Phages UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19765709?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+Biophysical+Research+Communications&rft.atitle=Discovery+of+a+Stable+Dimeric+Mutant+of+Cyanovirin-N+%28CV-N%29+from+a+T7+Phage-Displayed+CV-N+Mutant+Library&rft.au=Han%2C+Z%3BXiong%2C+C%3BMori%2C+T%3BBoyd%2C+M+R&rft.aulast=Han&rft.aufirst=Z&rft.date=2002-04-12&rft.volume=292&rft.issue=4&rft.spage=1036&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+Biophysical+Research+Communications&rft.issn=0006291X&rft_id=info:doi/10.1006%2Fbbrc.2002.6741 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-07-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Monomers; cyanovirin-N; Chromatography; Phage display; Probes; Polymerase chain reaction; Antiviral activity; Models; Human immunodeficiency virus; Escherichia DO - http://dx.doi.org/10.1006/bbrc.2002.6741 ER - TY - JOUR T1 - Physical activity and lung cancer risk in male smokers AN - 18300209; 5359130 AB - We examined the association between physical activity and lung cancer in a prospective cohort of 27,087 male smokers, ages 50-69 years, enrolled in the Alpha-Tocopherol, Beta Carotene Cancer Prevention (ATBC) Study. After an average of 10 years of follow-up, 1,442 lung cancer cases were diagnosed. Cox proportional hazards models were used to estimate the relative risk (RR) and 95% confidence intervals (CI) of lung cancer associated with self-reported occupational and leisure-time activity, adjusted for age, supplement group, body mass index, cigarettes smoked daily, years of smoking, education, energy intake and vegetable intake. There were no associations between occupational, leisure-time or combined categories of physical activity with lung cancer risk; however, age appeared to modify the effect of leisure-time activity (p = 0.02). Within increasing quartiles of age, the RRs (CI) for men active in leisure time compared to sedentary men were 0.77 (0.54-1.09), 0.74 (0.57-0.95), 1.09 (0.89-1.33) and 1.03 (0.88-1.21). These data suggest that among smokers, neither occupational nor leisure-time activity is associated with lung cancer risk. There may, however, be some modest risk reduction associated with leisure activity among younger smokers. JF - International Journal of Cancer AU - Colbert, L H AU - Hartman, T J AU - Tangrea, JA AU - Pietinen, P AU - Virtamo, J AU - Taylor, PR AU - Albanes, D AD - 7201 Wisconsin Ave, Suite 3C-309 Bethesda, MD 20892-9205, USA, COLBERTL@mail.nih.gov Y1 - 2002/04/10/ PY - 2002 DA - 2002 Apr 10 SP - 770 EP - 773 VL - 98 IS - 5 SN - 0020-7136, 0020-7136 KW - physical activity KW - risk reduction KW - Risk Abstracts; Toxicology Abstracts KW - Risk assessment KW - Smoking KW - Males KW - Cigarette smoking KW - Physical training KW - Lung cancer KW - R2 23060:Medical and environmental health KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18300209?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Cancer&rft.atitle=Physical+activity+and+lung+cancer+risk+in+male+smokers&rft.au=Colbert%2C+L+H%3BHartman%2C+T+J%3BTangrea%2C+JA%3BPietinen%2C+P%3BVirtamo%2C+J%3BTaylor%2C+PR%3BAlbanes%2C+D&rft.aulast=Colbert&rft.aufirst=L&rft.date=2002-04-10&rft.volume=98&rft.issue=5&rft.spage=770&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.10156 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Lung cancer; Smoking; Physical training; Cigarette smoking; Risk assessment; Males DO - http://dx.doi.org/10.1002/ijc.10156 ER - TY - JOUR T1 - Biochemical and electron paramagnetic resonance study of the iron superoxide dismutase from Plasmodium falciparum. AN - 71530894; 11897129 AB - Recombinant iron-containing superoxide dismutase (Fe-SOD) from Plasmodium falciparum was produced in a SOD-deficient strain of Escherichia coli, purified and characterised. The enzyme is a dimer, which contains 1.7 Fe equivalents and is sensitive to hydrogen peroxide (H(2)O(2)). Electron paramagnetic resonance (EPR) analysis showed two different signals, reflecting the presence of two different types of high-spin Fe sites with different symmetries. The role of the W71 residue during inactivation by H(2)O(2) of the P. falciparum Fe-SOD was studied by site-directed mutagenesis. First, the W71V mutation led to a change in the relative proportion of the two Fe-based EPR signals. Second, the mutant protein was almost as active as the wild-type (WT) protein but more sensitive to heat inactivation. Third, resistance to H(2)O(2) was only slightly increased indicating that W71 was marginally responsible for the sensitivity of Fe-SOD to H(2)O(2). A molecular model of the subunit was designed to assist in interpretation of the results. The fact that the parasite SOD does not belong to classes of SOD present in humans may provide a novel approach for the design of antimalarial drugs. JF - Molecular and biochemical parasitology AU - Gratepanche, Sylvie AU - Ménage, Stéphane AU - Touati, Danièle AU - Wintjens, René AU - Delplace, Patrick AU - Fontecave, Marc AU - Masset, Annick AU - Camus, Daniel AU - Dive, Daniel AD - Laboratory of Parasitic Diseases, Growth and Development Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0425, USA. Y1 - 2002/04/09/ PY - 2002 DA - 2002 Apr 09 SP - 237 EP - 246 VL - 120 IS - 2 SN - 0166-6851, 0166-6851 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Iron KW - E1UOL152H7 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Index Medicus KW - Animals KW - Mass Spectrometry KW - Models, Molecular KW - Hydrogen Peroxide -- pharmacology KW - Temperature KW - Iron -- metabolism KW - Molecular Weight KW - Electron Spin Resonance Spectroscopy KW - Enzyme Stability KW - Enzyme Activation -- drug effects KW - Time Factors KW - Mutation KW - Protein Conformation KW - Superoxide Dismutase -- isolation & purification KW - Plasmodium falciparum -- enzymology KW - Plasmodium falciparum -- genetics KW - Superoxide Dismutase -- genetics KW - Superoxide Dismutase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71530894?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+biochemical+parasitology&rft.atitle=Biochemical+and+electron+paramagnetic+resonance+study+of+the+iron+superoxide+dismutase+from+Plasmodium+falciparum.&rft.au=Gratepanche%2C+Sylvie%3BM%C3%A9nage%2C+St%C3%A9phane%3BTouati%2C+Dani%C3%A8le%3BWintjens%2C+Ren%C3%A9%3BDelplace%2C+Patrick%3BFontecave%2C+Marc%3BMasset%2C+Annick%3BCamus%2C+Daniel%3BDive%2C+Daniel&rft.aulast=Gratepanche&rft.aufirst=Sylvie&rft.date=2002-04-09&rft.volume=120&rft.issue=2&rft.spage=237&rft.isbn=&rft.btitle=&rft.title=Molecular+and+biochemical+parasitology&rft.issn=01666851&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-14 N1 - Date created - 2002-03-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of pentachlorophenol on DNA adduct formation in p53 wild-type and knockout mice exposed to benzo[a]pyrene. AN - 71451147; 11849736 AB - Previous studies have shown that pentachlorophenol (PCP) has both potentiative and antagonistic effects on the genotoxicity of benzo[a]pyrene (B[a]P). It has been suggested that these effects are due to inhibition and/or induction of enzymes involved in the biotransformation of B[a]P [Carcinogenesis 16 (1995) 2643]. However, B[a]P [J. Biol. Chem. 274 (1999) 35240] and a metabolite of PCP, tetrachlorohydroquinone (TCHQ) [Chem. Biol. Interact. 105 (1997) 1], induce p53 protein synthesis in vitro. To investigate this effect further, C57BL/6Tac trp53+/+ (wild-type, WT) and C57BL/6Tac trp53-/- (knockout, KO) mice were exposed to 55 microg B[a]P/g BW alone or in combination with 25 microg/g PCP. Hepatic and lung DNA were analyzed for the major B[a]P DNA adduct, 7R,8S,9S-trihydroxy-10R-(N2-2'-deoxyguanosyl)-7,8,9,10-tetrahydro-B[a]P (BPDE-N2G) and other minor adducts using the 32P-postlabeling assay. BPDE-N2G adducts were detected in all animals exposed to B[a]P. Similar adduct levels were observed in WT mice exposed to 55 microg/g B[a]P compared with KO mice exposed to B[a]P alone or in combination with PCP. Interestingly, hepatic and lung BPDE-N2G adducts were decreased in WT mice exposed to B[a]P with PCP (P<0.05). Total DNA adducts in the liver (P<0.05) were also decreased in WT mice exposed to B[a]P and PCP. Total DNA adducts in either hepatic or lung DNA isolated from KO mice were not different in mice treated with PCP and B[a]P. These results suggest that the decrease in BPDE-N2G adducts observed in WT mice may be a result of p53 accumulation or induction of repair pathways in response to damage induced by PCP. JF - Cancer letters AU - Ress, Nancy B AU - Donnelly, Kirby C AU - George, Susan E AD - Department of Veterinary Anatomy and Public Health, Texas A&M University, College Station, TX, USA. ress@niehs.nih.gov Y1 - 2002/04/08/ PY - 2002 DA - 2002 Apr 08 SP - 11 EP - 17 VL - 178 IS - 1 SN - 0304-3835, 0304-3835 KW - DNA Adducts KW - 0 KW - Tumor Suppressor Protein p53 KW - benzo(a)pyrene-DNA adduct KW - Benzo(a)pyrene KW - 3417WMA06D KW - DNA KW - 9007-49-2 KW - Pentachlorophenol KW - D9BSU0SE4T KW - Index Medicus KW - Animals KW - Liver -- drug effects KW - DNA -- metabolism KW - Mice, Inbred C57BL KW - Lung -- drug effects KW - Liver -- metabolism KW - Mice KW - Lung -- metabolism KW - Drug Synergism KW - Male KW - Mice, Knockout KW - Benzo(a)pyrene -- toxicity KW - Tumor Suppressor Protein p53 -- genetics KW - DNA Adducts -- drug effects KW - Tumor Suppressor Protein p53 -- metabolism KW - Pentachlorophenol -- pharmacology KW - DNA Adducts -- metabolism KW - Benzo(a)pyrene -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71451147?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=The+effect+of+pentachlorophenol+on+DNA+adduct+formation+in+p53+wild-type+and+knockout+mice+exposed+to+benzo%5Ba%5Dpyrene.&rft.au=Ress%2C+Nancy+B%3BDonnelly%2C+Kirby+C%3BGeorge%2C+Susan+E&rft.aulast=Ress&rft.aufirst=Nancy&rft.date=2002-04-08&rft.volume=178&rft.issue=1&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-15 N1 - Date created - 2002-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - US EPA's acute reference exposure methodology for acute inhalation exposures AN - 18386136; 5378777 AB - The US Environmental Protection Agency (EPA) National Center for Environmental Assessment is engaged in the development of a methodology for Agency use to perform risk assessments for non-cancer effects due to acute inhalation exposures. The methodology will provide general guidance for deriving chemical-specific acute exposure benchmarks called acute reference exposures (AREs). Chemical-specific AREs are analogous to reference concentrations (RfCs) for chronic non-cancer effects and will be incorporated in chemical-specific files in the US EPA's Integrated Risk Information System (IRIS) as they are developed and reviewed. AREs will have wide applicability in assessing the potential health risks of accidental and routine acute releases of chemicals to the environment. The proposed methodology for ARE development provides a framework for choosing an optimal derivation approach, depending on the type of data available, from the no-observed-adverse-effect level (NOAEL), benchmark concentration (BMC), or categorical regression approaches. Uncertainty factors are applied to the point of departure, determined by one of the recommended approaches, to derive the ARE. Due to the capability to use more exposure-response information than the NOAEL approach allows, exposure-response analyses such as BMC and categorical regression are favored as methods to develop the point of departure when the available database will support such analyses. The NOAEL approach is suitable when the data are insufficient to support exposure-response modeling. Applications of the proposed ARE methodology are illustrated by the derivation of example AREs for hydrogen sulfide and hexachlorocyclopentadiene, which showcase the categorical regression and NOAEL approaches, respectively. In addition, a recent review of the proposed ARE methodology by the US EPA Risk Assessment Forum is discussed. JF - Science of the Total Environment AU - Strickland, JA AU - Foureman, G L AD - Integrated Laboratory Systems, Inc., NIEHS MD EC-17, P.O. Box 12233, Research Triangle Park, NC 27709, USA, strickl2@niehs.nih.gov Y1 - 2002/04/08/ PY - 2002 DA - 2002 Apr 08 SP - 51 EP - 63 VL - 288 IS - 1-2 SN - 0048-9697, 0048-9697 KW - Environmental Protection Agency KW - acute exposure KW - hexachlorocyclopentadiene KW - man KW - Risk Abstracts; Toxicology Abstracts; Pollution Abstracts KW - X 24230:Legislation & recommended standards KW - R2 23060:Medical and environmental health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18386136?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+of+the+Total+Environment&rft.atitle=US+EPA%27s+acute+reference+exposure+methodology+for+acute+inhalation+exposures&rft.au=Strickland%2C+JA%3BFoureman%2C+G+L&rft.aulast=Strickland&rft.aufirst=JA&rft.date=2002-04-08&rft.volume=288&rft.issue=1-2&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Science+of+the+Total+Environment&rft.issn=00489697&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special issue: Issues and applications in toxicology and risk assessment. N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Src family kinases phosphorylate protein kinase C delta on tyrosine residues and modify the neoplastic phenotype of skin keratinocytes. AN - 71560900; 11812791 AB - Protein kinase C delta (PKC delta) is tyrosine-phosphorylated and catalytically inactive in mouse keratinocytes transformed by a ras oncogene. In several other model systems, Src kinases are upstream regulators of PKC delta. To examine this relationship in epidermal carcinogenesis, v-ras transformed mouse keratinocytes were treated with a selective Src kinase inhibitor (PD 173958). PD 173958 decreased autophosphorylation of Src, Fyn, and Lyn kinases and prevented tyrosine phosphorylation of the Src kinase substrate p120. PD 173958 also prevented PKC delta tyrosine phosphorylation and activated PKC delta as detected by membrane translocation. Expression of keratinocyte differentiation markers increased in PD 173958-treated v-ras-keratinocytes, and fluid-filled domes emerged, indicative of tight junction formation. Antisense PKC delta or bryostatin 1 inhibited dome formation, while overexpression of PKC delta in the presence of PD 173958 enhanced the formation of domes. Plasmids encoding phenylalanine mutants of PKC delta tyrosine residues 64 and 565 induced domes in the absence of PD 173958, while phenylalanine mutants of tyrosine residues 52, 155, and 187 were inactive. Thus, Src kinase mediated post-translational modification of PKC delta on specific tyrosine residues in ras-transformed mouse keratinocytes inactivates PKC delta and contributes to alterations in the differentiated phenotype and tight junction formation associated with neoplasia. JF - The Journal of biological chemistry AU - Joseloff, Elizabeth AU - Cataisson, Christophe AU - Aamodt, Heather AU - Ocheni, Henrietta AU - Blumberg, Peter AU - Kraker, Alan J AU - Yuspa, Stuart H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, NCI, Bethesda, Maryland 20892, USA. Y1 - 2002/04/05/ PY - 2002 DA - 2002 Apr 05 SP - 12318 EP - 12323 VL - 277 IS - 14 SN - 0021-9258, 0021-9258 KW - Antineoplastic Agents KW - 0 KW - Bryostatins KW - Enzyme Inhibitors KW - Isoenzymes KW - Lactones KW - Macrolides KW - Oligonucleotides, Antisense KW - PD 173958 KW - Pyridines KW - Pyrimidines KW - bryostatin 1 KW - 37O2X55Y9E KW - Tyrosine KW - 42HK56048U KW - Phenylalanine KW - 47E5O17Y3R KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - src-Family Kinases KW - EC 2.7.10.2 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-delta KW - Index Medicus KW - Animals KW - Immunoblotting KW - Dose-Response Relationship, Drug KW - Subcellular Fractions KW - Pyrimidines -- pharmacology KW - Cell Differentiation KW - Oligonucleotides, Antisense -- pharmacology KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Precipitin Tests KW - Mice, Inbred BALB C KW - Protein Binding KW - Lactones -- pharmacology KW - Phenylalanine -- chemistry KW - Phenotype KW - Phosphorylation KW - Transfection KW - Cells, Cultured KW - Enzyme Inhibitors -- pharmacology KW - Pyridines -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - Protein Kinase C -- metabolism KW - Skin Neoplasms -- enzymology KW - Keratinocytes -- enzymology KW - src-Family Kinases -- metabolism KW - Tyrosine -- metabolism KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71560900?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Src+family+kinases+phosphorylate+protein+kinase+C+delta+on+tyrosine+residues+and+modify+the+neoplastic+phenotype+of+skin+keratinocytes.&rft.au=Joseloff%2C+Elizabeth%3BCataisson%2C+Christophe%3BAamodt%2C+Heather%3BOcheni%2C+Henrietta%3BBlumberg%2C+Peter%3BKraker%2C+Alan+J%3BYuspa%2C+Stuart+H&rft.aulast=Joseloff&rft.aufirst=Elizabeth&rft.date=2002-04-05&rft.volume=277&rft.issue=14&rft.spage=12318&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-13 N1 - Date created - 2002-04-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The SELDI-TOF MS Approach to Proteomics: Protein Profiling and Biomarker Identification AN - 20793067; 5352735 AB - The need for methods to identify disease biomarkers is underscored by the survival-rate of patients diagnosed at early stages of cancer progression. Surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) is a novel approach to biomarker discovery that combines two powerful techniques: chromatography and mass spectrometry. One of the key features of SELDI-TOF MS is its ability to provide a rapid protein expression profile from a variety of biological and clinical samples. It has been used for biomarker identification as well as the study of protein-protein, and protein-DNA interaction. The versatility of SELDI-TOF MS has allowed its use in projects ranging from the identification of potential diagnostic markers for prostate, bladder, breast, and ovarian cancers and Alzheimer's disease, to the study of biomolecular interactions and the characterization of posttranslational modifications. In this minireview we discuss the application of SELDI-TOF MS to protein biomarker discovery and profiling. JF - Biochemical and Biophysical Research Communications AU - Issaq, HJ AU - Veenstra, T D AU - Conrads, T P AU - Felschow, D AD - SAIC-Frederick, Inc., National Cancer Institute at Frederick, Frederick, Maryland, 21702, issaqh@mail.ncifcrf.gov Y1 - 2002/04/05/ PY - 2002 DA - 2002 Apr 05 SP - 587 EP - 592 PB - Academic Press VL - 292 IS - 3 SN - 0006-291X, 0006-291X KW - Biotechnology and Bioengineering Abstracts KW - Ovarian cancer KW - Desorption KW - Urinary bladder KW - Chromatography KW - Alzheimer's disease KW - biomarkers KW - Mass spectroscopy KW - Neurodegenerative diseases KW - Reviews KW - Lasers KW - proteomics KW - Prostate KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20793067?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+Biophysical+Research+Communications&rft.atitle=The+SELDI-TOF+MS+Approach+to+Proteomics%3A+Protein+Profiling+and+Biomarker+Identification&rft.au=Issaq%2C+HJ%3BVeenstra%2C+T+D%3BConrads%2C+T+P%3BFelschow%2C+D&rft.aulast=Issaq&rft.aufirst=HJ&rft.date=2002-04-05&rft.volume=292&rft.issue=3&rft.spage=587&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+Biophysical+Research+Communications&rft.issn=0006291X&rft_id=info:doi/10.1006%2Fbbrc.2002.6678 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-08-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - biomarkers; Mass spectroscopy; Alzheimer's disease; Lasers; Reviews; Chromatography; Desorption; Prostate; Ovarian cancer; proteomics; Neurodegenerative diseases; Urinary bladder DO - http://dx.doi.org/10.1006/bbrc.2002.6678 ER - TY - JOUR T1 - Preferential Misincorporation of Purine Nucleotides by Human DNA Polymerase eta Opposite Benzo[a]pyrene 7,8-Diol 9,10-Epoxide Deoxyguanosine Adducts AN - 18292872; 5347076 AB - Human DNA polymerase eta was used to copy four stereoisomeric deoxyguanosine (dG) adducts derived from benzo[a]pyrene 7,8-diol 9,10-epoxide (diastereomer with the 7-hydroxyl group and epoxide oxygen trans (BaP DE-2)). The adducts, formed by either cis or trans epoxide ring opening of each enantiomer of BaP DE- 2 by N super(2) of dG, were placed at the fourth nucleotide from the 5'- end in two 16-mer sequence contexts, 5'~CG*A~ and 5'~GG*T. pol eta was remarkably error prone at all four diol epoxide adducts, preferring to misincorporate G and A at frequencies 3- to more than 50-fold greater than the frequencies for T or the correct C, although the highest rates were 60-fold below the rate of incorporation of C opposite a non-adducted G. Anti to syn rotation of the adducted base, consistent with previous NMR data for a BaP DE-2 dG adduct placed just beyond a primer terminus, provides a rationale for preferring purine misincorporation. Extension of purine misincorporations occurred preferentially, but extension beyond the adduct site was weak with V sub(max)/K sub(m) values generally 10-fold less than for misincorporation. Mostly A was incorporated opposite (+)-BaP DE-2 dG adducts, which correlates with published observations that G arrow right T is the most common type of mutation that (+)- BaP DE-2 induces in mammalian cells. JF - Journal of Biological Chemistry AU - Chiapperino, D AU - Kroth, H AU - Kramarczuk, I H AU - Sayer, J M AU - Masutani, C AU - Hanaoka, F AU - Jerina, D M AU - Cheh, A M AD - Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA, acheh@american.edu Y1 - 2002/04/05/ PY - 2002 DA - 2002 Apr 05 SP - 11765 EP - 11771 VL - 277 IS - 14 SN - 0021-9258, 0021-9258 KW - Benzo(a)pyrene-diol epoxide KW - DNA-directed DNA polymerase KW - benzo(a)pyrene-7,8-diol 9,10-epoxide KW - nucleotides KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - DNA adducts KW - N 14630:Chemical reactions & interactions, including effects of radiation KW - X 24190:Polycyclic hydrocarbons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18292872?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Preferential+Misincorporation+of+Purine+Nucleotides+by+Human+DNA+Polymerase+eta+Opposite+Benzo%5Ba%5Dpyrene+7%2C8-Diol+9%2C10-Epoxide+Deoxyguanosine+Adducts&rft.au=Chiapperino%2C+D%3BKroth%2C+H%3BKramarczuk%2C+I+H%3BSayer%2C+J+M%3BMasutani%2C+C%3BHanaoka%2C+F%3BJerina%2C+D+M%3BCheh%2C+A+M&rft.aulast=Chiapperino&rft.aufirst=D&rft.date=2002-04-05&rft.volume=277&rft.issue=14&rft.spage=11765&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - DNA adducts; DNA-directed DNA polymerase ER - TY - JOUR T1 - Engineering an obligate domain-swapped dimer of cyanovirin-N with enhanced anti-HIV activity. AN - 71561731; 11916396 AB - The anti-HIV cyanobacterial protein cyanovirin-N can undergo domain swapping to form an intertwined dimer. The dimeric form is stable at low pH and millimolar concentrations. By deleting an amino acid from the hinge linker about which domain swapping occurs, we have constructed an obligate domain-swapped dimer of cyanovirin-N that represents a new tetravalent carbohydrate binding protein that is stable over a large range of pH values. This obligate dimer displays enhanced anti-HIV activity relative to the wild-type cyanovirin-N monomer with an observed 3.5-fold decrease in IC(50) (9nM for the dimer vs 32 nM for the monomer) for inhibition of HIV-1 envelope-mediated cell fusion and, when expressed in Escherichia coli, can be rapidly obtained in >98% purity in a single chromatographic step. JF - Journal of the American Chemical Society AU - Kelley, Brendan S AU - Chang, Leng Chee AU - Bewley, Carole A AD - Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, MD 20892-0820, USA. Y1 - 2002/04/03/ PY - 2002 DA - 2002 Apr 03 SP - 3210 EP - 3211 VL - 124 IS - 13 SN - 0002-7863, 0002-7863 KW - Anti-HIV Agents KW - 0 KW - Bacterial Proteins KW - Carrier Proteins KW - cyanovirin N KW - 184539-38-6 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Hydrogen-Ion Concentration KW - Dimerization KW - HIV-1 -- physiology KW - Protein Structure, Tertiary KW - HIV-1 -- drug effects KW - Protein Conformation KW - Anti-HIV Agents -- chemistry KW - Carrier Proteins -- chemistry KW - Carrier Proteins -- genetics KW - Anti-HIV Agents -- pharmacology KW - Carrier Proteins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71561731?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Chemical+Society&rft.atitle=Engineering+an+obligate+domain-swapped+dimer+of+cyanovirin-N+with+enhanced+anti-HIV+activity.&rft.au=Kelley%2C+Brendan+S%3BChang%2C+Leng+Chee%3BBewley%2C+Carole+A&rft.aulast=Kelley&rft.aufirst=Brendan&rft.date=2002-04-03&rft.volume=124&rft.issue=13&rft.spage=3210&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Chemical+Society&rft.issn=00027863&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-19 N1 - Date created - 2002-03-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ligand discovery using the inter-ligand Overhauser effect: horse liver alcohol dehydrogenase AN - 18401136; 5386224 AB - Two dimensional nuclear Overhauser effect spectroscopy (NOESY) studies on horse liver alcohol dehydrogenase (LADH) in the presence of several ligands revealed unanticipated cross peaks arising from inter-ligand Overhasuer effects (ILOEs) connecting resonances of an inhibitor, m-methylbenzamide, and the reducing agent, cyanoborohydride, initially present to maintain NADH in the reduced state. The presence of NADH was not required to observe of these inter-ligand Overhauser effects. A model for the ternary complex was developed in which the methylbenzamide inhibitors bind to the hydrophobic pocket of the active site involved in benzyl alcohol binding, while the cyanoborohydride coordinates directly with Zn super(2+) at the active site. The observation of these effects supports the use of inter-ligand Overhauser effects for the identification of unanticipated ternary complexes that are of potential utility for the development of novel enzyme inhibitors. JF - Biotechnology Letters AU - Li, D AU - London, R E AD - MR-01, Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Box 12233, Research Triangle Park, NC 27709, USA, london@niehs.nih.gov Y1 - 2002/04/02/ PY - 2002 DA - 2002 Apr 02 SP - 623 EP - 629 VL - 24 IS - 8 SN - 0141-5492, 0141-5492 KW - cyanoborohydride KW - horses KW - m-methylbenzamide KW - Biotechnology and Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts KW - W2 32310:Enzymes and cofactors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18401136?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biotechnology+Letters&rft.atitle=Ligand+discovery+using+the+inter-ligand+Overhauser+effect%3A+horse+liver+alcohol+dehydrogenase&rft.au=Li%2C+D%3BLondon%2C+R+E&rft.aulast=Li&rft.aufirst=D&rft.date=2002-04-02&rft.volume=24&rft.issue=8&rft.spage=623&rft.isbn=&rft.btitle=&rft.title=Biotechnology+Letters&rft.issn=01415492&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - A small RNA regulates the expression of genes involved in iron metabolism in Escherichia coli AN - 18291368; 5348509 AB - A small RNA, RyhB, was found as part of a genomewide search for novel small RNAs in Escherichia coli. The RyhB 90-nt RNA down-regulates a set of iron- storage and iron-using proteins when iron is limiting; it is itself negatively regulated by the ferric uptake repressor protein, Fur (Ferric uptake regulator). RyhB RNA levels are inversely correlated with mRNA levels for the sdhCDAB operon, encoding succinate dehydrogenase, as well as five other genes previously shown to be positively regulated by Fur by an unknown mechanism. These include two other genes encoding enzymes in the tricarboxylic acid cycle, acnA and fumA, two ferritin genes, ftnA and bfr, and a gene for superoxide dismutase, sodB. Fur positive regulation of all these genes is fully reversed in an ryhB mutant. Our results explain the previously observed inability of fur mutants to grow on succinate. RyhB requires the RNA-binding protein, Hfq, for activity. Sequences within RyhB are complementary to regions within each of the target genes, suggesting that RyhB acts as an antisense RNA. In sdhCDAB, the complementary region is at the end of the first gene of the sdhCDAB operon; full-length sdhCDAB message disappears and a truncated message, equivalent in size to the region upstream of the complementarity, is detected when RyhB is expressed. RyhB provides a mechanism for the cell to down-regulate iron-storage proteins and nonessential ironcontaining proteins when iron is limiting, thus modulating intracellular iron usage to supplement mechanisms for iron uptake directly regulated by Fur. JF - Proceedings of the National Academy of Sciences, USA AU - Masse, E AU - Gottesman, S AD - Laboratory of Molecular Biology, National Cancer Institute, Building 37, Room 5132, National Institutes of Health, Bethesda, MD 20892, USA, susang@helix.nih.gov Y1 - 2002/04/02/ PY - 2002 DA - 2002 Apr 02 SP - 4620 EP - 4625 VL - 99 IS - 7 SN - 0027-8424, 0027-8424 KW - RyhB RNA KW - acnA gene KW - bfr gene KW - ftnA gene KW - fumA gene KW - sodB gene KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Superoxide dismutase KW - Gene regulation KW - Succinate dehydrogenase KW - Escherichia coli KW - Ferritin KW - Iron KW - J 02726:RNA and ribosomes KW - N 14662:Gene regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18291368?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=A+small+RNA+regulates+the+expression+of+genes+involved+in+iron+metabolism+in+Escherichia+coli&rft.au=Masse%2C+E%3BGottesman%2C+S&rft.aulast=Masse&rft.aufirst=E&rft.date=2002-04-02&rft.volume=99&rft.issue=7&rft.spage=4620&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.032066599 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Ferritin; Superoxide dismutase; Iron; Succinate dehydrogenase; Gene regulation DO - http://dx.doi.org/10.1073/pnas.032066599 ER - TY - JOUR T1 - Genome sequence and comparative microarray analysis of serotype M18 group A Streptococcus strains associated with acute rheumatic fever outbreaks AN - 18289857; 5348517 AB - Acute rheumatic fever (ARF), a sequelae of group A Streptococcus (GAS) infection, is the most common cause of preventable childhood heart disease worldwide. The molecular basis of ARF and the subsequent rheumatic heart disease are poorly understood. Serotype M18 GAS strains have been associated for decades with ARF outbreaks in the U.S. As a first step toward gaining new insight into ARF pathogenesis, we sequenced the genome of strain MGAS8232, a serotype M18 organism isolated from a patient with ARF. The genome is a circular chromosome of 1,895,017 bp, and it shares 1.7 Mb of closely related genetic material with strain SF370 (a sequenced serotype M1 strain). Strain MGAS8232 has 178 ORFs absent in SF370. Phages, phage-like elements, and insertion sequences are the major sources of variation between the genomes. The genomes of strain MGAS8232 and SF370 encode many of the same proven or putative virulence factors. Importantly, strain MGAS8232 has genes encoding many additional secreted proteins involved in human-GAS interactions, including streptococcal pyrogenic exotoxin A (scarlet fever toxin) and two uncharacterized pyrogenic exotoxin homologues, all phage-associated. DNA microarray analysis of 36 serotype M18 strains from diverse localities showed that most regions of variation were phages or phage-like elements. Two epidemics of ARF occurring 12 years apart in Salt Lake City, UT, were caused by serotype M18 strains that were genetically identical, or nearly so. Our analysis provides a critical foundation for accelerated research into ARF pathogenesis and a molecular framework to study the plasticity of GAS genomes. JF - Proceedings of the National Academy of Sciences, USA AU - Smoot, J C AU - Barbian, K D AU - Van Gompel, JJ AU - Smoot, L M AU - Chaussee AU - Sylva, G L AU - Sturdevant, DE AU - Ricklefs, S M AU - Porcella, S F AU - Parkins, L D AU - Beres, S B AU - Campbell, D S AU - Smith, T M AU - Zhang, Q AU - Kapur, V AU - Daly, JA AU - Veasy, L G AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA, jmusser@niaid.nih.gov Y1 - 2002/04/02/ PY - 2002 DA - 2002 Apr 02 SP - 4668 EP - 4673 VL - 99 IS - 7 SN - 0027-8424, 0027-8424 KW - streptococci KW - DNA microarrays KW - acute rheumatic fever KW - rheumatic fever KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Phages KW - Streptococcus KW - Nucleotide sequence KW - Toxins KW - Virulence KW - USA, Utah, Salt Lake City KW - Heart diseases KW - N 14640:Structure & sequence KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18289857?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Genome+sequence+and+comparative+microarray+analysis+of+serotype+M18+group+A+Streptococcus+strains+associated+with+acute+rheumatic+fever+outbreaks&rft.au=Smoot%2C+J+C%3BBarbian%2C+K+D%3BVan+Gompel%2C+JJ%3BSmoot%2C+L+M%3BChaussee%3BSylva%2C+G+L%3BSturdevant%2C+DE%3BRicklefs%2C+S+M%3BPorcella%2C+S+F%3BParkins%2C+L+D%3BBeres%2C+S+B%3BCampbell%2C+D+S%3BSmith%2C+T+M%3BZhang%2C+Q%3BKapur%2C+V%3BDaly%2C+JA%3BVeasy%2C+L+G%3BMusser%2C+J+M&rft.aulast=Smoot&rft.aufirst=J&rft.date=2002-04-02&rft.volume=99&rft.issue=7&rft.spage=4668&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.062526099 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus; USA, Utah, Salt Lake City; Heart diseases; Nucleotide sequence; Toxins; Phages; Virulence DO - http://dx.doi.org/10.1073/pnas.062526099 ER - TY - JOUR T1 - Contribution of Specific Cognitive Processes to Executive Functioning in an Aging Population AN - 85556933; 200206969 AB - The current study investigated executive function measures emphasizing Alpha Span (ASp) to understand relationships among executive & nonexecutive tasks. Nondemented older participants (N = 417) received a comprehensive cognitive battery. Age & vocabulary adjusted correlations revealed associations among ASp, Wechsler Adult Intelligence Scale-Revised (D. Wechsler, 1981) Digit Span subtests, & fluency tasks. Principal-components analysis with varimax rotation revealed a 4 component solution (86.4% of the variance) with executive variables contributing to all loadings. Calculated component indices were submitted to a regression analysis predicting ASp performance. After accounting for age (6.3% of the variance), Component 3 reflecting brief attention-mental manipulation accounted for 13.4% of ASp variance; Component 1, verbal language ability, 11.5%; Component 2, sustained attention-mental tracking, 1.9%; & Component 4, visuoperceptual spatial organization-planning, 0.9%. Results stress the importance of considering executive & nonexecutive aspects of cognition when conceptualizing executive functioning. 4 Tables, 49 References. [Copyright 2002 The American Psychological Association.] JF - Neuropsychology AU - Lamar, Melissa AU - Zonderman, Alan B AU - Resnick, Susan AD - National Instit Aging, Baltimore, MD lamarm@lpc.grc.nia.nih.gov Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 156 EP - 162 VL - 16 IS - 2 SN - 0894-4105, 0894-4105 KW - Cognitive Processes (12950) KW - Elderly (21350) KW - Psychometric Analysis (69210) KW - Attention (05350) KW - article KW - 4012: psycholinguistics; language and cognition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85556933?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychology&rft.atitle=Contribution+of+Specific+Cognitive+Processes+to+Executive+Functioning+in+an+Aging+Population&rft.au=Lamar%2C+Melissa%3BZonderman%2C+Alan+B%3BResnick%2C+Susan&rft.aulast=Lamar&rft.aufirst=Melissa&rft.date=2002-04-01&rft.volume=16&rft.issue=2&rft.spage=156&rft.isbn=&rft.btitle=&rft.title=Neuropsychology&rft.issn=08944105&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2003-10-01 N1 - Last updated - 2016-09-27 N1 - CODEN - NEUPEG N1 - SubjectsTermNotLitGenreText - Cognitive Processes (12950); Elderly (21350); Psychometric Analysis (69210); Attention (05350) ER - TY - JOUR T1 - Story processing in patients with damage to the prefrontal cortex. AN - 85375589; pmid-12056690 AB - The prefrontal cortex is known to be involved in performing complex cognitive tasks requiring reasoning, planning and decision-making. Neuropsychological evidence also supports the idea that the prefrontal cortex is generally involved in encoding and retrieving complex events, such as action and narrative knowledge. Patients with frontal lobe damage are reported to have difficulty in processing different aspects of narrative representations, such as the figurative moral meaning, syntactic features, and inference generation. In the present study, we examined story processing in 17 patients with frontal lobe lesions and compared their performance to 7 amnesic patients and 17 normal controls. Two stories were presented by using two slightly different processing demands in order to assess the subject's ability to draw inferences on-line during the course of comprehension or later retrieval. Although all patients had impaired story memory, patients with frontal lobe lesions showed a pattern of deficit at an early stage of story comprehension that specifically involved the ability to reconstruct the sequential links among events and to extract inferential knowledge from the text during encoding. Amnesic patients were severely impaired in recalling story semantic units, including single events and larger narrative constituents, as well as in the event recognition task. Consequently, they were unable to establish inferential relations among the events and, thus, the global sequential structure of the stories during retrieval. In contrast, they had no difficulty in extracting inferential knowledge during story comprehension on the basis of readily available information. This study shows that damage to different cortical regions may induce impairments at various levels of story processing. JF - Cortex; a journal devoted to the study of the nervous system and behavior AU - Zalla, Tiziana AU - Phipps, Michael AU - Grafman, Jordan AD - Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1440, USA. zalla@isc.cnrs.fr Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 215 EP - 231 VL - 38 IS - 2 SN - 0010-9452, 0010-9452 KW - Index Medicus KW - National Library of Medicine KW - Adult KW - Amnesia: physiopathology KW - *Cognition: physiology KW - Female KW - Functional Laterality KW - Humans KW - Male KW - *Memory: physiology KW - *Mental Recall: physiology KW - Middle Aged KW - Neuropsychological Tests KW - Prefrontal Cortex: injuries KW - Prefrontal Cortex: pathology KW - *Prefrontal Cortex: physiopathology KW - Psychomotor Performance: physiology KW - Semantics KW - Statistics, Nonparametric UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85375589?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cortex%3B+a+journal+devoted+to+the+study+of+the+nervous+system+and+behavior&rft.atitle=Story+processing+in+patients+with+damage+to+the+prefrontal+cortex.&rft.au=Zalla%2C+Tiziana%3BPhipps%2C+Michael%3BGrafman%2C+Jordan&rft.aulast=Zalla&rft.aufirst=Tiziana&rft.date=2002-04-01&rft.volume=38&rft.issue=2&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Cortex%3B+a+journal+devoted+to+the+study+of+the+nervous+system+and+behavior&rft.issn=00109452&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Auditory perception in auditory neuropathy: clinical similarity with auditory verbal agnosia. AN - 85366937; pmid-11934521 AB - The precise features of auditory perception in patients with auditory neuropathy have not been well described. In the present study, we examined auditory perception in a patient with auditory neuropathy. The patient was a right-handed 7-year-old boy. His chief complaint was delayed speech and suspected of verbal learning disability. He could talk, read and repeat rather fluently but could not understand fully what was asked. V-IQ, P-IQ and F-IQ of Wechsler Scale for Children III-R were 53, 118 and 81, respectively. Pure tone audiogram was completely normal. His speech discrimination ability was very poor. He could identify environmental sounds with visual matching. He could differentiate intensity difference but not time difference. This phenomenon was reported in patients with hemispheric symptoms. These clinical features are very similar to verbal auditory agnosia. ABR showed no response at 90dBnHL alternating clicks and tone bursts. Click evoked and distortion product otoacoustic emissions (OAE) were normal. Electrocochleogram was also normal. Motor and sensory nerve conduction velocity was completely normal. Pa of MLR and N1 of SVR were present. His diagnosis should be "pure type" of auditory neuropathy or auditory nerve disease. Importance of both ABR and OAE examination should be widely announced and auditory neuropathy must be campaigned stressed to be clinical entity among personnel who take care of children with speech delay. JF - Brain & development AU - Kaga, Makiko AU - Kon, Kaori AU - Uno, Akira AU - Horiguchi, Toshihiro AU - Yoneyama, Hitoshi AU - Inagaki, Masumi AD - Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry (NCNP), 1-7-3, Kohnodai, Ichikawa, Chiba 272-0827, Japan. kaga@ncnp-k.go.jp Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 197 EP - 202 VL - 24 IS - 3 SN - 0387-7604, 0387-7604 KW - Index Medicus KW - National Library of Medicine KW - Agnosia: diagnosis KW - Agnosia: physiopathology KW - Agnosia: psychology KW - *Auditory Perception KW - Child KW - *Cochlear Nerve KW - Diagnosis, Differential KW - Evoked Potentials, Auditory, Brain Stem KW - Hearing KW - Humans KW - Male KW - Nervous System: physiopathology KW - Neuropsychological Tests KW - Otoacoustic Emissions, Spontaneous KW - Perceptual Distortion KW - Psychology: methods KW - Speech Perception KW - Vestibulocochlear Nerve Diseases: diagnosis KW - *Vestibulocochlear Nerve Diseases: physiopathology KW - *Vestibulocochlear Nerve Diseases: psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85366937?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+%26+development&rft.atitle=Auditory+perception+in+auditory+neuropathy%3A+clinical+similarity+with+auditory+verbal+agnosia.&rft.au=Kaga%2C+Makiko%3BKon%2C+Kaori%3BUno%2C+Akira%3BHoriguchi%2C+Toshihiro%3BYoneyama%2C+Hitoshi%3BInagaki%2C+Masumi&rft.aulast=Kaga&rft.aufirst=Makiko&rft.date=2002-04-01&rft.volume=24&rft.issue=3&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=Brain+%26+development&rft.issn=03877604&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Adaptive evolution of a duplicated pancreatic ribonuclease gene in a leaf-eating monkey AN - 762278343; 13746350 AB - Although the complete genome sequences of over 50 representative species have revealed the many duplicated genes in all three domains of life, the roles of gene duplication in organismal adaptation and biodiversity are poorly understood. In addition, the evolutionary forces behind the functional divergence of duplicated genes are often unknown, leading to disagreement on the relative importance of positive Darwinian selection versus relaxation of functional constraints in this process. The methodology of earlier studies relied largely on DNA sequence analysis but lacked functional assays of duplicated genes, frequently generating contentious results. Here we use both computational and experimental approaches to address these questions in a study of the pancreatic ribonuclease gene (RNASE1) and its duplicate gene (RNASE1B) in a leaf-eating colobine monkey, douc langur. We show that RNASE1B has evolved rapidly under positive selection for enhanced ribonucleolytic activity in an altered microenvironment, a response to increased demands for the enzyme for digesting bacterial RNA. At the same time, the ability to degrade double-stranded RNA, a non-digestive activity characteristic of primate RNASE1, has been lost in RNASE1B, indicating functional specialization and relaxation of purifying selection. Our findings demonstrate the contribution of gene duplication to organismal adaptation and show the power of combining sequence analysis and functional assays in delineating the molecular basis of adaptive evolution. JF - Nature Genetics AU - Zhang, Jianzhi AU - Zhang, Ya-ping AU - Rosenberg, Helene F AD - [1] Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. [2] Departments of Ecology and Evolutionary Biology and Molecular, Cellular and Developmental Biology, University of Michigan, 3003 Natural Sciences Building, 830 North University Avenue, Ann Arbor, Michigan 48109, USA. Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 411 EP - 415 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 30 IS - 4 SN - 1061-4036, 1061-4036 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Sustainability Science Abstracts KW - Genomes KW - Adaptations KW - Nucleotide sequence KW - Double-stranded RNA KW - Biological diversity KW - Enzymes KW - Specialization KW - Biodiversity KW - Pancreatic ribonuclease KW - Computer applications KW - Primates KW - adaptability KW - gene duplication KW - Genetics KW - microenvironments KW - DNA KW - Microenvironments KW - Evolutionary genetics KW - Positive selection KW - Evolution KW - M3 1010:Issues in Sustainable Development KW - N 14815:Nucleotide Sequence KW - A 01490:Miscellaneous KW - G 07770:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/762278343?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Assamodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Genetics&rft.atitle=Adaptive+evolution+of+a+duplicated+pancreatic+ribonuclease+gene+in+a+leaf-eating+monkey&rft.au=Zhang%2C+Jianzhi%3BZhang%2C+Ya-ping%3BRosenberg%2C+Helene+F&rft.aulast=Zhang&rft.aufirst=Jianzhi&rft.date=2002-04-01&rft.volume=30&rft.issue=4&rft.spage=411&rft.isbn=&rft.btitle=&rft.title=Nature+Genetics&rft.issn=10614036&rft_id=info:doi/10.1038%2Fng852 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2013-10-04 N1 - SubjectsTermNotLitGenreText - Genomes; Adaptations; Double-stranded RNA; Nucleotide sequence; Biodiversity; Specialization; Enzymes; Pancreatic ribonuclease; Computer applications; gene duplication; Microenvironments; Evolutionary genetics; Positive selection; Evolution; Genetics; microenvironments; DNA; Biological diversity; Primates; adaptability DO - http://dx.doi.org/10.1038/ng852 ER - TY - JOUR T1 - Chromosome-mediated alterations of the MYC gene in human cancer. AN - 71988925; 12169201 AB - The step-wise accumulation of genetic and epigenetic alterations in cancer development includes chromosome rearrangements and viral integration-mediated genetic alterations that frequently involve proto-oncogenes. Proto-oncogenes deregulation lead to unlimited, self-sufficient cell growth and ultimately generates invasive and destructive tumors. C-MYC gene, the cellular homologue of the avian myelocitic leukemia virus, is implicated in a large number of human solid tumors, leukemias and lymphomas as well as in a variety of animal neoplasias. Deregulated MYC expression is a common denominator in cancer. Chromosomal rearrangements and integration of oncogenic viruses frequently target MYC locus, causing structural or functional alterations of the gene. In this article, we illustrate how genomic rearrangements and viruses integration affect MYC locus in certain human lymphomas and solid tumors. JF - Journal of cellular and molecular medicine AU - Popescu, N C AU - Zimonjic, D B AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, 37 Convent Drive MSC 4258, Bethesda, Maryland 20892-4258, USA. popescun@dc37a.nci.nih.gov PY - 2002 SP - 151 EP - 159 VL - 6 IS - 2 SN - 1582-1838, 1582-1838 KW - Index Medicus KW - Breast Neoplasms -- genetics KW - Tumor Cells, Cultured KW - Humans KW - Recombination, Genetic KW - Burkitt Lymphoma -- genetics KW - Liver Neoplasms -- virology KW - Virus Integration KW - Translocation, Genetic KW - Oncogenic Viruses -- genetics KW - Liver Neoplasms -- genetics KW - Gene Amplification KW - Oncogenes KW - Chromosome Aberrations KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71988925?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+and+molecular+medicine&rft.atitle=Chromosome-mediated+alterations+of+the+MYC+gene+in+human+cancer.&rft.au=Popescu%2C+N+C%3BZimonjic%2C+D+B&rft.aulast=Popescu&rft.aufirst=N&rft.date=2002-04-01&rft.volume=6&rft.issue=2&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+and+molecular+medicine&rft.issn=15821838&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-06 N1 - Date created - 2002-08-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficacy and toxicity of a protocol using sirolimus, tacrolimus and daclizumab in a nonhuman primate renal allotransplant model. AN - 71911207; 12118862 AB - A regimen combining sirolimus, tacrolimus, and daclizumab has recently been shown to provide adequate immunosuppression for allogeneic islet transplantation in humans, but remains unproven for primarily vascularized allografts. We evaluated this regimen for renal allograft transplantation in mismatched nonhuman primates. Dosages of sirolimus and tacrolimus were adjusted for trough levels of 10-15 ng/mL and 4-6 ng/mL, respectively. Treated monkeys (n = 5) had significantly prolonged allograft survival, with a mean survival of 36 days vs. 7 days in untreated controls (n = 6, p = 0.008). Four of five treated animals, but none of the controls, developed fibrinoid vascular necrosis of the small intestine. A review of gut histology from animals on other immunosuppressive protocols performed by our laboratory suggested that these lesions were a result of sirolimus exposure. In summary, this regimen prolongs the survival of vascularized renal allografts, but is limited by profound GI toxicity in rhesus macaques. JF - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons AU - Montgomery, Sean P AU - Mog, Steven R AU - Xu, He AU - Tadaki, Douglas K AU - Hirshberg, Boaz AU - Berning, Justin D AU - Leconte, John AU - Harlan, David M AU - Hale, Douglas AU - Kirk, Allan D AD - NIDDK/Navy Transplantation and Autoimmunity Branch, Naval Medical Research Center, Bethesda, Maryland 20892, USA. Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 381 EP - 385 VL - 2 IS - 4 SN - 1600-6135, 1600-6135 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Humanized KW - Immunoglobulin G KW - Immunosuppressive Agents KW - daclizumab KW - CUJ2MVI71Y KW - Sirolimus KW - W36ZG6FT64 KW - Tacrolimus KW - WM0HAQ4WNM KW - Index Medicus KW - Models, Animal KW - Evaluation Studies as Topic KW - Immune Tolerance -- drug effects KW - Animals KW - Immunosuppressive Agents -- toxicity KW - Intestine, Small -- drug effects KW - Macaca mulatta -- immunology KW - Intestine, Small -- pathology KW - Graft Survival -- drug effects KW - Immunosuppressive Agents -- pharmacology KW - Tacrolimus -- toxicity KW - Kidney Transplantation KW - Antibodies, Monoclonal -- toxicity KW - Tacrolimus -- pharmacology KW - Sirolimus -- pharmacology KW - Immunoglobulin G -- pharmacology KW - Antibodies, Monoclonal -- pharmacology KW - Immunoglobulin G -- toxicity KW - Sirolimus -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71911207?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+transplantation+%3A+official+journal+of+the+American+Society+of+Transplantation+and+the+American+Society+of+Transplant+Surgeons&rft.atitle=Efficacy+and+toxicity+of+a+protocol+using+sirolimus%2C+tacrolimus+and+daclizumab+in+a+nonhuman+primate+renal+allotransplant+model.&rft.au=Montgomery%2C+Sean+P%3BMog%2C+Steven+R%3BXu%2C+He%3BTadaki%2C+Douglas+K%3BHirshberg%2C+Boaz%3BBerning%2C+Justin+D%3BLeconte%2C+John%3BHarlan%2C+David+M%3BHale%2C+Douglas%3BKirk%2C+Allan+D&rft.aulast=Montgomery&rft.aufirst=Sean&rft.date=2002-04-01&rft.volume=2&rft.issue=4&rft.spage=381&rft.isbn=&rft.btitle=&rft.title=American+journal+of+transplantation+%3A+official+journal+of+the+American+Society+of+Transplantation+and+the+American+Society+of+Transplant+Surgeons&rft.issn=16006135&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-16 N1 - Date created - 2002-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The challenging interactions between antiretroviral agents and addiction drugs. AN - 71768695; 12038078 JF - American clinical laboratory AU - Khalsa, Jag AU - Genser, Sander AU - Vocci, Frank AU - Francis, Henry AU - Bean, Pamela AD - Center on AIDS and Other Medical Consequences of Drug Abuse (CAMCODA), National Institute on Drug Abuse, NIH, Rockville, MD, USA. Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 10 EP - 13 VL - 21 IS - 3 SN - 1041-3235, 1041-3235 KW - Narcotics KW - 0 KW - Street Drugs KW - Methadone KW - UC6VBE7V1Z KW - Health technology assessment KW - Drug Interactions KW - Humans KW - Street Drugs -- adverse effects KW - Methadone -- adverse effects KW - Antiretroviral Therapy, Highly Active -- adverse effects KW - HIV Infections -- drug therapy KW - Narcotics -- adverse effects KW - Substance-Related Disorders -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71768695?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+clinical+laboratory&rft.atitle=The+challenging+interactions+between+antiretroviral+agents+and+addiction+drugs.&rft.au=Khalsa%2C+Jag%3BGenser%2C+Sander%3BVocci%2C+Frank%3BFrancis%2C+Henry%3BBean%2C+Pamela&rft.aulast=Khalsa&rft.aufirst=Jag&rft.date=2002-04-01&rft.volume=21&rft.issue=3&rft.spage=10&rft.isbn=&rft.btitle=&rft.title=American+clinical+laboratory&rft.issn=10413235&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-28 N1 - Date created - 2002-05-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Histidine-rich glycoprotein plus zinc to neutralize heparin. AN - 71714273; 12024108 AB - Histidine-rich glycoprotein (HRG) binds heparin and neutralizes its anticoagulant effect. Because zinc greatly enhances this interaction, it is possible that the combination of HRG and zinc could be used as an antidote for heparin. We have determined the plasma concentrations of HRG and zinc necessary to neutralize clinically relevant concentrations of heparin. Using a thrombin-time assay, we found that HRG plus zinc can neutralize 0.2 to 4.5 units/mL heparin, although the maximal effect requires an HRG plasma concentration about six times normal and a zinc concentration about 10 times normal. In a system using purified proteins and a thrombin-specific chromogenic substrate, we found that both the concentration of HRG and the molar ratio of HRG to zinc are important in determining the potency of the anti-heparin activity. Whether HRG and zinc can be administered as an antidote for heparin will depend on whether the requisite doses can be achieved without toxicity. JF - The Journal of laboratory and clinical medicine AU - Fu, Chieh-Lin AU - Horn, McDonald K AD - Hematology Service, Department of Laboratory Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Room 2C306, Building 10, Bethesda, MD 20892, USA. mhorne@mail.cc.nih.gov. Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 211 EP - 217 VL - 139 IS - 4 SN - 0022-2143, 0022-2143 KW - Antidotes KW - 0 KW - Blood Proteins KW - Citrates KW - Heparin Antagonists KW - Proteins KW - histidine-rich proteins KW - Heparin KW - 9005-49-6 KW - Zinc KW - J41CSQ7QDS KW - Abridged Index Medicus KW - Index Medicus KW - Protein Binding -- drug effects KW - Humans KW - Blood Coagulation -- drug effects KW - In Vitro Techniques KW - Drug Synergism KW - Blood Proteins -- metabolism KW - Blood Proteins -- pharmacology KW - Thrombin Time KW - Proteins -- pharmacology KW - Zinc -- pharmacology KW - Heparin Antagonists -- pharmacology KW - Heparin -- pharmacology KW - Antidotes -- metabolism KW - Zinc -- metabolism KW - Heparin Antagonists -- metabolism KW - Heparin -- metabolism KW - Antidotes -- pharmacology KW - Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71714273?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+laboratory+and+clinical+medicine&rft.atitle=Histidine-rich+glycoprotein+plus+zinc+to+neutralize+heparin.&rft.au=Fu%2C+Chieh-Lin%3BHorn%2C+McDonald+K&rft.aulast=Fu&rft.aufirst=Chieh-Lin&rft.date=2002-04-01&rft.volume=139&rft.issue=4&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+laboratory+and+clinical+medicine&rft.issn=00222143&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-20 N1 - Date created - 2002-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Androgens and mammary growth and neoplasia. AN - 71687451; 12007899 AB - Evaluation of current clinical, experimental, genetic, and epidemiological data pertaining to the role of androgens in mammary growth and neoplasia. Literature review. National Institutes of Health. Recent, basic, clinical, and epidemiological studies. None. Effects of androgens on mammary epithelial proliferation and/or breast cancer incidence. Experimental data derived from rodents and cell lines provide conflicting results that appear be strain- and cell line-dependent. Epidemiologic studies have significant methodological limitations and provide inconclusive results. The study of molecular defects involving androgenic pathways in breast cancer is in its infancy. Clinical and nonhuman primate studies, however, suggest that androgens inhibit mammary epithelial proliferation and breast growth and that conventional estrogen treatment suppresses endogenous androgens. Abundant clinical evidence suggests that androgens normally inhibit mammary epithelial proliferation and breast growth. Suppression of androgens by conventional estrogen treatment may thus enhance estrogenic breast stimulation and possibly breast cancer risk. Clinical trials to evaluate the impact of combined estrogen and androgen hormone replacement regimens on mammary gland homeostasis are needed to address this issue. JF - Fertility and sterility AU - Dimitrakakis, Constantine AU - Zhou, Jian AU - Bondy, Carolyn A AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/04// PY - 2002 DA - April 2002 SP - S26 EP - S33 VL - 77 Suppl 4 SN - 0015-0282, 0015-0282 KW - Androgens KW - 0 KW - Contraceptives, Oral, Hormonal KW - Estrogens KW - Index Medicus KW - Contraceptives, Oral, Hormonal -- metabolism KW - Hormone Replacement Therapy -- adverse effects KW - Estrogens -- metabolism KW - Humans KW - Contraceptives, Oral, Hormonal -- adverse effects KW - Estrogens -- adverse effects KW - Female KW - Breast Neoplasms -- pathology KW - Androgens -- adverse effects KW - Androgens -- physiology KW - Breast Neoplasms -- etiology KW - Breast Neoplasms -- metabolism KW - Breast -- physiology KW - Breast -- growth & development KW - Breast -- metabolism KW - Androgens -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71687451?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fertility+and+sterility&rft.atitle=Androgens+and+mammary+growth+and+neoplasia.&rft.au=Dimitrakakis%2C+Constantine%3BZhou%2C+Jian%3BBondy%2C+Carolyn+A&rft.aulast=Dimitrakakis&rft.aufirst=Constantine&rft.date=2002-04-01&rft.volume=77+Suppl+4&rft.issue=&rft.spage=S26&rft.isbn=&rft.btitle=&rft.title=Fertility+and+sterility&rft.issn=00150282&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-11 N1 - Date created - 2002-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - How can I help my patient stop drinking? AN - 71663993; 11996430 JF - American family physician AU - Enoch, Mary-Anne AD - National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA. Y1 - 2002/04/01/ PY - 2002 DA - 2002 Apr 01 SP - 1475 EP - 1476 VL - 65 IS - 7 SN - 0002-838X, 0002-838X KW - Abridged Index Medicus KW - Index Medicus KW - Family Practice KW - Humans KW - Middle Aged KW - Treatment Refusal KW - Physician-Patient Relations KW - Female KW - Alcoholism -- rehabilitation KW - Alcoholism -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71663993?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+family+physician&rft.atitle=How+can+I+help+my+patient+stop+drinking%3F&rft.au=Enoch%2C+Mary-Anne&rft.aulast=Enoch&rft.aufirst=Mary-Anne&rft.date=2002-04-01&rft.volume=65&rft.issue=7&rft.spage=1475&rft.isbn=&rft.btitle=&rft.title=American+family+physician&rft.issn=0002838X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-30 N1 - Date created - 2002-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo copper-mediated free radical production: an ESR spin-trapping study. AN - 71656449; 11993471 AB - Copper has been suggested to facilitate oxidative tissue injury through a free radical-mediated pathway analogous to the Fenton reaction. By applying the electron spin resonance (ESR) spin-trapping technique, evidence for hydroxyl radical formation in vivo was obtained in rats treated simultaneously with copper and ascorbic acid or paraquat. A secondary radical spin-trapping technique was used in which the hydroxyl radical formed the methyl radical upon reaction with dimethylsulfoxide. The methyl radical was then detected by ESR spectroscopy as its adduct with the spin trap phenyl-N-t-butyl- nitrone (PBN). In contrast, lipid derived radical was detected in vivo in copper-challenged, vitamin E and selenium-deficient rats. These findings support the proposal that dietary selenium and vitamin E can protect against lipid peroxidation and copper toxicity. Since copper excreted into the bile from treated animals is expected to be maintained in the Cu(I) state (by ascorbic acid or glutathione), a chelating agent that would redox-stablilize it in the Cu(I) state was used to prevent ex vivo redox chemistry. Bile samples were collected directly into solutions of bathocuproinedisulfonic acid, a Cu(I)-stabilizing agent, and 2,2'-dipyridyl, a Fe(II)-stabilizing agent. If these precautions were not taken, radical adducts generated ex vivo could be mistaken for radical adducts produced in vivo and excreted into the bile. JF - Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy AU - Kadiiska, Maria B AU - Mason, Ronald P AD - National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709-2233, USA. kadiiska@niehs.nih.gov Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 1227 EP - 1239 VL - 58 IS - 6 SN - 1386-1425, 1386-1425 KW - Free Radicals KW - 0 KW - Vitamin E KW - 1406-18-4 KW - Hydroxyl Radical KW - 3352-57-6 KW - Copper KW - 789U1901C5 KW - Selenium KW - H6241UJ22B KW - Paraquat KW - PLG39H7695 KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Dimethyl Sulfoxide KW - YOW8V9698H KW - Index Medicus KW - Paraquat -- pharmacology KW - Animals KW - Dimethyl Sulfoxide -- pharmacology KW - Vitamin E -- metabolism KW - Bile -- metabolism KW - Ascorbic Acid -- pharmacology KW - Selenium -- deficiency KW - Oxidation-Reduction KW - Rats KW - Rats, Sprague-Dawley KW - Vitamin E Deficiency KW - Models, Chemical KW - Lipid Metabolism KW - Male KW - Electron Spin Resonance Spectroscopy -- methods KW - Copper -- pharmacology KW - Copper -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71656449?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Spectrochimica+acta.+Part+A%2C+Molecular+and+biomolecular+spectroscopy&rft.atitle=In+vivo+copper-mediated+free+radical+production%3A+an+ESR+spin-trapping+study.&rft.au=Kadiiska%2C+Maria+B%3BMason%2C+Ronald+P&rft.aulast=Kadiiska&rft.aufirst=Maria&rft.date=2002-04-01&rft.volume=58&rft.issue=6&rft.spage=1227&rft.isbn=&rft.btitle=&rft.title=Spectrochimica+acta.+Part+A%2C+Molecular+and+biomolecular+spectroscopy&rft.issn=13861425&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-11 N1 - Date created - 2002-05-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics of paclitaxel administered by hyperthermic retrograde isolated lung perfusion techniques. AN - 71647467; 11986596 AB - Although paclitaxel is widely used as a systemic agent for the treatment of solid tumors, limited information is available concerning administration of this taxane by regional techniques. The present study was undertaken to evaluate the pharmacokinetics and acute toxicity of paclitaxel administered by hyperthermic retrograde isolated lung perfusion techniques to ascertain its potential for the regional therapy of unresectable pulmonary neoplasms. Adult sheep underwent 90 minutes of retrograde isolated lung perfusion with escalating doses of paclitaxel and moderate hyperthermia using a protein-free, oxygenated extracorporeal circuit and a steady perfusion pressure of 14 to 16 mm Hg. An additional animal received paclitaxel by means of 1-hour central venous infusion. Paclitaxel concentrations in lung tissues, perfusates, and systemic circulation were determined by high-performance liquid chromotography techniques. Cytotoxicity of paclitaxel in cancer cells and in normal human bronchial epithelial cells was evaluated in vitro using 4, 5-dimethylthiazo-2-yl-25-dipagnyl tetrazolium bromide assays. Lung tissues were examined by hematoxylin-and-eosin techniques. Paclitaxel concentrations (maximum concentration and area under the plasma concentration time curve) in perfused tissues increased with escalating perfusate doses. Uptake of drug into lung parenchyma appeared saturable at high paclitaxel exposure; a substantial pharmacokinetic advantage was observed. Paclitaxel concentrations in systemic circulation were undetectable or exceedingly low after perfusion. Histopathologic examination of lung tissues harvested 3 hours after completion of isolated lung perfusion revealed no immediate toxicity, even at a paclitaxel exposure 20-fold higher than that achievable after 1 hour of intravenous administration at the maximum tolerable dose in human subjects. Moderate hyperthermia enhanced paclitaxel-mediated cytotoxicity 5- to 100-fold in cultured cancer lines. No paclitaxel toxicity was observed in cultured normal human bronchial epithelial cells after exposure to paclitaxel under normothermic or hyperthermic conditions. These data support further evaluation of paclitaxel administered by hyperthermic retrograde isolated lung perfusion techniques for the treatment of unresectable malignant pulmonary tumors. JF - The Journal of thoracic and cardiovascular surgery AU - Schrump, David S AU - Zhai, Suoping AU - Nguyen, Dao M AU - Weiser, Todd S AU - Fisher, Bradley A AU - Terrill, Richard E AU - Flynn, Bernard M AU - Duray, Paul H AU - Figg, William D AD - Thoracic Oncology Section, Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1502, USA. David_Schrump@nih.gov Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 686 EP - 694 VL - 123 IS - 4 SN - 0022-5223, 0022-5223 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Paclitaxel KW - P88XT4IS4D KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Epithelial Cells -- drug effects KW - Infusions, Intravenous KW - Bronchi -- cytology KW - Area Under Curve KW - Tumor Cells, Cultured -- drug effects KW - Dose-Response Relationship, Drug KW - Sheep KW - Humans KW - Treatment Outcome KW - Hyperthermia, Induced -- adverse effects KW - Disease Models, Animal KW - Paclitaxel -- administration & dosage KW - Antineoplastic Agents, Phytogenic -- pharmacokinetics KW - Paclitaxel -- blood KW - Lung Neoplasms -- blood KW - Paclitaxel -- pharmacokinetics KW - Chemotherapy, Cancer, Regional Perfusion KW - Lung Neoplasms -- drug therapy KW - Antineoplastic Agents, Phytogenic -- blood KW - Antineoplastic Agents, Phytogenic -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71647467?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+thoracic+and+cardiovascular+surgery&rft.atitle=Pharmacokinetics+of+paclitaxel+administered+by+hyperthermic+retrograde+isolated+lung+perfusion+techniques.&rft.au=Schrump%2C+David+S%3BZhai%2C+Suoping%3BNguyen%2C+Dao+M%3BWeiser%2C+Todd+S%3BFisher%2C+Bradley+A%3BTerrill%2C+Richard+E%3BFlynn%2C+Bernard+M%3BDuray%2C+Paul+H%3BFigg%2C+William+D&rft.aulast=Schrump&rft.aufirst=David&rft.date=2002-04-01&rft.volume=123&rft.issue=4&rft.spage=686&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+thoracic+and+cardiovascular+surgery&rft.issn=00225223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-07 N1 - Date created - 2002-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Calmodulin regulates Ca(2+)-dependent feedback inhibition of store-operated Ca(2+) influx by interaction with a site in the C terminus of TrpC1. AN - 71640975; 11983166 AB - The mechanism involved in [Ca(2+)](i)-dependent feedback inhibition of store-operated Ca(2+) entry (SOCE) is not yet known. Expression of Ca(2+)-insensitive calmodulin (Mut-CaM) but not wild-type CaM increased SOCE and decreased its Ca(2+)-dependent inactivation. Expression of TrpC1 lacking C terminus aa 664-793 (TrpC1DeltaC) also attenuated Ca(2+)-dependent inactivation of SOCE. CaM interacted with endogenous and expressed TrpC1 and with GST-TrpC1 C terminus but not with TrpC1DeltaC. Two CaM binding domains, aa 715-749 and aa 758-793, were identified. Expression of TrpC1Delta758-793 but not TrpC1Delta715-749 mimicked the effects of TrpC1DeltaC and Mut-CaM on SOCE. These data demonstrate that CaM mediates Ca(2+)-dependent feedback inhibition of SOCE via binding to a domain in the C terminus of TrpC1. These findings reveal an integral role for TrpC1 in the regulation of SOCE. JF - Molecular cell AU - Singh, Brij B AU - Liu, Xibao AU - Tang, Jisen AU - Zhu, Michael X AU - Ambudkar, Indu S AD - Secretory Physiology Section, Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 739 EP - 750 VL - 9 IS - 4 SN - 1097-2765, 1097-2765 KW - Calcium Channels KW - 0 KW - Calmodulin KW - DNA, Complementary KW - Peptide Fragments KW - Recombinant Fusion Proteins KW - TRPC Cation Channels KW - transient receptor potential cation channel, subfamily C, member 1 KW - Index Medicus KW - Peptide Fragments -- metabolism KW - DNA, Complementary -- genetics KW - Cell Line -- metabolism KW - Cell Line -- drug effects KW - Humans KW - Submandibular Gland -- cytology KW - Ion Transport -- physiology KW - Protein Binding KW - Recombinant Fusion Proteins -- chemistry KW - Binding Sites KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Epithelial Cells -- metabolism KW - Ion Channel Gating -- physiology KW - Patch-Clamp Techniques KW - Epithelial Cells -- drug effects KW - Protein Interaction Mapping KW - Transfection KW - Cell Compartmentation KW - Feedback KW - Protein Structure, Tertiary KW - Amino Acid Substitution KW - Sequence Deletion KW - Calcium Channels -- physiology KW - Calcium Channels -- metabolism KW - Calcium Signaling -- physiology KW - Calmodulin -- chemistry KW - Calmodulin -- physiology KW - Calcium Channels -- chemistry KW - Calmodulin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71640975?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+cell&rft.atitle=Calmodulin+regulates+Ca%282%2B%29-dependent+feedback+inhibition+of+store-operated+Ca%282%2B%29+influx+by+interaction+with+a+site+in+the+C+terminus+of+TrpC1.&rft.au=Singh%2C+Brij+B%3BLiu%2C+Xibao%3BTang%2C+Jisen%3BZhu%2C+Michael+X%3BAmbudkar%2C+Indu+S&rft.aulast=Singh&rft.aufirst=Brij&rft.date=2002-04-01&rft.volume=9&rft.issue=4&rft.spage=739&rft.isbn=&rft.btitle=&rft.title=Molecular+cell&rft.issn=10972765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-14 N1 - Date created - 2002-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ethical assessment of industry-sponsored clinical trials: a case analysis. AN - 71633660; 11948071 AB - The rapid growth of clinical trials sponsored by the pharmaceutical industry and conducted by community physicians raises concerns about the scientific quality of this research and the adequacy of protections for research participants. In this article, we present an in-depth ethical analysis of a recent industry-sponsored placebo-controlled study for treatment of asthma. The ethical analysis uses a proposed ethical framework for evaluating clinical research focusing on seven ethical requirements: (1) scientific value, (2) scientific validity, (3) fair subject selection, (4) favorable risk/benefit ratio, (5) independent review, (6) informed consent, and (7) respect for enrolled subjects. JF - Chest AU - Miller, Franklin G AU - Shorr, Andrew F AD - Department of Clinical Bioethics, National Institutes of Health, Bethesda, MD 20892-1156, USA. fmiller@nih.gov Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 1337 EP - 1342 VL - 121 IS - 4 SN - 0012-3692, 0012-3692 KW - Pregnadienediols KW - 0 KW - Mometasone Furoate KW - 04201GDN4R KW - Beclomethasone KW - KGZ1SLC28Z KW - Abridged Index Medicus KW - Bioethics KW - Index Medicus KW - Biomedical and Behavioral Research KW - Double-Blind Method KW - Humans KW - Adult KW - Treatment Outcome KW - Informed Consent KW - Adolescent KW - Administration, Inhalation KW - Male KW - Forced Expiratory Volume -- drug effects KW - Female KW - Ethics Committees, Research KW - Beclomethasone -- adverse effects KW - Drug Industry KW - Beclomethasone -- therapeutic use KW - Pregnadienediols -- adverse effects KW - Asthma -- drug therapy KW - Pregnadienediols -- therapeutic use KW - Ethics, Medical KW - Conflict of Interest KW - Controlled Clinical Trials as Topic -- statistics & numerical data KW - Controlled Clinical Trials as Topic -- economics KW - Patient Selection KW - Research Support as Topic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71633660?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chest&rft.atitle=Ethical+assessment+of+industry-sponsored+clinical+trials%3A+a+case+analysis.&rft.au=Miller%2C+Franklin+G%3BShorr%2C+Andrew+F&rft.aulast=Miller&rft.aufirst=Franklin&rft.date=2002-04-01&rft.volume=121&rft.issue=4&rft.spage=1337&rft.isbn=&rft.btitle=&rft.title=Chest&rft.issn=00123692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-09 N1 - Date created - 2002-04-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Chest. 2002 Nov;122(5):1869-70 [12426302] Chest. 2002 Apr;121(4):1019-21 [11948025] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The self-perceived survival ability and reproductive fitness (SPFit) theory of substance use disorders. AN - 71616149; 11964059 AB - A new theory of substance use disorders is proposed-the SPFit theory-that is based on evolutionary biology and adaptive systems. Self-perceived survival ability and reproductive fitness (SPFit) is proposed as a human psychobiological construct that prioritizes and organizes (i.e. motivates) behavior, but is highly vulnerable to temporary, artificial activation by drugs of abuse. Autoshaping/sign-tracking/feature positive phenomena are proposed to underlie the development of craving and expectations about drugs as the individual learns that abused drugs will easily and reliably inflate SPFit. The cortico-mesolimbic dopamine system and its modulating interconnections are viewed as the biological substrate of SPFit; it is proposed to be a survival and reproductive motivation system rather than a reward center or reward pathway. Finally, the concept of modularity of mind is applied to the SPFit construct. Although considerable empirical data are consistent with the theory, new research is needed to test specific hypotheses derived from SPFit theory. JF - Addiction (Abingdon, England) AU - Newlin, David B AD - National Institute on Drug Abuse--Intramural Research Program, Molecular Neurobiology Branch, Baltimore, MD 21224, USA. dnewlin@intra.nida.nih.gov Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 427 EP - 445 VL - 97 IS - 4 SN - 0965-2140, 0965-2140 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Models, Psychological KW - Humans KW - Dopamine -- physiology KW - Brain -- physiology KW - Biological Evolution KW - Substance-Related Disorders -- etiology KW - Survival KW - Reproduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71616149?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addiction+%28Abingdon%2C+England%29&rft.atitle=The+self-perceived+survival+ability+and+reproductive+fitness+%28SPFit%29+theory+of+substance+use+disorders.&rft.au=Newlin%2C+David+B&rft.aulast=Newlin&rft.aufirst=David&rft.date=2002-04-01&rft.volume=97&rft.issue=4&rft.spage=427&rft.isbn=&rft.btitle=&rft.title=Addiction+%28Abingdon%2C+England%29&rft.issn=09652140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-30 N1 - Date created - 2002-04-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Addiction. 2002 Apr;97(4):473-4 [11964064] Addiction. 2002 Apr;97(4):470-1 [11964062] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evolutionary underpinnings of excessive alcohol consumption. AN - 71610156; 11964058 AB - Given our close phylogenetic relatedness, non-human primates, in principle, could serve as an ideal model for alcoholism. Indeed, many studies in both humans and rhesus macaques show relationships between excessive alcohol consumption, aggression and serotonergic function, as measured by concentrations of the principal metabolite of serotonin, 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF). An important behavioral predictor of excessive alcohol consumption in both humans and rhesus monkeys is the propensity toward impulsivity. Integrating behavioral and neuroendocrine data from captive and semi-free-ranging rhesus macaques, we posit that benefits derived from impulsive and aggressive behaviors in some contexts might contribute indirectly to the maintenance of traits involved in alcoholism and excessive alcohol intake. JF - Addiction (Abingdon, England) AU - Gerald, Melissa S AU - Higley, J Dee AD - National Institute on Alcohol Abuse and Alcoholism, Intramural Research Program, NIH Animal Center, Poolesville, MD, USA. cayo_santiago@yahoo.com Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 415 EP - 425 VL - 97 IS - 4 SN - 0965-2140, 0965-2140 KW - Serotonin KW - 333DO1RDJY KW - Index Medicus KW - Animals KW - Serotonin -- physiology KW - Disease Susceptibility KW - Macaca mulatta KW - Selection, Genetic KW - Alcoholism -- etiology KW - Biological Evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71610156?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addiction+%28Abingdon%2C+England%29&rft.atitle=Evolutionary+underpinnings+of+excessive+alcohol+consumption.&rft.au=Gerald%2C+Melissa+S%3BHigley%2C+J+Dee&rft.aulast=Gerald&rft.aufirst=Melissa&rft.date=2002-04-01&rft.volume=97&rft.issue=4&rft.spage=415&rft.isbn=&rft.btitle=&rft.title=Addiction+%28Abingdon%2C+England%29&rft.issn=09652140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-30 N1 - Date created - 2002-04-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Addiction. 2002 Apr;97(4):473-4 [11964064] Addiction. 2002 Apr;97(4):470-1 [11964062] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transarterial perfusion of liver metastases. AN - 71602249; 11951211 AB - Progressive growth of unresectable metastatic or primary malignancies confined to the liver is a significant clinical problem. Approximately 25% of patients with colorectal cancer will develop metastatic disease exclusively or largely confined to liver, the vast majority of which are not amenable to surgical resection. Despite aggressive systemic or regional chemotherapy, survival is only 12 to 18 months. More than 80% of patients with ocular melanoma develop liver metastases as the first site of recurrent disease, and death from hepatic disease progression typically occurs 2 to 7 months after diagnosis. In addition, the liver is also the preferred site of metastatic disease for gastrointestinal or pancreatic neuroendocrine tumors. A number of physiological and anatomic features of the liver make it an ideal organ for regionally directed therapy to allow dose intensification to the cancer-burdened area while reducing or eliminating unnecessary systemic toxicity. To that end, complete vascular isolation and perfusion of the liver using a recirculating extracorporeal circuit, also called isolated hepatic perfusion (IHP), has been under clinical evaluation at our institution and others. In this article, we review the current results with IHP and its potential utility in the treatment of patients with unresectable hepatic malignancies. JF - Seminars in oncology AU - Weinreich, David M AU - Alexander, H Richard AD - Metabolism Section, Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 136 EP - 144 VL - 29 IS - 2 SN - 0093-7754, 0093-7754 KW - Antineoplastic Agents KW - 0 KW - Tumor Necrosis Factor-alpha KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Melanoma -- pathology KW - Combined Modality Therapy KW - Colorectal Neoplasms -- pathology KW - Humans KW - Hyperthermia, Induced KW - Clinical Trials as Topic KW - Melphalan -- therapeutic use KW - Tumor Necrosis Factor-alpha -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Liver Neoplasms -- therapy KW - Chemotherapy, Cancer, Regional Perfusion -- methods KW - Liver Neoplasms -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71602249?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+oncology&rft.atitle=Transarterial+perfusion+of+liver+metastases.&rft.au=Weinreich%2C+David+M%3BAlexander%2C+H+Richard&rft.aulast=Weinreich&rft.aufirst=David&rft.date=2002-04-01&rft.volume=29&rft.issue=2&rft.spage=136&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology&rft.issn=00937754&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-23 N1 - Date created - 2002-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ionizing radiation and cancer risk: evidence from epidemiology. AN - 71598357; 11956701 JF - Pediatric radiology AU - Ron, Elaine AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 6120 Executive Boulevard, Rockville, MD 20852, USA. eron@mail.nih.gov Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 232 EP - 7; discussion 242-4 VL - 32 IS - 4 SN - 0301-0449, 0301-0449 KW - Index Medicus KW - Risk KW - Radiation Dosage KW - Age Factors KW - Humans KW - Child KW - Scoliosis -- diagnostic imaging KW - Radiography KW - Radiation Effects KW - Thyroid Neoplasms -- epidemiology KW - Lymphoma, Non-Hodgkin -- epidemiology KW - Leukemia, Lymphocytic, Chronic, B-Cell -- epidemiology KW - Leukemia, Radiation-Induced -- epidemiology KW - Neoplasms, Radiation-Induced -- epidemiology KW - Leukemia, Lymphocytic, Chronic, B-Cell -- etiology KW - Thyroid Neoplasms -- etiology KW - Radiotherapy -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71598357?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatric+radiology&rft.atitle=Ionizing+radiation+and+cancer+risk%3A+evidence+from+epidemiology.&rft.au=Ron%2C+Elaine&rft.aulast=Ron&rft.aufirst=Elaine&rft.date=2002-04-01&rft.volume=32&rft.issue=4&rft.spage=232&rft.isbn=&rft.btitle=&rft.title=Pediatric+radiology&rft.issn=03010449&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-15 N1 - Date created - 2002-04-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Summary of the National Toxicology Program's report of the endocrine disruptors low-dose peer review. AN - 71595394; 11940462 AB - At the request of the U.S. Environmental Protection Agency (U.S. EPA), the National Toxicology Program organized an independent and open peer review to evaluate the scientific evidence on low-dose effects and nonmonotonic dose-response relationships for endocrine-disrupting chemicals in mammalian species. For this peer review, "low-dose effects" referred to biologic changes that occur in the range of human exposures or at doses lower than those typically used in the standard testing paradigm of the U.S. EPA for evaluating reproductive and developmental toxicity. The demonstration that an effect is adverse was not required because in many cases the long-term health consequences of altered endocrine function during development have not been fully characterized. A unique aspect of this peer review was the willing submission of individual animal data by principal investigators of primary research groups active in this field and the independent statistical reanalyses of selected parameters prior to the peer review meeting by a subpanel of statisticians. The expert peer-review panel (the panel) also considered mechanistic data that might influence the plausibility of low-dose effects and identified study design issues or other biologic factors that might account for differences in reported outcomes among studies. The panel found that low-dose effects, as defined for this review, have been demonstrated in laboratory animals exposed to certain endocrine-active agents. In some cases where low-dose effects have been reported, the findings have not been replicated. The shape of the dose-response curves for reported effects varied with the end point and dosing regimen and were low-dose linear, threshold-appearing, or nonmonotonic. The findings of the panel indicate that the current testing paradigm used for assessments of reproductive and developmental toxicity should be revisited to see whether changes are needed regarding dose selection, animal-model selection, age when animals are evaluated, and the end points being measured following exposure to endocrine-active agents. JF - Environmental health perspectives AU - Melnick, Ronald AU - Lucier, George AU - Wolfe, Mary AU - Hall, Roxanne AU - Stancel, George AU - Prins, Gail AU - Gallo, Michael AU - Reuhl, Kenneth AU - Ho, Shuk-Mei AU - Brown, Terry AU - Moore, John AU - Leakey, Julian AU - Haseman, Joseph AU - Kohn, Michael AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. melnickr@niehs.nih.gov Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 427 EP - 431 VL - 110 IS - 4 SN - 0091-6765, 0091-6765 KW - Androgens KW - 0 KW - Benzhydryl Compounds KW - Estrogens KW - Estrogens, Non-Steroidal KW - Phenols KW - bisphenol A KW - MLT3645I99 KW - Index Medicus KW - Phenols -- adverse effects KW - Animals KW - Public Health KW - Reproducibility of Results KW - Dose-Response Relationship, Drug KW - Humans KW - Disease Models, Animal KW - Estrogens, Non-Steroidal -- adverse effects KW - Research Design KW - Phenols -- analysis KW - Estrogens, Non-Steroidal -- analysis KW - Androgens -- analysis KW - Androgens -- adverse effects KW - Peer Review KW - Environmental Exposure KW - Endocrine System -- drug effects KW - Estrogens -- analysis KW - Estrogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71595394?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Summary+of+the+National+Toxicology+Program%27s+report+of+the+endocrine+disruptors+low-dose+peer+review.&rft.au=Melnick%2C+Ronald%3BLucier%2C+George%3BWolfe%2C+Mary%3BHall%2C+Roxanne%3BStancel%2C+George%3BPrins%2C+Gail%3BGallo%2C+Michael%3BReuhl%2C+Kenneth%3BHo%2C+Shuk-Mei%3BBrown%2C+Terry%3BMoore%2C+John%3BLeakey%2C+Julian%3BHaseman%2C+Joseph%3BKohn%2C+Michael&rft.aulast=Melnick&rft.aufirst=Ronald&rft.date=2002-04-01&rft.volume=110&rft.issue=4&rft.spage=427&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-14 N1 - Date created - 2002-04-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Toxicol Sci. 2001 Jun;61(2):201-10 [11353128] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Improved cytotoxic activity toward cell lines and fresh leukemia cells of a mutant anti-CD22 immunotoxin obtained by antibody phage display. AN - 71590771; 11948105 AB - Recombinant immunotoxins are fusion proteins composed of the Fv domains of antibodies fused to bacterial or plant toxins that are being developed for the targeted therapy of cancer. RFB4 (Fv)-Pseudomonas exotoxin 38 (PE38) is an immunotoxin that targets CD22 expressed on B cells and B-cell malignancies. A disulfide-stabilized form of RFB4 (Fv)-PE38 is being evaluated in a Phase I clinical trial. The aim of the present study was to improve the activity of RFB4 (Fv)-PE38 to more effectively treat patients with leukemias and lymphomas. To increase the affinity of RFB4 (Fv), we used the techniques of phage display and hot spot mutagenesis. We identified mutational hot spot sequences in heavy chain complementary determining region 3 (V(H) CDR3) and randomized these in a phage display library. Mutant phages were panned on CD22-positive Daudi cells. A variety of mutant Fvs were obtained, and the corresponding immunotoxins were prepared. Several mutant immunotoxins with increased binding affinity and cytotoxic activity were obtained. The most active immunotoxin contained amino acid residues Thr-His-Trp (THW) in place of Ser-Ser-Tyr (SSY) at positions 100, 100A, and 100B of the Fv and had an affinity improved from 85 nM to 6 nM. The THW mutant had a 5- to 10-fold increase in activity on various CD22-positive cell lines and was up to 50 times more cytotoxic to cells from patients with chronic lymphocytic leukemia and hairy-cell leukemia. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Salvatore, Giuliana AU - Beers, Richard AU - Margulies, Inger AU - Kreitman, Robert J AU - Pastan, Ira AD - Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-4264, USA. Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 995 EP - 1002 VL - 8 IS - 4 SN - 1078-0432, 1078-0432 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD KW - Antigens, Differentiation, B-Lymphocyte KW - CD22 protein, human KW - Cell Adhesion Molecules KW - Immunoglobulin Fragments KW - Immunotoxins KW - Lectins KW - Proteins KW - Sialic Acid Binding Ig-like Lectin 2 KW - immunoglobulin Fv KW - Index Medicus KW - Protein Biosynthesis KW - Tumor Cells, Cultured -- drug effects KW - Plasmids -- genetics KW - Immunoglobulin Fragments -- pharmacology KW - Humans KW - Bacteriophages -- genetics KW - Immunoglobulin Fragments -- genetics KW - Gene Expression KW - Amino Acid Sequence KW - Antibody Affinity KW - Proteins -- drug effects KW - Base Sequence KW - Inhibitory Concentration 50 KW - Mutation KW - Cell Line KW - Gene Library KW - Leukemia -- pathology KW - Leukemia -- drug therapy KW - Immunotoxins -- immunology KW - Antibodies, Monoclonal -- genetics KW - Antigens, Differentiation, B-Lymphocyte -- immunology KW - Immunotoxins -- genetics KW - Antibodies, Monoclonal -- pharmacology KW - Immunotoxins -- pharmacology KW - Antigens, CD -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71590771?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Improved+cytotoxic+activity+toward+cell+lines+and+fresh+leukemia+cells+of+a+mutant+anti-CD22+immunotoxin+obtained+by+antibody+phage+display.&rft.au=Salvatore%2C+Giuliana%3BBeers%2C+Richard%3BMargulies%2C+Inger%3BKreitman%2C+Robert+J%3BPastan%2C+Ira&rft.aulast=Salvatore&rft.aufirst=Giuliana&rft.date=2002-04-01&rft.volume=8&rft.issue=4&rft.spage=995&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-12 N1 - Date created - 2002-04-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Clin Cancer Res. 2002 Apr;8(4):942-4 [11948097] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The association of blood lead level and cancer mortality among whites in the United States. AN - 71589623; 11940448 AB - Lead is classified as a possible carcinogen in humans. We studied the relationship of blood lead level and all cancer mortality in the general population of the United States using data from the National Health and Nutrition Examination Survey II (NHANES II) Mortality Study, 1992, consisting of a total of 203 cancer deaths (117 men and 86 women) among 3,592 whites (1,702 men and 1,890 women) with average of 13.3 years of follow-up. We used Cox proportional hazard regression models to estimate the dose-response relationship between blood lead and all cancer mortality. Log-transformed blood lead was either categorized into quartiles or treated as a continuous variable in a cubic regression spline. Relative risks (RRs) were estimated for site-specific cancers by categorizing lead above and below the median. Among men and women combined, dose-response relationship between quartile of blood lead and all cancer mortality was not significant (ptrend = 0.16), with RRs of 1.24 [95% percent confidence interval (CI), 0.66-2.33], 1.33 (95% CI, 0.57-3.09), and 1.50 (95% CI, 0.75-3.01) for the second, third, and fourth quartiles, respectively, compared with the first quartile. Spline analyses found no dose response (p = 0.29), and none of the site-specific cancer RRs were significant. Among men, no significant dose-response relationships were found for quartile or spline analyses (p trend = 0.57 and p = 0.38, respectively). Among women, no dose-response relationship was found for quartile analysis (ptrend = 0.22). However, the spline dose-response results were significant (p = 0.001), showing a threshold effect at the 94th percentile of blood lead or a lead concentration of 24 microg/dL, with an RR of 2.4 (95% CI, 1.1-5.2) compared with the risk at 12.5 percentile. Because the dose-response relationship found in women was not found in men, occurred at only the highest levels of lead, and has no clear biologic explanation, further replication of this relationship is needed before it can be considered believable. In conclusion, individuals with blood lead levels in the range of NHANES II do not appear to have increased risk of cancer mortality. JF - Environmental health perspectives AU - Jemal, Ahmedin AU - Graubard, Barry I AU - Devesa, Susan S AU - Flegal, Katherine M AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA. ajemal@cancer.org Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 325 EP - 329 VL - 110 IS - 4 SN - 0091-6765, 0091-6765 KW - Lead KW - 2P299V784P KW - Index Medicus KW - Regression Analysis KW - Sex Factors KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - United States -- epidemiology KW - Male KW - Female KW - Risk Assessment KW - Lead -- adverse effects KW - Neoplasms -- mortality KW - Environmental Exposure KW - Neoplasms -- etiology KW - Lead -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71589623?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=The+association+of+blood+lead+level+and+cancer+mortality+among+whites+in+the+United+States.&rft.au=Jemal%2C+Ahmedin%3BGraubard%2C+Barry+I%3BDevesa%2C+Susan+S%3BFlegal%2C+Katherine+M&rft.aulast=Jemal&rft.aufirst=Ahmedin&rft.date=2002-04-01&rft.volume=110&rft.issue=4&rft.spage=325&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-14 N1 - Date created - 2002-04-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: CA Cancer J Clin. 2000 Jan-Feb;50(1):7-33 [10735013] Vital Health Stat 1. 1999 Jun;(38):1-16 [10464470] Am J Ind Med. 2000 Sep;38(3):255-70 [10940963] Am J Ind Med. 2000 Sep;38(3):295-9 [10940967] Bull World Health Organ. 2000;78(9):1068-77 [11019456] Int J Occup Environ Health. 2000 Oct-Dec;6(4):348-50 [11126329] Environ Health Perspect. 2000 Aug;108(8):719-22 [10964791] Vital Health Stat 1. 1981;(15):1-144 [7344293] N Engl J Med. 1982 Sep 2;307(10):573-9 [7110203] N Engl J Med. 1983 Jun 9;308(23):1373-7 [6188954] Environ Health Perspect. 1988 Jun;78:9-13 [3203651] Stat Med. 1989 May;8(5):551-61 [2657958] Environ Health Perspect. 1991 Aug;94:125-30 [1720096] Am J Epidemiol. 1992 Aug 15;136(4):464-74 [1415166] Am J Public Health. 1992 Dec;82(12):1641-4 [1456339] JAMA. 1994 Jul 27;272(4):284-91 [8028141] Occup Environ Med. 1995 Feb;52(2):73-81 [7757170] Am J Epidemiol. 1997 Jan 1;145(1):72-80 [8982025] Epidemiology. 1997 May;8(3):321-3 [9115031] Environ Health Perspect. 1998 Nov;106(11):745-50 [9799191] Int J Occup Environ Health. 2000 Jul-Sep;6(3):255-60 [10926731] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Renal flares are common in patients with severe proliferative lupus nephritis treated with pulse immunosuppressive therapy: long-term followup of a cohort of 145 patients participating in randomized controlled studies. AN - 71587449; 11953977 AB - Immunosuppressive agents have become the standard of therapy for proliferative lupus nephritis, but some patients may relapse after discontinuing treatment. We reviewed the cases of renal flares in a cohort of patients who participated in 2 randomized controlled clinical trials at the National Institutes of Health and explored the prevalence, outcome, and predictive factors of renal flares. Data were obtained on 145 patients treated with pulse cyclophosphamide, pulse methylprednisolone, or the combination of both. Patients had not received immunosuppressive therapy for at least 6 months and had experienced complete or partial response according to defined criteria. Renal flares were classified as either proteinuric or nephritic based on changes in urinary protein and sediment. Most patients who experienced a flare received additional immunosuppressive therapy. Seventy-three patients had a complete response, and 19 had partial response/stabilization. Forty-one of these patients (45%) experienced renal flares (nephritic in 33, proteinuric in 8) after a mean followup of 117 months; 31 of them received additional immunosuppressive therapy. The median time to renal flare was 36 months in the complete responders and 18 months in the partial responders. Eleven of the 41 patients (27%) progressed to end-stage renal disease (ESRD); 9 had nephritic flares (all severe except for 1) and 2 had proteinuric flares (1 in each responder group). Compared with patients who had a complete response, those with a partial response were more likely to experience a flare, to have a severe nephritic flare, or to progress to ESRD. Low C4 at the time of response and African American ethnicity were significant independent risk factors for renal flare, by multivariate Cox proportional hazards analysis. Nephritic flares are common in patients with proliferative lupus nephritis, even in those with a complete response to therapy, but they do not necessarily result in loss of renal function if treated with additional immunosuppressive agents. Renal flares are an important feature of the natural history of lupus nephritis and provide an opportunity for additional preventive strategies, as well as measures of efficacy in future therapeutic trials. JF - Arthritis and rheumatism AU - Illei, G G AU - Takada, K AU - Parkin, D AU - Austin, H A AU - Crane, M AU - Yarboro, C H AU - Vaughan, E M AU - Kuroiwa, T AU - Danning, C L AU - Pando, J AU - Steinberg, A D AU - Gourley, M F AU - Klippel, J H AU - Balow, J E AU - Boumpas, D T AD - Arthritis and Rheumatism Branch, NIAMS, NIH, Bethesda, Maryland 20892, USA. illeig@exchange.nih.gov Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 995 EP - 1002 VL - 46 IS - 4 SN - 0004-3591, 0004-3591 KW - Anti-Inflammatory Agents KW - 0 KW - Immunosuppressive Agents KW - Cyclophosphamide KW - 8N3DW7272P KW - Methylprednisolone KW - X4W7ZR7023 KW - Abridged Index Medicus KW - Index Medicus KW - Methylprednisolone -- administration & dosage KW - Pulse Therapy, Drug KW - Humans KW - Anti-Inflammatory Agents -- administration & dosage KW - Predictive Value of Tests KW - Recurrence KW - Drug Therapy, Combination KW - Adult KW - Cohort Studies KW - Treatment Outcome KW - Kidney Failure, Chronic -- mortality KW - Female KW - Male KW - Prevalence KW - Cyclophosphamide -- administration & dosage KW - Lupus Nephritis -- drug therapy KW - Lupus Nephritis -- mortality KW - Immunosuppressive Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71587449?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arthritis+and+rheumatism&rft.atitle=Renal+flares+are+common+in+patients+with+severe+proliferative+lupus+nephritis+treated+with+pulse+immunosuppressive+therapy%3A+long-term+followup+of+a+cohort+of+145+patients+participating+in+randomized+controlled+studies.&rft.au=Illei%2C+G+G%3BTakada%2C+K%3BParkin%2C+D%3BAustin%2C+H+A%3BCrane%2C+M%3BYarboro%2C+C+H%3BVaughan%2C+E+M%3BKuroiwa%2C+T%3BDanning%2C+C+L%3BPando%2C+J%3BSteinberg%2C+A+D%3BGourley%2C+M+F%3BKlippel%2C+J+H%3BBalow%2C+J+E%3BBoumpas%2C+D+T&rft.aulast=Illei&rft.aufirst=G&rft.date=2002-04-01&rft.volume=46&rft.issue=4&rft.spage=995&rft.isbn=&rft.btitle=&rft.title=Arthritis+and+rheumatism&rft.issn=00043591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-09 N1 - Date created - 2002-04-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exposure to particles stimulates superoxide production by human THP-1 macrophages and avian HD-11EM osteoclasts activated by tumor necrosis factor-alpha and PMA. AN - 71579587; 11938511 AB - Wear of orthopaedic implants generates particles capable of inducing bone resorption and aseptic loosening of the implant. The present study shows the combined effect of particles and cell activation on macrophage (THP-1) and osteoclast (HD-11EM) release of reactive oxygen and nitrogen species, providing insight into mechanisms that can lead to osteolysis. In the absence of cell activation, exposure of either cell type to submicron zirconia or latex particles did not elicit an increase in reactive oxygen and nitrogen species production. Suboptimal stimulation with 4 beta-phorbol-12-myristate-13-acetate (PMA) plus particles resulted in a synergistic release of superoxide (O2-), however, and a low-level production of nitric oxide small middle dot by THP-1 macrophages. Similarly, particle stimulation of tumor necrosis factor-alpha-activated THP-1 cells increased O2- release. Our findings show the synergistic effect of cell activation and wear particles on O2- production by activated macrophages and osteoclasts, suggesting O2- involvement in mediating osteolysis. JF - The Journal of arthroplasty AU - Wang, Mark L AU - Hauschka, Peter V AU - Tuan, Rocky S AU - Steinbeck, Marla J AD - Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 335 EP - 346 VL - 17 IS - 3 SN - 0883-5403, 0883-5403 KW - Latex KW - 0 KW - Polystyrenes KW - Reactive Oxygen Species KW - Tumor Necrosis Factor-alpha KW - Nitric Oxide KW - 31C4KY9ESH KW - Zirconium KW - C6V6S92N3C KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - zirconium oxide KW - S38N85C5G0 KW - Index Medicus KW - Phagocytosis -- physiology KW - Animals KW - Chickens KW - Cells, Cultured KW - Humans KW - Reactive Oxygen Species -- metabolism KW - Foreign-Body Reaction KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Osteoclasts -- metabolism KW - Osteoclasts -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Nitric Oxide -- metabolism KW - Macrophages -- drug effects KW - Macrophages -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71579587?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+arthroplasty&rft.atitle=Exposure+to+particles+stimulates+superoxide+production+by+human+THP-1+macrophages+and+avian+HD-11EM+osteoclasts+activated+by+tumor+necrosis+factor-alpha+and+PMA.&rft.au=Wang%2C+Mark+L%3BHauschka%2C+Peter+V%3BTuan%2C+Rocky+S%3BSteinbeck%2C+Marla+J&rft.aulast=Wang&rft.aufirst=Mark&rft.date=2002-04-01&rft.volume=17&rft.issue=3&rft.spage=335&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+arthroplasty&rft.issn=08835403&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-23 N1 - Date created - 2002-04-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of reversible inactivation of the neonatal ventral hippocampus on behavior in the adult rat. AN - 71574425; 11923448 AB - Rats with neonatal excitotoxic damage of the ventral hippocampus display in adulthood a variety of abnormalities reminiscent of schizophrenia and are used as an animal model of this disorder. In the present study, we hypothesized that transient inactivation of ventral hippocampal activity during a critical developmental period may be sufficient to disrupt normal maturation of relevant brain systems and produce similar lasting behavioral changes. We infused tetrodotoxin (TTX) or artificial CSF into the ventral hippocampus on postnatal day 7 (P7) and assessed behavioral changes in response to stress, amphetamine, and (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate in juvenile (P35) and young adult (P56) rats. In adulthood, rats infused neonatally with TTX displayed motor hyperactivity after pharmacological stimulation and after stress compared with sham controls. Analogous TTX infusions in adult animals did not alter these behaviors later in life. These data suggest that transient loss of ventral hippocampal function during a critical time in maturation of intracortical connections permanently changes the development of neural circuits mediating certain dopamine- and NMDA-related behaviors. These results represent a potential new model of aspects of schizophrenia without involving a gross anatomic lesion. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Lipska, Barbara K AU - Halim, Nader D AU - Segal, Pavan N AU - Weinberger, Daniel R AD - Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1385, USA. lipskab@intra.nimh.nih.gov Y1 - 2002/04/01/ PY - 2002 DA - 2002 Apr 01 SP - 2835 EP - 2842 VL - 22 IS - 7 KW - Central Nervous System Stimulants KW - 0 KW - Excitatory Amino Acid Antagonists KW - Tetrodotoxin KW - 4368-28-9 KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Amphetamine KW - CK833KGX7E KW - Index Medicus KW - Animals KW - Age Factors KW - Analysis of Variance KW - Central Nervous System Stimulants -- pharmacology KW - Psychomotor Agitation -- physiopathology KW - Interpersonal Relations KW - Disease Models, Animal KW - Tetrodotoxin -- administration & dosage KW - Microinjections KW - Dizocilpine Maleate -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Rats KW - Animals, Newborn KW - Rats, Sprague-Dawley KW - Psychomotor Agitation -- etiology KW - Cohort Studies KW - Motor Activity -- drug effects KW - Amphetamine -- pharmacology KW - Male KW - Behavior, Animal -- drug effects KW - Hippocampus -- growth & development KW - Aging KW - Hippocampus -- physiopathology KW - Schizophrenia -- chemically induced KW - Schizophrenia -- physiopathology KW - Schizophrenia -- complications KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71574425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Effects+of+reversible+inactivation+of+the+neonatal+ventral+hippocampus+on+behavior+in+the+adult+rat.&rft.au=Lipska%2C+Barbara+K%3BHalim%2C+Nader+D%3BSegal%2C+Pavan+N%3BWeinberger%2C+Daniel+R&rft.aulast=Lipska&rft.aufirst=Barbara&rft.date=2002-04-01&rft.volume=22&rft.issue=7&rft.spage=2835&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-08 N1 - Date created - 2002-03-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adipose tissue: a vital in vivo role in mammary gland development but not differentiation. AN - 71571809; 11921335 AB - Development and differentiation of the mammary gland occurs by means of critical stromal-epithelial interactions. Although many studies have attempted to understand these complex interactions, it has been difficult to demonstrate the essential role of adipose tissue in the development and function of the mammary gland. By using the A-ZIP/F-1 transgenic mice lacking in white adipose tissue (WAT), we have studied the role of adipocytes in mammary gland development and differentiation. In the absence of WAT, rudimentary mammary anlagen form but are unable to grow and branch normally, resulting in a few, short, severely distended ducts. However, during pregnancy, a tremendous amount of epithelial cell division and alveolar cell formation occurs even in the absence of adipocytes, illustrating that adipose tissue is not required for mammary gland differentiation. Mammary gland transplantation revealed that epithelial cells from these transgenic mice possess the potential for normal growth and differentiation when placed into a normal stromal environment. These experiments clearly demonstrate that the absence of adipocytes in the mammary gland results in disruption of stromal-epithelial interactions that prevent normal mammary gland development. The rudimentary epithelial anlage, however, contain mammary stem cells, which are fully capable of alveolar differentiation. Published 2002 Wiley-Liss, Inc. JF - Developmental dynamics : an official publication of the American Association of Anatomists AU - Couldrey, Christine AU - Moitra, Jaideep AU - Vinson, Charles AU - Anver, Miriam AU - Nagashima, Kunio AU - Green, Jeffrey AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 29896, USA. Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 459 EP - 468 VL - 223 IS - 4 SN - 1058-8388, 1058-8388 KW - Estradiol KW - 4TI98Z838E KW - Index Medicus KW - Animals KW - Estradiol -- blood KW - Epithelial Cells KW - Adipocytes KW - Morphogenesis KW - Cell Differentiation KW - Mice KW - Mice, Transgenic KW - Male KW - Female KW - Cell Division KW - Breast -- cytology KW - Adipose Tissue -- physiology KW - Breast -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71571809?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+dynamics+%3A+an+official+publication+of+the+American+Association+of+Anatomists&rft.atitle=Adipose+tissue%3A+a+vital+in+vivo+role+in+mammary+gland+development+but+not+differentiation.&rft.au=Couldrey%2C+Christine%3BMoitra%2C+Jaideep%3BVinson%2C+Charles%3BAnver%2C+Miriam%3BNagashima%2C+Kunio%3BGreen%2C+Jeffrey&rft.aulast=Couldrey&rft.aufirst=Christine&rft.date=2002-04-01&rft.volume=223&rft.issue=4&rft.spage=459&rft.isbn=&rft.btitle=&rft.title=Developmental+dynamics+%3A+an+official+publication+of+the+American+Association+of+Anatomists&rft.issn=10588388&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-06 N1 - Date created - 2002-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Environmental injustice and the Mississippi hog industry. AN - 71571195; 11929728 AB - The recent growth and restructuring of the swine industry in the state of Mississippi has raised various environmental and socioeconomic concerns. We spatially examined the location and attributes of 67 industrial hog operations to determine if African American and low-income communities have a high prevalence of industrial hog operations located near their neighborhoods at the census block group level. We used spatial data and cross-classification analysis to compare the prevalence of industrial hog operations in neighborhoods that are primarily African American and low income with the prevalence in neighborhoods that are African American and affluent. We also used logistic regression to evaluate the relationship between the environmental justice variables and the location of the industrial hog operations. The block group characterization showed a high prevalence of hog operations in the four highest quintiles compared with the lowest quintile for percentage African American and percentage poverty. At increasing levels of percentage African Americans and percentage of persons in poverty, there are 2.4-3.6 times more operations compared with the referent group; additionally, scale adjustment to only the hog counties reduces this to 1.8-3.1 more operations compared with the referent group. The inequitable distribution of hog-confined agricultural feeding operations in these communities may have adverse environmental impacts associated with industrial hog production, such as increased health risks and quality of life degradation, as have occurred in other areas having similar facilities. JF - Environmental health perspectives AU - Wilson, Sacoby M AU - Howell, Frank AU - Wing, Steve AU - Sobsey, Mark AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. smwilson@email.unc.edu Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 195 EP - 201 VL - 110 Suppl 2 SN - 0091-6765, 0091-6765 KW - Index Medicus KW - Information Systems KW - Animals KW - Rural Population KW - Environmental Health KW - Humans KW - Mississippi KW - Environmental Exposure KW - Geography KW - Risk Assessment KW - Prevalence KW - Swine KW - Agriculture KW - Prejudice KW - Poverty KW - African Americans UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71571195?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Environmental+injustice+and+the+Mississippi+hog+industry.&rft.au=Wilson%2C+Sacoby+M%3BHowell%2C+Frank%3BWing%2C+Steve%3BSobsey%2C+Mark&rft.aulast=Wilson&rft.aufirst=Sacoby&rft.date=2002-04-01&rft.volume=110+Suppl+2&rft.issue=&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-07 N1 - Date created - 2002-04-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Environ Health Perspect. 2000 Mar;108(3):225-31 [10706528] Environ Health Perspect. 2000 Mar;108(3):233-8 [10706529] J Expo Anal Environ Epidemiol. 1999 Jan-Feb;9(1):29-48 [10189625] J Anim Sci. 1998 May;76(5):1343-55 [9621940] Am J Ind Med. 1990;17(1):17-25 [2407112] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diallyl disulfide (DADS) induces the antitumorigenic NSAID-activated gene (NAG-1) by a p53-dependent mechanism in human colorectal HCT 116 cells. AN - 71561251; 11925476 AB - Garlic is appealing as an anti-carcinogenic agent due to its ability to induce apoptosis in vitro and inhibit the formation and growth of tumors in animals in vivo. Diallyl disulfide (DADS) is a constituent of garlic that suppresses neoplastic cell growth and induces apoptosis. We examined the effects of DADS on various cancer cell lines to better understand its effect on apoptosis and apoptosis-related genes. The nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1) has proapoptotic and antitumorigenic activities and is upregulated by anticancer agents such as NSAIDs. In this study, human colorectal HCT-116 (wild-type p53), HCT-15 (p53 mutant) and human prostate PC-3 (p53 mutant) cells were exposed to DADS. DADS inhibited cell proliferation in all cell lines albeit to a lesser extent in HCT-15 and PC-3 cells at 11.5 and 23 micromol/L. In HCT-116 cells, DADS induced p53 and NAG-1 in a dose-dependent manner and the induction of p53 preceded that of NAG-1. In HCT-116 cells, NAG-1 protein expression was increased 2.4-fold +/- 0.6 at 4.6 micromol/L and 6.1-fold +/- 1.7 at 23 micromol/L DADS, whereas p53 was induced 1.5-fold +/- 0.1 and 2.3-fold +/- 0.4. DADS did not induce NAG-1 or p53 in p53 mutant cell lines; however, NAG-1 expression was induced by sulindac sulfide. HCT-116 cells treated with 4.6 and 23 micromol/L DADS resulted in a 1.9- and 2.9-fold increase in apoptosis, respectively. In contrast, 23 micromol/L DADS induced apoptosis only 1.8-fold in HCT-15 cells and not at all in PC-3 cells. Thus, DADS-induced apoptosis and NAG-1 protein expression appear to occur via p53. JF - The Journal of nutrition AU - Bottone, Frank G AU - Baek, Seung Joon AU - Nixon, Jennifer B AU - Eling, Thomas E AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. . Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 773 EP - 778 VL - 132 IS - 4 SN - 0022-3166, 0022-3166 KW - Allyl Compounds KW - 0 KW - Antineoplastic Agents KW - Cytokines KW - Disulfides KW - GDF15 protein, human KW - Growth Differentiation Factor 15 KW - Tumor Suppressor Protein p53 KW - diallyl disulfide KW - 5HI47O6OA7 KW - Index Medicus KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Cytokines -- genetics KW - Cytokines -- drug effects KW - Tumor Suppressor Protein p53 -- drug effects KW - Apoptosis -- drug effects KW - Disulfides -- therapeutic use KW - Tumor Suppressor Protein p53 -- genetics KW - Antineoplastic Agents -- therapeutic use KW - Colorectal Neoplasms -- drug therapy KW - Allyl Compounds -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71561251?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+nutrition&rft.atitle=Diallyl+disulfide+%28DADS%29+induces+the+antitumorigenic+NSAID-activated+gene+%28NAG-1%29+by+a+p53-dependent+mechanism+in+human+colorectal+HCT+116+cells.&rft.au=Bottone%2C+Frank+G%3BBaek%2C+Seung+Joon%3BNixon%2C+Jennifer+B%3BEling%2C+Thomas+E&rft.aulast=Bottone&rft.aufirst=Frank&rft.date=2002-04-01&rft.volume=132&rft.issue=4&rft.spage=773&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nutrition&rft.issn=00223166&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-26 N1 - Date created - 2002-04-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transplacental genotoxicity of combined antiretroviral nucleoside analogue therapy in Erythrocebus patas monkeys. AN - 71556109; 11917235 AB - Antiretroviral nucleoside analogue drugs are a major constituent of highly active antiretroviral therapy (HAART), the most advanced form of treatment for HIV-1 infection. Currently, HAART combinations that include zidovudine (ZDV) and lamivudine (3TC) are highly effective in preventing HIV-1 vertical transmission; most children are born with no evident adverse clinical effects. However, ZDV is a moderately strong transplacental carcinogen in mice, and potential long-term consequences of fetal exposure to most HAART combinations remain unknown. To model human transplacental ZDV and 3TC exposures, experiments were performed in Erythrocebus patas monkeys given human-equivalent drug exposure protocols. Pregnant monkeys were dosed with either no drug (n = 2), 40.0 mg ZDV/d (about 6 mg/kg body weight/d) for the last 50% (10 weeks) of gestation (n = 3), or with the same regimen of ZDV plus 24.0 mg 3TC/d (about 3.6 mg/kg body weight/d) for the last 20% (4 weeks) of gestation (n = 3). Multiple fetal organs were examined at term for DNA incorporation of ZDV and 3TC using two separate radioimmunoassays (RIAs). Values for ZDV-DNA incorporation were similar in fetuses exposed to ZDV alone and those exposed to ZDV plus 3TC. Values for 3TC-DNA in fetal organs were greater than or equal to values for ZDV-DNA, indicating that the total DNA damage sustained by fetuses exposed to both drugs was at least double that observed in fetuses exposed to ZDV alone. Telomere shortening, determined by Southern blot with a telomeric probe, was observed in most organs of the three animals exposed in utero to ZDV plus 3TC. No telomere shortening was evident in the unexposed fetuses, and occasional telomere shortening was found in fetuses exposed to ZDV alone. Overall, these studies demonstrate that monkey fetuses exposed in utero to the combination ZDV plus 3TC sustain a higher level of drug-DNA incorporation and show evidence of more telomere damage than monkey fetuses exposed to ZDV alone. JF - Journal of acquired immune deficiency syndromes (1999) AU - Olivero, Ofelia A AU - Fernandez, Juan J AU - Antiochos, Brendan B AU - Wagner, Jessica L AU - St Claire, Marisa E AU - Poirier, Miriam C AD - Carcinogen-DNA Interactions Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. oliceroo@exchange.nih.gov Y1 - 2002/04/01/ PY - 2002 DA - 2002 Apr 01 SP - 323 EP - 329 VL - 29 IS - 4 SN - 1525-4135, 1525-4135 KW - Anti-HIV Agents KW - 0 KW - Reverse Transcriptase Inhibitors KW - Lamivudine KW - 2T8Q726O95 KW - Zidovudine KW - 4B9XT59T7S KW - DNA KW - 9007-49-2 KW - Index Medicus KW - AIDS/HIV KW - Infectious Disease Transmission, Vertical -- prevention & control KW - Animals KW - Telomere -- drug effects KW - Humans KW - DNA -- metabolism KW - HIV Infections -- drug therapy KW - Antiretroviral Therapy, Highly Active KW - Placenta -- drug effects KW - Erythrocebus patas KW - HIV-1 -- drug effects KW - Female KW - Pregnancy KW - DNA -- drug effects KW - Anti-HIV Agents -- toxicity KW - Reverse Transcriptase Inhibitors -- metabolism KW - Maternal-Fetal Exchange KW - Lamivudine -- toxicity KW - Lamivudine -- metabolism KW - Fetus -- drug effects KW - Zidovudine -- toxicity KW - Zidovudine -- metabolism KW - DNA Damage KW - Anti-HIV Agents -- metabolism KW - Reverse Transcriptase Inhibitors -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71556109?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+acquired+immune+deficiency+syndromes+%281999%29&rft.atitle=Transplacental+genotoxicity+of+combined+antiretroviral+nucleoside+analogue+therapy+in+Erythrocebus+patas+monkeys.&rft.au=Olivero%2C+Ofelia+A%3BFernandez%2C+Juan+J%3BAntiochos%2C+Brendan+B%3BWagner%2C+Jessica+L%3BSt+Claire%2C+Marisa+E%3BPoirier%2C+Miriam+C&rft.aulast=Olivero&rft.aufirst=Ofelia&rft.date=2002-04-01&rft.volume=29&rft.issue=4&rft.spage=323&rft.isbn=&rft.btitle=&rft.title=Journal+of+acquired+immune+deficiency+syndromes+%281999%29&rft.issn=15254135&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-23 N1 - Date created - 2002-03-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Acquir Immune Defic Syndr 2002 Jul 1;30(3):368 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Investigation of the prognostic and predictive value of thymidylate synthase, p53, and Ki-67 in patients with locally advanced colon cancer. AN - 71551196; 11919229 AB - To evaluate the value of thymidylate synthase (TS), Ki-67, and p53 as prognostic markers in patients with Dukes' B2 and C colon carcinoma. We conducted a retrospective analysis to evaluate the prognostic value of TS, Ki-67, and p53 in 465 patients with Dukes' B2 (220 patients) or Dukes' C (245 patients) colon carcinoma. Patients represent a nonrandom subset obtained from five randomized phase III trials and were treated with either surgery alone (151 patients) or surgery plus fluorouracil-based chemotherapy (314 patients). All three markers were assayed using immunohistochemical techniques. With a minimum follow-up of 5 years, our retrospective analysis failed to demonstrate a consistent and significant association between TS, Ki-67, or p53 and either disease-free survival or overall survival. Exploratory analyses did not reveal a convincing explanation for these results that are in conflict with the published literature. Notable interactions were observed. In particular, high Ki-67 levels were associated with increased (decreased) survival in patients with low (high) TS intensity. Patients whose tumors stained positively for p53 seemed to benefit substantially from the use of adjuvant chemotherapy compared with those who were not treated (P =.05). This retrospective investigation failed to demonstrate a significant association between TS, Ki-67, or p53 staining and clinical outcome. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Allegra, Carmen J AU - Parr, Allyson L AU - Wold, Lester E AU - Mahoney, Michelle R AU - Sargent, Daniel J AU - Johnston, Patrick AU - Klein, Pam AU - Behan, Katie AU - O'Connell, Michael J AU - Levitt, Ralph AU - Kugler, John W AU - Tria Tirona, Maria AU - Goldberg, Richard M AD - National Cancer Institute, Bethesda, MD, USA. Y1 - 2002/04/01/ PY - 2002 DA - 2002 Apr 01 SP - 1735 EP - 1743 VL - 20 IS - 7 SN - 0732-183X, 0732-183X KW - Antimetabolites, Antineoplastic KW - 0 KW - Biomarkers, Tumor KW - Ki-67 Antigen KW - Tumor Suppressor Protein p53 KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Disease-Free Survival KW - Colectomy KW - Neoplasm Staging KW - Humans KW - Retrospective Studies KW - Prognosis KW - Aged KW - Predictive Value of Tests KW - Fluorouracil -- administration & dosage KW - Middle Aged KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Immunohistochemistry KW - Female KW - Male KW - Survival Analysis KW - Thymidylate Synthase -- analysis KW - Tumor Suppressor Protein p53 -- analysis KW - Colonic Neoplasms -- therapy KW - Colonic Neoplasms -- mortality KW - Ki-67 Antigen -- analysis KW - Biomarkers, Tumor -- analysis KW - Colonic Neoplasms -- chemistry KW - Colonic Neoplasms -- pathology KW - Colonic Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71551196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Investigation+of+the+prognostic+and+predictive+value+of+thymidylate+synthase%2C+p53%2C+and+Ki-67+in+patients+with+locally+advanced+colon+cancer.&rft.au=Allegra%2C+Carmen+J%3BParr%2C+Allyson+L%3BWold%2C+Lester+E%3BMahoney%2C+Michelle+R%3BSargent%2C+Daniel+J%3BJohnston%2C+Patrick%3BKlein%2C+Pam%3BBehan%2C+Katie%3BO%27Connell%2C+Michael+J%3BLevitt%2C+Ralph%3BKugler%2C+John+W%3BTria+Tirona%2C+Maria%3BGoldberg%2C+Richard+M&rft.aulast=Allegra&rft.aufirst=Carmen&rft.date=2002-04-01&rft.volume=20&rft.issue=7&rft.spage=1735&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-10 N1 - Date created - 2002-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acute oxaliplatin-induced peripheral nerve hyperexcitability. AN - 71550837; 11919233 AB - Oxaliplatin is a novel platinum compound with clinical activity in several malignancies. Neurotoxicity is dose-limiting and occurs in two distinct forms, an acute neurologic symptom complex that occurs within hours or days of therapy and a chronic, cumulative sensory neuropathy. Patients were treated in a phase I study designed to establish the maximum-tolerated dose of capecitabine given with oxaliplatin. Because of the unusual neurosensory toxicity of oxaliplatin, detailed neurologic examination, needle electromyography (EMG), and nerve conduction studies (NCS) were performed before and the day after oxaliplatin in a subset of 13 patients. Carbamazepine therapy was tried in 12 additional patients to determine whether the neurologic effects might be relieved. All patients experienced acute, reversible neurotoxicities with oxaliplatin. Symptoms included paresthesias, dysesthesias, cold hypersensitivity, jaw pain, eye pain, pain in the arm used for drug infusion, ptosis, leg cramps, and visual and voice changes. Serial EMG and NCS revealed striking signs of hyperexcitability in motor nerves after oxaliplatin. In patients who achieved therapeutic levels, carbamazepine did not alter the clinical or electromyographic abnormalities. The acute neurotoxicity seen with oxaliplatin is characterized by peripheral-nerve hyperexcitability, and the findings are similar to the clinical manifestations of neuromyotonia. Carbamezepine, which provides symptomatic relief in acquired neuromytonia, did not seem to be beneficial. Efforts to identify a successful neuroprotectant strategy would have a major impact on improving patient quality of life and the ability to deliver full doses of oxaliplatin. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Wilson, Richard H AU - Lehky, Tanya AU - Thomas, Rebecca R AU - Quinn, Mary G AU - Floeter, Mary Kay AU - Grem, Jean L AD - Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2002/04/01/ PY - 2002 DA - 2002 Apr 01 SP - 1767 EP - 1774 VL - 20 IS - 7 SN - 0732-183X, 0732-183X KW - Anticonvulsants KW - 0 KW - Antineoplastic Agents KW - Organoplatinum Compounds KW - oxaliplatin KW - 04ZR38536J KW - Deoxycytidine KW - 0W860991D6 KW - Carbamazepine KW - 33CM23913M KW - Capecitabine KW - 6804DJ8Z9U KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Acute Disease KW - Treatment Failure KW - Isaacs Syndrome -- physiopathology KW - Humans KW - Aged KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Carbamazepine -- therapeutic use KW - Anticonvulsants -- therapeutic use KW - Clinical Trials, Phase I as Topic KW - Fluorouracil -- analogs & derivatives KW - Electromyography -- drug effects KW - Isaacs Syndrome -- chemically induced KW - Middle Aged KW - Male KW - Female KW - Peripheral Nervous System Diseases -- physiopathology KW - Organoplatinum Compounds -- adverse effects KW - Organoplatinum Compounds -- administration & dosage KW - Neural Conduction -- drug effects KW - Deoxycytidine -- analogs & derivatives KW - Deoxycytidine -- administration & dosage KW - Peripheral Nervous System Diseases -- drug therapy KW - Peripheral Nervous System Diseases -- chemically induced KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71550837?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Acute+oxaliplatin-induced+peripheral+nerve+hyperexcitability.&rft.au=Wilson%2C+Richard+H%3BLehky%2C+Tanya%3BThomas%2C+Rebecca+R%3BQuinn%2C+Mary+G%3BFloeter%2C+Mary+Kay%3BGrem%2C+Jean+L&rft.aulast=Wilson&rft.aufirst=Richard&rft.date=2002-04-01&rft.volume=20&rft.issue=7&rft.spage=1767&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-10 N1 - Date created - 2002-03-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Clin Oncol. 2002 Aug 15;20(16):3561-2; author reply 3562 [12177120] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine transporter mutants with cocaine resistance and normal dopamine uptake provide targets for cocaine antagonism. AN - 71544001; 11901228 AB - Cocaine's blockade of dopamine reuptake by brain dopamine transporters (DAT) is a central feature of current understanding of cocaine reward and addiction. Empirical screening of small-molecule chemical libraries has thus far failed to provide successful cocaine blockers that allow dopamine reuptake in the presence of cocaine and provide cocaine "antagonism". We have approached this problem by assessing expression, dopamine uptake, and cocaine analog affinities of 56 DAT mutants in residues located in or near transmembrane domains likely to play significant roles in cocaine recognition and dopamine uptake. A phenylalanine-to-alanine mutant in putative DAT transmembrane domain 3, F154A, retains normal dopamine uptake, lowers cocaine affinity 10-fold, and reduces cocaine stereospecificity. Such mutants provide windows into DAT structures that could serve as targets for selective cocaine blockers and document how combined strategies of mutagenesis and small molecule screening may improve our abilities to identify and design compounds with such selective properties. JF - Molecular pharmacology AU - Lin, Zhicheng AU - Uhl, George R AD - Molecular Neurobiology Branch, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 885 EP - 891 VL - 61 IS - 4 SN - 0026-895X, 0026-895X KW - Dopamine Plasma Membrane Transport Proteins KW - 0 KW - Dopamine Uptake Inhibitors KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Molecular Motor Proteins KW - Nerve Tissue Proteins KW - Tritium KW - 10028-17-8 KW - (1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester KW - 50370-56-4 KW - Mazindol KW - C56709M5NH KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Drug Interactions KW - COS Cells KW - Drug Resistance KW - Mazindol -- pharmacology KW - Transfection KW - Binding, Competitive KW - Cercopithecus aethiops KW - Mutation KW - Amino Acid Substitution KW - Dopamine Uptake Inhibitors -- pharmacology KW - Cocaine -- analogs & derivatives KW - Dopamine -- metabolism KW - Cocaine -- pharmacology KW - Membrane Transport Proteins -- metabolism KW - Membrane Transport Proteins -- genetics KW - Cocaine -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71544001?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Dopamine+transporter+mutants+with+cocaine+resistance+and+normal+dopamine+uptake+provide+targets+for+cocaine+antagonism.&rft.au=Lin%2C+Zhicheng%3BUhl%2C+George+R&rft.aulast=Lin&rft.aufirst=Zhicheng&rft.date=2002-04-01&rft.volume=61&rft.issue=4&rft.spage=885&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-11 N1 - Date created - 2002-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clonal polymorphism of Borrelia burgdorferi strain B31 MI: implications for mutagenesis in an infectious strain background. AN - 71539576; 11895980 AB - A major obstacle to studying the functions of particular gene products in the mouse-tick infectious cycle of Borrelia burgdorferi has been an inability to knock out genes in pathogenic strains. Here, we investigated conditions for site-directed mutagenesis in B31 MI, the low-passage-number, infectious B. burgdorferi strain whose genome was sequenced. We inactivated several plasmid and chromosomal genes in B31 MI and determined that clones carrying these mutations were not infectious for mice. However, we found extensive heterogeneity among clones and mutants derived from B31 MI based on colony phenotype, growth rate, plasmid content, protein profile, and transformability. Significantly, several B31 MI clones that were not subjected to mutagenesis but that lacked particular plasmids also exhibited defects at various stages in the infectious cycle. Therefore, the high degree of clonal polymorphism within B31 MI complicates the assessment of the contributions of individual genes to the observed phenotypes of the mutants. Our results indicate that B31 MI is not an appropriate strain background for genetic studies in infectious B. burgdorferi, and a well-defined isogenic clone is a prerequisite for targeted mutagenesis. To this end, we derived several wild-type clones from B31 MI that were infectious for mice, and gene inactivation was successful in one of these clones. Due to the instability of the genome with in vitro propagation, careful monitoring of plasmid content of derived mutants and complementation of inactivated genes will be crucial components of genetic studies with this pathogen. JF - Infection and immunity AU - Elias, Abdallah F AU - Stewart, Philip E AU - Grimm, Dorothee AU - Caimano, Melissa J AU - Eggers, Christian H AU - Tilly, Kit AU - Bono, James L AU - Akins, Darrin R AU - Radolf, Justin D AU - Schwan, Tom G AU - Rosa, Patricia AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA. abdallah.elias@charite.de Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 2139 EP - 2150 VL - 70 IS - 4 SN - 0019-9567, 0019-9567 KW - Antigens, Surface KW - 0 KW - Bacterial Outer Membrane Proteins KW - Bacterial Vaccines KW - Lipoproteins KW - OspA protein KW - Index Medicus KW - Animals KW - Transformation, Bacterial KW - Ticks -- microbiology KW - Bacterial Outer Membrane Proteins -- genetics KW - Temperature KW - Rabbits KW - Adaptation, Physiological KW - Antigens, Surface -- genetics KW - Mutagenesis KW - Borrelia burgdorferi -- genetics KW - Borrelia burgdorferi -- growth & development KW - Polymorphism, Genetic KW - Borrelia burgdorferi -- pathogenicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71539576?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+immunity&rft.atitle=Clonal+polymorphism+of+Borrelia+burgdorferi+strain+B31+MI%3A+implications+for+mutagenesis+in+an+infectious+strain+background.&rft.au=Elias%2C+Abdallah+F%3BStewart%2C+Philip+E%3BGrimm%2C+Dorothee%3BCaimano%2C+Melissa+J%3BEggers%2C+Christian+H%3BTilly%2C+Kit%3BBono%2C+James+L%3BAkins%2C+Darrin+R%3BRadolf%2C+Justin+D%3BSchwan%2C+Tom+G%3BRosa%2C+Patricia&rft.aulast=Elias&rft.aufirst=Abdallah&rft.date=2002-04-01&rft.volume=70&rft.issue=4&rft.spage=2139&rft.isbn=&rft.btitle=&rft.title=Infection+and+immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-11 N1 - Date created - 2002-03-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Clin Microbiol. 2000 Jan;38(1):382-8 [10618120] J Infect Dis. 1989 Dec;160(6):1018-29 [2584750] Annu Rev Entomol. 1991;36:587-609 [2006870] J Clin Microbiol. 1991 Feb;29(2):236-43 [2007630] Infect Immun. 1992 Nov;60(11):4662-72 [1398980] Mol Microbiol. 1992 Oct;6(20):3031-40 [1479892] Proc Natl Acad Sci U S A. 1993 May 1;90(9):4092-6 [7683420] Infect Immun. 1993 Sep;61(9):3590-6 [8359881] Infect Immun. 1994 Jan;62(1):303-7 [7505260] J Clin Microbiol. 1993 Dec;31(12):3096-108 [8308101] Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2909-13 [7708747] Infect Immun. 1995 Jun;63(6):2206-12 [7768600] Methods Mol Biol. 1995;47:253-9 [7550741] Infect Immun. 1995 Dec;63(12):4795-801 [7591138] J Bacteriol. 1996 Oct;178(20):5946-53 [8830691] Cell. 1997 Apr 18;89(2):275-85 [9108482] Mol Microbiol. 1997 Jul;25(2):361-73 [9282748] Nature. 1997 Dec 11;390(6660):580-6 [9403685] Microbiology. 1998 Apr;144 ( Pt 4):1033-44 [9579077] J Clin Invest. 1998 May 15;101(10):2240-50 [9593780] Infect Immun. 1998 Jun;66(6):2648-54 [9596729] Infect Immun. 1998 Aug;66(8):3698-704 [9673251] J Bacteriol. 1998 Nov;180(21):5676-81 [9791118] Mol Microbiol. 2000 Feb;35(3):490-516 [10672174] J Bacteriol. 2000 Apr;182(7):2048-51 [10715016] J Bacteriol. 2000 May;182(9):2445-52 [10762244] J Bacteriol. 2000 May;182(10):2909-18 [10781562] J Clin Invest. 2000 Aug;106(4):561-9 [10953031] Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10899-904 [10995478] J Mol Microbiol Biotechnol. 2000 Oct;2(4):433-42 [11075915] Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13865-70 [11106398] Infect Immun. 2001 Jan;69(1):446-55 [11119536] Mol Microbiol. 2001 Feb;39(3):714-21 [11169111] Infect Immun. 2001 Jun;69(6):3618-27 [11349022] J Immunol. 2001 Jun 15;166(12):7398-403 [11390491] J Bacteriol. 2001 Oct;183(19):5544-53 [11544216] Science. 1982 Jun 18;216(4552):1317-9 [7043737] N Engl J Med. 1983 Mar 31;308(13):733-40 [6828118] Yale J Biol Med. 1984 Jul-Aug;57(4):521-5 [6393604] Am J Trop Med Hyg. 1987 Jan;36(1):92-6 [3812887] J Clin Microbiol. 1988 Mar;26(3):475-8 [3356787] J Clin Microbiol. 1988 May;26(5):893-5 [3290239] Infect Immun. 1988 Aug;56(8):1831-6 [3397175] Proc Natl Acad Sci U S A. 1989 Apr;86(7):2172-5 [2648393] Infect Immun. 1989 Sep;57(9):2733-41 [2668185] N Engl J Med. 1989 Aug 31;321(9):586-96 [2668764] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Moderate G6PD deficiency increases mutation rates in the brain of mice. AN - 71538966; 11909700 AB - Mice that harbored the x-ray-induced low efficiency allele of the major X-linked isozyme of glucose-6-phospate dehydrogenase (G6PD), Gpdx(a-m2Neu), and, in addition, harbored the transgenic shuttle vector for the determination of mutagenesis in vivo, pUR288, were employed to further our understanding of the interdependence of general metabolism, oxidative stress control, and somatic mutagenesis. The Gpdx(a-m2Neu) mutation conferred moderate G6PD deficiency in hemizygous males (Gpdx(a-m2Neu/y)) displaying residual enzyme activities of 27% in red blood cells and 13% in brain (compared to wild-type controls, Gpdx(a/y) males). In spite of this mild phenotype, the brains of G6PD-deficient males exhibited a significant distortion of redox control ( approximately 3-fold decrease in the ratio of reduced glutathione to oxidized glutathione), a considerable accumulation of promutagenic etheno DNA adducts ( approximately 13-fold increase in ethenodeoxyadenosine and approximately 5-fold increase in ethenodeoxycytidine), and a substantial elevation of somatic mutation rates ( approximately 3-fold increase in mutant frequencies in lacZ, the target and reporter gene of mutagenesis in the shuttle vector, pUR288). The mutation pattern in the brain was dominated by illegitimate genetic recombinations, a presumed hallmark of oxidative mutagenesis. These findings suggested a critical function for G6PD in limiting oxidative mutagenesis in the mouse brain. JF - Free radical biology & medicine AU - Felix, Klaus AU - Rockwood, Lynne D AU - Pretsch, Walter AU - Nair, Jagadeesan AU - Bartsch, Helmut AU - Bornkamm, Georg Wilhelm AU - Janz, Siegfried AD - Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 2002/04/01/ PY - 2002 DA - 2002 Apr 01 SP - 663 EP - 673 VL - 32 IS - 7 SN - 0891-5849, 0891-5849 KW - DNA Adducts KW - 0 KW - Glucosephosphate Dehydrogenase KW - EC 1.1.1.49 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - DNA Adducts -- genetics KW - Animals KW - DNA Mutational Analysis KW - Glutathione -- metabolism KW - Mice KW - Mice, Knockout KW - Polymerase Chain Reaction KW - Promoter Regions, Genetic KW - Lac Operon -- physiology KW - Recombination, Genetic KW - Oxidative Stress KW - Point Mutation KW - Mice, Inbred C3H KW - Mice, Inbred C57BL KW - Anemia, Hemolytic -- metabolism KW - Male KW - Brain -- enzymology KW - Glucosephosphate Dehydrogenase Deficiency -- genetics KW - Mutation KW - Glucosephosphate Dehydrogenase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71538966?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Moderate+G6PD+deficiency+increases+mutation+rates+in+the+brain+of+mice.&rft.au=Felix%2C+Klaus%3BRockwood%2C+Lynne+D%3BPretsch%2C+Walter%3BNair%2C+Jagadeesan%3BBartsch%2C+Helmut%3BBornkamm%2C+Georg+Wilhelm%3BJanz%2C+Siegfried&rft.aulast=Felix&rft.aufirst=Klaus&rft.date=2002-04-01&rft.volume=32&rft.issue=7&rft.spage=663&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-20 N1 - Date created - 2002-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Double-blind, placebo-controlled study of single-dose metergoline in depressed patients with seasonal affective disorder. AN - 71538719; 11910270 AB - A role for serotonin in season affective disorder (SAD) has been explored with a variety of serotonergic pharmacologic agents. The authors initially hypothesized that metergoline, a nonspecific serotonin antagonist, would exacerbate depressive symptoms. In a small, open-label pilot study, the authors observed the opposite effect. They decided to follow up on this finding with this formal study. The study followed a double-blind, randomized cross-over design. Sixteen untreated, depressed patients with SAD received single oral doses of metergoline 8 mg and of placebo, spaced 1 week apart. Fourteen patients were restudied after 2 weeks of light treatment. Depression ratings using the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorder Version were performed at baseline and at 3 and 6 days after each intervention. These data were analyzed by baseline-corrected repeated measures with analysis of variance. In the off-lights condition, severity of depression was diminished after metergoline compared with placebo administration (p = 0.001). Patient daily self-ratings suggested that the peak effect occurred 2 to 4 days after study drug administration. In contrast, after 2 weeks of treatment with bright artificial light, metergoline did not demonstrate a significant effect on mood. These data suggest that single doses of metergoline may have antidepressant effects that last several days. Possible mechanisms include 5-hydroxytryptamine(2) receptor downregulation and dopamine agonism. JF - Journal of clinical psychopharmacology AU - Turner, Erick H AU - Schwartz, Paul J AU - Lowe, Catherine H AU - Nawab, Stefan S AU - Feldman-Naim, Susana AU - Drake, Christopher L AU - Myers, Frances S AU - Barnett, Ronald L AU - Rosenthal, Norman E AD - Section on Biological Rhythms, Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland, USA. Erick.Turner@med.va.gov Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 216 EP - 220 VL - 22 IS - 2 SN - 0271-0749, 0271-0749 KW - Antidepressive Agents KW - 0 KW - Dopamine Agonists KW - Receptors, Serotonin KW - Serotonin Antagonists KW - Metergoline KW - 1501393LY5 KW - Index Medicus KW - Receptors, Serotonin -- drug effects KW - Double-Blind Method KW - Combined Modality Therapy KW - Humans KW - Dopamine Agonists -- adverse effects KW - Adult KW - Cross-Over Studies KW - Middle Aged KW - Dopamine Agonists -- administration & dosage KW - Down-Regulation -- drug effects KW - Phototherapy KW - Female KW - Male KW - Seasonal Affective Disorder -- drug therapy KW - Metergoline -- adverse effects KW - Depressive Disorder, Major -- diagnosis KW - Depressive Disorder, Major -- drug therapy KW - Seasonal Affective Disorder -- diagnosis KW - Serotonin Antagonists -- administration & dosage KW - Depressive Disorder, Major -- psychology KW - Seasonal Affective Disorder -- psychology KW - Antidepressive Agents -- therapeutic use KW - Serotonin Antagonists -- adverse effects KW - Antidepressive Agents -- adverse effects KW - Metergoline -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71538719?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+psychopharmacology&rft.atitle=Double-blind%2C+placebo-controlled+study+of+single-dose+metergoline+in+depressed+patients+with+seasonal+affective+disorder.&rft.au=Turner%2C+Erick+H%3BSchwartz%2C+Paul+J%3BLowe%2C+Catherine+H%3BNawab%2C+Stefan+S%3BFeldman-Naim%2C+Susana%3BDrake%2C+Christopher+L%3BMyers%2C+Frances+S%3BBarnett%2C+Ronald+L%3BRosenthal%2C+Norman+E&rft.aulast=Turner&rft.aufirst=Erick&rft.date=2002-04-01&rft.volume=22&rft.issue=2&rft.spage=216&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+psychopharmacology&rft.issn=02710749&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-13 N1 - Date created - 2002-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor-specific CTL kill murine renal cancer cells using both perforin and Fas ligand-mediated lysis in vitro, but cause tumor regression in vivo in the absence of perforin. AN - 71533434; 11907109 AB - Kidney cancer is a devastating disease; however, biological therapies have achieved some limited success. The murine renal cancer Renca has been used as a model for developing new preclinical approaches to the treatment of renal cell carcinoma. Successful cytokine-based approaches require CD8(+) T cells, but the exact mechanisms by which T cells mediate therapeutic benefit have not been completely identified. After successful biological therapy of Renca in BALB/c mice, we generated CTLs in vitro using mixed lymphocyte tumor cultures. These CTL mediated tumor-specific H-2K(d)-restricted lysis and production of IFN-gamma, TNF-alpha, and Fas ligand (FasL) in response to Renca. CTL used both granule- and FasL-mediated mechanisms to lyse Renca, although granule-mediated killing was the predominant lytic mechanism in vitro. The cytokines IFN-gamma and TNF-alpha increased the sensitivity of Renca cells to CTL lysis by both granule- and FasL-mediated death pathways. Adoptive transfer of these anti-Renca CTL into tumor-bearing mice cured most mice of established experimental pulmonary metastases, and successfully treated mice were immune to tumor rechallenge. Interestingly, we were able to establish Renca-specific CTL from mice gene targeted for perforin (pfp(-/-)) mice. Although these pfp(-/-) CTL showed reduced cytotoxic activity against Renca, their IFN-gamma production in the presence of Renca targets was equivalent to that of wild-type CTL, and adoptive transfer of pfp(-/-) CTL was as efficient as wild-type CTL in causing regression of established Renca pulmonary metastases. Therefore, although granule-mediated killing is of paramount importance for CTL-mediated lysis in vitro, some major in vivo effector mechanisms clearly are independent of perforin. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Seki, Naoko AU - Brooks, Alan D AU - Carter, Clive R D AU - Back, Timothy C AU - Parsoneault, Erin M AU - Smyth, Mark J AU - Wiltrout, Robert H AU - Sayers, Thomas J AD - Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 2002/04/01/ PY - 2002 DA - 2002 Apr 01 SP - 3484 EP - 3492 VL - 168 IS - 7 SN - 0022-1767, 0022-1767 KW - Antigens, CD95 KW - 0 KW - Antineoplastic Agents KW - Apoptosis Regulatory Proteins KW - Epitopes, T-Lymphocyte KW - Fas Ligand Protein KW - Fasl protein, mouse KW - Ligands KW - Lymphocyte Function-Associated Antigen-1 KW - Membrane Glycoproteins KW - Pore Forming Cytotoxic Proteins KW - TNF-Related Apoptosis-Inducing Ligand KW - Tnfsf10 protein, mouse KW - Tumor Necrosis Factor-alpha KW - Perforin KW - 126465-35-8 KW - Intercellular Adhesion Molecule-1 KW - 126547-89-5 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Lung Neoplasms -- immunology KW - Immunotherapy, Adoptive -- methods KW - Mice, Inbred BALB C KW - Lymphocyte Function-Associated Antigen-1 -- physiology KW - Mice, Knockout KW - Intercellular Adhesion Molecule-1 -- physiology KW - Tumor Necrosis Factor-alpha -- toxicity KW - Apoptosis -- genetics KW - Antigens, CD95 -- metabolism KW - Lymphocyte Activation -- genetics KW - Tumor Cells, Cultured KW - Mice, Inbred C3H KW - Cell Line, Transformed KW - Intercellular Adhesion Molecule-1 -- metabolism KW - Lymphocyte Function-Associated Antigen-1 -- metabolism KW - Lung Neoplasms -- secondary KW - Apoptosis -- immunology KW - Lung Neoplasms -- therapy KW - Mice KW - Melanoma, Experimental -- immunology KW - Mice, Inbred DBA KW - Neoplasm Transplantation KW - Antineoplastic Agents -- toxicity KW - Mice, Inbred C57BL KW - Lung Neoplasms -- pathology KW - Carcinoma, Renal Cell -- pathology KW - Kidney Neoplasms -- pathology KW - Kidney Neoplasms -- therapy KW - Carcinoma, Renal Cell -- therapy KW - T-Lymphocytes, Cytotoxic -- immunology KW - Cytotoxicity, Immunologic -- genetics KW - Epitopes, T-Lymphocyte -- immunology KW - Epitopes, T-Lymphocyte -- administration & dosage KW - Membrane Glycoproteins -- deficiency KW - T-Lymphocytes, Cytotoxic -- transplantation KW - Membrane Glycoproteins -- toxicity KW - Membrane Glycoproteins -- biosynthesis KW - Carcinoma, Renal Cell -- immunology KW - Membrane Glycoproteins -- metabolism KW - Kidney Neoplasms -- immunology KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71533434?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Tumor-specific+CTL+kill+murine+renal+cancer+cells+using+both+perforin+and+Fas+ligand-mediated+lysis+in+vitro%2C+but+cause+tumor+regression+in+vivo+in+the+absence+of+perforin.&rft.au=Seki%2C+Naoko%3BBrooks%2C+Alan+D%3BCarter%2C+Clive+R+D%3BBack%2C+Timothy+C%3BParsoneault%2C+Erin+M%3BSmyth%2C+Mark+J%3BWiltrout%2C+Robert+H%3BSayers%2C+Thomas+J&rft.aulast=Seki&rft.aufirst=Naoko&rft.date=2002-04-01&rft.volume=168&rft.issue=7&rft.spage=3484&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-08 N1 - Date created - 2002-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinoembryonic antigen family receptor recognition by gonococcal Opa proteins requires distinct combinations of hypervariable Opa protein domains. AN - 71528471; 11895933 AB - Neisserial Opa proteins function as a family of adhesins that bind heparan sulfate proteoglycan (HSPG) or carcinoembryonic antigen family (CEACAM) receptors on human host cells. In order to define the CEACAM binding domain on Opa proteins, we tested the binding properties of a series of gonococcal (strain MS11) recombinants producing mutant and chimeric Opa proteins with alterations in one or more of the four surface-exposed loops. Mutagenesis demonstrated that the semivariable domain, present in the first loop, was completely dispensable for CEACAM binding. In contrast, the two hypervariable (HV) regions present in the second and third loops were essential for binding; deletion of either domain resulted in loss of receptor recognition. Deletion of the fourth loop resulted in a severe decrease in Opa expression at the cell surface and could therefore not be tested for CEACAM binding. Chimeric Opa variants, containing combinations of HV regions derived from different CEACAM binding Opa proteins, lost most of their receptor binding activity. Some chimeric variants gained HSPG binding activity. Together, our results indicate that full recognition of CEACAM receptors by Opa proteins requires a highly coordinate interplay between both HV regions. Furthermore, shuffling of HV regions may result in novel HSPG receptor binding activity. JF - Infection and immunity AU - Bos, Martine P AU - Kao, David AU - Hogan, Daniel M AU - Grant, Christopher C R AU - Belland, Robert J AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA. M.P.Bos@bio.uu.nl Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 1715 EP - 1723 VL - 70 IS - 4 SN - 0019-9567, 0019-9567 KW - Antigens, Bacterial KW - 0 KW - Antigens, CD KW - Antigens, Differentiation KW - Antigens, Neoplasm KW - CD66 antigens KW - CEACAM3 protein, human KW - Carcinoembryonic Antigen KW - Cell Adhesion Molecules KW - Heparan Sulfate Proteoglycans KW - Membrane Glycoproteins KW - opacity proteins KW - Index Medicus KW - HeLa Cells KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Heparan Sulfate Proteoglycans -- metabolism KW - Binding Sites KW - Carcinoembryonic Antigen -- metabolism KW - Antigens, Bacterial -- metabolism KW - Antigens, Differentiation -- metabolism KW - Antigens, CD -- metabolism KW - Antigens, Bacterial -- chemistry KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71528471?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+immunity&rft.atitle=Carcinoembryonic+antigen+family+receptor+recognition+by+gonococcal+Opa+proteins+requires+distinct+combinations+of+hypervariable+Opa+protein+domains.&rft.au=Bos%2C+Martine+P%3BKao%2C+David%3BHogan%2C+Daniel+M%3BGrant%2C+Christopher+C+R%3BBelland%2C+Robert+J&rft.aulast=Bos&rft.aufirst=Martine&rft.date=2002-04-01&rft.volume=70&rft.issue=4&rft.spage=1715&rft.isbn=&rft.btitle=&rft.title=Infection+and+immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-11 N1 - Date created - 2002-03-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Infect Immun. 1983 Apr;40(1):398-406 [6131872] Infect Immun. 1978 Jan;19(1):320-31 [415006] Mol Microbiol. 1987 Jul;1(1):5-12 [2455211] J Exp Med. 1988 Dec 1;168(6):2121-9 [3143800] Cell. 1989 Feb 24;56(4):539-47 [2492905] Infect Immun. 1989 May;57(5):1590-8 [2468608] Clin Microbiol Rev. 1989 Apr;2 Suppl:S83-91 [2497966] Cancer Res. 1990 Oct 15;50(20):6534-9 [2208113] Science. 1991 May 17;252(5008):934-8 [1674624] J Clin Lab Anal. 1991;5(5):344-66 [1941355] Mol Microbiol. 1991 Aug;5(8):1889-901 [1815562] Mol Microbiol. 1992 Jul;6(13):1729-37 [1630313] EMBO J. 1993 Feb;12(2):641-50 [8440254] J Infect Dis. 1993 May;167(5):1065-73 [8486938] J Biol Chem. 1993 Sep 15;268(26):19228-31 [8366075] Int J Cancer. 1993 Sep 9;55(2):303-10 [7690348] Mol Microbiol. 1994 Apr;12(2):171-80 [7520117] EMBO J. 1995 May 15;14(10):2144-54 [7774572] J Exp Med. 1995 Aug 1;182(2):511-7 [7629509] Mol Gen Genet. 1996 Mar 20;250(5):558-69 [8676859] Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14851-6 [8962144] Mol Microbiol. 1996 Dec;22(5):941-50 [8971715] J Exp Med. 1997 May 5;185(9):1557-64 [9151893] Infect Immun. 1997 Jun;65(6):2353-61 [9169774] Mol Microbiol. 1997 Dec;26(5):971-80 [9426134] Microbiology. 1998 Jan;144 ( Pt 1):157-66 [9467908] J Bacteriol. 1998 Mar;180(5):1323-30 [9495774] Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9584-9 [9689124] Trends Microbiol. 1998 Dec;6(12):489-95 [10036728] Mol Microbiol. 1999 Apr;32(2):233-42 [10231481] Mol Microbiol. 1999 Jun;32(6):1124-32 [10383754] J Exp Med. 1999 Aug 2;190(3):331-40 [10430622] Mol Microbiol. 1999 Nov;34(3):538-51 [10564495] Infect Immun. 2000 Jun;68(6):3601-7 [10816518] Trends Microbiol. 2000 Jun;8(6):258-60; discussion 260-1 [10838580] Cell Microbiol. 2000 Feb;2(1):69-82 [11207564] Cell Microbiol. 1999 Sep;1(2):169-81 [11207550] J Biol Chem. 2001 May 18;276(20):17413-9 [11278708] Exp Cell Res. 1999 Nov 1;252(2):243-9 [11501563] Cell. 1986 Oct 10;47(1):61-71 [3093085] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cloning of CYP2J2 gene and identification of functional polymorphisms. AN - 71527173; 11901223 AB - CYP2J2 is abundant in cardiovascular tissue and active in the metabolism of arachidonic acid to eicosanoids that possess potent anti-inflammatory, vasodilatory, and fibrinolytic properties. We cloned and sequenced the entire CYP2J2 gene (approximately 40.3 kb), which contains nine exons and eight introns. We then sequenced the CYP2J2 exons and intron-exon boundaries in 72 healthy persons representing African, Asian, and European/white populations as part of the National Institutes of Health/National Institute of Environmental Health Sciences Environmental Genome Single Nucleotide Polymorphism Program. A variety of polymorphisms were found, four of which resulted in coding changes (Arg158Cys, Ile192Asn, Asp342Asn, and Asn404Tyr). A fifth variant (Thr143Ala) was identified by screening a human heart cDNA library. All five variant cDNAs of CYP2J2 were generated by site-directed mutagenesis and expressed in Sf9 insect cells by using a baculovirus system. The recombinant wild-type and variant CYP2J2 proteins immunoreacted with peptide-based antibodies to CYP2J2 and displayed typical cytochrome P450 (P450) CO-difference spectra; however, the Asn404Tyr and Ile192Asn variants also had prominent spectral peaks at 420 nm. The ability of these variants to metabolize arachidonic acid and linoleic acid was compared with that of wild-type CYP2J2. Three variants (Asn404Tyr, Arg158Cys, and Thr143Ala) showed significantly reduced metabolism of both arachidonic acid and linoleic acid. The Ile192Asn variant showed significantly reduced activity toward arachidonic acid only. The Asp342Asn variant showed similar metabolism to wild-type CYP2J2 for both endogenous substrates. Based on these data, we conclude that allelic variants of the human CYP2J2 gene exist and that some of these variants result in a P450 protein that has reduced catalytic function. Insofar as CYP2J2 products have effects in the cardiovascular system, we speculate that these variants may be functionally relevant. JF - Molecular pharmacology AU - King, Lorraine M AU - Ma, Jixiang AU - Srettabunjong, Supawon AU - Graves, Joan AU - Bradbury, J Alyce AU - Li, Leping AU - Spiecker, Martin AU - Liao, James K AU - Mohrenweiser, Harvey AU - Zeldin, Darryl C AD - Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 840 EP - 852 VL - 61 IS - 4 SN - 0026-895X, 0026-895X KW - DNA, Complementary KW - 0 KW - Recombinant Proteins KW - Arachidonic Acid KW - 27YG812J1I KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Linoleic Acid KW - 9KJL21T0QJ KW - Oxygenases KW - EC 1.13.- KW - arachidonate epoxygenase KW - EC 1.14.14.1 KW - Index Medicus KW - Alleles KW - Genome, Human KW - Linoleic Acid -- metabolism KW - Recombinant Proteins -- metabolism KW - Exons KW - Humans KW - Molecular Sequence Data KW - Introns KW - Gene Expression KW - Transcription, Genetic KW - Sequence Analysis, DNA KW - DNA, Complementary -- analysis KW - Arachidonic Acid -- metabolism KW - Cloning, Molecular KW - Polymorphism, Genetic KW - Cytochrome P-450 Enzyme System -- genetics KW - Oxygenases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71527173?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Cloning+of+CYP2J2+gene+and+identification+of+functional+polymorphisms.&rft.au=King%2C+Lorraine+M%3BMa%2C+Jixiang%3BSrettabunjong%2C+Supawon%3BGraves%2C+Joan%3BBradbury%2C+J+Alyce%3BLi%2C+Leping%3BSpiecker%2C+Martin%3BLiao%2C+James+K%3BMohrenweiser%2C+Harvey%3BZeldin%2C+Darryl+C&rft.aulast=King&rft.aufirst=Lorraine&rft.date=2002-04-01&rft.volume=61&rft.issue=4&rft.spage=840&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-11 N1 - Date created - 2002-03-19 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF272142; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High Throughput Screening for Cyanovirin-N Mimetics Binding to HIV-1 gp4l AN - 21191464; 11617158 AB - The human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein gp4l is an important mediator of viral entry into host cells. Previous studies showed that the virucidal protein cyanovirin-N (CV-N) bound to both gpl20 and gp4l, and that this binding was associated with its antiviral activity. We constructed an HTS assay based on the interaction of europium-labeled CV-N with recombinant glycosylated gp4l ectodomain to support identification of small-molecule mimetics of CV-N that might be developed as antiviral drug leads. Primary screening of over 107,000 natural product extracts in the assay yielded 347 confirmed hits. Secondary assays eliminated extracts that bound directly to labeled CV-N or for which the simple sugars mannose and N-acetylglucosamine blocked the interaction with gp4l (lectin activity). Extracts were further prioritized based on anti-HIV activity and other biological, biochemical, and chemical criteria. The distribution of source organism taxonomy of active extracts was analyzed, as was the cross-correlation of activity between the CV-N-gp4l binding competition assay and the previously reported CV-N-gpl20 binding competition assay. A limited set of extracts was selected for bioassay-guided fractionation. JF - Journal of Biomolecular Screening AU - Beutler, John A AU - McMahon, James B AU - Johnson, Tanya R AU - O'Keefe, Barry R AU - Buzzell, Randy A AU - Robbins, Danielle AU - Gardella, Roberta AU - Wilson, Jennifer AU - Boyd, Michael R AD - Intramural Research Support Program, SAIC-Frederick, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD and Molecular Targets Drug Discovery Program, SAIC-Frederick, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 105 EP - 110 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 7 IS - 2 SN - 1087-0571, 1087-0571 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts; Biotechnology and Bioengineering Abstracts KW - Sugar KW - Mannose KW - natural products KW - Lectins KW - N-Acetylglucosamine KW - Antiviral activity KW - cyanovirin-N KW - Envelopes KW - Antiviral agents KW - Human immunodeficiency virus KW - Human immunodeficiency virus 1 KW - Taxonomy KW - high-throughput screening KW - Glycoproteins KW - A 01340:Antibiotics & Antimicrobials KW - V 22360:AIDS and HIV KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21191464?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biomolecular+Screening&rft.atitle=High+Throughput+Screening+for+Cyanovirin-N+Mimetics+Binding+to+HIV-1+gp4l&rft.au=Beutler%2C+John+A%3BMcMahon%2C+James+B%3BJohnson%2C+Tanya+R%3BO%27Keefe%2C+Barry+R%3BBuzzell%2C+Randy+A%3BRobbins%2C+Danielle%3BGardella%2C+Roberta%3BWilson%2C+Jennifer%3BBoyd%2C+Michael+R&rft.aulast=Beutler&rft.aufirst=John&rft.date=2002-04-01&rft.volume=7&rft.issue=2&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomolecular+Screening&rft.issn=10870571&rft_id=info:doi/10.1177%2F108705710200700202 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-01-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Sugar; cyanovirin-N; Envelopes; Antiviral agents; Mannose; high-throughput screening; Taxonomy; Lectins; natural products; Glycoproteins; N-Acetylglucosamine; Antiviral activity; Human immunodeficiency virus; Human immunodeficiency virus 1 DO - http://dx.doi.org/10.1177/108705710200700202 ER - TY - JOUR T1 - Predictors of sexual behavior patterns over one year among persons at high risk for HIV AN - 205934571; 11974642 AB - A recent study examined the sexual risk act patterns of individuals who participated in the NIMH National Multisite HIV Prevention Trial. Participants who responded to intervention with consistently protected behavior were significantly more likely to be older or young adults, recent immigrants to the US, and to not barter sex or have alcohol-related problems. JF - Archives of Sexual Behavior AU - National Institute of Mental Health Multisite HIV Prevention Trial Group AD - National Institute of Mental Health Multisite HIV Prevention Trial Group Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 165 EP - 76 CY - New York PB - Springer Science & Business Media VL - 31 IS - 2 SN - 00040002 KW - Medical Sciences KW - Sexual behavior KW - Human immunodeficiency virus KW - HIV KW - Prevention KW - Demographics KW - Intervention KW - Acquired Immunodeficiency Syndrome -- prevention & control KW - Prospective Studies KW - Random Allocation KW - Risk Factors KW - Humans KW - Adult KW - Sexually Transmitted Diseases -- prevention & control KW - Sexually Transmitted Diseases -- transmission KW - Male KW - Female KW - Sexually Transmitted Diseases -- epidemiology KW - HIV Seropositivity -- transmission KW - Sexual Behavior -- psychology KW - HIV Seropositivity -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/205934571?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+Sexual+Behavior&rft.atitle=Predictors+of+sexual+behavior+patterns+over+one+year+among+persons+at+high+risk+for+HIV&rft.au=National+Institute+of+Mental+Health+Multisite+HIV+Prevention+Trial+Group&rft.aulast=National+Institute+of+Mental+Health+Multisite+HIV+Prevention+Trial+Group&rft.aufirst=&rft.date=2002-04-01&rft.volume=31&rft.issue=2&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Archives+of+Sexual+Behavior&rft.issn=00040002&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Name - National Institute of Mental Health N1 - Copyright - Copyright Plenum Publishing Corporation Apr 2002 N1 - Last updated - 2014-07-27 N1 - CODEN - ASXBA8 ER - TY - JOUR T1 - Rb LOCALIZATION AND PHOSPHORYLATION KINETICS CORRELATE WITH THE CELLULAR PHENOTYPE OF CULTURED BREAST ADENOCARCINOMA CELLS AN - 19332552; 8696186 AB - Retinoblastoma protein (Rb) expression has been correlated with state of differentiation, proliferation rate, and metastatic potential in breast adenocarcinomas and established cell lines. These observations, based on immunoreactivity of total Rb rather than hypophosphorylated protein, do not address the relationship between functional Rb and indicators of an aggressive transformed cellular phenotype. We hypothesized that the distribution of functional Rb and the kinetics of Rb phosphorylation would differ between cell lines representing immortalized mammary epithelium (MCF10A), differentiated nonmetastatic mammary adenocarcinoma (MCF-7), and poorly differentiated, highly metastatic mammary adenocarcinoma (MDA-MB-231) and that these differences would be informative of the cellular phenotype. Direct immunofluorescence microscopy was used to compare qualitatively the subcellular localization of total and hypophosphorylated Rb protein in synchronized and asynchronous cells. This technique was also used to quantitatively assess the amounts of hypophosphorylated Rb throughout the cell cycle in these representative cell lines. Total Rb stained more prominently than hypophosphorylated Rb in the nucleus of all asynchronous cells. Rb phosphorylation was more rapid in MCF-7 cells than in MCF10A cells, whereas Rb dephosphorylation appeared deregulated in MDA-MB-231 cells. We conclude that assessment of hypophosphorylated Rb may be more useful than assessment of total Rb for the evaluation of transformed breast adenocarcinoma phenotypes. JF - In Vitro Cellular & Developmental Biology - Animal AU - Botos, Jeannine AU - Barhoumi, Rola AU - Burghardt, Robert AU - Kochevar, Deborah T AD - Departments of Veterinary Physiology and Pharmacology (J. B., D. T. K.) and Veterinary Anatomy and Public Health (R. Ba., R. Bu.), Texas A&M University, College Station, Texas 77843-4466, botosjea@mail.nih.gov Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 235 EP - 241 PB - Allen Press, Inc., 810 East Tenth St. VL - 38 IS - 4 SN - 1071-2690, 1071-2690 KW - Biotechnology and Bioengineering Abstracts KW - breast neoplasms KW - cell cycle proteins KW - nuclear proteins KW - retinoblastoma protein KW - phosphoproteins KW - Dephosphorylation KW - Cell cycle KW - Retinoblastoma protein KW - Immunofluorescence KW - Metastases KW - Differentiation KW - Phosphorylation KW - Kinetics KW - Immunoreactivity KW - Microscopy KW - Epithelium KW - Nuclei KW - Adenocarcinoma KW - W 30925:Genetic Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19332552?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+Vitro+Cellular+%26+Developmental+Biology+-+Animal&rft.atitle=Rb+LOCALIZATION+AND+PHOSPHORYLATION+KINETICS+CORRELATE+WITH+THE+CELLULAR+PHENOTYPE+OF+CULTURED+BREAST+ADENOCARCINOMA+CELLS&rft.au=Botos%2C+Jeannine%3BBarhoumi%2C+Rola%3BBurghardt%2C+Robert%3BKochevar%2C+Deborah+T&rft.aulast=Botos&rft.aufirst=Jeannine&rft.date=2002-04-01&rft.volume=38&rft.issue=4&rft.spage=235&rft.isbn=&rft.btitle=&rft.title=In+Vitro+Cellular+%26+Developmental+Biology+-+Animal&rft.issn=10712690&rft_id=info:doi/10.1290%2F1071-2690%282002%290382.0.CO%3B2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Cell cycle; Dephosphorylation; Retinoblastoma protein; Immunofluorescence; Metastases; Differentiation; Phosphorylation; Kinetics; Microscopy; Immunoreactivity; Epithelium; Adenocarcinoma; Nuclei DO - http://dx.doi.org/10.1290/1071-2690(2002)038<0235:RLAPKC>2.0.CO;2 ER - TY - JOUR T1 - Structured Treatment Interruption: Approaches and Risks. AN - 1859367704; 11927050 AB - Although highly active antiretroviral therapy suppresses HIV replication resulting in extraordinary clinical benefits, toxicity, adherence difficulties, and the monetary cost of medications limit the long-term effectiveness and availability of therapy for many HIV-infected individuals. Strategies to interrupt therapy have been proposed as a means to enhance the sustainability of antiretroviral treatment. Widely different approaches with varied patient populations, theoretical concepts, and clinical designs are frequently lumped together as "structured treatment interruptions." This review summarizes the approaches and risks of treatment interruptions in HIV infection. Currently, none of these strategies can be recommended in standard clinical practice. JF - Current infectious disease reports AU - Dybul, Mark AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 31/Rm 7A-03, Bethesda, MD 20892, USA. mdybul@nih.gov Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 175 EP - 180 VL - 4 IS - 2 SN - 1523-3847, 1523-3847 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859367704?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+infectious+disease+reports&rft.atitle=Structured+Treatment+Interruption%3A+Approaches+and+Risks.&rft.au=Dybul%2C+Mark&rft.aulast=Dybul&rft.aufirst=Mark&rft.date=2002-04-01&rft.volume=4&rft.issue=2&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Current+infectious+disease+reports&rft.issn=15233847&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2002-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Dendritic Cell Vaccine Induces Protective Immunity to Intracranial Growth of Glioma AN - 18577767; 5409543 AB - The central nervous system is an immunologically privileged site hidden behind the blood brain barrier. Nevertheless, immune effector cells induced peripherally can be recruited into the central nervous system. Active immunotherapy of intracranial malignancies is thus potentially feasible. In this study we describe a vaccine regimen, based on bone marrow-derived dendritic cells pulsed with the RNA derived from GL261 glioma cells that induces a specific T cell response and protection against intracerebrally implanted GL261 tumors. Immunohistochemical analysis of brain tumors from vaccinated mice was characterized by pronounced intratumoral infiltrates predominantly of CD4 super(+) as well as CD8 super(+) T cells. The efficacy of the vaccine was improved further by administration of recombinant interleukin-12 into the vaccine regimen. JF - Anticancer Research AU - Insug, O AU - Ku, G AU - Ertl, HCj AU - Blaszczyk-Thurin, M AD - Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA, thurinm@mail.nih.gov Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 613 EP - 622 VL - 22 IS - 2A SN - 0250-7005, 0250-7005 KW - man KW - mice KW - CD4 antigen KW - CD8 antigen KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts KW - Dendritic cells KW - Immunotherapy KW - Lymphocytes T KW - Vaccines KW - Glioma KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18577767?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+Research&rft.atitle=A+Dendritic+Cell+Vaccine+Induces+Protective+Immunity+to+Intracranial+Growth+of+Glioma&rft.au=Insug%2C+O%3BKu%2C+G%3BErtl%2C+HCj%3BBlaszczyk-Thurin%2C+M&rft.aulast=Insug&rft.aufirst=O&rft.date=2002-04-01&rft.volume=22&rft.issue=2A&rft.spage=613&rft.isbn=&rft.btitle=&rft.title=Anticancer+Research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Glioma; Vaccines; Dendritic cells; Immunotherapy; Lymphocytes T ER - TY - JOUR T1 - Sunlight and mortality from breast, ovarian, colon, prostate, and non-melanoma skin cancer: a composite death certificate based case-control study AN - 18463012; 5429482 AB - To explore whether mortality from female breast, ovarian, colon, and prostate cancer were negatively associated with exposure to sunlight. A death certificate based case-control study of mortality was conducted into five cancers: female breast, ovarian, colon, prostate, and non-melanoma skin cancer (as a positive control) to examine associations with residential and occupational exposure to sunlight. Cases were all deaths from these cancers between 1984 and 1995 in 24 states of the United States. Controls, which were age frequency matched to a series of cases, excluded deaths from cancer and certain neurological diseases. Multiple logistic regression was used in a model that included age, sex, race, residential exposure to sunlight (based on region), and socioeconomic status, occupational exposure to sunlight, and physical activity (the last three based on usual occupation). Residential exposure to sunlight was negatively and significantly associated with mortality from female breast, ovarian, prostate, and colon cancer. Only female breast and colon cancer, however, also showed significant negative associations with jobs with the highest occupational exposure to sunlight (odds ratio (OR) 0.82 (95% confidence interval (95% CI) 0.70 to 0.97) for female breast cancer; OR 0.90 (95% CI 0.86 to 0.94) for colon cancer). For both cancers, the negative association with occupational sunlight was greatest in the geographical region of highest exposure to sunlight and was independent of physical activity on the job. Non-melanoma skin cancer, as expected, was positively associated with both residential and occupational sunlight. In this exploratory study, unlike mortality from non-melanoma skin cancer, mortality from female breast cancer and colon cancer were negatively associated with both residential and occupational sunlight. JF - Occupational and Environmental Medicine AU - Freedman, D M AU - Dosemeci, M AU - McGlynn, K AD - Radiation Epidemiology Branch, Room 7087, National Cancer Institute, 6120 Executive Boulevard, Bethesda, MD 20892, USA, mf101e@nih.gov Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 257 EP - 262 VL - 59 IS - 4 SN - 1351-0711, 1351-0711 KW - sunlight KW - Toxicology Abstracts; Health & Safety Science Abstracts; Risk Abstracts KW - H 11000:Diseases/Injuries/Trauma KW - X 24210:Radiation & radioactive materials KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18463012?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=Sunlight+and+mortality+from+breast%2C+ovarian%2C+colon%2C+prostate%2C+and+non-melanoma+skin+cancer%3A+a+composite+death+certificate+based+case-control+study&rft.au=Freedman%2C+D+M%3BDosemeci%2C+M%3BMcGlynn%2C+K&rft.aulast=Freedman&rft.aufirst=D&rft.date=2002-04-01&rft.volume=59&rft.issue=4&rft.spage=257&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Decreased aerobic capacity in children with juvenile dermatomyositis AN - 18462758; 5429336 AB - To determine whether patients with juvenile dermatomyositis (DM) have limited aerobic capacity compared with healthy controls. Fourteen juvenile DM patients with inactive to moderately active, stable disease (age range 7-17 years) and 14 age- and sex-matched controls performed a maximal exercise test using a cycle ergometer. Oxygen uptake and power were measured at peak exercise (VO sub(2peak) and W sub(peak), respectively) and at anaerobic threshold (AT and W sub(AT)). Juvenile DM disease activity and damage were also assessed. Patients with juvenile DM had significantly reduced VO sub(2peak) (19.6 ml O sub(2)/kg/minute in juvenile DM versus 31.1 ml O sub(2)/kg/minute in controls), peak heart rate (166 versus 184 beats per minute), W sub(peak) (1.6 versus 2.7 watts/kg), AT (11.1 versus 18.0 ml O sub(2)/kg/minute) and W sub(AT) (0.6 versus 1.4 watts/kg), compared to controls (P less than or equal to 0.05 for each). Aerobic exercise parameters correlated with physician global disease activity and damage, T1-weighted magnetic resonance imaging, and Childhood Myositis Assessment Scale scores (r sub(s) = 0.58-0.82, P less than or equal to 0.05). Patients with juvenile DM with a range of disease activity have a decreased aerobic and work capacity compared to healthy children. Aerobic exercise limitation in juvenile DM correlates best with measures of disease damage (global damage assessment, T1-weighted magnetic resonance imaging, and disease duration). Aerobic exercise testing may be valuable in the assessment of physical endurance, and aerobic training may be indicated as part of the therapeutic regimen in myositis patients with inactive to moderately active, stable disease. JF - Arthritis Care and Research AU - Hicks, JE AU - Drinkard, B AU - Summers, R M AU - Rider, L G AD - National Institutes of Health, 10 Center Drive, Building 10 Room 65235, Bethesda, MD 20892-1604, USA, bart_drinkard@nih.gov Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 118 EP - 123 VL - 47 IS - 2 SN - 0893-7524, 0893-7524 KW - Physical Education Index KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18462758?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arthritis+Care+and+Research&rft.atitle=Decreased+aerobic+capacity+in+children+with+juvenile+dermatomyositis&rft.au=Hicks%2C+JE%3BDrinkard%2C+B%3BSummers%2C+R+M%3BRider%2C+L+G&rft.aulast=Hicks&rft.aufirst=JE&rft.date=2002-04-01&rft.volume=47&rft.issue=2&rft.spage=118&rft.isbn=&rft.btitle=&rft.title=Arthritis+Care+and+Research&rft.issn=08937524&rft_id=info:doi/10.1002%2Fart.10237 LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/art.10237 ER - TY - JOUR T1 - Quantitative Exposure-Response Assessment Approaches to Evaluate Acute Inhalation Toxicity of Phosgene AN - 18451590; 5426540 AB - Phosgene has been a long-term subject of toxicological research due to its widespread use, high toxicity, and status as a model of chemically induced lung injury. To take advantage of the abundant data set for the acute inhalation toxicity of phosgene, methods for exposure-response analysis that use more data than the traditional no-observed-adverse-effect level approach were used to perform an exposure-response assessment for phosgene. Categorical regression is particularly useful for acute exposures due to the ability to combine studies of various exposure durations, and thus provide estimates of effect severity for a range of both exposure concentrations and durations. Results from the categorical regression approach were compared to those from parametric curve fitting models (i.e., benchmark concentration models) that make use of information from an entire dose-response, but only for one exposure duration. While categorical regression analysis provided results that were comparable to benchmark concentration results, categorical regression provides an improvement over that technique by accounting for the effects of both exposure concentration and duration on response. The other major advantage afforded by categorical regression is the ability to combine studies, allowing the quantitative use of a larger data set, which increases confidence in the final result. JF - Human and Ecological Risk Assessment AU - Strickland, JA AU - Guth, D J AD - Integrated Laboratory Systems, Inc., NIEHS EC-17, P.O. Box 12233, Research Triangle Park, NC 27709, USA, strick12@niehs.nih.gov Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 511 EP - 536 VL - 8 IS - 3 SN - 1080-7039, 1080-7039 KW - acute toxicity KW - phosgene KW - Health & Safety Science Abstracts; Risk Abstracts; Toxicology Abstracts KW - X 24151:Acute exposure KW - H 14000:Toxicology KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18451590?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+and+Ecological+Risk+Assessment&rft.atitle=Quantitative+Exposure-Response+Assessment+Approaches+to+Evaluate+Acute+Inhalation+Toxicity+of+Phosgene&rft.au=Strickland%2C+JA%3BGuth%2C+D+J&rft.aulast=Strickland&rft.aufirst=JA&rft.date=2002-04-01&rft.volume=8&rft.issue=3&rft.spage=511&rft.isbn=&rft.btitle=&rft.title=Human+and+Ecological+Risk+Assessment&rft.issn=10807039&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Disposition of Inhaled Mercury Vapor in Pregnant Rats: Maternal Toxicity and Effects on Developmental Outcome AN - 18443732; 5420041 AB - The disposition and toxicity of inhaled elemental mercury (Hg super(0)) vapor for pregnant Long-Evans rats, and potential adverse effects on reproductive outcome were investigated. Rats were exposed to 0, 1, 2, 4, or 8 mg Hg super(0)/m super(3) for 2 h/day from gestation day (GD) 6 through GD 15. Maternal toxicity occurred primarily in rats exposed to 4 and 8 mg/m super(3) and was manifested as a concentration-related decrease in body weight gain and mild nephrotoxicity. Control rats gained about 13% of their initial body weight during the 10-day exposure. Rats exposed to 4 mg/m super(3) Hg super(0) gained about 7% less than controls, and rats exposed to 8 mg/m super(3) Hg super(0) lost about 17% of their initial body weight during the 10-day exposure period. Maternal kidney weights were significantly increased in the 4 and 8 mg/m super(3) concentration groups, and urinalysis revealed increased levels of protein and alkaline phosphatase activity in urine of all Hg super(0)-exposed rats. Dams exposed to 8 mg/m super(3) were euthanized in moribund condition on postnatal day (PND) 1. There was no histopathological evidence of toxicity in maternal lung, liver, or kidney of exposed rats at GD 6, GD 15, or PND 1. The incidence of resorptions was significantly increased, litter size and PND 1 neonatal body weights were significantly decreased only in the 8-mg/m super(3) group. Total Hg concentrations in maternal tissues increased with increasing number of exposure days and concentration. In general, approximately 70% of Hg was eliminated from maternal tissues during the week following the last exposure (GD 15 to PND 1). Elimination of Hg from maternal brain and kidney was slower than in other tissues, possibly due to higher levels of metallothionein. Total Hg concentrations in fetal tissues increased with increasing number of exposure days and concentration, demonstrating that a significant amount of Hg crossed the placenta. One week after the last exposure, significant amounts of Hg were still present in brain, liver, and kidney of PND 1 neonates. Metallothionein levels in neonatal tissues were not significantly increased by exposure to 4 mg/m super(3) Hg super(0). The total amount of Hg in neonatal brain (ng/brain) continued to increase after termination of inhalation exposure, suggesting a redistribution of Hg from the dam to neonatal brain. These data demonstrate that inhaled Hg super(0) vapor is distributed to all maternal and fetal tissues in a dose-dependent manner. Adverse effects of Hg on developmental outcome occurred only at a concentration that caused maternal toxicity. JF - Toxicological Sciences AU - Morgan, D L AU - Chanda, S M AU - Price, H C AU - Fernando, R AU - Liu, J AU - Brambila, E AU - O'Connor, R W AU - Beliles, R P AU - Barone, S Jr AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 261 EP - 273 VL - 66 IS - 2 SN - 1096-6080, 1096-6080 KW - Toxicology Abstracts KW - X 24164:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18443732?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Disposition+of+Inhaled+Mercury+Vapor+in+Pregnant+Rats%3A+Maternal+Toxicity+and+Effects+on+Developmental+Outcome&rft.au=Morgan%2C+D+L%3BChanda%2C+S+M%3BPrice%2C+H+C%3BFernando%2C+R%3BLiu%2C+J%3BBrambila%2C+E%3BO%27Connor%2C+R+W%3BBeliles%2C+R+P%3BBarone%2C+S+Jr&rft.aulast=Morgan&rft.aufirst=D&rft.date=2002-04-01&rft.volume=66&rft.issue=2&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Plasma pharmacokinetics of a liver-selective nitric oxide-donating diazeniumdiolate in the male C57BL/6 mouse AN - 18421330; 5408442 AB - The single-dose plasma pharmacokinetics of O super(2)-vinyl 1-(pyrrolidin-1-yl) diazen-1-ium-1,2-diolate (V-PYRRO/NO) following intravenous (i.v.) and intraperitoneal (i.p.) bolus administration to the male C57BL/6 mouse was studied in an effort to characterize the disposition of the agent and to serve as a basis for the design of in vivo efficacy studies. Plasma V-PYRRO/NO concentrations declined rapidly in a bi-exponential manner after i.v. administration of 5 mg kg super(-1) body weight to mouse. The terminal half-life was 9.4 min and the mean residence time was 3.4 min. V-PYRRO/NO was absorbed rapidly following i.p. administration, with peak plasma concentrations being observed 3 min after injection. Levels then declined with a terminal half-life of 11.7 min. The bioavailable fraction from the i.p. compartment was 19%, indicating a high first-pass effect. The results provide additional evidence for a liver-selective metabolism of this nitric oxide-donating prodrug. JF - Xenobiotica AU - Stinson, S F AU - House, T AU - Bramhall, C AU - Saavedra, JE AU - Keefer, L K AU - Nims, R W AD - Developmental Therapeutics Program, Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD 20702-1201, USA Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 339 EP - 347 VL - 32 IS - 4 SN - 0049-8254, 0049-8254 KW - diazeniumdiolate KW - mice KW - pharmacokinetics KW - plasma KW - Toxicology Abstracts KW - X 24153:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18421330?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Xenobiotica&rft.atitle=Plasma+pharmacokinetics+of+a+liver-selective+nitric+oxide-donating+diazeniumdiolate+in+the+male+C57BL%2F6+mouse&rft.au=Stinson%2C+S+F%3BHouse%2C+T%3BBramhall%2C+C%3BSaavedra%2C+JE%3BKeefer%2C+L+K%3BNims%2C+R+W&rft.aulast=Stinson&rft.aufirst=S&rft.date=2002-04-01&rft.volume=32&rft.issue=4&rft.spage=339&rft.isbn=&rft.btitle=&rft.title=Xenobiotica&rft.issn=00498254&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The Association between Biomarker-Based Exposure Estimates for Phthalates and Demographic Factors in a Human Reference Population AN - 18415983; 5403731 AB - Population-based estimates of environmental exposures using biomarkers can be difficult to obtain for a variety of reasons, including problems with limits of detection, undersampling of key strata, time between exposure and sampling, variation across individuals, variation within individuals, and the ability to find and interpret a given biomarker. In this article, we apply statistical likelihoods, weighted sampling, and regression methods for censored data to the analysis of biomarker data. Urinary metabolites for seven phthalates, reported by Blount et al., are analyzed using these methods. In the case of the phthalates data, we assumed the underlying model to be a log-normal distribution with the mean of the distribution defined as a function of a number of demographic variables that might affect phthalate levels in individuals. Included as demographic variables were age, sex, ethnicity, residency, family income, and education level. We conducted two analyses: an unweighted analysis where phthalate distributions were estimated with changes in the means of these distributions as a function of demographic variables, and a weighted prediction for the general population in which weights were assigned for a subset of the population depending on the frequency of their demographic variables in the general U.S. population. We used statistical tests to determine whether any of the demographic variables affected mean phthalate levels. Individuals with only a high school education had higher levels of di-n-butyl phthalate than individuals with education beyond high school. Subjects who had family income less than $1,500 in the month before sampling and/or only high school education had higher levels of n-butyl benzyl phthalate levels than other groupings. Di(2-ethylhexyl) phthalate was higher in males and/or in urban populations and/or in people who had family income less than $1,500 per month. Our findings suggest that there may be significant demographic variations in exposure and/or metabolism of phthalates and that health-risk assessments for phthalate exposure in humans should consider different potential risk groups. JF - Environmental Health Perspectives AU - Koo, Jung-Wan AU - Parham, F AU - Kohn, M C AU - Masten, SA AU - Brock, J W AU - Needham, L L AU - Portier, C J AD - National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, MD A3-02, Research Triangle Park, NC 27709, USA, portier@niehs.nih.gov Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 405 EP - 410 VL - 110 IS - 4 SN - 0091-6765, 0091-6765 KW - biomarkers KW - man KW - phthalic acid KW - Toxicology Abstracts KW - X 24156:Environmental impact UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18415983?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=The+Association+between+Biomarker-Based+Exposure+Estimates+for+Phthalates+and+Demographic+Factors+in+a+Human+Reference+Population&rft.au=Koo%2C+Jung-Wan%3BParham%2C+F%3BKohn%2C+M+C%3BMasten%2C+SA%3BBrock%2C+J+W%3BNeedham%2C+L+L%3BPortier%2C+C+J&rft.aulast=Koo&rft.aufirst=Jung-Wan&rft.date=2002-04-01&rft.volume=110&rft.issue=4&rft.spage=405&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Serotonin releasing agents: Neurochemical, therapeutic and adverse effects AN - 18411408; 5395460 AB - This review summarizes the neurochemical, therapeutic and adverse effects of serotonin (5-HT) releasing agents. The 5-HT releaser ( plus or minus )-fenfluramine is composed of two stereoisomers, (+)-fenfluramine and (-)-fenfluramine, which are N-de-ethylated to yield the metabolites, (+)-norfenfluramine and (-)-norfenfluramine. Fenfluramines and norfenfluramines are 5-HT transporter substrates and potent 5-HT releasers. Other 5-HT releasing agents include m-chlorophenylpiperazine (mCPP), a major metabolite of the antidepressant drug trazodone. Findings from in vitro and in vivo studies support the hypothesis that fenfluramines and mCPP release neuronal 5-HT via a non-exocytotic carrier-mediated exchange mechanism involving 5-HT transporters. (+)-Norfenfluramine is a potent 5-HT sub(2B) and 5-HT sub(2C) receptor agonist. The former activity may increase the risk of developing valvular heart disease (VHD), whereas the latter activity is implicated in the anorectic effect of systemic fenfluramine. Anorectic agents that increase the risk of developing primary pulmonary hypertension (PPH) share the common property of being 5-HT transporter substrates. However, these drugs vary considerably in their propensity to increase the risk of PPH. In this regard, neither trazodone nor mCPP is associated with PPH. Similarly, although some 5-HT substrates can deplete brain 5-HT (fenfluramine), others do not (mCPP). In addition to the established indication of obesity, 5-HT releasers may be helpful in treating psychiatric problems such as drug and alcohol dependence, depression and premenstrual syndrome. Viewed collectively, it seems possible to develop new medications that selectively release 5-HT without the adverse effects of PPH, VHD or neurotoxicity. Such agents may have utility in treating a variety of psychiatric disorders. JF - Pharmacology Biochemistry and Behavior AU - Rothman, R B AU - Baumann, M H AD - Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, P.O. Box 5180, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, rrothman@intra.nida.nih.gov Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 825 EP - 836 VL - 71 IS - 4 SN - 0091-3057, 0091-3057 KW - m-Chlorophenylpiperazine KW - man KW - serotonin-releasing agents KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - N3 11104:Mammals (except primates) KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18411408?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacology+Biochemistry+and+Behavior&rft.atitle=Serotonin+releasing+agents%3A+Neurochemical%2C+therapeutic+and+adverse+effects&rft.au=Rothman%2C+R+B%3BBaumann%2C+M+H&rft.aulast=Rothman&rft.aufirst=R&rft.date=2002-04-01&rft.volume=71&rft.issue=4&rft.spage=825&rft.isbn=&rft.btitle=&rft.title=Pharmacology+Biochemistry+and+Behavior&rft.issn=00913057&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special issue: Serotonin: Pharmacology, Biochemistry, and Behavior. N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Induction of Protective Immunity by Synthetic Vibrio cholerae Hexasaccharide Derived from V. cholerae O1 Ogawa Lipopolysaccharide Bound to a Protein Carrier AN - 18410826; 5394467 AB - Synthetic antigens that mimic the terminal hexasaccharide epitope of the O-specific polysaccharide of Vibrio cholerae O1, serotype Ogawa, were conjugated to bovine serum albumin (BSA). Conjugates with carbohydrate-to-carrier molar ratios of 15.5: 1, 9.2: 1, and 4.6: 1 were tested for immunogenicity and efficacy in mice. The role of preimmunity to BSA and the use of adjuvant in the generation of the serologic response to the O-specific polysaccharide and protection against virulent V. cholerae was examined. Preimmunity to BSA did not affect the anti-Ogawa titers but seemed to enhance the protective capacity of antiserum. All 3 conjugates were immunogenic, but adjuvant was effective at inducing higher and earlier antibody responses. In tertiary serum samples, a correlation was found between vibriocidal activity and protection. The protective capacity of antiserum was evident in serum from mice immunized with all conjugates, but it was highest in the groups that received the conjugate with the lowest level of substitution. Further studies are required to increase understanding of the reason for differential protection. JF - Journal of Infectious Diseases AU - Chernyak, A AU - Kondo, S AU - Wade, T K AU - Meeks, MD AU - Alzari, P M AU - Fournier, M AU - Taylor, R K AU - Kovac, P AU - Wade, W F AD - Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 950 EP - 962 VL - 185 IS - 7 SN - 0022-1899, 0022-1899 KW - carrier proteins KW - efficacy KW - hexasaccharides KW - immunogenicity KW - lipopolysaccharides KW - mice KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - F 06807:Active immunization KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18410826?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Induction+of+Protective+Immunity+by+Synthetic+Vibrio+cholerae+Hexasaccharide+Derived+from+V.+cholerae+O1+Ogawa+Lipopolysaccharide+Bound+to+a+Protein+Carrier&rft.au=Chernyak%2C+A%3BKondo%2C+S%3BWade%2C+T+K%3BMeeks%2C+MD%3BAlzari%2C+P+M%3BFournier%2C+M%3BTaylor%2C+R+K%3BKovac%2C+P%3BWade%2C+W+F&rft.aulast=Chernyak&rft.aufirst=A&rft.date=2002-04-01&rft.volume=185&rft.issue=7&rft.spage=950&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Production, recovery and immunogenicity of the protective antigen from a recombinant strain of Bacillus anthracis AN - 18396418; 5375568 AB - The protective antigen (PA) is one of the three components of the anthrax toxin. It is a secreted nontoxic protein with a molecular weight of 83 kDa and is the major component of the currently licensed human vaccine for anthrax. Due to limitations found in the existing vaccine formulation, it has been proposed that genetically modified PA may be more effective as a vaccine. The expression and the stability of two recombinant PA (rPA) variants, PA-SNKE- Delta FF-E308D and PA-N657A, were studied. These proteins were expressed in the nonsporogenic avirulent strain BH445. Initial results indicated that PA-SNKE- Delta FF-E308D, which lacks two proteolysis-sensitive sites, is more stable than PA-N657A. Process development was conducted to establish an efficient production and purification process for PA-SNKE- Delta FF-E308D. pH, media composition, growth strategy and protease inhibitors composition were analyzed. The production process chosen was based on batch growth of B. anthracis using tryptone and yeast extract as the only source of carbon, pH control at 7.5, and antifoam 289. Optimal harvest time was 14-18 h after inoculation, and EDTA (5 mM) was added upon harvest for proteolysis control. Recovery of the rPA was performed by expanded-bed adsorption (EBA) on a hydrophobic interaction chromatography (HIC) resin, eliminating the need for centrifugation, microfiltration and diafiltration. The EBA step was followed by ion exchange and gel filtration. rPA yields before and after purification were 130 and 90 mg/l, respectively. The purified rPA, without further treatment, treated with small amounts of formalin or adsorbed on alum, induced, high levels of IgG anti-PA with neutralization activities. JF - Journal of Industrial Microbiology & Biotechnology AU - Ramirez, D M AU - Leppla, SH AU - Schneerson, R AU - Shiloach, J AD - Biotechnology Unit, LCDB, NIDDK, National Institutes of Health (NIH), Bethesda, MD 20892, USA Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 232 EP - 238 VL - 28 IS - 4 SN - 1367-5435, 1367-5435 KW - protective antigen KW - Biotechnology and Bioengineering Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Agricultural and Environmental Biotechnology Abstracts KW - W2 32365:Vaccines KW - A 01099:Bacteria and fungi KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18396418?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Industrial+Microbiology+%26+Biotechnology&rft.atitle=Production%2C+recovery+and+immunogenicity+of+the+protective+antigen+from+a+recombinant+strain+of+Bacillus+anthracis&rft.au=Ramirez%2C+D+M%3BLeppla%2C+SH%3BSchneerson%2C+R%3BShiloach%2C+J&rft.aulast=Ramirez&rft.aufirst=D&rft.date=2002-04-01&rft.volume=28&rft.issue=4&rft.spage=232&rft.isbn=&rft.btitle=&rft.title=Journal+of+Industrial+Microbiology+%26+Biotechnology&rft.issn=13675435&rft_id=info:doi/10.1038%2Fsj%2Fjim%2F7000239 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1038/sj/jim/7000239 ER - TY - JOUR T1 - Over 1000 genes are involved in the DNA damage response of Escherichia coli AN - 18391081; 5380615 AB - Changes in gene expression after treatment of Escherichia coli cultures with mitomycin C were assessed using gene array technology. Unexpectedly, a large number of genes (nearly 30% of all genes) displayed significant changes in their expression level. Analysis and classification of expression profiles of the corresponding genes allowed us to assign this large number of genes into one or two dozen small clusters of genes with similar expression profiles. This assignment allowed us to describe systematically the changes in the level of gene expression in response to DNA damage. Among the damage-induced genes, more than 100 are novel. From those genes involved in DNA metabolism that have not previously been shown to be induced by DNA damage, the mutS gene involved in mismatch repair is especially noteworthy. In addition to the SOS response, we observed the induction of other stress response pathways, such as those of oxidative stress and osmotic protection. Among the genes that are downregulated in response to DNA damage are numerous protein biosynthesis genes. Analysis of the gene expression data highlighted the essential involvement of sigma super(s) -regulated genes and the general stress response network in the response to DNA damage. JF - Molecular Microbiology AU - Khil, P P AU - Camerini-Otero, R D AD - Genetics and Biochemistry Branch, NIDDK, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA., camerini@ncifcrf.gov Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 89 EP - 105 PB - Blackwell Science Ltd VL - 44 IS - 1 SN - 0950-382X, 0950-382X KW - mutS gene KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - J 02725:DNA KW - N 14652:DNA repair UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18391081?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Over+1000+genes+are+involved+in+the+DNA+damage+response+of+Escherichia+coli&rft.au=Khil%2C+P+P%3BCamerini-Otero%2C+R+D&rft.aulast=Khil&rft.aufirst=P&rft.date=2002-04-01&rft.volume=44&rft.issue=1&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2002.02878.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1046/j.1365-2958.2002.02878.x ER - TY - JOUR T1 - Effects of Pyrazinamide on Fatty Acid Synthesis by Whole Mycobacterial Cells and Purified Fatty Acid Synthase I AN - 18381596; 5348741 AB - The effects of low extracellular pH and intracellular accumulation of weak organic acids were compared with respect to fatty acid synthesis by whole cells of Mycobacterium tuberculosis and Mycobacterium smegmatis. The profile of fatty acids synthesized during exposure to benzoic, nicotinic, or pyrazinoic acids, as well as that observed during intracellular hydrolysis of the corresponding amides, was not a direct consequence of modulation of fatty acid synthesis by these compounds but reflected the response to inorganic acid stress. Analysis of fatty acid synthesis in crude mycobacterial cell extracts demonstrated that pyrazinoic acid failed to directly modulate the fatty acid synthase activity catalyzed by fatty acid synthase I (FAS-I). However, fatty acid synthesis was irreversibly inhibited by 5-chloro-pyrazinamide in a time- dependent fashion. Moreover, we demonstrate that pyrazinoic acid does not inhibit purified mycobacterial FAS-I, suggesting that this enzyme is not the immediate target of pyrazinamide. JF - Journal of Bacteriology AU - Boshoff, H I AU - Mizrahi, V AU - Barry, CE III AD - Tuberculosis Research Section, NIAID, Twinbrook II, Room 239, 12441 Parklawn Dr., Rockville, MD 20852., clifton_barry@nih.gov Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 2167 EP - 2172 VL - 184 IS - 8 SN - 0021-9193, 0021-9193 KW - pyrazinamide KW - pyrazinoic acid KW - Microbiology Abstracts B: Bacteriology KW - J 02731:Lipids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18381596?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Effects+of+Pyrazinamide+on+Fatty+Acid+Synthesis+by+Whole+Mycobacterial+Cells+and+Purified+Fatty+Acid+Synthase+I&rft.au=Boshoff%2C+H+I%3BMizrahi%2C+V%3BBarry%2C+CE+III&rft.aulast=Boshoff&rft.aufirst=H&rft.date=2002-04-01&rft.volume=184&rft.issue=8&rft.spage=2167&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.184.8.2167-2172.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JB.184.8.2167-2172.2002 ER - TY - JOUR T1 - Lung Cancer and Indoor Exposure to Coal and Biomass in Rural China AN - 18326674; 5375863 AB - Incomplete combustion of coal in homes has been linked with lung cancer in China. We report on a lung cancer case-control study in a rural area of China, where many residents live in underground dwellings and burn coal and unprocessed biomass (crop residues, wood, sticks, and twigs) for heating and cooking. We interviewed 846 patients with lung cancer (626 men, 220 women; aged 30 to 75 years) diagnosed between 1994 and 1998, and 1740 population-based controls. The odds ratio for lung cancer associated with coal use compared with that for biomass in the house of longest residence was 1.29 (95% confidence interval, 1.03 to 1.61), adjusted for smoking and socioeconomic status. The risk for lung cancer increased relative to the percentage of time that coal was used over the past 30 years (P = 0.02). Our findings suggest that coal may contribute to the risk of lung cancer in this rural area of China. JF - Journal of Occupational and Environmental Medicine AU - Kleinerman, R A AU - Wang, Zuoyuan AU - Wang, Longde AU - Metayer, C AU - Zhang, Shouzhi AU - Brenner, A V AU - Zhang, Shurong AU - Xia, Ying AU - Shang, Bing AU - Lubin, J H AD - Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, EPS 7044, MSC 7238, Bethesda, MD 20892, USA, kleinerr@mail.nih.gov Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 338 EP - 344 VL - 44 IS - 4 SN - 1076-2752, 1076-2752 KW - man KW - epidemiology KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts; Pollution Abstracts KW - Combustion products KW - Socioeconomics KW - Coal KW - Lung cancer KW - Houses KW - Biomass KW - Buildings KW - Air pollution KW - Socio-economic aspects KW - Residential areas KW - China, People's Rep. KW - X 24156:Environmental impact KW - R2 23060:Medical and environmental health KW - H 12000:Epidemiology and Public Health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18326674?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Occupational+and+Environmental+Medicine&rft.atitle=Lung+Cancer+and+Indoor+Exposure+to+Coal+and+Biomass+in+Rural+China&rft.au=Kleinerman%2C+R+A%3BWang%2C+Zuoyuan%3BWang%2C+Longde%3BMetayer%2C+C%3BZhang%2C+Shouzhi%3BBrenner%2C+A+V%3BZhang%2C+Shurong%3BXia%2C+Ying%3BShang%2C+Bing%3BLubin%2C+J+H&rft.aulast=Kleinerman&rft.aufirst=R&rft.date=2002-04-01&rft.volume=44&rft.issue=4&rft.spage=338&rft.isbn=&rft.btitle=&rft.title=Journal+of+Occupational+and+Environmental+Medicine&rft.issn=10762752&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - China, People's Rep.; Biomass; Coal; Socioeconomics; Combustion products; Residential areas; Lung cancer; Air pollution; Houses; Buildings; Socio-economic aspects ER - TY - JOUR T1 - Central mechanisms of motor skill learning AN - 18322039; 5376203 AB - Recent studies have shown that frontoparietal cortices and interconnecting regions in the basal ganglia and the cerebellum are related to motor skill learning. We propose that motor skill learning occurs independently and in different coordinates in two sets of loop circuits: cortex-basal ganglia and cortex-cerebellum. This architecture accounts for the seemingly diverse features of motor learning. JF - Current Opinion in Neurobiology AU - Hikosaka, Okihide AU - Nakamura, Kae AU - Sakai, Katsuyuki AU - Nakahara, Hiroyuki AD - Laboratory of Sensorimotor Research, National Eye Institute, National Institute of Health, Building 49, Room 2A50, Bethesda, MD 20892, USA, oh@lsr.nei.nih.gov Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 217 EP - 222 VL - 12 IS - 2 SN - 0959-4388, 0959-4388 KW - CSA Neurosciences Abstracts; Physical Education Index KW - Motor learning KW - Cortex KW - Reviews KW - Cerebellum KW - Brain KW - Motor skill learning KW - Basal ganglia KW - N3 11046:Memory and learning KW - PE 080:Motor Learning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18322039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Opinion+in+Neurobiology&rft.atitle=Central+mechanisms+of+motor+skill+learning&rft.au=Hikosaka%2C+Okihide%3BNakamura%2C+Kae%3BSakai%2C+Katsuyuki%3BNakahara%2C+Hiroyuki&rft.aulast=Hikosaka&rft.aufirst=Okihide&rft.date=2002-04-01&rft.volume=12&rft.issue=2&rft.spage=217&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Neurobiology&rft.issn=09594388&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Motor learning; Brain; Motor skill learning; Cortex; Basal ganglia; Cerebellum; Reviews ER - TY - JOUR T1 - An Overview of Toxicogenomics AN - 18309469; 5357965 AB - Toxicogenomics is a rapidly developing discipline that promises to aid scientists in understanding the molecular and cellular effects of chemicals in biological systems. This field encompasses global assessment of biological effects using technologies such as DNA microarrays or high throughput NMR and protein expression analysis. This review provides an overview of advancing multiple approaches (genomic, proteomic, metabonomic) that may extend our understanding of toxicology and highlights the importance of coupling such approaches with classical toxicity studies. JF - Current Issues in Molecular Biology AU - Hamadeh, H K AU - Amin, R P AU - Paules, R S AU - Afshari, CA AD - National Institute of Environmental Health Sciences, Intramural Microarray Center, PO Box 12233 MD2-04, 111 Alexander Drive Bldg. 101, Research Triangle Park, NC 27709, USA, afshari@niehs.nih.gov Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 45 EP - 56 VL - 4 IS - 2 SN - 1467-3037, 1467-3037 KW - DNA microarrays KW - Toxicogenomics KW - genomics KW - metabonomic KW - proteomics KW - toxicogenomics KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Gene expression KW - Genomes KW - Reviews KW - Metabolic pathways KW - Proteins KW - N.M.R. KW - Toxicology KW - N 14100:Reviews KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18309469?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Issues+in+Molecular+Biology&rft.atitle=An+Overview+of+Toxicogenomics&rft.au=Hamadeh%2C+H+K%3BAmin%2C+R+P%3BPaules%2C+R+S%3BAfshari%2C+CA&rft.aulast=Hamadeh&rft.aufirst=H&rft.date=2002-04-01&rft.volume=4&rft.issue=2&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Current+Issues+in+Molecular+Biology&rft.issn=14673037&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Toxicology; Reviews; Proteins; N.M.R.; Metabolic pathways; Genomes; Gene expression ER - TY - JOUR T1 - Regulation of Purine Hydroxylase and Xanthine Dehydrogenase from Clostridium purinolyticum in Response to Purines, Selenium, and Molybdenum AN - 18288278; 5339589 AB - The discovery that two distinct enzyme catalysts, purine hydroxylase (PH) and xanthine dehydrogenase (XDH), are required for the overall conversion of hypoxanthine to uric acid by Clostridium purinolyticum was unexpected. In this reaction sequence, hypoxanthine is hydroxylated to xanthine by PH and then xanthine is hydroxylated to uric acid by XDH. PH and XDH, which contain a labile selenium cofactor in addition to a molybdenum cofactor, flavin adenine dinucleotide, and FeS centers, were purified and partially characterized as reported previously. In the present study, the activities of these two enzymes were measured in cells grown in media containing various concentrations of selenite, molybdate, and various purine substrates. The levels of PH protein in extracts were determined by immunoblot assay. The amount of PH protein, as well as the specific activities of PH and XDH, increased when either selenite or molybdate was added to the culture medium. PH levels were highest in the cells cultured in the presence of either adenine or purine. XDH activity increased dramatically in cells grown with either xanthine or uric acid. The apparent increases in protein levels and activities of PH and XDH in response to selenium, molybdenum, and purine substrates demonstrate that these enzymes are tightly regulated in response to these nutrients. JF - Journal of Bacteriology AU - Self, W T AD - Laboratory of Biochemistry, NHLBI, NIH, 50 South Dr., Room 2126, MSC 8012, Bethesda, MD 20892-8012., selfw@nhlbi.nih.gov Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 2039 EP - 2044 VL - 184 IS - 7 SN - 0021-9193, 0021-9193 KW - hypoxanthine KW - purine hydroxylase KW - purines KW - xanthine KW - Microbiology Abstracts B: Bacteriology KW - Selenium KW - Xanthine dehydrogenase KW - Molybdenum KW - Clostridium purinolyticum KW - Uric acid KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18288278?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Regulation+of+Purine+Hydroxylase+and+Xanthine+Dehydrogenase+from+Clostridium+purinolyticum+in+Response+to+Purines%2C+Selenium%2C+and+Molybdenum&rft.au=Self%2C+W+T&rft.aulast=Self&rft.aufirst=W&rft.date=2002-04-01&rft.volume=184&rft.issue=7&rft.spage=2039&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.184.7.2039-2044.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Clostridium purinolyticum; Uric acid; Xanthine dehydrogenase; Selenium; Molybdenum DO - http://dx.doi.org/10.1128/JB.184.7.2039-2044.2002 ER - TY - JOUR T1 - Selenium Is Mobilized In Vivo from Free Selenocysteine and Is Incorporated Specifically into Formate Dehydrogenase H and tRNA Nucleosides AN - 18279329; 5339591 AB - Selenophosphate synthetase (SPS), the selD gene product from Escherichia coli, catalyzes the biosynthesis of monoselenophosphate, AMP, and orthophosphate in a 1:1:1 ratio from selenide and ATP. It was recently demonstrated that selenium delivered from selenocysteine by an E. coli NifS- like protein could replace free selenide in the in vitro SPS assay for selenophosphate formation (G. M. Lacourciere, H. Mihara, T. Kurihara, N. Esaki, and T. C. Stadtman, J. Biol. Chem. 275:23769-23773, 2000). During growth of E. coli in the presence of 0.1 mu M super(75)SeO sub(3) super(2-) and increasing amounts of L-selenocysteine, a concomitant decrease in super(75)Se incorporation into formate dehydrogenase H and nucleosides of bulk tRNA was observed. This is consistent with the mobilization of selenium from L-selenocysteine in vivo and its use in selenophosphate formation. The ability of E. coli to utilize selenocysteine as a selenium source for selenophosphate biosynthesis in vivo supports the participation of the NifS-like proteins in selenium metabolism. JF - Journal of Bacteriology AU - Lacourciere, G M AD - Laboratory of Biochemistry NHLBI, NIH 50 South Drive, Room 2126, Bethesda, MD 20892., lacourcg@nhlbi.nih.gov Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 1940 EP - 1946 VL - 184 IS - 7 SN - 0021-9193, 0021-9193 KW - selD gene KW - selenocysteine KW - selenophosphate KW - selenophosphate synthase KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - tRNA KW - Escherichia coli KW - Formate dehydrogenase KW - J 02726:RNA and ribosomes KW - N 14413:Biological properties, including effects of antibiotics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18279329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Selenium+Is+Mobilized+In+Vivo+from+Free+Selenocysteine+and+Is+Incorporated+Specifically+into+Formate+Dehydrogenase+H+and+tRNA+Nucleosides&rft.au=Lacourciere%2C+G+M&rft.aulast=Lacourciere&rft.aufirst=G&rft.date=2002-04-01&rft.volume=184&rft.issue=7&rft.spage=1940&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.184.7.1940-1946.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Formate dehydrogenase; tRNA DO - http://dx.doi.org/10.1128/JB.184.7.1940-1946.2002 ER - TY - JOUR T1 - Feasibility of Assessing the Carcinogenicity of Neutrons among Neutron Therapy Patients AN - 17862919; 5973941 AB - Nuclear workers, oil well loggers, astronauts, air flight crews, and frequent fliers can be exposed to low doses of neutrons, but the long-term human health consequences of neutron exposure are unknown. While few of these exposed populations are suitable for studying the effects of neutron exposure, patients treated with neutron-beam therapy might be a source of information. To assess the feasibility of conducting a multi-center international study of the late effects of neutron therapy, we surveyed 23 cancer centers that had used neutron beam therapy. For the 17 responding institutions, only 25% of the patients treated with neutrons (2,855 of 11,191) were alive more than 2 years after treatment. In a two-center U.S. pilot study of 484 neutron-treated cancer patients, we assessed the feasibility of obtaining radiotherapy records, cancer incidence and other follow-up data, and of estimating patient organ doses. Patients were treated with 42 MeV neutrons between 1972 and 1989. Applying a clinical equivalence factor of 3.2 for neutrons, total average organ doses outside the treatment beam ranged from 0.14 to 0.29 Gy for thyroid, 0.40 to 2.50 Gy for breast, 0.63 to 2.35 Gy for kidney, and 1.12 to 1.76 Gy for active bone marrow depending upon the primary cancer treatment site. We successfully traced 97% of the patients, but we found that patient survival was poor and that chemotherapy was not confirmable in a quarter of the patients. Based on our findings from the international survey and the feasibility study, we conclude that a large investigation could detect a fivefold or higher leukemia risk, but would be inadequate to evaluate the risk of solid cancers with long latent periods and therefore would likely not be informative with respect to neutron-related cancer risk in humans. JF - Radiation Research AU - Sigurdson, A J AU - Stovall, M AU - Kleinerman, R A AU - Maor, M H AU - Taylor, ME AU - Boice, J D AU - Ron, E AD - Radiation Epidemiology Branch, National Cancer Institute, 6120 Executive Boulevard, Bethesda, Maryland, 20892-7238 Y1 - 2002/04// PY - 2002 DA - Apr 2002 SP - 483 EP - 489 PB - Radiation Research Society VL - 157 IS - 4 SN - 0033-7587, 0033-7587 KW - Toxicology Abstracts KW - Breast KW - Thyroid KW - Bone marrow KW - Radiotherapy KW - Cancer KW - Flight KW - Leukemia KW - Carcinogenicity KW - Neutron radiation KW - Kidney KW - Latent period KW - Occupational exposure KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17862919?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+Research&rft.atitle=Feasibility+of+Assessing+the+Carcinogenicity+of+Neutrons+among+Neutron+Therapy+Patients&rft.au=Sigurdson%2C+A+J%3BStovall%2C+M%3BKleinerman%2C+R+A%3BMaor%2C+M+H%3BTaylor%2C+ME%3BBoice%2C+J+D%3BRon%2C+E&rft.aulast=Sigurdson&rft.aufirst=A&rft.date=2002-04-01&rft.volume=157&rft.issue=4&rft.spage=483&rft.isbn=&rft.btitle=&rft.title=Radiation+Research&rft.issn=00337587&rft_id=info:doi/10.1043%2F0033-7587%282002%291572.0.CO%3B2 L2 - http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0033-7587&volume=157&page=483 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Neutron radiation; Cancer; Occupational exposure; Carcinogenicity; Bone marrow; Kidney; Latent period; Leukemia; Thyroid; Flight; Breast; Radiotherapy DO - http://dx.doi.org/10.1043/0033-7587(2002)157<0483:FOATCO>2.0.CO;2 ER - TY - JOUR T1 - Lack of persistent changes in the dopaminergic system of rats withdrawn from methamphetamine self-administration. AN - 71578828; 11937093 AB - A continuing challenge for studies in the neurobiology of drug abuse is to identify and characterize long-lived neuroadaptations that can trigger craving and relapse. We previously reported that rats that had actively self-administered methamphetamine for 5 weeks and were then withdrawn from methamphetamine for 24 h showed marked decreases in somatodendritic dopamine D(2) autoreceptor levels in the ventral tegmental area and median and dorsal part of the substantia nigra zona compacta with a corresponding down-regulation of dopamine D(1) receptors in the shell of the nucleus accumbens. The purpose of the present study was to determine whether neuroadaptive changes in dopamine receptors or transporters in the brains of rats withdrawn for 24 h from chronic methamphetamine self-administration are persistent changes that can be demonstrated long after withdrawal. A "yoked" procedure was used in which rats were tested simultaneously in groups of three, with only one rat actively self-administering methamphetamine while the other two received yoked injections of either methamphetamine or saline. In vitro quantitative autoradiography was used to determine densities of dopamine uptake sites and dopamine D(1) and D(2) receptors in different brain regions following 7- and 30-day periods of withdrawal from chronic methamphetamine self-administration. No changes in dopamine transporter and dopamine receptor numbers were detected in any brain region examined in rats self-administering methamphetamine compared with littermates receiving yoked infusions of either methamphetamine or saline. Thus, neuroadaptive changes in densities of dopamine receptors or transporters in certain brain areas may contribute to the reinforcing effects of methamphetamine during the acquisition and maintenance phases of self-administration, but do not appear to contribute to the long-lasting neuroadaptive effects of chronic methamphetamine self-administration, which may trigger craving and relapse. JF - European journal of pharmacology AU - Stefanski, Roman AU - Lee, Sun-Hee AU - Yasar, Sevil AU - Cadet, Jean L AU - Goldberg, Steven R AD - Preclinical Pharmacology Section, National Institutes of Health, National Institute on Drug Abuse, Intramural Research Program, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2002/03/29/ PY - 2002 DA - 2002 Mar 29 SP - 59 EP - 68 VL - 439 IS - 1-3 SN - 0014-2999, 0014-2999 KW - Receptors, Dopamine KW - 0 KW - Methamphetamine KW - 44RAL3456C KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Index Medicus KW - Rats KW - Animals KW - Ventral Tegmental Area -- enzymology KW - Tyrosine 3-Monooxygenase -- metabolism KW - Rats, Sprague-Dawley KW - Self Administration -- methods KW - Ventral Tegmental Area -- drug effects KW - Immunohistochemistry KW - Male KW - Receptors, Dopamine -- drug effects KW - Receptors, Dopamine -- physiology KW - Substance Withdrawal Syndrome -- physiopathology KW - Methamphetamine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71578828?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+pharmacology&rft.atitle=Lack+of+persistent+changes+in+the+dopaminergic+system+of+rats+withdrawn+from+methamphetamine+self-administration.&rft.au=Stefanski%2C+Roman%3BLee%2C+Sun-Hee%3BYasar%2C+Sevil%3BCadet%2C+Jean+L%3BGoldberg%2C+Steven+R&rft.aulast=Stefanski&rft.aufirst=Roman&rft.date=2002-03-29&rft.volume=439&rft.issue=1-3&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-08 N1 - Date created - 2002-04-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biochemical and biological characterization of a dodecameric CD4-Ig fusion protein: implications for therapeutic and vaccine strategies. AN - 71542966; 11805109 AB - Drug toxicities associated with HAART lend urgency to the development of new anti-HIV therapies. Inhibition of viral replication at the entry stage of the viral life cycle is an attractive strategy because it prevents de novo infection. Soluble CD4 (sCD4), the first drug in this class, failed to suppress viral replication in vivo. At least three factors contributed to this failure: sCD4 demonstrated poor neutralizing activity against most primary isolates of HIV in vitro; it demonstrated an intrinsic capacity to enhance viral replication at low concentrations; and it exhibited a relatively short half-life in vivo. Many anti-gp120 monoclonal antibodies, including neutralizing monoclonal antibodies also enhance viral replication at suboptimal concentrations. Advances in our understanding of the events leading up to viral entry suggest strategies by which this activity can be diminished. We hypothesized that by constructing a sCD4-based molecule that is large, binds multiple gp120s simultaneously, and is highly avid toward gp120, we could remove its capacity to enhance viral entry. Here we describe the construction of a polymeric CD4-IgG1 fusion protein. The hydrodynamic radius of this molecule is approximately 12 nm. It can bind at least 10 gp120 subunits with binding kinetics that suggest a highly avid interaction toward virion-associated envelope. This protein does not enhance viral replication at suboptimal concentrations. These observations may aid in the design of new therapeutics and vaccines. JF - The Journal of biological chemistry AU - Arthos, James AU - Cicala, Claudia AU - Steenbeke, Tavis D AU - Chun, Tae-Wook AU - Dela Cruz, Charles AU - Hanback, Douglas B AU - Khazanie, Prateeti AU - Nam, Daniel AU - Schuck, Peter AU - Selig, Sara M AU - Van Ryk, Donald AU - Chaikin, Margery A AU - Fauci, Anthony S AD - Laboratory of Immunoregulation, NIAID, and the Molecular Interactions Resource Division of Bioengineering and Physical Science, National Institutes of Health, Bethesda, Maryland 20892, USA. jarthos@nih.gov Y1 - 2002/03/29/ PY - 2002 DA - 2002 Mar 29 SP - 11456 EP - 11464 VL - 277 IS - 13 SN - 0021-9258, 0021-9258 KW - AIDS Vaccines KW - 0 KW - Antibodies, Monoclonal KW - Biopolymers KW - CD4 Immunoadhesins KW - HIV Envelope Protein gp120 KW - Index Medicus KW - Coculture Techniques KW - HIV-1 -- immunology KW - HIV Envelope Protein gp120 -- immunology KW - Chromatography, Gel KW - Cells, Cultured KW - Humans KW - CD4-Positive T-Lymphocytes -- virology KW - Neutralization Tests KW - Membrane Fusion -- immunology KW - HIV-1 -- physiology KW - Virus Replication -- immunology KW - Antibodies, Monoclonal -- immunology KW - AIDS Vaccines -- metabolism KW - AIDS Vaccines -- therapeutic use KW - AIDS Vaccines -- immunology KW - CD4 Immunoadhesins -- immunology KW - CD4 Immunoadhesins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71542966?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Biochemical+and+biological+characterization+of+a+dodecameric+CD4-Ig+fusion+protein%3A+implications+for+therapeutic+and+vaccine+strategies.&rft.au=Arthos%2C+James%3BCicala%2C+Claudia%3BSteenbeke%2C+Tavis+D%3BChun%2C+Tae-Wook%3BDela+Cruz%2C+Charles%3BHanback%2C+Douglas+B%3BKhazanie%2C+Prateeti%3BNam%2C+Daniel%3BSchuck%2C+Peter%3BSelig%2C+Sara+M%3BVan+Ryk%2C+Donald%3BChaikin%2C+Margery+A%3BFauci%2C+Anthony+S&rft.aulast=Arthos&rft.aufirst=James&rft.date=2002-03-29&rft.volume=277&rft.issue=13&rft.spage=11456&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-10 N1 - Date created - 2002-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - AP-1 transrepressing retinoic acid does not deplete coactivators or AP-1 monomers but may target specific Jun or Fos containing dimers. AN - 71599327; 11948401 AB - Retinoic acid (RA) inhibits tumor promotion in many models in vivo and in vitro, among them mouse epidermal JB6 cells. RA treatment suppresses 12-O-tetradecanoylphorbol-13-acetate (TPA) induced AP-1 activity, an activity that is required for transformation of JB6 P+ cells. The molecular mechanism of AP-1 transrepression by retinoids is unclear, especially as related to inhibition of transformation. Overexpression of AP-1 components did not rescue TPA induced AP-1 activation nor did a GST pull down experiment implicate direct binding, thus rendering unlikely both a Jun/Fos-RA-RAR direct interaction and a Jun/Fos sequestration mechanism. Overexpression of p300, SRC-1 or pCAF did not abrogate AP-1 suppression by RA, thus arguing against coactivator competition. Overexpression of the corepressor silencing mediator for retinoic acid and thyroid hormone receptors (SMRT) suppressed AP-1 activity. However, SMRT but not RA inhibited cJun transactivation, suggesting SMRT does not mediate RA transrepression. RA treatment also did not block TPA induced ERK phosphorylation, Jun/Fos family protein expression except for cFos, or DNA binding of the AP-1 complex. The transcriptional activities of full-length JunB and full-length Fra-1, but not the transactivation domain fusions, were increased by TPA treatment and suppressed by RA. Since these full-length fusions have bzip domains, the results suggest that JunB and/or Fra-1-containing dimers may constitute one target of RA for transrepression of AP-1. JF - Oncogene AU - Suzukawa, Kazumi AU - Colburn, Nancy H AD - Gene Regulation Section, Basic Research Laboratory, National Cancer Institute at Frederick, Frederick, Maryland 21702-1201, USA. Y1 - 2002/03/28/ PY - 2002 DA - 2002 Mar 28 SP - 2181 EP - 2190 VL - 21 IS - 14 SN - 0950-9232, 0950-9232 KW - DNA-Binding Proteins KW - 0 KW - Fos-Related Antigen-2 KW - Fosl2 protein, mouse KW - Ncor2 protein, mouse KW - Nuclear Receptor Co-Repressor 2 KW - Proto-Oncogene Proteins c-fos KW - Proto-Oncogene Proteins c-jun KW - Repressor Proteins KW - Transcription Factor AP-1 KW - Transcription Factors KW - fos-related antigen 1 KW - Tretinoin KW - 5688UTC01R KW - DNA KW - 9007-49-2 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Transcription Factors -- metabolism KW - Dose-Response Relationship, Drug KW - Mitogen-Activated Protein Kinases -- metabolism KW - DNA -- metabolism KW - Dimerization KW - Repressor Proteins -- metabolism KW - DNA-Binding Proteins -- genetics KW - Mice KW - Repressor Proteins -- genetics KW - Protein Binding -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Line KW - DNA-Binding Proteins -- metabolism KW - Tretinoin -- pharmacology KW - Proto-Oncogene Proteins c-fos -- metabolism KW - Transcription Factor AP-1 -- metabolism KW - Proto-Oncogene Proteins c-fos -- genetics KW - Proto-Oncogene Proteins c-jun -- genetics KW - Proto-Oncogene Proteins c-jun -- metabolism KW - Gene Expression Regulation, Neoplastic -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71599327?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=AP-1+transrepressing+retinoic+acid+does+not+deplete+coactivators+or+AP-1+monomers+but+may+target+specific+Jun+or+Fos+containing+dimers.&rft.au=Suzukawa%2C+Kazumi%3BColburn%2C+Nancy+H&rft.aulast=Suzukawa&rft.aufirst=Kazumi&rft.date=2002-03-28&rft.volume=21&rft.issue=14&rft.spage=2181&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-30 N1 - Date created - 2002-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mitogenic synergy through multilevel convergence of hepatocyte growth factor and interleukin-4 signaling pathways. AN - 71595210; 11948403 AB - Hepatocyte growth factor (HGF) regulates various physiological and developmental processes in concert with other growth factors, cytokines and hormones. We examined interactions between cell signaling events elicited by HGF and the cytokine interleukin (IL)-4, in the IL-3-dependent murine myeloid cell line 32D transfected with the human HGF receptor, c-Met. HGF was a potent mitogen in these cells, and prevented apoptosis in response to IL-3 withdrawal. IL-4 showed modest anti-apoptotic activity, but no significant mitogenic activity. IL-4 synergistically enhanced HGF-stimulated DNA synthesis, whereas only additive prevention of apoptosis was observed. IL-4 did not enhance HGF-dependent tyrosine phosphorylation of c-Met or Shc. In contrast, HGF-stimulated activation of MAP kinases was enhanced by IL-4, suggesting that the IL-4 and HGF signaling pathways converge upstream of these events. Although phosphatidylinositol 3-kinase (PI3K) inhibitors diminished HGF-induced mitogenesis, anti-apoptosis, and MAP kinase activation, IL-4 enhanced HGF signaling persisted even in the presence of these inhibitors. IL-4 enhancement of HGF signaling was partially blocked in 32D/c-Met cells treated with inhibitors of MEK1 or c-Src kinases, completely blocked by expression of a catalytically inactive mutant of Janus kinase 3 (Jak3), and increased in 32D/c-Met cells overexpressing STAT6. Our results suggest that the IL-4 and HGF pathways converge at multiple levels, and that IL-4-dependent Jak3 and STAT6 activities modulate signaling events independent of PI3K to enhance HGF-dependent mitogenesis in myeloid cells, and possibly other common cellular targets. JF - Oncogene AU - Day, Regina M AU - Soon, Lilian AU - Breckenridge, Diane AU - Bridges, Benjamin AU - Patel, Bharvin K R AU - Wang, Ling Mei AU - Corey, Seth J AU - Bottaro, Donald P AD - Laboratory of Cellular and Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2002/03/28/ PY - 2002 DA - 2002 Mar 28 SP - 2201 EP - 2211 VL - 21 IS - 14 SN - 0950-9232, 0950-9232 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Adaptor Proteins, Vesicular Transport KW - Interleukin-3 KW - Mitogens KW - Proteins KW - SHC1 protein, human KW - STAT6 Transcription Factor KW - Shc Signaling Adaptor Proteins KW - Shc1 protein, mouse KW - Src Homology 2 Domain-Containing, Transforming Protein 1 KW - Stat6 protein, mouse KW - Trans-Activators KW - Interleukin-4 KW - 207137-56-2 KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Proto-Oncogene Proteins c-met KW - JAK3 protein, human KW - EC 2.7.10.2 KW - Jak3 protein, mouse KW - Janus Kinase 3 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - MAP Kinase Kinase 1 KW - EC 2.7.12.2 KW - MAP2K1 protein, human KW - Map2k1 protein, mouse KW - Mitogen-Activated Protein Kinase Kinases KW - Index Medicus KW - Trans-Activators -- metabolism KW - Animals KW - Hepatocytes -- drug effects KW - Protein-Serine-Threonine Kinases -- metabolism KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Dose-Response Relationship, Drug KW - Mitogen-Activated Protein Kinases -- metabolism KW - Interleukin-3 -- pharmacology KW - Mice KW - Protein-Tyrosine Kinases -- metabolism KW - Proteins -- metabolism KW - Mitogen-Activated Protein Kinase Kinases -- metabolism KW - Proteins -- antagonists & inhibitors KW - Tumor Cells, Cultured KW - Transfection KW - Proto-Oncogene Proteins c-met -- metabolism KW - Apoptosis -- drug effects KW - Hepatocytes -- cytology KW - Drug Synergism KW - Time Factors KW - Mitogens -- pharmacology KW - Hepatocyte Growth Factor -- pharmacology KW - Signal Transduction -- drug effects KW - Interleukin-4 -- pharmacology KW - Interleukin-4 -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71595210?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Mitogenic+synergy+through+multilevel+convergence+of+hepatocyte+growth+factor+and+interleukin-4+signaling+pathways.&rft.au=Day%2C+Regina+M%3BSoon%2C+Lilian%3BBreckenridge%2C+Diane%3BBridges%2C+Benjamin%3BPatel%2C+Bharvin+K+R%3BWang%2C+Ling+Mei%3BCorey%2C+Seth+J%3BBottaro%2C+Donald+P&rft.aulast=Day&rft.aufirst=Regina&rft.date=2002-03-28&rft.volume=21&rft.issue=14&rft.spage=2201&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-30 N1 - Date created - 2002-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The association between frequencies of mitomycin C-induced sister chromatid exchange and cancer risk in arseniasis. AN - 71505346; 11888707 AB - In order to examine whether biomarkers of cytogenetic damage and susceptibility, such as spontaneous and mitomycin C-induced sister chromatid exchange (SCE) can predict cancer development, a nested case-control study was performed in a blackfoot endemic area with known high cancer risk. A cohort of 686 residents was recruited from three villages in the arseniasis area. Personal characteristics were collected and venous blood was drawn for lymphocyte culture and stored in a refrigerator. The vital status and cancer development was followed using the National Death Registry, Cancer Registry, and Blackfoot Disease Registry. The follow up period was from August 1991 to July 1997. During this 6-year-period, 55 residents developed various types of cancer. Blood culture samples from 23 of these subjects were unsuitable for spontaneous SCE experiments and 45 of these subjects were unsuitable for mitomycin C-induced SCE experiments due to improper storage. Finally, a total of 32 cancer cases had cytogenetic samples that could be analyzed. About 32 control subjects were selected from those who did not develop cancer in the study period and these subjects were matched to cases by sex, age, smoking habits, and residential area. The results showed that there was no significant difference in the frequencies of spontaneous and mitomycin C-induced SCE between the case and control groups. There was also no significant difference in the net difference of spontaneous and mitomycin C-induced SCE between the case and control groups. These results suggest that SCEs, either spontaneous or mitomycin C-induced, might not be good markers to predict cancer risk. JF - Toxicology letters AU - Liou, Saou-Hsing AU - Chen, Yeong-Hwang AU - Loh, Ching-Hui AU - Yang, Tsan AU - Wu, Trong-Neng AU - Chen, Chien-Jen AU - Hsieh, Ling-Ling AD - Department of Public Health, National Defense Medical Center, National Defense University, Nei-Hu, Taipei, Taiwan, ROC. Y1 - 2002/03/28/ PY - 2002 DA - 2002 Mar 28 SP - 237 EP - 243 VL - 129 IS - 3 SN - 0378-4274, 0378-4274 KW - Biomarkers KW - 0 KW - Water Pollutants, Chemical KW - Mitomycin KW - 50SG953SK6 KW - Arsenic KW - N712M78A8G KW - Index Medicus KW - Humans KW - Risk Assessment KW - Registries KW - Mutagenicity Tests KW - Cells, Cultured KW - Logistic Models KW - Taiwan -- epidemiology KW - Follow-Up Studies KW - Drug Synergism KW - Lymphocytes -- drug effects KW - Female KW - Male KW - Arsenic -- adverse effects KW - Water Pollutants, Chemical -- adverse effects KW - Mitomycin -- pharmacology KW - Sister Chromatid Exchange -- drug effects KW - Neoplasms -- epidemiology KW - Sister Chromatid Exchange -- genetics KW - Arsenic Poisoning -- epidemiology KW - Arsenic Poisoning -- complications KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71505346?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=The+association+between+frequencies+of+mitomycin+C-induced+sister+chromatid+exchange+and+cancer+risk+in+arseniasis.&rft.au=Liou%2C+Saou-Hsing%3BChen%2C+Yeong-Hwang%3BLoh%2C+Ching-Hui%3BYang%2C+Tsan%3BWu%2C+Trong-Neng%3BChen%2C+Chien-Jen%3BHsieh%2C+Ling-Ling&rft.aulast=Liou&rft.aufirst=Saou-Hsing&rft.date=2002-03-28&rft.volume=129&rft.issue=3&rft.spage=237&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-02 N1 - Date created - 2002-03-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A simplified and rapid method for scoring micronucleated erythrocytes in human blood AN - 18291004; 5340441 JF - Mutation Research-Genetic Toxicology and Environmental Mutagenesis AU - Shelby, MD AD - NIEHS MD EC-32, Environmental Toxicology Program, Box 12233, 27709 Research Triangle Park, NC USA Y1 - 2002/03/25/ PY - 2002 DA - 2002 Mar 25 SP - 1 PB - Elsevier Science VL - 515 IS - 1-2 SN - 1383-5718, 1383-5718 KW - man KW - Toxicology Abstracts KW - Blood KW - Erythrocytes KW - Micronuclei KW - Genotoxicity testing KW - Toxicity testing KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18291004?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.atitle=A+simplified+and+rapid+method+for+scoring+micronucleated+erythrocytes+in+human+blood&rft.au=Shelby%2C+MD&rft.aulast=Shelby&rft.aufirst=MD&rft.date=2002-03-25&rft.volume=515&rft.issue=1-2&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.issn=13835718&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Micronuclei; Toxicity testing; Genotoxicity testing; Erythrocytes; Blood ER - TY - JOUR T1 - The roles of thioredoxin in protection against oxidative stress-induced apoptosis in SH-SY5Y cells. AN - 71532496; 11751890 AB - Using models of serum deprivation and 1-methyl-4-phenylpyridinium (MPP(+)), we investigated the mechanism by which thioredoxin (Trx) exerts its antiapoptotic protection in human neuroblastoma cells (SH-SY5Y) and preconditioning-induced neuroprotection. We showed that SH-SY5Y cells are highly sensitive to oxidative stress and responsive to both extracellularly administered and preconditioning-induced Trx. Serum deprivation and MPP(+) produced an elevation in the hydroxyl radicals, malondialdehyde and 4-hydroxy-2,3-nonenal (HNE), causing the cells to undergo mitochondria-mediated apoptosis. Trx in the submicromolar range blocked the observed apoptosis via a multiphasic protection mechanism that includes the suppression of cytochrome c release (most likely via the induction of Bcl-2), the inhibition of procaspase-9 and procaspase-3 activation, and the elevated level of Mn-SOD. The reduced form of Trx suppresses the serum-free-induced hydroxyl radicals, lipid peroxidation, and apoptosis, indicating that H(2)O(2) is removed by Trx peroxidase. The participation of Trx in preconditioning-induced neuroprotection is supported by the observation that inhibition of Trx synthesis with antisense oligonucleotides or of Trx reductase drastically reduced the hormesis effect. This effect of Trx-mediated hormesis against oxidative stress-induced apoptosis is striking. It induced a 30-fold shift in LD(50) in the MPP(+)-induced neurotoxicity. JF - The Journal of biological chemistry AU - Andoh, Tsugunobu AU - Chock, P Boon AU - Chiueh, Chuang Chin AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute and the Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland 20892, USA. Y1 - 2002/03/22/ PY - 2002 DA - 2002 Mar 22 SP - 9655 EP - 9660 VL - 277 IS - 12 SN - 0021-9258, 0021-9258 KW - Culture Media, Serum-Free KW - 0 KW - Cytochrome c Group KW - Oligonucleotides, Antisense KW - Thioredoxins KW - 52500-60-4 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - CASP3 protein, human KW - EC 3.4.22.- KW - CASP9 protein, human KW - Casp3 protein, mouse KW - Casp9 protein, mouse KW - Caspase 3 KW - Caspase 9 KW - Caspases KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - HeLa Cells KW - Humans KW - Superoxide Dismutase -- metabolism KW - Oligonucleotides, Antisense -- pharmacology KW - Mice KW - Lipid Peroxidation KW - Caspases -- metabolism KW - Tumor Cells, Cultured KW - Culture Media, Serum-Free -- pharmacology KW - Cytochrome c Group -- metabolism KW - Time Factors KW - Cell Line KW - Oxidative Stress KW - Apoptosis -- drug effects KW - Thioredoxins -- metabolism KW - Mitochondria -- metabolism KW - Thioredoxins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71532496?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+roles+of+thioredoxin+in+protection+against+oxidative+stress-induced+apoptosis+in+SH-SY5Y+cells.&rft.au=Andoh%2C+Tsugunobu%3BChock%2C+P+Boon%3BChiueh%2C+Chuang+Chin&rft.aulast=Andoh&rft.aufirst=Tsugunobu&rft.date=2002-03-22&rft.volume=277&rft.issue=12&rft.spage=9655&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-29 N1 - Date created - 2002-03-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - X-ray induced mutation in Syrian hamster fetal cells. AN - 71506422; 11890930 AB - Transabdominal X-rays are a risk factor for childhood leukemia, and X-ray exposure of mouse fetuses has led to increases in both mutations and initiated tumors in offspring. However, fetal sensitivity and dose-response characteristics with regard to transplacental mutagenesis by X-rays have never been quantified. In the current experiment, pregnant Syrian hamsters at day 12 of gestation were irradiated with 300-kV X-rays. Twenty-four hours later, the fetuses were removed and their cells were allowed a 5 day expression time in culture. They were then seeded for colony formation and also for mutation selection by 6-thioguanine (6-TG). Mutation frequency was linear over the entire dose range, 10-600 R. The average induced 6-TG mutant frequency was 4.7 x 10(-7) per R. These results suggest that fetal cells are highly sensitive to induction of mutations by X-rays, and that a no-effect threshold is not likely. The 10 R dose caused a 25-fold increase in mutation frequency over the historical control, 45 x 10(-7) versus 1.8 x 10(-7), an increase per R of 2.5-fold. Increased risk of childhood cancer related to obstetrical transabdominal X-ray has also been estimated at 2.5-fold per R. Thus, our results are consistent with mutation contributing to this effect. JF - Mutation research AU - Donovan, Paul J AU - Smith, George T AD - Laboratory of Comparative Carcinogenesis, Department of Health and Human Services, National Cancer Institute at Frederick, Building 538, Room 205E, Frederick, MD 21702-1201, USA. donovapa@mail.ncifcrf.gov Y1 - 2002/03/20/ PY - 2002 DA - 2002 Mar 20 SP - 9 EP - 15 VL - 500 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Index Medicus KW - Animals KW - X-Rays KW - Humans KW - Gestational Age KW - Mesocricetus KW - Dose-Response Relationship, Radiation KW - Cell Survival -- radiation effects KW - Female KW - Cell Line KW - Pregnancy KW - Cricetinae KW - Fetus -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71506422?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=X-ray+induced+mutation+in+Syrian+hamster+fetal+cells.&rft.au=Donovan%2C+Paul+J%3BSmith%2C+George+T&rft.aulast=Donovan&rft.aufirst=Paul&rft.date=2002-03-20&rft.volume=500&rft.issue=1-2&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-22 N1 - Date created - 2002-03-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic instability favoring transversions associated with ErbB2-induced mammary tumorigenesis. AN - 71549660; 11867754 AB - It has been argued that genetic instability is required to generate the myriad mutations that fuel tumor initiation and progression and, in fact, patients with heritable cancer susceptibility syndromes harbor defects in specific genes that normally maintain DNA integrity. However, the vast majority of human cancers arise sporadically, in the absence of deficiencies in known "mutator" genes. We used a cII-based mutation detection assay to show that the mean frequency of forward mutations in primary mammary adenocarcinomas arising in mouse mammary tumor virus-c-erbB2 transgenic mice harboring multiple copies of the lambda bacteriophage genome was significantly higher than in aged-matched, wild-type mammary tissue. Analysis of the cII mutational spectrum within the mammary tumor genomic DNA demonstrated a >6-fold elevation in transversion mutation frequency, resulting in a highly unusual inversion of the transition/transversion ratio characteristic of normal epithelium; frameshift mutation frequencies were unaltered. Arising oncogenic point mutations within the c-erbB2 transgene of such tumors were predominantly transversions as well. Data from this model system support the notion that elaboration of a mutator phenotype is a consequential event in breast cancer and suggest that a novel DNA replication/repair gene is a relatively early mutational target in c-erbB2-induced mammary tumorigenesis. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Liu, Shiquan AU - Liu, Wenjing AU - Jakubczak, John L AU - Erexson, Gregory L AU - Tindall, Kenneth R AU - Chan, Richard AU - Muller, William J AU - Adhya, Sankar AU - Garges, Susan AU - Merlino, Glenn AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892-4264, USA. Y1 - 2002/03/19/ PY - 2002 DA - 2002 Mar 19 SP - 3770 EP - 3775 VL - 99 IS - 6 SN - 0027-8424, 0027-8424 KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Mammary Tumor Virus, Mouse -- physiology KW - Bacteriophage lambda -- genetics KW - DNA Mutational Analysis KW - Aging KW - Mutation, Missense -- genetics KW - Mice KW - Adenocarcinoma -- genetics KW - Amino Acid Sequence KW - Transgenes -- genetics KW - Mice, Transgenic KW - Fibroblasts KW - Mammary Glands, Animal -- metabolism KW - Mammary Glands, Animal -- pathology KW - Kinetics KW - Molecular Sequence Data KW - Adenocarcinoma -- virology KW - Gene Frequency -- genetics KW - Female KW - Male KW - Receptor, ErbB-2 -- genetics KW - Receptor, ErbB-2 -- metabolism KW - Mammary Neoplasms, Animal -- genetics KW - Mutagenesis -- genetics KW - Mammary Neoplasms, Animal -- virology KW - DNA Damage -- genetics KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71549660?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Genetic+instability+favoring+transversions+associated+with+ErbB2-induced+mammary+tumorigenesis.&rft.au=Liu%2C+Shiquan%3BLiu%2C+Wenjing%3BJakubczak%2C+John+L%3BErexson%2C+Gregory+L%3BTindall%2C+Kenneth+R%3BChan%2C+Richard%3BMuller%2C+William+J%3BAdhya%2C+Sankar%3BGarges%2C+Susan%3BMerlino%2C+Glenn&rft.aulast=Liu&rft.aufirst=Shiquan&rft.date=2002-03-19&rft.volume=99&rft.issue=6&rft.spage=3770&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-24 N1 - Date created - 2002-03-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Annu Rev Genet. 1999;33:533-64 [10690417] Nucleic Acids Res. 1990 Feb 25;18(4):1068 [2156225] EMBO J. 2000 Apr 3;19(7):1691-702 [10747036] Nature. 1993 Sep 16;365(6443):274-6 [8371783] Cell. 1993 Dec 3;75(5):1027-38 [8252616] Cell. 1993 Dec 17;75(6):1215-25 [8261515] Science. 1994 Mar 18;263(5153):1625-9 [8128251] Nature. 1994 Mar 17;368(6468):258-61 [8145827] Mol Cell Biol. 1994 Nov;14(11):7068-77 [7935422] Biochim Biophys Acta. 1994 Dec 30;1198(2-3):165-84 [7819273] Toxicol Lett. 1995 Dec;82-83:131-4 [8597040] Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9073-8 [8799156] Oncogene. 1997 Jun 12;14(23):2857-61 [9190902] Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8010-5 [9223305] J Bacteriol. 1997 Oct;179(19):5987-91 [9324241] Nat Genet. 1997 Dec;17(4):431-4 [9398844] Curr Opin Pediatr. 1997 Dec;9(6):600-16 [9425594] Biochem Cell Biol. 1997;75(4):315-25 [9493954] Cancer Res. 1998 Jun 15;58(12):2675-9 [9635596] Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8739-43 [9671748] Mutagenesis. 1998 Sep;13(5):487-97 [9800194] Nature. 1998 Dec 17;396(6712):643-9 [9872311] Clin Cancer Res. 1999 Apr;5(4):839-44 [10213220] Am J Clin Pathol. 1999 Jul;112(1 Suppl 1):S53-67 [10396301] Mutat Res. 2000 Feb 14;447(2):165-77 [10751600] Genetics. 2000 Mar;154(3):1291-300 [10757770] Carcinogenesis. 2000 Jun;21(6):1259-62 [10837019] Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8403-8 [10900004] Nucleic Acids Res. 2000 Jul 15;28(14):2847-54 [10908344] Oncogene. 2000 Dec 11;19(53):6102-14 [11156523] Nat Rev Mol Cell Biol. 2001 Feb;2(2):127-37 [11252954] Breast Cancer Res. 2000;2(3):176-83 [11250707] Cancer Res. 2001 Mar 15;61(6):2632-40 [11289141] Semin Oncol. 2001 Feb;28(1 Suppl 3):13-9 [11301370] Mutat Res. 2001 Jun 2;477(1-2):7-21 [11376682] Mol Genet Genomics. 2001 Oct;266(2):336-42 [11683277] Cancer Res. 2001 Nov 1;61(21):7739-42 [11691786] Oncology. 2001;61 Suppl 2:37-42 [11694786] Cancer Res. 1974 Sep;34(9):2311-21 [4136142] Science. 1976 Oct 1;194(4260):23-8 [959840] Nature. 1984 Dec 6-12;312(5994):513-6 [6095109] Science. 1987 Jan 9;235(4785):177-82 [3798106] EMBO J. 1990 May;9(5):1431-5 [2158443] Mol Cell Biol. 1991 Jan;11(1):218-25 [1986222] Environ Mol Mutagen. 1991;18(4):316-21 [1836179] Genetics. 1992 Feb;130(2):285-94 [1311695] Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7022-5 [1495996] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10578-82 [1359541] Mutat Res. 1993 Jul;288(1):133-49 [7686257] Proc Natl Acad Sci U S A. 1988 Apr;85(8):2709-13 [3128795] Cell. 1988 Jul 1;54(1):105-15 [2898299] Science. 1989 May 12;244(4905):707-12 [2470152] Comment In: Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3368-9 [11904400] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Direct real-time evaluation of nitration with green fluorescent protein in solution and within human cells reveals the impact of nitrogen dioxide vs. peroxynitrite mechanisms. AN - 71538950; 11904413 AB - 3-Nitrotyrosyl adducts in proteins have been detected in a wide range of diseases. The mechanisms by which reactive nitrogen oxide species may impede protein function through nitration were examined by using a unique model system, which exploits a critical tyrosyl residue in the fluorophoric pocket of recombinant green fluorescent protein (GFP). Exposure of purified GFP suspended in phosphate buffer to synthetic peroxynitrite in either 0.5 or 5 microM steps resulted in progressively increased 3-nitrotyrosyl immunoreactivity concomitant with disappearance of intrinsic fluorescence (IC(50) approximately 20 microM). Fluorescence from an equivalent amount of GFP expressed within intact MCF-7 tumor cells was largely resistant to this bolus treatment (IC(50) > 250 microM). The more physiologically relevant conditions of either peroxynitrite infusion (1 microM/min) or de novo formation by simultaneous, equimolar generation of nitric oxide (NO) and superoxide (e.g., 3-morpholinosydnonimine; NONOates plus xanthine oxidase/hypoxanthine, menadione, or mitomycin C) were examined. Despite robust oxidation of dihydrorhodamine under each of these conditions, fluorescence decrease of both purified and intracellular GFP was not evident regardless of carbon dioxide presence, suggesting that oxidation and nitration are not necessarily coupled. Alternatively, both extra- and intracellular GFP fluorescence was exquisitely sensitive to nitration produced by heme-peroxidase/hydrogen peroxide-catalyzed oxidation of nitrite. Formation of nitrogen dioxide (NO(2)) during the reaction between NO and the nitroxide 2-phenyl-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide indicated that NO(2) can enter cells and alter peptide function through tyrosyl nitration. Taken together, these findings exemplified that heme-peroxidase-catalyzed formation of NO(2) may play a pivotal role in inflammatory and chronic disease settings while calling into question the significance of nitration by peroxynitrite. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Espey, Michael Graham AU - Xavier, Sandhya AU - Thomas, Douglas D AU - Miranda, Katrina M AU - Wink, David A AD - Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. SP@nih.gov Y1 - 2002/03/19/ PY - 2002 DA - 2002 Mar 19 SP - 3481 EP - 3486 VL - 99 IS - 6 SN - 0027-8424, 0027-8424 KW - Buffers KW - 0 KW - Luminescent Proteins KW - Nitrates KW - Rhodamines KW - Solutions KW - Superoxides KW - 11062-77-4 KW - Peroxynitrous Acid KW - 14691-52-2 KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Nitric Oxide KW - 31C4KY9ESH KW - Heme KW - 42VZT0U6YR KW - Hydrogen Peroxide KW - BBX060AN9V KW - Peroxidase KW - EC 1.11.1.7 KW - Nitrogen Dioxide KW - S7G510RUBH KW - Index Medicus KW - Rhodamines -- metabolism KW - Fluorescence KW - Humans KW - Hydrogen Peroxide -- metabolism KW - Peroxidase -- metabolism KW - Nitric Oxide -- metabolism KW - Superoxides -- metabolism KW - Tumor Cells, Cultured KW - Inhibitory Concentration 50 KW - Heme -- metabolism KW - Time Factors KW - Catalysis KW - Peroxynitrous Acid -- metabolism KW - Nitrogen Dioxide -- metabolism KW - Nitrates -- metabolism KW - Luminescent Proteins -- metabolism KW - Luminescent Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71538950?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Direct+real-time+evaluation+of+nitration+with+green+fluorescent+protein+in+solution+and+within+human+cells+reveals+the+impact+of+nitrogen+dioxide+vs.+peroxynitrite+mechanisms.&rft.au=Espey%2C+Michael+Graham%3BXavier%2C+Sandhya%3BThomas%2C+Douglas+D%3BMiranda%2C+Katrina+M%3BWink%2C+David+A&rft.aulast=Espey&rft.aufirst=Michael&rft.date=2002-03-19&rft.volume=99&rft.issue=6&rft.spage=3481&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-24 N1 - Date created - 2002-03-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1998 Jan 22;391(6665):393-7 [9450756] J Biol Chem. 1998 May 22;273(21):12716-24 [9582295] Nat Biotechnol. 1996 Oct;14(10):1246-51 [9631087] Proc Natl Acad Sci U S A. 1990 Feb;87(4):1620-4 [2154753] J Cardiovasc Pharmacol. 1989;14 Suppl 11:S13-22 [2484692] Arch Biochem Biophys. 1992 Nov 1;298(2):438-45 [1416975] Chem Res Toxicol. 1992 Nov-Dec;5(6):834-42 [1336991] Biochem Soc Trans. 1993 May;21(2):330-4 [8395426] Free Radic Res Commun. 1993;18(4):195-9 [8396550] J Biol Chem. 1994 Oct 21;269(42):26066-75 [7929318] Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12501-4 [7809066] Am J Physiol. 1995 May;268(5 Pt 1):L699-722 [7762673] Free Radic Biol Med. 1995 Jul;19(1):11-9 [7635352] Adv Pharmacol. 1995;34:17-43 [8562432] Biochemistry. 1996 Jun 18;35(24):7855-61 [8672486] Gene. 1996;173(1 Spec No):33-8 [8707053] Methods Enzymol. 1996;268:69-83 [8782574] Arch Biochem Biophys. 1996 Sep 1;333(1):49-58 [8806753] Chem Res Toxicol. 1996 Jul-Aug;9(5):836-44 [8828918] Am J Physiol. 1996 Nov;271(5 Pt 1):C1424-37 [8944624] J Biol Chem. 1997 Mar 21;272(12):7617-25 [9065416] J Biol Chem. 1997 Apr 25;272(17):11147-51 [9111012] Arch Biochem Biophys. 1998 Aug 1;356(1):1-11 [9681984] Arch Biochem Biophys. 1998 Aug 15;356(2):207-13 [9705211] J Biol Chem. 1998 Oct 16;273(42):27280-5 [9765252] Arch Biochem Biophys. 1999 May 1;365(1):92-100 [10222043] Arch Biochem Biophys. 1999 Nov 15;371(2):169-78 [10545203] Circ Res. 1999 Nov 12;85(10):950-8 [10559142] Free Radic Res. 1999 Dec;31(6):651-69 [10630688] J Biol Chem. 2000 Feb 4;275(5):3031-6 [10652282] J Biol Chem. 2000 Mar 3;275(9):6047-50 [10692389] J Biol Chem. 2000 Mar 3;275(9):6346-52 [10692434] J Biol Chem. 2000 Apr 14;275(15):11341-7 [10753947] Ann N Y Acad Sci. 2000;899:209-21 [10863541] J Biol Chem. 2000 Oct 20;275(42):32460-6 [10906340] J Biol Chem. 2000 Oct 20;275(42):32467-74 [10906338] Free Radic Biol Med. 2001 Mar 1;30(5):463-88 [11182518] J Biol Chem. 2001 Aug 10;276(32):30085-91 [11404354] J Biol Chem. 2001 Sep 7;276(36):34051-8 [11425852] J Biol Chem. 1969 Nov 25;244(22):6049-55 [5389100] Arch Biochem Biophys. 1985 Nov 15;243(1):125-34 [4062299] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Design of an HIV-1 lentiviral-based gene-trap vector to detect developmentally regulated genes in mammalian cells. AN - 71531600; 11891320 AB - The recent development of HIV-1 lentiviral vectors is especially useful for gene transfer because they achieve efficient integration into nondividing cell genomes and successful long-term expression of the transgene. These attributes make the vector useful for gene delivery, mutagenesis, and other applications in mammalian systems. Here we describe two HIV-1-based lentiviral vector derivatives, pZR-1 and pZR-2, that can be used in gene-trap experiments in mammalian cells in vitro and in vivo. Each lentiviral gene-trap vector contains a reporter gene, either beta-lactamase or enhanced green fluorescent protein (EGFP), that is inserted into the U3 region of the 3' long terminal repeat. Both of the trap vectors readily integrate into the host genome by using a convenient infection technique. Appropriate insertion of the vector into genes causes EGFP or beta-lactamase expression. This technique should facilitate the rapid enrichment and cloning of the trapped cells and provides an opportunity to select subpopulations of trapped cells based on the subcellular localization of reporter genes. Our findings suggest that the reporter gene is driven by an upstream, cell-specific promoter during cell culture and cell differentiation, which further supports the usefulness of lentivirus-based gene-trap vectors. Lentiviral gene-trap vectors appear to offer a wealth of possibilities for the study of cell differentiation and lineage commitment, as well as for the discovery of new genes. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Lai, Zhennan AU - Han, Ina AU - Park, Misun AU - Brady, Roscoe O AD - Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. laiz@ninds.nih.gov Y1 - 2002/03/19/ PY - 2002 DA - 2002 Mar 19 SP - 3651 EP - 3656 VL - 99 IS - 6 SN - 0027-8424, 0027-8424 KW - beta-Lactamases KW - EC 3.5.2.6 KW - Index Medicus KW - Animals KW - Cell Lineage KW - Humans KW - Transduction, Genetic KW - Cell Differentiation KW - Organ Specificity KW - Mice KW - Brain -- metabolism KW - Brain -- virology KW - Transgenes -- genetics KW - Stem Cells -- metabolism KW - Fibroblasts -- metabolism KW - beta-Lactamases -- genetics KW - Fibroblasts -- virology KW - Genes, Reporter -- genetics KW - Stem Cells -- cytology KW - Cells, Cultured KW - Promoter Regions, Genetic -- genetics KW - Stem Cells -- virology KW - Fluorescent Antibody Technique KW - beta-Lactamases -- metabolism KW - Cell Line KW - HIV-1 -- genetics KW - Genetic Engineering KW - Genetic Vectors -- genetics KW - Gene Expression Regulation, Developmental KW - Gene Expression Profiling -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71531600?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Design+of+an+HIV-1+lentiviral-based+gene-trap+vector+to+detect+developmentally+regulated+genes+in+mammalian+cells.&rft.au=Lai%2C+Zhennan%3BHan%2C+Ina%3BPark%2C+Misun%3BBrady%2C+Roscoe+O&rft.aulast=Lai&rft.aufirst=Zhennan&rft.date=2002-03-19&rft.volume=99&rft.issue=6&rft.spage=3651&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-24 N1 - Date created - 2002-03-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nat Genet. 2000 Jan;24(1):49-52 [10615126] J Virol. 1999 Aug;73(8):6946-52 [10400793] Cell. 2000 Apr 14;101(2):173-85 [10786833] Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11297-302 [11027330] J Virol. 2000 Nov;74(22):10589-99 [11044103] Mol Ther. 2000 Nov;2(5):458-69 [11082319] Nat Biotechnol. 2001 Jun;19(6):579-82 [11385465] J Biochem. 2001 Jun;129(6):875-80 [11388901] J Neurosci Res. 2002 Feb 1;67(3):363-71 [11813241] Virology. 1981 Apr 15;110(1):202-7 [7210505] Proc Natl Acad Sci U S A. 1986 May;83(10):3194-8 [3458176] J Virol. 1986 Aug;59(2):284-91 [3016298] Nature. 1986 Oct 2-8;323(6087):445-8 [3762693] Science. 1989 Apr 28;244(4903):463-5 [2497519] Bioessays. 1991 Dec;13(12):649-56 [1789782] Mol Cell Biol. 1993 Jan;13(1):473-86 [8417345] Science. 1996 Apr 12;272(5259):263-7 [8602510] Nature. 1996 Oct 31;383(6603):829-32 [8893009] Genes Dev. 1996 Dec 15;10(24):3141-55 [8985183] Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15266-71 [8986799] Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10319-23 [9294208] Nat Genet. 1997 Nov;17(3):314-7 [9354796] Science. 1998 Jan 2;279(5347):84-8 [9417030] Mol Cell Biol. 1998 May;18(5):3081-8 [9566926] J Virol. 1998 Oct;72(10):8150-7 [9733856] J Virol. 1998 Nov;72(11):8873-83 [9765432] J Virol. 1998 Dec;72(12):9873-80 [9811723] Hum Gene Ther. 1998 Dec 10;9(18):2717-26 [9874270] Exp Neurol. 1999 Nov;160(1):1-16 [10630186] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Aldose reductase: an aldehyde scavenging enzyme in the intraneuronal metabolism of norepinephrine in human sympathetic ganglia. AN - 71618761; 11958479 AB - The neurotransmitter norepinephrine is metabolized by monoamine oxidase into an aldehyde intermediate that is further metabolized to the stable glycol derivative, 3,4-dihydroxyphenylglycol (DHPG). In this study, the possible role of aldose reductase in reducing this aldehyde intermediate in human sympathetic neurons has been examined. DHPG is formed when norepinephrine is incubated with aldose reductase in the presence of monoamine oxidase. DHPG metabolism is inhibited by the monoamine oxidase inhibitor, pargyline which prevents the deamination of norepinephrine, and by the aldose reductase inhibitor AL 1576, which inhibits DHPG formation without affecting the deamination of norepinephrine. Although similar formation of DHPG was observed with human liver aldehyde reductase, the production of DHPG was more effective with aldose reductase than aldehyde reductase. Two peaks of reductase activity corresponding to aldose reductase and aldehyde reductase were observed when sympathetic ganglia were chromatofocused. Molecular modeling studies indicate that the energy-minimized structure of 3,4-dihydroxymandelaldehyde bound to aldose reductase is similar to that of glyceraldehyde where the 2'-hydroxyl group forms hydrogen bonds with Trp111 and NADPH. These results suggest that aldose reductase may be important in metabolizing the potentially toxic aldehyde intermediate formed from norepinephrine in human sympathetic ganglia. JF - Autonomic neuroscience : basic & clinical AU - Kawamura, Minoru AU - Eisenhofer, Graeme AU - Kopin, Irwin J AU - Kador, Peter F AU - Lee, Yong S AU - Fujisawa, Shigeki AU - Sato, Sanai AD - Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/03/18/ PY - 2002 DA - 2002 Mar 18 SP - 131 EP - 139 VL - 96 IS - 2 SN - 1566-0702, 1566-0702 KW - Aldehydes KW - 0 KW - Metanephrine KW - 5001-33-2 KW - Methoxyhydroxyphenylglycol KW - 534-82-7 KW - dihydroxyphenylethylene glycol KW - CF5G2G268A KW - Aldehyde Reductase KW - EC 1.1.1.21 KW - Monoamine Oxidase KW - EC 1.4.3.4 KW - Norepinephrine KW - X4W3ENH1CV KW - Epinephrine KW - YKH834O4BH KW - Index Medicus KW - Pheochromocytoma -- enzymology KW - Adrenal Gland Neoplasms -- enzymology KW - Amino Acid Motifs -- physiology KW - Humans KW - In Vitro Techniques KW - Aged KW - Middle Aged KW - Substrate Specificity KW - Monoamine Oxidase -- metabolism KW - Metanephrine -- analogs & derivatives KW - Epinephrine -- metabolism KW - Female KW - Methoxyhydroxyphenylglycol -- metabolism KW - Ganglia, Sympathetic -- cytology KW - Neurons -- metabolism KW - Norepinephrine -- metabolism KW - Aldehydes -- metabolism KW - Neurons -- enzymology KW - Methoxyhydroxyphenylglycol -- analogs & derivatives KW - Aldehyde Reductase -- metabolism KW - Ganglia, Sympathetic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71618761?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Autonomic+neuroscience+%3A+basic+%26+clinical&rft.atitle=Aldose+reductase%3A+an+aldehyde+scavenging+enzyme+in+the+intraneuronal+metabolism+of+norepinephrine+in+human+sympathetic+ganglia.&rft.au=Kawamura%2C+Minoru%3BEisenhofer%2C+Graeme%3BKopin%2C+Irwin+J%3BKador%2C+Peter+F%3BLee%2C+Yong+S%3BFujisawa%2C+Shigeki%3BSato%2C+Sanai&rft.aulast=Kawamura&rft.aufirst=Minoru&rft.date=2002-03-18&rft.volume=96&rft.issue=2&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Autonomic+neuroscience+%3A+basic+%26+clinical&rft.issn=15660702&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-08 N1 - Date created - 2002-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A deletion-insertion mutation in the phosphomannomutase 2 gene in an African American patient with congenital disorders of glycosylation-Ia. AN - 71514547; 11891694 AB - Congenital disorders of glycosylation (CDG) are a group of metabolic disorders with multisystemic involvement characterized by abnormalities in the synthesis of N-linked oligosaccharides. The most common form, CDG-Ia, resulting from mutations in the gene encoding the enzyme phosphomannomutase (PMM2), manifests with severe abnormalities in psychomotor development, dysmorphic features and visceral involvement. While this disorder is panethnic, we present the first cases of CDG-Ia identified in an African American family with two affected sisters. The proband had failure to thrive in infancy, hypotonia, ataxia, cerebellar hypoplasia and developmental delay. On examination, she also exhibited strabismus, inverted nipples and an atypical perineal fat distribution, all features characteristic of CDG-Ia. Direct sequencing demonstrated that the patient had a unique genotype, T237M/c.565-571 delAGAGAT insGTGGATTTCC. The novel deletion-insertion mutation, which was confirmed by subcloning and sequencing of each allele, introduces a stop codon 11 amino acids downstream from the site of the deletion. The presence of this deletion-insertion mutation at cDNA position 565 suggests that this site in the PMM2 gene may be a hotspot for chromosomal breakage. JF - American journal of medical genetics AU - Tayebi, Nahid AU - Andrews, David Q AU - Park, Joseph K AU - Orvisky, Eduard AU - McReynolds, John AU - Sidransky, Ellen AU - Krasnewich, Donna M AD - Clinical Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 SP - 241 EP - 246 VL - 108 IS - 3 SN - 0148-7299, 0148-7299 KW - Phosphotransferases (Phosphomutases) KW - EC 5.4.2.- KW - phosphomannomutase KW - EC 5.4.2.8 KW - Index Medicus KW - Base Sequence KW - African Continental Ancestry Group -- genetics KW - Humans KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - Glycosylation KW - Mutation KW - Mutagenesis, Insertional KW - Female KW - Sequence Deletion KW - Child, Preschool KW - Congenital Disorders of Glycosylation -- enzymology KW - Phosphotransferases (Phosphomutases) -- metabolism KW - Phosphotransferases (Phosphomutases) -- genetics KW - Congenital Disorders of Glycosylation -- pathology KW - Congenital Disorders of Glycosylation -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71514547?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+medical+genetics&rft.atitle=A+deletion-insertion+mutation+in+the+phosphomannomutase+2+gene+in+an+African+American+patient+with+congenital+disorders+of+glycosylation-Ia.&rft.au=Tayebi%2C+Nahid%3BAndrews%2C+David+Q%3BPark%2C+Joseph+K%3BOrvisky%2C+Eduard%3BMcReynolds%2C+John%3BSidransky%2C+Ellen%3BKrasnewich%2C+Donna+M&rft.aulast=Tayebi&rft.aufirst=Nahid&rft.date=2002-03-15&rft.volume=108&rft.issue=3&rft.spage=241&rft.isbn=&rft.btitle=&rft.title=American+journal+of+medical+genetics&rft.issn=01487299&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-03 N1 - Date created - 2002-03-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Kinetics of an IFN gamma response AN - 39566772; 3660307 AU - Culp, WD Jr AU - Perez-Diez, A AU - Massey, R D AU - Matzinger, P Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39566772?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Kinetics+of+an+IFN+gamma+response&rft.au=Culp%2C+WD+Jr%3BPerez-Diez%2C+A%3BMassey%2C+R+D%3BMatzinger%2C+P&rft.aulast=Culp&rft.aufirst=WD&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Poster Paper No. 305 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Unregulated signaling pathways in TGF-b1-deficient mice AN - 39561681; 3660106 AU - McCartney-Francis, N L AU - Wahl, S M Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39561681?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Unregulated+signaling+pathways+in+TGF-b1-deficient+mice&rft.au=McCartney-Francis%2C+N+L%3BWahl%2C+S+M&rft.aulast=McCartney-Francis&rft.aufirst=N&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Poster Paper No. 103 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Oncogene-dependent caspase activation AN - 39506682; 3665156 AU - Fearnhead, HO Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39506682?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Oncogene-dependent+caspase+activation&rft.au=Fearnhead%2C+HO&rft.aulast=Fearnhead&rft.aufirst=HO&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Cell Biology, 8120 Woodmont Ave, Suite 750, Bethesda, MD 20814, USA; phone: 301-347-9300; fax: 301-347-9310; URL: www.ascb.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Multiplexed cytokine assay of serum from HIV-infected patients with differing disease presentations AN - 39500516; 3660232 AU - Rossio, J L AU - Whitby, D AU - Hallett, K AU - Ryan, R AU - Arthur, LO AU - Lifson, J D Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39500516?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Multiplexed+cytokine+assay+of+serum+from+HIV-infected+patients+with+differing+disease+presentations&rft.au=Rossio%2C+J+L%3BWhitby%2C+D%3BHallett%2C+K%3BRyan%2C+R%3BArthur%2C+LO%3BLifson%2C+J+D&rft.aulast=Rossio&rft.aufirst=J&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Poster Paper No. 228 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Genetic analysis of chemokine roles in human disease AN - 39500275; 3660187 AU - Murphy, P M Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39500275?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Genetic+analysis+of+chemokine+roles+in+human+disease&rft.au=Murphy%2C+P+M&rft.aulast=Murphy&rft.aufirst=P&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Paper No. 181 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Leishmania species differentially modulates macrophage migration and expression of cell adhesion molecules AN - 39475532; 3660219 AU - Mendez, S AU - Belkaid, Y AU - Flowers, E AU - Sacks, D L Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39475532?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Leishmania+species+differentially+modulates+macrophage+migration+and+expression+of+cell+adhesion+molecules&rft.au=Mendez%2C+S%3BBelkaid%2C+Y%3BFlowers%2C+E%3BSacks%2C+D+L&rft.aulast=Mendez&rft.aufirst=S&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Poster Paper No. 215 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Chemokine receptor polymorphism and risk of acute rejection in human renal transplantation AN - 39475393; 3660189 AU - Abdi, R AU - Huong, TTB AU - Sahagun-Ruiz, A AU - Murphy, P M AU - Brenner, B M AU - Milford, EL AU - McDermott, D H Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39475393?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Chemokine+receptor+polymorphism+and+risk+of+acute+rejection+in+human+renal+transplantation&rft.au=Abdi%2C+R%3BHuong%2C+TTB%3BSahagun-Ruiz%2C+A%3BMurphy%2C+P+M%3BBrenner%2C+B+M%3BMilford%2C+EL%3BMcDermott%2C+D+H&rft.aulast=Abdi&rft.aufirst=R&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Paper No. 183 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - IL-6 regulation of the human methyltransferase (HDNMT) gene in human erythroleukemia cells AN - 39472977; 3660023 AU - Farrar, W L AU - Hodge, D Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39472977?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=IL-6+regulation+of+the+human+methyltransferase+%28HDNMT%29+gene+in+human+erythroleukemia+cells&rft.au=Farrar%2C+W+L%3BHodge%2C+D&rft.aulast=Farrar&rft.aufirst=W&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Paper No. 19 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Role of the G-protein coupled receptor FPRL1 in Alzheimer's disease: Its relevance to cellular uptake of b amyloid peptide and fibrillar formation by macrophages AN - 39472620; 3660352 AU - Wang, J M AU - Yazawa, H AU - Yu, Z-X AU - Takea, K AU - Le, Y AU - Gong, W AU - Ferrans, V J AU - Li, C C AU - Oppenheim, J J Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39472620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Role+of+the+G-protein+coupled+receptor+FPRL1+in+Alzheimer%27s+disease%3A+Its+relevance+to+cellular+uptake+of+b+amyloid+peptide+and+fibrillar+formation+by+macrophages&rft.au=Wang%2C+J+M%3BYazawa%2C+H%3BYu%2C+Z-X%3BTakea%2C+K%3BLe%2C+Y%3BGong%2C+W%3BFerrans%2C+V+J%3BLi%2C+C+C%3BOppenheim%2C+J+J&rft.aulast=Wang&rft.aufirst=J&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Paper No. 349 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Identification of the receptor that human LL-37 utilizes to activate human neutrophils, monocytes, and T cells AN - 39471803; 3660046 AU - Yang, D AU - Chen, Q AU - Chertov, O AU - Anderson, M AU - Hirata, M AU - Oppenheim, J J Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39471803?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Identification+of+the+receptor+that+human+LL-37+utilizes+to+activate+human+neutrophils%2C+monocytes%2C+and+T+cells&rft.au=Yang%2C+D%3BChen%2C+Q%3BChertov%2C+O%3BAnderson%2C+M%3BHirata%2C+M%3BOppenheim%2C+J+J&rft.aulast=Yang&rft.aufirst=D&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Poster Paper No. 42 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - IL-7 controls chromatin accessibility for the TCR gamma V(D)J recombination via histone acetylation AN - 39471697; 3660027 AU - Huang, J AU - Murray, R AU - Durum, S K AU - Muegge, K Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39471697?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=IL-7+controls+chromatin+accessibility+for+the+TCR+gamma+V%28D%29J+recombination+via+histone+acetylation&rft.au=Huang%2C+J%3BMurray%2C+R%3BDurum%2C+S+K%3BMuegge%2C+K&rft.aulast=Huang&rft.aufirst=J&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Paper No. 23 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Synergistic effect of IL-4 on IL-2- and IL-12-induction of murine IFN-g expression in NK cells AN - 39462295; 3660268 AU - Bream, J H AU - Rong-Yu, C AU - Curiel, R AU - Grusby, M AU - Aune, T AU - Young, HA Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39462295?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Synergistic+effect+of+IL-4+on+IL-2-+and+IL-12-induction+of+murine+IFN-g+expression+in+NK+cells&rft.au=Bream%2C+J+H%3BRong-Yu%2C+C%3BCuriel%2C+R%3BGrusby%2C+M%3BAune%2C+T%3BYoung%2C+HA&rft.aulast=Bream&rft.aufirst=J&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Poster Paper No. 265 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Mycobacterium avium regulation of macrophage cytokine production AN - 39462136; 3660221 AU - Greenwell-Wild, T AU - Vazquez, N AU - Sim, D AU - Wahl, S M Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39462136?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Mycobacterium+avium+regulation+of+macrophage+cytokine+production&rft.au=Greenwell-Wild%2C+T%3BVazquez%2C+N%3BSim%2C+D%3BWahl%2C+S+M&rft.aulast=Greenwell-Wild&rft.aufirst=T&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Poster Paper No. 217 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Contrasting evolution of the human leukocyte N-formylpeptide receptor subtypes FPR and FPRL1R AN - 39458980; 3660132 AU - Sahagun-Ruiz, A AU - Colla, J S AU - Juhn, J AU - Gao, J-L AU - Murphy, P M AU - McDermott, D H Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39458980?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Contrasting+evolution+of+the+human+leukocyte+N-formylpeptide+receptor+subtypes+FPR+and+FPRL1R&rft.au=Sahagun-Ruiz%2C+A%3BColla%2C+J+S%3BJuhn%2C+J%3BGao%2C+J-L%3BMurphy%2C+P+M%3BMcDermott%2C+D+H&rft.aulast=Sahagun-Ruiz&rft.aufirst=A&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Poster Paper No. 130 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Biological functions of tumor necrosis factor and lymphotoxin in vivo assessed using a novel panel of knockout mice AN - 39458914; 3660128 AU - Nedospasov, SA Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39458914?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Biological+functions+of+tumor+necrosis+factor+and+lymphotoxin+in+vivo+assessed+using+a+novel+panel+of+knockout+mice&rft.au=Nedospasov%2C+SA&rft.aulast=Nedospasov&rft.aufirst=SA&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Poster Paper No. 126 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Bax deletion restores thymocyte development in IL-7Ra -/- mice AN - 39458674; 3660038 AU - Durum, S K AU - Muegge, K AU - Khaled, A R Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39458674?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Bax+deletion+restores+thymocyte+development+in+IL-7Ra+-%2F-+mice&rft.au=Durum%2C+S+K%3BMuegge%2C+K%3BKhaled%2C+A+R&rft.aulast=Durum&rft.aufirst=S&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Paper No. 34 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Combined cytokine stimulation of human naive CD4 super(+) T cells results in IFN-g production in absence of hypomethylation of the IFN-g gene promoter AN - 39452348; 3660045 AU - Ruscetti, F W AU - Young, HA AU - Petrow-Sadowski, C AU - Bagni, R AU - Mikovits, JA Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39452348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Combined+cytokine+stimulation+of+human+naive+CD4+super%28%2B%29+T+cells+results+in+IFN-g+production+in+absence+of+hypomethylation+of+the+IFN-g+gene+promoter&rft.au=Ruscetti%2C+F+W%3BYoung%2C+HA%3BPetrow-Sadowski%2C+C%3BBagni%2C+R%3BMikovits%2C+JA&rft.aulast=Ruscetti&rft.aufirst=F&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Paper No. 41 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Contrasting roles of IL-2 and IL-15 in the life and death of lymphocytes: Implications for immunotherapy AN - 39449400; 3660358 AU - Waldmann, T AU - Azimi, N AU - Dubois, S AU - Tagaya, Y Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39449400?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Contrasting+roles+of+IL-2+and+IL-15+in+the+life+and+death+of+lymphocytes%3A+Implications+for+immunotherapy&rft.au=Waldmann%2C+T%3BAzimi%2C+N%3BDubois%2C+S%3BTagaya%2C+Y&rft.aulast=Waldmann&rft.aufirst=T&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Paper No. 355 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - IFN gamma depletion enhances inflammation and lesion progression of Leishmania major-infected IL-4-deficient C57BL/6 mice AN - 39449111; 3660277 AU - Caler, E AU - Noben-Trauth, N AU - Sacks, D AU - Belkaid, Y Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39449111?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=IFN+gamma+depletion+enhances+inflammation+and+lesion+progression+of+Leishmania+major-infected+IL-4-deficient+C57BL%2F6+mice&rft.au=Caler%2C+E%3BNoben-Trauth%2C+N%3BSacks%2C+D%3BBelkaid%2C+Y&rft.aulast=Caler&rft.aufirst=E&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Poster Paper No. 274 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Characterization of a novel Ly49 promoter that is active in immature cells AN - 39434001; 3660242 AU - Anderson, S K AU - Nalewaik, R AU - Makrigiannis, A AU - Saleh, A Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39434001?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Characterization+of+a+novel+Ly49+promoter+that+is+active+in+immature+cells&rft.au=Anderson%2C+S+K%3BNalewaik%2C+R%3BMakrigiannis%2C+A%3BSaleh%2C+A&rft.aulast=Anderson&rft.aufirst=S&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Poster Paper No. 238 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Signaling pathways and gene expression in HIV-1-infected macrophages AN - 39433844; 3660209 AU - Vazquez, N AU - Wild, T AU - Wahl, S M Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39433844?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Signaling+pathways+and+gene+expression+in+HIV-1-infected+macrophages&rft.au=Vazquez%2C+N%3BWild%2C+T%3BWahl%2C+S+M&rft.aulast=Vazquez&rft.aufirst=N&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Paper No. 203 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - IL-15 plays an important role in the pathogenesis of HAM/TSP through activation of the T cells and persistence of antigen-specific CD8 cells AN - 39431468; 3660356 AU - Azimi, N AU - Nagai, M AU - Mariner, J AU - Jacobson, S AU - Waldmann, T A Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39431468?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=IL-15+plays+an+important+role+in+the+pathogenesis+of+HAM%2FTSP+through+activation+of+the+T+cells+and+persistence+of+antigen-specific+CD8+cells&rft.au=Azimi%2C+N%3BNagai%2C+M%3BMariner%2C+J%3BJacobson%2C+S%3BWaldmann%2C+T+A&rft.aulast=Azimi&rft.aufirst=N&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Paper No. 332 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - CCR5 variants permissive for HIV-1 infection show distinct functional responses to CCL3, CCL4 and CCL5 AN - 39431065; 3660231 AU - Turpin, JA AU - Dong, H F AU - Howard, OMZ AU - Halverson, D AU - Carrington, M AU - Dean, M AU - Osterling, C AU - Oppenheim, J J Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39431065?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=CCR5+variants+permissive+for+HIV-1+infection+show+distinct+functional+responses+to+CCL3%2C+CCL4+and+CCL5&rft.au=Turpin%2C+JA%3BDong%2C+H+F%3BHoward%2C+OMZ%3BHalverson%2C+D%3BCarrington%2C+M%3BDean%2C+M%3BOsterling%2C+C%3BOppenheim%2C+J+J&rft.aulast=Turpin&rft.aufirst=JA&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Poster Paper No. 227 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - PMA inhibits plasmin-mediated release of aggregated LDL from macrophages AN - 39430426; 3660098 AU - Kruth, H S AU - Huang, W AU - Zhang, W-Y AU - Ishii, I Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39430426?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=PMA+inhibits+plasmin-mediated+release+of+aggregated+LDL+from+macrophages&rft.au=Kruth%2C+H+S%3BHuang%2C+W%3BZhang%2C+W-Y%3BIshii%2C+I&rft.aulast=Kruth&rft.aufirst=H&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Poster Paper No. 95 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - JAB/SOCS1/SSI-1 is an IL-2-induced inhibitor of IL-2 signaling AN - 39427586; 3660073 AU - Sporri, B AU - Kovanen, P E AU - Sasaki, A AU - Yoshimura, A AU - Leonard, W J Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39427586?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=JAB%2FSOCS1%2FSSI-1+is+an+IL-2-induced+inhibitor+of+IL-2+signaling&rft.au=Sporri%2C+B%3BKovanen%2C+P+E%3BSasaki%2C+A%3BYoshimura%2C+A%3BLeonard%2C+W+J&rft.aulast=Sporri&rft.aufirst=B&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Poster Paper No. 70 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Detection of a novel component of CCR5 ligand induced trafficking AN - 39427533; 3660055 AU - Howard, OMZ AU - Gertz, B AU - Wooters, J AU - Lockett, S AU - Oppenheim, J J Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39427533?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Detection+of+a+novel+component+of+CCR5+ligand+induced+trafficking&rft.au=Howard%2C+OMZ%3BGertz%2C+B%3BWooters%2C+J%3BLockett%2C+S%3BOppenheim%2C+J+J&rft.aulast=Howard&rft.aufirst=OMZ&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Poster Paper No. 51 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Transforming growth factor-b 1 induces anergic/suppressor CD4 super(+) CD25 super(+) CTLA-4 super(+) T cells AN - 39386094; 3660365 AU - Chen, W AU - Frank, M AU - Jin, W AU - Lei, K-J AU - Hardegen, N AU - Wahl, S M Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39386094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Transforming+growth+factor-b+1+induces+anergic%2Fsuppressor+CD4+super%28%2B%29+CD25+super%28%2B%29+CTLA-4+super%28%2B%29+T+cells&rft.au=Chen%2C+W%3BFrank%2C+M%3BJin%2C+W%3BLei%2C+K-J%3BHardegen%2C+N%3BWahl%2C+S+M&rft.aulast=Chen&rft.aufirst=W&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Paper No. 362 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Regulation of TNF-a and caspases by IFN-g results in differential MMP-1 and MMP-9 production by GM-CSF and TNF-a-treated monocytes AN - 39385616; 3660166 AU - Zhou, M AU - Zhang, Y AU - Ardans, JA AU - Wahl, L M Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39385616?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Regulation+of+TNF-a+and+caspases+by+IFN-g+results+in+differential+MMP-1+and+MMP-9+production+by+GM-CSF+and+TNF-a-treated+monocytes&rft.au=Zhou%2C+M%3BZhang%2C+Y%3BArdans%2C+JA%3BWahl%2C+L+M&rft.aulast=Zhou&rft.aufirst=M&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Poster Paper No. 165 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Expression profiling in lymphotoxin and tumor necrosis factor knockout mice AN - 39383398; 3660025 AU - Shakhov, AN AU - Nedospasov, SA Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39383398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Expression+profiling+in+lymphotoxin+and+tumor+necrosis+factor+knockout+mice&rft.au=Shakhov%2C+AN%3BNedospasov%2C+SA&rft.aulast=Shakhov&rft.aufirst=AN&rft.date=2002-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Leukocyte Biology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-5703; fax: 301-571-5704; email: slb@faseb.org; URL: www.biosci.ohio-state.edu/~slb. Paper No. 21 N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - Acute cadmium exposure induces stress-related gene expression in wild-type and metallothionein-I/II-null mice AN - 18323386; 5367815 AB - This study examined the effect of acute cadmium on stress-related gene expression and free radical production in wild-type and metallothionein-I/II-null (MT-null) mice. Atlas Toxicology arrays showed that acute cadmium (40 mu mol/kg as CdCl sub(2), ip for 3 h) markedly increased the expression of genes encoding heat-shock proteins, heme oxygenase-1, and genes in response to DNA damage/repair. The expression of genes encoding cytochrome P450 enzymes, UDP-glucuronosyltransferases, Mn-superoxide dismutase, and catalase was suppressed by cadmium. MT-null mice were more sensitive than wild-type mice to cadmium-induced, stress-related gene expression, in accord with greater activation of transcription factor AP-1 and phosphorylated JNK and ERK. To evaluate free radical production, mice were simultaneously given the spin trap agent, N-tert-butyl- alpha -phenylnitrone (PBN, 250 mg in DMSO/kg, ip) with cadmium, and livers were removed 30 min later for PBN-trapped radical extraction with chloroform:methanol (2:1), and detected with electron spin resonance (ESR). Cadmium treatment caused detectable ESR signals for PBN adducts as well as lipid peroxidation in the liver similarly in both wild-type and MT-null mice. Thus, the mechanism of acute cadmium toxicity involves multiple facets including oxidative damage and aberrant gene expression, and absence of MT exacerbates Cd-induced aberrant gene expression. JF - Free Radical Biology & Medicine AU - Liu, Jie AU - Kadiiska, M B AU - Corton, J C AU - Qu, Wei AU - Waalkes, M P AU - Mason, R P AU - Liu, Yaping AU - Klaassen, C D AD - NCI at NIEHS, Laboratory of Comparative Carcinogenesis, Mail Drop F0-09, Research Triangle Park, NC 27709, USA, Liu6@niehs.nih.gov Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 SP - 525 EP - 535 VL - 32 IS - 6 SN - 0891-5849, 0891-5849 KW - mice KW - N-Tert-butyl- alpha -phenylnitrone KW - N-tert-butyl- alpha -phenylnitrone KW - UDP-glucuronosyltransferase KW - metallothionein I KW - metallothionein II KW - Genetics Abstracts; Toxicology Abstracts KW - N-Tert-butyl-a-phenylnitrone KW - N-tert-butyl-^a-phenylnitrone KW - Heat shock proteins KW - Free radicals KW - AP-1 protein KW - Stress KW - DNA repair KW - ^AAP-1 protein KW - Catalase KW - Lipid peroxidation KW - Gene expression KW - DNA damage KW - Superoxide dismutase KW - Cadmium KW - X 24165:Biochemistry KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18323386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+Radical+Biology+%26+Medicine&rft.atitle=Acute+cadmium+exposure+induces+stress-related+gene+expression+in+wild-type+and+metallothionein-I%2FII-null+mice&rft.au=Liu%2C+Jie%3BKadiiska%2C+M+B%3BCorton%2C+J+C%3BQu%2C+Wei%3BWaalkes%2C+M+P%3BMason%2C+R+P%3BLiu%2C+Yaping%3BKlaassen%2C+C+D&rft.aulast=Liu&rft.aufirst=Jie&rft.date=2002-03-15&rft.volume=32&rft.issue=6&rft.spage=525&rft.isbn=&rft.btitle=&rft.title=Free+Radical+Biology+%26+Medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Superoxide dismutase; Lipid peroxidation; Catalase; Heat shock proteins; Free radicals; DNA damage; DNA repair; AP-1 protein; Stress; Gene expression; Cadmium; ^AAP-1 protein ER - TY - JOUR T1 - Crystallographic and Functional Studies of a Modified Form of Eosinophil-derived Neurotoxin (EDN) with Novel Biological Activities AN - 18307006; 5352886 AB - The crystal structure of a post-translationally modified form of eosinophil-derived neurotoxin (EDN) with four extra residues on its N terminus ((-4)EDN) has been solved and refined at atomic resolution (1 Aa). Two of the extra residues can be placed unambiguously, while the density corresponding to two others is poor. The modified N terminus appears to influence the position of the catalytically important His129, possibly explaining the diminished catalytic activity of this variant. However, (-4)EDN has been shown to be cytotoxic to a Kaposi's sarcoma tumor cell line and other endothelial cell lines. Analysis of the structure and function suggests that the reason for cytotoxicity is most likely due to cellular recognition by the N-terminal extension, since the intrinsic activity of the enzyme is not sufficient for cytotoxicity and the N-terminal extension does not affect the conformation of EDN. JF - Journal of Molecular Biology AU - Chang, C AU - Newton, D L AU - Rybak, S M AU - Wlodawer, A AD - Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD, 21702, USA Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 SP - 119 EP - 130 PB - Academic Press VL - 317 IS - 1 SN - 0022-2836, 0022-2836 KW - eosinophil-derived neurotoxin KW - Toxicology Abstracts KW - Crystal structure KW - Leukocytes (eosinophilic) KW - Neurotoxins KW - N-Terminus KW - Biological activity KW - X 24173:Animals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18307006?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Crystallographic+and+Functional+Studies+of+a+Modified+Form+of+Eosinophil-derived+Neurotoxin+%28EDN%29+with+Novel+Biological+Activities&rft.au=Chang%2C+C%3BNewton%2C+D+L%3BRybak%2C+S+M%3BWlodawer%2C+A&rft.aulast=Chang&rft.aufirst=C&rft.date=2002-03-15&rft.volume=317&rft.issue=1&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1006%2Fjmbi.2002.5406 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Neurotoxins; Crystal structure; Leukocytes (eosinophilic); Biological activity; N-Terminus DO - http://dx.doi.org/10.1006/jmbi.2002.5406 ER - TY - JOUR T1 - Dynamics of a protein polymer: the assembly and disassembly pathways of the MuB transposition target complex AN - 18298856; 5348373 AB - MuB assembles into a polymer on DNA in the presence of ATP and is directly involved in the selection of an appropriate site on the Escherichia coli chromosome for the insertion of the bacteriophage Mu genome. We have developed an assay using fluorescently tagged proteins to monitor the polymeric state of MuB via fluorescence resonance energy transfer. We show that polymer assembly is initiated by the formation of an ATP-MuB complex. MuB then self-associates into a protomer before binding to DNA. Upon binding to DNA, a dramatic increase in energy transfer is observed, suggesting a conformational change within MuB. Polymer disassembly is much slower than assembly and is greatly stimulated by the MuA transposase. Additionally, MuB is readily exchanged between polymers, and ATP hydrolysis is directly coupled to polymer disassembly. Our data support a model in which a combination of rapid polymer assembly, MuA-mediated disassembly, followed by rapid reassembly of the polymer allows MuB to sample multiple DNA targets until an appropriate site is located for the insertion of the bacteriophage genome. JF - EMBO Journal AU - Greene, E C AU - Mizuuchi, K AD - Laboratory of Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA, Kmizu@helix.nih.gov Y1 - 2002/03/15/ PY - 2002 DA - 2002 Mar 15 SP - 1477 EP - 1486 VL - 21 IS - 6 SN - 0261-4189, 0261-4189 KW - MuB protein KW - fluorescence resonance energy transfer KW - transposase KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids; Virology & AIDS Abstracts KW - Phage Mu KW - Transposition KW - ATP KW - Chromosomes KW - Escherichia coli KW - Polymers KW - V 22050:Viral genetics including virus reactivation KW - J 02750:Phage-host interactions KW - N 14675:Transposition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18298856?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=EMBO+Journal&rft.atitle=Dynamics+of+a+protein+polymer%3A+the+assembly+and+disassembly+pathways+of+the+MuB+transposition+target+complex&rft.au=Greene%2C+E+C%3BMizuuchi%2C+K&rft.aulast=Greene&rft.aufirst=E&rft.date=2002-03-15&rft.volume=21&rft.issue=6&rft.spage=1477&rft.isbn=&rft.btitle=&rft.title=EMBO+Journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Phage Mu; Escherichia coli; ATP; Chromosomes; Polymers; Transposition ER - TY - JOUR T1 - Development of long-acting dopamine transporter ligands as potential cocaine-abuse therapeutic agents: chiral hydroxyl-containing derivatives of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine and 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine. AN - 71502118; 11882001 AB - In our search for long-acting agents for the treatment of cocaine abuse, a series of optically pure hydroxylated derivatives of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (1) and 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine (2) (GBR 12909 and GBR 12935, respectively) were synthesized and evaluated in vitro and in vivo. The enantiomers of the 2-hydroxylated analogues displayed substantial enantioselectivity. The S enantiomers displayed higher dopamine transporter (DAT) affinity and the R enantiomers were found to interact at the serotonin transporter (SERT) with higher affinity. The two-carbon spacer between the hydroxyl group and the piperazine ring was essential for enantioselectivity, and the length of the alkyl chain between the phenyl group and the piperazine ring influenced binding affinity and selectivity for the DAT and SERT. Phenylethyl analogues had a higher binding affinity for the SERT and a weaker affinity and selectivity for the DAT than the corresponding phenylpropyl analogues. Thus, (S)-(+)-1-[4-[2-[bis(4-fluorophenyl)methoxy]ethyl]piperazinyl]-3-phenylpropan-2-ol (6) displayed the highest affinity to the DAT, and (S)-(+)-1-[4-[2-(diphenylmethoxy)ethyl]piperazinyl]-3-phenylpropan-2-ol (8) had the highest selectivity. The latter (8) is one of the most DAT selective ligands known. In accord with the in vitro data, 6 showed greater potency than 7 in elevating extracellular dopamine levels in a microdialysis assay and in inhibiting cocaine-maintained responding in rhesus monkeys. JF - Journal of medicinal chemistry AU - Hsin, Ling-Wei AU - Dersch, Christina M AU - Baumann, Michael H AU - Stafford, David AU - Glowa, John R AU - Rothman, Richard B AU - Jacobson, Arthur E AU - Rice, Kenner C AD - Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/03/14/ PY - 2002 DA - 2002 Mar 14 SP - 1321 EP - 1329 VL - 45 IS - 6 SN - 0022-2623, 0022-2623 KW - 1-(4-(2-(bis(4-fluorophenyl)methoxy)ethyl)piperazinyl)-3-phenylpropan-2-ol KW - 0 KW - 1-(4-(2-(diphenylmethoxy)ethyl)piperazinyl)-3-phenylpropan-2-ol KW - Benzhydryl Compounds KW - Dopamine Plasma Membrane Transport Proteins KW - Dopamine Uptake Inhibitors KW - Ligands KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Piperazines KW - Propanols KW - SLC6A3 protein, human KW - Slc6a3 protein, rat KW - Index Medicus KW - Animals KW - Stereoisomerism KW - Benzhydryl Compounds -- chemical synthesis KW - Benzhydryl Compounds -- pharmacology KW - Humans KW - Microdialysis KW - Rats KW - Behavior, Animal -- drug effects KW - Rats, Sprague-Dawley KW - Macaca mulatta KW - Male KW - Propanols -- chemical synthesis KW - Piperazines -- chemical synthesis KW - Propanols -- pharmacology KW - Dopamine Uptake Inhibitors -- chemical synthesis KW - Cocaine-Related Disorders -- drug therapy KW - Piperazines -- pharmacology KW - Membrane Transport Proteins -- metabolism KW - Dopamine Uptake Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71502118?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Development+of+long-acting+dopamine+transporter+ligands+as+potential+cocaine-abuse+therapeutic+agents%3A+chiral+hydroxyl-containing+derivatives+of+1-%5B2-%5Bbis%284-fluorophenyl%29methoxy%5Dethyl%5D-4-%283-phenylpropyl%29piperazine+and+1-%5B2-%28diphenylmethoxy%29ethyl%5D-4-%283-phenylpropyl%29piperazine.&rft.au=Hsin%2C+Ling-Wei%3BDersch%2C+Christina+M%3BBaumann%2C+Michael+H%3BStafford%2C+David%3BGlowa%2C+John+R%3BRothman%2C+Richard+B%3BJacobson%2C+Arthur+E%3BRice%2C+Kenner+C&rft.aulast=Hsin&rft.aufirst=Ling-Wei&rft.date=2002-03-14&rft.volume=45&rft.issue=6&rft.spage=1321&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=00222623&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-26 N1 - Date created - 2002-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Accuracy of muscle localization without EMG: implications for treatment of limb dystonia. AN - 71518758; 11889247 AB - Although botulinum toxin is an effective treatment for focal dystonia, the importance of electromyography (EMG) in identifying muscles and guiding injections is unclear. The authors examined the accuracy of muscle localization in 38 muscles in patients with focal hand dystonia without EMG guidance. Only 37% of needle placement attempts reached the target muscles or muscle fascicles. This study demonstrates that EMG guidance is needed for correct localization of desired muscles. JF - Neurology AU - Molloy, F M AU - Shill, H A AU - Kaelin-Lang, A AU - Karp, B I AD - Human Motor Control Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892-1428, USA. Y1 - 2002/03/12/ PY - 2002 DA - 2002 Mar 12 SP - 805 EP - 807 VL - 58 IS - 5 SN - 0028-3878, 0028-3878 KW - Botulinum Toxins KW - EC 3.4.24.69 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Botulinum Toxins -- therapeutic use KW - Humans KW - Injections, Intramuscular -- methods KW - Electromyography KW - Muscle, Skeletal -- physiopathology KW - Dystonia -- drug therapy KW - Dystonia -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71518758?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Accuracy+of+muscle+localization+without+EMG%3A+implications+for+treatment+of+limb+dystonia.&rft.au=Molloy%2C+F+M%3BShill%2C+H+A%3BKaelin-Lang%2C+A%3BKarp%2C+B+I&rft.aulast=Molloy&rft.aufirst=F&rft.date=2002-03-12&rft.volume=58&rft.issue=5&rft.spage=805&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-19 N1 - Date created - 2002-03-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Benzamide-based thiolcarbamates: a new class of HIV-1 NCp7 inhibitors. AN - 71457634; 11858998 AB - The HIV-1 nucleocapsid protein NCp7, which contains two highly conserved zinc fingers, is being used as a novel target for AIDS therapy due to its pivotal role in viral replication and its mutationally intolerant nature. Herein we report a new class of NCp7 inhibitors that possess good antiviral activity with low cellular toxicity. JF - Bioorganic & medicinal chemistry letters AU - Goel, Atul AU - Mazur, Sharlyn J AU - Fattah, Rasem J AU - Hartman, Tracy L AU - Turpin, Jim A AU - Huang, Mingjun AU - Rice, William G AU - Appella, Ettore AU - Inman, John K AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/03/11/ PY - 2002 DA - 2002 Mar 11 SP - 767 EP - 770 VL - 12 IS - 5 SN - 0960-894X, 0960-894X KW - Anti-HIV Agents KW - 0 KW - Benzamides KW - Capsid Proteins KW - Gene Products, gag KW - NCP7 protein, Human immunodeficiency virus 1 KW - Thiocarbamates KW - Tumor Necrosis Factor-alpha KW - Viral Proteins KW - gag Gene Products, Human Immunodeficiency Virus KW - Index Medicus KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Humans KW - Tumor Necrosis Factor-alpha -- pharmacology KW - HIV Infections -- drug therapy KW - Monocytes -- drug effects KW - Zinc Fingers KW - Structure-Activity Relationship KW - Anti-HIV Agents -- chemical synthesis KW - Benzamides -- chemistry KW - Capsid -- antagonists & inhibitors KW - Anti-HIV Agents -- pharmacology KW - Thiocarbamates -- chemical synthesis KW - Gene Products, gag -- antagonists & inhibitors KW - Thiocarbamates -- pharmacology KW - HIV-1 -- physiology KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71457634?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioorganic+%26+medicinal+chemistry+letters&rft.atitle=Benzamide-based+thiolcarbamates%3A+a+new+class+of+HIV-1+NCp7+inhibitors.&rft.au=Goel%2C+Atul%3BMazur%2C+Sharlyn+J%3BFattah%2C+Rasem+J%3BHartman%2C+Tracy+L%3BTurpin%2C+Jim+A%3BHuang%2C+Mingjun%3BRice%2C+William+G%3BAppella%2C+Ettore%3BInman%2C+John+K&rft.aulast=Goel&rft.aufirst=Atul&rft.date=2002-03-11&rft.volume=12&rft.issue=5&rft.spage=767&rft.isbn=&rft.btitle=&rft.title=Bioorganic+%26+medicinal+chemistry+letters&rft.issn=0960894X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-02 N1 - Date created - 2002-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - P53: an ubiquitous target of anticancer drugs. AN - 71468605; 11857402 AB - The p53 tumor suppressor can induce growth arrest, apoptosis and cell senescence. Not surprisingly, p53 is an appealing target for therapeutic intervention. Although current anticancer agents do not directly interact with p53, these agents (including DNA damaging drugs, antimetabolites, microtubule-active drugs and inhibitors of the proteasome) cause accumulation of wt p53. Depending on the p53 status of cancer cells, diverse therapeutic strategies are under development. These include pharmacological rescue of mutant p53 function and reactivation of wt p53 in E6-expressing cells. For protection of normal cells, strategies range from abrogation of wt p53 induction, thereby decreasing the toxicity of DNA damaging agents, to activation of wt p53-dependent checkpoints, thereby protecting cells against cell cycle-dependent therapeutics. Copyright 2001 Wiley-Liss, Inc. JF - International journal of cancer AU - Blagosklonny, Mikhail V AD - Medicine Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. mikhailb@box-m.nih.gov Y1 - 2002/03/10/ PY - 2002 DA - 2002 Mar 10 SP - 161 EP - 166 VL - 98 IS - 2 SN - 0020-7136, 0020-7136 KW - Antineoplastic Agents KW - 0 KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Drug Delivery Systems KW - Humans KW - Mutation KW - Models, Biological KW - Neoplasms -- drug therapy KW - Tumor Suppressor Protein p53 -- genetics KW - Antineoplastic Agents -- therapeutic use KW - Tumor Suppressor Protein p53 -- metabolism KW - Antineoplastic Agents -- pharmacology KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71468605?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=P53%3A+an+ubiquitous+target+of+anticancer+drugs.&rft.au=Blagosklonny%2C+Mikhail+V&rft.aulast=Blagosklonny&rft.aufirst=Mikhail&rft.date=2002-03-10&rft.volume=98&rft.issue=2&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-07 N1 - Date created - 2002-02-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of DNA polymerase beta stacking interactions with templating purines, but not pyrimidines, alters catalytic efficiency and fidelity. AN - 71532867; 11756435 AB - Structures of DNA polymerases bound with DNA reveal that the 5'-trajectory of the template strand is dramatically altered as it exits the polymerase active site. This distortion provides the polymerase access to the nascent base pair to interrogate proper Watson-Crick geometry. Upon binding a correct deoxynucleoside triphosphate, alpha-helix N of DNA polymerase beta is observed to form one face of the binding pocket for the new base pair. Asp-276 and Lys-280 stack with the bases of the incoming nucleotide and template, respectively. To determine the role of Lys-280, site-directed mutants were constructed at this position, and the proteins were expressed and purified, and their catalytic efficiency and fidelity were assessed. The catalytic efficiency for single-nucleotide gap filling with the glycine mutant (K280G) was strongly diminished relative to wild type for templating purines (>15-fold) due to a decreased binding affinity for the incoming nucleotide. In contrast, catalytic efficiency was hardly affected by glycine substitution for templating pyrimidines (<4-fold). The fidelity of the glycine mutant was identical to the wild type enzyme for misinsertion opposite a template thymidine, whereas the fidelity of misinsertion opposite a template guanine was modestly altered. The nature of the Lys-280 side-chain substitution for thymidine triphosphate insertion (templating adenine) indicates that Lys-280 "stabilizes" templating purines through van der Waals interactions. JF - The Journal of biological chemistry AU - Beard, William A AU - Shock, David D AU - Yang, Xiao-Ping AU - DeLauder, Saundra F AU - Wilson, Samuel H AD - Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/03/08/ PY - 2002 DA - 2002 Mar 08 SP - 8235 EP - 8242 VL - 277 IS - 10 SN - 0021-9258, 0021-9258 KW - Purines KW - 0 KW - Pyrimidines KW - Thymine Nucleotides KW - Aspartic Acid KW - 30KYC7MIAI KW - DNA KW - 9007-49-2 KW - Arginine KW - 94ZLA3W45F KW - DNA Polymerase beta KW - EC 2.7.7.- KW - Lysine KW - K3Z4F929H6 KW - thymidine 5'-triphosphate KW - QOP4K539MU KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Glycine -- chemistry KW - Protein Structure, Secondary KW - Thymine Nucleotides -- metabolism KW - Lysine -- chemistry KW - Models, Molecular KW - Arginine -- chemistry KW - Dose-Response Relationship, Drug KW - DNA -- metabolism KW - Humans KW - Protein Binding KW - Aspartic Acid -- chemistry KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Base Pair Mismatch KW - Kinetics KW - Models, Chemical KW - Protein Structure, Tertiary KW - Mutation KW - Hydrogen Bonding KW - Catalysis KW - Pyrimidines -- chemistry KW - DNA Polymerase beta -- chemistry KW - Purines -- chemistry KW - DNA Polymerase beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71532867?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Loss+of+DNA+polymerase+beta+stacking+interactions+with+templating+purines%2C+but+not+pyrimidines%2C+alters+catalytic+efficiency+and+fidelity.&rft.au=Beard%2C+William+A%3BShock%2C+David+D%3BYang%2C+Xiao-Ping%3BDeLauder%2C+Saundra+F%3BWilson%2C+Samuel+H&rft.aulast=Beard&rft.aufirst=William&rft.date=2002-03-08&rft.volume=277&rft.issue=10&rft.spage=8235&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-15 N1 - Date created - 2002-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Requirement of estrogen receptor-alpha in insulin-like growth factor-1 (IGF-1)-induced uterine responses and in vivo evidence for IGF-1/estrogen receptor cross-talk. AN - 71505086; 11751931 AB - In the uterus insulin-like growth factor-1 (IGF-1) signaling can be initiated by estradiol acting through its nuclear receptor (estrogen receptor (ER)) to stimulate the local synthesis of IGF-1. Conversely, in vitro studies have demonstrated that estradiol-independent ER transcriptional activity can be induced by IGF-1 signaling, providing evidence for a cross-talk mechanism between IGF-1 and ER. To investigate whether ER alpha is required for uterine responses to IGF-1 in vivo, both wild-type (WT) and ER alpha knockout (alpha ERKO) mice were administered IGF-1, and various uterine responses to IGF-1 were compared. In both WT and alpha ERKO mice, IGF-1 treatment resulted in phosphorylation of uterine IGF-1 receptor (IGF-1R) and formation of an IGF-1R/insulin receptor substrate-1/ phosphatidylinositol 3-kinase signaling complex. In addition, IGF-1 stimulated phosphorylation of uterine Akt and MAPK in both WT and alpha ERKO mice. However, IGF-1 treatment stimulated BrdUrd incorporation and proliferating cell nuclear antigen expression in WT uteri only. To determine whether ER alpha can be activated in vivo by IGF-1 signaling, transgenic mice carrying a luciferase gene driven by two estrogen response elements (ERE-luciferase mice) were utilized. Treatment of ovariectomized ERE-luciferase mice with IGF-1 resulted in an increase in uterine luciferase activity that was attenuated in the presence of the ER antagonist ICI 182,780. Together these data demonstrate that 1) functional signaling proximal to IGF-1R is maintained in the alpha ERKO mouse uterus, 2) ER alpha is necessary for IGF-1 induction of uterine nuclear proliferative responses, and 3) cross-talk between IGF-1R and ER signaling pathways exists in vivo. JF - The Journal of biological chemistry AU - Klotz, Diane M AU - Hewitt, Sylvia Curtis AU - Ciana, Paolo AU - Raviscioni, Michele AU - Lindzey, Jonathan K AU - Foley, Julie AU - Maggi, Adriana AU - DiAugustine, Richard P AU - Korach, Kenneth S AD - Laboratory of Molecular Carcinogenesis, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/03/08/ PY - 2002 DA - 2002 Mar 08 SP - 8531 EP - 8537 VL - 277 IS - 10 SN - 0021-9258, 0021-9258 KW - Estrogen Antagonists KW - 0 KW - Estrogen Receptor alpha KW - Proto-Oncogene Proteins KW - Receptors, Estrogen KW - fulvestrant KW - 22X328QOC4 KW - Estradiol KW - 4TI98Z838E KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Luciferases KW - EC 1.13.12.- KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-akt KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Index Medicus KW - Animals KW - Cell Nucleus -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Transcription, Genetic KW - Mice, Transgenic KW - Models, Biological KW - Mice, Knockout KW - Promoter Regions, Genetic KW - Estrogen Antagonists -- pharmacology KW - Response Elements KW - Time Factors KW - Signal Transduction KW - Cell Division KW - Bromodeoxyuridine -- metabolism KW - Immunoblotting KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Enzyme Activation KW - Luciferases -- metabolism KW - Mice KW - Precipitin Tests KW - Protein Binding KW - Immunohistochemistry KW - Female KW - Uterus -- metabolism KW - Estradiol -- analogs & derivatives KW - Estradiol -- pharmacology KW - Insulin-Like Growth Factor I -- metabolism KW - Receptors, Estrogen -- metabolism KW - Uterus -- enzymology KW - Receptors, Estrogen -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71505086?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Requirement+of+estrogen+receptor-alpha+in+insulin-like+growth+factor-1+%28IGF-1%29-induced+uterine+responses+and+in+vivo+evidence+for+IGF-1%2Festrogen+receptor+cross-talk.&rft.au=Klotz%2C+Diane+M%3BHewitt%2C+Sylvia+Curtis%3BCiana%2C+Paolo%3BRaviscioni%2C+Michele%3BLindzey%2C+Jonathan+K%3BFoley%2C+Julie%3BMaggi%2C+Adriana%3BDiAugustine%2C+Richard+P%3BKorach%2C+Kenneth+S&rft.aulast=Klotz&rft.aufirst=Diane&rft.date=2002-03-08&rft.volume=277&rft.issue=10&rft.spage=8531&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-15 N1 - Date created - 2002-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047. AN - 71484781; 11873000 AB - Lipid lowering therapy is used increasingly in persons with HIV infection in the absence of safety data or information on drug interactions with antiretroviral agents. The primary objectives of this study were to examine the effects of ritonavir (RTV) plus saquinavir soft-gel (SQVsgc) capsules on the pharmacokinetics of pravastatin, simvastatin, and atorvastatin, and the effect of pravastatin on the pharmacokinetics of nelfinavir (NFV) in order to determine clinically important drug-drug interactions. Randomized, open-label study in healthy, HIV seronegative adults at AIDS Clinical Trials Units across the USA. Three groups of subjects (arms 1, 2, and 3) received pravastatin, simvastatin or atorvastatin (40 mg daily each) from days 1-4 and 15-18. In these groups, RTV 400 mg and SQVsgc 400 mg twice daily were given from days 4-18. A fourth group (arm 4) received NFV 1250 mg twice daily from days 1-14 with pravastatin 40 mg daily added from days 15-18. Statin and NFV levels were measured by liquid chromatography/tandem mass spectrometry. Fifty-six subjects completed both pharmacokinetic study days. In arms 1-3, the median estimated area under the curves (AUC)(0-24) for the statins were: pravastatin (arm 1, n = 13), 151 and 75 ng.h/ml on days 4 and 18 (decline of 50% in presence of RTV/SQVsgc), respectively (P = 0.005); simvastatin (arm 2, n = 14), 17 and 548 ng.h/ml on days 4 and 18 (increase of 3059% in the presence of RTV/SQVsgc), respectively (P < 0.001); and total active atorvastatin (arm 3, n = 14), 167 and 289 ng.h/ml on days 4 and 18 (increase of 79% in the presence of RTV/SQVsgc), respectively (P < 0.001). In arm 4, the median estimated AUC(0-8) for NFV (24 319 versus 26 760 ng.h/ml; P = 0.58) and its active M8 metabolite (15 565 versus 14 571 ng.h/m; P = 0.63) were not statistically different from day 14 to day 18 (without or with pravastatin). Simvastatin should be avoided and atorvastatin may be used with caution in persons taking RTV and SQVsgc. Dose adjustment of pravastatin may be necessary with concomitant use of RTV and SQVsgc. Pravastatin does not alter the NFV pharmacokinetics, and thus appears to be safe for concomitant use. JF - AIDS (London, England) AU - Fichtenbaum, Carl J AU - Gerber, John G AU - Rosenkranz, Susan L AU - Segal, Yoninah AU - Aberg, Judith A AU - Blaschke, Terrence AU - Alston, Beverly AU - Fang, Fang AU - Kosel, Bradley AU - Aweeka, Francesca AU - NIAID AIDS Clinical Trials Group AD - University of Cincinnati College of Medicine, Holmes Hospital, Eden Avenue and Albert Sabin Way, Cincinnati, Ohio 45267-0405, USA. ; NIAID AIDS Clinical Trials Group Y1 - 2002/03/08/ PY - 2002 DA - 2002 Mar 08 SP - 569 EP - 577 VL - 16 IS - 4 SN - 0269-9370, 0269-9370 KW - Anticholesteremic Agents KW - 0 KW - HIV Protease Inhibitors KW - Heptanoic Acids KW - Pyrroles KW - Atorvastatin Calcium KW - 48A5M73Z4Q KW - Simvastatin KW - AGG2FN16EV KW - Pravastatin KW - KXO2KT9N0G KW - Saquinavir KW - L3JE09KZ2F KW - Ritonavir KW - O3J8G9O825 KW - Index Medicus KW - AIDS/HIV KW - Drug Interactions KW - Humans KW - Adult KW - Human Experimentation KW - Pyrroles -- adverse effects KW - Simvastatin -- adverse effects KW - Pyrroles -- pharmacokinetics KW - Ritonavir -- pharmacokinetics KW - Pravastatin -- pharmacokinetics KW - Saquinavir -- pharmacokinetics KW - Heptanoic Acids -- adverse effects KW - Pravastatin -- adverse effects KW - Anticholesteremic Agents -- pharmacokinetics KW - Heptanoic Acids -- pharmacokinetics KW - Simvastatin -- pharmacokinetics KW - HIV Protease Inhibitors -- pharmacokinetics KW - Anticholesteremic Agents -- adverse effects KW - HIV Seronegativity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71484781?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+%28London%2C+England%29&rft.atitle=Pharmacokinetic+interactions+between+protease+inhibitors+and+statins+in+HIV+seronegative+volunteers%3A+ACTG+Study+A5047.&rft.au=Fichtenbaum%2C+Carl+J%3BGerber%2C+John+G%3BRosenkranz%2C+Susan+L%3BSegal%2C+Yoninah%3BAberg%2C+Judith+A%3BBlaschke%2C+Terrence%3BAlston%2C+Beverly%3BFang%2C+Fang%3BKosel%2C+Bradley%3BAweeka%2C+Francesca%3BNIAID+AIDS+Clinical+Trials+Group&rft.aulast=Fichtenbaum&rft.aufirst=Carl&rft.date=2002-03-08&rft.volume=16&rft.issue=4&rft.spage=569&rft.isbn=&rft.btitle=&rft.title=AIDS+%28London%2C+England%29&rft.issn=02699370&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-20 N1 - Date created - 2002-03-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: AIDS. 2003;17 Suppl 4:S109-10 [15080191] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biophysical Characterization of Cyclic Nucleotide Phosphodiesterases AN - 18283297; 5331442 AB - We have compared selected biophysical properties of three phosphodiesterases, from Arabidopsis thaliana, Saccharomyces cerevisiae, and Escherichia coli. All of them belong to a recently identified family of cyclic nucleotide phosphodiesterases. Experiments elucidating folding stability, protein fluorescence, oligomerization behavior, and the effects of substrates were conducted, revealing differences between the plant and the yeast protein. According to CD spectroscopy, the latter protein exhibits an ( alpha + beta ) fold rather than an ( alpha / beta ) fold as found with CPDase (A. thaliana). The redox-dependent structural reorganization recently found for the plant protein by X-ray crystallography could not be detected by CD spectroscopy due to its only marginal effect on the total percentage of helical content. However, in the present study a redox-dependent effect was also observed for the yeast CPDase. The enzymatic activity of wild type CPDase (A. thaliana) as well as of four mutants were characterized by isothermal titration calorimetry and the results prove the requirement of all four residues of the previously identified tandem signature motif for the catalytic function. Within the comparison of the three proteins in this study, the PDase Homolog /RNA ligase (E. coli) shares more similarities with the plant than with the yeast protein. JF - Biochemical and Biophysical Research Communications AU - Hofmann, A AU - Tarasov, S AU - Grella, M AU - Ruvinov, S AU - Nasr, F AU - Filipowicz, W AU - Wlodawer, A AD - Protein Structure Section, Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, Maryland, 21702, hofmanna@ncifcrf.gov Y1 - 2002/03/08/ PY - 2002 DA - 2002 Mar 08 SP - 875 EP - 883 PB - Academic Press VL - 291 IS - 4 SN - 0006-291X, 0006-291X KW - budding yeast KW - cyclic-nucleotide phosphodiesterase KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Microbiology Abstracts B: Bacteriology KW - X-ray crystallography KW - Protein folding KW - C.D. KW - Escherichia coli KW - Calorimetry KW - Saccharomyces cerevisiae KW - K 03020:Fungi KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18283297?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+Biophysical+Research+Communications&rft.atitle=Biophysical+Characterization+of+Cyclic+Nucleotide+Phosphodiesterases&rft.au=Hofmann%2C+A%3BTarasov%2C+S%3BGrella%2C+M%3BRuvinov%2C+S%3BNasr%2C+F%3BFilipowicz%2C+W%3BWlodawer%2C+A&rft.aulast=Hofmann&rft.aufirst=A&rft.date=2002-03-08&rft.volume=291&rft.issue=4&rft.spage=875&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+Biophysical+Research+Communications&rft.issn=0006291X&rft_id=info:doi/10.1006%2Fbbrc.2002.6527 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Saccharomyces cerevisiae; Escherichia coli; Protein folding; X-ray crystallography; C.D.; Calorimetry DO - http://dx.doi.org/10.1006/bbrc.2002.6527 ER - TY - JOUR T1 - Mitochondrial DNA repair of oxidative damage in mammalian cells. AN - 71599914; 11943468 AB - Nuclear and mitochondrial DNA are constantly being exposed to damaging agents, from endogenous and exogenous sources. In particular, reactive oxygen species (ROS) are formed at high levels as by-products of the normal metabolism. Upon oxidative attack of DNA many DNA lesions are formed and oxidized bases are generated with high frequency. Mitochondrial DNA has been shown to accumulate high levels of 8-hydroxy-2'-deoxyguanosine, the product of hydroxylation of guanine at carbon 8, which is a mutagenic lesion. Most of these small base modifications are repaired by the base excision repair (BER) pathway. Despite the initial concept that mitochondria lack DNA repair, experimental evidences now show that mitochondria are very proficient in BER of oxidative DNA damage, and proteins necessary for this pathway have been isolated from mammalian mitochondria. Here, we examine the BER pathway with an emphasis on mtDNA repair. The molecular mechanisms involved in the formation and removal of oxidative damage from mitochondria are discussed. The pivotal role of the OGG1 glycosylase in removal of oxidized guanines from mtDNA will also be examined. Lastly, changes in mtDNA repair during the aging process and possible biological implications are discussed. JF - Gene AU - Bohr, Vilhelm A AU - Stevnsner, Tinna AU - de Souza-Pinto, Nadja C AD - Laboratory of Molecular Gerontology, Box 1, National Institute on Aging, NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. vbohr@nih.gov Y1 - 2002/03/06/ PY - 2002 DA - 2002 Mar 06 SP - 127 EP - 134 VL - 286 IS - 1 SN - 0378-1119, 0378-1119 KW - DNA, Mitochondrial KW - 0 KW - DNA-Binding Proteins KW - Reactive Oxygen Species KW - X-ray repair cross complementing protein 1 KW - Guanosine KW - 12133JR80S KW - 1,N(6)-ethenoadenine KW - 13875-63-3 KW - Hypoxanthine KW - 2TN51YD919 KW - 8-hydroxyguanosine KW - 3868-31-3 KW - DNA Glycosylases KW - EC 3.2.2.- KW - N-Glycosyl Hydrolases KW - DNA-Formamidopyrimidine Glycosylase KW - EC 3.2.2.23 KW - DNA Ligases KW - EC 6.5.1.- KW - Adenine KW - JAC85A2161 KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Mitochondria, Liver -- enzymology KW - Cell Nucleus -- metabolism KW - Humans KW - Aging KW - Hypoxanthine -- metabolism KW - Mitochondria, Heart -- enzymology KW - Mice KW - Rats KW - N-Glycosyl Hydrolases -- metabolism KW - Oxidative Stress KW - DNA Ligases -- metabolism KW - Cell Nucleus -- genetics KW - DNA-Binding Proteins -- metabolism KW - DNA Repair KW - Adenine -- metabolism KW - Guanosine -- analogs & derivatives KW - DNA Damage KW - DNA, Mitochondrial -- metabolism KW - Guanosine -- metabolism KW - Adenine -- analogs & derivatives KW - DNA, Mitochondrial -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71599914?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene&rft.atitle=Mitochondrial+DNA+repair+of+oxidative+damage+in+mammalian+cells.&rft.au=Bohr%2C+Vilhelm+A%3BStevnsner%2C+Tinna%3Bde+Souza-Pinto%2C+Nadja+C&rft.aulast=Bohr&rft.aufirst=Vilhelm&rft.date=2002-03-06&rft.volume=286&rft.issue=1&rft.spage=127&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-04 N1 - Date created - 2002-04-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endogenous ligand of alpha(1) sodium pump, marinobufagenin, is a novel mediator of sodium chloride--dependent hypertension. AN - 71503039; 11877366 AB - Digitalis-like sodium pump ligands (SPLs) effect natriuresis via inhibition of renal tubular Na(+),K(+)-ATPase but may induce vasoconstriction. The present study investigated the potential roles of 2 putative endogenous SPLs, an ouabain-like compound (OLC) and an alpha(1) Na(+),K(+)-ATPase inhibitor, marinobufagenin (MBG), in regulating natriuresis and blood pressure (BP) responses to sustained and acute NaCl loading in Dahl salt-sensitive rats (DS). During 4 weeks of an 8% NaCl diet, DS exhibited a progressive increase in MBG renal excretion (66 +/-13 pmol/24 hours at week 4 versus 11 +/- 1 pmol/24 hours at baseline, n=48), which paralleled an increase in systolic BP (174 +/- 10 mm Hg at week 4 versus 110 +/- 2 mm Hg at baseline). By contrast, OLC excretion peaked at week 1 and returned to baseline levels. Administration of an anti-MBG, but not anti-ouabain antibody, to DS after 3 weeks of a high NaCl diet lowered BP (139 +/- 7 versus 175 +/- 5 mm Hg, P<0.001, n=5). Acute NaCl loading (2 hours) of DS (n=5) increased MBG and OLC excretion and natriuresis. Pretreatment of acutely NaCl-loaded DS with an anti-MBG antibody (n=5) reduced the excretion of sodium and MBG but not that of OLC. An anti-ouabain antibody (n=5) reduced sodium excretion and both OLC and MBG. An initial transient stimulation of OLC induced by NaCl loading of DS precedes an MBG response. A sustained increase in MBG production in DS contributes to the chronic BP elevation induced by a sustained high NaCl intake. JF - Circulation AU - Fedorova, Olga V AU - Talan, Mark I AU - Agalakova, Natalia I AU - Lakatta, Edward G AU - Bagrov, Alexei Y AD - Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 2002/03/05/ PY - 2002 DA - 2002 Mar 05 SP - 1122 EP - 1127 VL - 105 IS - 9 KW - Antibodies KW - 0 KW - Bufanolides KW - Cardenolides KW - Enzyme Inhibitors KW - Ligands KW - Saponins KW - Sodium Chloride, Dietary KW - Vasoconstrictor Agents KW - digoxin-like factors KW - Sodium Chloride KW - 451W47IQ8X KW - marinobufagenin KW - 470-42-8 KW - Digoxin KW - 73K4184T59 KW - Sodium KW - 9NEZ333N27 KW - Sodium-Potassium-Exchanging ATPase KW - EC 3.6.3.9 KW - Potassium KW - RWP5GA015D KW - Abridged Index Medicus KW - Index Medicus KW - Models, Animal KW - Animals KW - Natriuresis -- drug effects KW - Adrenal Glands -- metabolism KW - Saponins -- antagonists & inhibitors KW - Rats, Inbred Dahl KW - Rats KW - Saponins -- metabolism KW - Antibodies -- pharmacology KW - Potassium -- blood KW - Enzyme Inhibitors -- metabolism KW - Sodium Chloride -- urine KW - Sodium -- blood KW - Blood Pressure -- drug effects KW - Pituitary Gland -- metabolism KW - Vasoconstrictor Agents -- metabolism KW - Male KW - Bufanolides -- metabolism KW - Bufanolides -- antagonists & inhibitors KW - Hypertension -- chemically induced KW - Sodium-Potassium-Exchanging ATPase -- metabolism KW - Sodium Chloride, Dietary -- adverse effects KW - Hypertension -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71503039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation&rft.atitle=Endogenous+ligand+of+alpha%281%29+sodium+pump%2C+marinobufagenin%2C+is+a+novel+mediator+of+sodium+chloride--dependent+hypertension.&rft.au=Fedorova%2C+Olga+V%3BTalan%2C+Mark+I%3BAgalakova%2C+Natalia+I%3BLakatta%2C+Edward+G%3BBagrov%2C+Alexei+Y&rft.aulast=Fedorova&rft.aufirst=Olga&rft.date=2002-03-05&rft.volume=105&rft.issue=9&rft.spage=1122&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=1524-4539&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-18 N1 - Date created - 2002-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug selection with paclitaxel restores expression of linked IL-2 receptor gamma -chain and multidrug resistance (MDR1) transgenes in canine bone marrow AN - 18276484; 5330671 AB - Unstable expression of transferred genes is a major obstacle to successful gene therapy of hematopoietic diseases. We have investigated in a canine large-animal model whether expression of transduced genes can be recovered in vivo. Mixed-breed dogs had undergone autologous bone marrow transplantation (BMT) with stem cell factor and granulocyte-colony-stimulating factor-mobilized retrovirally marked hematopoietic cells. The bicistronic retroviral vector construct allowed for coexpression of MDR1 and human IL-2 receptor common gamma -chain cDNAs. The latter gene is deficient in X-linked severe combined immunodeficiency. After initial high-level expression, P-glycoprotein and the gamma -chain were undetectable in blood and bone marrow 17 months post-BMT. Six months later, one dog was treated i.v. with 125 mg/m super(2) paclitaxel. Three administrations restored expression of the two linked genes to high levels in blood and bone marrow. Two dogs treated with higher paclitaxel doses died from myelosuppression after the first administration. As determined by flow cytometry, both genes were expressed in granulocytes, monocytes, and lymphocytes of the surviving animal. PCR analysis of DNA from peripheral blood confirmed that the retroviral cDNA was increased after paclitaxel treatment, suggesting enrichment of transduced cells. P-glycoprotein was detectable for more than 1 year after cessation of paclitaxel. Repeated analyses of blood and bone marrow aspirates gave no indication of hematopoietic disturbance after BMT with transduced cells and paclitaxel treatment. In summary, we have shown that with the use of a drug-selectable marker gene, chemotherapy can select for cells that express an otherwise nonselected therapeutic gene in blood and bone marrow. JF - Proceedings of the National Academy of Sciences, USA AU - Licht, T AU - Haskins, M AU - Henthorn, P AU - Kleiman, SE AU - Bodine, D M AU - Whitwam, T AU - Puck, J M AU - Gottesman, M M AU - Melniczek, J R AD - Laboratories of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA, mgottesman@nih.gov Y1 - 2002/03/05/ PY - 2002 DA - 2002 Mar 05 SP - 3123 EP - 3128 VL - 99 IS - 5 SN - 0027-8424, 0027-8424 KW - dogs KW - MDR1 gene KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - Gene therapy KW - Interleukin 2 KW - Chemotherapy KW - X chromosome KW - Gene expression KW - P-Glycoprotein KW - Paclitaxel KW - Severe combined immunodeficiency KW - Bone marrow transplantation KW - G 07240:Immunogenetics KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18276484?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Drug+selection+with+paclitaxel+restores+expression+of+linked+IL-2+receptor+gamma+-chain+and+multidrug+resistance+%28MDR1%29+transgenes+in+canine+bone+marrow&rft.au=Licht%2C+T%3BHaskins%2C+M%3BHenthorn%2C+P%3BKleiman%2C+SE%3BBodine%2C+D+M%3BWhitwam%2C+T%3BPuck%2C+J+M%3BGottesman%2C+M+M%3BMelniczek%2C+J+R&rft.aulast=Licht&rft.aufirst=T&rft.date=2002-03-05&rft.volume=99&rft.issue=5&rft.spage=3123&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.052712199 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chemotherapy; P-Glycoprotein; Interleukin 2; Gene therapy; Gene expression; X chromosome; Severe combined immunodeficiency; Paclitaxel; Bone marrow transplantation DO - http://dx.doi.org/10.1073/pnas.052712199 ER - TY - JOUR T1 - Oxygen uptake rate in production of xylitol by Candida guilliermondii with different aeration rates and initial xylose concentrations AN - 856761228; 13857864 AB - The global oxygen uptake rate (OUR) and specific oxygen uptake rates (SOUR) were determined for different values of the volumetric oxygen mass transfer coefficient (15, 43, and 108 h super(-1)), and for varying initial xylose concentrations (50, 100, 150, and 200 g/L) in shaking flasks. The initial cell concentration was 4.0 g/L, and there was only significant growth in the fermentation with the highest oxygen availability. In this condition, OUR increased proportionally to cell growth, reaching maximum values from 2.1 to 2.5 g of O sub(2)/(L.h) in the stationary phase when the initial substrate concentration was raised from 50 to 200 g/L, respectively. SOUR showed different behavior, growing to a maximum value coinciding with the beginning of the exponential growth phase, after which point it decreased. The maximum SOUR values varied from 265 to 370 mg of O sub(2)/(g of cell.h), indicating the interdependence of this parameter and the substrate concentration. Although the volumetric productivity dropped slightly from 1.55 to 1.18 g of xylitol/(L.h), the strain producing capacity (g sub(P/X)) rose from 9 to 20.6 g/g when the initial substrate concentration was increased from 50 to 200 g/L. As for the xylitol yield over xylose consumed (g sub(P/S)), there was no significant variation, resulting in a mean value of 0.76 g/g. The results are of interest in establishing a strategy for controlling the dynamic oxygen supply to maximize volumetric productivity. JF - Applied Biochemistry and Biotechnology AU - Gimenes, Maria Antonieta P AU - Carlos, Luiz Claudio S AU - Faria, Luis FF AU - Pereira, Nei AD - Departamento de Engenharia Bioquimica, Escola de Quimica/CT, Universidade Federal do Rio de Janeiro, Ilha do Fundao, CEP: 21949-900, Rio de Janeiro, RJ, Brazil, nei@eq.ufrj.br Y1 - 2002/03// PY - 2002 DA - Mar 2002 SP - 1049 EP - 1059 PB - Humana Press Inc., 999 Riverview Dr., Ste. 208 Totowa NJ 07512 USA VL - 98-100 IS - 1-9 SN - 0273-2289, 0273-2289 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Biotechnology and Bioengineering Abstracts KW - stationary phase KW - Oxygen KW - Sour taste KW - Xylose KW - Fermentation KW - Xylitol KW - Candida guilliermondii KW - Mass transfer KW - Aeration KW - W 30945:Fermentation & Cell Culture KW - K 03320:Cell Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/856761228?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+Biochemistry+and+Biotechnology&rft.atitle=Oxygen+uptake+rate+in+production+of+xylitol+by+Candida+guilliermondii+with+different+aeration+rates+and+initial+xylose+concentrations&rft.au=Gimenes%2C+Maria+Antonieta+P%3BCarlos%2C+Luiz+Claudio+S%3BFaria%2C+Luis+FF%3BPereira%2C+Nei&rft.aulast=Gimenes&rft.aufirst=Maria+Antonieta&rft.date=2002-03-01&rft.volume=98-100&rft.issue=1-9&rft.spage=1049&rft.isbn=&rft.btitle=&rft.title=Applied+Biochemistry+and+Biotechnology&rft.issn=02732289&rft_id=info:doi/10.1385%2FABAB%3A98-100%3A1-9%3A1049 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-03-01 N1 - Last updated - 2013-12-04 N1 - SubjectsTermNotLitGenreText - stationary phase; Sour taste; Oxygen; Xylose; Fermentation; Xylitol; Mass transfer; Aeration; Candida guilliermondii DO - http://dx.doi.org/10.1385/ABAB:98-100:1-9:1049 ER - TY - JOUR T1 - Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function AN - 856754157; 13746331 AB - Positional cloning of hereditary deafness genes is a direct approach to identify molecules and mechanisms underlying auditory function. Here we report a locus for dominant deafness, DFNA36, which maps to human chromosome 9q13-21 in a region overlapping the DFNB7/B11 locus for recessive deafness. We identified eight mutations in a new gene, transmembrane cochlear-expressed gene 1 (TMC1), in a DFNA36 family and eleven DFNB7/B11 families. We detected a 1.6-kb genomic deletion encompassing exon 14 of Tmc1 in the recessive deafness (dn) mouse mutant, which lacks auditory responses and has hair-cell degeneration. TMC1 and TMC2 on chromosome 20p13 are members of a gene family predicted to encode transmembrane proteins. Tmc1 mRNA is expressed in hair cells of the postnatal mouse cochlea and vestibular end organs and is required for normal function of cochlear hair cells. JF - Nature Genetics AU - Kurima, Kiyoto AU - Peters, Linda M AU - Yang, Yandan AU - Riazuddin, Saima AU - Ahmed, Zubair M AU - Naz, Sadaf AU - Arnaud, Deidre AU - Drury, Stacy AU - Mo, Jianhong AU - Makishima, Tomoko AU - Ghosh, Manju AU - Menon, PSN AU - Deshmukh, Dilip AU - Oddoux, Carole AU - Ostrer, Harry AU - Khan, Shaheen AU - Riazuddin, Sheikh AU - Deininger, Prescott L AU - Hampton, Lori L AU - Sullivan, Susan L AU - Battey, James F AU - Keats, Bronya JB AU - Wilcox, Edward R AU - Friedman, Thomas B AU - Griffith, Andrew J AD - G-protein Coupled Receptors' Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 50 Center Drive, Bethesda, Maryland, USA. Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 277 EP - 284 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 30 IS - 3 SN - 1061-4036, 1061-4036 KW - Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts; CSA Neurosciences Abstracts KW - Cochlea KW - Exons KW - Auditory system KW - Cloning KW - Membrane proteins KW - chromosome 20 KW - mRNA KW - chromosome 9 KW - Deafness KW - Hair cells KW - Vestibular system KW - Degeneration KW - genomics KW - Mutation KW - Gene mapping KW - N3 11023:Neurogenetics KW - X 24490:Other KW - N 14830:RNA KW - G 07870:Mammals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/856754157?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Genetics&rft.atitle=Dominant+and+recessive+deafness+caused+by+mutations+of+a+novel+gene%2C+TMC1%2C+required+for+cochlear+hair-cell+function&rft.au=Kurima%2C+Kiyoto%3BPeters%2C+Linda+M%3BYang%2C+Yandan%3BRiazuddin%2C+Saima%3BAhmed%2C+Zubair+M%3BNaz%2C+Sadaf%3BArnaud%2C+Deidre%3BDrury%2C+Stacy%3BMo%2C+Jianhong%3BMakishima%2C+Tomoko%3BGhosh%2C+Manju%3BMenon%2C+PSN%3BDeshmukh%2C+Dilip%3BOddoux%2C+Carole%3BOstrer%2C+Harry%3BKhan%2C+Shaheen%3BRiazuddin%2C+Sheikh%3BDeininger%2C+Prescott+L%3BHampton%2C+Lori+L%3BSullivan%2C+Susan+L%3BBattey%2C+James+F%3BKeats%2C+Bronya+JB%3BWilcox%2C+Edward+R%3BFriedman%2C+Thomas+B%3BGriffith%2C+Andrew+J&rft.aulast=Kurima&rft.aufirst=Kiyoto&rft.date=2002-03-01&rft.volume=30&rft.issue=3&rft.spage=277&rft.isbn=&rft.btitle=&rft.title=Nature+Genetics&rft.issn=10614036&rft_id=info:doi/10.1038%2Fng842 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-03-01 N1 - Last updated - 2016-02-29 N1 - SubjectsTermNotLitGenreText - Cochlea; Auditory system; Exons; Cloning; Membrane proteins; chromosome 20; mRNA; chromosome 9; Deafness; Hair cells; Vestibular system; Degeneration; genomics; Mutation; Gene mapping DO - http://dx.doi.org/10.1038/ng842 ER - TY - JOUR T1 - Piezoelectric reciprocal relationship of the membrane motor in the cochlear outer hair cell. AN - 85250961; pmid-11867442 AB - It has been shown that the membrane motor in the outer hair cell is driven by the membrane potential. Here we examine whether the motility satisfies the reciprocal relationship, the characteristic of piezoelectricity, by measuring charge displacement induced by stretching the cell with known force. The efficiency of inducing charge displacement was membrane potential dependent. The maximum efficiency of inducing charge displacement by force was approximately 20 fC/nN for 50-microm-long lateral membrane. The efficiency per cell stretching was 0.1 pC/microm. We found that these values are consistent with the reciprocal relationship based on the voltage sensitivity of approximately 20 nm/mV for 50-microm-long cell and force production of 0.1 nN/mV by the cell. We can thus conclude that the membrane motor in the outer hair cell satisfies a necessary condition for piezoelectricity and that the hair cell's piezoelectric coefficient of 20 fC/nN is four orders of magnitude greater than the best man-made material. JF - Biophysical Journal AU - Xiao-xia, Dong AU - Ospeck, Mark AU - Iwasa, Kuni H AD - Biophysics Section, Laboratory of Cellular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA.; National Institute on Deafness and Other Communication Disorders PY - 2002 SP - 1254 EP - 1259 VL - 82 IS - 3 SN - 0006-3495, 0006-3495 KW - Patch-Clamp Techniques KW - Thermodynamics KW - Guinea Pigs KW - Hair Cells, Outer KW - Animal KW - Models, Statistical KW - Electrophysiology KW - Time Factors KW - Microspheres KW - Biophysics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85250961?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biophysical+Journal&rft.atitle=Piezoelectric+reciprocal+relationship+of+the+membrane+motor+in+the+cochlear+outer+hair+cell.&rft.au=Xiao-xia%2C+Dong%3BOspeck%2C+Mark%3BIwasa%2C+Kuni+H&rft.aulast=Xiao-xia&rft.aufirst=Dong&rft.date=2002-03-01&rft.volume=82&rft.issue=3&rft.spage=1254&rft.isbn=&rft.btitle=&rft.title=Biophysical+Journal&rft.issn=00063495&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Effective time averaging of multiplexed measurements: a critical analysis. AN - 85238073; pmid-11922314 AB - Multiplexing and time averaging of signal are effective noise reduction protocols applied in many analytical measurement systems. The efficacy of these protocols may be reduced by random occurrences of high-magnitude noise that do not conform to the statistical distribution of noise for all other measurements in the data set. This high-magnitude noise, which may have an insignificant probability of occurrence for a single measurement, almost certainly affects data collected in a multichannel, multiplexed modality, such as Fourier transform infrared (FT-IR) spectroscopic imaging employing focal plane array detectors. To recover time-averaging advantages in these cases, we present a general coaddition method that uses two statistical measures, the mean and median of the ensemble of measurements of a signal, to obtain a better estimate of the true signal than that estimated by time averaging alone. This method, termed median filtered time averaging, is shown to be an effective noise removal procedure for FT-IR imaging data. The effects of noise removal on time averaging and multiplexing are examined theoretically and are demonstrated for hyperspectral infrared microspectroscopic imaging data obtained from human skin biopsies by using a rapid data acquisition procedure. JF - Analytical Chemistry AU - Bhargava Rohit AU - Levin, Ira W AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0510, USA. PY - 2002 SP - 1429 EP - 1435 VL - 74 IS - 6 SN - 0003-2700, 0003-2700 KW - Spectroscopy, Fourier Transform Infrared KW - Time and Motion Studies UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85238073?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Analytical+Chemistry&rft.atitle=Effective+time+averaging+of+multiplexed+measurements%3A+a+critical+analysis.&rft.au=Bhargava+Rohit%3BLevin%2C+Ira+W&rft.aulast=Bhargava+Rohit&rft.aufirst=&rft.date=2002-03-01&rft.volume=74&rft.issue=6&rft.spage=1429&rft.isbn=&rft.btitle=&rft.title=Analytical+Chemistry&rft.issn=00032700&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Atypical autonomic regulation in perpetrators of violent domestic abuse. AN - 72057318; 12212660 AB - Perpetrators of domestic violence describe symptoms that are compatible with exaggerated autonomic arousal at the time of the domestic violence. This inappropriate arousal may be reflected in altered heart rate regulation. If heart rate is systematically regulated by vagal mechanisms, then increases in heart rate should correlate with decreases in cardiac vagal activity, as indexed by respiratory sinus arrhythmia (RSA). We hypothesized that perpetrators of domestic violence have an alteration in heart rate regulation. To test this hypothesis we compared the results of a postural shift performed on perpetrators, healthy volunteers, and nonviolent alcoholics. Results showed there were no significant differences in heart rate, RSA, or catecholamines. However, the significant inverse relationship between posture-elicited changes in RSA and heart rate present in the healthy volunteers was not found in perpetrators. These differences in the covariation between heart rate and RSA may represent differences in the neural regulation of heart rate and may be related to difficulties in controlling autonomic state. JF - Psychophysiology AU - Umhau, John C AU - George, David T AU - Reed, Shawn AU - Petrulis, Sarah G AU - Rawlings, Robert AU - Porges, Stephen W AD - Laboratory of Clinical Studies, DICBR, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892, USA. Umhau@nih.gov Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 117 EP - 123 VL - 39 IS - 2 SN - 0048-5772, 0048-5772 KW - Index Medicus KW - Hemodynamics -- physiology KW - Humans KW - Adult KW - Heart Rate -- physiology KW - Alcoholism -- physiopathology KW - Posture -- physiology KW - Male KW - Autonomic Nervous System -- physiology KW - Domestic Violence -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72057318?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychophysiology&rft.atitle=Atypical+autonomic+regulation+in+perpetrators+of+violent+domestic+abuse.&rft.au=Umhau%2C+John+C%3BGeorge%2C+David+T%3BReed%2C+Shawn%3BPetrulis%2C+Sarah+G%3BRawlings%2C+Robert%3BPorges%2C+Stephen+W&rft.aulast=Umhau&rft.aufirst=John&rft.date=2002-03-01&rft.volume=39&rft.issue=2&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=Psychophysiology&rft.issn=00485772&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-01 N1 - Date created - 2002-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radiosensitivity in Fanconi's anemia patients. AN - 71990275; 12175566 AB - The risks of radiation therapy in patients with Fanconi's anemia who have cancer are not clear. Possible toxicity was reported in six of 14 patients: 1/1 with vaginal cancer, 4/10 with head and neck or esophageal cancer, and 1/3 with oral cancer following bone marrow transplant. JF - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology AU - Alter, Blanche P AD - Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, EPS 7020, Rockville, MD 20852, USA. Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 345 EP - 347 VL - 62 IS - 3 SN - 0167-8140, 0167-8140 KW - Index Medicus KW - Risk Factors KW - Humans KW - Adult KW - Treatment Outcome KW - Precancerous Conditions -- diagnosis KW - Child KW - Adolescent KW - Male KW - Female KW - Fanconi Anemia -- complications KW - Esophageal Neoplasms -- complications KW - Head and Neck Neoplasms -- complications KW - Vulvar Neoplasms -- complications KW - Radiation Tolerance KW - Head and Neck Neoplasms -- radiotherapy KW - Esophageal Neoplasms -- radiotherapy KW - Vulvar Neoplasms -- radiotherapy KW - Radiotherapy -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71990275?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiotherapy+and+oncology+%3A+journal+of+the+European+Society+for+Therapeutic+Radiology+and+Oncology&rft.atitle=Radiosensitivity+in+Fanconi%27s+anemia+patients.&rft.au=Alter%2C+Blanche+P&rft.aulast=Alter&rft.aufirst=Blanche&rft.date=2002-03-01&rft.volume=62&rft.issue=3&rft.spage=345&rft.isbn=&rft.btitle=&rft.title=Radiotherapy+and+oncology+%3A+journal+of+the+European+Society+for+Therapeutic+Radiology+and+Oncology&rft.issn=01678140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-06 N1 - Date created - 2002-08-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Radiother Oncol. 2002 Mar;62(3):350-1; author reply 351-2 [12175568] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Cohort study of mortality among leather tanners in the Lower Valdarno area]. TT - Studio di coorte di mortalità degli addetti alla concia del cuoio e delle pelli nel territorio dell'azienda USL 11--Zona Valdarno Inferiore. AN - 71864812; 12087805 AB - Epidemiological studies of tanners have shown increased risk for a number of cancer sites, namely: lung, bladder, kidney and urinary organs as well as stomach, intestine, pancreas, nose and nasal cavities, together with leukemias and soft tissue sarcomas. To study cause specific mortality of leather tanners in Tuscany (Valdarno Inferiore area). The cohort included 4874 workers (4150 males and 724 females) employed in 92 tanneries operating in 1996 (Valdarno Inferiore Tanneries Census) which were also operating on 31-12-1970. Ascertainment of vital status was completed for all individuals on 31-12-1998 (end of follow-up), and the cause of death was known for all deceased subjects. Demographic and work history data were obtained from factory payrolls. Regional mortality rates were used for comparison to calculate SMR (Standardised Mortality Ratio) and 90% Confidence Intervals (CI). In addition to the overall cohort analysis, for men only separate analyses were completed for finishers, chrome tanners and vegetable tanners. The study showed an increased mortality from lung cancer among finishers, Standardised Mortality Ratio (SMR) 145, 19 observed (obs) (90% Confidence Intervals, 90% CI 95-212), from bladder cancer in the overall cohort (SMR 134, 9 obs, 90% CI 70-233) and among finishers (SMR 125, 2 obs, 90% CI 22-393) and from pancreatic cancer among finishers (SMR 120, 2 obs, 90% CI 21-379). Mortality from lymphoemopoietic cancer is above expected, and the increase is mainly due to myeloid leukaemia, both in males (SMR 208, 5 obs, 90% CI 82-437) and females (SMR 599, 2 obs, 90% CI 106-1887). No deaths from soft tissue sarcoma were observed. A new finding of the study was the increased mortality from cancer of the endocrine glands (SMR 566, 4 obs, 90% CI 194-1297), psychiatric disorders (SMR 195, 6 obs, 90% CI 85-385) and blood diseases (SMR 329, 4 obs, IC 90% 112-752). The observations of increased lung cancer mortality among finishers, of bladder cancer in the overall cohort and among finishers, as well as an increase in pancreatic cancer among the latter, confirm previous epidemiological findings among tanners. The increase in myeloid leukemia mortality for both males and females, and the absence of deaths from cancer of the connective tissue, which includes soft tissue sarcomas, are worthy of note. The results should be valued with caution, given the small number of cases and the novelty of some observations. JF - La Medicina del lavoro AU - Iaia, T E AU - Bartoli, D AU - Calzoni, P AU - Comba, P AU - De Santis, M AU - Dini, F AU - Ercolanelli, M AU - Farina, G A AU - Pirastu, R AU - Seniori Costantini, A AU - Valiani, M AD - U.O Prevenzione Igiene e sicurezza nei Luoghi di Lavoro, Dipartimento della Prevenzione, Azienda USL 11, Valdarno Inferiore. t.iaia@USL11.tos.it PY - 2002 SP - 95 EP - 107 VL - 93 IS - 2 SN - 0025-7818, 0025-7818 KW - Index Medicus KW - Humans KW - Cohort Studies KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Italy KW - Female KW - Cause of Death KW - Tanning KW - Occupational Diseases -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71864812?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=%5BCohort+study+of+mortality+among+leather+tanners+in+the+Lower+Valdarno+area%5D.&rft.au=Iaia%2C+T+E%3BBartoli%2C+D%3BCalzoni%2C+P%3BComba%2C+P%3BDe+Santis%2C+M%3BDini%2C+F%3BErcolanelli%2C+M%3BFarina%2C+G+A%3BPirastu%2C+R%3BSeniori+Costantini%2C+A%3BValiani%2C+M&rft.aulast=Iaia&rft.aufirst=T&rft.date=2002-03-01&rft.volume=93&rft.issue=2&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-15 N1 - Date created - 2002-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of naphthal-NU, a 2-chloroethylnitrosourea derivative of naphthalimide, as a mixed-function anticancer agent. AN - 71842788; 12071535 AB - Naphthal-NU, 2-[2-[3-(2-chloroethyl)-3-nitrosoureido]ethyl]-1H-benz[de]isoquinoline-1,3-dione (Compound 1) has been synthesized as a rationally designed new mixed-function anticancer agent from 1,8-naphthalic anhydride. Its chemical alkylating activity compared with CCNU as standard compound indicated that it possesses greater alkylating activity than the latter. Its antitumour efficacy was assessed in vivo in two murine ascites tumours namely Sarcoma-180 (S-180) and Ehrlich ascites carcinoma (EAC) by measuring the increase in median survival times (MST) of drug treated (T) over untreated control (C) mice. Three clinical drugs namely CCNU (lomustine), endoxan (cyclophosphamide) and 5-fluorouracil (5-FU) were used as positive controls for comparison. Compound 1 has displayed excellent and reproducible antitumoural activity having curative effects in these tumours comparable with CCNU and 5-FU. It has also significantly increased the life span of mice bearing highly advanced tumour for 10 days before the drug challenge. Its toxicity was also assessed in vivo in normal and in S-180 bearing mice by measuring drug-induced changes in hematological parameters, femoral bone marrow and splenic cellularity sequentially on days 9, 15 and 21 following drug treatment at the optimum dose of 50 mg/kg from day 1 to 7. The results indicated that the compound did not adversely affect hematopoiesis. Drug-induced hepatotoxicity and nephrotoxicity were also evaluated at its optimum dose on those days but no such toxicities were detected. It was further screened in vitro in 6 different human tumour cell lines but no significant activity was observed in those lines. JF - Journal of experimental & clinical cancer research : CR AU - Samanta, S AU - Pain, A AU - Dutta, S AU - Sanyal, U AD - Dept. of Anticancer Drug Development & Chemotherapy, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 87 EP - 93 VL - 21 IS - 1 SN - 0392-9078, 0392-9078 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Lomustine KW - 7BRF0Z81KG KW - Index Medicus KW - Drug Screening Assays, Antitumor KW - Animals KW - Tumor Cells, Cultured KW - Liver -- drug effects KW - Humans KW - In Vitro Techniques KW - Kidney -- drug effects KW - Mice KW - Drug Evaluation, Preclinical KW - Male KW - Lomustine -- analogs & derivatives KW - Antineoplastic Agents, Alkylating -- therapeutic use KW - Antineoplastic Agents, Alkylating -- chemical synthesis KW - Sarcoma 180 -- mortality KW - Sarcoma 180 -- drug therapy KW - Lomustine -- therapeutic use KW - Carcinoma, Ehrlich Tumor -- drug therapy KW - Carcinoma, Ehrlich Tumor -- mortality KW - Lomustine -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71842788?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.atitle=Evaluation+of+naphthal-NU%2C+a+2-chloroethylnitrosourea+derivative+of+naphthalimide%2C+as+a+mixed-function+anticancer+agent.&rft.au=Samanta%2C+S%3BPain%2C+A%3BDutta%2C+S%3BSanyal%2C+U&rft.aulast=Samanta&rft.aufirst=S&rft.date=2002-03-01&rft.volume=21&rft.issue=1&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.issn=03929078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-21 N1 - Date created - 2002-06-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Exp Clin Cancer Res. 2002 Jun;21(2):299-300. N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Superfund Basic Research Program--making a difference: past, present, and future. AN - 71712709; 12018007 AB - Understanding exposure continues to be a paramount challenge and critical element in successfully managing Superfund sites. The Superfund Basic Research Program, administered by the National Institute of Environmental Health Sciences, an institute of the National Institutes of Health, is committed to providing the nation's decision makers with better tools to identify the routes and effects of exposure and develop innovative technologies to reduce exposures. In this article, we demonstrate how the program contributes to understanding the exposure disease link, highlight the cutting-edge and practical nature of this very fundamental research program and discuss its approach to addressing these problems. We also identify several broad themes that are likely to direct the program's future research endeavors. JF - International journal of hygiene and environmental health AU - Anderson, Beth AU - Thompson, Claudia AU - Suk, William A AD - Division of Extramural Research and Training, National Institute of Environmental Health Sciences, Durham, North Carolina, USA. Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 137 EP - 141 VL - 205 IS - 1-2 SN - 1438-4639, 1438-4639 KW - Hazardous Substances KW - 0 KW - Index Medicus KW - United States KW - Humans KW - National Institutes of Health (U.S.) KW - Research -- trends KW - Research Support as Topic KW - Financing, Government KW - Hazardous Substances -- adverse effects KW - Environmental Health KW - Environmental Exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71712709?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+hygiene+and+environmental+health&rft.atitle=The+Superfund+Basic+Research+Program--making+a+difference%3A+past%2C+present%2C+and+future.&rft.au=Anderson%2C+Beth%3BThompson%2C+Claudia%3BSuk%2C+William+A&rft.aulast=Anderson&rft.aufirst=Beth&rft.date=2002-03-01&rft.volume=205&rft.issue=1-2&rft.spage=137&rft.isbn=&rft.btitle=&rft.title=International+journal+of+hygiene+and+environmental+health&rft.issn=14384639&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-05 N1 - Date created - 2002-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Voriconazole in the treatment of aspergillosis, scedosporiosis and other invasive fungal infections in children. AN - 71677153; 12005089 AB - To describe the safety and efficacy of voriconazole in children treated within the compassionate release program. Children received voriconazole on a compassionate basis for treatment of an invasive fungal infection if they were refractory to or intolerant of conventional antifungal therapy. Voriconazole was administered as a loading dose of 6 mg/kg every 12 h i.v. on Day 1 followed by 4 mg/kg every 12 h i.v. thereafter. When feasible the route of administration of voriconazole was changed from i.v. to oral (100 or 200 mg twice a day for patients weighing or = 40 kg, respectively). Outcome was assessed by investigators at the end of therapy or at the last visit as success (complete or partial response), stable infection, or failure, based on protocol-defined criteria. Sixty-nine children (ages 9 months to 15 years; median, 7 years) received voriconazole; 58 had a proven or probable fungal infection. Among these 58 patients 27 had hematologic malignancies and 13 had chronic granulomatous disease as the most frequent underlying conditions. Forty-two patients had aspergillosis, 8 had scedosporiosis, 4 had invasive candidiasis and 4 had other invasive fungal infections. The median duration of voriconazole therapy was 93 days. At the end of therapy 26 patients (45%) had a complete or partial response. Four patients (7%) had a stable response, 25 (43%) failed therapy and 4 (7%) were discontinued from voriconazole because of intolerance. Success rates were highest in patients with chronic granulomatous disease (62%) and lowest in patients with hematologic malignancies (33%). Two patients experienced treatment-related serious adverse events (ulcerated lips with rash, elevated hepatic transaminases or bilirubin). A total of 23 patients had voriconazole-related adverse events, 3 (13%) of which caused discontinuation of voriconazole therapy. The most commonly reported adverse events included elevation in hepatic transaminases or bilirubin (n = 8), skin rash (n = 8), abnormal vision (n = 3) and a photosensitivity reaction (n = 3). These data support the use of voriconazole for treatment of invasive fungal infections in pediatric patients who are intolerant of or refractory to conventional antifungal therapy. JF - The Pediatric infectious disease journal AU - Walsh, Thomas J AU - Lutsar, Irja AU - Driscoll, Timothy AU - Dupont, Bertrand AU - Roden, Maureen AU - Ghahramani, Parvis AU - Hodges, Michael AU - Groll, Andreas H AU - Perfect, John R AD - Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA. walsht@mail.nih.gov Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 240 EP - 248 VL - 21 IS - 3 SN - 0891-3668, 0891-3668 KW - Antifungal Agents KW - 0 KW - Pyrimidines KW - Triazoles KW - Voriconazole KW - JFU09I87TR KW - Index Medicus KW - Infant KW - Treatment Failure KW - Hematologic Neoplasms -- complications KW - Drug Administration Schedule KW - Humans KW - Granulomatous Disease, Chronic -- complications KW - Child KW - Adolescent KW - Male KW - Female KW - Child, Preschool KW - Pyrimidines -- adverse effects KW - Antifungal Agents -- adverse effects KW - Pyrimidines -- therapeutic use KW - Aspergillosis -- drug therapy KW - Triazoles -- adverse effects KW - Pyrimidines -- administration & dosage KW - Antifungal Agents -- therapeutic use KW - Aspergillosis -- complications KW - Mycoses -- complications KW - Antifungal Agents -- administration & dosage KW - Mycoses -- drug therapy KW - Triazoles -- therapeutic use KW - Triazoles -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71677153?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Pediatric+infectious+disease+journal&rft.atitle=Voriconazole+in+the+treatment+of+aspergillosis%2C+scedosporiosis+and+other+invasive+fungal+infections+in+children.&rft.au=Walsh%2C+Thomas+J%3BLutsar%2C+Irja%3BDriscoll%2C+Timothy%3BDupont%2C+Bertrand%3BRoden%2C+Maureen%3BGhahramani%2C+Parvis%3BHodges%2C+Michael%3BGroll%2C+Andreas+H%3BPerfect%2C+John+R&rft.aulast=Walsh&rft.aufirst=Thomas&rft.date=2002-03-01&rft.volume=21&rft.issue=3&rft.spage=240&rft.isbn=&rft.btitle=&rft.title=The+Pediatric+infectious+disease+journal&rft.issn=08913668&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-10 N1 - Date created - 2002-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolation perfusion of the liver. AN - 71671169; 12004803 AB - Thousands of patients die annually from unresectable metastatic or primary hepatic cancers confined to liver. Isolated hepatic perfusion (IHP) is a regional treatment strategy in which the vascular supply to the liver is isolated and perfused with a therapeutic regimen using an extracorporeal circuit consisting of a reservoir, heat exchanger, and oxygenator. Drug doses that would cause severe toxicities if delivered systemically can be confined to the liver by isolated hepatic perfusion, resulting in the ability to intensify treatment to the cancer-burdened region of the body. Agents and mechanisms commonly used in IHP include melphaIan, hyperthermia, and tumor necrosis factor. IHP appears to be efficacious for patients with advanced disease, as reflected by large tumor size, high number of lesions, or significant overall tumor burden in the liver. In addition, responses are observed for patients whose cancer is refractory to systemic and hepatic arterial infusion chemotherapy. Recent clinical trials have demonstrated that IHP has anti-tumor efficacy against primary hepatic neoplasms and metastases from various primary tumors, such as colorectal carcinoma, ocular melanoma, and neuroendocrine tumors. Current studies demonstrate that combining hepatic arterial infusion with floxuridine after IHP for patients with colorectal cancer metastases is associated with significant and durable response rates. Continued clinical evaluation is warranted for the use of IHP in the treatment of unresectable liver metastases. JF - Cancer journal (Sudbury, Mass.) AU - Carroll, Nancy M AU - Alexander, H Richard AD - Surgical Metabolism Section, Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1502, USA. PY - 2002 SP - 181 EP - 193 VL - 8 IS - 2 SN - 1528-9117, 1528-9117 KW - Antineoplastic Agents KW - 0 KW - Tumor Necrosis Factor-alpha KW - Index Medicus KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Antineoplastic Agents -- administration & dosage KW - Humans KW - Melanoma -- drug therapy KW - Hyperthermia, Induced KW - Eye Neoplasms -- drug therapy KW - Liver Neoplasms -- drug therapy KW - Chemotherapy, Cancer, Regional Perfusion -- instrumentation KW - Chemotherapy, Cancer, Regional Perfusion -- methods KW - Chemotherapy, Cancer, Regional Perfusion -- adverse effects KW - Liver Neoplasms -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71671169?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+journal+%28Sudbury%2C+Mass.%29&rft.atitle=Isolation+perfusion+of+the+liver.&rft.au=Carroll%2C+Nancy+M%3BAlexander%2C+H+Richard&rft.aulast=Carroll&rft.aufirst=Nancy&rft.date=2002-03-01&rft.volume=8&rft.issue=2&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=Cancer+journal+%28Sudbury%2C+Mass.%29&rft.issn=15289117&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-17 N1 - Date created - 2002-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biochemical and molecular effects of UCN-01 in combination with 5-fluorodeoxyuridine in A431 human epidermoid cancer cells. AN - 71668669; 11984070 AB - Concurrent and pre-exposure of A431 human epidermoid cancer cells to UCN-01, an investigational anticancer drug, with 5-fluoro--2'-deoxyuridine (FdUrd), which targets thymidylate synthase, produced more than additive cytotoxicty. A 24-h exposure to 10 nM FdUrd led to inhibition of TS, a 2.5-fold increase in total thymidylate synthase protein content, profound dTTP depletion and a 6.3-fold increase in the ratio of dATP to dTTP, but did not cause single-strand breaks in DNA. However, FdUrd enhanced UCN-01-associated DNA strand breaks. Concurrent thymidine exposure led to repletion of dTTP pools, and cytoprotection against FdUrd alone and with UCN-01. UCN-01 arrested cells in G1, decreased the percentage of FdUrd-treated cells in S phase and reduced FdUrd-DNA incorporation, suggesting the latter was not important for cytotoxicity. Delayed induction of high molecular mass DNA fragmentation and poly(ADP-ribose) polymerase cleavage was observed with the combination of UCN-01 and FdUrd. These findings suggest that while FdUrd-mediated deoxynucleotide imbalance alone was insufficient to induce apoptosis in this p53-mutant cell line, it magnified UCN-01's effects, most likely by interfering with DNA repair. The clinical evaluation of UCN-01 combined with 5-fluoropyrimidines may be of interest. JF - Anti-cancer drugs AU - Grem, Jean L AU - Danenberg, Kathleen D AU - Kao, Vivian AU - Danenberg, Peter V AU - Nguyen, Diana AD - Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute-Navy Medical Oncology, National Naval Medical Center, Bethesda, MD 20889-5105, USA. gremj@mail.nih.gov Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 259 EP - 270 VL - 13 IS - 3 SN - 0959-4973, 0959-4973 KW - Alkaloids KW - 0 KW - Antimetabolites, Antineoplastic KW - DNA, Neoplasm KW - Deoxyribonucleotides KW - Drug Combinations KW - Enzyme Inhibitors KW - RNA, Messenger KW - Floxuridine KW - 039LU44I5M KW - 7-hydroxystaurosporine KW - 7BU5H4V94A KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Staurosporine KW - H88EPA0A3N KW - Index Medicus KW - Humans KW - Lung Neoplasms -- drug therapy KW - Staurosporine -- analogs & derivatives KW - DNA Damage -- drug effects KW - DNA, Neoplasm -- drug effects KW - Polymerase Chain Reaction KW - RNA, Messenger -- metabolism KW - Genes, p53 KW - Carcinoma, Squamous Cell -- pathology KW - Deoxyribonucleotides -- metabolism KW - DNA Fragmentation -- drug effects KW - Carcinoma, Squamous Cell -- drug therapy KW - DNA, Neoplasm -- metabolism KW - Cell Cycle -- drug effects KW - Lung Neoplasms -- pathology KW - Thymidylate Synthase -- genetics KW - Thymidylate Synthase -- antagonists & inhibitors KW - Floxuridine -- pharmacology KW - Cell Survival -- drug effects KW - Tumor Cells, Cultured -- drug effects KW - Enzyme Inhibitors -- pharmacology KW - Alkaloids -- pharmacology KW - Thymidylate Synthase -- metabolism KW - Tumor Cells, Cultured -- enzymology KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71668669?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anti-cancer+drugs&rft.atitle=Biochemical+and+molecular+effects+of+UCN-01+in+combination+with+5-fluorodeoxyuridine+in+A431+human+epidermoid+cancer+cells.&rft.au=Grem%2C+Jean+L%3BDanenberg%2C+Kathleen+D%3BKao%2C+Vivian%3BDanenberg%2C+Peter+V%3BNguyen%2C+Diana&rft.aulast=Grem&rft.aufirst=Jean&rft.date=2002-03-01&rft.volume=13&rft.issue=3&rft.spage=259&rft.isbn=&rft.btitle=&rft.title=Anti-cancer+drugs&rft.issn=09594973&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-19 N1 - Date created - 2002-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Smad3 in the mammary epithelium has a nonredundant role in the induction of apoptosis, but not in the regulation of proliferation or differentiation by transforming growth factor-beta. AN - 71612099; 11959813 AB - Transforming growth factor-beta (TGF-beta) regulates proliferation, morphogenesis, and functional differentiation in the mammary gland and plays complex roles in mammary tumorigenesis. Here we show that the signaling mediators Smad1-Smad5 are expressed at all stages of mammary gland development. To begin to investigate which Smads mediate which TGF-beta responses, we have analyzed mammary gland development in Smad3 null mice. Smad3 null virgin females showed delayed mammary gland development. However, this phenotype was secondary to ovarian insufficiency because Smad3 null mammary epithelium developed normally in hormonally supplemented Smad3 null mice or when transplanted into wild-type hosts. Absence of Smad3 had no effect on the ability of TGF-beta to inhibit the growth of mammary epithelial cells in culture, and no compensatory changes in expression or activation of Smad2 were seen in the Smad3 null epithelium. A small but significant decrease in apoptotic cells was seen in involuting glands from Smad3 null transplants. The results suggest that epithelial Smad3 is dispensable for TGF-beta effects on proliferation and differentiation in the mammary gland, but that it contributes in a nonredundant manner to the induction of apoptosis. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Yang, Yu-an AU - Tang, Binwu AU - Robinson, Gertraud AU - Hennighausen, Lothar AU - Brodie, Steven G AU - Deng, Chu-Xia AU - Wakefield, Lalage M AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892-5055, USA. Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 123 EP - 130 VL - 13 IS - 3 SN - 1044-9523, 1044-9523 KW - DNA-Binding Proteins KW - 0 KW - Hormones KW - Smad Proteins KW - Smad1 Protein KW - Smad1 protein, mouse KW - Smad2 Protein KW - Smad2 protein, mouse KW - Smad3 Protein KW - Smad3 protein, mouse KW - Trans-Activators KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - Cell Differentiation KW - Mice KW - Lactation KW - Mice, Knockout KW - Mice, Inbred Strains KW - Ovary -- cytology KW - Hormones -- physiology KW - Epithelium -- physiology KW - Mice, Inbred C57BL KW - Ovary -- physiology KW - Female KW - Male KW - Cell Division KW - Transforming Growth Factor beta -- pharmacology KW - Trans-Activators -- metabolism KW - Apoptosis KW - Mammary Glands, Animal -- cytology KW - Mammary Glands, Animal -- physiology KW - Mammary Glands, Animal -- growth & development KW - DNA-Binding Proteins -- physiology KW - Trans-Activators -- physiology KW - Transforming Growth Factor beta -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71612099?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Smad3+in+the+mammary+epithelium+has+a+nonredundant+role+in+the+induction+of+apoptosis%2C+but+not+in+the+regulation+of+proliferation+or+differentiation+by+transforming+growth+factor-beta.&rft.au=Yang%2C+Yu-an%3BTang%2C+Binwu%3BRobinson%2C+Gertraud%3BHennighausen%2C+Lothar%3BBrodie%2C+Steven+G%3BDeng%2C+Chu-Xia%3BWakefield%2C+Lalage+M&rft.aulast=Yang&rft.aufirst=Yu-an&rft.date=2002-03-01&rft.volume=13&rft.issue=3&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-03 N1 - Date created - 2002-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association of adrenal pheochromocytoma and lung pathology in inhalation studies with particulate compounds in the male F344 rat--the National Toxicology Program experience. AN - 71603167; 11950170 AB - Systemic hypoxemia, occurring in space-occupying lung pathologies such as inflammation and neoplasms. reduces the gas exchange area and stimulates catecholamine secretion from the adrenal medulla where chronic endocrine hyperactivity may lead to hyperplasia and neoplasia. We investigated the possible correlation between nonneoplastic chronic pulmonary lesions and adrenal pheochromocytoma in 9 recent, NTP, 2-year particulate inhalation studies in male F344 rats. Re-evaluation for chronic active inflammation, interstitial fibrosis, alveolar epithelial hyperplasia, squamous metaplasia, proteinosis, and histiocytosis revealed significant associations of pheochromocytoma only with the severity of inflammation and fibrosis. Nickel oxide, cobalt sulfate, indium phosphide, talc, and nickel subsulfide studies showed chemical-related incidences of adrenal pheochromocytoma and significant (p < 0.01) associations with inflammation and fibrosis. Gallium arsenide, vanadium pentoxide, molybdenum trioxide, and nickel sulfate hexahydrate studies revealed an increased incidence and/or severity of nonneoplastic lung lesions, but no increased incidence of pheochromocytoma. Although gallium arsenide and molybdenum trioxide showed no dose-related increase in pheochromocvtoma, a significant (p < 0.01) correlation of the latter with the severity of fibrosis and inflammation occurred. In the vanadium pentoxide and nickel sulfate hexahydrate studies, no relationship between nonneoplastic lung lesions and pheochromocytoma was manifested. Our investigation assessed the strength of these various associations and supports the possible roles of 2 chronic pulmonary lesions-fibrosis and inflammation-and hypoxemia in the induction of pheochromocytoma in the F344 male rat. JF - Toxicologic pathology AU - Ozaki, Keisuke AU - Haseman, Joseph K AU - Hailey, James R AU - Maronpot, Robert R AU - Nyska, Abraham AD - Laboratory of Experimental Pathology National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 2002 SP - 263 EP - 270 VL - 30 IS - 2 SN - 0192-6233, 0192-6233 KW - nickel subsulfide KW - 12035-72-2 KW - Nickel KW - 7OV03QG267 KW - Index Medicus KW - Rats KW - Hypoxia -- complications KW - Animals KW - Rats, Inbred F344 KW - Hyperplasia KW - Pulmonary Fibrosis -- complications KW - Nickel -- toxicity KW - Administration, Inhalation KW - Male KW - Inflammation -- complications KW - Pheochromocytoma -- etiology KW - Adrenal Gland Neoplasms -- etiology KW - Adrenal Gland Neoplasms -- pathology KW - Pheochromocytoma -- pathology KW - Lung -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71603167?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Association+of+adrenal+pheochromocytoma+and+lung+pathology+in+inhalation+studies+with+particulate+compounds+in+the+male+F344+rat--the+National+Toxicology+Program+experience.&rft.au=Ozaki%2C+Keisuke%3BHaseman%2C+Joseph+K%3BHailey%2C+James+R%3BMaronpot%2C+Robert+R%3BNyska%2C+Abraham&rft.aulast=Ozaki&rft.aufirst=Keisuke&rft.date=2002-03-01&rft.volume=30&rft.issue=2&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-25 N1 - Date created - 2002-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lysosomal-storage disorder induced by elmiron following 90-days gavage administration in rats and mice. AN - 71597485; 11950161 AB - Elmiron, a highly sulfated, semisynthetic pentose polysaccharide with properties similar to heparin, is used for the treatment of interstitial cystitis. Thirteen-week gavage studies were conducted by administering the drug in deionized water to F344/N rats and B6C3F1 mice once daily, 5 days per week for up to 13 consecutive weeks, at doses of 0, 63, 125, 250, 500, and 1,000 mg/kg body weight. No significant drug-related effects were observed in body weight, survival, clinical, and necropsy results. Significant organ weight increases were seen in the liver, lungs, and spleen of both species and the kidneys of rats, mainly in groups treated with 250 mg/kg/day and above. Hematological analysis indicated increases for both species in the white blood cell and lymphocyte counts. Sites of toxicity identified histopathologically were the rectum, liver, mesenteric and mandibular lymph nodes (both sexes), spleen (mice only), and lungs and kidneys (rats only). Lesions consisted mainly of infiltration into multiple tissues of vacuolated histiocytes, which, by histochemical investigation, indicated the presence of neutral and acidic mucins and lipidic material within the vacuoles. Transmission electron microscopy identified these vacuoles as lysosomal structures that exhibited a variety of contents. On the basis of our findings, we propose that Elmiron was absorbed through the focally disrupted rectal mucosa, was deposited in the lamina propria, accumulated within macrophages, and then was distributed by these cells or as a free chemical via the lymphatics and blood, to the various organ sites manifesting histiocytic infiltration. The cytoplasmic membrane-bound structures within macrophages were lysosomes containing membranous material of cellular origin and, perhaps, remnants of the deposited test material, Elmiron. JF - Toxicologic pathology AU - Nyska, Abraham AU - Nold, James B AU - Johnson, Jerry D AU - Abdo, Kamal AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. nyska@niehs.nih.gov PY - 2002 SP - 178 EP - 187 VL - 30 IS - 2 SN - 0192-6233, 0192-6233 KW - Anticoagulants KW - 0 KW - Pentosan Sulfuric Polyester KW - 37300-21-3 KW - Index Medicus KW - Lymph Nodes -- ultrastructure KW - Animals KW - Liver -- pathology KW - Lymph Nodes -- pathology KW - Mice KW - Rats KW - Rectum -- ultrastructure KW - Rats, Inbred F344 KW - Rectum -- pathology KW - Body Weight -- drug effects KW - Lung -- ultrastructure KW - Microscopy, Electron KW - Female KW - Male KW - Organ Size -- drug effects KW - Anticoagulants -- toxicity KW - Lysosomal Storage Diseases -- chemically induced KW - Pentosan Sulfuric Polyester -- pharmacokinetics KW - Pentosan Sulfuric Polyester -- toxicity KW - Lysosomal Storage Diseases -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71597485?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Lysosomal-storage+disorder+induced+by+elmiron+following+90-days+gavage+administration+in+rats+and+mice.&rft.au=Nyska%2C+Abraham%3BNold%2C+James+B%3BJohnson%2C+Jerry+D%3BAbdo%2C+Kamal&rft.aulast=Nyska&rft.aufirst=Abraham&rft.date=2002-03-01&rft.volume=30&rft.issue=2&rft.spage=178&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-25 N1 - Date created - 2002-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Spontaneous lesions in control B6C3F1 mice and recommended sectioning of male accessory sex organs. AN - 71590703; 11950166 AB - Because sampling of the paired lobes (ventral, dorsal, lateral, and anterior) of the mouse prostate has often been inconsistent, comparisons among different investigations have lacked validity. The absence of site identification for prostatic lesions has made reported incidences relatively nonspecific. We present here the lobe-specific incidences and degree of severity of spontaneous lesions in prostate, coagulating gland (anterior prostatic lobe), seminal vesicles, and ampullary glands in 612 control B6C3F1 mice from 12 recent National Toxicology Program 2-year carcinogenicity and toxicity studies conducted in 1 of 4 different laboratories. Lymphocytic infiltration, inflammation, epithelial hyperplasia, mucinous cyst, and mucinous metaplasia were observed in the dorsolateral lobes. Lymphocytic infiltration, inflammation, epithelial hyperplasia, and edema were present in the ventral lobes. Lymphocytic infiltration, acinar dilatation, inflammation, epithelial hyperplasia, and atrophy occurred in the coagulating glands. No neoplastic lesions were observed in the prostate or coagulating gland. Lymphocytic infiltration, acinar dilatation, inflammation, atrophy, adenoma, adenocarcinoma, and a granular cell tumor were observed in the seminal vesicles. Lymphocytic infiltration was also present in the ampullary glands. The results of our survey indicate that the amounts of glandular tissues were not present consistently in slides from the different laboratories. Landmarks for uniform tissue trimming are needed. We therefore suggest an optimal trimming and embedding method for mouse prostate and seminal vesicles to ensure adequate, consistent sampling. JF - Toxicologic pathology AU - Suwa, Takahiko AU - Nyska, Abraham AU - Haseman, Joseph K AU - Mahler, Joel F AU - Maronpot, Robert R AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 2002 SP - 228 EP - 234 VL - 30 IS - 2 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Animals KW - Mice KW - Male KW - Prostate -- pathology KW - Seminal Vesicles -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71590703?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Spontaneous+lesions+in+control+B6C3F1+mice+and+recommended+sectioning+of+male+accessory+sex+organs.&rft.au=Suwa%2C+Takahiko%3BNyska%2C+Abraham%3BHaseman%2C+Joseph+K%3BMahler%2C+Joel+F%3BMaronpot%2C+Robert+R&rft.aulast=Suwa&rft.aufirst=Takahiko&rft.date=2002-03-01&rft.volume=30&rft.issue=2&rft.spage=228&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-25 N1 - Date created - 2002-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The metallothionein-null phenotype is associated with heightened sensitivity to lead toxicity and an inability to form inclusion bodies. AN - 71568147; 11891201 AB - Susceptibility to lead toxicity in MT-null mice and cells, lacking the major forms of the metallothionein (MT) gene, was compared to wild-type (WT) mice or cells. Male MT-null and WT mice received lead in the drinking water (0 to 4000 ppm) for 10 to 20 weeks. Lead did not alter body weight in any group. Unlike WT mice, lead-treated MT-null mice showed dose-related nephromegaly. In addition, after lead exposure renal function was significantly diminished in MT-null mice in comparison to WT mice. MT-null mice accumulated less renal lead than WT mice and did not form lead inclusion bodies, which were present in the kidneys of WT mice. In gene array analysis, renal glutathione S-transferases were up-regulated after lead in MT-null mice only. In vitro studies on fibroblast cell lines derived from MT-null and WT mice showed that MT-null cells were much more sensitive to lead cytotoxicity. MT-null cells accumulated less lead and formed no inclusion bodies. The MT-null phenotype seems to preclude lead-induced inclusion body formation and increases lead toxicity at the organ and cellular level despite reducing lead accumulation. This study reveals important roles for MT in chronic lead toxicity, lead accumulation, and inclusion body formation. JF - The American journal of pathology AU - Qu, Wei AU - Diwan, Bhalchandra A AU - Liu, Jie AU - Goyer, Robert A AU - Dawson, Tammy AU - Horton, John L AU - Cherian, M George AU - Waalkes, Michael P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 1047 EP - 1056 VL - 160 IS - 3 SN - 0002-9440, 0002-9440 KW - Lead KW - 2P299V784P KW - Metallothionein KW - 9038-94-2 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Kidney -- metabolism KW - Kidney -- pathology KW - Cells, Cultured KW - Mice KW - Kidney -- ultrastructure KW - Genetic Predisposition to Disease KW - Lead -- metabolism KW - Male KW - Mice, Knockout KW - Inclusion Bodies -- metabolism KW - Lead Poisoning -- genetics KW - Metallothionein -- genetics KW - Lead Poisoning -- metabolism KW - Metallothionein -- metabolism KW - Inclusion Bodies -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71568147?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+pathology&rft.atitle=The+metallothionein-null+phenotype+is+associated+with+heightened+sensitivity+to+lead+toxicity+and+an+inability+to+form+inclusion+bodies.&rft.au=Qu%2C+Wei%3BDiwan%2C+Bhalchandra+A%3BLiu%2C+Jie%3BGoyer%2C+Robert+A%3BDawson%2C+Tammy%3BHorton%2C+John+L%3BCherian%2C+M+George%3BWaalkes%2C+Michael+P&rft.aulast=Qu&rft.aufirst=Wei&rft.date=2002-03-01&rft.volume=160&rft.issue=3&rft.spage=1047&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+pathology&rft.issn=00029440&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-02 N1 - Date created - 2002-03-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Virchows Arch. 2000 Nov;437(5):528-33 [11147174] Toxicol Sci. 1998 Dec;46(2):254-9 [10048128] Arch Environ Health. 1970 Jun;20(6):705-11 [5443344] Am J Pathol. 1971 Jul;64(1):167-82 [4326632] Science. 1972 Sep 29;177(4055):1194-5 [4341569] Int Rev Exp Pathol. 1973;12:1-77 [4349348] Lab Invest. 1973 Nov;29(5):488-94 [4356630] Environ Health Perspect. 1974 May;7:121-7 [4364645] Virchows Arch B Cell Pathol. 1974;15(4):345-50 [4367546] Lab Invest. 1975 Feb;32(2):149-56 [163419] Am J Pathol. 1976 Apr;83(1):135-48 [179327] Toxicol Appl Pharmacol. 1980 Dec;56(3):418-31 [7222026] Toxicol Appl Pharmacol. 1982 Oct;66(1):134-42 [7157381] Toxicology. 1983 Sep;28(1-2):1-15 [6314607] Toxicol Lett. 1984 Jan;20(1):33-9 [6695394] Fundam Appl Toxicol. 1985 Jun;5(3):473-7 [4007305] Biochem J. 1986 Jan 15;233(2):541-6 [3954751] Toxicol Appl Pharmacol. 1986 Apr;83(2):211-7 [3961811] Biochem Biophys Res Commun. 1986 Apr 29;136(2):535-41 [3518716] Arch Biochem Biophys. 1987 Feb 15;253(1):48-55 [3813567] J Biol Chem. 1989 Oct 15;264(29):16969-72 [2571613] Chem Biol Interact. 1989;72(3):347-61 [2605674] Toxicol Appl Pharmacol. 1991 Jan;107(1):27-34 [1987657] Chem Biol Interact. 1991;78(3):347-54 [2070437] Fundam Appl Toxicol. 1992 Jan;18(1):1-16 [1601199] Toxicology. 1992;73(2):127-46 [1319092] Toxicol Sci. 2000 Apr;54(2):500-8 [10774833] Toxicology. 2000 Jul 5;147(3):157-66 [10924798] J Toxicol Environ Health A. 2000 Dec 15;61(7):553-67 [11127411] J Inorg Biochem. 1993 Jan;49(1):55-68 [8433087] Environ Health Perspect. 1993 Apr;100:177-87 [8354166] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):584-8 [8290567] Toxicol Appl Pharmacol. 1994 May;126(1):1-5 [8184419] Toxicol Appl Pharmacol. 1995 Mar;131(1):85-93 [7878682] Toxicol Appl Pharmacol. 1995 Mar;131(1):94-107 [7878683] J Biol Chem. 1995 Mar 10;270(10):5506-10 [7890668] Cancer Res. 1995 Nov 15;55(22):5265-71 [7585586] Drug Metab Rev. 1997 Feb-May;29(1-2):79-102 [9187512] Chem Biol Interact. 1998 Aug 14;115(1):39-52 [9817074] Lab Invest. 1970 Mar;22(3):245-51 [5436518] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53-Independent induction of Fas and apoptosis in leukemic cells by an adenosine derivative, Cl-IB-MECA. AN - 71551649; 11911839 AB - A(3) adenosine receptor (A(3)AR) agonists have been reported to influence cell death and survival. The effects of an A(3)AR agonist, 1-[2-chloro-6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxy-N-methyl-beta-D-ribofuranonamide (Cl-IB-MECA), on apoptosis in two human leukemia cell lines, HL-60 and MOLT-4, were investigated. Cl-IB-MECA (> or =30 microM) increased the apoptotic fractions, as determined using fluorescence-activated cell sorting (FACS) analysis, and activated caspase 3 and poly-ADP-ribose-polymerase. Known messengers coupled to A(3)AR (phospholipase C and intracellular calcium) did not seem to play a role in the induction of apoptosis. Neither dantrolene nor BAPTA-AM affected the Cl-IB-MECA-induced apoptosis. Cl-IB-MECA failed to activate phospholipase C in HL-60 cells, while UTP activated it through endogenous P2Y(2) receptors. Induction of apoptosis during a 48hr exposure to Cl-IB-MECA was not prevented by the A(3)AR antagonists [5-propyl-2-ethyl-4-propyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate] (MRS 1220) or N-[9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]benzeneacetamide (MRS 1523). Furthermore, higher concentrations of MRS 1220, which would also antagonize A(1) and A(2A) receptors, were ineffective in preventing the apoptosis. Although Cl-IB-MECA has been shown in other systems to cause apoptosis through an A(3)AR-mediated mechanism, in these cells it appeared to be an adenosine receptor-independent effect, which required prolonged incubation. In both HL-60 and MOLT-4 cells, Cl-IB-MECA induced the expression of Fas, a death receptor. This induction of Fas was not dependent upon p53, because p53 is not expressed in an active form in either HL-60 or MOLT-4 cells. Cl-IB-MECA-induced apoptosis in HL-60 cells was augmented by an agonistic Fas antibody, CH-11, and this increase was suppressed by the antagonistic anti-Fas antibody ZB-4. Therefore, Cl-IB-MECA induced apoptosis via a novel, p53-independent up-regulation of Fas. JF - Biochemical pharmacology AU - Kim, Seong Gon AU - Ravi, Gnana AU - Hoffmann, Carsten AU - Jung, Yun Jin AU - Kim, Min AU - Chen, Aishe AU - Jacobson, Kenneth A AD - Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/03/01/ PY - 2002 DA - 2002 Mar 01 SP - 871 EP - 880 VL - 63 IS - 5 SN - 0006-2952, 0006-2952 KW - Antibodies KW - 0 KW - Antigens, CD95 KW - Purinergic P1 Receptor Antagonists KW - Receptor, Adenosine A3 KW - Tumor Suppressor Protein p53 KW - Type C Phospholipases KW - EC 3.1.4.- KW - Adenosine KW - K72T3FS567 KW - Calcium KW - SY7Q814VUP KW - 2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide KW - Z07JR07J6C KW - Index Medicus KW - Leukemia -- pathology KW - Calcium -- metabolism KW - Drug Interactions KW - Blotting, Western KW - Tumor Cells, Cultured KW - HL-60 Cells KW - Humans KW - Antibodies -- pharmacology KW - Adenosine -- pharmacology KW - Apoptosis KW - Antigens, CD95 -- biosynthesis KW - Adenosine -- analogs & derivatives KW - Tumor Suppressor Protein p53 -- metabolism KW - Type C Phospholipases -- metabolism KW - Antigens, CD95 -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71551649?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=p53-Independent+induction+of+Fas+and+apoptosis+in+leukemic+cells+by+an+adenosine+derivative%2C+Cl-IB-MECA.&rft.au=Kim%2C+Seong+Gon%3BRavi%2C+Gnana%3BHoffmann%2C+Carsten%3BJung%2C+Yun+Jin%3BKim%2C+Min%3BChen%2C+Aishe%3BJacobson%2C+Kenneth+A&rft.aulast=Kim&rft.aufirst=Seong&rft.date=2002-03-01&rft.volume=63&rft.issue=5&rft.spage=871&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-07 N1 - Date created - 2002-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer's disease. AN - 71541655; 11880504 AB - Recent epidemiological and clinical data suggest that persons with low folic acid levels and elevated homocysteine levels are at increased risk of Alzheimer's disease (AD), but the underlying mechanism is unknown. We tested the hypothesis that impaired one-carbon metabolism resulting from folic acid deficiency and high homocysteine levels promotes accumulation of DNA damage and sensitizes neurons to amyloid beta-peptide (Abeta) toxicity. Incubation of hippocampal cultures in folic acid-deficient medium or in the presence of methotrexate (an inhibitor of folic acid metabolism) or homocysteine induced cell death and rendered neurons vulnerable to death induced by Abeta. Methyl donor deficiency caused uracil misincorporation and DNA damage and greatly potentiated Abeta toxicity as the result of reduced repair of Abeta-induced oxidative modification of DNA bases. When maintained on a folic acid-deficient diet, amyloid precursor protein (APP) mutant transgenic mice, but not wild-type mice, exhibited increased cellular DNA damage and hippocampal neurodegeneration. Levels of Abeta were unchanged in the brains of folate-deficient APP mutant mice. Our data suggest that folic acid deficiency and homocysteine impair DNA repair in neurons, which sensitizes them to oxidative damage induced by Abeta. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Kruman, Inna I AU - Kumaravel, T S AU - Lohani, Althaf AU - Pedersen, Ward A AU - Cutler, Roy G AU - Kruman, Yuri AU - Haughey, Norman AU - Lee, Jaewon AU - Evans, Michele AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, Maryland 21224, USA. Y1 - 2002/03/01/ PY - 2002 DA - 2002 Mar 01 SP - 1752 EP - 1762 VL - 22 IS - 5 KW - Amyloid beta-Peptides KW - 0 KW - Homocysteine KW - 0LVT1QZ0BA KW - Uracil KW - 56HH86ZVCT KW - Index Medicus KW - Animals KW - Uracil -- metabolism KW - Hippocampus -- metabolism KW - Disease Models, Animal KW - Mice KW - Hyperhomocysteinemia -- chemically induced KW - Mice, Transgenic KW - DNA Damage -- drug effects KW - Hippocampus -- drug effects KW - Rats KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Apoptosis -- drug effects KW - Hippocampus -- cytology KW - Diet KW - Hyperhomocysteinemia -- blood KW - Homocysteine -- blood KW - Neurons -- metabolism KW - Amyloid beta-Peptides -- metabolism KW - Neurons -- drug effects KW - Folic Acid Deficiency -- metabolism KW - Amyloid beta-Peptides -- toxicity KW - Homocysteine -- pharmacology KW - Alzheimer Disease -- metabolism KW - DNA Repair -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71541655?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Folic+acid+deficiency+and+homocysteine+impair+DNA+repair+in+hippocampal+neurons+and+sensitize+them+to+amyloid+toxicity+in+experimental+models+of+Alzheimer%27s+disease.&rft.au=Kruman%2C+Inna+I%3BKumaravel%2C+T+S%3BLohani%2C+Althaf%3BPedersen%2C+Ward+A%3BCutler%2C+Roy+G%3BKruman%2C+Yuri%3BHaughey%2C+Norman%3BLee%2C+Jaewon%3BEvans%2C+Michele%3BMattson%2C+Mark+P&rft.aulast=Kruman&rft.aufirst=Inna&rft.date=2002-03-01&rft.volume=22&rft.issue=5&rft.spage=1752&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-22 N1 - Date created - 2002-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overexpression of pyrimidine nucleoside phosphorylase enhances the sensitivity to 5'-deoxy-5-fluorouridine in tumour cells in vitro and in vivo. AN - 71537249; 11916555 AB - 5-Fluorouracil (5-FU) and 5'-deoxy-5-fluorouridine (5'-DFUR), a prodrug of 5-FU, are representative of the chemotherapeutic agents for colorectal adenocarcinomas. Pyrimidine nucleoside phosphorylase (PyNPase) catalyses the conversion of 5'-DFUR to 5-FU, the activated form. Murine adenocarcinoma CT26 cells were transfected with human PyNPase cDNA. The engineered transfectants producing PyNPase augmented the response to 5'-DFUR in vitro and in vivo. Animals were administered by means of intraperitoneal (i.p.) injection, and not orally, in order to obtain a better efficiency of absorption. The tumours of the transfected cells nearly all disappeared, even following treatment with quite a small amount of the anticancer agent. The animals injected with the tranfected cells were protected against subsequent challenge with the parental tumour cell line. These findings demonstrate that PyNPase gene transfection increases the sensitivity to 5'-DFUR, and thereby decreases the toxicity of the agent. JF - European journal of cancer (Oxford, England : 1990) AU - Nagata, T AU - Nakamori, M AU - Iwahashi, M AU - Yamaue, H AD - Second Department of Surgery, Wakayama Medical School, Kimiidera, Japan. nagatat@mail.nih.gov Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 712 EP - 717 VL - 38 IS - 5 SN - 0959-8049, 0959-8049 KW - Antimetabolites, Antineoplastic KW - 0 KW - DNA, Complementary KW - Prodrugs KW - Floxuridine KW - 039LU44I5M KW - Pentosyltransferases KW - EC 2.4.2.- KW - Pyrimidine Phosphorylases KW - Fluorouracil KW - U3P01618RT KW - doxifluridine KW - V1JK16Y2JP KW - Index Medicus KW - Animals KW - Drug Screening Assays, Antitumor KW - DNA, Complementary -- genetics KW - Combined Modality Therapy KW - Dose-Response Relationship, Drug KW - Humans KW - Mice KW - Mice, Inbred BALB C KW - Neoplasm Transplantation KW - Prodrugs -- therapeutic use KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Transfection KW - Prodrugs -- pharmacology KW - Fluorouracil -- pharmacology KW - Female KW - Pentosyltransferases -- genetics KW - Floxuridine -- pharmacology KW - Floxuridine -- therapeutic use KW - Adenocarcinoma -- pathology KW - Antimetabolites, Antineoplastic -- pharmacology KW - Colonic Neoplasms -- enzymology KW - Adenocarcinoma -- enzymology KW - Colonic Neoplasms -- drug therapy KW - Genetic Therapy -- methods KW - Adenocarcinoma -- drug therapy KW - Colonic Neoplasms -- pathology KW - Pentosyltransferases -- biosynthesis KW - Antimetabolites, Antineoplastic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71537249?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.atitle=Overexpression+of+pyrimidine+nucleoside+phosphorylase+enhances+the+sensitivity+to+5%27-deoxy-5-fluorouridine+in+tumour+cells+in+vitro+and+in+vivo.&rft.au=Nagata%2C+T%3BNakamori%2C+M%3BIwahashi%2C+M%3BYamaue%2C+H&rft.aulast=Nagata&rft.aufirst=T&rft.date=2002-03-01&rft.volume=38&rft.issue=5&rft.spage=712&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.issn=09598049&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-17 N1 - Date created - 2002-03-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV-1 and the brain: connections between HIV-1-associated dementia, neuropathology and neuroimmunology. AN - 71536184; 11909740 AB - AIDS patients frequently exhibit neurological disorders due to the neurotoxic events that result from HIV-1 and/or opportunistic infections in the brain. This review examines recent clinical findings related to HIV-1-associated dementia, and outlines current areas of basic research that may clarify how HIV-1-associated encephalopathy produces clinical symptoms of brain dysfunction. JF - Microbes and infection AU - Lawrence, Diane M AU - Major, Eugene O AD - Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 36, Room 5W21, 36 Convent Drive, MSC 4164, Bethesda, MD 20892-4164, USA. lawrencd@ninds.nih.gov Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 301 EP - 308 VL - 4 IS - 3 SN - 1286-4579, 1286-4579 KW - Index Medicus KW - Encephalitis, Viral -- immunology KW - Models, Immunological KW - Humans KW - Brain -- pathology KW - Brain -- immunology KW - HIV-1 -- pathogenicity KW - AIDS Dementia Complex -- immunology KW - AIDS Dementia Complex -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71536184?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Microbes+and+infection&rft.atitle=HIV-1+and+the+brain%3A+connections+between+HIV-1-associated+dementia%2C+neuropathology+and+neuroimmunology.&rft.au=Lawrence%2C+Diane+M%3BMajor%2C+Eugene+O&rft.aulast=Lawrence&rft.aufirst=Diane&rft.date=2002-03-01&rft.volume=4&rft.issue=3&rft.spage=301&rft.isbn=&rft.btitle=&rft.title=Microbes+and+infection&rft.issn=12864579&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-01 N1 - Date created - 2002-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel neurotrophic property of glucagon-like peptide 1: a promoter of nerve growth factor-mediated differentiation in PC12 cells. AN - 71534506; 11861804 AB - The insulinotropic hormone glucagon-like peptide-1 (7-36)-amide (GLP-1) has potent effects on glucose-dependent insulin secretion, insulin gene expression, and pancreatic islet cell formation and is presently in clinical trials as a therapy for type 2 diabetes mellitus. We report on the effects of GLP-1 and two of its long-acting analogs, exendin-4 and exendin-4 WOT, on neuronal proliferation and differentiation, and on the metabolism of two neuronal proteins in the rat pheochromocytoma (PC12) cell line, which has been shown to express the GLP-1 receptor. We observed that GLP-1 and exendin-4 induced neurite outgrowth in a manner similar to nerve growth factor (NGF), which was reversed by coincubation with the selective GLP-1 receptor antagonist exendin (9-39). Furthermore, exendin-4 could promote NGF-initiated differentiation and may rescue degenerating cells after NGF-mediated withdrawal. These effects were induced in the absence of cellular dysfunction and toxicity as quantitatively measured by 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase assays, respectively. Our findings suggest that such peptides may be used in reversing or halting the neurodegenerative process observed in neurodegenerative diseases, such as the peripheral neuropathy associated with type 2 diabetes mellitus and Alzheimer's and Parkinson's diseases. Due to its novel twin action, GLP-1 and exendin-4 have therapeutic potential for the treatment of diabetic peripheral neuropathy and these central nervous system disorders. JF - The Journal of pharmacology and experimental therapeutics AU - Perry, TracyAnn AU - Lahiri, Debomoy K AU - Chen, Demao AU - Zhou, Jie AU - Shaw, Karen T Y AU - Egan, Josephine M AU - Greig, Nigel H AD - Section of Drug, Design, and Development, Laboratory of Neuroscience, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. perryt@grc.nia.nih.gov Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 958 EP - 966 VL - 300 IS - 3 SN - 0022-3565, 0022-3565 KW - Antimetabolites KW - 0 KW - Glp1r protein, rat KW - Glucagon-Like Peptide-1 Receptor KW - Peptide Fragments KW - Peptides KW - Protein Precursors KW - Receptors, Glucagon KW - Tetrazolium Salts KW - Thiazoles KW - Venoms KW - Glucagon-Like Peptide 1 KW - 89750-14-1 KW - Glucagon KW - 9007-92-5 KW - Nerve Growth Factor KW - 9061-61-4 KW - exenatide KW - 9P1872D4OL KW - Cyclic AMP KW - E0399OZS9N KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - thiazolyl blue KW - EUY85H477I KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Index Medicus KW - Animals KW - Neurodegenerative Diseases -- pathology KW - Amino Acid Sequence KW - Peptides -- pharmacology KW - DNA Replication -- drug effects KW - Stimulation, Chemical KW - Receptors, Glucagon -- biosynthesis KW - Rats KW - Blotting, Western KW - Apoptosis -- drug effects KW - Molecular Sequence Data KW - Cyclic AMP -- metabolism KW - Cell Differentiation -- drug effects KW - Immunohistochemistry KW - L-Lactate Dehydrogenase -- metabolism KW - PC12 Cells KW - Protein Precursors -- pharmacology KW - Peptide Fragments -- pharmacology KW - Glucagon -- pharmacology KW - Nerve Growth Factor -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71534506?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=A+novel+neurotrophic+property+of+glucagon-like+peptide+1%3A+a+promoter+of+nerve+growth+factor-mediated+differentiation+in+PC12+cells.&rft.au=Perry%2C+TracyAnn%3BLahiri%2C+Debomoy+K%3BChen%2C+Demao%3BZhou%2C+Jie%3BShaw%2C+Karen+T+Y%3BEgan%2C+Josephine+M%3BGreig%2C+Nigel+H&rft.aulast=Perry&rft.aufirst=TracyAnn&rft.date=2002-03-01&rft.volume=300&rft.issue=3&rft.spage=958&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-28 N1 - Date created - 2002-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidants painting the cysteine chapel: redox regulation of PTPs. AN - 71533171; 11879627 AB - Growth factors and cytokines appear to stimulate the intracellular production of reactive oxygen species (ROS). Evidence suggests that this alteration in the cellular redox state is essential for downstream signaling, but the precise mechanism has remained elusive. A new study now demonstrates that ligand-stimulated intracellular hydrogen peroxide can specifically and reversibly regulate the activity of protein tyrosine phosphatases. JF - Developmental cell AU - Xu, Dong AU - Rovira, Ilsa I AU - Finkel, Toren AD - Cardiovascular Branch, NHLBI, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 251 EP - 252 VL - 2 IS - 3 SN - 1534-5807, 1534-5807 KW - Oxidants KW - 0 KW - Protein Tyrosine Phosphatases KW - EC 3.1.3.48 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Oxidation-Reduction KW - Cysteine -- metabolism KW - Protein Tyrosine Phosphatases -- metabolism KW - Oxidants -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71533171?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+cell&rft.atitle=Oxidants+painting+the+cysteine+chapel%3A+redox+regulation+of+PTPs.&rft.au=Xu%2C+Dong%3BRovira%2C+Ilsa+I%3BFinkel%2C+Toren&rft.aulast=Xu&rft.aufirst=Dong&rft.date=2002-03-01&rft.volume=2&rft.issue=3&rft.spage=251&rft.isbn=&rft.btitle=&rft.title=Developmental+cell&rft.issn=15345807&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-04 N1 - Date created - 2002-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro inhibition of the enzymatic activity of tumor suppressor FHIT gene product by carcinogenic transition metals. AN - 71526530; 11896678 AB - FHIT (Fragile Histidine Triad) is a human tumor suppressor gene. The Fhit protein is believed to inhibit tumor growth by inducing apoptosis through interaction with diadenosine triphosphate (Ap(3)A). The latter is first sequestered and eventually hydrolyzed by Fhit to ADP and AMP. Thus, the balance between the cellular Ap(3)A level and Fhit enzymatic activity may affect cell death or survival. Increasing the Ap(3)A level, e.g., by inhibition of the enzyme, should prevent apoptosis and thus sustain tumorigenesis. To test if certain carcinogenic transition metals could inhibit the enzymatic activity of Fhit, purified human Fhit protein [30 nM in 1.25 mM poly(vinylpyrrolidone)], expressed in and isolated from E. coli, was incubated at pH 6.8 (50 mM HEPES buffer in 150 mM NaCl) with 120 microM Ap(3)A in the presence of 5 mM Mg(II) (activating cation) and 0-100 microM Ni(II), Cu(II), Zn(II), Cd(II), Co(II), Cr(III), As(III), or As(V). The reaction mixtures were analyzed by HPLC. The results revealed a strong inhibitory potential of Cu(II) [0.4], followed by Ni(II) [3.5] >or= Zn(II) [7.0] >> Cr(III) [73] > Cd(II) [98] >> Co(II) [432] [the numbers in brackets are IC(50) values, microM]. As(III) and As(V) had no effect. As revealed by spectrophotometry, mass spectrometry, and gel electrophoresis, the exceptionally strong inhibition by Cu(II) was associated with Fhit dimerization through formation of a disulfide bond. The other metals and also H(2)O(2) and NO did not cause the dimerization. Thus, the effect of Cu(II) must be due to its reaction with Cys-39 bearing the only thiol group in Fhit monomer. Since Cys-39 is not readily accessible in the Fhit molecule, the reaction is most likely facilitated by conformational changes which follow the coordination of Cu(II) by the surface histidines 35, 94, and/or 96. The observed inhibition of Fhit may be mechanistically involved in metal-mediated toxicity and carcinogenesis. JF - Chemical research in toxicology AU - Kowara, Renata AU - Karaczyn, Aldona A AU - Fivash, Matthew J AU - Kasprzak, Kazimierz S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, Maryland 21702-1201, USA. Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 319 EP - 325 VL - 15 IS - 3 SN - 0893-228X, 0893-228X KW - Buffers KW - 0 KW - Carcinogens KW - Cations, Divalent KW - Dinucleoside Phosphates KW - Enzyme Inhibitors KW - Neoplasm Proteins KW - Transition Elements KW - fragile histidine triad protein KW - diadenosine triphosphate KW - 56432-02-1 KW - Acid Anhydride Hydrolases KW - EC 3.6.- KW - Magnesium KW - I38ZP9992A KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Cysteine -- chemistry KW - Dinucleoside Phosphates -- chemistry KW - Hydrogen-Ion Concentration KW - Humans KW - Spectrophotometry, Ultraviolet KW - Enzyme Inhibitors -- pharmacology KW - Binding Sites KW - Carcinogens -- pharmacology KW - Neoplasm Proteins -- antagonists & inhibitors KW - Genes, Tumor Suppressor KW - Transition Elements -- pharmacology KW - Neoplasm Proteins -- chemistry KW - Acid Anhydride Hydrolases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71526530?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=In+vitro+inhibition+of+the+enzymatic+activity+of+tumor+suppressor+FHIT+gene+product+by+carcinogenic+transition+metals.&rft.au=Kowara%2C+Renata%3BKaraczyn%2C+Aldona+A%3BFivash%2C+Matthew+J%3BKasprzak%2C+Kazimierz+S&rft.aulast=Kowara&rft.aufirst=Renata&rft.date=2002-03-01&rft.volume=15&rft.issue=3&rft.spage=319&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-16 N1 - Date created - 2002-03-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Significant variability in response to inhaled corticosteroids for persistent asthma. AN - 71523255; 11897984 AB - A clinical model is needed to compare inhaled corticosteroids (ICSs) with respect to efficacy. The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs. A 24-week, parallel, open-label, multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma. Benefit was assessed by improvements in FEV(1) and PC(20); risk was assessed by overnight plasma cortisol suppression. Thirty subjects were randomized to either beclomethasone dipropionate (BDP) 168, 672, and 1344 microg/day (n = 15) or fluticasone propionate (FP) 88, 352, and 704 microg/day (n = 15), both administered by means of a metered dose inhaler (MDI) with chlorofluorocarbon propellant via a spacer, in 3 consecutive 6-week intervals; this was followed by 3 weeks of FP dry powder inhaler (DPI) 2000 microg/day. Maximum FEV(1) response occurred with the low dose for FP-MDI and the medium dose for BDP-MDI and was not further increased by treatment with FP-DPI. Near-maximum methacholine PC(20) improvement occurred with the low dose for FP-MDI and the medium dose for BDP-MDI. Both BDP-MDI and FP-MDI caused dose-dependent cortisol suppression. Responsiveness to ICS treatment was found to vary markedly among subjects. Good (>15%) FEV(1) response, in contrast to poor (3 doubling dilutions) improvement in PC(20), in contrast to poor (<1 doubling dilution) improvement, was found to be associated with high sputum eosinophil levels (3.4% vs 0.1%) and older age at onset of asthma (age, 20-29 years vs <10 years). Near-maximal FEV(1) and PC(20) effects occurred with low-medium dose for both ICSs in the subjects studied. High-dose ICS therapy did not significantly increase the efficacy measures that were evaluated, but it did increase the systemic effect measure, overnight cortisol secretion. Significant intersubject variability in response occurred with both ICSs. It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study, such as prevention of asthma exacerbations. JF - The Journal of allergy and clinical immunology AU - Szefler, Stanley J AU - Martin, Richard J AU - King, Tonya Sharp AU - Boushey, Homer A AU - Cherniack, Reuben M AU - Chinchilli, Vernon M AU - Craig, Timothy J AU - Dolovich, Myrna AU - Drazen, Jeffrey M AU - Fagan, Joanne K AU - Fahy, John V AU - Fish, James E AU - Ford, Jean G AU - Israel, Elliot AU - Kiley, James AU - Kraft, Monica AU - Lazarus, Stephen C AU - Lemanske, Robert F AU - Mauger, Elizabeth AU - Peters, Stephen P AU - Sorkness, Christine A AU - Asthma Clinical Research Network of the National Heart Lung, and Blood Institute AD - National Jewish Medical and Research Center, Department of Pediatrics, Denver, CO 80206, USA. ; Asthma Clinical Research Network of the National Heart Lung, and Blood Institute Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 410 EP - 418 VL - 109 IS - 3 SN - 0091-6749, 0091-6749 KW - Androstadienes KW - 0 KW - Anti-Asthmatic Agents KW - Methacholine Chloride KW - 0W5ETF9M2K KW - Fluticasone KW - CUT2W21N7U KW - Beclomethasone KW - KGZ1SLC28Z KW - Hydrocortisone KW - WI4X0X7BPJ KW - Abridged Index Medicus KW - Index Medicus KW - Methacholine Chloride -- pharmacology KW - Prospective Studies KW - Humans KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Chronic Disease KW - Forced Expiratory Volume KW - Adolescent KW - Administration, Inhalation KW - Male KW - Hydrocortisone -- blood KW - Female KW - Beclomethasone -- adverse effects KW - Beclomethasone -- therapeutic use KW - Androstadienes -- adverse effects KW - Asthma -- drug therapy KW - Anti-Asthmatic Agents -- administration & dosage KW - Androstadienes -- therapeutic use KW - Androstadienes -- administration & dosage KW - Beclomethasone -- administration & dosage KW - Anti-Asthmatic Agents -- therapeutic use KW - Anti-Asthmatic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71523255?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+allergy+and+clinical+immunology&rft.atitle=Significant+variability+in+response+to+inhaled+corticosteroids+for+persistent+asthma.&rft.au=Szefler%2C+Stanley+J%3BMartin%2C+Richard+J%3BKing%2C+Tonya+Sharp%3BBoushey%2C+Homer+A%3BCherniack%2C+Reuben+M%3BChinchilli%2C+Vernon+M%3BCraig%2C+Timothy+J%3BDolovich%2C+Myrna%3BDrazen%2C+Jeffrey+M%3BFagan%2C+Joanne+K%3BFahy%2C+John+V%3BFish%2C+James+E%3BFord%2C+Jean+G%3BIsrael%2C+Elliot%3BKiley%2C+James%3BKraft%2C+Monica%3BLazarus%2C+Stephen+C%3BLemanske%2C+Robert+F%3BMauger%2C+Elizabeth%3BPeters%2C+Stephen+P%3BSorkness%2C+Christine+A%3BAsthma+Clinical+Research+Network+of+the+National+Heart+Lung%2C+and+Blood+Institute&rft.aulast=Szefler&rft.aufirst=Stanley&rft.date=2002-03-01&rft.volume=109&rft.issue=3&rft.spage=410&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+allergy+and+clinical+immunology&rft.issn=00916749&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-18 N1 - Date created - 2002-03-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Allergy Clin Immunol. 2005 Mar;115(3):466-9 [15753889] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bayesian models for multivariate current status data with informative censoring. AN - 71519574; 11890330 AB - Multivariate current status data, consist of indicators of whether each of several events occur by the time of a single examination. Our interest focuses on inferences about the joint distribution of the event times. Conventional methods for analysis of multiple event-time data cannot be used because all of the event times are censored and censoring may be informative. Within a given subject, we account for correlated event times through a subject-specific latent variable, conditional upon which the various events are assumed to occur independently. We also assume that each event contributes independently to the hazard of censoring. Nonparametric step functions are used to characterize the baseline distributions of the different event times and of the examination times. Covariate and subject-specific effects are incorporated through generalized linear models. A Markov chain Monte Carlo algorithm is described for estimation of the posterior distributions of the unknowns. The methods are illustrated through application to multiple tumor site data from an animal carcinogenicity study. JF - Biometrics AU - Dunson, David B AU - Dinse, Gregg E AD - Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. dunson1@niehs.nih.gov Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 79 EP - 88 VL - 58 IS - 1 SN - 0006-341X, 0006-341X KW - Chloroprene KW - 126-99-8 KW - Index Medicus KW - Uterine Neoplasms -- epidemiology KW - Animals KW - Humans KW - Uterine Neoplasms -- diagnosis KW - Stochastic Processes KW - Mice KW - Monte Carlo Method KW - Leiomyoma -- diagnosis KW - Rats KW - Rats, Inbred F344 KW - Leiomyoma -- epidemiology KW - Adrenal Gland Neoplasms -- chemically induced KW - Carcinogenicity Tests KW - Crosses, Genetic KW - Chloroprene -- toxicity KW - Markov Chains KW - Lung Neoplasms -- chemically induced KW - Female KW - Male KW - Bayes Theorem KW - Models, Statistical KW - Multivariate Analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71519574?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometrics&rft.atitle=Bayesian+models+for+multivariate+current+status+data+with+informative+censoring.&rft.au=Dunson%2C+David+B%3BDinse%2C+Gregg+E&rft.aulast=Dunson&rft.aufirst=David&rft.date=2002-03-01&rft.volume=58&rft.issue=1&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-05 N1 - Date created - 2002-03-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Resveratrol enhances the expression of non-steroidal anti-inflammatory drug-activated gene (NAG-1) by increasing the expression of p53. AN - 71518180; 11895857 AB - Dietary phenolic substances including resveratrol, a stillbene compound, are found in several fruits and vegetables, and these compounds have been reported to have anti-oxidant, anti-inflammatory and antitumorigenic activities. However, the molecular mechanisms underlying the antitumorigenic or chemopreventive activities of these compounds remain largely unknown. The expression of NAG-1 [non-steroidal anti-inflammatory (NSAID) drug-activated gene-1], a member of the transforming growth factor-beta (TGF-beta) superfamily, has been shown to be associated with pro-apoptotic and antitumorigenic activities. Here, we have demonstrated that resveratrol induces NAG-1 expression and apoptosis in a concentration-dependent manner. Resveratrol increases the expression of p53, tumor suppressor protein, prior to NAG-1 induction, indicating that NAG-1 expression by resveratrol is mediated by p53 expression. We also show that the p53 binding sites within the promoter region of NAG-1 play a pivotal role to control NAG-1 expression by resveratrol. Derivatives of resveratrol were examined for NAG-1 induction, and the data suggest that resveratrol-induced NAG-1 and p53 induction is not dependent on its anti-oxidant activity. The data may provide linkage between p53, NAG-1 and resveratrol, and in part, a new clue to the molecular mechanism of the antitumorigenic activity of natural polyphenolic compounds. JF - Carcinogenesis AU - Baek, Seung Joon AU - Wilson, Leigh C AU - Eling, Thomas E AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 425 EP - 434 VL - 23 IS - 3 SN - 0143-3334, 0143-3334 KW - Cytokines KW - 0 KW - GDF15 protein, human KW - Growth Differentiation Factor 15 KW - RNA, Messenger KW - Stilbenes KW - Tumor Suppressor Protein p53 KW - resveratrol KW - Q369O8926L KW - Index Medicus KW - Blotting, Western KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Dose-Response Relationship, Drug KW - Humans KW - Apoptosis -- drug effects KW - Cell Division -- drug effects KW - Flow Cytometry KW - RNA, Messenger -- genetics KW - Time Factors KW - Structure-Activity Relationship KW - Stilbenes -- pharmacology KW - Stilbenes -- chemistry KW - Gene Expression Regulation -- drug effects KW - Cytokines -- metabolism KW - Tumor Suppressor Protein p53 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71518180?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Resveratrol+enhances+the+expression+of+non-steroidal+anti-inflammatory+drug-activated+gene+%28NAG-1%29+by+increasing+the+expression+of+p53.&rft.au=Baek%2C+Seung+Joon%3BWilson%2C+Leigh+C%3BEling%2C+Thomas+E&rft.aulast=Baek&rft.aufirst=Seung&rft.date=2002-03-01&rft.volume=23&rft.issue=3&rft.spage=425&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-08 N1 - Date created - 2002-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The insulinotropic effect of acute exendin-4 administered to humans: comparison of nondiabetic state to type 2 diabetes. AN - 71516980; 11889200 AB - Exendin-4 is a potent and long-acting agonist of the glucagon-like peptide-1 (GLP-1) receptor. GLP-1 is an insulinotropic gut peptide and is being evaluated for the regulation of plasma glucose in type 2 diabetes. The purpose of the present study was to ascertain whether exendin-4 is insulinotropic and whether it has long-lived biological effects in nondiabetic and type 2 diabetic subjects. Because incretins are glucose dependent with respect to their insulin-releasing capacity, we used the hyperglycemic glucose clamp technique to begin to address these issues in two separate protocols. In one protocol, we infused exendin-4 (0.15 pmol x kg(-1) x min(-1)) in seven nondiabetic and seven type 2 diabetic subjects during the second hour of a 5-h hyperglycemic clamp in which fasting plasma glucose was raised by 5.4 mmol/liter. The second protocol was identical to the first except that plasma glucose was allowed to fall to the fasting levels during the fourth hour and again raised by 5.4 mmol/liter during the fifth hour in four nondiabetic and four diabetic subjects. With the initiation of exendin-4 infusion at 60 min, plasma insulin response was potentiated 4- to 5-fold in both groups. Despite termination of exendin-4 at the end of the second hour, the insulin levels remained elevated for several hours and hyperglycemia was maintained. All volunteers ate a meal 5.5 h after inducing hyperglycemia. Postprandial plasma glucose, insulin, and GLP-1 did not rise in any subject, possibly because of delayed gastric emptying by exendin-4 even though its infusion had been terminated 4 h previously. We concluded that exendin-4 is a potent and long-lasting insulinotropic agent in nondiabetic and diabetic subjects. JF - The Journal of clinical endocrinology and metabolism AU - Egan, Josephine M AU - Clocquet, Astrid R AU - Elahi, Dariush AD - Diabetes and Metabolism Section, Laboratory of Clinical Investigation, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 1282 EP - 1290 VL - 87 IS - 3 SN - 0021-972X, 0021-972X KW - Blood Glucose KW - 0 KW - Insulin KW - Peptides KW - Venoms KW - exenatide KW - 9P1872D4OL KW - Abridged Index Medicus KW - Index Medicus KW - Reference Values KW - Postprandial Period KW - Half-Life KW - Humans KW - Glucose Clamp Technique KW - Adult KW - Aged KW - Middle Aged KW - Blood Glucose -- analysis KW - Male KW - Female KW - Insulin -- blood KW - Peptides -- chemistry KW - Diabetes Mellitus, Type 2 -- blood KW - Peptides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71516980?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+endocrinology+and+metabolism&rft.atitle=The+insulinotropic+effect+of+acute+exendin-4+administered+to+humans%3A+comparison+of+nondiabetic+state+to+type+2+diabetes.&rft.au=Egan%2C+Josephine+M%3BClocquet%2C+Astrid+R%3BElahi%2C+Dariush&rft.aulast=Egan&rft.aufirst=Josephine&rft.date=2002-03-01&rft.volume=87&rft.issue=3&rft.spage=1282&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+endocrinology+and+metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-08 N1 - Date created - 2002-03-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Extracellular Bad fused to toxin transport domains induces apoptosis. AN - 71516546; 11888916 AB - Bad, a proapoptotic member of the Bcl-2 family, is inactivated by phosphorylation, and this loss of activity may contribute to the malignancy of certain types of tumors such as glioblastoma and prostate cancer. To determine whether extracellular Bad can be delivered into cells via cell surface receptor binding and induce apoptosis, we genetically fused the mouse Bad gene to the gene for the translocation and receptor-binding domains of diphtheria toxin (DTTR). The purified Bad (wild-type)-DTTR protein showed cytotoxicity to human glioma cells in a dose-dependent manner. Bad phosphorylation sites at codons 112 and 136 were mutated from serine to alanine to prevent Bad inactivation by kinases and to increase the toxicity of Bad. The Bad (S112A S136A)-DTTR protein was at least 5 times more toxic than Bad (wild-type)-DTTR with an IC(50) of 5 x 10(-8) M. The Bad (S112A S136A)-DTTR protein altered the subcellular distribution of Bcl-X(L), indicating that it enters the cell cytoplasm and binds Bcl-X(L). Bad (S112D S136A)-DTTR, mutated to mimic phosphorylation of Bad, showed lower toxicity than either Bad (wild-type)-DTTR or Bad (S112A S136A)-DTTR, additionally indicating that Bad-DTTR must bind Bcl-X(L) to stimulate apoptosis. We conclude that extracellular Bad can be delivered into cells via the transport domain of a bacterial toxin and may be used to induce apoptosis. JF - Cancer research AU - Ichinose, Makoto AU - Liu, Xiu-Huai AU - Hagihara, Naoshi AU - Youle, Richard J AD - Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/03/01/ PY - 2002 DA - 2002 Mar 01 SP - 1433 EP - 1438 VL - 62 IS - 5 SN - 0008-5472, 0008-5472 KW - BAD protein, human KW - 0 KW - BCL2L1 protein, human KW - Carrier Proteins KW - Diphtheria Toxin KW - Proto-Oncogene Proteins c-bcl-2 KW - Recombinant Fusion Proteins KW - Tumor Suppressor Proteins KW - bcl-Associated Death Protein KW - bcl-X Protein KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - PTEN Phosphohydrolase KW - EC 3.1.3.67 KW - PTEN protein, human KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Phosphorylation KW - Humans KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - Tumor Suppressor Proteins -- genetics KW - Biological Transport KW - Phosphoric Monoester Hydrolases -- genetics KW - Recombinant Fusion Proteins -- metabolism KW - Apoptosis -- drug effects KW - Recombinant Fusion Proteins -- isolation & purification KW - Diphtheria Toxin -- pharmacology KW - Carrier Proteins -- pharmacology KW - Recombinant Fusion Proteins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71516546?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Extracellular+Bad+fused+to+toxin+transport+domains+induces+apoptosis.&rft.au=Ichinose%2C+Makoto%3BLiu%2C+Xiu-Huai%3BHagihara%2C+Naoshi%3BYoule%2C+Richard+J&rft.aulast=Ichinose&rft.aufirst=Makoto&rft.date=2002-03-01&rft.volume=62&rft.issue=5&rft.spage=1433&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-05 N1 - Date created - 2002-03-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mice lacking Smad3 are protected against cutaneous injury induced by ionizing radiation. AN - 71514485; 11891202 AB - Transforming growth factor-beta (TGF-beta) plays a central role in the pathogenesis of inflammatory and fibrotic diseases, including radiation-induced fibrosis. We previously reported that mice null for Smad3, a key downstream mediator of TGF-beta, show accelerated healing of cutaneous incisional wounds with reduced inflammation and accumulation of matrix. To determine if loss of Smad3 decreases radiation-induced injury, skin of Smad3+/+ [wild-type (WT)] and -/- [knockout (KO)] mice was exposed to a single dose of 30 to 50 Gy of gamma-irradiation. Six weeks later, skin from KO mice showed significantly less epidermal acanthosis and dermal influx of mast cells, macrophages, and neutrophils than skin from WT littermates. Skin from irradiated KO mice exhibited less immunoreactive TGF-beta and fewer myofibroblasts, suggesting that these mice will have a significantly reduced fibrotic response. Although irradiation induced no change in the immunohistochemical expression of the TGF-beta type I receptor, the epidermal expression of the type II receptor was lost after irradiation whereas its dermal expression remained high. Primary keratinocytes and dermal fibroblasts prepared from WT and KO mice showed similar survival when irradiated, as did mice exposed to whole-body irradiation. These results suggest that inhibition of Smad3 might decrease tissue damage and reduce fibrosis after exposure to ionizing irradiation. JF - The American journal of pathology AU - Flanders, Kathleen C AU - Sullivan, Catherine D AU - Fujii, Makiko AU - Sowers, Anastasia AU - Anzano, Mario A AU - Arabshahi, Alidad AU - Major, Christopher AU - Deng, Chuxia AU - Russo, Angelo AU - Mitchell, James B AU - Roberts, Anita B AD - Laboratory of Cell Regulation and Carcinogenesis and Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-5055, USA. flanderk@dce41.nci.nih.gov Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 1057 EP - 1068 VL - 160 IS - 3 SN - 0002-9440, 0002-9440 KW - DNA-Binding Proteins KW - 0 KW - Smad3 Protein KW - Smad3 protein, mouse KW - Trans-Activators KW - Transforming Growth Factor beta KW - Abridged Index Medicus KW - Index Medicus KW - Keratinocytes -- radiation effects KW - Animals KW - Gamma Rays KW - Mice KW - Fibroblasts -- physiology KW - Mice, Knockout KW - Keratinocytes -- physiology KW - Transforming Growth Factor beta -- physiology KW - Fibroblasts -- pathology KW - Fibroblasts -- radiation effects KW - Keratinocytes -- pathology KW - Cell Survival -- radiation effects KW - Skin -- radiation effects KW - Trans-Activators -- genetics KW - Skin -- pathology KW - Radiation Injuries, Experimental -- genetics KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- physiology KW - Trans-Activators -- physiology KW - Radiation Injuries, Experimental -- physiopathology KW - Radiation Injuries, Experimental -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71514485?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+pathology&rft.atitle=Mice+lacking+Smad3+are+protected+against+cutaneous+injury+induced+by+ionizing+radiation.&rft.au=Flanders%2C+Kathleen+C%3BSullivan%2C+Catherine+D%3BFujii%2C+Makiko%3BSowers%2C+Anastasia%3BAnzano%2C+Mario+A%3BArabshahi%2C+Alidad%3BMajor%2C+Christopher%3BDeng%2C+Chuxia%3BRusso%2C+Angelo%3BMitchell%2C+James+B%3BRoberts%2C+Anita+B&rft.aulast=Flanders&rft.aufirst=Kathleen&rft.date=2002-03-01&rft.volume=160&rft.issue=3&rft.spage=1057&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+pathology&rft.issn=00029440&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-02 N1 - Date created - 2002-03-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Physiol. 1997 Sep;172(3):361-72 [9284956] Cancer J Sci Am. 1996 Sep-Oct;2(5):273-8 [9166544] J Clin Invest. 1997 Nov 1;100(9):2182-8 [9410894] Cell. 1998 Mar 20;92(6):797-808 [9529255] Curr Opin Genet Dev. 1998 Feb;8(1):103-11 [9529613] Nature. 1998 Jun 25;393(6687):786-90 [9655392] Mol Cell. 1998 Mar;1(4):611-7 [9660945] Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9378-83 [9689088] J Cell Biol. 1998 Aug 10;142(3):873-81 [9700173] Cell. 1998 Sep 18;94(6):703-14 [9753318] Nat Cell Biol. 1999 Sep;1(5):260-6 [10559937] Microbes Infect. 1999 Dec;1(15):1349-65 [10611762] Radiat Res. 2000 Mar;153(3):245-57 [10669545] Cytokine Growth Factor Rev. 2000 Mar-Jun;11(1-2):159-68 [10708963] J Leukoc Biol. 2000 Mar;67(3):350-6 [10733095] Int J Radiat Oncol Biol Phys. 2000 May 1;47(2):277-90 [10802350] J Invest Dermatol. 2000 Jun;114(6):1075-84 [10844548] J Natl Cancer Inst. 2000 Sep 6;92(17):1388-402 [10974075] J Biol Chem. 2000 Dec 15;275(50):39237-45 [11007770] Nat Rev Mol Cell Biol. 2000 Dec;1(3):169-78 [11252892] FASEB J. 2001 Mar;15(3):553-5 [11259364] Biochem Biophys Res Commun. 2001 May 11;283(3):554-62 [11341760] J Biol Chem. 2001 May 18;276(20):17058-62 [11279127] J Biol Chem. 2001 Jun 8;276(23):19945-53 [11262418] Oncogene. 2001 Jun 7;20(26):3332-40 [11423983] Am J Pathol. 2001 Jul;159(1):263-72 [11438473] J Biol Chem. 2001 Jul 13;276(28):26349-56 [11320083] Chest. 2001 Jul;120(1 Suppl):43S-47S [11451911] Blood. 1978 Aug;52(2):447-52 [352443] Cancer Res. 1986 Apr;46(4 Pt 2):2068-71 [2418960] J Exp Med. 1987 Jan 1;165(1):251-6 [3491869] Proc Natl Acad Sci U S A. 1987 Aug;84(16):5788-92 [2886992] J Cell Biol. 1989 Feb;108(2):653-60 [2465297] Agents Actions Suppl. 1991;35:29-34 [1781421] Int Arch Allergy Immunol. 1992;98(4):410-4 [1422267] Radiat Res. 1993 Apr;134(1):63-70 [8475255] J Cell Biol. 1993 Jul;122(1):103-11 [8314838] J Invest Dermatol. 1993 Jul;101(1 Suppl):124S-129S [8326145] J Clin Invest. 1994 Feb;93(2):892-9 [8113421] J Immunol. 1994 Jun 15;152(12):5860-7 [7515916] N Engl J Med. 1994 Nov 10;331(19):1286-92 [7935686] Methods Enzymol. 1995;254:3-20 [8531694] Int J Radiat Biol. 1996 Sep;70(3):351-60 [8800206] Cytokine Growth Factor Rev. 1996 Jun;7(1):93-102 [8864357] Inflammation. 1996 Aug;20(4):339-52 [8872498] Radiat Res. 1996 Dec;146(6):619-27 [8955711] Exp Cell Res. 1997 Mar 15;231(2):328-36 [9087174] Cell. 1997 Jun 27;89(7):1165-73 [9215638] Oncogene. 1997 Aug 18;15(8):981-9 [9285693] Radiat Res. 1990 Apr;122(1):77-85 [2181527] J Biol Chem. 1991 Feb 25;266(6):3444-8 [1847373] Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6805-9 [1650483] Development. 1991 Sep;113(1):183-91 [1764993] Radiat Res. 1998 Dec;150(6):673-80 [9840187] Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14769-74 [9843964] J Biol Chem. 1999 Jan 8;274(2):703-9 [9873005] J Invest Dermatol. 1999 Jan;112(1):49-57 [9886263] EMBO J. 1999 Mar 1;18(5):1280-91 [10064594] Mol Cell Biol. 1999 Apr;19(4):2495-504 [10082515] J Cell Sci. 1999 Jun;112 ( Pt 12):1843-53 [10341204] Radiat Res. 1999 Jun;151(6):703-9 [10360790] Immunol Cell Biol. 1999 Jun;77(3):263-71 [10361259] Nature. 1997 Oct 9;389(6651):631-5 [9335507] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hes-1, a known transcriptional repressor, acts as a transcriptional activator for the human acid alpha-glucosidase gene in human fibroblast cells. AN - 71513439; 11855828 AB - Hes-1, the mammalian homologue 1 of Drosophila hairy and Enhancer of split proteins, belongs to a family of basic helix-loop-helix proteins that are essential to neurogenesis, myogenesis, hematopoiesis, and sex determination. Hes-1 is a transcriptional repressor for a number of known genes including the human acid alpha-glucosidase (GAA) gene as we have previously shown in Hep G2 cells. The human GAA gene encodes the enzyme for glycogen breakdown in lysosomes, deficiency of which results in Glycogen Storage Disease type II (Pompe syndrome). Using constructs containing the DNA element that demonstrates repressive activity in Hep G2 cells and conditions in which the same transcription factors, Hes-1 and YY1, bind, we have shown that this element functions as an enhancer in human fibroblasts. Site-directed mutagenesis and overexpression of Hes-1 showed that Hes-1 functions as a transcriptional activator. The dual function of Hes-1 we have found is likely to contribute to the subtle tissue-specific control of this housekeeping gene. ©2002 Elsevier Science (USA). JF - Biochemical and biophysical research communications AU - Yan, Bo AU - Raben, Nina AU - Plotz, Paul H AD - Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Building 10, Room 9N244, 9000 Rockville Pike, Bethesda, Maryland 20892-1820, USA. Y1 - 2002/03/01/ PY - 2002 DA - 2002 Mar 01 SP - 582 EP - 587 VL - 291 IS - 3 SN - 0006-291X, 0006-291X KW - Basic Helix-Loop-Helix Transcription Factors KW - 0 KW - Homeodomain Proteins KW - Repressor Proteins KW - Trans-Activators KW - Transcription Factor HES-1 KW - HES1 protein, human KW - 149348-15-2 KW - Glucan 1,4-alpha-Glucosidase KW - EC 3.2.1.3 KW - Index Medicus KW - Humans KW - Electrophoretic Mobility Shift Assay KW - Plasmids KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Gene Expression Regulation, Enzymologic KW - Transfection KW - Enhancer Elements, Genetic KW - Adult KW - Genes, Reporter KW - Response Elements KW - Cell Line KW - Fibroblasts -- enzymology KW - Homeodomain Proteins -- genetics KW - Trans-Activators -- genetics KW - Repressor Proteins -- physiology KW - Homeodomain Proteins -- physiology KW - Trans-Activators -- physiology KW - Repressor Proteins -- genetics KW - Glucan 1,4-alpha-Glucosidase -- genetics KW - Fibroblasts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71513439?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Hes-1%2C+a+known+transcriptional+repressor%2C+acts+as+a+transcriptional+activator+for+the+human+acid+alpha-glucosidase+gene+in+human+fibroblast+cells.&rft.au=Yan%2C+Bo%3BRaben%2C+Nina%3BPlotz%2C+Paul+H&rft.aulast=Yan&rft.aufirst=Bo&rft.date=2002-03-01&rft.volume=291&rft.issue=3&rft.spage=582&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-01 N1 - Date created - 2002-02-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dose finding using the biased coin up-and-down design and isotonic regression. AN - 71510621; 11890313 AB - We are interested in finding a dose that has a prespecified toxicity rate in the target population. In this article, we investigate five estimators of the target dose to be used with the up-and-down biased coin design (BCD) introduced by Durham and Flournoy (1994, Statistical Decision Theory and Related Topics). These estimators are derived using maximum likelihood, weighted least squares, sample averages, and isotonic regression. A linearly interpolated isotonic regression estimate is shown to be simple to derive and to perform as well as or better than the other target dose estimators in terms of mean square error and average number of subjects needed for convergence in most scenarios studied. JF - Biometrics AU - Stylianou, Mario AU - Flournoy, Nancy AD - Office of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892, USA. StylianM@nih.gov Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 171 EP - 177 VL - 58 IS - 1 SN - 0006-341X, 0006-341X KW - Pharmaceutical Preparations KW - 0 KW - Index Medicus KW - Computer Simulation KW - Logistic Models KW - Humans KW - Toxicity Tests -- methods KW - Monte Carlo Method KW - Pharmaceutical Preparations -- administration & dosage KW - Clinical Trials, Phase I as Topic -- methods KW - Statistics as Topic -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71510621?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometrics&rft.atitle=Dose+finding+using+the+biased+coin+up-and-down+design+and+isotonic+regression.&rft.au=Stylianou%2C+Mario%3BFlournoy%2C+Nancy&rft.aulast=Stylianou&rft.aufirst=Mario&rft.date=2002-03-01&rft.volume=58&rft.issue=1&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-05 N1 - Date created - 2002-03-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Defective repair of 8-hydroxyguanine in mitochondria of MCF-7 and MDA-MB-468 human breast cancer cell lines. AN - 71507475; 11888904 AB - Breast cancer is one of the major causes of mortality among women in the United States. Although the causes of breast cancer remain unclear, it has been speculated that DNA base damage may lead to mutations that subsequently can be carcinogenic. Recently, defective oxidative DNA damage repair has been implicated in breast tumorigenesis. The major oxidative DNA lesion, 8-hydroxyguanine (8-oxoG), is increased in breast cancer, suggesting that this lesion may play a crucial role in the etiology of breast cancer. However, it is not known whether the repair of 8-oxoG or other oxidative base lesions is altered during breast carcinogenesis. We examined the ability of nuclear and mitochondrial extracts of two human breast cancer cell lines, MCF-7 and MDA-MB-468, to repair 8-oxoG lesion. We report that mitochondrial extracts from the two breast cancer cell lines are defective in the base excision repair of 8-oxoG relative to two noncancer cell lines. We also show that the incision activity of 8-oxoG was significantly lower in mitochondrial than in nuclear extracts in the breast cancer cell lines. The defective mitochondrial repair activity was not attributable to lower levels of human 8-hydroxyguanine DNA glycosylase, the base excision repair enzyme known to incise 8-oxoG in DNA. The repair of thymine glycol, another major oxidative DNA base lesion that blocks transcription and causes cell death, was similar in cancer and noncancer cells. Furthermore, nuclear extracts incised thymine glycol with a much higher efficiency than 8-oxoG. These data provide evidence for defective repair of 8-oxoG in mitochondria of MCF-7 and MDA-MB-468 breast cancer cell lines. These results may implicate 8-oxoG repair mechanisms in mitochondria of certain breast cancers. JF - Cancer research AU - Mambo, Elizabeth AU - Nyaga, Simon G AU - Bohr, Vilhelm A AU - Evans, Michele K AD - Laboratory of Cellular and Molecular Biology, National Institute on Aging National Institutes of Health, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2002/03/01/ PY - 2002 DA - 2002 Mar 01 SP - 1349 EP - 1355 VL - 62 IS - 5 SN - 0008-5472, 0008-5472 KW - 8-hydroxyguanine KW - 5614-64-2 KW - Guanine KW - 5Z93L87A1R KW - Electron Transport Complex IV KW - EC 1.9.3.1 KW - N-Glycosyl Hydrolases KW - EC 3.2.2.- KW - DNA-Formamidopyrimidine Glycosylase KW - EC 3.2.2.23 KW - Index Medicus KW - Blotting, Western KW - Tumor Cells, Cultured KW - N-Glycosyl Hydrolases -- genetics KW - N-Glycosyl Hydrolases -- metabolism KW - Cell Nucleus -- metabolism KW - Humans KW - Reverse Transcriptase Polymerase Chain Reaction KW - Electron Transport Complex IV -- metabolism KW - Female KW - DNA Repair KW - Mitochondria -- metabolism KW - Breast Neoplasms -- metabolism KW - Guanine -- analogs & derivatives KW - Guanine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71507475?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Defective+repair+of+8-hydroxyguanine+in+mitochondria+of+MCF-7+and+MDA-MB-468+human+breast+cancer+cell+lines.&rft.au=Mambo%2C+Elizabeth%3BNyaga%2C+Simon+G%3BBohr%2C+Vilhelm+A%3BEvans%2C+Michele+K&rft.aulast=Mambo&rft.aufirst=Elizabeth&rft.date=2002-03-01&rft.volume=62&rft.issue=5&rft.spage=1349&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-05 N1 - Date created - 2002-03-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gemcitabine in advanced adult soft-tissue sarcomas. A phase II study of the EORTC Soft Tissue and Bone Sarcoma Group. AN - 71501509; 11872349 AB - Gemcitabine (2'-deoxy-2'-difluorocytidine monohydrochloride) at a dose of 1250 mg/m(2) was given as a 30-min intravenous (i.v.) infusion on days 1 and 8 in a 3-weekly schedule to 32 patients with advanced soft-tissue sarcoma (STS) failing first-line chemotherapy. One patient was ineligible due to a delay between the previous chemotherapy and the start of treatment. Of the eligible patients, median age was 53 years (range 23-73 years). The predominant histological subtype was leiomyosarcoma in 12 patients (38%). The median number of cycles was three (range 1-8 cycles) with a median total dose of gemcitabine of 6.25 g/m(2) (range 1.25-19.97 g/m(2)). The relative dose intensity of gemcitabine was 96% (range 50-103%). Treatment was tolerated very well with non-complicated haematological toxicity as the most frequently observed side-effect. Only one partial tumour response was documented, giving a response rate of 3.23% (95% Confidence Interval (CI): 0.08-16.2%). The median overall survival was 268 days (95% CI: 129-377) and the median time to progression was 45 days (95% CI: 41-79). These results indicate that gemcitabine given at this dose and schedule is not active as second-line therapy in advanced STS. JF - European journal of cancer (Oxford, England : 1990) AU - Svancárová, L AU - Blay, J Y AU - Judson, I R AU - van Hoesel, Q G C M AU - van Oosterom, A T AU - le Cesne, A AU - Keizer, H J AU - Hermans, C AU - van Glabbeke, M AU - Verweij, J AU - Hogendoorn, P C W AU - Nielsen, O S AD - National Cancer Institute, Bratislava, Slovakia. Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 556 EP - 559 VL - 38 IS - 4 SN - 0959-8049, 0959-8049 KW - Antimetabolites, Antineoplastic KW - 0 KW - Deoxycytidine KW - 0W860991D6 KW - gemcitabine KW - B76N6SBZ8R KW - Index Medicus KW - Infusions, Intravenous KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - Male KW - Female KW - Survival Analysis KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Deoxycytidine -- adverse effects KW - Antimetabolites, Antineoplastic -- adverse effects KW - Deoxycytidine -- analogs & derivatives KW - Deoxycytidine -- administration & dosage KW - Sarcoma -- drug therapy KW - Sarcoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71501509?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.atitle=Gemcitabine+in+advanced+adult+soft-tissue+sarcomas.+A+phase+II+study+of+the+EORTC+Soft+Tissue+and+Bone+Sarcoma+Group.&rft.au=Svanc%C3%A1rov%C3%A1%2C+L%3BBlay%2C+J+Y%3BJudson%2C+I+R%3Bvan+Hoesel%2C+Q+G+C+M%3Bvan+Oosterom%2C+A+T%3Ble+Cesne%2C+A%3BKeizer%2C+H+J%3BHermans%2C+C%3Bvan+Glabbeke%2C+M%3BVerweij%2C+J%3BHogendoorn%2C+P+C+W%3BNielsen%2C+O+S&rft.aulast=Svanc%C3%A1rov%C3%A1&rft.aufirst=L&rft.date=2002-03-01&rft.volume=38&rft.issue=4&rft.spage=556&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.issn=09598049&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-30 N1 - Date created - 2002-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dendritic calcium encodes striatal neuron output during up-states. AN - 71500328; 11880480 AB - Striatal spiny projection neurons control basal ganglia outputs via action potential bursts conveyed to the globus pallidus and substantia nigra. Accordingly, burst activity in these neurons contributes importantly to basal ganglia function and dysfunction. These bursts are driven by multiple corticostriatal inputs that depolarize spiny projection neurons from their resting potential of approximately -85 mV, which is the down-state, to a subthreshold up-state of -55 mV. To understand dendritic processing of bursts during up-states, changes in intracellular calcium concentration ([Ca2+]i) were measured in striatal spiny projection neurons from cortex-striatum-substantia nigra organotypic cultures grown for 5-6 weeks using somatic whole-cell patch recording and Fura-2. During up-states, [Ca2+]i transients at soma and primary, secondary, and tertiary dendrites were highly correlated with burst strength (i.e., the number of spontaneous action potentials). During down-states, the action potentials evoked by somatic current pulses elicited [Ca2+]i transients in higher-order dendrites that were also correlated with burst strength. Evoked bursts during up-states increased dendritic [Ca2+]i transients supralinearly by >200% compared with the down-state. In the presence of tetrodotoxin, burst-like voltage commands failed to elicit [Ca2+]i transients at higher-order dendrites. Thus, dendritic [Ca2+]i transients in spiny projection neurons encode somatic bursts supralinearly during up-states through active propagation of action potentials along dendrites. We suggest that this conveys information about the contribution of a spiny projection neuron to a basal ganglia output specifically back to the corticostriatal synapses involved in generating these outputs. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Kerr, Jason N D AU - Plenz, Dietmar AD - Unit of Neural Network Physiology, Laboratory of Systems Neuroscience, National Institute of Mental Health, Bethesda, Maryland 20892, USA. Y1 - 2002/03/01/ PY - 2002 DA - 2002 Mar 01 SP - 1499 EP - 1512 VL - 22 IS - 5 KW - Fluorescent Dyes KW - 0 KW - Tetrodotoxin KW - 4368-28-9 KW - Calcium KW - SY7Q814VUP KW - Fura-2 KW - TSN3DL106G KW - Index Medicus KW - Action Potentials -- physiology KW - Animals KW - Sensory Thresholds -- physiology KW - Membrane Potentials -- physiology KW - Intracellular Fluid -- metabolism KW - Electric Stimulation KW - Rats KW - Rats, Sprague-Dawley KW - Calcium Signaling -- drug effects KW - Patch-Clamp Techniques KW - Calcium Signaling -- physiology KW - Cells, Cultured KW - In Vitro Techniques KW - Membrane Potentials -- drug effects KW - Tetrodotoxin -- pharmacology KW - Calcium -- metabolism KW - Corpus Striatum -- cytology KW - Neurons -- metabolism KW - Dendrites -- metabolism KW - Synaptic Transmission -- drug effects KW - Neurons -- drug effects KW - Corpus Striatum -- metabolism KW - Corpus Striatum -- drug effects KW - Synaptic Transmission -- physiology KW - Dendrites -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71500328?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Dendritic+calcium+encodes+striatal+neuron+output+during+up-states.&rft.au=Kerr%2C+Jason+N+D%3BPlenz%2C+Dietmar&rft.aulast=Kerr&rft.aufirst=Jason+N&rft.date=2002-03-01&rft.volume=22&rft.issue=5&rft.spage=1499&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-22 N1 - Date created - 2002-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic polymorphisms in heterocyclic amine metabolism and risk of colorectal adenomas. AN - 71495957; 11875368 AB - High red meat intake has been linked with an increased risk of colorectal cancer and adenomas. During high temperature cooking of red meats, heterocyclic amines (HCAs) are generated; however, to be carcinogenic, they must be metabolized by enzymes including cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 1 (NAT1) and/or N-acetyltransferase 2 (NAT2). We have conducted a clinic-based case-control study of colorectal adenomas that focused on assessment of exposure to HCAs (estimated by use of a HCA database and meat cooking module) and modification of these exposures by genetic factors. We have previously reported that intake of MeIQx was associated with an increased risk of colorectal adenomas [overall association at 80th percentile, > 27.00 ng/day: odds ratio (OR) = 2.68, 95% confidence interval (CI) 1.58-4.55]. Here, we report our evaluation of whether variation in CYP1A2, NAT1 and/or NAT2 modify the association between HCAs and colorectal adenoma formation in 146 cases and 228 frequency-matched controls. The NAT1*10 allele was associated with a nonsignificant increased risk of colorectal adenomas (OR = 1.43; 95% CI 0.86-2.36). Further, when we analysed 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) intake as a categorical variable, we observed a six-fold increase in adenoma risk among rapid NAT1 acetylators who consumed more than 27 ng a day (OR = 6.50; 95% CI 2.16-19.7), whereas among slow NAT1 acetylators, the increase in risk was two-fold (OR = 2.32; 95% CI 1.12-4.81). While suggestive, the results were not significantly different from each other on either an additive or multiplicative scale. In contrast, NAT2 genotype and CYP1A2 and NAT2 hepatic activity measured by caffeine urinary metabolites were not associated with adenoma risk, although an increase in risk with rapid CYP1A2 activity could not be ruled out (OR = 1.46; 95% CI 0.76-2.81). Moreover, there was no evidence that the effect of MeIQx was enhanced among subjects in any subgroup defined by variation in these measures. These results are compatible with the hypothesis that high HCA exposure is associated with an increased risk of colorectal adenomas, particularly in genetically susceptible subgroups. Further study of larger populations is needed to confirm and extend these observations. JF - Pharmacogenetics AU - Ishibe, Naoko AU - Sinha, Rashmi AU - Hein, David W AU - Kulldorff, Martin AU - Strickland, Paul AU - Fretland, Adrian J AU - Chow, Wong-Ho AU - Kadlubar, Fred F AU - Lang, Nicholas P AU - Rothman, Nathaniel AD - Genetic Epidemioly Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20892, USA. ishiben@exchange.nih.gov Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 145 EP - 150 VL - 12 IS - 2 SN - 0960-314X, 0960-314X KW - Heterocyclic Compounds KW - 0 KW - Isoenzymes KW - Quinolines KW - Cytochrome P-450 CYP1A2 KW - EC 1.14.14.1 KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - N-acetyltransferase 1 KW - NAT2 protein, human KW - 2-amino-3,4-dimethylimidazo(4,5-f)quinoline KW - G2Q7M1P33X KW - Index Medicus KW - Phenotype KW - Genotype KW - Heterocyclic Compounds -- metabolism KW - Odds Ratio KW - Risk Factors KW - Humans KW - Cooking KW - Case-Control Studies KW - Middle Aged KW - Diet KW - Sequence Analysis, DNA KW - Meat KW - Quinolines -- metabolism KW - Adenoma -- metabolism KW - Cytochrome P-450 CYP1A2 -- genetics KW - Colorectal Neoplasms -- metabolism KW - Polymorphism, Genetic -- genetics KW - Colorectal Neoplasms -- genetics KW - Adenoma -- genetics KW - Isoenzymes -- genetics KW - Arylamine N-Acetyltransferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71495957?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenetics&rft.atitle=Genetic+polymorphisms+in+heterocyclic+amine+metabolism+and+risk+of+colorectal+adenomas.&rft.au=Ishibe%2C+Naoko%3BSinha%2C+Rashmi%3BHein%2C+David+W%3BKulldorff%2C+Martin%3BStrickland%2C+Paul%3BFretland%2C+Adrian+J%3BChow%2C+Wong-Ho%3BKadlubar%2C+Fred+F%3BLang%2C+Nicholas+P%3BRothman%2C+Nathaniel&rft.aulast=Ishibe&rft.aufirst=Naoko&rft.date=2002-03-01&rft.volume=12&rft.issue=2&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-20 N1 - Date created - 2002-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Individualized chemotherapy for elderly patients with nonsmall cell lung cancer. AN - 71493337; 11880711 AB - Approximately one third of all patients with nonsmall cell lung cancer (NSCLC) are over the age of seventy. Elderly patients tolerate chemotherapy poorly because of impaired organ function and comorbidities. For this reason, these patients are often not considered eligible for aggressive cisplatin-based chemotherapy. A multidimensional geriatric evaluation is important to plan appropriate treatments. At present, there are no indications for adjuvant and neoadjuvant chemotherapy. Combined chemoradiotherapy in locally advanced disease increases toxicity and seems determine no survival advantage as compared with radiation therapy alone. In advanced disease, single-agent vinorelbine proves to be active and well-tolerated, and compared with best supportive care, improves survival and perhaps quality of life. Gemcitabine is active and also well tolerated. Taxanes are in advanced phase of evaluation. A phase III randomized trial showed that polychemotherapy with gemcitabine and vinorelbine does not improve any outcome as compared with single-agent chemotherapy with vinorelbine or gemcitabine. In clinical practice, single-agent chemotherapy should remain the standard treatment. The choice of the drug should be based on the toxicity profile of each drug and type of comorbid conditions. In the near future, new therapeutic strategies and biologic agents could improve present results. JF - Current opinion in oncology AU - Gridelli, Cesare AU - Maione, Paolo AU - Barletta, Emiddio AD - Division of Medical Oncology B, National Cancer Institute, Naples, Italy. cgridelli@sirio-oncology.it Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 199 EP - 203 VL - 14 IS - 2 SN - 1040-8746, 1040-8746 KW - Index Medicus KW - Age Factors KW - Risk Factors KW - Humans KW - Clinical Trials as Topic KW - Aged KW - Lung Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Carcinoma, Non-Small-Cell Lung -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71493337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+oncology&rft.atitle=Individualized+chemotherapy+for+elderly+patients+with+nonsmall+cell+lung+cancer.&rft.au=Gridelli%2C+Cesare%3BMaione%2C+Paolo%3BBarletta%2C+Emiddio&rft.aulast=Gridelli&rft.aufirst=Cesare&rft.date=2002-03-01&rft.volume=14&rft.issue=2&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+oncology&rft.issn=10408746&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-01 N1 - Date created - 2002-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thioglycollate peritonitis in mice lacking C5, 5-lipoxygenase, or p47(phox): complement, leukotrienes, and reactive oxidants in acute inflammation. AN - 71493016; 11867678 AB - Leukotriene B(4) (LTB(4)) is an easily diffusible proinflammatory chemotactic factor that has been posited to prime the initial inflammatory response for the action of other mediators, including C5a. 5-Lipoxygenase-deficient (5LX(-/-)) and C5-deficient mice only generated about 50% as much peritoneal leukocytosis as wild-type mice following intraperitoneal (IP) challenge with the sterile irritant, thioglycollate (P<0.005). Pretreatment of C5- mice with the specific 5-lipoxygenase inhibitor, zileuton, reduced peritoneal leukocytosis to almost unstimulated levels, suggesting that LTB(4) can act independently of C5a. Previously, LTB(4) and C5a have been shown in vitro to be inactivated by metabolites of superoxide. In the current study, we examined the fate of LTB(4) in the p47(phox-/-) mouse model of chronic granulomatous disease (CGD) in which the phagocyte NADPH oxidase is unable to produce superoxide. p47(phox-/-) mice generated more thioglycollate-elicited peritoneal leukocytosis than wild-type mice. Pretreatment with zileuton caused a 76% reduction in peritoneal leukocytosis in p47(phox-/-) mice (P<0.005) and a 54% reduction in wild-type mice (P<0.05), whereas pretreatment with dexamethasone or toradol (a cyclooxygenase inhibitor) had no effect. Following IP LTB(4) (1 microg/mouse), total recovered peritoneal LTB(4) was similar between p47(phox-/-) and wild-type mice at 10 and 30 min, but was approximately fivefold greater in p47(phox-/-) mice at 180 min. These data suggest that LTB(4) and C5a have separate but overlapping roles in thioglycollate-elicited peritonitis, and at least the leukotriene component is, in turn, regulated by reactive oxidants. JF - Journal of leukocyte biology AU - Segal, Brahm H AU - Kuhns, Douglas B AU - Ding, Li AU - Gallin, John I AU - Holland, Steven M AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA. Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 410 EP - 416 VL - 71 IS - 3 SN - 0741-5400, 0741-5400 KW - Complement C5 KW - 0 KW - Cyclooxygenase Inhibitors KW - Leukotrienes KW - Phosphoproteins KW - Reactive Oxygen Species KW - Thioglycolates KW - Ketorolac Tromethamine KW - 4EVE5946BQ KW - Dexamethasone KW - 7S5I7G3JQL KW - Arachidonate 5-Lipoxygenase KW - EC 1.13.11.34 KW - NADPH Oxidase KW - EC 1.6.3.1 KW - neutrophil cytosolic factor 1 KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Dexamethasone -- pharmacology KW - Thioglycolates -- toxicity KW - Signal Transduction -- genetics KW - Mice KW - Mice, Transgenic KW - Leukotrienes -- metabolism KW - Ketorolac Tromethamine -- pharmacology KW - Female KW - Mice, Knockout KW - Cyclooxygenase Inhibitors -- pharmacology KW - Complement C5 -- metabolism KW - Arachidonate 5-Lipoxygenase -- metabolism KW - Phosphoproteins -- genetics KW - Peritonitis -- chemically induced KW - Peritonitis -- metabolism KW - Peritonitis -- genetics KW - Complement C5 -- genetics KW - Arachidonate 5-Lipoxygenase -- genetics KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71493016?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+leukocyte+biology&rft.atitle=Thioglycollate+peritonitis+in+mice+lacking+C5%2C+5-lipoxygenase%2C+or+p47%28phox%29%3A+complement%2C+leukotrienes%2C+and+reactive+oxidants+in+acute+inflammation.&rft.au=Segal%2C+Brahm+H%3BKuhns%2C+Douglas+B%3BDing%2C+Li%3BGallin%2C+John+I%3BHolland%2C+Steven+M&rft.aulast=Segal&rft.aufirst=Brahm&rft.date=2002-03-01&rft.volume=71&rft.issue=3&rft.spage=410&rft.isbn=&rft.btitle=&rft.title=Journal+of+leukocyte+biology&rft.issn=07415400&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-20 N1 - Date created - 2002-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Up-regulation of HIV coreceptor CXCR4 expression in human T lymphocytes is mediated in part by a cAMP-responsive element. AN - 71491463; 11874984 AB - The chemokine and HIV receptor CXCR4 has been shown to play a role in chemotaxis and HIV-1 entry into T cells. Dibutyryl cAMP (DcAMP), an analog of cAMP, has been shown to increase CXCR4 cell surface expression and HIV-1 infectivity, but the molecular mechanism(s) responsible is unknown. Here we show that DcAMP treatment of purified human T lymphocytes increased transcription of CXCR4 mRNA as well as cell surface and intracellular CXCR4 protein expression. DcAMP-mediated stimulation of human PBL increased T-trophic HIV-1 (X4) fusion and viral replication as measured by syncytia formation and p24 levels, respectively. To determine the region(s) of the CXCR4 promoter required for cAMP responsiveness, truncations and point mutations of the CXCR4 promoter (nucleotides -1098 to +59) fused to luciferase were constructed and transiently transfected into human PBL. Deletional analysis demonstrated that the -1098 to -93 region of the CXCR4 promoter construct could be eliminated; the residual (-93 to +59) promoter retained cAMP responsiveness. Site-directed mutagenesis of a putative cAMP-responsive element (CRE) in the 5' UTR (+41 to +49) significantly and specifically attenuated the ability of DcAMP to drive the minimal CXCR4 promoter. Electrophoretic mobility shift assays demonstrated the formation of a complex between the CREB transcription factor and the putative CXCR4 CRE site. Our findings demonstrate a CRE element within the CXCR4 promoter that regulates CXCR4 transcription in response to changes in cAMP signaling. The cAMP-dependent up-regulation of CXCR4 mRNA results in increased CXCR4 intracellular and cell surface protein expression as well as increased HIV infectivity. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Cristillo, Anthony D AU - Highbarger, Helene C AU - Dewar, Robin L AU - Dimitrov, Dimiter S AU - Golding, Hana AU - Bierer, Barbara E AD - Laboratory of Lymphocyte Biology, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892, USA. Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 354 EP - 364 VL - 16 IS - 3 KW - Cyclic AMP Response Element-Binding Protein KW - 0 KW - Macromolecular Substances KW - RNA, Messenger KW - Receptors, CXCR4 KW - Bucladesine KW - 63X7MBT2LQ KW - Cyclic AMP KW - E0399OZS9N KW - Index Medicus KW - Virus Replication KW - Promoter Regions, Genetic KW - Cyclic AMP Response Element-Binding Protein -- metabolism KW - Cells, Cultured KW - Kinetics KW - Humans KW - Up-Regulation KW - Bucladesine -- pharmacology KW - Giant Cells -- virology KW - Transcriptional Activation KW - RNA, Messenger -- biosynthesis KW - T-Lymphocytes -- metabolism KW - Receptors, CXCR4 -- biosynthesis KW - HIV-1 -- growth & development KW - Receptors, CXCR4 -- genetics KW - Cyclic AMP -- physiology KW - Response Elements KW - T-Lymphocytes -- virology KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71491463?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.atitle=Up-regulation+of+HIV+coreceptor+CXCR4+expression+in+human+T+lymphocytes+is+mediated+in+part+by+a+cAMP-responsive+element.&rft.au=Cristillo%2C+Anthony+D%3BHighbarger%2C+Helene+C%3BDewar%2C+Robin+L%3BDimitrov%2C+Dimiter+S%3BGolding%2C+Hana%3BBierer%2C+Barbara+E&rft.aulast=Cristillo&rft.aufirst=Anthony&rft.date=2002-03-01&rft.volume=16&rft.issue=3&rft.spage=354&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=1530-6860&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-19 N1 - Date created - 2002-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dioxin inhibition of estrogen-induced mouse uterine epithelial mitogenesis involves changes in cyclin and transforming growth factor-beta expression. AN - 71484148; 11861973 AB - A single dose of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin or TCDD; 5 microg/kg, ip) inhibits 17beta-estradiol (E2)-induced uterine epithelial mitogenesis, apparently through disruption of stromal-epithelial interactions. To understand if TCDD alters early uterine (Ut) responses to E2, young adult C57BL/6J mice were ovariectomized and given (i.p.) either oil or 5 microg/kg TCDD. After 24 h, TCDD-treated mice received E2, and oil-treated mice were given E2 or oil. Body and Ut weights were collected 6 and 18 h later. Ut were flash-frozen at 6 h. E2 increased Ut weight (p < 0.0001) and Ut/body weight ratio (p < 0.0001), compared to mice given oil alone. Ut cyclin expression was assessed by an RNase protection assay. E2 increased mRNA expression for cyclin A2 and B1 (p < 0.05), in addition to D1, D2, and D3 (p < 0.001), while cyclin C was unchanged from oil controls and cyclins A1 and B2 were undetectable. In contrast, TCDD completely abolished E2-induced cyclin A2, which has been associated with S phase initiation, and reduced B1 and D2 (p < 0.05). Interestingly, TCDD did not alter E2-induced Ut weight increases at 6 h, but inhibited E2-induced Ut weight gain at 18 h. A 10-microg/kg TCDD dose was necessary for attenuation of the early E2-induced Ut weight increases (p < 0.01). Since TGF-beta regulates cyclins, Ut TGF-beta was also assessed in TCDD + E2-treated and control mice. TGF-beta mRNA levels were increased after TCDD compared to E2 alone (p < 0.01), suggesting a possible mechanism for TCDD inhibition of Ut cyclin A2. Thus, TCDD alters specific E2-regulated Ut G(1) phase activities and may inhibit E2-induced Ut epithelial mitogenesis by disrupting specific cell signaling mechanisms necessary for S phase initiation in vivo. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Buchanan, David L AU - Ohsako, Seiichiro AU - Tohyama, Chiharu AU - Cooke, Paul S AU - Iguchi, Taisen AD - Center for Integrative Bioscience, Okazaki National Research Institutes, Okazaki, Aichi 444-8585, Japan. buchanal@nieyhs.nih.gov Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 62 EP - 68 VL - 66 IS - 1 SN - 1096-6080, 1096-6080 KW - Cyclins KW - 0 KW - Environmental Pollutants KW - Estrogens KW - Polychlorinated Dibenzodioxins KW - Transforming Growth Factor beta KW - Estradiol KW - 4TI98Z838E KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Drug Interactions KW - Liver -- growth & development KW - Estradiol -- pharmacology KW - Mice KW - Epithelium -- drug effects KW - Epithelial Cells -- metabolism KW - Epithelial Cells -- drug effects KW - Liver -- drug effects KW - Signal Transduction -- drug effects KW - Body Weight -- drug effects KW - Mice, Inbred C57BL KW - Mitosis -- drug effects KW - Epithelium -- metabolism KW - Female KW - Organ Size -- drug effects KW - Uterus -- growth & development KW - Environmental Pollutants -- pharmacology KW - Estrogens -- pharmacology KW - Cyclins -- antagonists & inhibitors KW - Polychlorinated Dibenzodioxins -- pharmacology KW - Transforming Growth Factor beta -- genetics KW - Uterus -- drug effects KW - Cyclins -- genetics KW - Transforming Growth Factor beta -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71484148?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Dioxin+inhibition+of+estrogen-induced+mouse+uterine+epithelial+mitogenesis+involves+changes+in+cyclin+and+transforming+growth+factor-beta+expression.&rft.au=Buchanan%2C+David+L%3BOhsako%2C+Seiichiro%3BTohyama%2C+Chiharu%3BCooke%2C+Paul+S%3BIguchi%2C+Taisen&rft.aulast=Buchanan&rft.aufirst=David&rft.date=2002-03-01&rft.volume=66&rft.issue=1&rft.spage=62&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-25 N1 - Date created - 2002-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Binding and invasion of liver cells by Plasmodium falciparum sporozoites. Essential involvement of the amino terminus of circumsporozoite protein. AN - 71483816; 11751898 AB - Plasmodium sporozoites display circumsporozoite (CS) protein on their surface, which is involved in the attachment of sporozoites to liver cells. CS protein is a member of the thrombospondin type I repeat (TSR) domain family and possess a single copy of TSR domain toward its carboxyl terminus. We show by a direct measurement the correlation between the binding activity of various segments of the CS protein and their ability to inhibit the invasion of liver cells by the sporozoites. We made eight truncated versions of Plasmodium falciparum CS protein to elucidate the role of various regions in the binding and invasion process. Deletion of the TSR domain actually enhanced binding activity by 2-3-fold without the loss of receptor specificity, indicating that TSR may not be the only domain in defining the specificity of binding. These same deletions blocked invasion of live sporozoites more efficiently than proteins that include the TSR domain. Deletion of as little as six amino acids from amino terminus of the protein, however, renders it incapable of binding to liver cells and as an inhibitor of sporozoite invasion. Hence, the binding of CS protein to liver cells and its ability to inhibit the invasion process are affected in a parallel manner, both positively and negatively, by sequence changes in the encoded CS gene. This indicates that both assays are measuring interrelated phenomenon and points to the essential involvement for the amino-terminal portion of the CS protein in these processes. JF - The Journal of biological chemistry AU - Rathore, Dharmendar AU - Sacci, John B AU - de la Vega, Patricia AU - McCutchan, Thomas F AD - Growth and Development Section, Laboratory of Malaria and Vector Research, NIAID/National Institutes of Health, 4 Center Drive MSC 0425, Bethesda, MD 20892-0425, USA. Y1 - 2002/03/01/ PY - 2002 DA - 2002 Mar 01 SP - 7092 EP - 7098 VL - 277 IS - 9 SN - 0021-9258, 0021-9258 KW - Amino Acids KW - 0 KW - Peptides KW - Polysaccharides KW - Protozoan Proteins KW - Recombinant Proteins KW - circumsporozoite protein, Protozoan KW - Heparin KW - 9005-49-6 KW - Dextran Sulfate KW - 9042-14-2 KW - fucoidan KW - 9072-19-9 KW - Chondroitin ABC Lyase KW - EC 4.2.2.20 KW - Heparin Lyase KW - EC 4.2.2.7 KW - Index Medicus KW - Animals KW - Plasmids -- metabolism KW - Escherichia coli -- metabolism KW - Dose-Response Relationship, Drug KW - Humans KW - Heparin -- pharmacology KW - Heparin -- chemistry KW - Protein Binding KW - Polysaccharides -- pharmacology KW - Gene Deletion KW - Heparin Lyase -- metabolism KW - Recombinant Proteins -- metabolism KW - Amino Acids -- chemistry KW - Binding, Competitive KW - Peptides -- chemistry KW - Dextran Sulfate -- pharmacology KW - Inhibitory Concentration 50 KW - Protein Structure, Tertiary KW - Mutation KW - Cell Line KW - Chondroitin ABC Lyase -- metabolism KW - Protozoan Proteins -- chemistry KW - Plasmodium falciparum -- pathogenicity KW - Liver -- parasitology KW - Protozoan Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71483816?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Binding+and+invasion+of+liver+cells+by+Plasmodium+falciparum+sporozoites.+Essential+involvement+of+the+amino+terminus+of+circumsporozoite+protein.&rft.au=Rathore%2C+Dharmendar%3BSacci%2C+John+B%3Bde+la+Vega%2C+Patricia%3BMcCutchan%2C+Thomas+F&rft.aulast=Rathore&rft.aufirst=Dharmendar&rft.date=2002-03-01&rft.volume=277&rft.issue=9&rft.spage=7092&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-01 N1 - Date created - 2002-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurobiology of relapse to heroin and cocaine seeking: a review. AN - 71479419; 11870259 AB - The objective of this article is to review data from studies that used a reinstatement model in rats to elucidate the neural mechanisms underlying relapse to heroin and cocaine seeking induced by exposure to the self-administered drug (drug priming), conditioned drug cues, and stressors. These factors were reported to contribute to relapse to drug use in humans following prolonged abstinence periods. In the reinstatement model, the ability of acute exposure to drug or nondrug stimuli to reinstate drug seeking is determined following training for drug self-administration and subsequent extinction of the drug-reinforced behavior. We will review studies in which pharmacological agents were injected systemically or intracranially to block (or mimic) reinstatement by drug priming, drug cues, and stressors. We also will review studies in which brain lesions, in vivo microdialysis and electrochemistry, and gene expression methods were used to map brain sites involved in relapse to drug seeking. Subsequently, we will discuss theoretical issues related to the processes underlying relapse to drugs and address methodological issues in studies on reinstatement of drug seeking. Finally, the implications of the findings from the studies reviewed for addiction theories and treatment will be discussed. The main conclusion of this review is that the neuronal mechanisms involved in relapse to heroin and cocaine seeking induced by drug priming, drug cues, and stressors are to a large degree dissociable. The data reviewed also suggest that the neuronal events mediating drug-induced reinstatement are to some degree dissociable from those mediating drug reinforcement. JF - Pharmacological reviews AU - Shalev, Uri AU - Grimm, Jeffrey W AU - Shaham, Yavin AD - Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 1 EP - 42 VL - 54 IS - 1 SN - 0031-6997, 0031-6997 KW - Heroin KW - 70D95007SX KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Rats KW - Behavior, Animal -- drug effects KW - Animals KW - Heroin -- pharmacology KW - Extinction, Psychological KW - Self Administration KW - Cues KW - Behavior, Animal -- physiology KW - Cocaine -- pharmacology KW - Cocaine -- administration & dosage KW - Recurrence KW - Heroin -- administration & dosage KW - Stress, Psychological -- complications KW - Heroin Dependence -- etiology KW - Heroin Dependence -- physiopathology KW - Cocaine-Related Disorders -- psychology KW - Cocaine-Related Disorders -- physiopathology KW - Cocaine-Related Disorders -- etiology KW - Heroin Dependence -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71479419?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacological+reviews&rft.atitle=Neurobiology+of+relapse+to+heroin+and+cocaine+seeking%3A+a+review.&rft.au=Shalev%2C+Uri%3BGrimm%2C+Jeffrey+W%3BShaham%2C+Yavin&rft.aulast=Shalev&rft.aufirst=Uri&rft.date=2002-03-01&rft.volume=54&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Pharmacological+reviews&rft.issn=00316997&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-05 N1 - Date created - 2002-02-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular determinants of voltage-dependent slow inactivation of the Ca2+ channel. AN - 71478332; 11751866 AB - Ba(2+) current through the L-type Ca(2+) channel inactivates essentially by voltage-dependent mechanisms with fast and slow kinetics. Here we found that slow inactivation is mediated by an annular determinant composed of hydrophobic amino acids located near the cytoplasmic ends of transmembrane segments S6 of each repeat of the alpha(1C) subunit. We have determined the molecular requirements that completely obstruct slow inactivation. Critical interventions include simultaneous substitution of A752T in IIS6, V1165T in IIIS6, and I1475T in IVS6, each preventing in additive manner a considerable fraction of Ba(2+) current from inactivation. In addition, it requires the S405I mutation in segment IS6. The fractional inhibition of slow inactivation in tested mutants caused an acceleration of fast inactivation, suggesting that fast and slow inactivation mechanisms are linked. The channel lacking slow inactivation showed approximately 45% of the sustained Ba(2+) or Ca(2+) current with no indication of decay. The remaining fraction of the current was inactivated with a single-exponential decay (pi(f) approximately 10 ms), completely recovered from inactivation within 100 ms and did not exhibit Ca(2+)-dependent inactivation properties. No voltage-dependent characteristics were significantly changed, consistent with the C-type inactivation model suggesting constriction of the pore as the main mechanism possibly targeted by Ca(2+) sensors of inactivation. JF - The Journal of biological chemistry AU - Shi, Chengzhang AU - Soldatov, Nikolai M AD - NIA, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2002/03/01/ PY - 2002 DA - 2002 Mar 01 SP - 6813 EP - 6821 VL - 277 IS - 9 SN - 0021-9258, 0021-9258 KW - Amino Acids KW - 0 KW - Calcium Channels KW - Barium KW - 24GP945V5T KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Calcium -- chemistry KW - Electrophysiology KW - Protein Binding KW - Calcium -- metabolism KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Oocytes -- metabolism KW - Amino Acids -- chemistry KW - Cytoplasm -- metabolism KW - Barium -- chemistry KW - Barium -- metabolism KW - Kinetics KW - Xenopus KW - Cell Membrane -- metabolism KW - Protein Structure, Tertiary KW - Mutation KW - Calcium Channels -- chemistry KW - Calcium Channels -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71478332?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Molecular+determinants+of+voltage-dependent+slow+inactivation+of+the+Ca2%2B+channel.&rft.au=Shi%2C+Chengzhang%3BSoldatov%2C+Nikolai+M&rft.aulast=Shi&rft.aufirst=Chengzhang&rft.date=2002-03-01&rft.volume=277&rft.issue=9&rft.spage=6813&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-01 N1 - Date created - 2002-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Positive effects of glucocorticoids on T cell function by up-regulation of IL-7 receptor alpha. AN - 71477599; 11859107 AB - Despite the effects of glucocorticoids on immune function, relatively little is known about glucocorticoid-inducible genes and how their products may regulate lymphocyte function. Using DNA microarray technology to analyze gene expression in PBMC from healthy donors, we identified IL-7Ralpha as a glucocorticoid-inducible gene. This observation was confirmed at the mRNA and protein levels. Conversely, TCR signaling decreased IL-7Ralpha expression, and the relative strength of signaling between these two receptors determined the final IL-7Ralpha levels. The up-regulation of IL-7Ralpha by glucocorticoids was associated with enhanced IL-7-mediated signaling and function. Moreover, IL-7-mediated inhibition of apoptosis at increasing concentrations of glucocorticoids is consistent with enhanced cell sensitivity to IL-7 following glucocorticoid exposure. These observations provide a mechanism by which glucocorticoids may have a positive influence on T cell survival and function. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Franchimont, Denis AU - Galon, Jérôme AU - Vacchio, Melanie S AU - Fan, Samuel AU - Visconti, Roberta AU - Frucht, David M AU - Geenen, Vincent AU - Chrousos, George P AU - Ashwell, Jonathan D AU - O'Shea, John J AD - Lymphocyte Cell Biology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/03/01/ PY - 2002 DA - 2002 Mar 01 SP - 2212 EP - 2218 VL - 168 IS - 5 SN - 0022-1767, 0022-1767 KW - Glucocorticoids KW - 0 KW - Interleukin-7 KW - RNA, Messenger KW - Receptors, Antigen, T-Cell KW - Receptors, Interleukin-2 KW - Receptors, Interleukin-7 KW - interleukin-7 receptor, alpha chain KW - Dexamethasone KW - 7S5I7G3JQL KW - Abridged Index Medicus KW - Index Medicus KW - Gene Expression Profiling KW - Receptors, Interleukin-2 -- metabolism KW - Oligonucleotide Array Sequence Analysis KW - Cells, Cultured KW - Humans KW - Receptors, Antigen, T-Cell -- metabolism KW - Apoptosis -- drug effects KW - Flow Cytometry KW - Drug Synergism KW - Interleukin-7 -- pharmacology KW - Transcriptional Activation KW - RNA, Messenger -- biosynthesis KW - Receptors, Interleukin-7 -- biosynthesis KW - Dexamethasone -- pharmacology KW - Receptors, Interleukin-7 -- genetics KW - Up-Regulation KW - T-Lymphocytes -- drug effects KW - T-Lymphocytes -- immunology KW - Glucocorticoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71477599?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Positive+effects+of+glucocorticoids+on+T+cell+function+by+up-regulation+of+IL-7+receptor+alpha.&rft.au=Franchimont%2C+Denis%3BGalon%2C+J%C3%A9r%C3%B4me%3BVacchio%2C+Melanie+S%3BFan%2C+Samuel%3BVisconti%2C+Roberta%3BFrucht%2C+David+M%3BGeenen%2C+Vincent%3BChrousos%2C+George+P%3BAshwell%2C+Jonathan+D%3BO%27Shea%2C+John+J&rft.aulast=Franchimont&rft.aufirst=Denis&rft.date=2002-03-01&rft.volume=168&rft.issue=5&rft.spage=2212&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-15 N1 - Date created - 2002-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dendritic cells transduced with protein antigens induce cytotoxic lymphocytes and elicit antitumor immunity. AN - 71476782; 11859130 AB - Dendritic cell (DC)-based vaccines are being developed for treatment of patients with cancer, in part because DC are potent inducers of CD8(+) CTL. DC MHC class I:antigenic peptide complexes that are required for CTL elicitation are most often generated by incubating DC with peptides or by transfecting (or transducing) DC with cDNAs (or viral vectors) that encode protein Ags. The former approach is feasible when MHC class I Ags and relevant peptides are known. The latter approach may be hampered by inefficient DC transfection (transduction) and/or difficulties associated with preparation and use of viral vectors. Herein we demonstrate that a bacterial recombinant model tumor-associated Ag (OVA) that contains the HIV TAT protein transduction domain (PTD) was readily engineered and purified, efficiently transduced murine lymphocytes and DC, and was processed by proteasomes for MHC class I-restricted presentation to CTL. In addition, PTD-containing rOVA was processed and presented by DC to CD4 T cells as efficiently as native OVA or rOVA lacking the PTD. PTD-OVA-transduced DC induced CTL in vivo in a Th cell-independent fashion and vaccinated against OVA-expressing tumors. In contrast, rOVA lacking the PTD did not enter the DC MHC class I presentation pathway and DC treated with this protein did not prime OVA-specific CTL in vivo. Treatment of mice harboring clinically apparent OVA-expressing tumors with PTD-OVA-transduced DC resulted in tumor regression in some animals. This straightforward vaccination strategy may translate into DC-based treatments for patients with cancer and other serious diseases. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Shibagaki, Naotaka AU - Udey, Mark C AD - Dermatology Branch, Center for Cancer Research, National Cancer Institute, Building 10 Room 12N238, Bethesda, MD 20892, USA. Y1 - 2002/03/01/ PY - 2002 DA - 2002 Mar 01 SP - 2393 EP - 2401 VL - 168 IS - 5 SN - 0022-1767, 0022-1767 KW - Antigens KW - 0 KW - Cancer Vaccines KW - Epitopes KW - Gene Products, tat KW - Histocompatibility Antigens Class I KW - Recombinant Fusion Proteins KW - Ovalbumin KW - 9006-59-1 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Histocompatibility Antigens Class I -- metabolism KW - CD4-Positive T-Lymphocytes -- immunology KW - Mice KW - Recombinant Fusion Proteins -- metabolism KW - Lymphocyte Activation KW - Gene Products, tat -- chemistry KW - Protein Structure, Tertiary -- genetics KW - Antigens -- metabolism KW - Tumor Cells, Cultured KW - Antigens -- genetics KW - Kinetics KW - Mice, Inbred C57BL KW - Cytotoxicity Tests, Immunologic KW - Epitopes -- immunology KW - Gene Products, tat -- genetics KW - Antigens -- immunology KW - Female KW - Protein Transport KW - Ovalbumin -- immunology KW - Dendritic Cells -- immunology KW - Cancer Vaccines -- immunology KW - Ovalbumin -- genetics KW - Neoplasms, Experimental -- immunology KW - T-Lymphocytes, Cytotoxic -- immunology KW - Neoplasms, Experimental -- prevention & control KW - Ovalbumin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71476782?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Dendritic+cells+transduced+with+protein+antigens+induce+cytotoxic+lymphocytes+and+elicit+antitumor+immunity.&rft.au=Shibagaki%2C+Naotaka%3BUdey%2C+Mark+C&rft.aulast=Shibagaki&rft.aufirst=Naotaka&rft.date=2002-03-01&rft.volume=168&rft.issue=5&rft.spage=2393&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-15 N1 - Date created - 2002-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Monoclonally integrated HTLV type 1 in epithelial cancers from rabbits infected with an HTLV type 1 molecular clone. AN - 71476099; 11860672 AB - In addition to T cell leukemias and lymphomas, human T cell leukemia virus type 1 (HTLV-1) infection has been associated with nonhematologic malignancies and described as the cause of one case of small-cell lung carcinoma. Infected primary epithelial cells have been isolated from sweat gland and oral mucosae of HTLV-1-infected human patients. In the present study, epithelial neoplasms developed in two rabbits experimentally infected with a molecular clone of HTLV-1 (strain K30p). Serologic detection of anti-HTLV-1 and isolation of virus from blood lymphocytes at multiple time points postinjection established a course of chronic asymptomatic infection in both. One rabbit, infected for 5.5 years after intramuscular injection of HTLV-1 DNA, developed a thymoma having features of medullary differentiation. HTLV-1 provirus was detected in both thymocytes and neoplastic epithelium isolated discretely from the thymoma by laser capture microdissection. These findings provide the first experimental evidence of HTLV-1 disease after infection by HTLV-1 DNA injection. Endometrial adenocarcinoma occurred in a second rabbit 2.5 years after its inoculation with cell-associated virus. In this second case, an epithelial cell line derived ex vivo from a metastatic lesion produced virus in culture. In tumors from each of the two rabbits, the neoplastic epithelium was infected and harbored monoclonally integrated HTLV-1 provirus. Although monoclonal provirus integration alone does not establish retroviral cause of carcinogenesis unequivocally, these and other accumulating data indicate that there may be a role for HTLV-1 in diseases associated with infection of epithelia, including some epithelial cancers. JF - AIDS research and human retroviruses AU - Zhao, Tong Mao AU - Bryant, Mark A AU - Kindt, Thomas J AU - Simpson, R Mark AD - Molecular and Cellular Immunogenetics Research Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA. Y1 - 2002/03/01/ PY - 2002 DA - 2002 Mar 01 SP - 253 EP - 258 VL - 18 IS - 4 SN - 0889-2229, 0889-2229 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Rabbits KW - Microscopy, Electron, Scanning KW - Neoplasms, Experimental -- ultrastructure KW - Human T-lymphotropic virus 1 -- physiology KW - Neoplasms, Experimental -- virology KW - Human T-lymphotropic virus 1 -- genetics KW - HTLV-I Infections -- virology KW - Virus Integration UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71476099?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+research+and+human+retroviruses&rft.atitle=Monoclonally+integrated+HTLV+type+1+in+epithelial+cancers+from+rabbits+infected+with+an+HTLV+type+1+molecular+clone.&rft.au=Zhao%2C+Tong+Mao%3BBryant%2C+Mark+A%3BKindt%2C+Thomas+J%3BSimpson%2C+R+Mark&rft.aulast=Zhao&rft.aufirst=Tong&rft.date=2002-03-01&rft.volume=18&rft.issue=4&rft.spage=253&rft.isbn=&rft.btitle=&rft.title=AIDS+research+and+human+retroviruses&rft.issn=08892229&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-18 N1 - Date created - 2002-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Production and purification of a recombinant Staphylococcal enterotoxin B vaccine candidate expressed in Escherichia coli. AN - 71473352; 11858726 AB - An attenuated, recombinant form of Staphylococcus enterotoxin B (rSEB) was overexpressed in Escherichia coli under transcriptional control of the T7 promoter. The 28-kDa rSEB was partially purified from soluble, intracellular protein by tangential flow filtration and differential ammonium sulfate precipitation. The intermediate product was then further purified using low-pressure liquid chromatography including hydrophobic interaction, cation exchange, and size-exclusion matrices. The final vialed product was >95% pure as determined by Coomassie blue-stained sodium dodecyl sulfate-polyacrylamide gel electrophoresis, high-pressure size-exclusion chromatography, and capillary zonal electrophoresis. The endotoxin level was <0.6 EU/mg. Final estimated yield of purified rSEB was 147 mg/L of starting culture. Purified rSEB was stable, elicited an immune response in mice, and protected mice against a lethal challenge with the native toxin. Copyright 2002 Elsevier Science (USA). JF - Protein expression and purification AU - Coffman, J Daniel AU - Zhu, Jianwei AU - Roach, John M AU - Bavari, Sina AU - Ulrich, Robert G AU - Giardina, Steven L AD - Biopharmaceutical Development Program, SAIC Frederick, National Cancer Institute at Frederick, Maryland 21702-1201, USA. Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 302 EP - 312 VL - 24 IS - 2 SN - 1046-5928, 1046-5928 KW - Antigens, Bacterial KW - 0 KW - Enterotoxins KW - Recombinant Proteins KW - Staphylococcal Vaccines KW - enterotoxin B, staphylococcal KW - 39424-53-8 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Chromatography KW - Escherichia coli KW - Recombinant Proteins -- isolation & purification KW - Enterotoxins -- immunology KW - Recombinant Proteins -- biosynthesis KW - Enterotoxins -- isolation & purification KW - Enterotoxins -- biosynthesis KW - Recombinant Proteins -- immunology KW - Antigens, Bacterial -- biosynthesis KW - Antigens, Bacterial -- isolation & purification KW - Antigens, Bacterial -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71473352?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+expression+and+purification&rft.atitle=Production+and+purification+of+a+recombinant+Staphylococcal+enterotoxin+B+vaccine+candidate+expressed+in+Escherichia+coli.&rft.au=Coffman%2C+J+Daniel%3BZhu%2C+Jianwei%3BRoach%2C+John+M%3BBavari%2C+Sina%3BUlrich%2C+Robert+G%3BGiardina%2C+Steven+L&rft.aulast=Coffman&rft.aufirst=J&rft.date=2002-03-01&rft.volume=24&rft.issue=2&rft.spage=302&rft.isbn=&rft.btitle=&rft.title=Protein+expression+and+purification&rft.issn=10465928&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-05 N1 - Date created - 2002-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Jolly SAD. AN - 71466174; 11856836 AB - Examples of phasing macromolecular crystal structures based on single-wavelength anomalous dispersion (SAD) show that this approach is more powerful and may have more general application in structural biology than was anticipated. Better data-collection facilities and cryogenic techniques, coupled with powerful programs for data processing, phasing, density modification and automatic model building, means that the SAD approach may gain wide popularity owing to its simplicity, less stringent wavelength requirements and faster data collection and phasing than the multi-wavelength (MAD) approach. It can be performed at any wavelength where anomalous scattering can be observed, in many cases using laboratory X-ray sources. JF - Acta crystallographica. Section D, Biological crystallography AU - Dauter, Zbigniew AU - Dauter, Miroslawa AU - Dodson, Eleanor AD - Synchrotron Radiation Research Section, Macromolecular Crystallography Laboratory, NCI, Brookhaven National Laboratory, Building 725A-X9, Upton, NY 11973, USA. dauter@bnl.gov Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 494 EP - 506 VL - 58 SN - 0907-4449, 0907-4449 KW - Ferredoxins KW - 0 KW - Insulin KW - Lithium Compounds KW - Metals, Heavy KW - Oligopeptides KW - Rubredoxins KW - Sulfates KW - Phosphorus KW - 27YLU75U4W KW - Manganese KW - 42Z2K6ZL8P KW - Chlorine KW - 4R7X1O2820 KW - Sulfur KW - 70FD1KFU70 KW - DNA KW - 9007-49-2 KW - lithium sulfate KW - 919XA137JK KW - Selenomethionine KW - 964MRK2PEL KW - Iron KW - E1UOL152H7 KW - Thiolester Hydrolases KW - EC 3.1.2.- KW - Muramidase KW - EC 3.2.1.17 KW - Carboxypeptidases KW - EC 3.4.- KW - serine carboxypeptidase KW - EC 3.4.16.5 KW - Subtilisin KW - EC 3.4.21.62 KW - Pyrophosphatases KW - EC 3.6.1.- KW - dUTP pyrophosphatase KW - EC 3.6.1.23 KW - Aldose-Ketose Isomerases KW - EC 5.3.1.- KW - xylose isomerase KW - EC 5.3.1.5 KW - Zinc KW - J41CSQ7QDS KW - Bromine KW - SBV4XY874G KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Calcium -- chemistry KW - Oligopeptides -- chemistry KW - Sulfur -- chemistry KW - Zinc -- chemistry KW - Molecular Weight KW - Phosphorus -- chemistry KW - Bromine -- chemistry KW - Carboxypeptidases -- chemistry KW - DNA -- chemistry KW - Protein Conformation KW - Pyrophosphatases -- chemistry KW - Selenomethionine -- chemistry KW - Aldose-Ketose Isomerases -- chemistry KW - Models, Molecular KW - Subtilisin -- chemistry KW - Lithium Compounds -- chemistry KW - Iron -- chemistry KW - Insulin -- chemistry KW - Ferredoxins -- chemistry KW - Sulfates -- chemistry KW - Muramidase -- chemistry KW - Thiolester Hydrolases -- chemistry KW - Manganese -- chemistry KW - Rubredoxins -- chemistry KW - Chlorine -- chemistry KW - Models, Chemical KW - Metals, Heavy -- chemistry KW - Crystallography, X-Ray -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71466174?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+crystallographica.+Section+D%2C+Biological+crystallography&rft.atitle=Jolly+SAD.&rft.au=Dauter%2C+Zbigniew%3BDauter%2C+Miroslawa%3BDodson%2C+Eleanor&rft.aulast=Dauter&rft.aufirst=Zbigniew&rft.date=2002-03-01&rft.volume=58&rft.issue=&rft.spage=494&rft.isbn=&rft.btitle=&rft.title=Acta+crystallographica.+Section+D%2C+Biological+crystallography&rft.issn=09074449&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-18 N1 - Date created - 2002-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Surgical results of maximal local-regional treatment (cisplatin-enhanced high-dose radiotherapy and adjuvant surgery) in initially non-resectable stage III lung cancer. AN - 71453057; 11844601 AB - We report the surgical short- and long-term results in 42 patients treated in a phase II trial with 50-60 Gy cisplatin-enhanced radiotherapy (RT) and adjuvant resection, for initially non-resectable stage III non-small cell lung cancer. Six of the 42 patients had a complete response, 31 a partial response and five stable disease at the presurgical clinical restaging. A complete pathologic response was observed in 19 cases (R0a surgery); 15 complete resections were performed due to persistent disease (R0b). There were eight non-radical operations (R+). Operative deaths were seen after right pneumonectomy (five cases) and in case of a non-radical operation after no response following the chemo-radiotherapy schedule (two cases). Surgery should be contraindicated in these cases. Overall eight-year-survival was 26% (37% in R0a and 27% in R0b patients). No patient with R+ surgery survived at the eighth year. A local progression as initial failure occurred in four of the 34 R0 patients, and in five of the eighth with a R+ procedure. Resection seems to improve local control, but its role needs further definition. However, advanced stage III patients treated only with a local therapy were not precluded from a long-term survival. JF - Lung cancer (Amsterdam, Netherlands) AU - Bedini, Amedeo Vittorio AU - Tavecchio, Luca AU - Palazzi, Mauro AD - Thoracic Surgery Unit, National Cancer Institute, Via Venezian 1, 20133 Milan, Italy. amvitbedini@yahoo.com Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 271 EP - 277 VL - 35 IS - 3 SN - 0169-5002, 0169-5002 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Survival Rate KW - Neoplasm Staging KW - Humans KW - Aged KW - Middle Aged KW - Dose-Response Relationship, Radiation KW - Time Factors KW - Male KW - Female KW - Combined Modality Therapy -- methods KW - Cisplatin -- therapeutic use KW - Lung Neoplasms -- radiotherapy KW - Lung Neoplasms -- drug therapy KW - Radiotherapy, High-Energy -- methods KW - Lung Neoplasms -- surgery KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71453057?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lung+cancer+%28Amsterdam%2C+Netherlands%29&rft.atitle=Surgical+results+of+maximal+local-regional+treatment+%28cisplatin-enhanced+high-dose+radiotherapy+and+adjuvant+surgery%29+in+initially+non-resectable+stage+III+lung+cancer.&rft.au=Bedini%2C+Amedeo+Vittorio%3BTavecchio%2C+Luca%3BPalazzi%2C+Mauro&rft.aulast=Bedini&rft.aufirst=Amedeo&rft.date=2002-03-01&rft.volume=35&rft.issue=3&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Lung+cancer+%28Amsterdam%2C+Netherlands%29&rft.issn=01695002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-10 N1 - Date created - 2002-02-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neural systems and cue-induced cocaine craving. AN - 71452222; 11850152 AB - We have extended our previous work investigating the neural correlates of cue-induced cocaine craving through the use of positron emission tomography with greater spatial resolution (<4.6 mm), an evocative script, and a pixel-by-pixel analysis. Craving and cerebral glucose metabolism were measured after presentation of cocaine-related or neutral cues to 11 cocaine abusers. Cocaine cues elicited a higher degree of craving than has been previously reported and resulted in left hemispheric activation of lateral amygdala, lateral orbitofrontal cortex, and rhinal cortex and right hemispheric activation of dorsolateral prefrontal cortex and cerebellum. The intensity of activation in these areas (except cerebellum), as well as left insula, was also correlated with craving. Deactivation occurred in left ventral pole and left medial prefrontal cortex. The results suggest that induction of drug craving involves a neural network that assigns incentive motivational value to environmental stimuli through the coactivation of brain regions that process information about memories and emotions. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Bonson, Katherine R AU - Grant, Steven J AU - Contoreggi, Carlo S AU - Links, Jonathan M AU - Metcalfe, Janet AU - Weyl, H Lloyd AU - Kurian, Varughese AU - Ernst, Monique AU - London, Edythe D AD - Brain Imaging Center, National Institute on Drug Abuse, Baltimore, MD 21224, USA. bonsonk@cder.fda.gov Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 376 EP - 386 VL - 26 IS - 3 SN - 0893-133X, 0893-133X KW - Index Medicus KW - Humans KW - Linear Models KW - Adult KW - Brain -- physiology KW - Male KW - Female KW - Tomography, Emission-Computed -- methods KW - Nerve Net -- diagnostic imaging KW - Cocaine-Related Disorders -- psychology KW - Cues KW - Behavior, Addictive -- psychology KW - Behavior, Addictive -- diagnostic imaging KW - Cocaine-Related Disorders -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71452222?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=Neural+systems+and+cue-induced+cocaine+craving.&rft.au=Bonson%2C+Katherine+R%3BGrant%2C+Steven+J%3BContoreggi%2C+Carlo+S%3BLinks%2C+Jonathan+M%3BMetcalfe%2C+Janet%3BWeyl%2C+H+Lloyd%3BKurian%2C+Varughese%3BErnst%2C+Monique%3BLondon%2C+Edythe+D&rft.aulast=Bonson&rft.aufirst=Katherine&rft.date=2002-03-01&rft.volume=26&rft.issue=3&rft.spage=376&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-02 N1 - Date created - 2002-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amphetamine-induced dopamine release and post-synaptic specific binding in patients with mild tardive dyskinesia. AN - 71452174; 11850144 AB - Several lines of evidence suggest that changes in dopamine release and/or post-synaptic sensitivity may be involved in the pathogenesis of tardive dyskinesia (TD). Preclinically, increased D(2) receptor sensitivity and dopamine turnover are associated with D(2) receptor antagonism. Clinically, development of TD is associated with D(2) receptor antagonist administration. Eight patients with mild evidence of TD (AIMS ratings > or =14) and six without (AIMS = 10), underwent [(11)C]raclopride PET scans. Baseline and amphetamine-induced decrements in striatal specific binding were assessed. Baseline and amphetamine-induced decrements in specific binding did not differ between patients with and without evidence of mild TD (p =.53). AIMS ratings did not significantly correlate with baseline (p =.76) or decrements in specific binding (p =.45). This study provides evidence that TD is not associated with increased amphetamine-induced presynaptic dopamine release and/or D(2) receptor binding as measured by [(11)C]raclopride PET. More research is needed to unravel the neurobiology of this debilitating disorder. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Adler, Caleb M AU - Malhotra, Anil K AU - Elman, Igor AU - Pickar, David AU - Breier, Alan AD - Experimental Therapeutics Branch, National Institute of Mental Health/NIH, Bethesda, MD, USA. Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 295 EP - 300 VL - 26 IS - 3 SN - 0893-133X, 0893-133X KW - Dopamine Antagonists KW - 0 KW - Dopamine Uptake Inhibitors KW - Receptors, Dopamine D2 KW - Raclopride KW - 430K3SOZ7G KW - Amphetamine KW - CK833KGX7E KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Analysis of Variance KW - Corpus Striatum -- metabolism KW - Humans KW - Receptors, Dopamine D2 -- metabolism KW - Corpus Striatum -- diagnostic imaging KW - Dopamine Antagonists -- metabolism KW - Binding Sites -- drug effects KW - Adult KW - Corpus Striatum -- drug effects KW - Raclopride -- metabolism KW - Female KW - Male KW - Tomography, Emission-Computed -- methods KW - Dopamine -- secretion KW - Dyskinesia, Drug-Induced -- metabolism KW - Dyskinesia, Drug-Induced -- diagnostic imaging KW - Dopamine -- metabolism KW - Synapses -- metabolism KW - Amphetamine -- pharmacology KW - Dopamine Uptake Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71452174?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=Amphetamine-induced+dopamine+release+and+post-synaptic+specific+binding+in+patients+with+mild+tardive+dyskinesia.&rft.au=Adler%2C+Caleb+M%3BMalhotra%2C+Anil+K%3BElman%2C+Igor%3BPickar%2C+David%3BBreier%2C+Alan&rft.aulast=Adler&rft.aufirst=Caleb&rft.date=2002-03-01&rft.volume=26&rft.issue=3&rft.spage=295&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-02 N1 - Date created - 2002-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dansyl-PQRamide, a possible neuropeptide FF receptor antagonist, induces conditioned place preference. AN - 71451846; 11835998 AB - Neuropeptide FF (NPFF) is an endogenous anti-opioid peptide. NPFF could potentiate the naloxone-precipitated morphine withdrawal syndromes in morphine-dependent rats, indicating the possible involvement of the endogenous NPFF system in opioid analgesia and dependence. The present study was performed to examine the effects of dansyl-PQRamide (dns-PQRa), a putative NPFF antagonist, on conditioned place preference (CPP), in addition, its interaction with the opioid system. Two CPP experiments were conducted. First, rats were treated with dns-PQRa (4-13 mg/kg, i.p.) and paired with the non-preferred compartment while the vehicle was paired with the preferred compartment. Second, similar to experiment 1 except naloxone (1 mg/kg, i.p.) was given 10 min prior to each dns-PQRa administration. The post-drug place preference was examined after 4 alternative pairings. Another group of animals after repetitive dns-PQRa treatments were analyzed for levels of neurotransmitters in discrete brain areas. Dns-PQRa (4-13 mg/kg, i.p.) induced a significant dose-dependent CPP. The dns-PQRa-induced CPP was completely blocked by pretreatment with 1 mg/kg i.p. naloxone, while naloxone alone did not induce any place aversion. The chronic dns-PQRa-treated (13 mg/kg, i.p., b.i.d.) rats caused a significant increase in 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid in the olfactory tubercle compared to the vehicle-treated controls. There was also an increase in the turnover of serotonin in the olfactory tubercle, nucleus accumbens and medial prefrontal cortex. These results suggest that blockade of the NPFF system produces rewarding, possibly via an inhibition of the anti-opioid action of NPFF. These results also reveal a close relationship between NPFF, drug rewarding and the dopaminergic and serotoninergic neurons in the mesolimbic system. JF - Peptides AU - Huang, E Y K AU - Li, J Y AU - Wong, C H AU - Tan, P P C AU - Chen, J C AD - Department of Pharmacology, National Defense Medical Center, Nei-Hu 114, Taipei, Taiwan, ROC. eyh58@ndmctsgh.edu Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 489 EP - 496 VL - 23 IS - 3 SN - 0196-9781, 0196-9781 KW - Narcotic Antagonists KW - 0 KW - Neuropeptides KW - Receptors, Neuropeptide KW - dansyl-prolyl-glutaminyl-argininamide KW - neuropeptide FF receptor KW - Aspartic Acid KW - 30KYC7MIAI KW - Naloxone KW - 36B82AMQ7N KW - Glutamic Acid KW - 3KX376GY7L KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Index Medicus KW - Rats KW - Models, Animal KW - Aspartic Acid -- metabolism KW - Naloxone -- pharmacology KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - Glutamic Acid -- metabolism KW - gamma-Aminobutyric Acid -- metabolism KW - Narcotic Antagonists -- pharmacology KW - Male KW - Conditioning (Psychology) -- drug effects KW - Neuropeptides -- pharmacology KW - Prefrontal Cortex -- metabolism KW - Receptors, Neuropeptide -- antagonists & inhibitors KW - Receptors, Neuropeptide -- metabolism KW - Prefrontal Cortex -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71451846?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Peptides&rft.atitle=Dansyl-PQRamide%2C+a+possible+neuropeptide+FF+receptor+antagonist%2C+induces+conditioned+place+preference.&rft.au=Huang%2C+E+Y+K%3BLi%2C+J+Y%3BWong%2C+C+H%3BTan%2C+P+P+C%3BChen%2C+J+C&rft.aulast=Huang&rft.aufirst=E+Y&rft.date=2002-03-01&rft.volume=23&rft.issue=3&rft.spage=489&rft.isbn=&rft.btitle=&rft.title=Peptides&rft.issn=01969781&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-15 N1 - Date created - 2002-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pilot trial of tumor-specific peptide vaccination and continuous infusion interleukin-2 in patients with recurrent Ewing sarcoma and alveolar rhabdomyosarcoma: an inter-institute NIH study. AN - 71445023; 11836714 AB - Patients with recurrent Ewing sarcoma and alveolar rhabdomyosarcoma have poor prognoses and limited therapeutic options. We have investigated the use of peptide pulsed vaccination in an attempt to immunologically target the breakpoint region of tumor specific fusion proteins expressed in these tumors. Sixteen patients with recurrent, translocation positive, Ewing sarcoma, and alveolar rhabdomyosarcoma underwent apheresis for collection of peripheral blood mononuclear cells. Following countercurrent centrifugal elutriation, an apheresis product comprised predominantly of monocytes but containing small numbers of circulating immature dendritic cells was pulsed with peptides derived from the breakpoint region of the fusion proteins. Vaccines were administered intravenously concomitant with continuous intravenous rhIL-2 at 9 x 10(6) IU/m(2)/day. Toxicity was limited to IL-2 related effects and was generally mild. Following vaccination, all patients showed progressive disease, most in a rapid fashion following the first vaccine. One patient showed evidence of an immunologic response and another showed a mixed clinical response. Patients enrolled on this tumor vaccine trial showed significant immunosuppression and large bulky tumors. Peptide vaccination as administered in this trial did not alter the dismal clinical outcome for patients with recurrent pediatric sarcomas. Future trials of tumor vaccines in this population should target patient populations with improved immune competence and smaller tumor burdens. Furthermore, optimization of the antigen presenting cell populations may be important for inducing immune responses to peptide antigens. Published 2002 Wiley-Liss, Inc. JF - Medical and pediatric oncology AU - Dagher, Ramzi AU - Long, Lauren M AU - Read, Elizabeth J AU - Leitman, Susan F AU - Carter, Charles S AU - Tsokos, Maria AU - Goletz, Theresa J AU - Avila, Nilo AU - Berzofsky, Jay A AU - Helman, Lee J AU - Mackall, Crystal L AD - Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. dagherr@cder.fda.gov Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 158 EP - 164 VL - 38 IS - 3 SN - 0098-1532, 0098-1532 KW - Antineoplastic Agents KW - 0 KW - Cancer Vaccines KW - Interleukin-2 KW - Oncogene Proteins, Fusion KW - Index Medicus KW - Combined Modality Therapy KW - Humans KW - Oncogene Proteins, Fusion -- genetics KW - Adult KW - Pilot Projects KW - Child KW - Adolescent KW - Translocation, Genetic KW - Recurrence KW - Male KW - Female KW - Sarcoma, Ewing -- immunology KW - Interleukin-2 -- adverse effects KW - Cancer Vaccines -- adverse effects KW - Rhabdomyosarcoma, Alveolar -- genetics KW - Interleukin-2 -- therapeutic use KW - Rhabdomyosarcoma, Alveolar -- therapy KW - Cancer Vaccines -- therapeutic use KW - Rhabdomyosarcoma, Alveolar -- immunology KW - Antineoplastic Agents -- therapeutic use KW - Sarcoma, Ewing -- therapy KW - Sarcoma, Ewing -- genetics KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71445023?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medical+and+pediatric+oncology&rft.atitle=Pilot+trial+of+tumor-specific+peptide+vaccination+and+continuous+infusion+interleukin-2+in+patients+with+recurrent+Ewing+sarcoma+and+alveolar+rhabdomyosarcoma%3A+an+inter-institute+NIH+study.&rft.au=Dagher%2C+Ramzi%3BLong%2C+Lauren+M%3BRead%2C+Elizabeth+J%3BLeitman%2C+Susan+F%3BCarter%2C+Charles+S%3BTsokos%2C+Maria%3BGoletz%2C+Theresa+J%3BAvila%2C+Nilo%3BBerzofsky%2C+Jay+A%3BHelman%2C+Lee+J%3BMackall%2C+Crystal+L&rft.aulast=Dagher&rft.aufirst=Ramzi&rft.date=2002-03-01&rft.volume=38&rft.issue=3&rft.spage=158&rft.isbn=&rft.btitle=&rft.title=Medical+and+pediatric+oncology&rft.issn=00981532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-27 N1 - Date created - 2002-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming growth factor beta 1 induces apoptosis through cleavage of BAD in a Smad3-dependent mechanism in FaO hepatoma cells. AN - 71439464; 11839804 AB - Transforming growth factor beta (TGF-beta) induces apoptosis in a variety of cells. We have previously shown that TGF-beta 1 rapidly induces apoptosis in the FaO rat hepatoma cell line. We have now studied the effect of TGF-beta 1 on the expression of different members of the Bcl-2 family in these cells. We observed no detectable changes in the steady-state levels of Bcl-2, Bcl-X(L), and Bax. However, TGF-beta 1 induced caspase-dependent cleavage of BAD at its N terminus to generate a 15-kDa truncated protein. Overexpression of the 15-kDa truncated BAD protein enhanced TGF-beta 1-induced apoptosis, whereas a mutant BAD resistant to caspase 3 cleavage blocked TGF-beta 1-induced apoptosis. Overexpression of Smad3 dramatically enhanced TGF-beta 1-induced cleavage of BAD and apoptosis, whereas antisense Smad3 blocked TGF-beta 1-induced apoptosis and BAD cleavage. These results suggest that TGF-beta 1 induces apoptosis through the cleavage of BAD in a Smad3-dependent mechanism. JF - Molecular and cellular biology AU - Kim, Byung-Chul AU - Mamura, Mizuko AU - Choi, Kyeong Sook AU - Calabretta, Bruno AU - Kim, Seong-Jin AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-50551, USA. Y1 - 2002/03// PY - 2002 DA - March 2002 SP - 1369 EP - 1378 VL - 22 IS - 5 SN - 0270-7306, 0270-7306 KW - Bad protein, rat KW - 0 KW - Carrier Proteins KW - DNA-Binding Proteins KW - Madh3 protein, rat KW - Proto-Oncogene Proteins c-bcl-2 KW - Smad3 Protein KW - Tgfb1 protein, rat KW - Trans-Activators KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - bcl-Associated Death Protein KW - Index Medicus KW - Rats KW - Animals KW - Liver Neoplasms -- metabolism KW - Carcinoma, Hepatocellular -- metabolism KW - Tumor Cells, Cultured KW - Transforming Growth Factor beta -- pharmacology KW - Trans-Activators -- metabolism KW - Carrier Proteins -- metabolism KW - Apoptosis KW - Carrier Proteins -- genetics KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - Proto-Oncogene Proteins c-bcl-2 -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71439464?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Transforming+growth+factor+beta+1+induces+apoptosis+through+cleavage+of+BAD+in+a+Smad3-dependent+mechanism+in+FaO+hepatoma+cells.&rft.au=Kim%2C+Byung-Chul%3BMamura%2C+Mizuko%3BChoi%2C+Kyeong+Sook%3BCalabretta%2C+Bruno%3BKim%2C+Seong-Jin&rft.aulast=Kim&rft.aufirst=Byung-Chul&rft.date=2002-03-01&rft.volume=22&rft.issue=5&rft.spage=1369&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-02 N1 - Date created - 2002-02-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell Growth Differ. 1998 Oct;9(10):869-75 [9790498] J Biol Chem. 1999 Nov 5;274(45):31775-83 [10542199] Genes Dev. 2000 Mar 15;14(6):627-44 [10733523] EMBO J. 2000 Apr 17;19(8):1745-54 [10775259] EMBO J. 2000 May 15;19(10):2237-46 [10811615] Blood. 2000 Jul 15;96(2):676-84 [10887134] J Natl Cancer Inst. 2000 Sep 6;92(17):1388-402 [10974075] J Biol Chem. 2000 Nov 17;275(46):36295-302 [10942775] J Biol Chem. 2000 Dec 15;275(50):39137-45 [10993901] Genes Dev. 2000 Dec 15;14(24):3093-101 [11124802] Nat Cell Biol. 2000 Dec;2(12):915-21 [11146656] Cold Spring Harb Symp Quant Biol. 1999;64:343-50 [11232306] Blood. 2001 Mar 1;97(5):1289-97 [11222372] Mol Cell Biol. 2001 May;21(9):3025-36 [11287608] Toxicol Lett. 2001 Mar 31;120(1-3):307-15 [11323189] J Biol Chem. 2001 Jul 13;276(28):26614-21 [11320089] Nat Cell Biol. 2001 Aug;3(8):708-14 [11483955] J Clin Invest. 2001 Sep;108(6):807-16 [11560950] Cancer Res. 1992 Jan 15;52(2):385-8 [1309441] Cell. 1994 Oct 21;79(2):189-92 [7954787] Cell. 1995 Jan 27;80(2):285-91 [7834748] Oncogene. 1995 Oct 19;11(8):1615-22 [7478586] Oncogene. 1996 May 2;12(9):1909-19 [8649852] Immunity. 1996 Jul;5(1):31-40 [8758892] Cancer Res. 1996 Nov 15;56(22):5146-9 [8912849] Cell. 1996 Nov 15;87(4):619-28 [8929531] Cell. 1997 Jun 27;89(7):1067-76 [9215629] Cell Growth Differ. 1997 Jul;8(7):821-7 [9218876] J Biol Chem. 1997 Sep 26;272(39):24101-4 [9305851] Cell Growth Differ. 1997 Oct;8(10):1049-59 [9342183] Nature. 1997 Nov 13;390(6656):116-7 [9367147] Mol Cell Biol. 1997 Dec;17(12):7040-6 [9372935] J Biol Chem. 1997 Dec 5;272(49):30866-72 [9388232] Nature. 1997 Dec 4;390(6659):465-71 [9393997] Hepatology. 1998 Feb;27(2):415-21 [9462639] Mol Cell. 1998 Mar;1(4):611-7 [9660945] Science. 1998 Sep 25;281(5385):2027-31 [9748162] Cell Growth Differ. 1998 Sep;9(9):815-25 [9751125] Mol Cell Biol. 1998 Nov;18(11):6595-604 [9774674] Oncogene. 1998 Oct 1;17(13):1743-7 [9796704] Cell. 1998 Dec 11;95(6):737-40 [9865691] J Biol Chem. 1999 Jan 22;274(4):2225-33 [9890985] Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1427-32 [9990040] Science. 1999 Apr 9;284(5412):339-43 [10195903] Mol Cell. 1999 Apr;3(4):413-22 [10230394] Nature. 1999 Jun 3;399(6735):483-7 [10365962] Hepatology. 1999 Nov;30(5):1215-22 [10534343] Mol Biol Cell. 1999 Nov;10(11):3801-13 [10564272] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Minimal reactivation of Kaposi's sarcoma-associated herpesvirus by corticosteroids in latently infected B cell lines. AN - 71414830; 11793390 AB - Corticosteroid use in transplant recipients increases the incidence and severity of Kaposi's sarcoma (KS), a disease associated with KS-associated herpesvirus (KSHV) infection. Recently, the prototypic corticosteroid, hydrocortisone, was shown to directly induce lytic cycle reactivation of KSHV in latently-infected BCBL-1 cells. The purpose of this study was to examine this phenomenon in further detail. After incubation with dexamethasone ( 3 cm) or locally advanced (Stage III) breast carcinoma, including patients with inflammatory breast carcinoma. In this single-center, open-label, single-stage, Phase II trial, epirubicin (75 mg/m(2); intravenous bolus) followed by docetaxel (80 mg/m(2); 1-hour intravenous infusion) was administered on Day 1 of each cycle for four cycles. Nine of 30 patients (30%) had inflammatory breast carcinoma. Twenty-three patients (76.7%; 95% confidence interval, 57.7-90.1) had a clinical objective response that was complete in 6 patients (20%). Twenty-seven patients (90%) underwent surgery that was conservative in 5 patients (16.7%). Pathologic response evaluation revealed four complete responses (13.3%; 95% confidence interval, 3.8-30.7). Grade 4 neutropenia was recorded in 80.0% of patients, and febrile neutropenia was recorded in one-third of patients. Anemia and thrombocytopenia were never severe. Other side effects were diarrhea (26.6%), oral mucositis (43.3%), and emesis (26.6%). Neoadjuvant chemotherapy with epirubicin plus docetaxel was a feasible treatment and was active in an unfavorable series of patients with locally advanced breast carcinoma, including patients with inflammatory breast carcinoma. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.20335 JF - Cancer AU - de Matteis, Andrea AU - Nuzzo, Francesco AU - D'Aiuto, Giuseppe AU - Labonia, Vincenzo AU - Landi, Gabriella AU - Rossi, Emanuela AU - Mastro, Angelo Antonio AU - Botti, Gerardo AU - De Maio, Ermelinda AU - Perrone, Francesco AD - Department of Medical Oncology C, National Cancer Institute, Naples, Italy. f.conuzzo@libero.it Y1 - 2002/02/15/ PY - 2002 DA - 2002 Feb 15 SP - 895 EP - 901 VL - 94 IS - 4 SN - 0008-543X, 0008-543X KW - Taxoids KW - 0 KW - docetaxel KW - 15H5577CQD KW - Epirubicin KW - 3Z8479ZZ5X KW - Paclitaxel KW - P88XT4IS4D KW - Abridged Index Medicus KW - Index Medicus KW - Injections, Intravenous KW - Infusions, Intravenous KW - Humans KW - Neoadjuvant Therapy KW - Adult KW - Treatment Outcome KW - Neutropenia -- chemically induced KW - Aged KW - Middle Aged KW - Epirubicin -- administration & dosage KW - Female KW - Paclitaxel -- administration & dosage KW - Breast Neoplasms -- drug therapy KW - Breast Neoplasms -- pathology KW - Paclitaxel -- analogs & derivatives KW - Breast Neoplasms -- surgery KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71596999?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=Docetaxel+plus+epidoxorubicin+as+neoadjuvant+treatment+in+patients+with+large+operable+or+locally+advanced+carcinoma+of+the+breast%3A+a+single-center%2C+phase+II+study.&rft.au=de+Matteis%2C+Andrea%3BNuzzo%2C+Francesco%3BD%27Aiuto%2C+Giuseppe%3BLabonia%2C+Vincenzo%3BLandi%2C+Gabriella%3BRossi%2C+Emanuela%3BMastro%2C+Angelo+Antonio%3BBotti%2C+Gerardo%3BDe+Maio%2C+Ermelinda%3BPerrone%2C+Francesco&rft.aulast=de+Matteis&rft.aufirst=Andrea&rft.date=2002-02-15&rft.volume=94&rft.issue=4&rft.spage=895&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-15 N1 - Date created - 2002-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Proteasome inhibitor PS-341, a potential therapeutic agent for adult T-cell leukemia. AN - 71468525; 11861386 AB - Nuclear factor kappaB (NF-kappaB) plays a major role in the pathogenesis of human T-cell lymphotrophic virus I-associated malignancy. Proteasome inhibitors provide a rational approach to control constitutively activated NF-kappaB in human T-cell lymphotrophic virus I-infected T cells. We report that the proteasome inhibitor PS-341 decreased NF-kappaB DNA binding activity by preventing degradation of IkappaB(alpha). In our murine model of adult T-cell leukemia, PS-341 used alone did not yield prolongation of the survival of tumor-bearing mice. However, when combined with the current clinically approved drug humanized anti-Tac, therapy with PS-341 was associated with a complete remission in a proportion of treated animals, whereas only a partial response was observed in animals treated with humanized anti-Tac alone. JF - Cancer research AU - Tan, Chalet AU - Waldmann, Thomas A AD - Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-1374, USA. Y1 - 2002/02/15/ PY - 2002 DA - 2002 Feb 15 SP - 1083 EP - 1086 VL - 62 IS - 4 SN - 0008-5472, 0008-5472 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Humanized KW - Antineoplastic Agents KW - Boronic Acids KW - DNA, Neoplasm KW - DNA-Binding Proteins KW - I-kappa B Proteins KW - Immunoglobulin G KW - Multienzyme Complexes KW - NF-kappa B KW - NFKBIA protein, human KW - Nfkbia protein, mouse KW - Protease Inhibitors KW - Pyrazines KW - Receptors, IgG KW - NF-KappaB Inhibitor alpha KW - 139874-52-5 KW - Bortezomib KW - 69G8BD63PP KW - daclizumab KW - CUJ2MVI71Y KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Index Medicus KW - Animals KW - Receptors, IgG -- immunology KW - Neutrophils -- immunology KW - Humans KW - Receptors, IgG -- metabolism KW - Immunoglobulin G -- pharmacology KW - Antibodies, Monoclonal -- pharmacology KW - Antibody-Dependent Cell Cytotoxicity -- drug effects KW - Immunoglobulin G -- administration & dosage KW - Adult KW - Drug Synergism KW - DNA-Binding Proteins -- metabolism KW - Mice, Inbred NOD KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Mice KW - Antibodies, Monoclonal -- administration & dosage KW - Monocytes -- immunology KW - Multienzyme Complexes -- antagonists & inhibitors KW - Mice, SCID KW - Antibody-Dependent Cell Cytotoxicity -- immunology KW - DNA, Neoplasm -- metabolism KW - NF-kappa B -- metabolism KW - Boronic Acids -- pharmacology KW - Protease Inhibitors -- pharmacology KW - Pyrazines -- administration & dosage KW - Boronic Acids -- administration & dosage KW - Pyrazines -- pharmacology KW - Leukemia-Lymphoma, Adult T-Cell -- immunology KW - Leukemia-Lymphoma, Adult T-Cell -- enzymology KW - Leukemia-Lymphoma, Adult T-Cell -- drug therapy KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71468525?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Proteasome+inhibitor+PS-341%2C+a+potential+therapeutic+agent+for+adult+T-cell+leukemia.&rft.au=Tan%2C+Chalet%3BWaldmann%2C+Thomas+A&rft.aulast=Tan&rft.aufirst=Chalet&rft.date=2002-02-15&rft.volume=62&rft.issue=4&rft.spage=1083&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-27 N1 - Date created - 2002-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional regulation of the transforming growth factor beta type II receptor gene by histone acetyltransferase and deacetylase is mediated by NF-Y in human breast cancer cells. AN - 71453790; 11744689 AB - Transcriptional repression of the transforming growth factor-beta (TGF-beta) type II receptor (TbetaRII) gene is one of several mechanisms leading to TGF-beta resistance. Previously, we have shown that MS-275, a synthetic inhibitor of histone deacetylase (HDAC), specifically induces the expression of the TbetaRII gene and restores the TGF-beta signaling in human breast cancer cell lines. However, little is known about the mechanism by which inhibition of HDAC activates TbetaRII expression. MS-275 treatment of cells expressing a wild-type TbetaRII promoter/luciferase construct resulted in a 10-fold induction of the promoter activity. DNA transfection and an electrophoretic mobility shift assay showed that the induction of the TbetaRII promoter by MS-275 requires the inverted CCAAT box and its cognate binding protein, NF-Y. In addition, a DNA affinity pull-down assay indicated that the PCAF protein, a transcriptional coactivator with intrinsic histone acetyltransferase (HAT) activity, is specifically recruited to the NF-Y complex in the presence of either MS-275 or trichostatin A. Based on these results, we suggest that treatment with the HDAC inhibitor induces TbetaRII promoter activity by the recruitment of the PCAF protein to the NF-Y complex, interacting with the inverted CCAAT box in the TbetaRII promoter. JF - The Journal of biological chemistry AU - Park, Seok Hee AU - Lee, Sae Ra AU - Kim, Byung Chul AU - Cho, Eun Ah AU - Patel, Sejal P AU - Kang, Hee-Bum AU - Sausville, Edward A AU - Nakanishi, Osamu AU - Trepel, Jane B AU - Lee, Byoung Ick AU - Kim, Seong-Jin AD - Laboratory of Cell Regulation and Carcinogenesis, the Developmental Therapeutics Program, and the Medicine Branch, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/02/15/ PY - 2002 DA - 2002 Feb 15 SP - 5168 EP - 5174 VL - 277 IS - 7 SN - 0021-9258, 0021-9258 KW - Benzamides KW - 0 KW - CCAAT-Binding Factor KW - Enzyme Inhibitors KW - Hydroxamic Acids KW - Pyridines KW - Receptors, Transforming Growth Factor beta KW - Saccharomyces cerevisiae Proteins KW - entinostat KW - 1ZNY4FKK9H KW - trichostatin A KW - 3X2S926L3Z KW - DNA KW - 9007-49-2 KW - Luciferases KW - EC 1.13.12.- KW - Acetyltransferases KW - EC 2.3.1.- KW - Histone Acetyltransferases KW - EC 2.3.1.48 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Histone Deacetylases KW - EC 3.5.1.98 KW - Index Medicus KW - Plasmids -- metabolism KW - Cell Nucleus -- metabolism KW - DNA -- metabolism KW - Humans KW - Luciferases -- metabolism KW - Reverse Transcriptase Polymerase Chain Reaction KW - Protein Binding KW - Mutagenesis, Site-Directed KW - Promoter Regions, Genetic KW - Base Sequence KW - Tumor Cells, Cultured KW - Benzamides -- pharmacology KW - Transfection KW - Genes, Reporter KW - Molecular Sequence Data KW - Enzyme Inhibitors -- pharmacology KW - Pyridines -- pharmacology KW - Hydroxamic Acids -- pharmacology KW - CCAAT-Binding Factor -- metabolism KW - Receptors, Transforming Growth Factor beta -- genetics KW - Acetyltransferases -- metabolism KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Histone Deacetylases -- metabolism KW - Transcription, Genetic KW - Gene Expression Regulation KW - Breast Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71453790?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Transcriptional+regulation+of+the+transforming+growth+factor+beta+type+II+receptor+gene+by+histone+acetyltransferase+and+deacetylase+is+mediated+by+NF-Y+in+human+breast+cancer+cells.&rft.au=Park%2C+Seok+Hee%3BLee%2C+Sae+Ra%3BKim%2C+Byung+Chul%3BCho%2C+Eun+Ah%3BPatel%2C+Sejal+P%3BKang%2C+Hee-Bum%3BSausville%2C+Edward+A%3BNakanishi%2C+Osamu%3BTrepel%2C+Jane+B%3BLee%2C+Byoung+Ick%3BKim%2C+Seong-Jin&rft.aulast=Park&rft.aufirst=Seok&rft.date=2002-02-15&rft.volume=277&rft.issue=7&rft.spage=5168&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-21 N1 - Date created - 2002-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Maternal serum level of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene and risk of cryptorchidism, hypospadias, and polythelia among male offspring. AN - 71448319; 11836195 AB - 1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) is a metabolite of the insecticide 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (DDT) and is a ubiquitous environmental contaminant. Nearly everyone in the United States has a detectable serum level of DDE. DDE was recently found to inhibit binding of androgen to its receptor and to block androgen action in rodents. Normal development of male genitalia in mammals depends on androgen action. The authors used stored serum samples to examine the relation between maternal DDE levels during pregnancy and adjusted odds of cryptorchidism (n = 219), hypospadias (n = 199), and polythelia (extra nipples) (n = 167) among male offspring, using a nested case-control design with one control group (n = 552). Subjects were selected from the Collaborative Perinatal Project, a US birth cohort study begun in 1959-1966, when DDE levels were much higher than they are at present. Compared with boys whose mother's recovery-adjusted serum DDE level was less than 21.4 microg/liter, boys with maternal levels greater than or equal to 85.6 microg/liter had adjusted odds ratios of 1.3 (95% confidence interval (CI): 0.7, 2.4) for crypt-orchidism, 1.2 (95% CI: 0.6, 2.4) for hypospadias, and 1.9 (95% CI: 0.9, 4.0) for polythelia. For cryptorchidism and polythelia, the results were consistent with a modest-to-moderate association, but in no instance was the estimate very precise. The results were inconclusive. JF - American journal of epidemiology AU - Longnecker, Matthew P AU - Klebanoff, Mark A AU - Brock, John W AU - Zhou, Haibo AU - Gray, Kimberly A AU - Needham, Larry L AU - Wilcox, Allen J AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. longnecker@niehs.nih.gov Y1 - 2002/02/15/ PY - 2002 DA - 2002 Feb 15 SP - 313 EP - 322 VL - 155 IS - 4 SN - 0002-9262, 0002-9262 KW - Androgens KW - 0 KW - Insecticides KW - Dichlorodiphenyl Dichloroethylene KW - 4M7FS82U08 KW - Index Medicus KW - Odds Ratio KW - Risk Factors KW - Humans KW - Cohort Studies KW - Adult KW - Infant, Newborn KW - Case-Control Studies KW - Androgens -- pharmacology KW - Male KW - Female KW - Pregnancy KW - Maternal-Fetal Exchange KW - Insecticides -- adverse effects KW - Nipples -- abnormalities KW - Pregnancy Complications -- etiology KW - Hypospadias -- etiology KW - Environmental Exposure KW - Dichlorodiphenyl Dichloroethylene -- adverse effects KW - Dichlorodiphenyl Dichloroethylene -- blood KW - Cryptorchidism -- etiology KW - Insecticides -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71448319?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+epidemiology&rft.atitle=Maternal+serum+level+of+1%2C1-dichloro-2%2C2-bis%28p-chlorophenyl%29ethylene+and+risk+of+cryptorchidism%2C+hypospadias%2C+and+polythelia+among+male+offspring.&rft.au=Longnecker%2C+Matthew+P%3BKlebanoff%2C+Mark+A%3BBrock%2C+John+W%3BZhou%2C+Haibo%3BGray%2C+Kimberly+A%3BNeedham%2C+Larry+L%3BWilcox%2C+Allen+J&rft.aulast=Longnecker&rft.aufirst=Matthew&rft.date=2002-02-15&rft.volume=155&rft.issue=4&rft.spage=313&rft.isbn=&rft.btitle=&rft.title=American+journal+of+epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-19 N1 - Date created - 2002-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Impaired NK cell development in an IFN-gamma transgenic mouse: aberrantly expressed IFN-gamma enhances hematopoietic stem cell apoptosis and affects NK cell differentiation. AN - 71440697; 11823506 AB - Aberrant expression of IFN-gamma has been demonstrated to cause a wide variety of alterations in cell function and development. Previously we reported that constitutive expression of IFN-gamma in bone marrow (BM) and thymus results in a total absence of B cells and a substantial decrease in the number of hematopoietic progenitor cells. In this study, we demonstrate a severe deficiency of NK1.1(+)CD3(-) cells in this transgenic mouse model. Compared with normal control littermates, we found a pronounced reduction of NK cells in IFN-gamma transgenic mouse spleen and liver despite maintenance of normal function. In addition, we observed a reduced number of BM cells in the IFN-gamma transgenic mouse despite normal expression of hematopoietic growth factors in the BM. Interestingly, these cells were less responsive to stem cell factor (SCF) despite c-kit expression on hematopoietic stem cells (HSCs). We observed that addition of exogenous IFN-gamma inhibited proliferation of HSCs and differentiation of NK precursors from HSCs in normal mice in response to SCF, IL-7, fms-like tyrosine kinase 3 ligand, and IL-15. Furthermore, we found that HSCs express the IFN-gammaRalpha subunit and undergo apoptosis in response to exogenous IFN-gamma. Thus, we have demonstrated the occurrence of a severe deficiency of NK cells and lower numbers of BM cells in an IFN-gamma transgenic mouse model. Furthermore, because exogenous IFN-gamma affects the responsiveness to hematopoietic growth factors such as SCF in vitro, our results indicate that chronic expression of IFN-gamma in vivo leads to widespread immune system defects, including alterations in NK cell differentiation. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Shimozato, Osamu AU - Ortaldo, John R AU - Komschlies, Kristin L AU - Young, Howard A AD - Laboratory of Experimental Immunology, Center for Cancer Research, and Intramural Research Support Program, Science Applications International Corp.-Frederick, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 2002/02/15/ PY - 2002 DA - 2002 Feb 15 SP - 1746 EP - 1752 VL - 168 IS - 4 SN - 0022-1767, 0022-1767 KW - Cytokines KW - 0 KW - Membrane Proteins KW - flt3 ligand protein KW - Interferon-gamma KW - 82115-62-6 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Cell Count KW - Cells, Cultured KW - Cytokines -- biosynthesis KW - Mice, Inbred C57BL KW - Membrane Proteins -- pharmacology KW - Cytotoxicity Tests, Immunologic KW - Cell Differentiation KW - Mice KW - Flow Cytometry KW - Mice, Transgenic KW - Immunophenotyping KW - Killer Cells, Natural -- classification KW - Interferon-gamma -- genetics KW - Hematopoietic Stem Cells -- immunology KW - Apoptosis KW - Hematopoietic Stem Cells -- classification KW - Interferon-gamma -- metabolism KW - Interferon-gamma -- physiology KW - Killer Cells, Natural -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71440697?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Impaired+NK+cell+development+in+an+IFN-gamma+transgenic+mouse%3A+aberrantly+expressed+IFN-gamma+enhances+hematopoietic+stem+cell+apoptosis+and+affects+NK+cell+differentiation.&rft.au=Shimozato%2C+Osamu%3BOrtaldo%2C+John+R%3BKomschlies%2C+Kristin+L%3BYoung%2C+Howard+A&rft.aulast=Shimozato&rft.aufirst=Osamu&rft.date=2002-02-15&rft.volume=168&rft.issue=4&rft.spage=1746&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-04 N1 - Date created - 2002-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Decrease in K-ras p21 and Increase in Raf1 and Activated Erk 1 and 2 in Murine Lung Tumors Initiated by N -Nitrosodimethylamine and Promoted by 2,3,7,8-Tetrachlorodibenzo- p -dioxin AN - 18275832; 5331761 AB - Recent evidence suggests that K-ras protooncogene protein p21 may have a tumor-suppressive role in the context of development of lung adenocarcinoma. Levels of K-ras p21, raf-1, mitogen-activated protein kinases Erk 1 and 2, the phosphorylated-activated forms of Erk 1 and 2 (Erk 1P and 2P), and proliferating cell nuclear antigen (PCNA) were measured by immunoblotting in mouse lung tumors (5 to 9 mm in size) caused by N-nitrosodimethylamine (NDMA) and in control lungs. In tumors compared with normal lung, cell membrane-associated K-ras p21 was significantly decreased and cytosolic K-ras p21 increased. Total, membrane, and cytosolic raf-1 and Erk 1P and 2P were increased in tumors compared with normal lung. A single dose of 5 nmol/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) given after NDMA resulted in a significant 2.4-fold increase in tumor multiplicity. A significantly greater decrease in membrane-associated K-ras p21 and increase in total and membrane associated raf-1 occurred in the NDMA/TCDD tumors compared with the NDMA-only tumors. PCNA levels increased in tumors, a finding confirmed by immunohistochemistry, and correlated with tumor size after NDMA/TCDD treatment but not after NDMA only. The increase in raf-1 in the tumors was confirmed by immunohistochemistry, which also revealed an increase in raf-1-positive alveolar macrophages specifically associating with tumors from the earliest stages. These results suggest a possible tumor-suppressive function for K-ras p21 in lung and a positive role for raf-1 and Erk 1/2 in lung tumorigenesis. TCDD may promote tumors by contributing to downregulation of K-ras and stimulation of raf-1. [copy ]2002 Elsevier Science (USA). JF - Toxicology and Applied Pharmacology AU - Ramakrishna, G AU - Perella, C AU - Birely, L AU - Diwan, BA AU - Fornwald, L W AU - Anderson, L M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, Maryland, 21702, Andersol@mail.ncifcrf.gov Y1 - 2002/02/15/ PY - 2002 DA - 2002 Feb 15 SP - 21 EP - 34 PB - Academic Press VL - 179 IS - 1 SN - 0041-008X, 0041-008X KW - mice KW - ERK1 protein KW - K-ras gene KW - p21 protein KW - raf-1 gene KW - Toxicology Abstracts KW - Nitrosamines KW - Lung KW - Tumorigenesis KW - N-Nitrosodimethylamine KW - TCDD KW - X 24200:Nitrosamines & related compounds KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18275832?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=Decrease+in+K-ras+p21+and+Increase+in+Raf1+and+Activated+Erk+1+and+2+in+Murine+Lung+Tumors+Initiated+by+N+-Nitrosodimethylamine+and+Promoted+by+2%2C3%2C7%2C8-Tetrachlorodibenzo-+p+-dioxin&rft.au=Ramakrishna%2C+G%3BPerella%2C+C%3BBirely%2C+L%3BDiwan%2C+BA%3BFornwald%2C+L+W%3BAnderson%2C+L+M&rft.aulast=Ramakrishna&rft.aufirst=G&rft.date=2002-02-15&rft.volume=179&rft.issue=1&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1006%2Ftaap.2001.9344 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Nitrosamines; TCDD; Lung; Tumorigenesis; N-Nitrosodimethylamine DO - http://dx.doi.org/10.1006/taap.2001.9344 ER - TY - JOUR T1 - Thermal Unfolding Molecular Dynamics Simulation of Escherichia coli Dihydrofolate Reductase: Thermal Stability of Protein Domains and Unfolding Pathway AN - 18271397; 5329391 AB - Temperature-induced unfolding of Escherichia coli dihydrofolate reductase was carried out by using molecular dynamic simulations. The simulations show that the unfolding generally involves an initial end-to-end collapse of the adenine binding domain into partially extended loops, followed by a gradual breakdown of the remaining beta -sheet core structure. The core, which consists of beta -strands 5-7, was observed to be the most resistant to thermal unfolding. This region, which is made up of part of the N-terminus domain and part of the large domain of the E. coli dihydrofolate reductase, may constitute the nucleation site for protein folding and may be important for the eventual formation of both domains. The unfolding of different domains at different stages of the unfolding process suggests that protein domains vary in stability and that the rate at which they unfold can affect the overall outcome of the unfolding pathway. This observation is compared with the recently proposed hierarchical folding model. Finally, the results of the simulation were found to be consistent with a previous experimental study (Frieden, Proc Natl Acad Sci USA 1990; 87:4413-4416) which showed that the folding process of E. coli dihydrofolate reductase involves sequential formation of the substrate-binding sites. JF - Proteins: Structure, Function & Genetics AU - Sham, Y Y AU - Ma, B AU - Tsai, C-J AU - Nussinov, R AD - NCI-FCRDC Bldg 469, Rm. 151, Frederick, MD 21702, USA, ruthn@ncifcrf.gov Y1 - 2002/02/15/ PY - 2002 DA - 2002 Feb 15 SP - 308 EP - 320 VL - 46 IS - 3 SN - 0887-3585, 0887-3585 KW - dihydrofolate reductase KW - Microbiology Abstracts B: Bacteriology KW - Protein folding KW - Escherichia coli KW - Molecular dynamics KW - Thermal stability KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18271397?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proteins%3A+Structure%2C+Function+%26+Genetics&rft.atitle=Thermal+Unfolding+Molecular+Dynamics+Simulation+of+Escherichia+coli+Dihydrofolate+Reductase%3A+Thermal+Stability+of+Protein+Domains+and+Unfolding+Pathway&rft.au=Sham%2C+Y+Y%3BMa%2C+B%3BTsai%2C+C-J%3BNussinov%2C+R&rft.aulast=Sham&rft.aufirst=Y&rft.date=2002-02-15&rft.volume=46&rft.issue=3&rft.spage=308&rft.isbn=&rft.btitle=&rft.title=Proteins%3A+Structure%2C+Function+%26+Genetics&rft.issn=08873585&rft_id=info:doi/10.1002%2Fprot.10040 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Protein folding; Thermal stability; Molecular dynamics DO - http://dx.doi.org/10.1002/prot.10040 ER - TY - JOUR T1 - Long-Term Expression after Infection by the Hybrid Vector AdLTR-luc Is from Integrated Transgene AN - 18264619; 5320667 AB - The novel adenoretroviral vector, AdLTR-luc, infects dividing and nondividing cells, and mediates long-term transgene expression(Zheng, C., Baum, B. J., Iadarola, M. J., and O'Connell, B. C., Nat. Biotech. 18, 176-180, 2000). To determine the source of this expression we examined two epithelial cell lines. One, HSG, permits E1 super(-) recombinant adenoviral replication, while the other, A5, does not. An HSG clone, that expressed luciferase stably for >6 months, was obtained following infection at similar to 0.2 AdLTR-luc particles/cell. Southern and PCR analyses showed that luciferase cDNA present was integrated. A5 cells were infected with AdLTR-luc at similar to 1000 particles/cell, and colonies were obtained by limiting dilution. Eight clones showed stable luciferase activity for >9 months. High molecular weight DNA extracts from clones were positive for genomic integration by Southern, PCR, and quantitative PCR analyses. Similar analyses of low molecular weight DNA extracts indicated the absence of intact extrachromosomal vector. These data demonstrate that long-term luciferase expression after infection by AdLTR-luc is derived from the integrated cDNA. JF - Biochemical and Biophysical Research Communications AU - Zheng, C AU - Baum, B J AD - Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, 20892-1190, bbaum@dir.nidcr.nih.gov Y1 - 2002/02/15/ PY - 2002 DA - 2002 Feb 15 SP - 34 EP - 40 PB - Academic Press VL - 291 IS - 1 SN - 0006-291X, 0006-291X KW - luciferase KW - transgenes KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - Replication KW - Adenovirus KW - Gene expression KW - cDNA KW - Reporter gene KW - Cell lines KW - Epithelium KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18264619?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+Biophysical+Research+Communications&rft.atitle=Long-Term+Expression+after+Infection+by+the+Hybrid+Vector+AdLTR-luc+Is+from+Integrated+Transgene&rft.au=Zheng%2C+C%3BBaum%2C+B+J&rft.aulast=Zheng&rft.aufirst=C&rft.date=2002-02-15&rft.volume=291&rft.issue=1&rft.spage=34&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+Biophysical+Research+Communications&rft.issn=0006291X&rft_id=info:doi/10.1006%2Fbbrc.2002.6401 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adenovirus; Gene expression; Replication; Epithelium; Cell lines; Reporter gene; cDNA DO - http://dx.doi.org/10.1006/bbrc.2002.6401 ER - TY - JOUR T1 - Accelerated hyperfractionation (AHF) compared to conventional fractionation (CF) in the postoperative radiotherapy of locally advanced head and neck cancer: influence of proliferation. AN - 71488453; 11870530 AB - Based on the assumption that an accelerated proliferation process prevails in tumour cell residues after surgery, the possibility that treatment acceleration would offer a therapeutic advantage in postoperative radiotherapy of locally advanced head and neck cancer was investigated. The value of T(pot) in predicting the treatment outcome and in selecting patients for accelerated fractionation was tested. Seventy patients with (T2/N1-N2) or (T3-4/any N) squamous cell carcinoma of the oral cavity, larynx and hypopharynx who underwent radical surgery, were randomized to either (a) accelerated hyperfractionation: 46.2 Gy per 12 days, 1.4 Gy per fraction, three fractions per day with 6 h interfraction interval, treating 6 days per week or (b) Conventional fractionation: 60 Gy per 6 weeks, 2 Gy per fraction, treating 5 days per week. The 3-year locoregional control rate was significantly better in the accelerated hyperfractionation (88 +/- 4%) than in the CF (57+/- 9%) group, P=0.01 (and this was confirmed by multivariate analysis), but the difference in survival (60 +/- 10% vs 46 +/- 9%) was not significant (P=0.29). The favourable influence of a short treatment time was further substantiated by demonstrating the importance of the gap between surgery and radiotherapy and the overall treatment time between surgery and end of radiotherapy. Early mucositis progressed more rapidly and was more severe in the accelerated hyperfractionation group; reflecting a faster rate of dose accumulation. Xerostomia was experienced by all patients with a tendency to be more severe after accelerated hyperfractionation. Fibrosis and oedema also tended to be more frequent after accelerated hyperfractionation and probably represent consequential reactions. T(pot) showed a correlation with disease-free survival in a univariate analysis but did not prove to be an independent factor. Moreover, the use of the minimum and corrected P-values did not identify a significant cut-off. Compared to conventional fractionation, accelerated hyperfractionation did not seem to offer a survival advantage in fast tumours though a better local control rate was noted. This limits the use of T(pot) as a guide for selecting patients for accelerated hyperfractionation. For slowly growing tumours, tumour control and survival probabilities were not significantly different in the conventional fractionation and accelerated hyperfractionation groups. A rapid tumour growth was associated with a higher risk of distant metastases (P=0.01). In conclusion, tumour cell repopulation seems to be an important determinant of postoperative radiotherapy of locally advanced head and neck cancer despite lack of a definite association between T(pot) and treatment outcome. In fast growing tumours accelerated hyperfractionation provided an improved local control but without a survival advantage. To gain a full benefit from treatment acceleration, the surgery-radiotherapy gap and the overall treatment time should not exceed 6 and 10 weeks respectively. JF - British journal of cancer AU - Awwad, H K AU - Lotayef, M AU - Shouman, T AU - Begg, A C AU - Wilson, G AU - Bentzen, S M AU - Abd El-Moneim, H AU - Eissa, S AD - Department of Radiotherapy, National Cancer Institute, University of Cairo, Fom El Khalig 11796, Cairo, Egypt. awwad@internetegypt.com Y1 - 2002/02/12/ PY - 2002 DA - 2002 Feb 12 SP - 517 EP - 523 VL - 86 IS - 4 SN - 0007-0920, 0007-0920 KW - Index Medicus KW - Disease-Free Survival KW - Fibrosis -- etiology KW - Postoperative Care KW - Combined Modality Therapy KW - Dose Fractionation KW - Lymphatic Metastasis KW - Humans KW - Aged KW - Xerostomia -- etiology KW - Radiotherapy Dosage KW - Adult KW - Middle Aged KW - Neoplasm Recurrence, Local KW - Female KW - Male KW - Radiation Injuries -- etiology KW - Carcinoma, Squamous Cell -- surgery KW - Carcinoma, Squamous Cell -- pathology KW - Head and Neck Neoplasms -- radiotherapy KW - Head and Neck Neoplasms -- pathology KW - Head and Neck Neoplasms -- surgery KW - Carcinoma, Squamous Cell -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71488453?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+cancer&rft.atitle=Accelerated+hyperfractionation+%28AHF%29+compared+to+conventional+fractionation+%28CF%29+in+the+postoperative+radiotherapy+of+locally+advanced+head+and+neck+cancer%3A+influence+of+proliferation.&rft.au=Awwad%2C+H+K%3BLotayef%2C+M%3BShouman%2C+T%3BBegg%2C+A+C%3BWilson%2C+G%3BBentzen%2C+S+M%3BAbd+El-Moneim%2C+H%3BEissa%2C+S&rft.aulast=Awwad&rft.aufirst=H&rft.date=2002-02-12&rft.volume=86&rft.issue=4&rft.spage=517&rft.isbn=&rft.btitle=&rft.title=British+journal+of+cancer&rft.issn=00070920&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-29 N1 - Date created - 2002-02-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cytometry. 1985 Nov;6(6):620-6 [4064842] Radiother Oncol. 1999 Jan;50(1):13-23 [10225552] Br J Cancer. 1988 Oct;58(4):423-31 [3207597] Radiother Oncol. 1990 Nov;19(3):219-35 [2281152] Br J Cancer. 1992 Jun;65(6):870-8 [1616858] Int J Radiat Oncol Biol Phys. 1992;24(1):87-91 [1512167] Radiother Oncol. 1992 Dec;25(4):261-6 [1480771] Int J Radiat Oncol Biol Phys. 1993 Apr 30;26(1):3-11 [8482629] Int J Radiat Oncol Biol Phys. 2000 Oct 1;48(3):871-87 [11020586] Int J Radiat Oncol Biol Phys. 2001 Nov 1;51(3):571-8 [11597795] Int J Radiat Oncol Biol Phys. 1993 Aug 1;26(5):793-9 [8344848] J Natl Cancer Inst. 1994 Jun 1;86(11):829-35 [8182763] J Clin Oncol. 1995 Aug;13(8):1843-50 [7636527] Radiother Oncol. 1997 Feb;42(2):99-106 [9106919] Int J Radiat Oncol Biol Phys. 1997 Jul 1;38(4):677-83 [9240632] Lancet. 1997 Jul 19;350(9072):161-5 [9250182] Radiother Oncol. 1997 Aug;44(2):111-21 [9288839] Int J Radiat Oncol Biol Phys. 1997 Nov 1;39(4):831-6 [9369130] Int J Radiat Oncol Biol Phys. 1997 Nov 1;39(4):849-53 [9369133] Head Neck. 1998 Mar;20(2):119-23 [9484942] Radiother Oncol. 1998 Feb;46(2):147-55 [9510042] Acta Oncol. 1988;27(2):131-46 [3390344] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Flow Cytometry Analysis of Adenosine Deaminase (ADA) Expression: A Simple and Reliable Tool for the Assessment of ADA-Deficient Patients Before and After Gene Therapy AN - 18276704; 5336012 AB - Clinical gene therapy trials for adenosine deaminase (ADA) deficiency have shown limited success of corrective gene transfer into autologous T lymphocytes and CD34 super(+) cells. In these trials, the levels of gene transduction and expression in hematopoietic cells have been assessed by DNA- or RNA-based assays and measurement of ADA enzyme activity. Although informative, these methods are rarely applied to clonal analysis. The results of these assays therefore provide best estimates of transduction efficiency and gene expression in bulk populations based on the assumption that gene transfer and expression are uniformly distributed among transduced cells. As a useful additional tool for evaluation of ADA gene expression, we have developed a flow cytometry (fluorescence-activated cell sorting, FACS) assay capable of estimating the levels of intracellular ADA on a single-cell basis. We validated this technique with T cell lines and peripheral blood mononuclear cells (PBMCs) from ADA-deficient patients that showed severely reduced levels of ADA expression (ADA-dull) by FACS and Western blot analyses. After retrovirus-mediated ADA gene transfer, these cells showed clearly distinguishable populations exhibiting ADA expression (ADA-bright), thus allowing estimation of transduction efficiency. By mixing ADA-deficient and normal cells and using enzymatic amplification, we determined that our staining procedure could detect as little as 5% ADA-bright cells. This technique, therefore, will be useful to quickly assess the expression of ADA in hematopoietic cells of severe combined immunodeficient patients and represents an important tool for the follow-up of patients treated in clinical gene transfer protocols. JF - Human Gene Therapy AU - Otsu, Makoto AU - Hershfield AU - Tuschong, L M AU - Muul, L M AU - Onodera, Masafumi AU - Ariga, Tadashi AU - Sakiyama, Yukio AU - Candotti, F AD - Genetics and Molecular Biology Branch, NHGRI, NIH, 10 Center Drive, Building 10, Room 10C103, MSC 1851, Bethesda, MD 20892-1851, USA, fabio@nhgri.nih.gov Y1 - 2002/02/10/ PY - 2002 DA - 2002 Feb 10 SP - 425 EP - 432 VL - 13 IS - 3 SN - 1043-0342, 1043-0342 KW - man KW - CD34 antigen KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Flow cytometry KW - Gene therapy KW - Gene transfer KW - Transduction KW - Adenosine deaminase KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18276704?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Flow+Cytometry+Analysis+of+Adenosine+Deaminase+%28ADA%29+Expression%3A+A+Simple+and+Reliable+Tool+for+the+Assessment+of+ADA-Deficient+Patients+Before+and+After+Gene+Therapy&rft.au=Otsu%2C+Makoto%3BHershfield%3BTuschong%2C+L+M%3BMuul%2C+L+M%3BOnodera%2C+Masafumi%3BAriga%2C+Tadashi%3BSakiyama%2C+Yukio%3BCandotti%2C+F&rft.aulast=Otsu&rft.aufirst=Makoto&rft.date=2002-02-10&rft.volume=13&rft.issue=3&rft.spage=425&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adenosine deaminase; Gene therapy; Gene transfer; Flow cytometry; Transduction ER - TY - JOUR T1 - Evolutionary Patterns of Diversity in Spadefoot Toad Metamorphosis (Anura: Pelobatidae) AN - 18577987; 5384775 AB - The larvae of spadefoot toads exhibit extreme developmental/endocrinological diversity. For example, New World spadefoot toads (Scaphiopus and Spea) have the shortest larval periods known among anurans, and the tadpoles of Old World spadefoot taxa (Pelobates) are among the largest known. To analyze the patterns of this diversity in an evolutionary context, we generated comparable larval growth and development data from 10 of the 11 taxa of spadefoot toads and from one taxon of parsley frog (Pelodytes), the nearest spadefoot toad relative. We found dramatic differences in growth and development among taxa, which indicated that taxon-specific physiology, rather than phenotypic plasticity, underlies larval period diversity. For all eight response variables (development rate, three growth rates, time to forelimb emergence, time to tail resorption, mass at tail resorption, and body length at tail resorption), taxa within genera were similar to each other and were different from taxa in other genera. Larvae of Scaphiopus were small with short larval periods, larvae of Spea were large with short larval periods, larvae of Pelobates were large with long larval periods, and larvae of Pelodytes were small with long larval periods. Even though taxa within the same genus live in different environments, larval growth and development correlated with phylogenetic groupings rather than breeding habitat. Mapping larval data onto a molecular phylogeny indicated that short larval periods, as well as rapid embryonic development and high temperature tolerance, originated within the spadefoot toad family. JF - Copeia AU - Buchholz AU - Hayes, T B AD - LME/NICHD/NIH, Building 18T, Room 106, 18 Library Drive, MSC 5431, Bethesda, Maryland 20892, USA, dbuchholz@nih.gov Y1 - 2002/02/08/ PY - 2002 DA - 2002 Feb 08 SP - 180 EP - 189 PB - Allen Press, Inc., 810 East Tenth St. Lawrence KS 66044 USA, [mailto:webmaster@allenpress.com] VL - 2002 IS - 1 SN - 0045-8511, 0045-8511 KW - Western spadefoots KW - Ecology Abstracts; ASFA 1: Biological Sciences & Living Resources KW - Classification systems KW - Spea KW - Developmental stages KW - Pelobates KW - Freshwater KW - Life history KW - Endocrinology KW - Ontogeny KW - Metamorphosis KW - Scaphiopus KW - Evolution KW - Phylogenetics KW - Q1 08325:Genetics and evolution KW - D 04669:Amphibians UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18577987?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Copeia&rft.atitle=Evolutionary+Patterns+of+Diversity+in+Spadefoot+Toad+Metamorphosis+%28Anura%3A+Pelobatidae%29&rft.au=Buchholz%3BHayes%2C+T+B&rft.aulast=Buchholz&rft.aufirst=&rft.date=2002-02-08&rft.volume=2002&rft.issue=1&rft.spage=180&rft.isbn=&rft.btitle=&rft.title=Copeia&rft.issn=00458511&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2016-05-27 N1 - SubjectsTermNotLitGenreText - Classification systems; Endocrinology; Developmental stages; Ontogeny; Phylogenetics; Evolution; Life history; Metamorphosis; Spea; Pelobates; Scaphiopus; Freshwater ER - TY - JOUR T1 - Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease. AN - 71433385; 11830608 AB - Lung cancer is a frequent cause of death in patients cured of Hodgkin's disease, but the contributions of chemotherapy, radiotherapy, and smoking are not well described. We quantified the risk of treatment-associated lung cancer, taking into account tobacco use. Within a population-based cohort of 19 046 Hodgkin's disease patients (diagnosed from 1965 through 1994), a case-control study of lung cancer was conducted. The cumulative amount of cytotoxic drugs, the radiation dose to the specific location in the lung where cancer developed, and tobacco use were compared for 222 patients who developed lung cancer and for 444 matched control patients. All statistical tests were two-sided. Treatment with alkylating agents without radiotherapy was associated with increased lung cancer risk (relative risk [RR] = 4.2; 95% confidence interval [CI] = 2.1 to 8.8), as was radiation dose of 5 Gy or more without alkylating agents (RR = 5.9; 95% CI = 2.7 to 13.5). Risk increased with both increasing number of cycles of alkylating agents and increasing radiation dose (P for trend <.001). Among patients treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), risk increased with cumulative amounts of mechlorethamine and procarbazine (P<.001) when evaluated separately. Statistically significantly elevated risks of lung cancer were apparent within 1-4 years after treatment with alkylating agents, whereas excess risk after radiotherapy began 5 years after treatment and persisted for more than 20 years. Risk after treatment with alkylating agents and radiotherapy together was as expected if individual excess risks were summed. Tobacco use increased lung cancer risk more than 20-fold; risks from smoking appeared to multiply risks from treatment. Past treatments with alkylating agents and radiation therapy for Hodgkin's disease were associated with an increased risk of lung cancer in a dose-dependent and additive fashion. The precise risk estimates, however, should be interpreted cautiously, given the possible residual and enhancing effects of tobacco. JF - Journal of the National Cancer Institute AU - Travis, Lois B AU - Gospodarowicz, Mary AU - Curtis, Rochelle E AU - Clarke, E Aileen AU - Andersson, Michael AU - Glimelius, Bengt AU - Joensuu, Timo AU - Lynch, Charles F AU - van Leeuwen, Flora E AU - Holowaty, Eric AU - Storm, Hans AU - Glimelius, Ingrid AU - Pukkala, Eero AU - Stovall, Marilyn AU - Fraumeni, Joseph F AU - Boice, John D AU - Gilbert, Ethel AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. travisl@epndce.nci.nih.gov Y1 - 2002/02/06/ PY - 2002 DA - 2002 Feb 06 SP - 182 EP - 192 VL - 94 IS - 3 SN - 0027-8874, 0027-8874 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Disease-Free Survival KW - Dose-Response Relationship, Drug KW - Humans KW - Smoking -- adverse effects KW - Aged KW - Child KW - Dose-Response Relationship, Radiation KW - Radiotherapy -- adverse effects KW - Antineoplastic Agents -- adverse effects KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Neoplasms, Second Primary -- complications KW - Lung Neoplasms -- complications KW - Lung Neoplasms -- etiology KW - Hodgkin Disease -- radiotherapy KW - Neoplasms, Second Primary -- etiology KW - Hodgkin Disease -- drug therapy KW - Hodgkin Disease -- therapy KW - Hodgkin Disease -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71433385?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Lung+cancer+following+chemotherapy+and+radiotherapy+for+Hodgkin%27s+disease.&rft.au=Travis%2C+Lois+B%3BGospodarowicz%2C+Mary%3BCurtis%2C+Rochelle+E%3BClarke%2C+E+Aileen%3BAndersson%2C+Michael%3BGlimelius%2C+Bengt%3BJoensuu%2C+Timo%3BLynch%2C+Charles+F%3Bvan+Leeuwen%2C+Flora+E%3BHolowaty%2C+Eric%3BStorm%2C+Hans%3BGlimelius%2C+Ingrid%3BPukkala%2C+Eero%3BStovall%2C+Marilyn%3BFraumeni%2C+Joseph+F%3BBoice%2C+John+D%3BGilbert%2C+Ethel&rft.aulast=Travis&rft.aufirst=Lois&rft.date=2002-02-06&rft.volume=94&rft.issue=3&rft.spage=182&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-14 N1 - Date created - 2002-02-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Discrimination against purine-pyrimidine mispairs in the polymerase active site of DNA polymerase I: a structural explanation. AN - 71447400; 11830658 AB - We previously identified five derivatives of Klenow fragment DNA polymerase that have lower fidelity because of amino acid substitutions in the polymerase active site. One of these has alanine substituted for the invariant Glu-710, whose side chain interacts with the deoxyribose of the incoming dNTP. Here we show that the E710A enzyme has reduced fidelity for five of the 12 possible mismatches. All but one of these involve misinsertion of pyrimidines, including two transition mismatches A-dCTP and G-dTTP. In contrast, E710A polymerase error rates for the reciprocal C-dATP and T-dGTP transition mismatches were similar to those of the wild-type enzyme. The kinetics of formation of correct base pairs and transition mismatches by the wild-type and E710A polymerases, combined with information on the structure of the DNA polymerase active site and the asymmetry of wobble base pairs, provides a plausible explanation for the differential effects of the E710A mutation on fidelity. The data suggest that the Glu-710 side chain plays a pivotal role in excluding wobble base pairs between template pyrimidines and purine triphosphates by steric clash. Moreover, this same side chain enhances the stability of incoming correct dNTPs, such that loss of this interaction on removal of the side chain leads to lower selectivity against mismatches involving incoming pyrimidines. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Minnick, Dana T AU - Liu, Lixing AU - Grindley, Nigel D F AU - Kunkel, Thomas A AU - Joyce, Catherine M AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2002/02/05/ PY - 2002 DA - 2002 Feb 05 SP - 1194 EP - 1199 VL - 99 IS - 3 SN - 0027-8424, 0027-8424 KW - Deoxyribonucleotides KW - 0 KW - Purines KW - Pyrimidines KW - Recombinant Proteins KW - DNA Polymerase I KW - EC 2.7.7.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Deoxyribonucleotides -- metabolism KW - Deoxyribonucleotides -- chemistry KW - Recombinant Proteins -- chemistry KW - Amino Acid Substitution KW - Protein Conformation KW - Binding Sites KW - Base Pair Mismatch KW - DNA Polymerase I -- chemistry KW - DNA Polymerase I -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71447400?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Discrimination+against+purine-pyrimidine+mispairs+in+the+polymerase+active+site+of+DNA+polymerase+I%3A+a+structural+explanation.&rft.au=Minnick%2C+Dana+T%3BLiu%2C+Lixing%3BGrindley%2C+Nigel+D+F%3BKunkel%2C+Thomas+A%3BJoyce%2C+Catherine+M&rft.aulast=Minnick&rft.aufirst=Dana&rft.date=2002-02-05&rft.volume=99&rft.issue=3&rft.spage=1194&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-07 N1 - Date created - 2002-02-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 2001 Jun 1;276(22):18836-42 [11278911] Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9491-6 [10449720] Mol Cell. 2001 Aug;8(2):427-37 [11545744] Anal Biochem. 1976 May 7;72:248-54 [942051] Biochemistry. 1982 Feb 2;21(3):437-44 [7066295] Annu Rev Biochem. 1982;51:429-57 [6214209] Nature. 1985 Mar 21-27;314(6008):235-8 [3845322] Nature. 1985 Jun 13-19;315(6020):604-6 [4010774] Nature. 1986 Apr 10-16;320(6062):552-5 [3960137] J Mol Biol. 1986 Aug 20;190(4):605-18 [3783714] J Biol Chem. 1987 Dec 15;262(35):16973-84 [3680285] Science. 1988 Apr 8;240(4849):199-201 [2832946] Biochim Biophys Acta. 1988 Nov 10;951(1):1-15 [2847793] J Biol Chem. 1990 Aug 15;265(23):13878-87 [2199444] J Biol Chem. 1990 Aug 25;265(24):14579-91 [2201688] Biochemistry. 1991 Jan 22;30(3):804-13 [1899034] Annu Rev Biochem. 1991;60:477-511 [1883202] J Biol Chem. 1992 Dec 5;267(34):24485-500 [1447195] Crit Rev Biochem Mol Biol. 1993;28(2):83-126 [8485987] Trends Biochem Sci. 1993 May;18(5):160-3 [8328014] Annu Rev Biochem. 1994;63:777-822 [7526780] Methods Enzymol. 1995;262:3-13 [8594356] Methods Enzymol. 1995;262:217-32 [8594349] Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1619-22 [9050827] J Biol Chem. 1997 Mar 14;272(11):7345-51 [9054433] Nature. 1998 Jan 15;391(6664):251-8 [9440688] Nature. 1998 Jan 15;391(6664):304-7 [9440698] Curr Opin Genet Dev. 2000 Apr;10(2):162-8 [10753775] Proc Natl Acad Sci U S A. 2000 May 23;97(11):5681-3 [10811923] Annu Rev Biochem. 2000;69:497-529 [10966467] Protein Sci. 2001 Jun;10(6):1225-33 [11369861] J Biol Chem. 2001 Feb 16;276(7):5044-51 [11069916] Electrophoresis. 1997 Dec;18(15):2714-23 [9504803] Curr Opin Struct Biol. 1998 Feb;8(1):54-63 [9519297] Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3402-7 [9520378] J Mol Biol. 1998 Apr 24;278(1):147-65 [9571040] EMBO J. 1998 Dec 15;17(24):7514-25 [9857206] J Biol Chem. 1999 Jan 29;274(5):3067-75 [9915846] Structure. 1999 Feb 15;7(2):R31-5 [10368292] J Biol Chem. 1999 Jul 23;274(30):20749-52 [10409611] Mol Cell. 2001 Jul;8(1):7-8 [11515498] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol consumption and risk for congestive heart failure in the Framingham Heart Study. AN - 71439242; 11827493 AB - Although excessive alcohol consumption can promote cardiomyopathy, little is known about the association between alcohol consumption and risk for congestive heart failure in the community. To determine the relation between alcohol consumption and risk for congestive heart failure in the community. Community-based, prospective observational study. Framingham, Massachusetts. Participants in the Framingham Heart Study who were free of congestive heart failure and coronary heart disease. Self-reported alcohol consumption; sex-specific rates of congestive heart failure per 1000 person-years of follow-up by level of alcohol consumption. In men, 99 cases of congestive heart failure occurred during 26 035 person-years of follow-up. In women, 120 cases of congestive heart failure occurred during 35 563 person-years of follow-up. After adjustment for multiple confounders, risk for congestive heart failure was lower among men at all levels of alcohol consumption compared with men who consumed less than 1 drink/wk. The hazard ratio for congestive heart failure was lowest among men who consumed 8 to 14 drinks/wk (0.41 [95% CI, 0.21 to 0.81]) compared with those who consumed less than 1 drink/wk. In women, the age-adjusted hazard ratio for congestive heart failure was lowest among those who consumed 3 to 7 drinks/wk (0.49 [CI, 0.25 to 0.96]) compared with those who consumed less than 1 drink/wk. However, after adjustment for multiple predictors of congestive heart failure, this association was no longer statistically significant. In the community, alcohol consumption is not associated with increased risk for congestive heart failure, even among heavy drinkers (> or = 15 drinks/wk in men and > or = 8 drinks/wk in women). To the contrary, when consumed in moderation, alcohol appears to protect against congestive heart failure. JF - Annals of internal medicine AU - Walsh, Craig R AU - Larson, Martin G AU - Evans, Jane C AU - Djousse, Luc AU - Ellison, R Curtis AU - Vasan, Ramachandran S AU - Levy, Daniel AD - National Heart, Lung, and Blood Institute's Framingham Heart Study, National Institutes of Health, Framingham, Massachusetts 01702, USA. Y1 - 2002/02/05/ PY - 2002 DA - 2002 Feb 05 SP - 181 EP - 191 VL - 136 IS - 3 KW - Abridged Index Medicus KW - Index Medicus KW - Myocardial Infarction -- etiology KW - Prospective Studies KW - Sex Factors KW - Ventricular Dysfunction, Left -- etiology KW - Risk Factors KW - Humans KW - Confounding Factors (Epidemiology) KW - Adult KW - Hypertension -- etiology KW - Middle Aged KW - Male KW - Female KW - Heart Failure -- etiology KW - Heart Failure -- prevention & control KW - Heart Failure -- complications KW - Alcohol Drinking -- adverse effects KW - Alcoholism -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71439242?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+internal+medicine&rft.atitle=Alcohol+consumption+and+risk+for+congestive+heart+failure+in+the+Framingham+Heart+Study.&rft.au=Walsh%2C+Craig+R%3BLarson%2C+Martin+G%3BEvans%2C+Jane+C%3BDjousse%2C+Luc%3BEllison%2C+R+Curtis%3BVasan%2C+Ramachandran+S%3BLevy%2C+Daniel&rft.aulast=Walsh&rft.aufirst=Craig&rft.date=2002-02-05&rft.volume=136&rft.issue=3&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=Annals+of+internal+medicine&rft.issn=1539-3704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-11 N1 - Date created - 2002-03-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Ann Intern Med. 2002 Feb 5;136(3):247-9 [11827501] Ann Intern Med. 2003 Jan 7;138(1):75-6 [12513052] Ann Intern Med. 2003 Jan 7;138(1):75-6; author reply 75-6 [12513051] Summary For Patients In: Ann Intern Med. 2002 Feb 5;136(3):I16 [11928738] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Muscle, Adipose, and Connective Tissue Variations in Intrinsic Musculature of the Adult Human Tongue AN - 85569850; 200306227 AB - Previous research on the musculature of the tongue has not focused on providing a complete description of all constituent elements of the human tongue. In this study, lingual histology is examined by identifying three types of connective tissues, including collagen, elastin, & adipose tissue, within defined muscle regions. Using stained tissue components, the percent concentration of each of these tissues was derived. Tissue samples (N = 10) were taken from the same section of multiple tongues for the anterior, medial, & posterior regions. The results of statistical analyses of tissue concentration percentage demonstrate that the anterior region contains a greater proportion of connective tissue & fat, whereas posterior regions contained the greatest amount of muscle content. The distribution & organization of lingual tissue in each of the three regions showed a high degree of variation. No statistical effects of age or sex-related differences were found in any of the constituent elements of the tongue. Implications of this research for lingual biomechanics & histopathology are discussed. 3 Tables, 70 References. L. Davidson JF - Journal of Speech, Language, and Hearing Research AU - Miller, Jeri L AU - Watkin, Kenneth L AU - Chen, Moy Fong AD - Warren G. Magnuson Clinical Center, National Instits Health, Bethesda, MD jmiller@cc.nih.gov Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 51 EP - 65 VL - 45 IS - 1 SN - 1092-4388, 1092-4388 KW - Articulation (04600) KW - Oral Cavity (61200) KW - Speech Production (82780) KW - Statistical Analysis (83850) KW - article UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85569850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Speech%2C+Language%2C+and+Hearing+Research&rft.atitle=Muscle%2C+Adipose%2C+and+Connective+Tissue+Variations+in+Intrinsic+Musculature+of+the+Adult+Human+Tongue&rft.au=Miller%2C+Jeri+L%3BWatkin%2C+Kenneth+L%3BChen%2C+Moy+Fong&rft.aulast=Miller&rft.aufirst=Jeri&rft.date=2002-02-01&rft.volume=45&rft.issue=1&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Journal+of+Speech%2C+Language%2C+and+Hearing+Research&rft.issn=10924388&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2003-10-01 N1 - Last updated - 2016-09-27 N1 - SubjectsTermNotLitGenreText - Oral Cavity (61200); Speech Production (82780); Articulation (04600); Statistical Analysis (83850) ER - TY - JOUR T1 - Auditory manifestations of Keratitis-Ichthyosis-Deafness (KID) syndrome. AN - 85369303; pmid-11889383 AB - Evaluation of the auditory manifestations of Keratitis-Ichthyosis-Deafness (KID) syndrome, a rare genodermatosis characterized by follicular hyperkeratosis, vascularizing keratitis, and congenital hearing loss.Five individuals with sporadic KID syndrome were evaluated in the outpatient audiology clinic at the Warren Grant Magnuson Clinical Center of the National Institutes of Health.Audiologic examinations included pure-tone audiometry, speech audiometry, and middle ear immittance testing. Auditory brainstem responses and otoacoustic emissions were analyzed in 2 subjects.Four subjects had prelingual, bilateral, profound sensorineural hearing loss, whereas the fifth subject had significant residual hearing that exhibited no progression on serial audiograms. All 5 subjects had a history of non-erosive keratosis obturans and cutaneous cysts in the external ear canals that prevented continuous use of ear molds.The sensorineural hearing loss in KID syndrome is generally prelingual and profound. This combination of auditory and cutaneous phenotypes is similar to those previously reported for KID syndrome. KID syndrome presents a difficult challenge for communication rehabilitation because keratitis may impair the perception of sign and spoken language, and the cutaneous manifestations routinely curtail use of external amplification devices. JF - The Laryngoscope AU - Szymko-Bennett, Yvonne M AU - Russell, Laura J AU - Bale, Sherri J AU - Griffith, Andrew J AD - National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA. szymkoy@nidcd.nih.gov Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 272 EP - 280 VL - 112 IS - 2 SN - 0023-852X, 0023-852X KW - Index Medicus KW - National Library of Medicine KW - Adolescent KW - Audiometry: methods KW - Child KW - Cochlear Implants KW - Deafness: complications KW - Deafness: diagnosis KW - Deafness: genetics KW - Deafness: therapy KW - Female KW - Hearing Aids KW - Hearing Loss, Sensorineural: complications KW - *Hearing Loss, Sensorineural: congenital KW - *Hearing Loss, Sensorineural: diagnosis KW - Humans KW - Ichthyosis: complications KW - *Ichthyosis: diagnosis KW - Ichthyosis: genetics KW - Infant KW - Keratitis: complications KW - *Keratitis: diagnosis KW - Keratitis: genetics KW - Male KW - Otolaryngology: instrumentation KW - Prognosis KW - Sampling Studies KW - Syndrome UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85369303?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Laryngoscope&rft.atitle=Auditory+manifestations+of+Keratitis-Ichthyosis-Deafness+%28KID%29+syndrome.&rft.au=Szymko-Bennett%2C+Yvonne+M%3BRussell%2C+Laura+J%3BBale%2C+Sherri+J%3BGriffith%2C+Andrew+J&rft.aulast=Szymko-Bennett&rft.aufirst=Yvonne&rft.date=2002-02-01&rft.volume=112&rft.issue=2&rft.spage=272&rft.isbn=&rft.btitle=&rft.title=The+Laryngoscope&rft.issn=0023852X&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Low-grade follicular lymphoma of the small intestine. AN - 85366086; pmid-11782611 AB - Although the gastrointestinal tract is the most common site of extranodal non-Hodgkin's lymphoma (NHL), primary small intestine lymphomas remain relatively rare, especially localized low-grade follicular B-cell lymphomas. When lymphomas do occur at this site, most are high grade and require aggressive therapy. We report three cases of small intestinal follicular lymphoma diagnosed on endoscopic biopsy and review the clinical history, pathologic features, and treatment outcome.A review of the medical records and pathology from three cases of small intestine follicular NHL was performed. The pathology specimens were formalin-fixed, paraffin-embedded tissues processed for routine microscopic examination, immunohistochemical staining, and molecular analysis.Histologic and immunophenotypical studies were diagnostic of grade 1 follicular lymphoma (Revised European-American Lymphoma classification/World Health Organization classification). All cases expressed bcl-2 protein, and polymerase chain reaction analysis supported the diagnosis in two cases with adequate DNA. With 23.3 months' median follow-up, one untreated and one treated patient were alive without symptoms; a third untreated patient died of a nonlymphoma cause.Isolated indolent lymphomas of the small intestine are rare. Accurate pathologic staging and histologic classification are paramount in delineating treatment options. JF - Journal of clinical gastroenterology AU - Poggi, Matthew M AU - Cong, Peijie J AU - Coleman, C Norman AU - Jaffe, Elaine S AD - Radiation Oncology Sciences Program, National Institutes of Health, National Cancer Institute, Bethesda, Maryland, USA. mpoggi@usuhs.mil Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 155 EP - 159 VL - 34 IS - 2 SN - 0192-0790, 0192-0790 KW - Index Medicus KW - National Library of Medicine KW - Aged KW - *Duodenal Neoplasms: pathology KW - Female KW - Humans KW - *Ileal Neoplasms: pathology KW - *Lymphoma, Follicular: pathology KW - Male KW - Middle Aged UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85366086?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+gastroenterology&rft.atitle=Low-grade+follicular+lymphoma+of+the+small+intestine.&rft.au=Poggi%2C+Matthew+M%3BCong%2C+Peijie+J%3BColeman%2C+C+Norman%3BJaffe%2C+Elaine+S&rft.aulast=Poggi&rft.aufirst=Matthew&rft.date=2002-02-01&rft.volume=34&rft.issue=2&rft.spage=155&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+gastroenterology&rft.issn=01920790&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - The effect of neuromuscular stimulation of the genioglossus on the hypopharyngeal airway. AN - 85365525; pmid-11889396 AB - To determine the effects of neuromuscular stimulation (NS) of the genioglossus muscle on hypopharyngeal airway size.Fourteen consecutively recruited healthy volunteers underwent percutaneous electrical NS of the genioglossus muscle.Bipolar hooked wires were inserted percutaneously into the genioglossus muscle and used for NS. The anterior--posterior diameter of the hypopharynx was measured at the level of the superior edge of the epiglottis at baseline and during NS from recorded video endoscopic examinations.NS of the genioglossus muscle resulted in a significant increase in the diameter of the hypopharyngeal airway (P =.002) compared with baseline, ranging from a 33% to 284% increase in airway diameter. Three of the 14 patients demonstrated modest decreases in airway diameter, likely the result of faulty electrode placement in surrounding tongue retrusive muscles.NS of the genioglossus muscle was effective in increasing the hypopharyngeal airway and may provide a useful alternative to direct stimulation of the hypoglossal nerve with a nerve cuff electrode in the development of neuroprosthetic treatments for obstructive sleep apnea. JF - The Laryngoscope AU - Mann, Eric A AU - Burnett, Theresa AU - Cornell, Sonia AU - Ludlow, Christy L AD - Laryngeal and Speech Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1416, USA. manne@ninds.nih.gov Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 351 EP - 356 VL - 112 IS - 2 SN - 0023-852X, 0023-852X KW - Index Medicus KW - National Library of Medicine KW - Adult KW - Airway Resistance KW - Analysis of Variance KW - *Electric Stimulation: methods KW - Female KW - Humans KW - *Hypopharynx: physiology KW - Laryngoscopy: methods KW - Male KW - Middle Aged KW - Muscle Contraction KW - Muscle Relaxation KW - *Pharyngeal Muscles: innervation KW - *Pharyngeal Muscles: physiology KW - Prospective Studies KW - Reference Values KW - Respiratory Mechanics: physiology KW - Sensitivity and Specificity KW - Video Recording UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85365525?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Laryngoscope&rft.atitle=The+effect+of+neuromuscular+stimulation+of+the+genioglossus+on+the+hypopharyngeal+airway.&rft.au=Mann%2C+Eric+A%3BBurnett%2C+Theresa%3BCornell%2C+Sonia%3BLudlow%2C+Christy+L&rft.aulast=Mann&rft.aufirst=Eric&rft.date=2002-02-01&rft.volume=112&rft.issue=2&rft.spage=351&rft.isbn=&rft.btitle=&rft.title=The+Laryngoscope&rft.issn=0023852X&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - A new method for the study of velopharyngeal function using gated magnetic resonance imaging. AN - 85248188; pmid-11818823 AB - The purpose of this project was to assess the feasibility of imaging the velopharynx of adult volunteers during repetitive speech, using gated magnetic resonance imaging (MRI). Although a number of investigators have used conventional MRI in the study of the human vocal tract, the mismatch between the lengthy time necessary to acquire sufficiently detailed images and the rapidity of movement of the vocal tract during speech has forced investigators to acquire images either while the subject is at rest or during sustained utterances. The technique used here acquired a portion of each image during repetitive utterances, building the full image over multiple utterance cycles. The velopharyngeal portal was imaged on a 1.5-Tesla GE Signa LX 8.2 platform with gated fast spoiled gradient echo protocol. An external 1-Hertz trigger was fed to the cardiac gate. Subjects synchronized utterance of consonant-vowel syllables to a flashing light synchronized with the external trigger. Each acquisition of 30 phases per second at a single-slice location took 22 to 29 seconds. Four consonant-vowel syllables (/pa/, /ma/, /sa/, and /ka/) were evaluated. Subjects vocalized throughout the acquisition, beginning 5 to 6 seconds beforehand to establish a regular rhythm. Imaging of the velopharyngeal portal was performed for sagittal, velopharyngeal axial (aligned perpendicular to the "knee" of the velum), axial, and coronal planes. Volumes were obtained by sequential acquisition of six to 10 slices (each with 30 phases) in the axial or sagittal planes during repetition of the /pa/ syllable. Spatiotemporal volumes of the single-slice data were sectioned to provide time-motion images (analogous to M-mode echocardiograms). Three-dimensional dynamic volume renderings of palate motion were displayed interactively (Vortex; CieMed, Singapore). A method suitable for the collection and visualization of four-dimensional information regarding monosyllabic speech using gated MRI was developed. These techniques were applied to a population of adult volunteer subjects with no history of speech problems and two patients with a history of cleft lip and palate. The techniques allowed good real-time visualization of velopharyngeal anatomy during its entire range of motion and was also able to image pathology-specific anatomic differences in the subjects with cleft lip and cleft palate. These methods may be applicable to a wide spectrum of problems in speech physiology research and for clinical decision-making regarding surgery for speech and outcomes analysis. JF - Plastic and Reconstructive Surgery AU - Kane, Alex A AU - Butman, John A AU - Mullick Rakesh AU - Skopec Marlene AU - Choyke, Peter AD - Imaging Sciences Training Program, Laboratory for Diagnostic Radiology Research, Diagnostic Radiology Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, USA. PY - 2002 SP - 472 EP - 481 VL - 109 IS - 2 SN - 0032-1052, 0032-1052 KW - Cleft Palate KW - Imaging, Three-Dimensional KW - Feasibility Studies KW - Reference Values KW - Pharynx KW - Cleft Lip KW - Human KW - Adult KW - Palate, Soft KW - Image Processing, Computer-Assisted KW - Male KW - Female KW - Magnetic Resonance Imaging KW - Speech UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85248188?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Plastic+and+Reconstructive+Surgery&rft.atitle=A+new+method+for+the+study+of+velopharyngeal+function+using+gated+magnetic+resonance+imaging.&rft.au=Kane%2C+Alex+A%3BButman%2C+John+A%3BMullick+Rakesh%3BSkopec+Marlene%3BChoyke%2C+Peter&rft.aulast=Kane&rft.aufirst=Alex&rft.date=2002-02-01&rft.volume=109&rft.issue=2&rft.spage=472&rft.isbn=&rft.btitle=&rft.title=Plastic+and+Reconstructive+Surgery&rft.issn=00321052&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Reactive oxygen species as double-edged swords in cellular processes: low-dose cell signaling versus high-dose toxicity. AN - 71885715; 12102499 AB - ROS are diverse and abundant in biological systems. While excessive ROS production clearly damages DNA, low levels of ROS affect cell signaling particularly at the level of redox modulation. Moreover, the specific contributions of ROS to apoptosis and mitogenesis in maintenance of cell number homeostasis remains to be elucidated. ROS dose is a critical parameter in determining the ultimate cellular response; however the shape of the dose response curve is unpredictable. When cells are stimulated with ROS, cell-signaling cascades are activated. It appears that the cellular redox potential is an important determinant of cell function and interruption of redox balance may adversely affect cell function. As a result, compounds such as antioxidants may intercept critical ROS signaling molecules and both protect cells and foster pathogenesis. As a result, further study is needed to unravel the role of ROS in redox regulation and the potential outcome of antioxidant administration on cellular responses. JF - Human & experimental toxicology AU - Martin, K R AU - Barrett, J C AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina 27709, USA. martin9@niehs.nih.gov Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 71 EP - 75 VL - 21 IS - 2 SN - 0960-3271, 0960-3271 KW - Antioxidants KW - 0 KW - Reactive Oxygen Species KW - Index Medicus KW - Oxidation-Reduction -- drug effects KW - Antioxidants -- pharmacology KW - Dose-Response Relationship, Drug KW - Humans KW - Signal Transduction -- drug effects KW - Apoptosis -- drug effects KW - Mitosis -- drug effects KW - Neoplasms -- metabolism KW - DNA Damage -- drug effects KW - Reactive Oxygen Species -- metabolism KW - Reactive Oxygen Species -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71885715?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+%26+experimental+toxicology&rft.atitle=Reactive+oxygen+species+as+double-edged+swords+in+cellular+processes%3A+low-dose+cell+signaling+versus+high-dose+toxicity.&rft.au=Martin%2C+K+R%3BBarrett%2C+J+C&rft.aulast=Martin&rft.aufirst=K&rft.date=2002-02-01&rft.volume=21&rft.issue=2&rft.spage=71&rft.isbn=&rft.btitle=&rft.title=Human+%26+experimental+toxicology&rft.issn=09603271&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-07 N1 - Date created - 2002-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Redox-modulated xenobiotic action and ROS formation: a mirror or a window? AN - 71883615; 12102500 AB - A number of xenobiotics require redox reactions to form the reactive intermediates involved in the ultimate toxic events (e.g., adduct formation). The same mechanisms lead to the formation of reactive oxygen species (ROS), which can themselves exert direct toxicity including, e.g., DNA oxidative damage or glutathione depletion. The occurence of both mechanistic features in xenobiotic activation and toxicity may raise some difficulties in ascertaining the respective roles of reactive intermediates versus ROS-related mechnisms. An example is provided by the toxicity mechanisms of mitomycin C (MMC) and diepoxybutane (DEB), which are commonly referred to as 'cross-linkers'. Their toxic actions, however, are well-known to be modulated via redox parameters, such as oxygen tension, antioxidants levels, or thioredoxin overexpression. The diagnostic assessment of Fanconi's anaemia (FA) relies on MMC and DEB sensitivity, which is usually referred to as 'cross-linker sensitivity'; thus the redox-dependent toxicities of MMC and DEB may have direct implications for the definition of FA phenotype. Another major aspect in ROS formation relies on the extensive evidence pointing to the requirement for oxidative, as well as nitrosative activities in triggering a number of key events in cell division and differentiation, and in early embryogenesis. In turn, antioxidants that may prevent ROS-associated cellular damage in adult cells may prove to exert adverse or fatal outcomes when administered in early life stages. The overall information available on xenobiotic redox biotransformation and on the physiopathological roles of ROS points to the need of addressing ad hoc studies that should take into account the multiplicity of mechanistic events involved. JF - Human & experimental toxicology AU - Pagano, G AD - Italian National Cancer Institute, G Pascale Foundation, Naples, Italy. gbpagano@tin.it Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 77 EP - 81 VL - 21 IS - 2 SN - 0960-3271, 0960-3271 KW - Epoxy Compounds KW - 0 KW - Reactive Oxygen Species KW - Xenobiotics KW - Mitomycin KW - 50SG953SK6 KW - erythritol anhydride KW - 60OB65YNAB KW - Index Medicus KW - Chromosome Aberrations -- chemically induced KW - Oxidation-Reduction -- drug effects KW - Fanconi Anemia -- diagnosis KW - Epoxy Compounds -- pharmacology KW - Mitomycin -- pharmacology KW - Humans KW - Oxidative Stress -- drug effects KW - Cell Division -- drug effects KW - Cell Differentiation -- drug effects KW - Fanconi Anemia -- genetics KW - DNA Damage -- drug effects KW - Reactive Oxygen Species -- metabolism KW - Xenobiotics -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71883615?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+%26+experimental+toxicology&rft.atitle=Redox-modulated+xenobiotic+action+and+ROS+formation%3A+a+mirror+or+a+window%3F&rft.au=Pagano%2C+G&rft.aulast=Pagano&rft.aufirst=G&rft.date=2002-02-01&rft.volume=21&rft.issue=2&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=Human+%26+experimental+toxicology&rft.issn=09603271&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-07 N1 - Date created - 2002-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reserpine: interactions with batrachotoxin and brevetoxin sites on voltage-dependent sodium channels. AN - 71822809; 12064513 AB - Reserpine inhibited batrachotoxin-elicited sodium influx in guinea pig brain synaptoneurosomes with an IC50 of about 1 microM. In the presence of brevetoxin the IC50 increased to about 80 microM. Reserpine inhibited binding of batrachotoxinin-A [3H]benzoate ([3H]BTX-B) binding in a complex manner causing a partial inhibition from 0.001 to 0.08 microM, then a rebound stimulation from 0.1 to 0.8 microM, followed by complete inhibition by 80 microM. The stimulation was prevented by the presence of brevetoxin; reserpine then smoothly inhibited binding with an IC50 of about 1 microM. Reserpine at 1 microM slightly reduced the off-rate of [3H]BTX-B binding measured in the presence of veratridine, while at a concentration of 50 microM it enhanced the off-rate, presumably by an allosteric mechanism. Reserpine at 0.3-10 microM elicited a partial inhibition of the binding of [3H]brevetoxin-3. The local anesthetic dibucaine had effects similar to reserpine: It partially inhibited binding of [3H]brevetoxin. The presence of brevetoxin reduced the potency of dibucaine as an inhibitor of batrachotoxin-elicited sodium influx from an IC50 of about 2 microM to an IC50 of about 50 microM. The results suggest that reserpine binds at both a local anesthetic site to cause allosteric inhibition of batrachotoxin-binding and action, but that it also binds to another site causing, like brevetoxin, an enhancement of batrachotoxin-binding and action. Local anesthetics also may bind to the brevetoxin site. JF - Cellular and molecular neurobiology AU - Flowers, Andrew AU - Onwueme, Kenolisa AU - Creveling, Cyrus R AU - Daly, John W AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 1 EP - 12 VL - 22 IS - 1 SN - 0272-4340, 0272-4340 KW - Antitoxins KW - 0 KW - Batrachotoxins KW - Marine Toxins KW - Neurotoxins KW - Oxocins KW - Sodium Channels KW - Reserpine KW - 8B1QWR724A KW - brevetoxin KW - 98225-48-0 KW - Dibucaine KW - L6JW2TJG99 KW - Index Medicus KW - Antitoxins -- pharmacology KW - Animals KW - Cerebral Cortex -- physiology KW - Guinea Pigs KW - Kinetics KW - Dibucaine -- pharmacology KW - Binding Sites KW - Reserpine -- pharmacology KW - Synapses -- physiology KW - Batrachotoxins -- toxicity KW - Synapses -- drug effects KW - Oxocins -- pharmacokinetics KW - Batrachotoxins -- pharmacokinetics KW - Sodium Channels -- physiology KW - Sodium Channels -- drug effects KW - Neurotoxins -- toxicity KW - Oxocins -- toxicity KW - Marine Toxins -- toxicity KW - Marine Toxins -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71822809?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+and+molecular+neurobiology&rft.atitle=Reserpine%3A+interactions+with+batrachotoxin+and+brevetoxin+sites+on+voltage-dependent+sodium+channels.&rft.au=Flowers%2C+Andrew%3BOnwueme%2C+Kenolisa%3BCreveling%2C+Cyrus+R%3BDaly%2C+John+W&rft.aulast=Flowers&rft.aufirst=Andrew&rft.date=2002-02-01&rft.volume=22&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Cellular+and+molecular+neurobiology&rft.issn=02724340&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-04 N1 - Date created - 2002-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Safety and pharmacokinetics of intravitreal 2-methoxyestradiol implants in normal rabbit and pharmacodynamics in a rat model of choroidal neovascularization. AN - 71596843; 11950241 AB - Choroidal neovascularization (CNV) is the leading cause of severe vision loss associated with age-related macular degeneration. As the pathogenesis of CNV formation is better understood, mechanism-based therapies, including the use of antiangiogenesis inhibitors, have been investigated. 2-methoxyestradiol (2ME2), an endogenous metabolite of estradiol, has been shown in the chick allantoic membrane model and the corneal micropocket assay to have antiangiogenic properties. The authors sought to determine the safety and pharmacokinetics of sustained-release intravitreal 2ME2 implants in normal rabbit and their efficacy in a rat model of CNV. 2ME2 implants were constructed using two designs: implant A, a silicone-based reservoir implant for the rabnbit eye, and implant B, a microimplant matrix design for the rat eye. In vitro release rates of both implants were determined. New Zealand white (NZW) rabbits had implant A placed in the vitreous cavity of one eye and the ocular toxicity was evaluated by clinical examination, serial electroretinography (ERG), and histopathology over a 28 week period. The steady state clearance of 2ME2 in the rabbit eye was calculated from in vivo release rates divided by steady state vitreous concentrations. A CNV model in the Brown-Norway rat was performed by injecting an adenoviral vector encoding human vascular endothelial growth factor in the subretinal space. Following the injection, a 2ME2 or sham (no drug) microimplant was placed in the vitreous cavity. Animals were killed over a 3 week period and the eyes examined for CNV by histopathology. Results showed that following a short burst, the release rate of implant A followed zero-order kinetics, typical of reservoir devices, and the cumulative release of implant B was proportional to the square root of time, as expected for a matrix delivery device. The safety studies in normal rabbit showed no ocular toxicities by clinical examination, ERG, and histopathology. Pharmacokinetic evaluation in the rabbit showed mean 2ME2 vitreous levels within the therapeutic range for the inhibition of endothelial cell proliferation. The experimental rat model showed a significant reduction in CNV in eyes treated with the 2ME2 implant. In conclusion, sustained-release 2ME2 intravitreal implants, which can be designed to deliver potentially therapeutic vitreous levels of 2ME2 for an extended period of time, appeared to be safe in normal rabbit and effective in a rat model of CNV. Sustained-release 2ME2 intravitreal implants may hold promise in the treatment of recurrent CNV refractory to standard therapy. Copyright 2002 Elsevier Science Ltd. JF - Experimental eye research AU - Robinson, M R AU - Baffi, J AU - Yuan, P AU - Sung, C AU - Byrnes, G AU - Cox, T A AU - Csaky, K G AD - National Eye Institute, NIH, 10 Center Dr/MSC 1863, Bldg 10/Room 10N112, Bethesda, MD 20892-1863, USA. robinsonm@nei.nih.gov Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 309 EP - 317 VL - 74 IS - 2 SN - 0014-4835, 0014-4835 KW - Angiogenesis Inhibitors KW - 0 KW - Drug Implants KW - Estradiol KW - 4TI98Z838E KW - 2-methoxyestradiol KW - 6I2QW73SR5 KW - Index Medicus KW - Rats KW - Models, Animal KW - Animals KW - Equipment Design KW - Vitreous Body -- drug effects KW - Vitreous Body -- chemistry KW - Rabbits KW - Rats, Inbred BN KW - Statistics, Nonparametric KW - Electroretinography KW - Estradiol -- analogs & derivatives KW - Estradiol -- administration & dosage KW - Choroidal Neovascularization -- drug therapy KW - Angiogenesis Inhibitors -- pharmacokinetics KW - Estradiol -- pharmacokinetics KW - Angiogenesis Inhibitors -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71596843?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+eye+research&rft.atitle=Safety+and+pharmacokinetics+of+intravitreal+2-methoxyestradiol+implants+in+normal+rabbit+and+pharmacodynamics+in+a+rat+model+of+choroidal+neovascularization.&rft.au=Robinson%2C+M+R%3BBaffi%2C+J%3BYuan%2C+P%3BSung%2C+C%3BByrnes%2C+G%3BCox%2C+T+A%3BCsaky%2C+K+G&rft.aulast=Robinson&rft.aufirst=M&rft.date=2002-02-01&rft.volume=74&rft.issue=2&rft.spage=309&rft.isbn=&rft.btitle=&rft.title=Experimental+eye+research&rft.issn=00144835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-29 N1 - Date created - 2002-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemoprevention of colorectal carcinogenesis. AN - 71578228; 11942045 AB - The field of cancer prevention is advancing rapidly, largely owing to post-genomic technology that has revolutionized our ability to identify and characterize molecular profiles for cancer. Advances in colorectal cancer screening (e.g., endoscopy, fecal occult blood testing, and mutational analysis) have made the detection and eradication of preinvasive neoplastic lesions the standard of care. Basic and translational sciences are building on these advances, and continue to expose molecular hallmarks of carcinogenesis that can be exploited as targets for molecularly targeted preventive interventions (i.e., chemoprevention). These targets will help identify more effective and better tolerated preventive agents. Carcinogenesis is now recognized as a disease in itself and has become the target of an ever-expanding array of preventive interventions. JF - International journal of clinical oncology AU - Umar, Asad AU - Viner, Jaye L AU - Richmond, Ellen AU - Anderson, William F AU - Hawk, Ernest T AD - Gastrointestinal and Other Cancers Research Group, National Cancer Institute, Division of Cancer Prevention, EPN, Suite 2141, 6130 Executive Boulevard, Bethesda, MD 20892-7317, USA. eh51p@nih.gov Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 2 EP - 26 VL - 7 IS - 1 SN - 1341-9625, 1341-9625 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Anticarcinogenic Agents KW - Calcium, Dietary KW - Dietary Fats KW - Index Medicus KW - Adenomatous Polyposis Coli -- prevention & control KW - Animals KW - Anticarcinogenic Agents -- therapeutic use KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Humans KW - Clinical Trials as Topic KW - Disease Models, Animal KW - Mice KW - Dietary Fiber KW - Rats KW - Chemoprevention KW - Cell Transformation, Neoplastic KW - Colorectal Neoplasms -- pathology KW - Colorectal Neoplasms -- genetics KW - Colorectal Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71578228?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+clinical+oncology&rft.atitle=Chemoprevention+of+colorectal+carcinogenesis.&rft.au=Umar%2C+Asad%3BViner%2C+Jaye+L%3BRichmond%2C+Ellen%3BAnderson%2C+William+F%3BHawk%2C+Ernest+T&rft.aulast=Umar&rft.aufirst=Asad&rft.date=2002-02-01&rft.volume=7&rft.issue=1&rft.spage=2&rft.isbn=&rft.btitle=&rft.title=International+journal+of+clinical+oncology&rft.issn=13419625&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-02 N1 - Date created - 2002-04-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic and functional analysis of single nucleotide polymorphisms in the beta2-neuronal nicotinic acetylcholine receptor gene (CHRNB2). AN - 71554197; 11906688 AB - The beta2-neuronal nicotinic acetylcholine receptor gene (CHRNB2) is a logical candidate for influencing smoking behavior and nicotine dependence. We discovered six single nucleotide polymorphisms (SNPs) in the CHRNB2 gene by surveying 15.4 kb of genomic sequence including a previously undescribed 3' untranslated region that extends 4.0 kb downstream of the coding region. One of the SNPs causes an amino acid substitution in exon 5, one occurs in the promoter region, one changes an intronic base, and three occur in the 3' untranslated region. The ethnically dependent allele frequencies and the marker-to-marker linkage disequilibrium patterns of five of these polymorphisms were determined. The SNPs were assayed in 743 individuals for whom information on smoking history and lifelong nicotine dependence was available. No significant associations of the individual markers or their haplotypes to smoking behavior or level of nicotine dependence were found. JF - Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco AU - Lueders, Kira K AU - Hu, Stella AU - McHugh, Louise AU - Myakishev, Max V AU - Sirota, Leo A AU - Hamer, Dean H AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 115 EP - 125 VL - 4 IS - 1 SN - 1462-2203, 1462-2203 KW - DNA Primers KW - 0 KW - Receptors, Nicotinic KW - nicotinic receptor beta2 KW - Index Medicus KW - Genotype KW - Polymerase Chain Reaction KW - Humans KW - Surveys and Questionnaires KW - Polymorphism, Single Nucleotide -- genetics KW - Tobacco Use Disorder -- genetics KW - Smoking -- genetics KW - Receptors, Nicotinic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71554197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.atitle=Genetic+and+functional+analysis+of+single+nucleotide+polymorphisms+in+the+beta2-neuronal+nicotinic+acetylcholine+receptor+gene+%28CHRNB2%29.&rft.au=Lueders%2C+Kira+K%3BHu%2C+Stella%3BMcHugh%2C+Louise%3BMyakishev%2C+Max+V%3BSirota%2C+Leo+A%3BHamer%2C+Dean+H&rft.aulast=Lueders&rft.aufirst=Kira&rft.date=2002-02-01&rft.volume=4&rft.issue=1&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.issn=14622203&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-13 N1 - Date created - 2002-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence of solvent inhalation among junior high school students in Japan and their background lifestyle: results of Chiba prefecture survey 1994. AN - 71552062; 11915304 AB - To estimate the lifetime prevalence of solvent abuse among general junior high school students in Chiba prefecture and to understand their background lifestyle, in 1994 the author surveyed 6,795 students enrolled in 15 junior high schools. The lifetime prevalence of solvent abuse was 1.9% in males, 1.1% in females and 1.5% of the total. This implied that the lifetime prevalence of solvent abuse was decreasing year-on-year in males, had recovered to the 1990 level in total, but had stagnated between the 1990 level and the 1992 level in females. The regularity of daily life was more significantly disturbed in Lifetime Users than in Non-Users. School life and family life were significantly less relaxed for Lifetime Users than for Non-Users. Cigarette smoking and some types of alcohol drinking were strongly related to solvent abuse. More Lifetime Users than Non-Users were aware of harmful effects of solvent abuse. The author suggests that developing practical educative measures to promote behavioral change, as well as increasing the frequency with which the entire family eats dinner together, is necessary. JF - Nihon Arukoru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence AU - Wada, Kiyoshi AD - Division of Drug Dependence Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, 1-7-3 Kohnodai, Ichikawa-shi, Chiba-ken 272-0827, Japan. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 41 EP - 56 VL - 37 IS - 1 SN - 1341-8963, 1341-8963 KW - Solvents KW - 0 KW - Index Medicus KW - Japan -- epidemiology KW - Sex Factors KW - Humans KW - Surveys and Questionnaires KW - Alcohol Drinking -- epidemiology KW - Adolescent KW - Time Factors KW - Smoking -- epidemiology KW - Male KW - Female KW - Social Environment KW - Prevalence KW - Students -- psychology KW - Life Style KW - Schools KW - Students -- statistics & numerical data KW - Solvents -- adverse effects KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71552062?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nihon+Arukoru+Yakubutsu+Igakkai+zasshi+%3D+Japanese+journal+of+alcohol+studies+%26+drug+dependence&rft.atitle=Prevalence+of+solvent+inhalation+among+junior+high+school+students+in+Japan+and+their+background+lifestyle%3A+results+of+Chiba+prefecture+survey+1994.&rft.au=Wada%2C+Kiyoshi&rft.aulast=Wada&rft.aufirst=Kiyoshi&rft.date=2002-02-01&rft.volume=37&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Nihon+Arukoru+Yakubutsu+Igakkai+zasshi+%3D+Japanese+journal+of+alcohol+studies+%26+drug+dependence&rft.issn=13418963&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-16 N1 - Date created - 2002-03-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Renewal of drug seeking by contextual cues after prolonged extinction in rats. AN - 71524444; 11895178 AB - Contextual stimuli associated with drug exposure can modulate various effects of drugs, but little is known about their role in relapse to drug seeking. Using a renewal procedure, the authors report that drug-associated contextual stimuli play a critical role in relapse to drug-seeking previously maintained by a heroin-cocaine mixture (speedball). Rats were trained to self-administer speedball, after which drug-reinforced behavior was extinguished over 20 days in the self-administration context or in a different context. On the test day, rats exposed to the drug-associated context, after extinction in a different context, reliably renewed drug seeking. The authors suggest that the renewal procedure can be used to study mechanisms underlying relapse to drug seeking elicited by drug-associated contextual stimuli. JF - Behavioral neuroscience AU - Crombag, Hans S AU - Shaham, Yavin AD - Behavioral Neuroscience Branch, National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland 21224, USA. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 169 EP - 173 VL - 116 IS - 1 SN - 0735-7044, 0735-7044 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Long-Evans KW - Cues KW - Self Administration -- psychology KW - Male KW - Social Environment KW - Extinction, Psychological KW - Motivation KW - Association Learning KW - Cocaine-Related Disorders -- psychology KW - Mental Recall KW - Heroin Dependence -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71524444?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Behavioral+neuroscience&rft.atitle=Renewal+of+drug+seeking+by+contextual+cues+after+prolonged+extinction+in+rats.&rft.au=Crombag%2C+Hans+S%3BShaham%2C+Yavin&rft.aulast=Crombag&rft.aufirst=Hans&rft.date=2002-02-01&rft.volume=116&rft.issue=1&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=Behavioral+neuroscience&rft.issn=07357044&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-03 N1 - Date created - 2002-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rescue of hematopoietic stem cells following high-dose radiation injury using ex vivo culture on endothelial monolayers. AN - 71504393; 11878265 AB - Military personnel are at significant risk for potentially lethal myeloablative injury secondary to nuclear accident, nuclear attack, or chemical weapons attack. In an attempt to develop culture conditions in which hematopoietic stem cells might be rescued from the effects of radiation, we irradiated (1,000 cGy split dose) 6-week-old C57BL/6 (Ly 5.1) and syngeneic C57BL/6 (Ly 5.2) mice and tested whether bone marrow mononuclear cells (MNCs) harvested postirradiation could be rescued via coculture in porcine microvascular endothelial cell (PMVEC) monolayers. We found that a subpopulation of bone marrow MNCs exposed to 1,000 cGy could be maintained and expanded over 10 days in a PMVEC culture (3.8-fold expansion), whereas liquid suspension culture did not maintain a significant number of hematopoietic cells postirradiation. Colony-forming assays demonstrated that murine MNCs exposed to 1,000 cGy did not give rise to granulocyte/macrophage colony-forming units (CFU-GM), erythroid burst-forming units (BFU-e), or CFU-Mix in 14-day cultures, whereas irradiated MNCs that were subsequently cultured in PMVEC-generated CFU-GM, BFU-e, and CFU-Mix at cloning efficiencies of 1.3%, 0.2%, and 0.2%, respectively. In survival studies, we found that 78% of mice that were irradiated and then transplanted with irradiated/PMVEC-expanded MNCs were alive at day 50, compared with 18% of irradiated control mice (p < 0.05). We also observed that mice transplanted with irradiated/PMVEC-expanded MNCs showed complete hematologic recovery. At 8 weeks post-transplant, we found evidence of Ly 5.1 donor cells in both the bone marrow and the spleen of the transplanted animals, but the levels of engraftment were low (range, 0-5.1%; mean, 1.9%). These results demonstrate that a subpopulation of bone marrow stem cells are capable of surviving the effects of high-dose radiation if these cells are placed in coculture with endothelial cell monolayers. JF - Military medicine AU - Chute, John P AU - Clark, William AU - Saini, Abha AU - Wells, Mark AU - Harlan, David AD - Navy/National Institute of Diabetes and Digestive and Kidney Diseases-Transplantation and Autoimmunity Branch, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 74 EP - 77 VL - 167 IS - 2 Suppl SN - 0026-4075, 0026-4075 KW - Index Medicus KW - Swine KW - Animals KW - Cells, Cultured KW - Mice, Inbred C57BL KW - Mice KW - Endothelium -- cytology KW - Radiation Injuries, Experimental -- pathology KW - Hematopoietic Stem Cells -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71504393?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Military+medicine&rft.atitle=Rescue+of+hematopoietic+stem+cells+following+high-dose+radiation+injury+using+ex+vivo+culture+on+endothelial+monolayers.&rft.au=Chute%2C+John+P%3BClark%2C+William%3BSaini%2C+Abha%3BWells%2C+Mark%3BHarlan%2C+David&rft.aulast=Chute&rft.aufirst=John&rft.date=2002-02-01&rft.volume=167&rft.issue=2+Suppl&rft.spage=74&rft.isbn=&rft.btitle=&rft.title=Military+medicine&rft.issn=00264075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-20 N1 - Date created - 2002-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Absorbed dose and the quantification of physical events at low-dose irradiation of tissue. AN - 71504309; 11873509 JF - Military medicine AU - Feinendegen, Ludwig E AU - Neumann, Ronald D AU - Bond, Victor P AU - Sondhaus, Charles A AD - Department of Nuclear Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 36 EP - 38 VL - 167 IS - 2 Suppl SN - 0026-4075, 0026-4075 KW - Index Medicus KW - Animals KW - Cells -- radiation effects KW - Radiation Dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71504309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Military+medicine&rft.atitle=Absorbed+dose+and+the+quantification+of+physical+events+at+low-dose+irradiation+of+tissue.&rft.au=Feinendegen%2C+Ludwig+E%3BNeumann%2C+Ronald+D%3BBond%2C+Victor+P%3BSondhaus%2C+Charles+A&rft.aulast=Feinendegen&rft.aufirst=Ludwig&rft.date=2002-02-01&rft.volume=167&rft.issue=2+Suppl&rft.spage=36&rft.isbn=&rft.btitle=&rft.title=Military+medicine&rft.issn=00264075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-20 N1 - Date created - 2002-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specific cell-signal targets for cancer chemotherapy. AN - 71502438; 11885686 AB - Attempts to develop drugs, specific for cancer cells, are dealt here according to the intended cell-target. While many target specific drugs were developed, they reach only moderate successes in clinics for reasons, such as, delivery problem, lack of in vivo efficacy or toxicity. However, recent efforts focusing on the diversity of tyrosine kinases, participating in cell-signal transduction, brought fruit. The firs such drug, Givec, approved by the USFDA recently, is used in clinics with great success to threat CML. The drug inhibits tyrosin kinase of bcr-abl, c-abl and v-abl. Work is progressing on other tyrosin kinase inhibitors and on other type of specific cancer cell signal protein inhibitors. These efforts are hoped to yield better cures for cancer in the near future. JF - Archives of pharmacal research AU - Aszalos, Adorjan AD - National Cancer Institute, National Institute of Health, Bethesda, MD, USA. aszalosa@mail.nih.gov Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 1 EP - 10 VL - 25 IS - 1 SN - 0253-6269, 0253-6269 KW - Antineoplastic Agents KW - 0 KW - Protein Kinase Inhibitors KW - Receptors, Cell Surface KW - Alkyl and Aryl Transferases KW - EC 2.5.- KW - Farnesyltranstransferase KW - EC 2.5.1.29 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Telomerase KW - EC 2.7.7.49 KW - Index Medicus KW - Protein-Tyrosine Kinases -- antagonists & inhibitors KW - Telomerase -- antagonists & inhibitors KW - Animals KW - Immune System -- drug effects KW - Humans KW - Receptors, Cell Surface -- antagonists & inhibitors KW - Alkyl and Aryl Transferases -- antagonists & inhibitors KW - Cell Differentiation -- drug effects KW - Neoplasms -- drug therapy KW - Neoplasms -- enzymology KW - Signal Transduction -- drug effects KW - Antineoplastic Agents -- pharmacology KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71502438?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+pharmacal+research&rft.atitle=Specific+cell-signal+targets+for+cancer+chemotherapy.&rft.au=Aszalos%2C+Adorjan&rft.aulast=Aszalos&rft.aufirst=Adorjan&rft.date=2002-02-01&rft.volume=25&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Archives+of+pharmacal+research&rft.issn=02536269&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-29 N1 - Date created - 2002-03-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Photophysical and photochemical studies of 2-phenylbenzimidazole and UVB sunscreen 2-phenylbenzimidazole-5-sulfonic acid. AN - 71500063; 11883597 AB - The sunscreen agent 2-phenylbenzimidazole-5-sulfonic acid (PBSA) and its parent 2-phenylbenzimidazole (PBI) cause DNA photodamage via both Type-I and Type-II mechanisms when UVB irradiated. We have studied the photophysical and photochemical properties of these compounds and their ability to photogenerate reactive oxygen species including free radicals. PBI and PBSA exhibit both oxidizing and reducing properties in their excited state. The absorption and fluorescence properties of PBSA depend strongly upon pH, and hence the photochemistry of PBSA was studied in both neutral and alkaline solutions. PBSA showed strong oxidizing properties when UV irradiated in neutral aqueous solution (pH 7.4) in the presence of cysteine, glutathione and azide, as evidenced by the detection of the corresponding S-cysteinyl, glutathiyl and azidyl radicals with the aid of the spin trap, 5,5-dimethyl-1-pyrroline N-oxide (DMPO). However, when an aqueous anaerobic solution (pH 10) of PBSA and either nitromethane (NM) or 4-nitrobenzoic acid (4-NBA) were irradiated, the corresponding nitro anion radicals were observed. This finding suggests that both NM and 4-NBA are reduced by direct electron transfer from the excited state PBSA. During UV irradiation of an aerobic solution of PBSA, O2*- and *OH radical were generated and trapped by DMPO. Further, PBI (in ethanol) and PBSA (in ethylene glycol : water 2: 1 mixture) showed low temperature (77 K) phosphorescence (lambdamax = 443, 476 and 509 nm) and also an electron paramagnetic resonance half-field transition (deltaMs = +/-2), which is evidence for a triplet state. This triplet produced singlet oxygen (1O2) with quantum yields 0.07 and 0.04 in MeCN for PBI and PBSA, respectively. These studies demonstrate that UV irradiation of PBSA and PBI generates a variety of free radicals and active oxygen species that may be involved in the photodamage of DNA. JF - Photochemistry and photobiology AU - Inbaraj, J Johnson AU - Bilski, Piotr AU - Chignell, Colin F AD - Laboratory of Pharmacology and Chemistry, NIEHS, Research Triangle Park, NC 27709, USA. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 107 EP - 116 VL - 75 IS - 2 SN - 0031-8655, 0031-8655 KW - Benzimidazoles KW - 0 KW - Reactive Oxygen Species KW - Sulfonic Acids KW - Sunscreening Agents KW - ensulizole KW - 9YQ9DI1W42 KW - 2-phenylbenzimidazole KW - CB9ZJ140SB KW - Index Medicus KW - Photochemistry KW - Ultraviolet Rays KW - DNA Damage KW - Benzimidazoles -- radiation effects KW - Sunscreening Agents -- radiation effects KW - Benzimidazoles -- chemistry KW - Sunscreening Agents -- chemistry KW - Sunscreening Agents -- toxicity KW - Benzimidazoles -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71500063?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Photochemistry+and+photobiology&rft.atitle=Photophysical+and+photochemical+studies+of+2-phenylbenzimidazole+and+UVB+sunscreen+2-phenylbenzimidazole-5-sulfonic+acid.&rft.au=Inbaraj%2C+J+Johnson%3BBilski%2C+Piotr%3BChignell%2C+Colin+F&rft.aulast=Inbaraj&rft.aufirst=J&rft.date=2002-02-01&rft.volume=75&rft.issue=2&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Photochemistry+and+photobiology&rft.issn=00318655&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-18 N1 - Date created - 2002-03-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Stress-gene induction by low-dose gamma irradiation. AN - 71499529; 11873496 AB - Using a human myeloid tumor cell line (ML-1), we detected induction of mRNA expression of several stress-responsive genes by doses of gamma rays as low as 2 cGy. For instance, the dose response for induction of CIP1/WAF1 and GADD45 appears to be linear over the range of 2 to 50 cGy and shows no evidence of a threshold for induction. Although 2 and 5 cGy exposures did not result in any detectable reduction in cloning efficiency nor in increased apoptosis in ML-1 cells, these exposures did produce a brief cell-cycle delay. We also used fluorescent cDNA microarray hybridization to investigate transcriptional stress responses following low doses of gamma rays and to identify additional radiation-responsive genes for inclusion in a stress-specific microarray we are developing. These studies provide insight into the molecular responses to physiologically relevant doses, which cannot necessarily be extrapolated from high-dose studies. The use of high throughput arrays will allow the identification of multiple stress-responsive genes that are radiation inducible in a variety of cell types and tissues. The expectation is that transcriptional stress responses will provide a molecular approach to monitoring for radiation exposure and detecting interindividual differences. JF - Military medicine AU - Fornace, Albert J AU - Amundson, Sally A AU - Do, Khanh T AU - Meltzer, Paul AU - Trent, Jeffrey AU - Bittner, Michael AD - National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 13 EP - 15 VL - 167 IS - 2 Suppl SN - 0026-4075, 0026-4075 KW - Index Medicus KW - Tumor Cells, Cultured KW - Gamma Rays KW - Humans KW - Transcription, Genetic KW - Gene Expression Regulation KW - Transcriptional Activation KW - Radiation Dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71499529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Military+medicine&rft.atitle=Stress-gene+induction+by+low-dose+gamma+irradiation.&rft.au=Fornace%2C+Albert+J%3BAmundson%2C+Sally+A%3BDo%2C+Khanh+T%3BMeltzer%2C+Paul%3BTrent%2C+Jeffrey%3BBittner%2C+Michael&rft.aulast=Fornace&rft.aufirst=Albert&rft.date=2002-02-01&rft.volume=167&rft.issue=2+Suppl&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Military+medicine&rft.issn=00264075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-20 N1 - Date created - 2002-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Testing a model of exposure to environmental tobacco smoke in military women with children. AN - 71497399; 11873532 AB - The purpose of this study was to test a model of exposure to environmental tobacco smoke (ETS) in military women and their children. The convenience sample consisted of 238 women, 81 smokers and 157 nonsmokers, with a mean age of 37 years (SD = 9.9). Participants were either on active duty or were reservists and/or military dependents. Model constructs, some of which were adapted from the transtheoretical model of behavior change, measured personal and situational factors, pros and cons of ETS exposure, self-efficacy to resist ETS, mother's expectation for child's ETS exposure, and mother's self-efficacy to reduce child's ETS exposure. The mediating variable was the mother's daily ETS exposure, and the outcome variable was the child's daily ETS exposure. The trimmed model showed that 32% of the variance in mother's daily exposure (mediating variable) was accounted for by living with a smoker, having high ETS "pros" (as opposed to ETS "cons"), having less self-efficacy to resist ETS, and having greater self-efficacy to reduce the child's exposure. There was a significant, positive relationship (r = 0.51, p = 0.01) between the mother's and child's daily ETS exposure (outcome variable). JF - Military medicine AU - Martinelli, Angela M AU - Agazio, Janice AU - Flaherty, Norma AU - Ephraim, Paula M AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 113 EP - 120 VL - 167 IS - 2 SN - 0026-4075, 0026-4075 KW - Tobacco Smoke Pollution KW - 0 KW - Index Medicus KW - Regression Analysis KW - Humans KW - Adult KW - Surveys and Questionnaires KW - Health Behavior KW - Child KW - Female KW - Models, Theoretical KW - Child, Preschool KW - Environmental Exposure -- statistics & numerical data KW - Military Personnel KW - Environmental Exposure -- analysis KW - Tobacco Smoke Pollution -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71497399?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Military+medicine&rft.atitle=Testing+a+model+of+exposure+to+environmental+tobacco+smoke+in+military+women+with+children.&rft.au=Martinelli%2C+Angela+M%3BAgazio%2C+Janice%3BFlaherty%2C+Norma%3BEphraim%2C+Paula+M&rft.aulast=Martinelli&rft.aufirst=Angela&rft.date=2002-02-01&rft.volume=167&rft.issue=2&rft.spage=113&rft.isbn=&rft.btitle=&rft.title=Military+medicine&rft.issn=00264075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-09 N1 - Date created - 2002-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitroxides as radiation protectors. AN - 71495241; 11873514 AB - Selective protection of normal tissues from the damaging effects of ionizing radiation is an important objective in cancer treatment research. Likewise, radioprotective agents may be useful in protecting the human population in the event of radiation-related accidents or military conflicts. Over the past decade, we have identified stable nitroxide compounds as a unique class of antioxidants with demonstrated radioprotective properties. We have shown that nitroxides at nontoxic concentrations are effective as in vitro and in vivo antioxidants when oxidation is induced by superoxide, hydrogen peroxide, organic hydroperoxides, ionizing radiation, or specific DNA-damaging anticancer agents. Studies have shown that nitroxides protect against radiation-induced DNA damage, chromosome aberrations, mutation induction, cell killing, and lethality in mice that receive whole-body irradiation. Whether these agents provide radioprotection for low-level radiation doses remains to be determined. JF - Military medicine AU - Mitchell, James B AU - Krishna, Murali C AD - Radiation Biology Branch, Division of Clinical Sciences, National Cancer Institute, Building 10, Room B3-B69, Bethesda, MD 20892, USA. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 49 EP - 50 VL - 167 IS - 2 Suppl SN - 0026-4075, 0026-4075 KW - Nitrogen Oxides KW - 0 KW - Radiation-Protective Agents KW - Index Medicus KW - Radiation Dosage KW - Animals KW - Humans KW - Mice KW - Nitrogen Oxides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71495241?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Military+medicine&rft.atitle=Nitroxides+as+radiation+protectors.&rft.au=Mitchell%2C+James+B%3BKrishna%2C+Murali+C&rft.aulast=Mitchell&rft.aufirst=James&rft.date=2002-02-01&rft.volume=167&rft.issue=2+Suppl&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=Military+medicine&rft.issn=00264075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-20 N1 - Date created - 2002-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Larger phase angle between sleep propensity and melatonin rhythms in sighted humans with non-24-hour sleep-wake syndrome. AN - 71493465; 11833864 AB - This study was aimed to clarify phase angle between sleep propensity and the circadian pacemaker in patients with non-24-hour sleep-wake syndrome (Non-24). A case-control study was underaken. Sighted patient with Non-24 (4 males and 1 female, aged 16 to 39 y), and sex- and age-matched healthy controls (12 males and 3 females, aged 19 to 35 y) participated the study. MEASUREMENT AND INTERVENTION: Following an actigraphic assessment of the sleep-wake cycle in their homes, the participants entered an ultra-short sleep-wake schedule together with simultaneous measurement of dim light melatonin rhythm after 24-hour sleep deprivation. The period of the sleep-wake cycle observed at home was longer in the Non-24 patients (25.12 hours) than in the controls (24.02 hours, p<0.0001). The interval from sleep propensity (SP) onset to the melatonin midpoint (MLmid) was significantly shorter in the Non-24 patients than in the controls. The interval from the MLmid to the SP offset was significantly longer in the Non-24 patients than in the controls. It was postulated that Non-24 sufferers' delayed SP onset relative to the circadian pacemaker may accelerate the light-induced phase-delay, leading to sleep-wake cycle that is longer than 24 hours. JF - Sleep AU - Uchiyama, Makoto AU - Shibui, Kayo AU - Hayakawa, Tatsuro AU - Kamei, Yuichi AU - Ebisawa, Takashi AU - Tagaya, Hirokuni AU - Okawa, Masako AU - Takahashi, Kiyohisa AD - Department of Psychophysiology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Ichikawa, Japan. macoto@ncnp-k.go.jp Y1 - 2002/02/01/ PY - 2002 DA - 2002 Feb 01 SP - 83 EP - 88 VL - 25 IS - 1 SN - 0161-8105, 0161-8105 KW - Melatonin KW - JL5DK93RCL KW - Index Medicus KW - Space life sciences KW - Polysomnography KW - Circadian Rhythm -- physiology KW - Humans KW - Adult KW - Case-Control Studies KW - Adolescent KW - Male KW - Female KW - Melatonin -- blood KW - Sleep Disorders, Circadian Rhythm -- metabolism KW - Sleep Disorders, Circadian Rhythm -- diagnosis KW - Sleep Disorders, Circadian Rhythm -- epidemiology KW - Melatonin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71493465?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Sleep&rft.atitle=Larger+phase+angle+between+sleep+propensity+and+melatonin+rhythms+in+sighted+humans+with+non-24-hour+sleep-wake+syndrome.&rft.au=Uchiyama%2C+Makoto%3BShibui%2C+Kayo%3BHayakawa%2C+Tatsuro%3BKamei%2C+Yuichi%3BEbisawa%2C+Takashi%3BTagaya%2C+Hirokuni%3BOkawa%2C+Masako%3BTakahashi%2C+Kiyohisa&rft.aulast=Uchiyama&rft.aufirst=Makoto&rft.date=2002-02-01&rft.volume=25&rft.issue=1&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Sleep&rft.issn=01618105&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-31 N1 - Date created - 2002-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Determination of tamoxifen and metabolites in mouse fetal tissue using nonaqueous capillary electrophoresis. AN - 71487631; 11870753 AB - Tamoxifen (TAM), an antiestrogen, has been approved for use by women at risk for developing hormone-dependent breast cancer. Administration of TAM to pregnant CD-1 mice apparently results in reproductive tract toxicity in female offspring. However, there is little or no data describing potential TAM-induced fetal toxicity to women who may become pregnant while receiving prophylactic TAM treatment. In support of the National Toxicology Program's characterization of reproductive and developmental effects of TAM, the present work describes a capillary electrophoresis (CE)-based analytical technique used for detection of TAM and two major metabolites, N-desmethyltamoxifen (DMT), and 4-hydroxytamoxifen (4-HT) in CD-1 mouse fetal tissue. TAM-derived material was extracted from CD-1 mouse fetuses 2-12 h following TAM administration (100 mg/kg) to dams on gestation day 16. The presence of TAM, DMT, and 4-HT was confirmed in the solvent extracts by nonaqueous CE. The limit of detection of TAM by UV absorption was approximately 675 amol at a signal-to-noise ratio of 2:1. This work demonstrates both transplacental transport of TAM in CD-1 mice and a sensitive analytical technique for detecting low concentrations of TAM and similar compounds in biological tissues. JF - Electrophoresis AU - Sanders, J M AU - Cunningham, M L AD - Laboratory of Pharmacology and Chemistry, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709-2233, USA. sandersm@niehs.nih.gov Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 502 EP - 505 VL - 23 IS - 3 SN - 0173-0835, 0173-0835 KW - Tamoxifen KW - 094ZI81Y45 KW - afimoxifene KW - 17197F0KYM KW - N-desmethyltamoxifen KW - OOJ759O35C KW - Index Medicus KW - Animals KW - Mice KW - Electrophoresis, Capillary -- methods KW - Female KW - Pregnancy KW - Tamoxifen -- analysis KW - Fetus -- chemistry KW - Tamoxifen -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71487631?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Electrophoresis&rft.atitle=Determination+of+tamoxifen+and+metabolites+in+mouse+fetal+tissue+using+nonaqueous+capillary+electrophoresis.&rft.au=Sanders%2C+J+M%3BCunningham%2C+M+L&rft.aulast=Sanders&rft.aufirst=J&rft.date=2002-02-01&rft.volume=23&rft.issue=3&rft.spage=502&rft.isbn=&rft.btitle=&rft.title=Electrophoresis&rft.issn=01730835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-25 N1 - Date created - 2002-02-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Autoantibodies against cytochrome P450s in sera of children treated with immunosuppressive drugs. AN - 71487394; 11876753 AB - Treatment with the immunosuppressive drugs cyclosporin and tacrolimus, the mainstays of anti-graft rejection and autoimmune disease therapy, is limited by their hepato- and nephrotoxicity. The metabolic conversion of these compounds to more easily excretable products is catalysed mainly by hepatic cytochrome P4503A4 (CYP3A4) but also involves extrahepatic CYP3A5 and other P450 forms. We set out to study whether or not exposure to cyclosporin and FK506 in children undergoing organ transplantation leads to formation of autoantibodies against P450s. Immunoblotting analysis revealed anti-CYP reactivity in 16% of children on CyA for anti-graft rejection or treatment of nephrosis (n = 67), 31% of kidney transplant patients switched from CyA to FK506 (n = 16), and 21% of kidney and or liver transplant patients on FK506 (n = 14). In contrast, the frequency of reactive immunoblots was only 8.5% among the normal paediatric controls (n = 25) and 7% among adult kidney transplant patients on CyA or FK506 (n = 30). The CYP2C9+ sera were able to immunoprecipitate in vitro translated CYP2C9 and the immunoblot reactivity showed striking correlation to peaks in the age at onset of drug exposure. Sera were isoform selective as evidenced from Western blotting using human liver microsomes and heterologously expressed human P450s. These findings suggest that anti-cytochrome P450 autoantibodies, identified on the basis of their specific binding in immunoblots, are significantly increased among children on immunosuppressive drugs and in some cases are associated with drug toxicity and organ rejection. JF - Clinical and experimental immunology AU - Lytton, S D AU - Berg, U AU - Nemeth, A AU - Ingelman-Sundberg, M AD - Division of Molecular Toxicology, Institute for Environmental Medicine, Karolinska Institute, and Department of Paediatrics, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden. lyttons@intra.nei.nih.gov Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 293 EP - 302 VL - 127 IS - 2 SN - 0009-9104, 0009-9104 KW - Autoantibodies KW - 0 KW - Autoantigens KW - Epitopes KW - Immunoglobulin G KW - Immunosuppressive Agents KW - Isoenzymes KW - Recombinant Fusion Proteins KW - Cyclosporine KW - 83HN0GTJ6D KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Steroid Hydroxylases KW - EC 1.14.- KW - CYP2C9 protein, human KW - EC 1.14.13.- KW - Cytochrome P-450 CYP2C9 KW - Cytochrome P-450 CYP2E1 KW - CYP3A4 protein, human KW - EC 1.14.13.67 KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP1A2 protein, human KW - CYP3A protein, human KW - CYP3A5 protein, human KW - Cytochrome P-450 CYP1A2 KW - Cytochrome P-450 CYP3A KW - Steroid 16-alpha-Hydroxylase KW - Azathioprine KW - MRK240IY2L KW - Prednisone KW - VB0R961HZT KW - Tacrolimus KW - WM0HAQ4WNM KW - Index Medicus KW - Humans KW - Child KW - Chemical and Drug Induced Liver Injury -- immunology KW - Mixed Function Oxygenases -- immunology KW - Infant KW - Antibody Specificity KW - Chemical and Drug Induced Liver Injury -- etiology KW - Cytochrome P-450 CYP2E1 -- immunology KW - Azathioprine -- administration & dosage KW - Adult KW - Kidney Diseases -- immunology KW - Adolescent KW - Prednisone -- administration & dosage KW - Male KW - Kidney Diseases -- chemically induced KW - Liver Transplantation -- immunology KW - Recombinant Fusion Proteins -- immunology KW - Cytochrome P-450 CYP1A2 -- immunology KW - Prednisone -- therapeutic use KW - Azathioprine -- therapeutic use KW - Kidney Transplantation -- immunology KW - Child, Preschool KW - Steroid Hydroxylases -- immunology KW - Drug Therapy, Combination KW - Postoperative Complications -- chemically induced KW - Blotting, Western KW - Liver Cirrhosis, Biliary -- immunology KW - Middle Aged KW - Epitopes -- immunology KW - Female KW - Tacrolimus -- adverse effects KW - Tacrolimus -- therapeutic use KW - Cyclosporine -- therapeutic use KW - Isoenzymes -- immunology KW - Autoantigens -- immunology KW - Autoantibodies -- immunology KW - Immunoglobulin G -- immunology KW - Tacrolimus -- administration & dosage KW - Graft Rejection -- prevention & control KW - Tacrolimus -- pharmacokinetics KW - Cyclosporine -- administration & dosage KW - Cyclosporine -- adverse effects KW - Cytochrome P-450 Enzyme System -- immunology KW - Graft Rejection -- immunology KW - Immunosuppressive Agents -- therapeutic use KW - Immunosuppressive Agents -- pharmacokinetics KW - Cyclosporine -- pharmacokinetics KW - Immunosuppressive Agents -- adverse effects KW - Immunosuppressive Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71487394?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+and+experimental+immunology&rft.atitle=Autoantibodies+against+cytochrome+P450s+in+sera+of+children+treated+with+immunosuppressive+drugs.&rft.au=Lytton%2C+S+D%3BBerg%2C+U%3BNemeth%2C+A%3BIngelman-Sundberg%2C+M&rft.aulast=Lytton&rft.aufirst=S&rft.date=2002-02-01&rft.volume=127&rft.issue=2&rft.spage=293&rft.isbn=&rft.btitle=&rft.title=Clinical+and+experimental+immunology&rft.issn=00099104&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-02 N1 - Date created - 2002-03-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Transplantation. 2000 May 27;69(10):2049-54 [10852595] J Pediatr Gastroenterol Nutr. 1999 Nov;29(5):551-5 [10554122] Nat Med. 2001 Mar;7(3):285-7 [11231620] Nature. 1970 Aug 15;227(5259):680-5 [5432063] J Biol Chem. 1976 Sep 10;251(17):5337-44 [821951] Drug Metab Dispos. 1989 Mar-Apr;17(2):197-207 [2565211] J Clin Endocrinol Metab. 1997 Mar;82(3):939-42 [9062510] Toxicology. 1997 Apr 11;119(1):37-43 [9129193] Annu Rev Pharmacol Toxicol. 1997;37:91-117 [9131248] J Clin Endocrinol Metab. 1997 May;82(5):1353-61 [9141515] Clin Exp Immunol. 1997 Jun;108(3):381-3 [9182879] Pharmacogenetics. 1997 Jun;7(3):181-6 [9241657] Clin Exp Pharmacol Physiol. 1997 Jul;24(7):465-70 [9248661] Int J Biochem Cell Biol. 1997 Jun;29(6):921-8 [9304807] Hepatology. 1997 Oct;26(4):1054-66 [9328334] Transplantation. 1997 Nov 15;64(9):1336-42 [9371677] Lancet. 1998 Feb 7;351(9100):409-13 [9482295] Pharmacol Rev. 1998 Mar;50(1):107-41 [9549760] Arch Toxicol. 1998 Apr;72(5):257-63 [9630010] J Pharm Sci. 1998 Nov;87(11):1322-30 [9811484] Immunol Today. 1998 Nov;19(11):514-9 [9818546] J Hepatol. 1998 Nov;29(5):819-25 [9833921] Pediatr Rev. 1998 Dec;19(12):423-8 [9849072] Mol Pharmacol. 1999 Feb;55(2):223-33 [9927612] J Hepatol. 1999 Feb;30(2):222-7 [10068099] J Hepatol. 1999 Jul;31(1):149-55 [10424295] Clin Pharmacol Ther. 1999 Jul;66(1):66-75 [10430111] Lancet. 1992 Mar 28;339(8796):770-3 [1347802] Arch Biochem Biophys. 1994 Jul;312(1):59-66 [8031147] J Biol Chem. 1994 Jul 15;269(28):18378-83 [8034584] Arch Biochem Biophys. 1994 Aug 1;312(2):436-46 [8037457] Toxicol Appl Pharmacol. 1994 Aug;127(2):222-32 [8048065] Ren Physiol Biochem. 1995 May-Jun;18(3):128-39 [7542793] Clin Biochem. 1995 Dec;28(6):547-59 [8595701] Mol Pharmacol. 1996 Feb;49(2):234-43 [8632755] Mol Pharmacol. 1996 Jul;50(1):52-9 [8700118] Mol Pharmacol. 1996 Aug;50(2):326-33 [8700140] Pediatr Clin North Am. 1997 Feb;44(1):55-77 [9057784] Clin Exp Immunol. 2000 Aug;121(2):179-80 [10970156] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Problem drinking and alcoholism: diagnosis and treatment. AN - 71477974; 11858627 AB - Alcoholism is one of the most common psychiatric disorders with a prevalence of 8 to 14 percent. This heritable disease is frequently accompanied by other substance abuse disorders (particularly nicotine), anxiety and mood disorders, and antisocial personality disorder. Although associated with considerable morbidity and mortality, alcoholism often goes unrecognized in a clinical or primary health care setting. Several brief screening instruments are available to quickly identify problem drinking, often a pre-alcoholism condition. Problem drinking can be successfully treated with brief intervention by primary care physicians. Alcohol addiction is a lifelong disease with a relapsing, remitting course. Because of the potentially serious implications of the diagnosis, assessment for alcoholism should be detailed. Alcoholism is treated by a variety of psychosocial methods with or without newly developed pharmacotherapies that improve relapse rates. Screening for problem drinking and alcoholism needs to become an integral part of the routine health screening questionnaire for adolescents and all adults, particularly women of child-bearing age, because of the risk of fetal alcohol syndrome. JF - American family physician AU - Enoch, Mary-Anne AU - Goldman, David AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-8110, USA. maenoch@niaaa.nih.gov Y1 - 2002/02/01/ PY - 2002 DA - 2002 Feb 01 SP - 441 EP - 448 VL - 65 IS - 3 SN - 0002-838X, 0002-838X KW - Abridged Index Medicus KW - Index Medicus KW - Mass Screening KW - Humans KW - Alcoholism -- diagnosis KW - Alcoholism -- therapy KW - Alcohol Drinking UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71477974?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+family+physician&rft.atitle=Problem+drinking+and+alcoholism%3A+diagnosis+and+treatment.&rft.au=Enoch%2C+Mary-Anne%3BGoldman%2C+David&rft.aulast=Enoch&rft.aufirst=Mary-Anne&rft.date=2002-02-01&rft.volume=65&rft.issue=3&rft.spage=441&rft.isbn=&rft.btitle=&rft.title=American+family+physician&rft.issn=0002838X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-06 N1 - Date created - 2002-02-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am Fam Physician. 2002 Jul 15;66(2):209 [12152956] Summary For Patients In: Am Fam Physician. 2002 Feb 1;65(3):449-50 [11858628] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ask the right questions and make good use of the answers: a response to Humphreys & Tucker. AN - 71473002; 11860381 JF - Addiction (Abingdon, England) AU - Perl, Harold I AU - Hilton, Michael E AD - Health Services Research Branch National Institute on Alcohol Abuse and Alcoholism 6000 Executive Blvd Suite 505, MSC 7003 Bethesda, MD 20892-7003 USA. hperl@willco.niaaa.nih.gov Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 134 EP - 6; discussion 138-40 VL - 97 IS - 2 SN - 0965-2140, 0965-2140 KW - Index Medicus KW - Humans KW - Evidence-Based Medicine KW - Alcoholism -- therapy KW - Research UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71473002?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addiction+%28Abingdon%2C+England%29&rft.atitle=Ask+the+right+questions+and+make+good+use+of+the+answers%3A+a+response+to+Humphreys+%26amp%3B+Tucker.&rft.au=Perl%2C+Harold+I%3BHilton%2C+Michael+E&rft.aulast=Perl&rft.aufirst=Harold&rft.date=2002-02-01&rft.volume=97&rft.issue=2&rft.spage=134&rft.isbn=&rft.btitle=&rft.title=Addiction+%28Abingdon%2C+England%29&rft.issn=09652140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-15 N1 - Date created - 2002-02-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Addiction. 2002 Feb;97(2):126-32 [11860378] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The exposure-time-response relationship between occupational asbestos exposure and lung cancer in two German case-control studies. AN - 71472201; 11813213 AB - Numerous studies have been carried out to evaluate the association between lung cancer and occupational asbestos exposure. However, the effects of timing of exposure have not been analyzed thoroughly. Two German case-control studies with data on occupational asbestos exposure histories have been pooled. Duration of work in potentially asbestos exposed jobs and two derived weighted exposure measures are analyzed together with time since last exposure. A spline function is used to model the effect of time since exposure. The odds ratios (OR) and corresponding 95% confidence intervals were 1.8 (1.2, 2.7) and 2.4 (1.7, 3.4) for subjects having worked for 3 to 7 years and 8 or more years, respectively, in a job with potential asbestos exposure compared to never-exposed. Based on an evaluation of time since last exposure, the OR decreased significantly to about one-half after more than 20 years since exposure ceased. Using a spline function, applied to workers' complete exposure histories, the effect of an increment of exposure is greatest 10-15 years after that exposure was received. In contrast to previous indications, the risk of lung cancer increases soon after asbestos exposure, with its maximum effect from 10 to 15 years after the exposure was received. JF - American journal of industrial medicine AU - Hauptmann, Michael AU - Pohlabeln, Hermann AU - Lubin, Jay H AU - Jöckel, Karl-Heinz AU - Ahrens, Wolfgang AU - Brüske-Hohlfeld, Irene AU - Wichmann, H -Erich AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7244, USA. hauptmann@nih.gov Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 89 EP - 97 VL - 41 IS - 2 SN - 0271-3586, 0271-3586 KW - Carcinogens KW - 0 KW - Asbestos KW - 1332-21-4 KW - Index Medicus KW - Odds Ratio KW - Humans KW - Germany -- epidemiology KW - Aged KW - Aged, 80 and over KW - Logistic Models KW - Risk Factors KW - Smoking Cessation KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Occupations -- statistics & numerical data KW - Time Factors KW - Male KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - Occupational Diseases -- etiology KW - Occupational Exposure -- adverse effects KW - Asbestos -- adverse effects KW - Occupational Diseases -- epidemiology KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71472201?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=The+exposure-time-response+relationship+between+occupational+asbestos+exposure+and+lung+cancer+in+two+German+case-control+studies.&rft.au=Hauptmann%2C+Michael%3BPohlabeln%2C+Hermann%3BLubin%2C+Jay+H%3BJ%C3%B6ckel%2C+Karl-Heinz%3BAhrens%2C+Wolfgang%3BBr%C3%BCske-Hohlfeld%2C+Irene%3BWichmann%2C+H+-Erich&rft.aulast=Hauptmann&rft.aufirst=Michael&rft.date=2002-02-01&rft.volume=41&rft.issue=2&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-22 N1 - Date created - 2002-01-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulatory effects of deoxycholic acid, a component of the anti-inflammatory traditional Chinese medicine Niuhuang, on human leukocyte response to chemoattractants. AN - 71467352; 11853704 AB - Niuhuang is a commonly used Chinese traditional medicine with immunoregulatory and anti-inflammatory properties. Deoxycholic acid (DCA) is a major active constituent of Niuhuang. The reaction of human leukocytes to chemoattractants is an important part of the host immune response and also plays a crucial role in the development of inflammation. We, therefore, investigated the in vitro effects of DCA on human monocyte and neutrophil responses to classic chemoattractants [fMet-Leu-Phe (fMLP), complement fraction 5a (C5a)], CC chemokine [monocyte chemoattractant protein-1 (MCP-1/CCL2)], and/or CXC chemokines [stromal cell-derived factor-1 (SDF-1alpha/CXCL12), interleukin-8 (IL-8/CXCL8)]. The results showed that DCA significantly inhibited fMLP-induced monocyte and neutrophil chemotaxis and calcium mobilization, and also blocked the binding of [3H]fMLP and anti-formyl peptide receptor (FPR) monoclonal antibodies (mAb) to the cells. The inhibitory effects of DCA on calcium mobilization and anti-FPR-mAb binding to the receptor could be abrogated by washing DCA out of the cell suspension, suggesting that DCA blocked fMLP receptors via a steric hindrance mechanism, not via receptor internalization. DCA had no significant inhibitory effects on MCP-1-, SDF-1alpha-, or C5a-induced monocyte function, or C5a- or IL-8-induced neutrophil function. Taken together, our experimental results suggest that blockade of fMLP receptors may contribute to the anti-inflammatory effects of traditional medicine containing DCA. JF - Biochemical pharmacology AU - Chen, Xin AU - Mellon, Richard Daniel AU - Yang, Lu AU - Dong, Huifang AU - Oppenheim, Joost J AU - Howard, Ola Mae Zack AD - The Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute-Frederick, Bldg. 560, Rm. 31-19, Frederick, MD 21702-1201, USA. Y1 - 2002/02/01/ PY - 2002 DA - 2002 Feb 01 SP - 533 EP - 541 VL - 63 IS - 3 SN - 0006-2952, 0006-2952 KW - Anti-Inflammatory Agents KW - 0 KW - Antibodies KW - Chemokines KW - Chemotactic Factors KW - Interleukin-8 KW - Receptors, Formyl Peptide KW - Receptors, Immunologic KW - Receptors, Interleukin-8A KW - Receptors, Interleukin-8B KW - Receptors, Peptide KW - Deoxycholic Acid KW - 005990WHZZ KW - Tritium KW - 10028-17-8 KW - N-Formylmethionine Leucyl-Phenylalanine KW - 59880-97-6 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Antibodies -- immunology KW - Drug Interactions KW - Receptors, Peptide -- metabolism KW - Receptors, Interleukin-8A -- metabolism KW - Cell Respiration -- drug effects KW - Humans KW - Receptors, Peptide -- immunology KW - Calcium -- metabolism KW - Receptors, Interleukin-8B -- immunology KW - Receptors, Immunologic -- immunology KW - Receptors, Interleukin-8A -- immunology KW - Chemokines -- pharmacology KW - Receptors, Immunologic -- metabolism KW - In Vitro Techniques KW - Medicine, Chinese Traditional KW - Interleukin-8 -- metabolism KW - Chemotactic Factors -- pharmacology KW - Receptors, Interleukin-8B -- metabolism KW - N-Formylmethionine Leucyl-Phenylalanine -- metabolism KW - Deoxycholic Acid -- pharmacology KW - Leukocytes -- physiology KW - Cell Movement -- drug effects KW - Leukocytes -- drug effects KW - Anti-Inflammatory Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71467352?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Regulatory+effects+of+deoxycholic+acid%2C+a+component+of+the+anti-inflammatory+traditional+Chinese+medicine+Niuhuang%2C+on+human+leukocyte+response+to+chemoattractants.&rft.au=Chen%2C+Xin%3BMellon%2C+Richard+Daniel%3BYang%2C+Lu%3BDong%2C+Huifang%3BOppenheim%2C+Joost+J%3BHoward%2C+Ola+Mae+Zack&rft.aulast=Chen&rft.aufirst=Xin&rft.date=2002-02-01&rft.volume=63&rft.issue=3&rft.spage=533&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-25 N1 - Date created - 2002-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phorbol diacetate potentiates na(+)-k(+) ATPase inhibition by a putative endogenous ligand, marinobufagenin. AN - 71463937; 11847201 AB - Several vasoconstrictor agents can regulate the phosphorylation status of the Na(+)-K(+) ATPase (NKA). We have recently demonstrated that mammalian tissues contain an endogenous bufadienolide, digitalis-like alpha(1)-NKA-selective ligand, marinobufagenin (MBG). Protein kinase C induces phosphorylation of the alpha(1)-NKA isoform, the major isoform in vascular smooth muscle, kidney, and heart cells. We hypothesized that protein kinase C-induced phosphorylation of NKA can potentiate the effect of endogenous digitalis-like ligands, and that such potentiation can occur in an NKA isoform-specific fashion. A protein kinase C activator, phorbol 12,13-diacetate (PDA, 50 nmol/L), induced phosphorylation of the alpha1-NKA from human mesenteric artery (HMA) sarcolemma and rat kidney but not that of the alpha(3)-NKA from rat fetal brain. In HMA sarcolemma, which predominantly contains alpha(1)-NKA, PDA (50 nmol/L) potentiated the NKA-inhibitory effect of MBG at the level of high-affinity binding sites (0.05 +/- 0.03 nmol/L versus 4.0 +/- 1.7 nmol/L, P<0.05). In contrast, PDA did not affect the NKA inhibition by ouabain, an alpha(3)-NKA ligand. In isolated endothelium-denuded HMA artery rings, 50 nmol/L PDA potentiated the MBG-induced vasoconstriction (EC(50), 17 +/- 6 nmol/L versus 150 +/- 40 nmol/L; P<0.01). Our results suggest that alpha(1)-isoform-specific NKA inhibition by the endogenous digitalis-like ligand, MBG, is substantially enhanced via NKA phosphorylation by protein kinase C. Thus, an interaction of protein kinase C-dependent phosphorylation and MBG on NKA activity may underlie the synergistic vasoactive effects of MBG and other endogenous vasoconstrictors in hypertension. JF - Hypertension (Dallas, Tex. : 1979) AU - Fedorova, Olga V AU - Dorofeeva, Natalia A AU - Lopatin, Denis A AU - Lakatta, Edward G AU - Bagrov, Alexei Y AD - Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 298 EP - 302 VL - 39 IS - 2 KW - Bufanolides KW - 0 KW - Enzyme Inhibitors KW - Phorbol Esters KW - phorbol-12,13-diacetate KW - 24928-15-2 KW - marinobufagenin KW - 470-42-8 KW - Ouabain KW - 5ACL011P69 KW - Sodium-Potassium-Exchanging ATPase KW - EC 3.6.3.9 KW - Index Medicus KW - Animals KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Brain -- drug effects KW - Humans KW - Kidney -- drug effects KW - Kidney -- enzymology KW - Rats KW - Brain -- enzymology KW - Sarcolemma -- enzymology KW - In Vitro Techniques KW - Brain -- embryology KW - Vasoconstriction -- drug effects KW - Middle Aged KW - Mesenteric Arteries -- enzymology KW - Drug Synergism KW - Sarcolemma -- drug effects KW - Ouabain -- pharmacology KW - Mesenteric Arteries -- physiology KW - Mesenteric Arteries -- drug effects KW - Male KW - Sodium-Potassium-Exchanging ATPase -- antagonists & inhibitors KW - Phorbol Esters -- pharmacology KW - Sodium-Potassium-Exchanging ATPase -- metabolism KW - Bufanolides -- pharmacology KW - Enzyme Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71463937?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hypertension+%28Dallas%2C+Tex.+%3A+1979%29&rft.atitle=Phorbol+diacetate+potentiates+na%28%2B%29-k%28%2B%29+ATPase+inhibition+by+a+putative+endogenous+ligand%2C+marinobufagenin.&rft.au=Fedorova%2C+Olga+V%3BDorofeeva%2C+Natalia+A%3BLopatin%2C+Denis+A%3BLakatta%2C+Edward+G%3BBagrov%2C+Alexei+Y&rft.aulast=Fedorova&rft.aufirst=Olga&rft.date=2002-02-01&rft.volume=39&rft.issue=2&rft.spage=298&rft.isbn=&rft.btitle=&rft.title=Hypertension+%28Dallas%2C+Tex.+%3A+1979%29&rft.issn=1524-4563&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-25 N1 - Date created - 2002-02-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conditional knockout of the Smad1 gene. AN - 71462229; 11857782 JF - Genesis (New York, N.Y. : 2000) AU - Huang, Shixia AU - Tang, Binwu AU - Usoskin, Dmitry AU - Lechleider, Robert J AU - Jamin, Soazik P AU - Li, Cuiling AU - Anzano, Mario A AU - Ebendal, Ted AU - Deng, Chuxia AU - Roberts, Anita B AD - Laboratory of Cell Regulation and Carcinogenesis, NCI, NIH, Bethesda, Maryland 20892-5055, USA. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 76 EP - 79 VL - 32 IS - 2 SN - 1526-954X, 1526-954X KW - DNA-Binding Proteins KW - 0 KW - Smad Proteins KW - Smad1 Protein KW - Smad1 protein, mouse KW - Trans-Activators KW - Index Medicus KW - Animals KW - Mice KW - Male KW - Female KW - Trans-Activators -- genetics KW - Mice, Knockout -- genetics KW - DNA-Binding Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71462229?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genesis+%28New+York%2C+N.Y.+%3A+2000%29&rft.atitle=Conditional+knockout+of+the+Smad1+gene.&rft.au=Huang%2C+Shixia%3BTang%2C+Binwu%3BUsoskin%2C+Dmitry%3BLechleider%2C+Robert+J%3BJamin%2C+Soazik+P%3BLi%2C+Cuiling%3BAnzano%2C+Mario+A%3BEbendal%2C+Ted%3BDeng%2C+Chuxia%3BRoberts%2C+Anita+B&rft.aulast=Huang&rft.aufirst=Shixia&rft.date=2002-02-01&rft.volume=32&rft.issue=2&rft.spage=76&rft.isbn=&rft.btitle=&rft.title=Genesis+%28New+York%2C+N.Y.+%3A+2000%29&rft.issn=1526954X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-27 N1 - Date created - 2002-02-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lithium protection against glutamate excitotoxicity in rat cerebral cortical neurons: involvement of NMDA receptor inhibition possibly by decreasing NR2B tyrosine phosphorylation. AN - 71458607; 11841566 AB - The therapeutic mechanisms of lithium for treating bipolar mood disorder remain poorly understood. Recent studies demonstrate that lithium has neuroprotective actions against a variety of insults. Here, we studied neuroprotective effects of lithium against excitotoxicity in cultured cerebral cortical neurons. Glutamate-induced excitotoxicity in cortical neurons was exclusively mediated by NMDA receptors. Pre-treatment of cortical neurons with LiCl time-dependently suppressed excitotoxicity with maximal protection after 6 days of pre-treatment. Significant protection was observed at the therapeutic and subtherapeutic concentration of 0.2-1.6 mm LiCl with almost complete protection at 1 mM. Neuroprotection was also elicited by valproate, another major mood-stabilizer. The neuroprotective effects of lithium coincided with inhibition of NMDA receptor-mediated calcium influx. Lithium pre-treatment did not alter total protein levels of NR1, NR2A and NR2B subunits of NMDA receptors. However, it did markedly reduce the level of NR2B phosphorylation at Tyr1472 and this was temporally associated with its neuroprotective effect. Because NR2B tyrosine phosphorylation has been positively correlated with NMDA receptor-mediated synaptic activity and excitotoxicity, the suppression of NR2B phosphorylation by lithium is likely to result in the inactivation of NMDA receptors and contributes to neuroprotection against excitotoxicity. This action could also be relevant to its clinical efficacy for bipolar patients. JF - Journal of neurochemistry AU - Hashimoto, Ryota AU - Hough, Christopher AU - Nakazawa, Takanobu AU - Yamamoto, Tadashi AU - Chuang, De-Maw AD - Section on Molecular Neurobiology, Mood and Anxiety Disorder Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1363, USA. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 589 EP - 597 VL - 80 IS - 4 SN - 0022-3042, 0022-3042 KW - Antimanic Agents KW - 0 KW - NR2B NMDA receptor KW - Receptors, N-Methyl-D-Aspartate KW - Glutamic Acid KW - 3KX376GY7L KW - Tyrosine KW - 42HK56048U KW - Valproic Acid KW - 614OI1Z5WI KW - Lithium KW - 9FN79X2M3F KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Antimanic Agents -- pharmacology KW - Ion Transport -- drug effects KW - Dose-Response Relationship, Drug KW - Cytoprotection -- drug effects KW - Phosphorylation -- drug effects KW - Valproic Acid -- pharmacology KW - Calcium -- metabolism KW - Cerebral Cortex KW - Rats KW - Cells, Cultured KW - Tyrosine -- metabolism KW - Time Factors KW - Cytoprotection -- physiology KW - Glutamic Acid -- toxicity KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Neurons -- cytology KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Lithium -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71458607?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Lithium+protection+against+glutamate+excitotoxicity+in+rat+cerebral+cortical+neurons%3A+involvement+of+NMDA+receptor+inhibition+possibly+by+decreasing+NR2B+tyrosine+phosphorylation.&rft.au=Hashimoto%2C+Ryota%3BHough%2C+Christopher%3BNakazawa%2C+Takanobu%3BYamamoto%2C+Tadashi%3BChuang%2C+De-Maw&rft.aulast=Hashimoto&rft.aufirst=Ryota&rft.date=2002-02-01&rft.volume=80&rft.issue=4&rft.spage=589&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-04 N1 - Date created - 2002-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of rituximab and chemotherapy in aggressive B-cell lymphoma: a preliminary report of dose-adjusted EPOCH-R. AN - 71452269; 11842388 AB - Accumulating evidence suggests that the ability to activate apoptotic pathways may be an important determinant of chemotherapy sensitivity and presents a potentially important new therapeutic strategy. Monoclonal antibodies against the CD20 antigen directly induce apoptosis and may serve to modulate the threshold for chemotherapy-induced apoptosis. Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA), a monoclonal antibody against CD20, was combined with dose-adjusted EPOCH (infusional etoposide/vincristine/doxorubicin/bolus cyclophosphamide/prednisone) chemotherapy and tested in 38 untreated or relapsed poor-prognosis aggressive lymphomas. Twenty-three patients were untreated. Of these patients, all had large B-cell histologies, a median age of 52 years, Eastern Cooperative Oncology Group performance status > or = 2 in 30%, and high-intermediate or high International Prognostic Index scores in 61%. Fifteen patients had relapsed or refractory lymphomas. These patients had received a median of two (range, one to four) prior regimens, 67% had aggressive histologies, and 60% had high-intermediate or high International Prognostic Index scores. Complete remissions were achieved in 85% and 64% of untreated and previously treated patients, respectively; additionally 42% of patients with disease refractory before therapy achieved complete remission. At a median follow-up of 12 months, progression-free and overall survival in the previously untreated group was 85% and 79%, respectively, and no patient in complete remission has relapsed. These results suggest that rituximab may modulate the sensitivity of B-cell lymphomas to chemotherapy. JF - Seminars in oncology AU - Wilson, Wyndham H AU - Gutierrez, Martin AU - O'Connor, Paula AU - Frankel, Stanley AU - Jaffe, Elaine AU - Chabner, Bruce A AU - Grossbard, Michael L AD - Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 41 EP - 47 VL - 29 IS - 1 Suppl 2 SN - 0093-7754, 0093-7754 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Murine-Derived KW - Antigens, CD20 KW - Rituximab KW - 4F4X42SYQ6 KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Humans KW - Vincristine -- administration & dosage KW - Aged KW - Doxorubicin -- administration & dosage KW - Etoposide -- administration & dosage KW - Adult KW - Middle Aged KW - Prednisone -- administration & dosage KW - Remission Induction KW - Lymphoma, B-Cell -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Antibodies, Monoclonal -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71452269?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+oncology&rft.atitle=The+role+of+rituximab+and+chemotherapy+in+aggressive+B-cell+lymphoma%3A+a+preliminary+report+of+dose-adjusted+EPOCH-R.&rft.au=Wilson%2C+Wyndham+H%3BGutierrez%2C+Martin%3BO%27Connor%2C+Paula%3BFrankel%2C+Stanley%3BJaffe%2C+Elaine%3BChabner%2C+Bruce+A%3BGrossbard%2C+Michael+L&rft.aulast=Wilson&rft.aufirst=Wyndham&rft.date=2002-02-01&rft.volume=29&rft.issue=1+Suppl+2&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology&rft.issn=00937754&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-07 N1 - Date created - 2002-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Modifying normal tissue damage postirradiation. Report of a workshop sponsored by the Radiation Research Program, National Cancer Institute, Bethesda, Maryland, September 6-8, 2000. AN - 71451974; 11835685 AB - Late effects that develop in normal tissues adjacent to the tumor site in the months to years after radiotherapy can reduce the quality of life of cancer survivors. They can be dose-limiting and debilitating or life-threatening. There is now evidence that some late effects may be preventable or partially reversible. A workshop, "Modifying Normal Tissue Damage Postirradiation", was sponsored by the Radiation Research Program of the National Cancer Institute to identify the current status of and research needs and opportunities in this area. Mechanistic, genetic and physiological studies of the development of late effects are needed and will provide a rational basis for development of treatments. Interdisciplinary teams will be needed to carry out this research, including pathologists, physiologists, geneticists, molecular biologists, experts in functional imaging, wound healing, burn injury, molecular biology, and medical oncology, in addition to radiation biologists, physicists and oncologists. The participants emphasized the need for developing and choosing appropriate models, and for radiation dose-response studies to determine whether interventions remain effective at the radiation doses used clinically. Both preclinical and clinical studies require long-term follow-up, and easier-to-use, more objective clinical scoring systems must be developed and standardized. New developments in biomedical imaging should provide useful tools in all these endeavors. The ultimate goals are to improve the quality of life and efficacy of treatment for cancer patients treated with radiotherapy. JF - Radiation research AU - Stone, Helen B AU - McBride, William H AU - Coleman, C Norman Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 204 EP - 223 VL - 157 IS - 2 KW - Chemokines KW - 0 KW - Cytokines KW - Growth Substances KW - Receptors, Growth Factor KW - Transforming Growth Factor beta KW - Endopeptidases KW - EC 3.4.- KW - Index Medicus KW - Space life sciences KW - Models, Animal KW - Hyperbaric Oxygenation KW - Animals KW - Radiation Injuries, Experimental -- pathology KW - Extracellular Matrix -- physiology KW - Cytokines -- therapeutic use KW - Receptors, Growth Factor -- physiology KW - Humans KW - Cytokines -- secretion KW - Radiation Tolerance KW - Quality of Life KW - Chemokines -- secretion KW - Growth Substances -- physiology KW - Endopeptidases -- physiology KW - Rats KW - Transforming Growth Factor beta -- physiology KW - Neoplasms -- radiotherapy KW - Mice, Inbred C3H KW - Radiation Injuries, Experimental -- etiology KW - Time Factors KW - Renin-Angiotensin System -- drug effects KW - Swine KW - Severity of Illness Index KW - Proto-Oncogenes -- radiation effects KW - Growth Substances -- therapeutic use KW - Diagnostic Imaging KW - Mice KW - Cell Hypoxia KW - Primates KW - Neoplasms -- complications KW - Radiation Injuries, Experimental -- therapy KW - Mice, Inbred C57BL KW - Renin-Angiotensin System -- physiology KW - Radiation Injuries -- prevention & control KW - Radiation Injuries -- therapy KW - Radiation Injuries -- pathology KW - Radiotherapy -- adverse effects KW - Radiation Injuries -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71451974?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Radiation+research&rft.atitle=Modifying+normal+tissue+damage+postirradiation.+Report+of+a+workshop+sponsored+by+the+Radiation+Research+Program%2C+National+Cancer+Institute%2C+Bethesda%2C+Maryland%2C+September+6-8%2C+2000.&rft.au=Stone%2C+Helen+B%3BMcBride%2C+William+H%3BColeman%2C+C+Norman&rft.aulast=Stone&rft.aufirst=Helen&rft.date=2002-02-01&rft.volume=157&rft.issue=2&rft.spage=204&rft.isbn=&rft.btitle=&rft.title=Radiation+research&rft.issn=00337587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-13 N1 - Date created - 2002-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagenesis by O(6)-[4-oxo-4-(3-pyridyl)butyl]guanine in Escherichia coli and human cells. AN - 71448635; 11849042 AB - Site-specific mutagenesis by O(6)-[4-oxo-4-(3-pyridyl)butyl]guanine (O(6)-pobGua), a product of DNA pyridyloxobutylation by metabolites of the tobacco-specific nitrosamines N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), was studied in Escherichia coli strain DH10B and human kidney cells (293) when the modified base was incorporated in either a double-stranded or a gapped shuttle vector. In the repair-competent E. coli strain, less than 3% of the colonies produced by double-stranded vectors harboring the modified base were mutant whereas 96% were mutant when DH10B cells were transformed with modified gapped vectors. By contrast, transformation of DH10B cells with plasmids derived from O(6)-pobGua-containing double-stranded and gapped vectors previously replicated in 293 cells produced 7 and 16% mutant colonies, respectively. These percentages increased to 42 and 82%, respectively, when the 293 cells were pretreated with O(6)-benzylguanine to inactivate the O(6)-alkylguanine-DNA alkyltransferase protein. These findings confirm that the adduct is readily repaired by the human O(6)-alkylguanine-DNA alkyltransferase in both double-stranded and gapped vectors and suggest that it is also highly mutagenic in both human cells and E. coli. In the E. coli strain, the adduct produced exclusively G --> A transition mutations although in human 293 cells it also produced G --> T transversions and more complex mutations in addition to G --> A transitions. These data suggest that O(6)-[4-oxo-4-(3-pyridyl)butyl]guanine can contribute significantly to the mutagenic risk posed by exposure to both NNN and NNK in tobacco smoke. JF - Chemical research in toxicology AU - Pauly, Gary T AU - Peterson, Lisa A AU - Moschel, Robert C AD - Chemistry of Carcinogenesis Laboratory, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 165 EP - 169 VL - 15 IS - 2 SN - 0893-228X, 0893-228X KW - DNA Adducts KW - 0 KW - Mutagens KW - O(6)-benzyl-8-oxoguanine KW - Guanine KW - 5Z93L87A1R KW - Index Medicus KW - Kidney -- metabolism KW - Mutagenesis, Site-Directed -- drug effects KW - Kidney -- embryology KW - Kidney -- cytology KW - DNA Repair -- drug effects KW - Cell Line KW - Guanine -- toxicity KW - DNA Adducts -- toxicity KW - Mutagens -- metabolism KW - Escherichia coli -- drug effects KW - Mutagens -- toxicity KW - Escherichia coli -- genetics KW - Guanine -- analogs & derivatives KW - Guanine -- metabolism KW - DNA Adducts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71448635?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Mutagenesis+by+O%286%29-%5B4-oxo-4-%283-pyridyl%29butyl%5Dguanine+in+Escherichia+coli+and+human+cells.&rft.au=Pauly%2C+Gary+T%3BPeterson%2C+Lisa+A%3BMoschel%2C+Robert+C&rft.aulast=Pauly&rft.aufirst=Gary&rft.date=2002-02-01&rft.volume=15&rft.issue=2&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-23 N1 - Date created - 2002-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mapping the transcription and replication promoters of respiratory syncytial virus. AN - 71445702; 11799161 AB - An important, unresolved issue in mononegavirus biology is whether or not transcription is initiated by the same promoter as RNA replication. In this study, residues important for respiratory syncytial virus (RSV) transcription and RNA replication were identified by subjecting the first 26 nucleotides of genome RNA to saturation mutagenesis. This analysis was performed using a genome analog that allowed transcription and RNA replication to be dissociated from each other and monitored as independent events in an intracellular assay. This analysis showed that nucleotides 3C, 5C, 8U, 9U, 10U, and 11U were important for transcription and RNA replication. Additional nucleotides (1U, 2G, 6U, and 7U) were important for RNA replication, but not transcription. At position 4, G versus C or U augmented transcription and decreased replication, showing that the naturally occurring assignments in the genomic (4G) and antigenomic (4U) promoters are optimal for transcription and RNA replication, respectively. These data show that RSV transcription and RNA replication each involve a cis-acting signal at the very 3" end of the genome. This signal appears to contain a minimum, common element that functions in both transcription and RNA replication, defined by those substitutions that had similar effects on the two processes. Apart from these common nucleotides, other positions were involved in RNA replication but not transcription or had different effects on the two processes. This indicates that the promoters for transcription and replication involve overlapping sets of nucleotides at the very 3" end of the genome and provides evidence that the nucleotide preferences for the two processes are not identical. JF - Journal of virology AU - Fearns, Rachel AU - Peeples, Mark E AU - Collins, Peter L AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0720, USA. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 1663 EP - 1672 VL - 76 IS - 4 SN - 0022-538X, 0022-538X KW - 3' Untranslated Regions KW - 0 KW - RNA, Viral KW - Index Medicus KW - Base Sequence KW - Blotting, Northern KW - Transfection KW - Plasmids -- genetics KW - Humans KW - Molecular Sequence Data KW - Genome, Viral KW - RNA, Viral -- genetics KW - 3' Untranslated Regions -- genetics KW - Cell Line KW - Mutagenesis KW - Virus Replication KW - Respiratory Syncytial Virus, Human -- genetics KW - Respiratory Syncytial Virus, Human -- physiology KW - Transcription, Genetic KW - Promoter Regions, Genetic -- genetics KW - Respiratory Syncytial Virus, Human -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71445702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Mapping+the+transcription+and+replication+promoters+of+respiratory+syncytial+virus.&rft.au=Fearns%2C+Rachel%3BPeeples%2C+Mark+E%3BCollins%2C+Peter+L&rft.aulast=Fearns&rft.aufirst=Rachel&rft.date=2002-02-01&rft.volume=76&rft.issue=4&rft.spage=1663&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-22 N1 - Date created - 2002-01-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1990 Jan;64(1):222-30 [1688383] J Virol. 2000 Jan;74(1):74-82 [10590093] Virology. 1991 Dec;185(2):615-24 [1840712] Virology. 1993 Jan;192(1):254-63 [8390755] Virology. 1993 Jul;195(1):252-6 [8317100] J Virol. 1995 Sep;69(9):5677-86 [7637014] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):81-5 [8552680] J Virol. 1996 Aug;70(8):5075-82 [8764015] J Virol. 1996 Oct;70(10):6892-901 [8794332] Virology. 1996 Nov 15;225(2):419-22 [8918930] J Virol. 1997 Feb;71(2):1466-75 [8995672] J Virol. 1997 Mar;71(3):2127-37 [9032346] Vaccine. 1996 Dec;14(17-18):1637-46 [9032893] J Mol Biol. 1997 May 30;269(1):41-51 [9192999] Virology. 1997 Sep 15;236(1):188-201 [9299631] J Virol. 1997 Nov;71(11):8718-25 [9343230] J Virol. 1997 Dec;71(12):9849-54 [9371659] Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13961-6 [9391135] J Virol. 1998 Jan;72(1):520-6 [9420254] J Virol. 1998 Feb;72(2):1452-61 [9445048] J Mol Biol. 1998 Sep 4;281(5):777-92 [9719634] Virology. 1998 Nov 10;251(1):206-14 [9813216] J Virol. 1999 Jan;73(1):251-9 [9847328] J Virol. 1999 Jan;73(1):297-306 [9847333] J Virol. 1999 Jan;73(1):444-52 [9847350] Nature. 1999 May 6;399(6731):80-3 [10331394] J Virol. 1999 Jul;73(7):5852-64 [10364337] J Virol. 1999 Oct;73(10):8384-92 [10482589] Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11259-64 [10500164] J Virol. 2000 Jan;74(1):146-55 [10590101] Curr Opin Struct Biol. 2000 Feb;10(1):117-23 [10679468] Virology. 2000 Mar 30;269(1):201-11 [10725212] J Virol. 2000 Jul;74(13):6006-14 [10846082] J Virol. 2001 Jul;75(14):6265-72 [11413292] Cell. 1981 Feb;23(2):477-84 [6258804] Cell. 1982 Dec;31(3 Pt 2):635-42 [6297777] Cell. 1983 Feb;32(2):559-67 [6297799] Proc Natl Acad Sci U S A. 1986 Nov;83(21):8122-6 [3095828] Nucleic Acids Res. 1987 Jul 10;15(13):5413-32 [3299271] J Virol. 1989 May;63(5):1951-8 [2539496] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9663-7 [1946383] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High extracellular gamma-aminobutyric acid protects cultured neurons against damage induced by the accumulation of endogenous extracellular glutamate. AN - 71440116; 11813246 AB - The glutamate uptake inhibitor L-trans-2,4-pyrrolidine-dicarboxylate (PDC) induces glutamate accumulation and neuronal damage in cultured cells. We have used dissociated cortical cells in culture to study whether the toxicity induced by inhibiting glutamate uptake with PDC could be blocked by the simultaneous inhibition of gamma-aminobutyric acid (GABA) uptake, because both types of transporters are affected during an ischemic event. After 6 hr of exposure to 100 microM GABA or to four different GABA uptake inhibitors, the concentration of extracellular GABA was augmented from the basal 2 microM value to about 25 microM and 5 microM, respectively. These increases, however, did not result in protection against the neuronal damage induced by the accumulation of extracellular glutamate because of the simultaneous exposure to PDC. In contrast, when 100 microM GABA and an inhibitor of GABA uptake were added, after 6 hr the concentrations of GABA reached 50 microM, and neurons were protected from PDC-induced toxicity. The addition of the GABA(A) and GABA(B) receptor agonists muscimol and baclofen also partially protected against PDC-induced damage. The results suggest that the excitotoxic damage resulting from chronic gradual elevation of extracellular glutamate may be prevented by high concentrations of extracellular GABA, an effect mediated by activation of GABA(A) and GABA(B) receptors. Copyright 2002 Wiley-Liss, Inc. JF - Journal of neuroscience research AU - Velasco, Iván AU - Tapia, Ricardo AD - Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México DF, México. velascoi@ninds.nih.gov Y1 - 2002/02/01/ PY - 2002 DA - 2002 Feb 01 SP - 406 EP - 410 VL - 67 IS - 3 SN - 0360-4012, 0360-4012 KW - Dicarboxylic Acids KW - 0 KW - GABA Agonists KW - GABA-A Receptor Agonists KW - GABA-B Receptor Agonists KW - Neurotransmitter Uptake Inhibitors KW - Pyrrolidines KW - Glutamic Acid KW - 3KX376GY7L KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - pyrrolidine-2,4-dicarboxylic acid KW - 99319-03-6 KW - Index Medicus KW - Rats KW - Dicarboxylic Acids -- toxicity KW - Animals KW - GABA Agonists -- pharmacology KW - Cell Survival -- drug effects KW - Extracellular Space -- metabolism KW - Cells, Cultured KW - Neurotransmitter Uptake Inhibitors -- pharmacology KW - Rats, Wistar KW - Pyrrolidines -- toxicity KW - Glutamic Acid -- toxicity KW - Neurons -- metabolism KW - Glutamic Acid -- metabolism KW - gamma-Aminobutyric Acid -- pharmacology KW - Neurons -- drug effects KW - Neurons -- cytology KW - gamma-Aminobutyric Acid -- metabolism KW - Cytoprotection -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71440116?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuroscience+research&rft.atitle=High+extracellular+gamma-aminobutyric+acid+protects+cultured+neurons+against+damage+induced+by+the+accumulation+of+endogenous+extracellular+glutamate.&rft.au=Velasco%2C+Iv%C3%A1n%3BTapia%2C+Ricardo&rft.aulast=Velasco&rft.aufirst=Iv%C3%A1n&rft.date=2002-02-01&rft.volume=67&rft.issue=3&rft.spage=406&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroscience+research&rft.issn=03604012&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-25 N1 - Date created - 2002-01-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Distinct role for microglia in rotenone-induced degeneration of dopaminergic neurons. AN - 71437343; 11826108 AB - Increasing evidence has suggested an important role for environmental factors such as exposure to pesticides in the pathogenesis of Parkinson's disease. In experimental animals the exposure to a common herbicide, rotenone, induces features of parkinsonism; mechanistically, rotenone-induced destruction of dopaminergic neurons has been attributed to its inhibition of the activity of neuronal mitochondrial complex I. However, the role of microglia, the resident brain immune cells in rotenone-induced neurodegeneration, has not been reported. Using primary neuron-enriched and neuron/glia cultures from the rat mesencephalon, we discovered an extraordinary feature for rotenone-induced degeneration of cultured dopaminergic neurons. Although little neurotoxicity was detected in neuron-enriched cultures after treatment for 8 d with up to 20 nm rotenone, significant and selective dopaminergic neurodegeneration was observed in neuron/glia cultures 2 d after treatment with 20 nm rotenone or 8 d after treatment with 1 nm rotenone. The greatly enhanced neurodegenerative ability of rotenone was attributed to the presence of glia, especially microglia, because the addition of microglia to neuron-enriched cultures markedly increased their susceptibility to rotenone. Mechanistically, rotenone stimulated the release of superoxide from microglia that was attenuated by inhibitors of NADPH oxidase. Furthermore, inhibition of NADPH oxidase or scavenging of superoxide significantly reduced the rotenone-induced neurotoxicity. This is the first report demonstrating that microglia play a pivotal role in rotenone-induced degeneration of dopaminergic neurons. The results of this study should advance our understanding of the mechanism of action for pesticides in the pathogenesis of Parkinson's disease. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Gao, Hui-Ming AU - Hong, Jau-Shyong AU - Zhang, Wanqin AU - Liu, Bin AD - Neuropharmacology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/02/01/ PY - 2002 DA - 2002 Feb 01 SP - 782 EP - 790 VL - 22 IS - 3 KW - Uncoupling Agents KW - 0 KW - Rotenone KW - 03L9OT429T KW - Superoxides KW - 11062-77-4 KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - NADPH Oxidase KW - EC 1.6.3.1 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - NADPH Oxidase -- metabolism KW - Animals KW - Coculture Techniques KW - Dose-Response Relationship, Drug KW - Humans KW - gamma-Aminobutyric Acid -- pharmacokinetics KW - Rats KW - Uncoupling Agents -- toxicity KW - Rats, Inbred F344 KW - Superoxides -- metabolism KW - Neutrophils KW - Monocytes -- metabolism KW - Time Factors KW - Male KW - Parkinson Disease -- etiology KW - Rotenone -- toxicity KW - Mesencephalon -- drug effects KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Neurons -- cytology KW - Microglia -- cytology KW - Dopamine -- pharmacokinetics KW - Dopamine -- metabolism KW - Mesencephalon -- embryology KW - Mesencephalon -- cytology KW - Microglia -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71437343?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Distinct+role+for+microglia+in+rotenone-induced+degeneration+of+dopaminergic+neurons.&rft.au=Gao%2C+Hui-Ming%3BHong%2C+Jau-Shyong%3BZhang%2C+Wanqin%3BLiu%2C+Bin&rft.aulast=Gao&rft.aufirst=Hui-Ming&rft.date=2002-02-01&rft.volume=22&rft.issue=3&rft.spage=782&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-27 N1 - Date created - 2002-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of interferon alfa signaling components in human alcoholic liver disease. AN - 71436759; 11826419 AB - Interferon alfa (IFN-alpha) is currently the only well-established therapy for viral hepatitis. However, its effectiveness is much reduced (<10%) in alcoholic patients. The mechanism underlying this resistance is not fully understood. In this study, we examined the expression of IFN-alpha signaling components and its inhibitory factors in 9 alcoholic liver disease (ALD) and 8 healthy control liver tissues. In comparison with normal control livers, expression of IFN-beta, IFN-alpha receptor 1/2, Jak1, and Tyk2 remained unchanged in ALD livers, whereas expression of IFN-alpha, signal transducer and activator of transcription factor 1 (STAT1), and p48 were up-regulated and expression of STAT2 was down-regulated. Expression of antiviral MxA a karyophilic 75 kd protein induced by IFN in mouse cells carrying the influenza virus resistance allele Mx(+) and 2'-5' oligoadenylate synthetase (OAS) proteins was not regulated, whereas expression of double-stranded RNA-activated protein kinase (PKR) was decreased by 55% in ALD livers. Three families of inhibitory factors for the JAK-STAT signaling pathway were examined in ALD livers. Members of the suppressor of cytokine signaling (SOCS) family, including SOCS 1, 2, 3, and CIS, and the protein tyrosine phosphatases, including Shp-1, Shp-2, and CD45, were not up-regulated in ALD livers, whereas the phosphorylation of and protein levels of p42/44 mitogen-activated protein kinase (p42/44MAP kinase) were increased about 3.9- and 3.2-fold in ALD livers in comparison with normal control livers, respectively. In conclusion, these findings suggest that chronic alcohol consumption down-regulates STAT2 and PKR, but up-regulates p42/44 mitogen-activated protein kinase (p42/44MAP kinase), which may cause down-regulation of IFN-alpha signaling in the liver of ALD patients. JF - Hepatology (Baltimore, Md.) AU - Nguyen, Van-Anh AU - Gao, Bin AD - Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 425 EP - 432 VL - 35 IS - 2 SN - 0270-9139, 0270-9139 KW - Carrier Proteins KW - 0 KW - DNA-Binding Proteins KW - Interferon-alpha KW - Intracellular Signaling Peptides and Proteins KW - MX1 protein, human KW - Membrane Proteins KW - Mx1 protein, mouse KW - Myxovirus Resistance Proteins KW - Proteins KW - Receptors, Interferon KW - Repressor Proteins KW - SOCS1 protein, human KW - SOCS2 protein, human KW - SOCS3 protein, human KW - STAT1 Transcription Factor KW - STAT1 protein, human KW - Socs1 protein, mouse KW - Socs2 protein, mouse KW - Socs3 protein, mouse KW - Suppressor of Cytokine Signaling 1 Protein KW - Suppressor of Cytokine Signaling 3 Protein KW - Suppressor of Cytokine Signaling Proteins KW - Trans-Activators KW - Transcription Factors KW - Receptor, Interferon alpha-beta KW - 156986-95-7 KW - Interferon-beta KW - 77238-31-4 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - JAK1 protein, human KW - EC 2.7.10.2 KW - Jak1 protein, mouse KW - Janus Kinase 1 KW - eIF-2 Kinase KW - EC 2.7.11.1 KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - Mitogen-Activated Protein Kinases KW - 2',5'-Oligoadenylate Synthetase KW - EC 2.7.7.84 KW - Protein Tyrosine Phosphatases KW - EC 3.1.3.48 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Trans-Activators -- metabolism KW - Protein Tyrosine Phosphatases -- metabolism KW - Humans KW - Liver -- metabolism KW - Phosphorylation KW - 2',5'-Oligoadenylate Synthetase -- metabolism KW - DNA-Binding Proteins -- metabolism KW - Reference Values KW - Carrier Proteins -- metabolism KW - Mitogen-Activated Protein Kinases -- metabolism KW - Protein-Tyrosine Kinases -- metabolism KW - Proteins -- metabolism KW - Interferon-beta -- metabolism KW - eIF-2 Kinase -- metabolism KW - Mitogen-Activated Protein Kinase 1 -- metabolism KW - Receptors, Interferon -- metabolism KW - Signal Transduction -- physiology KW - Interferon-alpha -- metabolism KW - Liver Diseases, Alcoholic -- physiopathology KW - Interferon-alpha -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71436759?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Expression+of+interferon+alfa+signaling+components+in+human+alcoholic+liver+disease.&rft.au=Nguyen%2C+Van-Anh%3BGao%2C+Bin&rft.aulast=Nguyen&rft.aufirst=Van-Anh&rft.date=2002-02-01&rft.volume=35&rft.issue=2&rft.spage=425&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=02709139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-28 N1 - Date created - 2002-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Matrix metalloproteinase-9 undergoes expression and activation during dendritic remodeling in adult hippocampus. AN - 71432963; 11826121 AB - Neurons of adult brain are able to remodel their synaptic connections in response to various stimuli. Modifications of the peridendritic environment, including the extracellular matrix, are likely to play a role during synapse remodeling. Proteolytic disassembly of ECM is a complex process using the regulated actions of specific extracellular proteinases. One of best-characterized families of matrix-modifying enzymes is the matrix metalloproteinase (MMP) family. Here, we describe changes in the expression and function of two well known MMPs, MMP-9 and MMP-2, in adult rat brain before and after systemic administration of the glutamate receptor agonist kainate. Kainate application results in enhanced synaptic transmission and seizures followed by selective tissue remodeling, primarily in hippocampal dentate gyrus. MMP-9 but not MMP-2 was highly expressed by neurons in normal adult rat brain. MMP-9 protein was localized in neuronal cell bodies and dendrites. Kainate upregulated the level of MMP-9 mRNA and protein within hours after drug administration. This was followed several hours later by MMP-9 enzymatic activation. Within hippocampus, MMP-9 mRNA and activity were increased selectively in dentate gyrus, including its dendritic layer. In addition, MMP-9 mRNA levels decreased in areas undergoing neuronal cell loss. This unique spatiotemporal pattern of MMP-9 expression suggests its involvement in activity-dependent remodeling of dendritic architecture with possible effects on synaptic physiology. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Szklarczyk, Arek AU - Lapinska, Joanna AU - Rylski, Marcin AU - McKay, Ronald D G AU - Kaczmarek, Leszek AD - Laboratory of Molecular Neurobiology, Nencki Institute, PL-02-093 Warsaw, Poland. szklarca@ninds.nih.gov Y1 - 2002/02/01/ PY - 2002 DA - 2002 Feb 01 SP - 920 EP - 930 VL - 22 IS - 3 KW - Excitatory Amino Acid Agonists KW - 0 KW - RNA, Messenger KW - Matrix Metalloproteinase 2 KW - EC 3.4.24.24 KW - Matrix Metalloproteinase 9 KW - EC 3.4.24.35 KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Seizures -- chemically induced KW - Animals KW - Extracellular Matrix -- metabolism KW - Neurons -- drug effects KW - Enzyme Activation -- physiology KW - Neuronal Plasticity -- physiology KW - Organ Specificity KW - Reverse Transcriptase Polymerase Chain Reaction KW - Matrix Metalloproteinase 2 -- metabolism KW - Rats KW - In Situ Hybridization KW - RNA, Messenger -- metabolism KW - Neurons -- cytology KW - Matrix Metalloproteinase 2 -- genetics KW - Rats, Wistar KW - Enzyme Activation -- drug effects KW - Neurons -- enzymology KW - Seizures -- metabolism KW - Immunohistochemistry KW - Male KW - Matrix Metalloproteinase 9 -- metabolism KW - Dendrites -- enzymology KW - Hippocampus -- cytology KW - Matrix Metalloproteinase 9 -- genetics KW - Hippocampus -- enzymology KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71432963?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Matrix+metalloproteinase-9+undergoes+expression+and+activation+during+dendritic+remodeling+in+adult+hippocampus.&rft.au=Szklarczyk%2C+Arek%3BLapinska%2C+Joanna%3BRylski%2C+Marcin%3BMcKay%2C+Ronald+D+G%3BKaczmarek%2C+Leszek&rft.aulast=Szklarczyk&rft.aufirst=Arek&rft.date=2002-02-01&rft.volume=22&rft.issue=3&rft.spage=920&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-27 N1 - Date created - 2002-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protection against acetaminophen-induced liver injury and lethality by interleukin 10: role of inducible nitric oxide synthase. AN - 71430674; 11826401 AB - Mechanistic study of idiosyncratic drug-induced hepatitis (DIH) continues to be a challenging problem because of the lack of animal models. The inability to produce this type of hepatotoxicity in animals, and its relative rarity in humans, may be linked to the production of anti-inflammatory factors that prevent drug-protein adducts from causing liver injury by immune and nonimmune mechanisms. We tested this hypothesis by using a model of acetaminophen (APAP)-induced liver injury in mice. After APAP treatment, a significant increase was observed in serum levels of interleukin (IL)-4, IL-10, and IL-13, cytokines that regulate inflammatory mediator production and cell-mediated autoimmunity. When IL-10 knockout (KO) mice were treated with APAP, most of these mice died within 24 to 48 hours from liver injury. This increased susceptibility to APAP-induced liver injury appeared to correlate with an elevated expression of liver proinflammatory cytokines, tumor necrosis factor (TNF)-alpha, and IL-1, as well as inducible nitric oxide synthase (iNOS). In this regard, mice lacking both IL-10 and iNOS genes were protected from APAP-induced liver injury and lethality when compared with IL-10 KO mice. All strains, including wild-type animals, generated similar amounts of liver APAP-protein adducts, indicating that the increased susceptibility of IL-10 KO mice to APAP hepatotoxicity was not caused by an enhanced formation of APAP-protein adducts. In conclusion, these findings suggest that an important feature of the normal response to drug-induced liver injury may be the increased expression of anti-inflammatory factors such as IL-10. Certain polymorphisms of these factors may have a role in determining the susceptibility of individuals to idiosyncratic DIH. JF - Hepatology (Baltimore, Md.) AU - Bourdi, Mohammed AU - Masubuchi, Yasuhiro AU - Reilly, Timothy P AU - Amouzadeh, Hamid R AU - Martin, Jackie L AU - George, John W AU - Shah, Anjali G AU - Pohl, Lance R AD - Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1760, USA. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 289 EP - 298 VL - 35 IS - 2 SN - 0270-9139, 0270-9139 KW - Cytokines KW - 0 KW - Inflammation Mediators KW - Interleukin-10 KW - 130068-27-8 KW - Nitric Oxide KW - 31C4KY9ESH KW - Acetaminophen KW - 362O9ITL9D KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Nitric Oxide Synthase Type II KW - Nos2 protein, mouse KW - Index Medicus KW - Cytokines -- blood KW - Animals KW - Inflammation Mediators -- blood KW - Mice, Knockout -- genetics KW - Mice, Inbred C57BL KW - Drug Resistance KW - Cytokines -- physiology KW - Nitric Oxide -- physiology KW - Mice KW - Male KW - Nitric Oxide Synthase -- genetics KW - Chemical and Drug Induced Liver Injury KW - Nitric Oxide Synthase -- physiology KW - Liver Diseases -- mortality KW - Interleukin-10 -- genetics KW - Liver Diseases -- prevention & control KW - Interleukin-10 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71430674?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Protection+against+acetaminophen-induced+liver+injury+and+lethality+by+interleukin+10%3A+role+of+inducible+nitric+oxide+synthase.&rft.au=Bourdi%2C+Mohammed%3BMasubuchi%2C+Yasuhiro%3BReilly%2C+Timothy+P%3BAmouzadeh%2C+Hamid+R%3BMartin%2C+Jackie+L%3BGeorge%2C+John+W%3BShah%2C+Anjali+G%3BPohl%2C+Lance+R&rft.aulast=Bourdi&rft.aufirst=Mohammed&rft.date=2002-02-01&rft.volume=35&rft.issue=2&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=02709139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-28 N1 - Date created - 2002-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Brain and body hyperthermia associated with heroin self-administration in rats. AN - 71429541; 11826136 AB - Intravenous heroin self-administration in trained rats was accompanied by robust brain hyperthermia (+2.0-2.5 degrees C); parallel changes were found in the dorsal and ventral striatum, mediodorsal thalamus, and deep temporal muscle. Temperature began to increase at variable latency after a signal of drug availability, increased reliably (approximately 0.4 degrees C) before the first lever press for heroin, increased further (approximately 1.2 degrees C) after the first heroin injection, and rose more slowly after the second and third injections to stabilize at an elevated plateau (39-40 degrees C) for the remainder of the session. Brain and body temperature declined slowly when drug self-administration was terminated; naloxone precipitated a much more rapid decrease to baseline levels. Changes in temperature were similar across repeated daily sessions, except for the increase associated with the first self-administration of each session, which had progressively shorter latency and greater acceleration. Despite consistent biphasic fluctuations in movement activity associated with heroin self-administrations (gradual increase preceding the lever press, followed by an abrupt hypodynamia after drug infusion), mean brain temperature was very stable at an elevated plateau. Only mean muscle temperature showed evidence of biphasic fluctuations (+/-0.2 degrees C) that were time locked to and correlated with lever pressing and associated movements. Drug- and behavior-related changes in brain temperature thus appear to reflect some form of neuronal activation, and, because temperature is a factor capable of affecting numerous neural functions, it may be an important variable in the control of behavior by drugs of abuse. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Kiyatkin, Eugene A AU - Wise, Roy A AD - Behavioral Neuroscience Branch, National Institute on Drug Abuse-Intramural Research Program, Baltimore, Maryland 21224, USA. ekiyatkin@intra.nida.nih.gov Y1 - 2002/02/01/ PY - 2002 DA - 2002 Feb 01 SP - 1072 EP - 1080 VL - 22 IS - 3 KW - Naloxone KW - 36B82AMQ7N KW - Heroin KW - 70D95007SX KW - Index Medicus KW - Animals KW - Naloxone -- administration & dosage KW - Reaction Time -- drug effects KW - Rats, Long-Evans KW - Injections, Intravenous KW - Temporal Muscle -- physiopathology KW - Thalamus -- drug effects KW - Rats KW - Behavior, Animal -- drug effects KW - Corpus Striatum -- physiopathology KW - Self Administration KW - Corpus Striatum -- drug effects KW - Thalamus -- physiopathology KW - Temporal Muscle -- drug effects KW - Male KW - Brain -- physiopathology KW - Fever -- etiology KW - Heroin Dependence -- physiopathology KW - Brain -- drug effects KW - Fever -- physiopathology KW - Heroin Dependence -- complications KW - Heroin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71429541?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Brain+and+body+hyperthermia+associated+with+heroin+self-administration+in+rats.&rft.au=Kiyatkin%2C+Eugene+A%3BWise%2C+Roy+A&rft.aulast=Kiyatkin&rft.aufirst=Eugene&rft.date=2002-02-01&rft.volume=22&rft.issue=3&rft.spage=1072&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-27 N1 - Date created - 2002-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 5'-OH-thalidomide, a metabolite of thalidomide, inhibits angiogenesis. AN - 71423050; 11805730 AB - Despite its known teratogenic effects, thalidomide has been used to treat a variety of diseases ranging from alleviation of autoimmune disorders to prevention of metastasis of cancers. The exact method of action of thalidomide and its derivatives is still under investigation. Thalidomide undergoes very little metabolism by the cytochrome P 450 system in vitro, but at least two hydroxylated metabolites have been found in humans. The two metabolites are 5-hydroxythalidomide, formed by hydroxylation of the phthalimide ring, possibly via arene oxides, and 5'-hydroxythalidomide, formed by hydroxylation of the glutarimide ring, leading to diastereomeric products. These two metabolites, along with another minor metabolite of thalidomide, were tested in a rat aortic ring assay, a human saphenous vein model, and a tube formation assay to assess the metabolite's ability to inhibit angiogenesis. Of the metabolites tested, only 5'-OH-thalidomide showed biologic activity in the rat aortic ring assay, and none of the metabolites showed activity in the human model. The studies with thalidomide and thalidomide metabolites underline the difficulty and complexity of trying to isolate and evaluate a single biologically active agent. These studies, however, do suggest that at least one metabolite, 5'-OH-thalidomide, has moderate antiangiogenic activity at high concentrations. Unfortunately, because of the lack of observed activity of 5'-OH-thalidomide in the human saphenous vein assay, it remains unclear whether there is species specificity for the activity of this metabolite. JF - Therapeutic drug monitoring AU - Price, Douglas K AU - Ando, Yuichi AU - Kruger, Erwin A AU - Weiss, Michael AU - Figg, William D AD - Molecular Pharmacology Section, Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 104 EP - 110 VL - 24 IS - 1 SN - 0163-4356, 0163-4356 KW - 5'-hydroxythalidomide KW - 0 KW - Angiogenesis Inhibitors KW - Thalidomide KW - 4Z8R6ORS6L KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Endothelium, Vascular -- drug effects KW - Aorta, Thoracic -- drug effects KW - Humans KW - Saphenous Vein -- drug effects KW - Organ Culture Techniques KW - Male KW - Angiogenesis Inhibitors -- pharmacology KW - Neovascularization, Physiologic -- drug effects KW - Thalidomide -- pharmacology KW - Thalidomide -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71423050?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Therapeutic+drug+monitoring&rft.atitle=5%27-OH-thalidomide%2C+a+metabolite+of+thalidomide%2C+inhibits+angiogenesis.&rft.au=Price%2C+Douglas+K%3BAndo%2C+Yuichi%3BKruger%2C+Erwin+A%3BWeiss%2C+Michael%3BFigg%2C+William+D&rft.aulast=Price&rft.aufirst=Douglas&rft.date=2002-02-01&rft.volume=24&rft.issue=1&rft.spage=104&rft.isbn=&rft.btitle=&rft.title=Therapeutic+drug+monitoring&rft.issn=01634356&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-23 N1 - Date created - 2002-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Qualitative thin-layer and high-performance liquid chromatographic analysis of 1-substituted diazen-1-ium-1,2-diolates on aminopropyl-bonded silica gel. AN - 71422489; 11811972 AB - High-performance liquid (HPLC) and thin-layer (TLC) chromatographic methods for the detection and quantification of diazeniumdiolates are described. The HPLC determinations were made using a Rocket Platinum NH2 column (7 x 53 mm, 100-A pore size, 3-microm particle size), under isocratic conditions with mixtures of acetonitrile, methanol, and water containing 0.1% diethylamine (v/v), at a flow rate of 2.5 ml/min, a column temperature of 22 degrees C, and UV detection at 250 nm. The TLC determinations were similarly made using Merck NH2 F254S precoated glass plates (approximately 2 x 5 cm, 5-microm particle size, 0.2-mm layer thickness) with mixtures of acetonitrile, methanol, and water containing 0.1% diethylamine (v/v). Preexisting traces of carcinogenic nitrosamines were detected in some samples of diazeniumdiolates. The methods provide a more efficient means of characterizing the purity of diazeniumdiolate samples prepared for use in biomedical applications than older procedures which rely on differential absorbance measurements at 250 and 350 nm, respectively. JF - Analytical biochemistry AU - Fitzhugh, Anthony L AU - Anadu, Nwanne O AU - Waterhouse, David J AU - Hrabie, Joseph A AU - Saavedra, Joseph E AU - Keefer, Larry K AD - Intramural Research Support Program, SAIC Frederick, National Cancer Institute at Frederick, Maryland 21702-1201, USA. afitzhugh@mail.ncifcrf.gov Y1 - 2002/02/01/ PY - 2002 DA - 2002 Feb 01 SP - 97 EP - 102 VL - 301 IS - 1 SN - 0003-2697, 0003-2697 KW - Azo Compounds KW - 0 KW - Nitrosamines KW - aminopropyl silica gel KW - diazeniumdiolate KW - Silicon Dioxide KW - 7631-86-9 KW - Index Medicus KW - Silicon Dioxide -- chemistry KW - Chromatography, Thin Layer -- methods KW - Azo Compounds -- analysis KW - Chromatography, High Pressure Liquid -- methods KW - Nitrosamines -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71422489?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Analytical+biochemistry&rft.atitle=Qualitative+thin-layer+and+high-performance+liquid+chromatographic+analysis+of+1-substituted+diazen-1-ium-1%2C2-diolates+on+aminopropyl-bonded+silica+gel.&rft.au=Fitzhugh%2C+Anthony+L%3BAnadu%2C+Nwanne+O%3BWaterhouse%2C+David+J%3BHrabie%2C+Joseph+A%3BSaavedra%2C+Joseph+E%3BKeefer%2C+Larry+K&rft.aulast=Fitzhugh&rft.aufirst=Anthony&rft.date=2002-02-01&rft.volume=301&rft.issue=1&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Analytical+biochemistry&rft.issn=00032697&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-25 N1 - Date created - 2002-01-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prolactin regulates antitumor immune response through induction of tumoricidal macrophages and release of IL-12. AN - 71422484; 11802212 AB - The involvement of PRL in regulating monocyte/macrophage functions is suggested by the presence of PRL-Rs in these cells. Here, we show that PRL, though it failed to activate mouse peritoneal resident macrophages (RMs), acted as a second signal and activated mouse peritoneal inflammatory macrophages (EMs) to a tumoricidal state. The cytotoxicity of mouse tumor-associated macrophages (TAMs) isolated at day 1 of tumor (Ehrlich ascites carcinoma, EAC) growth was enhanced by PRL. However, with progression of tumor growth, TAMs became nonresponsive to the hormone. PRL-induced killing of P815 target cells by EMs and TAMs was independent of TNF but correlated with the hormone-induced augmentation of NO2(-) and O2(-) release in these macrophages. Administration of PRL in vivo inhibited EAC growth and augmented NO2(-) release by TAMs. PRL synergized with the TH1 cytokine IFN-gamma, a known activator of macrophages, in inducing tumor killing and release of NO2(-) from EMs and TAMs. The hormone might activate macrophages at least partially, through the release of IFN-gamma as anti-IFN-gamma blocked IFN-gamma- as well as PRL-induced cytotoxicity in EMs. The TH2 cytokine IL-4 suppressed PRL-induced activation of macrophages. PRL induced release of IL-12 from EMs also, which suggested that the hormone might drive the TH1 response through IL-12. Our observations further suggest that PRL alone and in synergy with IFN-gamma, released through induction of IL-12, may generate tumoricidal macrophages and thus regulate the antitumor immune response of tumor hosts. Copyright 2001 Wiley-Liss, Inc. JF - International journal of cancer AU - Majumder, Biswanath AU - Biswas, Ratna AU - Chattopadhyay, Utpala AD - Department of Immunoregulation and Immunodiagnosis, Chittaranjan National Cancer Institute, Kolkata, India. Y1 - 2002/02/01/ PY - 2002 DA - 2002 Feb 01 SP - 493 EP - 500 VL - 97 IS - 4 SN - 0020-7136, 0020-7136 KW - Adjuvants, Immunologic KW - 0 KW - Culture Media, Conditioned KW - Nitrites KW - Recombinant Proteins KW - Superoxides KW - 11062-77-4 KW - Interleukin-12 KW - 187348-17-0 KW - Nitric Oxide KW - 31C4KY9ESH KW - Interferon-gamma KW - 82115-62-6 KW - Prolactin KW - 9002-62-4 KW - Index Medicus KW - Animals KW - Nitrites -- metabolism KW - Humans KW - Nitric Oxide -- metabolism KW - Interferon-gamma -- pharmacology KW - Cells, Cultured -- drug effects KW - Mice KW - Inflammation KW - Macrophage Activation -- drug effects KW - Superoxides -- metabolism KW - Cells, Cultured -- secretion KW - Cytotoxicity, Immunologic -- drug effects KW - Phagocytosis KW - Drug Synergism KW - Female KW - Macrophages, Peritoneal -- physiology KW - Adjuvants, Immunologic -- physiology KW - Prolactin -- physiology KW - Carcinoma, Ehrlich Tumor -- pathology KW - Carcinoma, Ehrlich Tumor -- drug therapy KW - Carcinoma, Ehrlich Tumor -- immunology KW - Interleukin-12 -- secretion KW - Prolactin -- therapeutic use KW - Adjuvants, Immunologic -- pharmacology KW - Prolactin -- pharmacology KW - Adjuvants, Immunologic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71422484?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Prolactin+regulates+antitumor+immune+response+through+induction+of+tumoricidal+macrophages+and+release+of+IL-12.&rft.au=Majumder%2C+Biswanath%3BBiswas%2C+Ratna%3BChattopadhyay%2C+Utpala&rft.aulast=Majumder&rft.aufirst=Biswanath&rft.date=2002-02-01&rft.volume=97&rft.issue=4&rft.spage=493&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-12 N1 - Date created - 2002-01-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polymorphisms of UDP-glucuronosyltransferase and pharmacokinetics of irinotecan. AN - 71419298; 11805731 AB - Irinotecan is a prodrug that is hydrolyzed by carboxylesterase in vivo to form an active metabolite SN-38. SN-38 is further conjugated and detoxified by UDP-glucuronosyltransferase (UGT) to yield its beta-glucuronide (SN-38G). Although irinotecan is widely used, the drug causes unpredictably severe, occasionally fatal, toxicity of leukopenia or diarrhea. Interindividual variation of sensitivity to irinotecan is related to large variations of biotransformation of the active metabolite SN-38, some of which would be caused by genetic polymorphism of UGT1A1, an isozyme responsible for the SN-38 glucuronidation. As a surrogate for the UGT activity, the polymorphic frequency distribution of the area under the concentration-time curve (AUC) ratios of SN-38 to SN-38G (AUC(SN-38)/AUC(SN-38G)) using pooled pharmacokinetic data from four independent study groups in Japan was explored. The data from 100 cancer patients was analyzed, including 14 who were genotyped for UGT1A1 gene in the previous studies. The median ratios of AUC(SN-38)/AUC(SN-38G) was 0.40 (interquartile range, 0.30 to 0.55; range, 0.09 to 2.32). Frequency distribution of the AUC (SN-38)/AUC(SN-38G) was skewed to the right without bimodality and the patient population could not be segregated into discrete subgroups that differ in the UGT activity by the AUC ratios. The 4 subjects carrying UGT1A1*28 allele had values of the AUC(SN-38)/AUC(SN-38G) above the 75th percentile of the total population, suggesting a potential pharmacogenetic/pharmacokinetic relationship. Ordinary values with a median of 0.41 (interquartile range, 0.33 to 0.49) were obtained for the UGT1A1*6 heterozygous patient and the 9 UGT1A1*1 homozygous patients (the reference sequence). The large variation in the UGT activity being related to the genetic status would warrant pharmacogenetic-guided dosing of irinotecan. JF - Therapeutic drug monitoring AU - Ando, Yuichi AU - Ueoka, Hiroshi AU - Sugiyama, Toru AU - Ichiki, Masao AU - Shimokata, Kaoru AU - Hasegawa, Yoshinori AD - First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan. yando@mail.nih.gov Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 111 EP - 116 VL - 24 IS - 1 SN - 0163-4356, 0163-4356 KW - 7-ethyl-10-hydroxycamptothecin beta-glucuronide KW - 0 KW - Antineoplastic Agents, Phytogenic KW - Enzyme Inhibitors KW - Glucuronates KW - irinotecan KW - 0H43101T0J KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - Bilirubin KW - RFM9X3LJ49 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Glucuronates -- blood KW - Infusions, Intravenous KW - Area Under Curve KW - Bilirubin -- metabolism KW - Polymorphism, Genetic -- genetics KW - Humans KW - Adult KW - Enzyme Inhibitors -- blood KW - Male KW - Female KW - Antineoplastic Agents, Phytogenic -- pharmacokinetics KW - Glucuronosyltransferase -- genetics KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Camptothecin -- pharmacokinetics KW - Camptothecin -- analogs & derivatives KW - Camptothecin -- adverse effects KW - Camptothecin -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71419298?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Therapeutic+drug+monitoring&rft.atitle=Polymorphisms+of+UDP-glucuronosyltransferase+and+pharmacokinetics+of+irinotecan.&rft.au=Ando%2C+Yuichi%3BUeoka%2C+Hiroshi%3BSugiyama%2C+Toru%3BIchiki%2C+Masao%3BShimokata%2C+Kaoru%3BHasegawa%2C+Yoshinori&rft.aulast=Ando&rft.aufirst=Yuichi&rft.date=2002-02-01&rft.volume=24&rft.issue=1&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Therapeutic+drug+monitoring&rft.issn=01634356&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-23 N1 - Date created - 2002-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rgg influences the expression of multiple regulatory loci to coregulate virulence factor expression in Streptococcus pyogenes. AN - 71415197; 11796609 AB - The human pathogen Streptococcus pyogenes secretes many proteins to the cell wall and extracellular environment that contribute to virulence. Rgg regulates the expression of several exoproteins including a cysteine protease (SPE B), a nuclease (MF-1), a putative nuclease (MF-3), and autolysin. The functional heterogeneity of Rgg-regulated exoproteins and the lack of a conserved regulatory motif in the promoter regions of the genes suggested that Rgg interacts with additional regulatory networks to influence gene expression. DNA microarrays were used to test this hypothesis by comparing genomewide transcript profiles of S. pyogenes NZ131 and isogenic derivative NZ131 rgg during the exponential phase of growth. Transcripts of known and putative virulence-associated genes were more abundant in the rgg mutant, including emm, scpA, orfX, scl1, hasAB, slo, sagA, ska, speH, grab, mac, mf-1, and mf-3. Increased transcription of emm, scpA, and orfX in the rgg mutant was associated with increased production of the corresponding proteins. Differences in the expression of virulence-associated genes were associated with changes in the expression of several regulatory genes, including mga, sagA, csrRS, and fasBCA. The results show that Rgg influences the expression of multiple regulatory networks to coregulate virulence factor expression in S. pyogenes. JF - Infection and immunity AU - Chaussee, Michael S AU - Sylva, Gail L AU - Sturdevant, Daniel E AU - Smoot, Laura M AU - Graham, Morag R AU - Watson, Robert O AU - Musser, James M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA. mchausse@usd.edu Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 762 EP - 770 VL - 70 IS - 2 SN - 0019-9567, 0019-9567 KW - Bacterial Proteins KW - 0 KW - CsrR protein, Streptococcus pyogenes KW - DNA-Binding Proteins KW - Repressor Proteins KW - Trans-Activators KW - Transcription Factors KW - mry protein, Streptococcus pyogenes KW - 136653-49-1 KW - rgg protein, Streptococcus KW - 147415-86-9 KW - Protein Kinases KW - EC 2.7.- KW - CsrS protein, bacteria KW - EC 2.7.1.- KW - Index Medicus KW - Virulence KW - Humans KW - Protein Kinases -- genetics KW - Transcription, Genetic KW - Reverse Transcriptase Polymerase Chain Reaction KW - Regulon KW - Transcription Factors -- genetics KW - Repressor Proteins -- genetics KW - Mutagenesis KW - Gene Expression Regulation, Bacterial KW - Genes, Bacterial KW - Bacterial Proteins -- genetics KW - Streptococcus pyogenes -- genetics KW - Bacterial Proteins -- metabolism KW - Streptococcus pyogenes -- pathogenicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71415197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+immunity&rft.atitle=Rgg+influences+the+expression+of+multiple+regulatory+loci+to+coregulate+virulence+factor+expression+in+Streptococcus+pyogenes.&rft.au=Chaussee%2C+Michael+S%3BSylva%2C+Gail+L%3BSturdevant%2C+Daniel+E%3BSmoot%2C+Laura+M%3BGraham%2C+Morag+R%3BWatson%2C+Robert+O%3BMusser%2C+James+M&rft.aulast=Chaussee&rft.aufirst=Michael&rft.date=2002-02-01&rft.volume=70&rft.issue=2&rft.spage=762&rft.isbn=&rft.btitle=&rft.title=Infection+and+immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-21 N1 - Date created - 2002-01-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Bacteriol. 1995 Nov;177(22):6619-24 [7592441] Infect Immun. 1995 Jan;63(1):9-20 [7806389] Mol Microbiol. 1996 Sep;21(5):1087-99 [8885277] Med Microbiol Immunol. 1996 Nov;185(3):171-81 [9007823] Infect Immun. 1997 May;65(5):1956-9 [9125588] J Clin Invest. 1997 Jun 1;99(11):2574-80 [9169486] J Bacteriol. 1997 Aug;179(16):5178-87 [9260962] Infect Immun. 1998 Apr;66(4):1671-9 [9529097] Infect Immun. 1998 Aug;66(8):3931-5 [9673282] Mol Microbiol. 1998 Jun;28(6):1323-34 [9680220] Mol Microbiol. 1998 Oct;30(1):209-19 [9786197] EMBO J. 1998 Nov 2;17(21):6263-75 [9799235] J Exp Med. 1999 Jan 4;189(1):89-102 [9874566] J Biol Chem. 1999 Feb 19;274(8):4786-93 [9988717] Infect Immun. 1999 Apr;67(4):1715-22 [10085009] Infect Immun. 1999 Apr;67(4):1779-88 [10085018] Mol Microbiol. 1999 Feb;31(4):1051-64 [10096074] J Biol Chem. 1999 May 28;274(22):15336-44 [10336419] J Bacteriol. 1999 Jun;181(12):3649-57 [10368137] J Bacteriol. 1999 Sep;181(17):5373-83 [10464209] Infect Immun. 1999 Oct;67(10):5298-305 [10496909] J Bacteriol. 1999 Oct;181(19):6019-27 [10498714] Infect Immun. 2000 Mar;68(3):1019-25 [10678902] Infect Immun. 2000 Jun;68(6):3226-32 [10816467] Cell. 2000 Jul 7;102(1):109-26 [10929718] Infect Immun. 1995 Feb;63(2):622-31 [7822031] J Biol Chem. 1995 Apr 28;270(17):9862-7 [7730368] FEMS Microbiol Lett. 1995 Apr 15;128(1):45-51 [7744238] J Biol Chem. 1995 Aug 4;270(31):18452-8 [7629171] Science. 2000 Oct 13;290(5490):354-7 [11030657] Infect Immun. 2000 Nov;68(11):6370-7 [11035747] Microbiology. 2000 Nov;146 ( Pt 11):2785-92 [11065357] Infect Immun. 2000 Dec;68(12):6542-53 [11083763] Infect Immun. 2001 Jan;69(1):534-7 [11119547] Mol Microbiol. 2001 Jan;39(2):392-406 [11136460] Infect Immun. 2001 Feb;69(2):822-31 [11159974] Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4658-63 [11296296] Mol Microbiol. 2001 May;40(4):976-90 [11401704] Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10416-21 [11517341] Nat Med. 2001 Dec;7(12):1298-305 [11726969] Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 [388439] Proc Natl Acad Sci U S A. 1987 Dec;84(23):8677-81 [2446327] J Bacteriol. 1990 Feb;172(2):696-700 [2404953] J Exp Med. 1992 May 1;175(5):1291-9 [1569398] J Biol Chem. 1993 Jul 15;268(20):14568-71 [8325836] Infect Immun. 1993 Sep;61(9):3719-23 [8359893] Mol Microbiol. 1994 Feb;11(4):671-84 [8196542] Microb Pathog. 1993 Nov;15(5):327-46 [7516997] Mol Microbiol. 1994 Jun;12(6):873-9 [7523828] Infect Immun. 1996 Jul;64(7):2548-55 [8698478] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Childhood sexual abuse and risk behaviors among men at high risk for HIV infection. AN - 71411850; 11818294 AB - This study examined the association between unwanted sexual activity during childhood and risky behaviors among a sample of predominantly African American and Hispanic men. Data were obtained from baseline interviews completed by 2676 men enrolled in a multisite HIV prevention trial. Approximately 25% of the men reported unwanted or uninvited sexual activity before 13 years of age, with Hispanic men more likely than African American men to report unwanted sexual activity during childhood. Men with a history of unwanted sexual activity during childhood were more likely to report unwanted sexual activity since age 13, the buying and selling of sex, problems with alcohol, and drug use. Men who reported unwanted sexual activity during childhood also reported a significantly greater frequency of unprotected sexual acts and more partners. Among men at high risk for HIV infection, unwanted sexual activity during childhood is more widespread than previously described and can increase the risk of participating in harmful health practices during adulthood, including risky sexual behaviors. JF - American journal of public health AU - DiIorio, Colleen AU - Hartwell, Tyler AU - Hansen, Nellie AU - NIMH Multisite HIV Prevention Trial Group AD - Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA. cdiiori@sph.emory.edu ; NIMH Multisite HIV Prevention Trial Group Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 214 EP - 219 VL - 92 IS - 2 SN - 0090-0036, 0090-0036 KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Regression Analysis KW - Humans KW - Aged KW - Child KW - Child, Preschool KW - Sex Work -- statistics & numerical data KW - Alcoholism -- epidemiology KW - Risk Factors KW - Adult KW - Middle Aged KW - Adolescent KW - Male KW - Substance-Related Disorders -- epidemiology KW - Child Abuse, Sexual -- psychology KW - Safe Sex KW - Risk-Taking KW - HIV Infections -- prevention & control KW - HIV Infections -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71411850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+public+health&rft.atitle=Childhood+sexual+abuse+and+risk+behaviors+among+men+at+high+risk+for+HIV+infection.&rft.au=DiIorio%2C+Colleen%3BHartwell%2C+Tyler%3BHansen%2C+Nellie%3BNIMH+Multisite+HIV+Prevention+Trial+Group&rft.aulast=DiIorio&rft.aufirst=Colleen&rft.date=2002-02-01&rft.volume=92&rft.issue=2&rft.spage=214&rft.isbn=&rft.btitle=&rft.title=American+journal+of+public+health&rft.issn=00900036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-06 N1 - Date created - 2002-01-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Psychiatry. 1974 Oct;131(10):1121-3 [4416585] Psychol Med. 1986 Feb;16(1):213-7 [3961046] Ann N Y Acad Sci. 1988;528:327-34 [3421604] AIDS. 1997 Dec;11 Suppl 2:S29-35 [9475709] J Sex Marital Ther. 1997 Winter;23(4):305-16 [9427209] Child Abuse Negl. 1994 Sep;18(9):747-61 [8000905] Child Abuse Negl. 1995 May;19(5):595-605 [7664139] J Adolesc Health. 1997 Jun;20(6):414-9 [9178077] Am J Public Health. 1991 May;81(5):572-5 [2014856] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential ATP binding and intrinsic ATP hydrolysis by amino-terminal domains of the yeast Mlh1 and Pms1 proteins. AN - 71410348; 11717305 AB - MutL homologs belong to a family of proteins that share a conserved ATP binding site. We demonstrate that amino-terminal domains of the yeast MutL homologs Mlh1 and Pms1 required for DNA mismatch repair both possess independent, intrinsic ATPase activities. Amino acid substitutions in the conserved ATP binding sites concomitantly reduce ATP binding, ATP hydrolysis, and DNA mismatch repair in vivo. The ATPase activities are weak, consistent with the hypothesis that ATP binding is primarily responsible for modulating interactions with other MMR components. Three approaches, ATP hydrolysis assays, limited proteolysis protection, and equilibrium dialysis, provide evidence that the amino-terminal domain of Mlh1 binds ATP with >10-fold higher affinity than does the amino-terminal domain of Pms1. This is consistent with a model wherein ATP may first bind to Mlh1, resulting in events that permit ATP binding to Pms1 and later steps in DNA mismatch repair. JF - The Journal of biological chemistry AU - Hall, Mark C AU - Shcherbakova, Polina V AU - Kunkel, Thomas A AD - Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/02/01/ PY - 2002 DA - 2002 Feb 01 SP - 3673 EP - 3679 VL - 277 IS - 5 SN - 0021-9258, 0021-9258 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Bacterial Proteins KW - Carrier Proteins KW - Escherichia coli Proteins KW - Fungal Proteins KW - MLH1 protein, S cerevisiae KW - MutL protein, E coli KW - PMS1 protein, S cerevisiae KW - Recombinant Proteins KW - Saccharomyces cerevisiae Proteins KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - MutL Protein Homolog 1 KW - EC 3.6.1.3 KW - MutL Proteins KW - Index Medicus KW - DNA Repair KW - Bacterial Proteins -- metabolism KW - Adenosine Triphosphatases -- metabolism KW - Escherichia coli -- genetics KW - Amino Acid Sequence KW - Hydrolysis KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Sequence Alignment KW - Bacterial Proteins -- chemistry KW - Recombinant Proteins -- metabolism KW - Base Pair Mismatch KW - Kinetics KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Amino Acid Substitution KW - Protein Conformation KW - Saccharomyces cerevisiae -- genetics KW - Fungal Proteins -- chemistry KW - Fungal Proteins -- metabolism KW - Saccharomyces cerevisiae -- metabolism KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry KW - Carrier Proteins -- genetics KW - Adenosine Triphosphate -- metabolism KW - Fungal Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71410348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Differential+ATP+binding+and+intrinsic+ATP+hydrolysis+by+amino-terminal+domains+of+the+yeast+Mlh1+and+Pms1+proteins.&rft.au=Hall%2C+Mark+C%3BShcherbakova%2C+Polina+V%3BKunkel%2C+Thomas+A&rft.aulast=Hall&rft.aufirst=Mark&rft.date=2002-02-01&rft.volume=277&rft.issue=5&rft.spage=3673&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-28 N1 - Date created - 2002-01-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cyclin-dependent kinase 5 (cdk5) activation requires interaction with three domains of p35. AN - 71409314; 11813240 AB - Cyclin-dependent kinase 5 (cdk5), in contrast to other members of the cyclin-dependent kinase family, is not activated by cyclins but instead is activated by complexing with neuron-specific activator molecules (p35, p39, and p67). The most effective activator of cdk5 both in vitro and in vivo is p35. We have taken a kinetic approach to study the interaction between p35, its various truncated forms, and cdk5 to understand better the mechanism of its activation. The cdk5 complexes formed with the truncated forms p25 and p21 produced similar maximum active kinase, whereas the cdk5 complexed with full-length p35 and a further truncated form spanning amino acid residues from 138 to 291, with approximate molecular weight of 16 kDa (p16), produced slightly less (80%) activation than p25. P16 was the smallest fragment of p35 that produced activation equal to or greater than that of full-length p35. By examination of further truncations of p16, we found that a small number of residues, 11 and 4 at the N- and C-termini, respectively, of p16, are essential for cdk5 activation. Further truncation, removing both essential N- and C-terminal domains, produces a peptide with markedly higher affinity for cdk5 compared with the peptides that retain either of these domains. Using these inactive truncated peptides as inhibitors, we examined the kinetics of activation. From these studies we conclude that activation involves at least three cdk5-interacting domains, one located at each end of p16 and at least one located in a central domain. The cdk5 activation process is slow: The second-order rate constant for p16 is about 1.2 microM(-1) hr(-1). On the basis of kinetic data, we suggest that cdk5 exists in two conformations. The inactive kinase conformation predominates in the absence of the activator. Activation occurs in two stages: a rapid and reversible interaction of cdk5 with its activator, which involves only one or two binding domains, followed by a slow stabilization of the active conformation as interaction with all three domains is achieved. Published 2002 Wiley-Liss, Inc. JF - Journal of neuroscience research AU - Amin, Niranjana D AU - Albers, Wayne AU - Pant, Harish C AD - Laboratory of Neurochemistry, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/02/01/ PY - 2002 DA - 2002 Feb 01 SP - 354 EP - 362 VL - 67 IS - 3 SN - 0360-4012, 0360-4012 KW - Nerve Tissue Proteins KW - 0 KW - Recombinant Fusion Proteins KW - neuronal Cdk5 activator (p25-p35) KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Cyclin-Dependent Kinase 5 KW - EC 2.7.11.1 KW - Cdk5 protein, mouse KW - EC 2.7.11.22 KW - Cyclin-Dependent Kinases KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Kinetics KW - Binding, Competitive -- physiology KW - Recombinant Fusion Proteins -- genetics KW - Protein Structure, Tertiary -- physiology KW - Enzyme Activation -- physiology KW - Mice KW - Glutathione Transferase -- genetics KW - Structure-Activity Relationship KW - Recombinant Fusion Proteins -- chemistry KW - Cyclin-Dependent Kinases -- genetics KW - Cyclin-Dependent Kinases -- chemistry KW - Nerve Tissue Proteins -- genetics KW - Nerve Tissue Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71409314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuroscience+research&rft.atitle=Cyclin-dependent+kinase+5+%28cdk5%29+activation+requires+interaction+with+three+domains+of+p35.&rft.au=Amin%2C+Niranjana+D%3BAlbers%2C+Wayne%3BPant%2C+Harish+C&rft.aulast=Amin&rft.aufirst=Niranjana&rft.date=2002-02-01&rft.volume=67&rft.issue=3&rft.spage=354&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroscience+research&rft.issn=03604012&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-25 N1 - Date created - 2002-01-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cooking oil fumes and risk of lung cancer in women in rural Gansu, China. AN - 71408080; 11804682 AB - Cooking oil fumes have been suggested to increase the risk of lung cancer in Chinese women by exposing them to mutagenic substances. We investigated the association between lung cancer and locally made rapeseed and linseed oils in a population-based case-control study in Gansu Province, China. Two hundred and thirty-three incident, female lung cancer cases diagnosed from 1994-98 were identified. A control group of 459 women was selected from census lists and were frequency matched on age and prefecture. Interviewers obtained information on cooking practices and cooking oil use. The odds ratio (OR) for lung cancer associated with ever-use of rapeseed oil, alone or in combination with linseed oil, was 1.67 (95% CI 1.0-2.5), compared to use of linseed oil alone. ORs for stir-frying with either linseed or rapeseed oil 15-29, 30 and > or =31 times per month were 1.96,1.73, and 2.24, respectively (trend, P=0.03), relative to a lower frequency of stir-frying. Lung cancer risks also increased with total number of years cooking (trend, P<0.09). Women exposed to cooking fumes from rapeseed oil appeared to be at increased risk of lung cancer, and there was some evidence that fumes from linseed oil may have also contributed to the risk. JF - Lung cancer (Amsterdam, Netherlands) AU - Metayer, Catherine AU - Wang, Zuoyuan AU - Kleinerman, Ruth A AU - Wang, Longde AU - Brenner, Alina V AU - Cui, Hongxing AU - Cao, Jisheng AU - Lubin, Jay H AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Rockville EPS/7044, Bethesda, MD 20892, USA. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 111 EP - 117 VL - 35 IS - 2 SN - 0169-5002, 0169-5002 KW - Fatty Acids, Monounsaturated KW - 0 KW - Plant Oils KW - canola oil KW - 331KBJ17RK KW - Linseed Oil KW - 8001-26-1 KW - Index Medicus KW - Odds Ratio KW - Rural Population KW - Epidemiologic Studies KW - Humans KW - China -- epidemiology KW - Adult KW - Middle Aged KW - Time Factors KW - Female KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - Inhalation Exposure KW - Linseed Oil -- adverse effects KW - Cooking KW - Plant Oils -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71408080?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lung+cancer+%28Amsterdam%2C+Netherlands%29&rft.atitle=Cooking+oil+fumes+and+risk+of+lung+cancer+in+women+in+rural+Gansu%2C+China.&rft.au=Metayer%2C+Catherine%3BWang%2C+Zuoyuan%3BKleinerman%2C+Ruth+A%3BWang%2C+Longde%3BBrenner%2C+Alina+V%3BCui%2C+Hongxing%3BCao%2C+Jisheng%3BLubin%2C+Jay+H&rft.aulast=Metayer&rft.aufirst=Catherine&rft.date=2002-02-01&rft.volume=35&rft.issue=2&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Lung+cancer+%28Amsterdam%2C+Netherlands%29&rft.issn=01695002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-16 N1 - Date created - 2002-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TGF-beta signaling: positive and negative effects on tumorigenesis. AN - 71405225; 11790550 AB - TGF-beta binding to the cell surface triggers activation of multiple signal transduction pathways that are connected in intricate ways with each other, and with other response networks involved in sensing cellular information input. Recent data indicate that changes in signal intensity and connectivity of these pathways may underlie the complex transition of the TGF-beta pathway from tumor suppressor to oncogene during tumorigenesis. JF - Current opinion in genetics & development AU - Wakefield, Lalage M AU - Roberts, Anita B AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Building 41, Room C629, 41 Library Drive, MSC 5055, Bethesda, Maryland 20892-5055, USA. Wakefiel@dce41.nci.nih.gov Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 22 EP - 29 VL - 12 IS - 1 SN - 0959-437X, 0959-437X KW - DNA-Binding Proteins KW - 0 KW - Proto-Oncogene Proteins KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor beta KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Animals KW - Genes, Tumor Suppressor KW - Humans KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Transcription, Genetic KW - Proto-Oncogene Proteins -- genetics KW - Gene Dosage KW - Transcriptional Activation KW - DNA-Binding Proteins -- metabolism KW - Signal Transduction -- physiology KW - Transforming Growth Factor beta -- physiology KW - Transforming Growth Factor beta -- genetics KW - Transforming Growth Factor beta -- metabolism KW - Neoplasms -- genetics KW - Neoplasms -- etiology KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71405225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+genetics+%26+development&rft.atitle=TGF-beta+signaling%3A+positive+and+negative+effects+on+tumorigenesis.&rft.au=Wakefield%2C+Lalage+M%3BRoberts%2C+Anita+B&rft.aulast=Wakefield&rft.aufirst=Lalage&rft.date=2002-02-01&rft.volume=12&rft.issue=1&rft.spage=22&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+genetics+%26+development&rft.issn=0959437X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-11 N1 - Date created - 2002-01-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A potent human immunodeficiency virus type 1 protease inhibitor, UIC-94003 (TMC-126), and selection of a novel (A28S) mutation in the protease active site. AN - 71366429; 11773409 AB - We identified UIC-94003, a nonpeptidic human immunodeficiency virus (HIV) protease inhibitor (PI), containing 3(R),3a(S),6a(R)-bis-tetrahydrofuranyl urethane (bis-THF) and a sulfonamide isostere, which is extremely potent against a wide spectrum of HIV (50% inhibitory concentration, 0.0003 to 0.0005 microM). UIC-94003 was also potent against multi-PI-resistant HIV-1 strains isolated from patients who had no response to any existing antiviral regimens after having received a variety of antiviral agents (50% inhibitory concentration, 0.0005 to 0.0055 microM). Upon selection of HIV-1 in the presence of UIC-94003, mutants carrying a novel active-site mutation, A28S, in the presence of L10F, M46I, I50V, A71V, and N88D appeared. Modeling analysis revealed that the close contact of UIC-94003 with the main chains of the protease active-site amino acids (Asp29 and Asp30) differed from that of other PIs and may be important for its potency and wide-spectrum activity against a variety of drug-resistant HIV-1 variants. Thus, introduction of inhibitor interactions with the main chains of key amino acids and seeking a unique inhibitor-enzyme contact profile should provide a framework for developing novel PIs for treating patients harboring multi-PI-resistant HIV-1. JF - Journal of virology AU - Yoshimura, Kazuhisa AU - Kato, Ryohei AU - Kavlick, Mark F AU - Nguyen, Aline AU - Maroun, Victor AU - Maeda, Kenji AU - Hussain, Khaja A AU - Ghosh, Arun K AU - Gulnik, Sergei V AU - Erickson, John W AU - Mitsuya, Hiroaki AD - Experimental Retrovirology Section, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 1349 EP - 1358 VL - 76 IS - 3 SN - 0022-538X, 0022-538X KW - HIV Protease Inhibitors KW - 0 KW - Sulfonamides KW - UIC-94003 KW - Urethane KW - 3IN71E75Z5 KW - Serine KW - 452VLY9402 KW - HIV Protease KW - EC 3.4.23.- KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Molecular Structure KW - Models, Molecular KW - Humans KW - Laboratories KW - Catalytic Domain KW - Amino Acid Sequence KW - Serine -- genetics KW - Mutagenesis, Site-Directed KW - Molecular Sequence Data KW - Alanine -- genetics KW - Protein Structure, Tertiary KW - Sequence Homology, Amino Acid KW - Cell Line KW - HIV Protease -- genetics KW - HIV-1 -- isolation & purification KW - HIV-1 -- enzymology KW - Urethane -- chemistry KW - HIV Protease -- chemistry KW - HIV-1 -- classification KW - Sulfonamides -- chemistry KW - Sulfonamides -- pharmacology KW - HIV Protease Inhibitors -- chemistry KW - HIV Protease Inhibitors -- pharmacology KW - Urethane -- analogs & derivatives KW - Urethane -- pharmacology KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71366429?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=A+potent+human+immunodeficiency+virus+type+1+protease+inhibitor%2C+UIC-94003+%28TMC-126%29%2C+and+selection+of+a+novel+%28A28S%29+mutation+in+the+protease+active+site.&rft.au=Yoshimura%2C+Kazuhisa%3BKato%2C+Ryohei%3BKavlick%2C+Mark+F%3BNguyen%2C+Aline%3BMaroun%2C+Victor%3BMaeda%2C+Kenji%3BHussain%2C+Khaja+A%3BGhosh%2C+Arun+K%3BGulnik%2C+Sergei+V%3BErickson%2C+John+W%3BMitsuya%2C+Hiroaki&rft.aulast=Yoshimura&rft.aufirst=Kazuhisa&rft.date=2002-02-01&rft.volume=76&rft.issue=3&rft.spage=1349&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-12 N1 - Date created - 2002-01-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1986 Jul 18;233(4761):343-6 [2425430] Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8675-80 [10411934] Annu Rev Biochem. 1993;62:543-85 [8352596] Biochemistry. 1994 Mar 1;33(8):2004-10 [8117657] Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5597-601 [8202533] Virology. 1994 Jul;202(1):471-6 [8009858] J Med Chem. 1994 Aug 5;37(16):2506-8 [8057296] Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):2398-402 [7534421] Nature. 1995 Apr 6;374(6522):569-71 [7700387] Biochemistry. 1995 Jul 25;34(29):9282-7 [7626598] J Virol. 1995 Sep;69(9):5228-35 [7636964] Structure. 1995 Jun 15;3(6):581-90 [8590019] Nat Med. 1996 Jul;2(7):760-6 [8673921] Annu Rev Pharmacol Toxicol. 1996;36:545-71 [8725401] Antiviral Res. 1996 Jul;31(3):159-64 [8811200] Antimicrob Agents Chemother. 1996 Feb;40(2):292-7 [8834868] J Virol. 1996 Dec;70(12):8270-6 [8970946] Antimicrob Agents Chemother. 1997 May;41(5):1094-8 [9145875] Antimicrob Agents Chemother. 1997 Jun;41(6):1313-8 [9174190] N Engl J Med. 1997 Sep 11;337(11):725-33 [9287227] N Engl J Med. 1997 Sep 11;337(11):734-9 [9287228] Clin Microbiol Rev. 1997 Oct;10(4):674-93 [9336668] Protein Sci. 1998 Feb;7(2):300-5 [9521105] Adv Exp Med Biol. 1998;436:75-83 [9561202] J Virol. 1998 Jun;72(6):5303-6 [9573309] JAMA. 1998 Jun 24;279(24):1977-83 [9643862] N Engl J Med. 1999 Dec 16;341(25):1865-73 [10601505] Vitam Horm. 2000;58:213-56 [10668400] Clin Infect Dis. 2000 Feb;30(2):313-8 [10671334] AIDS. 2000 Jan 28;14(2):141-9 [10708284] AIDS. 1999;13 Suppl A:S189-204 [10885776] Science. 1986 Jul 11;233(4760):215-9 [3014648] Antimicrob Agents Chemother. 1998 Oct;42(10):2637-44 [9756769] Bioorg Med Chem Lett. 1998 Apr 21;8(8):979-82 [9871524] Bioorg Med Chem Lett. 1998 Mar 17;8(6):687-90 [9871583] J Infect Dis. 1999 Apr;179(4):790-8 [10068573] J Virol Methods. 1988 Aug;20(4):309-21 [2460479] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mucosal immunization of rhesus monkeys against respiratory syncytial virus subgroups A and B and human parainfluenza virus type 3 by using a live cDNA-derived vaccine based on a host range-attenuated bovine parainfluenza virus type 3 vector backbone. AN - 71358931; 11773385 AB - Reverse genetics was used to develop a two-component, trivalent live attenuated vaccine against human parainfluenza virus type 3 (HPIV3) and respiratory syncytial virus (RSV) subgroups A and B. The backbone for each of the two components of this vaccine was the attenuated recombinant bovine/human PIV3 (rB/HPIV3), a recombinant BPIV3 in which the bovine HN and F protective antigens are replaced by their HPIV3 counterparts (48). This chimera retains the well-characterized host range attenuation phenotype of BPIV3, which appears to be appropriate for immunization of young infants. The open reading frames (ORFs) for the G and F major protective antigens of RSV subgroup A and B were each placed under the control of PIV3 transcription signals and inserted individually or in homologous pairs as supernumerary genes in the promoter proximal position of rB/HPIV3. The level of replication of rB/HPIV3-RSV chimeric viruses in the respiratory tract of rhesus monkeys was similar to that of their parent virus rB/HPIV3, and each of the chimeras induced a robust immune response to both RSV and HPIV3. RSV-neutralizing antibody titers induced by rB/HPIV3-RSV chimeric viruses were equivalent to those induced by infection with wild-type RSV, and HPIV3-specific antibody responses were similar to, or slightly less than, after infection with the rB/HPIV3 vector itself. This study describes a novel vaccine strategy against RSV in which vaccine viruses with a common attenuated backbone, specifically rB/HPIV3 derivatives expressing the G and/or F major protective antigens of RSV subgroup A and of RSV subgroup B, are used to immunize by the intranasal route against RSV and HPIV3, which are the first and second most important viral agents of pediatric respiratory tract disease worldwide. JF - Journal of virology AU - Schmidt, Alexander C AU - Wenzke, Daniel R AU - McAuliffe, Josephine M AU - St Claire, Marisa AU - Elkins, William R AU - Murphy, Brian R AU - Collins, Peter L AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. aschmidt@niaid.nih.gov Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 1089 EP - 1099 VL - 76 IS - 3 SN - 0022-538X, 0022-538X KW - Antibodies, Viral KW - 0 KW - Antigens, Viral KW - DNA, Viral KW - HN Protein KW - Parainfluenza Vaccines KW - Respiratory Syncytial Virus Vaccines KW - Vaccines, Attenuated KW - Vaccines, DNA KW - Viral Fusion Proteins KW - Viral Proteins KW - F protein, parainfluenza virus 3 KW - 109300-94-9 KW - Index Medicus KW - Viral Proteins -- genetics KW - Animals KW - Humans KW - Open Reading Frames KW - Disease Models, Animal KW - Transcription, Genetic KW - Mutagenesis, Insertional -- methods KW - Viral Fusion Proteins -- immunology KW - Antibodies, Viral -- immunology KW - HN Protein -- genetics KW - Tumor Cells, Cultured KW - Vaccines, Attenuated -- immunology KW - Molecular Sequence Data KW - Immunity, Mucosal -- immunology KW - Macaca mulatta KW - Virus Replication KW - Viral Proteins -- immunology KW - Genome, Viral KW - Viral Fusion Proteins -- genetics KW - Vaccination KW - HN Protein -- immunology KW - Antibodies, Viral -- biosynthesis KW - Antibodies, Viral -- blood KW - Cattle KW - Base Sequence KW - Antigens, Viral -- immunology KW - Cercopithecus aethiops KW - Vaccines, Attenuated -- genetics KW - Vero Cells KW - Antigens, Viral -- genetics KW - Cell Line KW - Respiratory Syncytial Virus Vaccines -- immunology KW - Vaccines, DNA -- immunology KW - Parainfluenza Virus 3, Bovine -- genetics KW - Respirovirus Infections -- prevention & control KW - Parainfluenza Vaccines -- genetics KW - Respiratory Syncytial Virus Infections -- immunology KW - Respiratory Syncytial Virus Vaccines -- genetics KW - Respiratory Syncytial Viruses -- immunology KW - Respiratory Syncytial Viruses -- genetics KW - Parainfluenza Vaccines -- immunology KW - Respirovirus Infections -- immunology KW - Genetic Vectors -- physiology KW - Parainfluenza Virus 3, Human -- genetics KW - Vaccines, DNA -- genetics KW - Parainfluenza Virus 3, Bovine -- physiology KW - Respiratory Syncytial Virus Infections -- prevention & control KW - Genetic Vectors -- genetics KW - Parainfluenza Virus 3, Human -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71358931?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Mucosal+immunization+of+rhesus+monkeys+against+respiratory+syncytial+virus+subgroups+A+and+B+and+human+parainfluenza+virus+type+3+by+using+a+live+cDNA-derived+vaccine+based+on+a+host+range-attenuated+bovine+parainfluenza+virus+type+3+vector+backbone.&rft.au=Schmidt%2C+Alexander+C%3BWenzke%2C+Daniel+R%3BMcAuliffe%2C+Josephine+M%3BSt+Claire%2C+Marisa%3BElkins%2C+William+R%3BMurphy%2C+Brian+R%3BCollins%2C+Peter+L&rft.aulast=Schmidt&rft.aufirst=Alexander&rft.date=2002-02-01&rft.volume=76&rft.issue=3&rft.spage=1089&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-12 N1 - Date created - 2002-01-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Pediatr Infect Dis J. 1996 Aug;15(8):650-4 [8858666] Virus Res. 1995 Dec;39(2-3):105-18 [8837878] Vaccine. 1997 Apr;15(5):533-40 [9160521] Virology. 1997 Sep 1;235(2):323-32 [9281512] Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13961-6 [9391135] J Infect Dis. 1997 Dec;176(6):1428-36 [9395351] J Virol. 1998 Feb;72(2):891-9 [9444980] J Virol. 1998 Apr;72(4):3117-28 [9525637] Trop Med Int Health. 1998 Apr;3(4):268-80 [9623927] Clin Microbiol Rev. 1998 Jul;11(3):430-9 [9665976] Pediatrics. 1998 Sep;102(3 Pt 1):531-7 [9738173] Pediatr Infect Dis J. 1998 Oct;17(10):919-20 [9802636] J Virol. 1999 Feb;73(2):871-7 [9882287] J Virol. 1999 Jan;73(1):466-73 [9847352] J Virol. 1999 Apr;73(4):3438-42 [10074199] Vaccine. 1999 Jun 4;17(20-21):2715-25 [10418923] Virology. 1999 Sep 1;261(2):319-30 [10497117] J Virol. 1987 Oct;61(10):3163-6 [3305988] J Infect Dis. 1988 Apr;157(4):640-7 [3346563] J Infect Dis. 1988 Apr;157(4):655-62 [2831282] JAMA. 1999 Oct 20;282(15):1440-6 [10535434] J Virol. 1999 Dec;73(12):9773-80 [10559287] Vaccine. 2000 Jan 31;18(14):1359-66 [10618533] J Virol. 2000 Feb;74(3):1187-99 [10627529] J Virol. 2000 Apr;74(7):3188-95 [10708435] Virus Genes. 2000;20(2):173-82 [10872880] Virology. 2000 Jun 20;272(1):225-34 [10873765] J Virol. 2000 Aug;74(15):6821-31 [10888621] J Virol. 2000 Sep;74(17):7895-902 [10933697] J Virol. 2000 Oct;74(19):8922-9 [10982335] J Virol. 2000 Oct;74(19):9317-21 [10982380] J Infect Dis. 2000 Nov;182(5):1331-42 [11010838] Virology. 2001 Feb 15;280(2):211-20 [11162835] J Virol. 2001 May;75(10):4594-603 [11312329] Virology. 2001 Apr 25;283(1):59-68 [11312662] J Bacteriol. 1966 Mar;91(3):1263-9 [5929754] Am J Epidemiol. 1969 Apr;89(4):422-34 [4305198] Pediatrics. 1971 Nov;48(5):745-55 [4330595] J Med Virol. 1977;1(3):157-62 [416176] Infect Immun. 1982 Jul;37(1):397-400 [7107009] Virus Res. 1985 Oct;3(3):193-206 [3907188] J Med Virol. 1986 Feb;18(2):131-7 [3005486] Virus Res. 1988 Aug;11(1):1-15 [2845680] J Virol. 1989 Jul;63(7):2941-50 [2470922] J Gen Virol. 1989 Aug;70 ( Pt 8):2185-90 [2671259] Rev Infect Dis. 1991 Sep-Oct;13(5):926-39 [1660184] J Virol. 1992 Feb;66(2):1277-81 [1731105] J Clin Microbiol. 1992 Mar;30(3):655-62 [1551982] Vaccine. 1992;10(7):475-84 [1609551] Virus Res. 1992 Mar;22(3):173-84 [1320790] Virus Res. 1992 Sep 1;25(1-2):37-50 [1413993] Adv Exp Med Biol. 1992;327:59-69 [1295353] J Virol. 1993 Aug;67(8):4822-30 [8392616] Vaccine. 1993 Nov;11(14):1395-404 [8310760] J Virol. 1995 Feb;69(2):1261-4 [7815502] J Infect Dis. 1995 May;171(5):1107-14 [7751684] Virology. 1995 Jun 20;210(1):202-5 [7793072] Vaccine. 1995 Mar;13(4):415-21 [7793140] J Infect Dis. 1995 Dec;172(6):1445-50 [7594701] J Virol. 1996 Apr;70(4):2318-23 [8642658] J Infect Dis. 1996 Mar;173(3):592-7 [8627022] J Virol. 1996 Oct;70(10):6634-41 [8794298] Vaccine. 1996 Oct;14(15):1417-20 [8994316] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The ever-increasing complexity of TGF-beta signaling. AN - 71348394; 11750874 JF - Cytokine & growth factor reviews AU - Roberts, Anita B AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Building 41, Room C629, 41 Library Drive, MSC 5055, Bethesda, MD 20892-5055, USA. robertsa@dce41.nci.nih.gov Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 3 EP - 5 VL - 13 IS - 1 SN - 1359-6101, 1359-6101 KW - DNA-Binding Proteins KW - 0 KW - Smad Proteins KW - Trans-Activators KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - Phosphorylation KW - Humans KW - Trans-Activators -- metabolism KW - Transforming Growth Factor beta -- metabolism KW - Signal Transduction KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71348394?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytokine+%26+growth+factor+reviews&rft.atitle=The+ever-increasing+complexity+of+TGF-beta+signaling.&rft.au=Roberts%2C+Anita+B&rft.aulast=Roberts&rft.aufirst=Anita&rft.date=2002-02-01&rft.volume=13&rft.issue=1&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Cytokine+%26+growth+factor+reviews&rft.issn=13596101&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-20 N1 - Date created - 2001-12-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - What Research with Stored Samples Teaches Us about Research with Human Subjects AN - 60424947; 200217207 AB - There is widespread discussion concerning the safeguards appropriate for human research subjects. Less discussed is the fact that the safeguards one deems appropriate depend, in large part, on the model of research participation that one assumes. Therefore, to determine what safeguards are appropriate, it is necessary first to clarify the competing models of research participation. The ostensibly obscure debate over informed consent for research on stored biological samples is of particular interest in this regard because such research can involve varying subsets of the three central elements of research involvement. As a result, analysis of this debate provides an opportunity to identify the competing models of research participation. Based on this analysis, this paper describes a new model of research participation that is emerging, & considers its implications for clinical research. Adapted from the source document. JF - Bioethics AU - Wendler, David AD - Dept Clinical Bioethics, National Institutes Health, Bethesda, MD wendler@nih.gov Y1 - 2002/02// PY - 2002 DA - February 2002 SP - 33 EP - 54 VL - 16 IS - 1 SN - 0269-9702, 0269-9702 KW - Informed Consent KW - Research Subjects KW - Research Ethics KW - article KW - 2499: policy, planning, forecasting; sociology of ethics & ethical decision making UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/60424947?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioethics&rft.atitle=What+Research+with+Stored+Samples+Teaches+Us+about+Research+with+Human+Subjects&rft.au=Wendler%2C+David&rft.aulast=Wendler&rft.aufirst=David&rft.date=2002-02-01&rft.volume=16&rft.issue=1&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=Bioethics&rft.issn=02699702&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Last updated - 2016-09-28 N1 - CODEN - BIETEE N1 - SubjectsTermNotLitGenreText - Research Ethics; Research Subjects; Informed Consent ER - TY - JOUR T1 - Childhood sexual abuse and risk behaviors among men at high risk for HIV infection AN - 215110043; 11818294 AB - A recent study examined the association between unwanted sexual activity during childhood and risky behaviors among a sample of predominantly African American and Hispanic men. The study concluded that, among men at high risk for HIV infection, unwanted sexual activity during childhood is more widespread than previously described and can increase the risk of participating in harmful health practices during adulthood, including risky sexual behaviors. JF - American Journal of Public Health AU - Dilorio, Colleen AU - Hartwell, Tyler AU - Hansen, Nellie Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 214 EP - 9 CY - Washington PB - American Public Health Association VL - 92 IS - 2 SN - 00900036 KW - Medical Sciences KW - Men KW - Human immunodeficiency virus KW - HIV KW - Health risk assessment KW - Sexual behavior KW - Child abuse & neglect KW - United States KW - Regression Analysis KW - Humans KW - Aged KW - Child KW - Child, Preschool KW - Alcoholism -- epidemiology KW - Risk Factors KW - Adult KW - Middle Aged KW - Adolescent KW - HIV Infections -- psychology KW - Male KW - Substance-Related Disorders -- epidemiology KW - Prostitution -- statistics & numerical data KW - Child Abuse, Sexual -- psychology KW - Safe Sex KW - Risk-Taking KW - HIV Infections -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/215110043?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aabiglobal&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Public+Health&rft.atitle=Childhood+sexual+abuse+and+risk+behaviors+among+men+at+high+risk+for+HIV+infection&rft.au=Dilorio%2C+Colleen%3BHartwell%2C+Tyler%3BHansen%2C+Nellie&rft.aulast=Dilorio&rft.aufirst=Colleen&rft.date=2002-02-01&rft.volume=92&rft.issue=2&rft.spage=214&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Public+Health&rft.issn=00900036&rft_id=info:doi/ LA - English DB - ProQuest Central; ProQuest Environmental Science Collection N1 - Copyright - Copyright American Public Health Association Feb 2002 N1 - Last updated - 2015-02-14 N1 - CODEN - AJPHDS ER - TY - JOUR T1 - The role of MRI as a surrogate outcome measure in multiple sclerosis AN - 18579034; 5353674 AB - The need for more specific and more sensitive outcome measures for use in testing new therapies in multiple sclerosis (MS) is generally accepted. This need has been accentuated by the realization that the ability to conduct large placebo-controlled trials will be limited in the future. From the first use of magnetic resonance imaging (MRI) to study MS, the ability of this imaging technique to identify areas of the central nervous system damage by the disease process in MS has been impressive. Thus, the possibility that MRI could serve as a surrogate outcome measure in clinical trials in MS has been attractive. The use of MRI as a surrogate outcome measure has been examined by an international group of investigators with expertise in clinical aspects of MS, the use of MRI in MS, and in experimental therapeutics. The group agreed that MRI does not represent a validated surrogate in any clinical form of MS. It was also agreed, however, that MRI does provide a reflection of the underlying pathology in the disease, but no single MRI measurement in isolation was seen as sufficient to monitor disease. The use for multiple imaging techniques, especially new, emerging techniques that may better reflect the underlying pathology, was seen as particularly important in monitoring studies of patients with either secondary or primary progressive MS. The choice of MRI techniques used to monitor new therapies needs to be consistent with the proposed mechanisms of the new therapy and phase of the disease. It was also noted, however, that additional validation is required for nonconventional imaging techniques. Finally, the participants noted that clinical trials using MRI as a primary outcome measure may fail to fully identify the effects of the therapy on clinical measures and that the risk and cost-benefit ratio of the treatment might be unresolved. Thus, before MRI is used as a primary outcome measure, new approaches to trial design must be given careful consideration. JF - Multiple Sclerosis AU - McFarland, H F AU - Barkhof, F AU - Antel, J AU - Miller, D H AD - Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA, mcfarlandh@ninds.nih.gov Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 40 EP - 51 VL - 8 IS - 1 SN - 1352-4585, 1352-4585 KW - outcome measure KW - man KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; CSA Neurosciences Abstracts KW - Central nervous system KW - Multiple sclerosis KW - Magnetic resonance imaging KW - N3 11021:Neuroimaging techniques KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18579034?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Multiple+Sclerosis&rft.atitle=The+role+of+MRI+as+a+surrogate+outcome+measure+in+multiple+sclerosis&rft.au=McFarland%2C+H+F%3BBarkhof%2C+F%3BAntel%2C+J%3BMiller%2C+D+H&rft.aulast=McFarland&rft.aufirst=H&rft.date=2002-02-01&rft.volume=8&rft.issue=1&rft.spage=40&rft.isbn=&rft.btitle=&rft.title=Multiple+Sclerosis&rft.issn=13524585&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; Multiple sclerosis; Central nervous system ER - TY - JOUR T1 - Occupational exposures and autoimmune diseases AN - 18573344; 5329798 AB - Autoimmune diseases are pathologic conditions defined by abnormal autoimmune responses and characterized by immune system reactivity in the form of autoantibodies and T cell responses to self-structures. Here we review the limited but growing epidemiologic and experimental literature pertaining to the association between autoimmune diseases and occupational exposure to silica, solvents, pesticides, and ultraviolet radiation. The strongest associations (i.e., relative risks of 3.0 and higher) have been documented in investigations of silica dust and rheumatoid arthritis, lupus, scleroderma and glomerulonephritis. Weaker associations are seen, however, for solvent exposures (in scleroderma, undifferentiated connective tissue disease, and multiple sclerosis) and for farming or pesticide exposures (in rheumatoid arthritis). Experimental studies suggest two different effects of these exposures: an enhanced proinflammatory (TH1) response (e.g., TNF- alpha and IL-1 cytokine production with T cell activation), and increased apoptosis of lymphocytes leading to exposure to or modification of endogenous proteins and subsequent autoantibody formation. The former is a general mechanism that may be relevant across a spectrum of autoimmune diseases, whereas the latter may be a mechanism more specific to particular diseases (e.g., ultraviolet radiation, Ro autoantibodies, and lupus). Occupational exposures are important risk factors for some autoimmune diseases, but improved exposure assessment methods and better coordination between experimental/animal models and epidemiologic studies are needed to define these risks more precisely. JF - International Immunopharmacology AU - Cooper, G S AU - Miller, F W AU - Germolec AD - Environmental Immunology Laboratory, National Institute of Environmental Health Sciences, 111 Alexander Dr., P.O. Box 12233, Research Triangle Park, NC 27709, USA, germolec@niehs.nih.gov Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 303 EP - 313 VL - 2 IS - 2-3 SN - 1567-5769, 1567-5769 KW - man KW - Immunology Abstracts; Toxicology Abstracts KW - U.V. radiation KW - Reviews KW - Pesticides KW - Autoimmune diseases KW - Solvents KW - Occupational exposure KW - Silicon dioxide KW - F 06874:General KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18573344?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Immunopharmacology&rft.atitle=Occupational+exposures+and+autoimmune+diseases&rft.au=Cooper%2C+G+S%3BMiller%2C+F+W%3BGermolec&rft.aulast=Cooper&rft.aufirst=G&rft.date=2002-02-01&rft.volume=2&rft.issue=2-3&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=International+Immunopharmacology&rft.issn=15675769&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Occupational exposure; Autoimmune diseases; Pesticides; Silicon dioxide; Solvents; U.V. radiation ER - TY - JOUR T1 - Clinical and functional target validation using tissue and cell microarrays AN - 18570362; 5394252 AB - Expression levels of thousands of genes or proteins can be readily determined using microarray techniques. However, this represents only the first step in understanding the biological and medical significance of these molecules. New high-throughput techniques, such as tissue and cell microarrays, will facilitate clinical and functional analysis of molecular targets. JF - Current Opinion in Chemical Biology AU - Mousses, S AU - Kallioniemi, A AU - Kauraniemi, P AU - Elkahloun, A AU - Kallioniemi, O-P AD - Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-8000, USA, okalli@nhgri.nih.gov Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 97 EP - 101 VL - 6 IS - 1 SN - 1367-5931, 1367-5931 KW - microarrays KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts KW - Gene expression KW - Tissues KW - Protein biosynthesis KW - Cells KW - Reviews KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews KW - W3 33250:Methods: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18570362?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Opinion+in+Chemical+Biology&rft.atitle=Clinical+and+functional+target+validation+using+tissue+and+cell+microarrays&rft.au=Mousses%2C+S%3BKallioniemi%2C+A%3BKauraniemi%2C+P%3BElkahloun%2C+A%3BKallioniemi%2C+O-P&rft.aulast=Mousses&rft.aufirst=S&rft.date=2002-02-01&rft.volume=6&rft.issue=1&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Chemical+Biology&rft.issn=13675931&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Tissues; Cells; Reviews; Gene expression; Protein biosynthesis ER - TY - JOUR T1 - Vector Interactions and Molecular Adaptations of Lyme Disease and Relapsing Fever Spirochetes Associated with Transmission by Ticks AN - 18495257; 5463560 AB - Pathogenic spirochetes in the genus Borrelia are transmitted primarily by two families of ticks. The Lyme disease spirochete, Borrelia burgdorferi, is transmitted by the slow-feeding ixodid tick Ixodes scapularis, whereas the relapsing fever spirochete, B. hermsii, is transmitted by Ornithodoros hermsi, a fast-feeding argasid tick. Lyme disease spirochetes are generally restricted to the midgut in unfed I. scapularis. When nymphal ticks feed, the bacteria pass through the hemocoel to the salivary glands and are transmitted to a new host in the saliva after 2 days. Relapsing fever spirochetes infect the midgut in unfed O. hermsi but persist in other sites including the salivary glands. Thus, relapsing, fever spirochetes are efficiently transmitted in saliva by these fast-feeding ticks within minutes of their attachment to a mammalian host. We describe how B. burgdorferi and B. hermsii change their outer surface during their alternating infections in ticks and mammals, which in turn suggests biological functions for a few surface-exposed lipoproteins. JF - Emerging Infectious Diseases AU - Schwan, T G AU - Piesman, J AD - National Institutes of Health, Hamilton, Montana, USA Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 115 EP - 121 PB - Centers for Disease Control and Prevention VL - 8 IS - 2 SN - 1080-6040, 1080-6040 KW - Acari KW - Deer tick KW - Ixodidae KW - Microbiology Abstracts B: Bacteriology; Entomology Abstracts KW - J 02855:Human Bacteriology: Others KW - Z 05206:Medical & veterinary entomology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18495257?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Emerging+Infectious+Diseases&rft.atitle=Vector+Interactions+and+Molecular+Adaptations+of+Lyme+Disease+and+Relapsing+Fever+Spirochetes+Associated+with+Transmission+by+Ticks&rft.au=Schwan%2C+T+G%3BPiesman%2C+J&rft.aulast=Schwan&rft.aufirst=T&rft.date=2002-02-01&rft.volume=8&rft.issue=2&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Emerging+Infectious+Diseases&rft.issn=10806040&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Why have cells selected reactive oxygen species to regulate cell signaling events? AN - 18442877; 5419094 AB - There is a growing body of evidence demonstrating that exposure of cells to reactive oxygen species (ROS) leads to oxidative modification of nucleic acids, proteins, and lipids, and that such modifications can contribute to the development of a number of diseases and aging. This raises the question: If ROS are so damaging to cells, why have cells selected ROS to trigger activation of so many cell signaling pathways? JF - Human & Experimental Toxicology AU - Stadtman, E R AU - Levine, R L AD - Laboratory of Biochemistry, NHLBI/NIH, 50 South Drive, Room 2140 (MSC 8012), Bethesda, MD 20892-8012, USA, stadtmae@nhlbi.nih.gov Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 83 VL - 21 IS - 2 SN - 0960-3271, 0960-3271 KW - Toxicology Abstracts KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18442877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+%26+Experimental+Toxicology&rft.atitle=Why+have+cells+selected+reactive+oxygen+species+to+regulate+cell+signaling+events%3F&rft.au=Stadtman%2C+E+R%3BLevine%2C+R+L&rft.aulast=Stadtman&rft.aufirst=E&rft.date=2002-02-01&rft.volume=21&rft.issue=2&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Human+%26+Experimental+Toxicology&rft.issn=09603271&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Sequence-Specific Gene Cleavage in Intact Mammalian Cells by super(125)I-Labeled Triplex-Forming Oligonucleotides Conjugated with Nuclear Localization Signal Peptide AN - 18408259; 5398049 AB - Triplex-forming oligonucleotides (TFO) are designed to bind sequence specifically to their DNA targets without a significant disturbance of the double helix. They have been proposed to deliver DNA-reactive agents to specific DNA sequences for gene targeting applications. We suggested the use of super(125)I-labeled TFO for delivery of the energy of radioiodine decay to specific genes. This approach is called antigene radiotherapy. Here we demonstrate the ability of super(125)I-labeled TFO to produce sequence-specific breaks within a target in the human mdr1 gene in cultured cells. TFO and TFO conjugated with a nuclear localization signal peptide (NLS) were delivered into cells using cationic liposomes. This was done either alone or in the presence of an excess of a "ballast" oligonucleotide with an unrelated sequence. In all cases, nuclear localization of TFO and survival of the cells after treatment has been confirmed. Breaks in the gene target were analyzed by restriction enzyme digestion of the DNA recovered from the TFO-treated cells followed by Southern hybridization with DNA probes flanking the target sequence. We have found that TFO/NLS conjugates cleave the target in a concentration-dependent manner regardless of the presence of the "ballast" oligonucleotide. In contrast, TFO without NLS cleaved the target only in the presence of an excess of the "ballast." We hypothesize that TFO and TFO/NLS are delivered into the nucleus by different pathways. These results provide a new insight into the mechanism of intracellular transport of oligonucleotides and open new avenues for improvement of the efficacy of antigene therapies. JF - Antisense and Nucleic Acid Drug Development AU - Sedelnikova, O A AU - Karamychev, V N AU - Panyutin, I G AU - Neumann, R D AD - Bldg. 10/1C401, Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA, igorp@helix.nih.gov Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 43 EP - 49 VL - 12 IS - 1 SN - 1087-2906, 1087-2906 KW - Triplex-forming oligonucleotides KW - antigene radiotherapy KW - nuclear localization signal KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - N 14681:Mutagenesis techniques KW - W 30965:Miscellaneous, Reviews KW - W3 33380:Antisense UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18408259?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antisense+and+Nucleic+Acid+Drug+Development&rft.atitle=Sequence-Specific+Gene+Cleavage+in+Intact+Mammalian+Cells+by+super%28125%29I-Labeled+Triplex-Forming+Oligonucleotides+Conjugated+with+Nuclear+Localization+Signal+Peptide&rft.au=Sedelnikova%2C+O+A%3BKaramychev%2C+V+N%3BPanyutin%2C+I+G%3BNeumann%2C+R+D&rft.aulast=Sedelnikova&rft.aufirst=O&rft.date=2002-02-01&rft.volume=12&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Antisense+and+Nucleic+Acid+Drug+Development&rft.issn=10872906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Chronic Arsenic Poisoning from Burning High-Arsenic-Containing Coal in Guizhou, China AN - 18398164; 5385753 AB - Arsenic is an environmental hazard and the reduction of drinking water arsenic levels is under consideration. People are exposed to arsenic not only through drinking water but also through arsenic-contaminated air and food. Here we report the health effects of arsenic exposure from burning high arsenic-containing coal in Guizhou, China. Coal in this region has undergone mineralization and thus produces high concentrations of arsenic. Coal is burned inside the home in open pits for daily cooking and crop drying, producing a high concentration of arsenic in indoor air. Arsenic in the air coats and permeates food being dried producing high concentrations in food; however, arsenic concentrations in the drinking water are in the normal range. The estimated sources of total arsenic exposure in this area are from arsenic-contaminated food (50-80%), air (10-20%), water (1-5%), and direct contact in coal-mining workers (1%). At least 3,000 patients with arsenic poisoning were found in the Southwest Prefecture of Guizhou, and approximately 200,000 people are at risk for such overexposures. Skin lesions are common, including keratosis of the hands and feet, pigmentation on the trunk, skin ulceration, and skin cancers. Toxicities to internal organs, including lung dysfunction, neuropathy, and nephrotoxicity, are clinically evident. The prevalence of hepatomegaly was 20%, and cirrhosis, ascites, and liver cancer are the most serious outcomes of arsenic poisoning. The Chinese government and international organizations are attempting to improve the house conditions and the coal source, and thereby protect human health in this area. JF - Environmental Health Perspectives AU - Liu, J AU - Zheng, B AU - Aposhian, H V AU - Zhou, Y AU - Chen, M-L AU - Zhang, A AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, NCI at NIEHS, Mail Drop F0-09, Room F-017, 111 Alexander Drive, Research Triangle Park, NC 27713 USA, Liu6@niehs.nih.gov Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 119 EP - 122 VL - 110 IS - 2 SN - 0091-6765, 0091-6765 KW - chronic toxicity KW - man KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts; Pollution Abstracts KW - R2 23060:Medical and environmental health KW - H 12000:Epidemiology and Public Health KW - X 24162:Chronic exposure KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18398164?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Chronic+Arsenic+Poisoning+from+Burning+High-Arsenic-Containing+Coal+in+Guizhou%2C+China&rft.au=Liu%2C+J%3BZheng%2C+B%3BAposhian%2C+H+V%3BZhou%2C+Y%3BChen%2C+M-L%3BZhang%2C+A%3BWaalkes%2C+M+P&rft.aulast=Liu&rft.aufirst=J&rft.date=2002-02-01&rft.volume=110&rft.issue=2&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - In Vitro Engineered Cartilage Constructs Produced by Press-Coating Biodegradable Polymer with Human Mesenchymal Stem Cells AN - 18376117; 5351376 AB - Cartilage constructs were fabricated by press-coating D,D-L,L-polylactic acid polymer blocks of 1 x 0.5 x 0.5 cm onto high-density cell pellets of 1.5 x 10 super(6) human mesenchymal stem cells (mhMSCs) isolated from the femoral head of patients undergoing total hip arthroplasty. Following attachment of the cell pellets to the polymer surfaces, chondrogenesis was induced by culturing the constructs for 3 weeks in a serum-free, chemically defined, chondrogenic differentiation medium supplemented with transforming growth factor beta -1 (TGF- beta 1). Histochemical analysis showed that the press-coated pellets formed cell layers composed of morphologically distinct, chondrocyte-like cells, surrounded by a fibrous, sulfated proteoglycanrich extracellular matrix. Immunohistochemical analysis detected collagen type II and cartilage proteoglycan link protein within the extracellular matrix. Expression of the cartilage-specific marker genes collagen types II, IX, X, and XI, and aggrecan was detected by RT-PCR. Scanning electron microscopy revealed organized and spatially distinct zones of cells within the cell-polymer constructs, with the superficial layer resembling compact hyaline cartilage. The fabrication method of press-coating biodegradable polymers with mhMSCs allows the in vitro production of cartilage constructs without harvesting chondrocytes from intact articular cartilage surfaces. These constructs may be applicable as prototypes for the reconstruction of articular cartilage defects in humans. JF - Tissue Engineering AU - Noeth, U AU - Tuli, R AU - Osyczka, A M AU - Danielson, K G AU - Tuan, R S AD - Chief, Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bldg. 13, Room 3W17, 13 South Drive, MSC 5755, Bethesda, MD 20892-5755, USA, Tuanr@mail.nih.gov Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 131 EP - 144 VL - 8 IS - 1 SN - 1076-3279, 1076-3279 KW - man KW - transforming growth factor- beta 1 KW - Biotechnology and Bioengineering Abstracts; Calcium & Calcified Tissue Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33220:Cell culture KW - T 20018:Cartilage and cartilage diseases KW - W4 110:Biomedical Materials & Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18376117?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tissue+Engineering&rft.atitle=In+Vitro+Engineered+Cartilage+Constructs+Produced+by+Press-Coating+Biodegradable+Polymer+with+Human+Mesenchymal+Stem+Cells&rft.au=Noeth%2C+U%3BTuli%2C+R%3BOsyczka%2C+A+M%3BDanielson%2C+K+G%3BTuan%2C+R+S&rft.aulast=Noeth&rft.aufirst=U&rft.date=2002-02-01&rft.volume=8&rft.issue=1&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Tissue+Engineering&rft.issn=10763279&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - A stimulating presentation [Adoptive immunotherapy using engineered APCs] AN - 18362258; 5333480 AB - How can we arm and train a patient's own immune system to destroy a tumor or repel a chronic viral infection? A promising approach is to bypass normal immune regulatory mechanisms by generating an immune response ex vivo, and then to transfer the fully activated immune cells back into the patient. This treatment strategy requires the in vitro expansion of disease-specific T cells to numbers in the billions. In this issue, Maus et al. describe an "artificial APC" that, for the first time, provides a defined system with the capacity to drive large expansions of T cells ex vivo. This powerful artificial APC could augment current methods of T-cell stimulation; and moreover, it may herald a new generation of effector T cells for adoptive therapy. JF - Nature Biotechnology AU - Dudley, ME AD - Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA, Mark_Dudley@nih.gov Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 125 EP - 126 VL - 20 IS - 2 SN - 1087-0156, 1087-0156 KW - 4-1BB antigen KW - CD28 antigen KW - CD8 antigen KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - T-cell receptor KW - ^AT-cell receptor KW - Reviews KW - Adoptive immunotherapy KW - Lymphocytes T KW - Antigen-presenting cells KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W3 33170:Cellular based KW - F 06756:Function KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18362258?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=A+stimulating+presentation+%5BAdoptive+immunotherapy+using+engineered+APCs%5D&rft.au=Dudley%2C+ME&rft.aulast=Dudley&rft.aufirst=ME&rft.date=2002-02-01&rft.volume=20&rft.issue=2&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adoptive immunotherapy; Antigen-presenting cells; Lymphocytes T; Reviews; T-cell receptor; ^AT-cell receptor ER - TY - JOUR T1 - Recombinant lemA without adjuvant induces extensive expansion of H2-M3-restricted CD8 effectors, which can suppress primary listeriosis in mice AN - 18305546; 5345687 AB - Mice infected with Listeria monocytogenes (LM) produce large numbers of H2-M3-restricted CD8 T cells directed against the formylated peptides, f-MIGWII and f-MIVIL. To examine responsiveness to these epitopes in the absence of infection, we inoculated mice with recombinant lemA (r-lemA) containing f-MIGWII or r-vemA (a variant of r-lemA containing f-MIVIL in place of f-MIGWII) without adjuvant. To monitor responses, we measured peptide-specific cytoplasmic IFN- gamma production ex vivo by freshly harvested splenocytes at varying times post-inoculation. B6 mice inoculated with r-lemA produced substantial numbers of epitope-specific CD8 cells with peak levels on day 7 when there were 1.1 x 10 super(6) f-MIGWII-specific CD8 cells in the spleen (8.2% of total CD8 splenocytes). The r-vemA-treated animals accumulated 0.25 x 10 super(6) cells (1.8% of total CD8 cells) at this time point. Comparable responses were observed after rechallenge of immunized animals. Other elements in the lemA moiety distinct from the immunogenic peptide were required since mice did not respond to equimolar amounts of synthetic f-MIGWII or f-MIVIL alone. In comparative studies, B6 and C3H/HeJ mice responded to r-vemA much more vigorously than BALB/c animals. When r-lemA- or r-vemA-treated B6 animals were challenged i.v. with LM 7 days later, they suppressed splenic accumulation of bacteria much more effectively than controls. On the other hand, antigen-treated animals were not protected against infection 1 month later. Thus, responsive strains of mice respond vigorously to H2-M3-restricted epitopes, even in the absence of bacterial infection or adjuvant. The resulting effectors acutely enhance antimicrobial resistance but do not confer long-term memory protection. JF - International Immunology AU - Tawab, A AU - Fields, J AU - Chao, E AU - Kurlander, R J AD - Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892-1508, USA, rkurlander@mail.cc.nih.gov Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 225 EP - 232 VL - 14 IS - 2 SN - 0953-8178, 0953-8178 KW - M3 determinant KW - mice KW - CD8 antigen KW - LemA protein KW - gamma -Interferon KW - histocompatibility antigen H-2 KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - g-Interferon KW - ^g-Interferon KW - Splenocytes KW - Listeria monocytogenes KW - Listeriosis KW - Lymphocytes T KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18305546?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Immunology&rft.atitle=Recombinant+lemA+without+adjuvant+induces+extensive+expansion+of+H2-M3-restricted+CD8+effectors%2C+which+can+suppress+primary+listeriosis+in+mice&rft.au=Tawab%2C+A%3BFields%2C+J%3BChao%2C+E%3BKurlander%2C+R+J&rft.aulast=Tawab&rft.aufirst=A&rft.date=2002-02-01&rft.volume=14&rft.issue=2&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=International+Immunology&rft.issn=09538178&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Listeria monocytogenes; Listeriosis; Splenocytes; Lymphocytes T ER - TY - JOUR T1 - Lentiviral Vectors for Gene Therapy of HIV-1 Infection AN - 18299401; 5351841 AB - Lentiviral vectors based on HIV-1, HIV-2, or SIV have the ability to transduce dividing and non-dividing T cells, dendritic cells, hematopoietic stem cells and macrophages, which are the main target cells for gene therapy of HIV-1 infection. Besides their function as gene delivery vehicles, lentiviral vector backbones containing the cis-acting sequences necessary to perform a complete replication cycle in the presence of viral proteins provided in trans, have the ability to inhibit HIV-1 replication by several mechanisms that include sequestration of the regulatory proteins Tat and Rev, competition for packaging into virions and possibly by inhibition of reverse transcription in heterodimeric virions. Expression of anti-HIV-1 genes in these vectors would strengthen the potency of this inhibition. To avoid self-inhibition of the vector packaging system, lentiviral vectors have to be modified to become resistant to the anti-HIV-1 genes encoded by them. This review discusses the different genetic intervention strategies for gene therapy of HIV-1 infection focusing in the use of lentiviral vectors as the main agents to mediate inhibition of HIV-1 replication. It also discusses possible strategies to adapt HIV-1 or HIV-2 vectors to express the different classes of anti-HIV-1 genes and approaches to improve in vivo vector mobilization. JF - Current Gene Therapy AU - Mautino, M R AD - Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, Bldg. 10, Room 10C103, Bethesda, MD 20892, USA, mmautino@nhgri.nih.gov Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 23 EP - 43 VL - 2 IS - 1 SN - 1566-5232, 1566-5232 KW - HIV-1 KW - HIV-2 KW - SIV KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Acquired immune deficiency syndrome KW - Gene therapy KW - Expression vectors KW - Reviews KW - Human immunodeficiency virus 1 KW - Human immunodeficiency virus 2 KW - Transduction KW - Simian immunodeficiency virus KW - W3 33181:Gene therapy vectors KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews KW - V 22004:AIDS: Clinical aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18299401?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Gene+Therapy&rft.atitle=Lentiviral+Vectors+for+Gene+Therapy+of+HIV-1+Infection&rft.au=Mautino%2C+M+R&rft.aulast=Mautino&rft.aufirst=M&rft.date=2002-02-01&rft.volume=2&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Current+Gene+Therapy&rft.issn=15665232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Human immunodeficiency virus 2; Simian immunodeficiency virus; Reviews; Expression vectors; Acquired immune deficiency syndrome; Gene therapy; Transduction ER - TY - JOUR T1 - Sensory and physiologic effects of menthol and nonmenthol cigarettes with differing nicotine delivery AN - 18295279; 5337366 AB - Many smokers choose menthol-flavored cigarettes, however, the influence of menthol on the effects of smoke-delivered nicotine is unknown. Research and commercial cigarettes, menthol and nonmenthol, that delivered a wide range of nicotine were evaluated. Menthol (n = 18) and nonmenthol (n = 18) cigarette smokers participated in a single session during which three cigarettes were smoked 45 min apart, in random order. Federal Trade Commission (ETC) nicotine yields of the three cigarettes were: research, low yield, 0.2 mg, commercial cigarettes (average), 1.2 mg; research, high yield, 2.5 mg. Commercial and high-yield cigarettes increased heart rate (HR) and blood pressure more than low-yield cigarettes; although, no differences in exhaled carbon monoxide (CO) occurred. Participants smoked commercial cigarettes faster and with fewer puffs than either of the research cigarette indicating production differences can affect topography. There was a significant group by cigarette interaction on satisfaction, and relief from cigarette craving. High-yield nonmenthol cigarettes reduced craving and were rated as more satisfying than high-yield menthol cigarettes. No differences between menthol and nonmenthol cigarettes on other subjective measures (strength, psychological reward, negative effects) were observed. Our findings indicate that nicotine delivery, but not mentholation, influences cardiovascular and most subjective measures. These results illustrate the importance of threshold levels of nicotine on subjective responses to cigarette smoking. JF - Pharmacology Biochemistry and Behavior AU - Pickworth, W B AU - Moolchan, E T AU - Berlin, I AU - Murty, R AD - Clinical Pharmacology Branch, National Institute on Drug Abuse, Intramural Research Program, Addiction Research Center, PO Box 5180, Baltimore, MD 21224, USA, wpickwo@intra.nida.nih.gov Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 55 EP - 61 VL - 71 IS - 1-2 SN - 0091-3057, 0091-3057 KW - man KW - normal subjects KW - menthol KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - Cardiovascular system KW - Nicotine KW - Heart rate KW - Cigarette smoking KW - Blood pressure KW - N3 11106:Neurobiology of drug abuse KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18295279?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacology+Biochemistry+and+Behavior&rft.atitle=Sensory+and+physiologic+effects+of+menthol+and+nonmenthol+cigarettes+with+differing+nicotine+delivery&rft.au=Pickworth%2C+W+B%3BMoolchan%2C+E+T%3BBerlin%2C+I%3BMurty%2C+R&rft.aulast=Pickworth&rft.aufirst=W&rft.date=2002-02-01&rft.volume=71&rft.issue=1-2&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Pharmacology+Biochemistry+and+Behavior&rft.issn=00913057&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Cigarette smoking; Nicotine; Cardiovascular system; Blood pressure; Heart rate ER - TY - JOUR T1 - Fluorine-18 labeled mouse bone marrow-derived dendritic cells can be detected in vivo by high resolution projection imaging AN - 18261310; 5313587 AB - Immunization with ex vivo generated dendritic cells has become a focus for many clinical applications. The optimal site of injection and the migration pattern of these cells remain to be elucidated. We therefore developed a novel method for labeling mouse bone marrow-derived dendritic cells (BMDC) with the positron emitting radioisotope F-18 using N-succinimidyl-4-[F-18]fluorobenzoate, which covalently binds to the lysine residues of cell surface proteins. When we determined the stability of F-18 labeled BMDC, we found that at 4 h only 44 plus or minus 10% of the initial cell-bound activity was retained at 37 degree C, whereas considerably more (91 plus or minus 3%) was retained at 4 degree C. Labeled cells did not exhibit any significant alteration in cell viability or phenotype as determined by trypan blue exclusion and FACS analysis 24 h after radiolabeling. Furthermore, F-18-labeled BMDC stimulated allogeneic T cells in a mixed leukocyte reaction as potently as did sham-treated BMDC and migrated towards secondary lymphoid tissue chemokine (SLC) in a chemotaxis assay in vitro with the same efficiency as sham-treated BMDC. Migration of F-18-labeled BMDC was studied after footpad injection by (1) ex vivo counting of dissected tissues using a gamma counter and (2) in vivo by imaging mice with PiPET, a 2-mm resolution positron projection imager. After 4 h, the ratio between measured activity in draining vs. contralateral (D/C) lymph nodes (LN) was 166 plus or minus 96 (n=7) in the case of live cell injections, whereas if we injected heat-killed F-18-labeled BMDC or F-18-labeled macrophages the D/C ratios were 17 plus or minus 2 (n=2) and 14 plus or minus 4 (n=2), respectively. Injection of cell-free activity in the form of F-18-labeled 4-fluorobenzoic acid resulted in a D/C ratio of 7 plus or minus 2 (n=3), suggesting that the activity measured in the draining lymph node was associated with migrated F-18-labeled BMDC. When F-18-labeled live cells were injected into the footpad, 0.18 plus or minus 0.04% (n=7) of footpad activity was found in the draining LN within 4 h, whereas none was found in the contralateral LN. Quantitative assessment of cell migration by PET projection imaging of mice confirmed the ex-vivo counting results. These studies indicate that PET imaging offers a new approach for in vivo studies of dendritic cell biodistribution and migration. JF - Journal of Immunological Methods AU - Olasz, E B AU - Lang, L AU - Seidel, J AU - Green, M V AU - Eckelman, W C AU - Katz, SI AD - Dermatology Branch, National Cancer Institute, National Institutes of Health, Bldg. 10, Room 12N238, 10 Center Drive, MSC 1908, 20892-1908 Bethesda, MD USA Y1 - 2002/02/01/ PY - 2002 DA - 2002 Feb 01 SP - 137 EP - 148 PB - Elsevier Science VL - 260 IS - 1-2 SN - 0022-1759, 0022-1759 KW - mice KW - fluorine-18 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Dendritic cells KW - Radioactive labelling KW - Radioisotopes KW - Bone marrow KW - W3 33240:Immunology KW - F 06713:Physicochemical methods KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18261310?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunological+Methods&rft.atitle=Fluorine-18+labeled+mouse+bone+marrow-derived+dendritic+cells+can+be+detected+in+vivo+by+high+resolution+projection+imaging&rft.au=Olasz%2C+E+B%3BLang%2C+L%3BSeidel%2C+J%3BGreen%2C+M+V%3BEckelman%2C+W+C%3BKatz%2C+SI&rft.aulast=Olasz&rft.aufirst=E&rft.date=2002-02-01&rft.volume=260&rft.issue=1-2&rft.spage=137&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Dendritic cells; Bone marrow; Radioactive labelling; Radioisotopes ER - TY - JOUR T1 - Crystal structure of the Yersinia pestis GTPase activator YopE AN - 18259701; 5316514 AB - Yersinia pestis, the causative agent of bubonic plague, evades the immune response of the infected organism by using a type III (contact-dependent) secretion system to deliver effector proteins into the cytosol of mammalian cells, where they interfere with signaling pathways that regulate inflammation and cytoskeleton dynamics. The cytotoxic effector YopE functions as a potent GTPase-activating protein (GAP) for Rho family GTP-binding proteins, including RhoA, Rac1, and Cdc42. Down-regulation of these molecular switches results in the loss of cell motility and inhibition of phagocytosis, enabling Y. pestis to thrive on the surface of macrophages. We have determined the crystal structure of the GAP domain of YopE (YopE sub(GAP); residues 90-219) at 2.2-Angstrom resolution. Apart from the fact that it is composed almost entirely of alpha -helices, YopE sub(GAP) shows no obvious structural similarity with eukaryotic RhoGAP domains. Moreover, unlike the catalytically equivalent arginine fingers of the eukaryotic GAPs, which are invariably contained within flexible loops, the critical arginine in YopE sub(GAP) (Arg144) is part of an alpha -helix. The structure of YopE sub(GAP) is strikingly similar to the GAP domains from Pseudomonas aeruginosa (ExoS sub(GAP)) and Salmonella enterica (SptP sub(GAP)), despite the fact that the three amino acid sequences are not highly conserved. A comparison of the YopE sub(GAP) structure with those of the Rac1-ExoS sub(GAP) and Rac1-SptP complexes indicates that few, if any, significant conformational changes occur in YopE sub(GAP) when it interacts with its G protein targets. The structure of YopE sub(GAP) may provide an avenue for the development of novel therapeutic agents to combat plague. JF - Protein Science AU - Evdokimov, A G AU - Tropea, JE AU - Routzahn, K M AU - Waugh, D S AD - Protein Engineering Section, Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, P.O. Box B, Frederick, MD 21702-1201, USA, waughd@ncifcrf.gov Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 401 EP - 408 VL - 11 IS - 2 SN - 0961-8368, 0961-8368 KW - YopE protein KW - Microbiology Abstracts B: Bacteriology KW - Motility KW - Host-pathogen interactions KW - Yersinia pestis KW - Drug development KW - Immune response KW - Plague KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18259701?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+Science&rft.atitle=Crystal+structure+of+the+Yersinia+pestis+GTPase+activator+YopE&rft.au=Evdokimov%2C+A+G%3BTropea%2C+JE%3BRoutzahn%2C+K+M%3BWaugh%2C+D+S&rft.aulast=Evdokimov&rft.aufirst=A&rft.date=2002-02-01&rft.volume=11&rft.issue=2&rft.spage=401&rft.isbn=&rft.btitle=&rft.title=Protein+Science&rft.issn=09618368&rft_id=info:doi/10.1110%2Fps.34102 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Yersinia pestis; Plague; Host-pathogen interactions; Drug development; Immune response; Motility DO - http://dx.doi.org/10.1110/ps.34102 ER - TY - JOUR T1 - In Vivo Assessment of Gene Delivery to Keratinocytes by Lentiviral Vectors AN - 18238342; 5291551 AB - For skin gene therapy, introduction of a desired gene into keratinocyte progenitor or stem cells could overcome the problem of achieving persistent gene expression in a significant percentage of keratinocytes. Although keratinocyte stem cells have not yet been completely characterized and purified for gene targeting purposes, lentiviral vectors may be superior to retroviral vectors at gene introduction into these stem cells, which are believed to divide and cycle slowly. Our initial in vitro studies demonstrate that lentiviral vectors are able to efficiently transduce nondividing keratinocytes, unlike retroviral vectors, and do not require the lentiviral accessory genes for keratinocyte transduction. When lentiviral vectors expressing green fluorescent protein (GFP) were directly injected into the dermis of human skin grafted onto immunocompromised mice, transduction of dividing basal and nondividing suprabasal keratinocytes could be demonstrated, which was not the case when control retroviral vectors were used. However, flow cytometry analysis demonstrated low transduction efficiency, and histological analysis at later time points provided no evidence for progenitor cell targeting. In an alternative in vivo method, human keratinocytes were transduced in tissue culture (ex vivo) with either lentiviral or retroviral vectors and grafted as skin equivalents onto immunocompromised mice. GFP expression was analyzed in these human skin grafts after several cycles of epidermal turnover, and both the lentiviral and retroviral vector-transduced grafts had similar percentages of GFP-expressing keratinocytes. This ex vivo grafting study provides a good in vivo assessment of gene introduction into progenitor cells and suggests that lentiviral vectors are not necessarily superior to retroviral vectors at introducing genes into keratinocyte progenitor cells during in vitro culture. JF - Journal of Virology AU - Kuhn, U AU - Terunuma, Atsushi AU - Pfutzner, W AU - Foster, R A AU - Vogel, J C AD - Dermatology Branch, National Cancer Institute, NIH, Bldg. 10, Room 12N260, 10 Center Dr., MSC 1908, Bethesda, MD 20892-1908., jonvogel@mail.nih.gov Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 1496 EP - 1504 VL - 76 IS - 3 SN - 0022-538X, 0022-538X KW - man KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Skin KW - Gene therapy KW - Gene transfer KW - Immunocompromised hosts KW - Keratinocytes KW - Transduction KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18238342?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=In+Vivo+Assessment+of+Gene+Delivery+to+Keratinocytes+by+Lentiviral+Vectors&rft.au=Kuhn%2C+U%3BTerunuma%2C+Atsushi%3BPfutzner%2C+W%3BFoster%2C+R+A%3BVogel%2C+J+C&rft.aulast=Kuhn&rft.aufirst=U&rft.date=2002-02-01&rft.volume=76&rft.issue=3&rft.spage=1496&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/10.1128%2FJVI.76.3.1496-1504.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Expression vectors; Transduction; Gene therapy; Gene transfer; Skin; Keratinocytes; Immunocompromised hosts DO - http://dx.doi.org/10.1128/JVI.76.3.1496-1504.2002 ER - TY - JOUR T1 - Two "Wild-Type" Variants of Escherichia coli sigma super(70): Context-Dependent Effects of the Identity of Amino Acid 149 AN - 18234609; 5298109 AB - The identity of amino acid 149 of Escherichia coli sigma super(70) has been reported variably as either arginine or aspartic acid. We show that the behavior of both a region 1.2 deletion and a single-amino-acid substitution at position 122 are greatly affected by the identity of amino acid 149. JF - Journal of Bacteriology AU - Baldwin, N E AU - McCracken, A AU - Dombroski, A J AD - NIH, Center for Scientific Review, 6701 Rockledge Dr., Mailstop 7808, Bethesda, MD 20892., dombrosa@csr.nih.gov Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 1192 EP - 1195 VL - 184 IS - 4 SN - 0021-9193, 0021-9193 KW - amino acid sequence KW - sigma 70 factor KW - arginine KW - aspartic acid KW - Microbiology Abstracts B: Bacteriology KW - ^s70 factor KW - Deletion mutant KW - Escherichia coli KW - Proteins KW - Sigma factor KW - J 02726:RNA and ribosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18234609?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Two+%22Wild-Type%22+Variants+of+Escherichia+coli+sigma+super%2870%29%3A+Context-Dependent+Effects+of+the+Identity+of+Amino+Acid+149&rft.au=Baldwin%2C+N+E%3BMcCracken%2C+A%3BDombroski%2C+A+J&rft.aulast=Baldwin&rft.aufirst=N&rft.date=2002-02-01&rft.volume=184&rft.issue=4&rft.spage=1192&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2Fjb.184.4.1192-1195.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Deletion mutant; Proteins; Sigma factor DO - http://dx.doi.org/10.1128/jb.184.4.1192-1195.2002 ER - TY - JOUR T1 - Cytochrome aa sub(3) in Haloferax volcanii AN - 18229618; 5294833 AB - A cytochrome in an extremely halophilic archaeon, Haloferax volcanii, was purified to homogeneity. This protein displayed a redox difference spectrum that is characteristic of a-type cytochromes and a CN super(-) complex spectrum that indicates the presence of heme a and heme a sub(3). This cytochrome aa sub(3) consisted of 44- and 35-kDa subunits. The amino acid sequence of the 44-kDa subunit was similar to that of the heme-copper oxidase subunit I, and critical amino acid residues for metal binding, such as histidines, were highly conserved. The reduced cytochrome c partially purified from the bacterial membrane fraction was oxidized by the cytochrome aa sub(3), providing physiological evidence for electron transfer from cytochrome c to cytochrome aa sub(3) in archaea. JF - Journal of Bacteriology AU - Tanaka, M AU - Ogawa, N AU - Ihara, K AU - Sugiyama, Y AU - Mukohata, Y AD - Genetic Pharmacology Unit, Experimental Therapeutics Branch, NINDS, National Institutes of Health, 10 Center Dr., MSC 1406, Bethesda, MD 10892-1406., TanakaM@ninds.nih.gov Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 840 EP - 845 VL - 184 IS - 3 SN - 0021-9193, 0021-9193 KW - cytochrome aa3 KW - Microbiology Abstracts B: Bacteriology KW - Haloferax volcanii KW - Histidine KW - Electron transfer KW - Halophilic archaea KW - J 02723:Photosynthesis, electron transport and related phenomena UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18229618?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Cytochrome+aa+sub%283%29+in+Haloferax+volcanii&rft.au=Tanaka%2C+M%3BOgawa%2C+N%3BIhara%2C+K%3BSugiyama%2C+Y%3BMukohata%2C+Y&rft.aulast=Tanaka&rft.aufirst=M&rft.date=2002-02-01&rft.volume=184&rft.issue=3&rft.spage=840&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.184.3.840-845.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Haloferax volcanii; Halophilic archaea; Histidine; Electron transfer DO - http://dx.doi.org/10.1128/JB.184.3.840-845.2002 ER - TY - JOUR T1 - Construction and Characterization of a Replication-Competent Retroviral Shuttle Vector Plasmid AN - 18226530; 5296321 AB - We constructed two versions of an RCASBP-based retroviral shuttle vector, RSVP (RCASBP shuttle vector plasmid), containing either the zeocin or blasticidin resistance gene. In this vector, the drug resistance gene is expressed in avian cells from the long terminal repeat (LTR) promoter, whereas in bacteria the resistance gene is expressed from a bacterial promoter. The vector contains a bacterial origin of replication (ColE1) to allow circular viral DNA to replicate as a plasmid in bacteria. The vector also contains the lac operator sequence, which binds to the lac repressor protein, providing a simple and rapid way to purify the vector DNA. The RSVP plasmid contains the following sequence starting with the 5" end: LTR, gag, pol, env, drug resistance gene, lac operator, ColE1, LTR. After this plasmid was transfected into DF-1 cells, we were able to rescue the circularized unintegrated viral DNA from RSVP simply by transforming the Hirt DNA into Escherichia coli. Furthermore, we were able to rescue the integrated provirus. DNA from infected cells was digested with an appropriate restriction enzyme (ClaI) and the vector-containing segments were enriched using lac repressor protein and then self-ligated. These enriched fractions were used to transform E. coli. The transformation was successful and we did recover integration sites, but higher-efficiency rescue was obtained with electroporation. The vector is relatively stable upon passage in avian cells. Southern blot analyses of genomic DNAs derived from successive viral passages under nonselective conditions showed that the cassette (drug resistance gene- lac operator-ColE1) insert was present in the vector up to the third viral passage for both resistance genes, which suggests that the RSVP vectors are stable for approximately three viral passages. Together, these results showed that RSVP vectors are useful tools for cloning unintegrated or integrated viral DNAs. JF - Journal of Virology AU - Oh, J AU - Julias, J G AU - Ferris, AL AU - Hughes, SH AD - HIV Drug Resistance Program, National Cancer Institute, NCI-Frederick, P.O. Box B, Frederick, MD 21702-1201., hughes@ncifrcf.gov Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 1762 EP - 1768 VL - 76 IS - 4 SN - 0022-538X, 0022-538X KW - birds KW - shuttle vectors KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts KW - Transformation KW - Replication KW - Long terminal repeat KW - Drug resistance KW - Plasmids KW - Retrovirus KW - Escherichia coli KW - N 14682:Cloning vectors KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18226530?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=Construction+and+Characterization+of+a+Replication-Competent+Retroviral+Shuttle+Vector+Plasmid&rft.au=Oh%2C+J%3BJulias%2C+J+G%3BFerris%2C+AL%3BHughes%2C+SH&rft.aulast=Oh&rft.aufirst=J&rft.date=2002-02-01&rft.volume=76&rft.issue=4&rft.spage=1762&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/10.1128%2FJVI.76.4.1762-1768.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Drug resistance; Plasmids; Transformation; Retrovirus; Long terminal repeat; Replication DO - http://dx.doi.org/10.1128/JVI.76.4.1762-1768.2002 ER - TY - JOUR T1 - Modifying Normal Tissue Damage Postirradiation AN - 17863395; 5973906 AB - Late effects that develop in normal tissues adjacent to the tumor site in the months to years after radiotherapy can reduce the quality of life of cancer survivors. They can be dose-limiting and debilitating or life-threatening. There is now evidence that some late effects may be preventable or partially reversible. A workshop, 'Modifying Normal Tissue Damage Postirradiationa, was sponsored by the Radiation Research Program of the National Cancer Institute to identify the current status of and research needs and opportunities in this area. Mechanistic, genetic and physiological studies of the development of late effects are needed and will provide a rational basis for development of treatments. Interdisciplinary teams will be needed to carry out this research, including pathologists, physiologists, geneticists, molecular biologists, experts in functional imaging, wound healing, burn injury, molecular biology, and medical oncology, in addition to radiation biologists, physicists and oncologists. The participants emphasized the need for developing and choosing appropriate models, and for radiation dose-response studies to determine whether interventions remain effective at the radiation doses used clinically. Both preclinical and clinical studies require long-term follow-up, and easier-to-use, more objective clinical scoring systems must be developed and standardized. New developments in biomedical imaging should provide useful tools in all these endeavors. The ultimate goals are to improve the quality of life and efficacy of treatment for cancer patients treated with radiotherapy. JF - Radiation Research AU - Stone, H B AU - McBride, W H AU - Coleman, C N AD - Radiation Research Program, National Cancer Institute, 6130 Executive Boulevard, 6010, Bethesda, Maryland 20892-7440 Y1 - 2002/02// PY - 2002 DA - Feb 2002 SP - 204 EP - 223 PB - Radiation Research Society VL - 157 IS - 2 SN - 0033-7587, 0033-7587 KW - Toxicology Abstracts KW - Burns KW - Injuries KW - Radiation KW - Wound healing KW - Radiotherapy KW - Oncology KW - imaging KW - Research programs KW - Cancer KW - Quality of life KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17863395?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+Research&rft.atitle=Modifying+Normal+Tissue+Damage+Postirradiation&rft.au=Stone%2C+H+B%3BMcBride%2C+W+H%3BColeman%2C+C+N&rft.aulast=Stone&rft.aufirst=H&rft.date=2002-02-01&rft.volume=157&rft.issue=2&rft.spage=204&rft.isbn=&rft.btitle=&rft.title=Radiation+Research&rft.issn=00337587&rft_id=info:doi/10.1043%2F0033-7587%282002%291572.0.CO%3B2 L2 - http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0033-7587&volume=157&page=204 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - imaging; Quality of life; Cancer; Radiotherapy; Burns; Research programs; Wound healing; Radiation; Oncology; Injuries DO - http://dx.doi.org/10.1043/0033-7587(2002)157<0204:MNTDP>2.0.CO;2 ER - TY - JOUR T1 - Serial analysis of gene expression in renal carcinoma cells reveals VHL-dependent sensitivity to TNFalpha cytotoxicity. AN - 71482353; 11840338 AB - We have used serial analysis of gene expression (SAGE) to investigate the influence of the von Hippel-Lindau (VHL) gene on global gene expression profiles. SAGE libraries were prepared from renal cell carcinoma (RCC) lines that either lack (parental) or express wild-type VHL (wtVHL). Comparison of these libraries revealed some differentially expressed genes (Glut-1, for example) that were known to be influenced by VHL, but the majority of genes had not previously been reported to be affected by the cell's VHL status. The identification of several genes involved in TNFalpha-mediated events prompted us to compare the sensitivity of cells with different VHL status in TNFalpha cytotoxicity assays. Strikingly, VHL-deficient cells were much more resistant to the toxic influence of TNFalpha. We propose that VHL-dependent sensitization of RCC cells to TNFalpha-mediated killing may contribute to VHL's growth suppressive function. JF - Oncogene AU - Caldwell, M Craig AU - Hough, Colleen AU - Fürer, Stefanie AU - Linehan, W Marston AU - Morin, Patrice J AU - Gorospe, Myriam AD - Laboratory of Cellular and Molecular Biology, National Institute on Aging-IRP, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2002/01/31/ PY - 2002 DA - 2002 Jan 31 SP - 929 EP - 936 VL - 21 IS - 6 SN - 0950-9232, 0950-9232 KW - Neoplasm Proteins KW - 0 KW - RNA, Messenger KW - RNA, Neoplasm KW - Recombinant Fusion Proteins KW - Tumor Necrosis Factor-alpha KW - Tumor Suppressor Proteins KW - Ubiquitin-Protein Ligases KW - EC 2.3.2.27 KW - Von Hippel-Lindau Tumor Suppressor Protein KW - Ligases KW - EC 6.- KW - VHL protein, human KW - EC 6.3.2.- KW - Index Medicus KW - RNA, Neoplasm -- biosynthesis KW - Computer Systems KW - Drug Resistance -- genetics KW - Blotting, Northern KW - Tumor Cells, Cultured -- metabolism KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - RNA, Neoplasm -- genetics KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Recombinant Fusion Proteins -- physiology KW - Polymerase Chain Reaction KW - Blotting, Western KW - Transfection KW - Gene Library KW - Carcinoma, Renal Cell -- pathology KW - Kidney Neoplasms -- genetics KW - Ligases -- genetics KW - Kidney Neoplasms -- pathology KW - Gene Expression Regulation, Neoplastic -- physiology KW - Gene Expression Profiling -- methods KW - Ligases -- physiology KW - Tumor Necrosis Factor-alpha -- toxicity KW - Carcinoma, Renal Cell -- metabolism KW - Neoplasm Proteins -- physiology KW - Neoplasm Proteins -- genetics KW - Kidney Neoplasms -- metabolism KW - Carcinoma, Renal Cell -- genetics KW - Ligases -- deficiency KW - Gene Expression Regulation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71482353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Serial+analysis+of+gene+expression+in+renal+carcinoma+cells+reveals+VHL-dependent+sensitivity+to+TNFalpha+cytotoxicity.&rft.au=Caldwell%2C+M+Craig%3BHough%2C+Colleen%3BF%C3%BCrer%2C+Stefanie%3BLinehan%2C+W+Marston%3BMorin%2C+Patrice+J%3BGorospe%2C+Myriam&rft.aulast=Caldwell&rft.aufirst=M&rft.date=2002-01-31&rft.volume=21&rft.issue=6&rft.spage=929&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-05 N1 - Date created - 2002-02-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Centrosome abnormalities, recurring deletions of chromosome 4, and genomic amplification of HER2/neu define mouse mammary gland adenocarcinomas induced by mutant HER2/neu. AN - 71449448; 11840334 AB - The conditional expression of activated HER2/neu gene under its endogenous promoter in the mammary epithelium of the mouse results in accelerated lobular development and focal mammary tumors. Carcinogenesis, however, requires amplification and considerably increased expression levels of oncogenic neu. Deducing from the multiple genetic aberrations required for human breast cancer to develop, we hypothesized that in addition to the over-expression of an activated HER2/neu, secondary aberrations would occur. We have therefore conducted a genomic screen for chromosomal imbalances and translocations using comparative genomic hybridization and spectral karyotyping. The results reveal a moderate degree of chromosomal instability and micronuclei formation in short-term cultures established from primary tumors. Genomic instability appears to be linked to the amplification of functional centrosomes, a phenomenon that we frequently observed in other tumor types. Seventy per cent of the tumors revealed genomic amplification of HER2/neu, often in the form of double minute chromosomes, which correlated with recurring loss of mouse chromosome 4D-E, a region that is orthologous to distal human chromosome 1p. It is likely that this region contains putative tumor suppressor genes whose inactivation is required for tumor formation in this model of human breast cancer. JF - Oncogene AU - Montagna, Cristina AU - Andrechek, Eran R AU - Padilla-Nash, Hesed AU - Muller, William J AU - Ried, Thomas AD - Genetics Branch, Center for Cancer Research, National Cancer Institute/NIH, Bldg. 9, Rm. 1N105, 9 Memorial Drive, Bethesda, MD 20892, USA. Y1 - 2002/01/31/ PY - 2002 DA - 2002 Jan 31 SP - 890 EP - 898 VL - 21 IS - 6 SN - 0950-9232, 0950-9232 KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Index Medicus KW - Models, Animal KW - Animals KW - Receptor, ErbB-2 -- physiology KW - Karyotyping -- methods KW - Gene Silencing KW - In Situ Hybridization, Fluorescence KW - Mice KW - Flow Cytometry KW - Nucleic Acid Hybridization KW - Centrosome -- ultrastructure KW - Chromosome Mapping KW - Female KW - Chromosome Deletion KW - Genes, erbB-2 KW - Genes, Tumor Suppressor KW - Chromosome Aberrations KW - Mammary Neoplasms, Experimental -- genetics KW - Adenocarcinoma -- genetics KW - Cell Transformation, Neoplastic -- genetics KW - Gene Amplification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71449448?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Centrosome+abnormalities%2C+recurring+deletions+of+chromosome+4%2C+and+genomic+amplification+of+HER2%2Fneu+define+mouse+mammary+gland+adenocarcinomas+induced+by+mutant+HER2%2Fneu.&rft.au=Montagna%2C+Cristina%3BAndrechek%2C+Eran+R%3BPadilla-Nash%2C+Hesed%3BMuller%2C+William+J%3BRied%2C+Thomas&rft.aulast=Montagna&rft.aufirst=Cristina&rft.date=2002-01-31&rft.volume=21&rft.issue=6&rft.spage=890&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-05 N1 - Date created - 2002-02-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacological characterization of vanilloid receptor located in the brain. AN - 71441926; 11834295 AB - Specific [3H]resiniferatoxin (RTX) binding detects the vanilloid receptor type I (VR1). In the present study we demonstrate specific, high-affinity, saturable [3H]RTX binding in various areas of monkey brain not known to be innervated by primary afferent neurons as well as in spinal cord and dorsal root ganglion neurons of the same origin. Detailed pharmacological characterization and comparison revealed no major difference in binding affinities between the peripheral and the central sites as measured by K(d)/K(i) values. In general, lower receptor density was measured in selected brain areas than in the periphery. Areas with higher receptor density were detected in the locus ceruleus, preoptic area, and medial basal hypothalamus of the brain. Both capsaicin and the competitive antagonist capsazepine inhibited the specific binding of [3H]RTX to membrane preparations of the dorsal horn of the spinal cord and dorsal root ganglia with K(i) values of 4.3+/-0.32 microM and 2.7+/-0.33 microM, respectively. Inhibition was observed in the central areas (hypothalamus) with K(i) values of 0.95+/-0.1 microM for capsaicin and 0.86+/-0.11 microM for capsazepine. Previous biological and pharmacological evidence suggested that vanilloid receptors were present in the brain. Our results demonstrate that the pharmacological properties of both the peripheral and central receptor sites display appropriate pharmacological similarity to represent the same receptor class. The modest differences in ligand affinities for the vanilloid receptor expressed in the brain nuclei and the dorsal root ganglion neurons may correspond to differences in sequence, modification or associated proteins. JF - Brain research. Molecular brain research AU - Szabo, Tamas AU - Biro, Tamas AU - Gonzalez, Adamar F AU - Palkovits, Miklos AU - Blumberg, Peter M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institute of Mental Health, Bldg. 37, Room 3A01, 37 Convent Drive, MSC 4255, Bethesda, MD 20892, USA. Y1 - 2002/01/31/ PY - 2002 DA - 2002 Jan 31 SP - 51 EP - 57 VL - 98 IS - 1-2 SN - 0169-328X, 0169-328X KW - Diterpenes KW - 0 KW - Receptors, Drug KW - TRPV Cation Channels KW - TRPV1 receptor KW - resiniferatoxin KW - A5O6P1UL4I KW - capsazepine KW - LFW48MY844 KW - Capsaicin KW - S07O44R1ZM KW - Index Medicus KW - Diterpenes -- pharmacology KW - Animals KW - Macaca fascicularis KW - Spinal Cord -- metabolism KW - Hippocampus -- metabolism KW - Organ Specificity KW - Locus Coeruleus -- metabolism KW - Reverse Transcriptase Polymerase Chain Reaction KW - Diterpenes -- metabolism KW - Structure-Activity Relationship KW - Hippocampus -- drug effects KW - Neurons, Afferent -- metabolism KW - Ganglia, Spinal -- cytology KW - Preoptic Area -- metabolism KW - Locus Coeruleus -- drug effects KW - Ganglia, Spinal -- metabolism KW - Kinetics KW - Spinal Cord -- drug effects KW - Binding, Competitive KW - Preoptic Area -- drug effects KW - Neurons, Afferent -- drug effects KW - Ganglia, Spinal -- drug effects KW - Receptors, Drug -- metabolism KW - Receptors, Drug -- drug effects KW - Brain Chemistry -- drug effects KW - Capsaicin -- metabolism KW - Capsaicin -- analogs & derivatives KW - Capsaicin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71441926?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research.+Molecular+brain+research&rft.atitle=Pharmacological+characterization+of+vanilloid+receptor+located+in+the+brain.&rft.au=Szabo%2C+Tamas%3BBiro%2C+Tamas%3BGonzalez%2C+Adamar+F%3BPalkovits%2C+Miklos%3BBlumberg%2C+Peter+M&rft.aulast=Szabo&rft.aufirst=Tamas&rft.date=2002-01-31&rft.volume=98&rft.issue=1-2&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Molecular+brain+research&rft.issn=0169328X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-29 N1 - Date created - 2002-02-08 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEAS) regulate apoptosis during neurogenesis by triggering the Akt signaling pathway in opposing ways. AN - 71439112; 11834296 AB - Dehydroepiandrosterone (DHEA) can function to protect neural precursors and their progeny targeted with toxic insults; however, the molecular mechanisms underlying the neuroprotective effects of DHEA are not understood. We cultured neural precursors from the embryonic forebrain of rats and examined the effects of DHEA and its sulfated derivative (DHEAS) on the activation of the serine-threonine protein kinase Akt, which is widely implicated in cell survival signaling. We found that DHEA activated Akt in neural precursor culture, in association with a decrease in apoptosis. In contrast, DHEAS decreased activated Akt levels and increased apoptosis. The effects of DHEA on neural cell survival and activation of Akt were not blocked by the steroid hormone antagonists flutamide and tamoxifen, but both were blocked by a PI3-K inhibitor, LY294002. These findings suggest that during neurogenesis in the developing cortex, DHEA and DHEAS regulate the survival of neural precursors and progeny through the Akt signaling pathway. JF - Brain research. Molecular brain research AU - Zhang, Lei AU - Li, Bing shen AU - Ma, Wu AU - Barker, Jeffery L AU - Chang, Yoong H AU - Zhao, Weiqin AU - Rubinow, David R AD - Behavioral Endocrinology Branch, National Institute of Mental Health, Building 36, Room 2C02, Bethesda, MD 20892, USA. zhangl@codon.nih.gov Y1 - 2002/01/31/ PY - 2002 DA - 2002 Jan 31 SP - 58 EP - 66 VL - 98 IS - 1-2 SN - 0169-328X, 0169-328X KW - Androgen Antagonists KW - 0 KW - Chromones KW - Enzyme Inhibitors KW - Fetal Proteins KW - Morpholines KW - Nerve Tissue Proteins KW - Proto-Oncogene Proteins KW - Selective Estrogen Receptor Modulators KW - Tamoxifen KW - 094ZI81Y45 KW - 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one KW - 31M2U1DVID KW - Dehydroepiandrosterone KW - 459AG36T1B KW - Dehydroepiandrosterone Sulfate KW - 57B09Q7FJR KW - Flutamide KW - 76W6J0943E KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Akt1 protein, rat KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - Index Medicus KW - Tamoxifen -- pharmacology KW - Animals KW - Protein Processing, Post-Translational -- drug effects KW - Androgen Antagonists -- pharmacology KW - Dose-Response Relationship, Drug KW - Morpholines -- pharmacology KW - Selective Estrogen Receptor Modulators -- pharmacology KW - Phosphorylation -- drug effects KW - Rats KW - Rats, Sprague-Dawley KW - Chromones -- pharmacology KW - Enzyme Activation -- drug effects KW - Flutamide -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Phosphatidylinositol 3-Kinases -- antagonists & inhibitors KW - Nerve Tissue Proteins -- physiology KW - Telencephalon -- embryology KW - Neurons -- drug effects KW - Telencephalon -- cytology KW - Nerve Tissue Proteins -- antagonists & inhibitors KW - Proto-Oncogene Proteins -- physiology KW - Dehydroepiandrosterone Sulfate -- pharmacology KW - Fetal Proteins -- physiology KW - Apoptosis -- drug effects KW - Neurons -- cytology KW - Signal Transduction -- drug effects KW - Dehydroepiandrosterone -- pharmacology KW - Fetal Proteins -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71439112?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research.+Molecular+brain+research&rft.atitle=Dehydroepiandrosterone+%28DHEA%29+and+its+sulfated+derivative+%28DHEAS%29+regulate+apoptosis+during+neurogenesis+by+triggering+the+Akt+signaling+pathway+in+opposing+ways.&rft.au=Zhang%2C+Lei%3BLi%2C+Bing+shen%3BMa%2C+Wu%3BBarker%2C+Jeffery+L%3BChang%2C+Yoong+H%3BZhao%2C+Weiqin%3BRubinow%2C+David+R&rft.aulast=Zhang&rft.aufirst=Lei&rft.date=2002-01-31&rft.volume=98&rft.issue=1-2&rft.spage=58&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Molecular+brain+research&rft.issn=0169328X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-29 N1 - Date created - 2002-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequence analysis and phenotypes of five temperature sensitive mutator alleles of dnaE, encoding modified alpha-catalytic subunits of Escherichia coli DNA polymerase III holoenzyme. AN - 71416920; 11804607 AB - In the 1970s, several thermosensitive alleles of dnaE (encoding the alpha-catalytic subunit of pol III) were isolated. Genetic characterization of these dnaE mutants revealed that some are mutator alleles at permissive temperature. We have determined the nucleotide changes of five such temperature sensitive mutator alleles (dnaE9, dnaE74, dnaE486, dnaE511, and dnaE1026) and find that most are single missense mutations. The exception is dnaE1026 which is a compound allele consisting of multiple missense mutations. When the previously characterized mutator alleles were moved into a lexA51(Def) recA730 strain, dnaE486, dnaE1026 and dnaE74 conferred a modest approximately two-six-fold increase in spontaneous mutagenesis when grown at the permissive temperature of 28 degrees C, while dnaE9 and dnaE511 actually resulted in a slight decrease in spontaneous mutagenesis. In isogenic DeltaumuDC derivatives, the level of spontaneous mutagenesis dropped significantly, although in each case, the overall mutator effect conferred by the dnaE allele was relatively larger, with all five dnaE alleles conferring an increased spontaneous mutation rate approximately 5-22-fold over the isogenic dnaE+ DeltaumuDC strain. Interestingly, the temperature sensitivity conferred by each allele varied considerably in the lexA51(Def) recA730 background and in many cases, this phenotype was dependent upon the presence of functional pol V (UmuD'2C). Our data suggest that pol V can compete effectively with the impaired alpha-subunit for a 3' primer terminus and as a result, a large proportion of the phenotypic effects observed with strains carrying missense temperature sensitive mutations in dnaE can, in fact, be attributed to the actions of pol V rather than pol III. JF - Mutation research AU - Vandewiele, Dominique AU - Fernández de Henestrosa, Antonio R AU - Timms, Andrew R AU - Bridges, Bryn A AU - Woodgate, Roger AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2725, USA. Y1 - 2002/01/29/ PY - 2002 DA - 2002 Jan 29 SP - 85 EP - 95 VL - 499 IS - 1 SN - 0027-5107, 0027-5107 KW - Bacterial Proteins KW - 0 KW - DNA Transposable Elements KW - LexA protein, Bacteria KW - DNA Polymerase III KW - EC 2.7.7.- KW - DNA polymerase III, alpha subunit KW - Rec A Recombinases KW - Serine Endopeptidases KW - EC 3.4.21.- KW - Index Medicus KW - Phenotype KW - Bacterial Proteins -- genetics KW - Rec A Recombinases -- genetics KW - Serine Endopeptidases -- genetics KW - Transduction, Genetic KW - Chromosomes, Bacterial KW - Temperature KW - Catalytic Domain KW - Sequence Analysis, DNA KW - Chromosome Mapping KW - DNA Polymerase III -- genetics KW - Escherichia coli -- physiology KW - DNA Polymerase III -- metabolism KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71416920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Sequence+analysis+and+phenotypes+of+five+temperature+sensitive+mutator+alleles+of+dnaE%2C+encoding+modified+alpha-catalytic+subunits+of+Escherichia+coli+DNA+polymerase+III+holoenzyme.&rft.au=Vandewiele%2C+Dominique%3BFern%C3%A1ndez+de+Henestrosa%2C+Antonio+R%3BTimms%2C+Andrew+R%3BBridges%2C+Bryn+A%3BWoodgate%2C+Roger&rft.aulast=Vandewiele&rft.aufirst=Dominique&rft.date=2002-01-29&rft.volume=499&rft.issue=1&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-19 N1 - Date created - 2002-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of developmentally expressed proteins that functionally interact with Nedd4 ubiquitin ligase. AN - 71440632; 11717310 AB - Nedd4 is a HECT domain-containing ubiquitin ligase that mediates ubiquitylation and proteasome degradation of target proteins. The molecular basis for the interaction of Nedd4 with substrates lies in its WW domains, which can bind proline-rich (PY) domains in target proteins. Nedd4 is a developmentally expressed protein and may have a fundamental role to play in embryonic processes. However, whether Nedd4 has such a function is currently unknown, in part because few developmentally regulated ubiquitylation substrates have been identified or characterized. We have carried out a yeast two-hybrid screen and identified four proteins expressed in the mid-gestation embryo that are able to interact with Nedd4. Characterization of their functional interaction with Nedd4 in vitro and in vivo demonstrated that three of the four are bona fide Nedd4 binding partners, and two have the capacity to be ubiquitylation substrates. One of these is the first identified nonviral substrate for Nedd4-mediated monoubiquitylation. Interestingly, neither of these two ubiquitylated proteins interacts with Nedd4 through PY-mediated mechanisms. For one of the three Nedd4 binding partners, there was no discernable evidence of ubiquitylation. However, this protein clearly associates with Nedd4 through its PY domains and can alter the location of Nedd4 in cells, suggesting a role other than as a ubiquitylation substrate. JF - The Journal of biological chemistry AU - Murillas, Rodolfo AU - Simms, Kimberly S AU - Hatakeyama, Shigetsugu AU - Weissman, Allan M AU - Kuehn, Michael R AD - Experimental Immunology Branch, NCI, National Institutes of Health, Bethesda, Maryland 20892-1360, USA. Y1 - 2002/01/25/ PY - 2002 DA - 2002 Jan 25 SP - 2897 EP - 2907 VL - 277 IS - 4 SN - 0021-9258, 0021-9258 KW - Calcium-Binding Proteins KW - 0 KW - DNA, Complementary KW - Endosomal Sorting Complexes Required for Transport KW - Multienzyme Complexes KW - Recombinant Fusion Proteins KW - Ubiquitin KW - Ubiquitin-Protein Ligases KW - EC 2.3.2.27 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Ligases KW - EC 6.- KW - Nedd4 ubiquitin protein ligases KW - EC 6.3.2.- KW - Index Medicus KW - Protein Biosynthesis KW - Plasmids -- metabolism KW - Cell Nucleus -- metabolism KW - Humans KW - Two-Hybrid System Techniques KW - Glutathione Transferase -- metabolism KW - Precipitin Tests KW - Protein Binding KW - Recombinant Fusion Proteins -- metabolism KW - Microscopy, Fluorescence KW - Mutagenesis, Site-Directed KW - Blotting, Western KW - Ubiquitin -- metabolism KW - Transfection KW - DNA, Complementary -- metabolism KW - Multienzyme Complexes -- antagonists & inhibitors KW - Protein Structure, Tertiary KW - Expressed Sequence Tags KW - Cell Line KW - Ligases -- metabolism KW - Calcium-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71440632?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Identification+of+developmentally+expressed+proteins+that+functionally+interact+with+Nedd4+ubiquitin+ligase.&rft.au=Murillas%2C+Rodolfo%3BSimms%2C+Kimberly+S%3BHatakeyama%2C+Shigetsugu%3BWeissman%2C+Allan+M%3BKuehn%2C+Michael+R&rft.aulast=Murillas&rft.aufirst=Rodolfo&rft.date=2002-01-25&rft.volume=277&rft.issue=4&rft.spage=2897&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-25 N1 - Date created - 2002-01-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In Vitro Repression of the gal Promoters by GalR and HU Depends on the Proper Helical Phasing of the Two Operators AN - 18235033; 5298015 AB - Repression of transcription initiation from the two gal promoters, P1 and P2, requires binding of GalR protein to two flanking operators, O sub(E) and O sub(I), binding of HU to a site, hbs, located between the two operators, and supercoiled DNA template. Previous experiments suggested that repression involves the interaction of two DNA-bound GalR proteins, which generates a 113-bp DNA loop encompassing the promoter region. Interaction between two DNA-bound proteins would be allowed if the binding sites on DNA are properly aligned. To test the idea that the observed repression of gal transcription in vitro is mediated by DNA looping, we investigated the effect of changing the relative angular orientation of O sub(E) and O sub(I) in the DNA helix. We found that repression is a periodic function of the distance between the two operator sites. Since repression recurred commensurate with DNA helical repeat, we conclude that the observed in vitro repression is mediated by DNA looping and the in vitro conditions reflect the in vivo situation. JF - Journal of Biological Chemistry AU - Lewis, DEA AU - Adhya, S AD - Laboratory of Molecular Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892-4255, USA, sadhya@helix.nih.gov Y1 - 2002/01/25/ PY - 2002 DA - 2002 Jan 25 SP - 2498 EP - 2504 VL - 277 IS - 4 SN - 0021-9258, 0021-9258 KW - DNA looping KW - GalR protein KW - HU protein KW - double prime HU protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - ^AHU protein KW - Promoters KW - Repression KW - DNA structure KW - Escherichia coli KW - Transcription KW - N 14640:Structure & sequence KW - J 02726:RNA and ribosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18235033?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=In+Vitro+Repression+of+the+gal+Promoters+by+GalR+and+HU+Depends+on+the+Proper+Helical+Phasing+of+the+Two+Operators&rft.au=Lewis%2C+DEA%3BAdhya%2C+S&rft.aulast=Lewis&rft.aufirst=DEA&rft.date=2002-01-25&rft.volume=277&rft.issue=4&rft.spage=2498&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA structure; Transcription; Promoters; Repression ER - TY - JOUR T1 - Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever AN - 223944912; 11807146 AB - Background Patients with neutropenia and persistent fever are often treated empirically with amphotericin B or liposomal amphotericin B to prevent invasive fungal infections. Antifungal triazoles offer a potentially safer and effective alternative. Methods In a randomized, international, multicenter trial, we compared voriconazole, a new second-generation triazole, with liposomal amphotericin B for empirical antifungal therapy. Results A total of 837 patients (415 assigned to voriconazole and 422 to liposomal amphotericin B) were evaluated for success of treatment. The overall success rates were 26.0 percent with voriconazole and 30.6 percent with liposomal amphotericin B (95 percent confidence interval for the difference, -10.6 to 1.6 percentage points); these rates were independent of the administration of antifungal prophylaxis or the use of colony-stimulating factors. There were fewer documented breakthrough fungal infections in patients treated with voriconazole than in those treated with liposomal amphotericin B (8 [1.9 percent] vs. 21 [5.0 percent], P=0.02). The voriconazole group had fewer cases of severe infusion-related reactions (P<0.01) and of nephrotoxicity (P<0.001). The incidence of hepatotoxicity was similar in the two groups. Patients receiving voriconazole had more episodes of transient visual changes than those receiving liposomal amphotericin B (22 percent vs. 1 percent, P<0.001) and more hallucinations (4.3 percent vs. 0.5 percent, P<0.001). Parenteral voriconazole was changed to the oral formulation in 22 percent of the voriconazole group, with a reduction in the mean duration of hospitalization by one day in all patients (P=0.17) but by two days in patients at high risk (P=0.03). Conclusions Voriconazole is a suitable alternative to amphotericin B preparations for empirical antifungal therapy in patients with neutropenia and persistent fever. JF - The New England Journal of Medicine AU - Walsh, Thomas J, MD AU - Pappas, Peter, MD AU - Winston, Drew J, MD AU - Lazarus, Hillard M, MD AU - Petersen, Finn, MD AU - Raffalli, John, MD AU - Yanovich, Saul, MD AU - Stiff, Patrick, MD AU - Greenberg, Richard, MD AU - Donowitz, Gerald, MD AU - Schuster, Mindy, MD AU - Reboli, Annette, MD AU - Wingard, John, MD AU - Arndt, Carola, MD AU - Reinhardt, John, MD AU - Hadley, Susan, MD AU - Finberg, Robert, MD AU - Laverdière, Michél, MD AU - Perfect, John, MD AU - Garber, Gary, MD AU - Fioritoni, Giuseppe, MD AU - Anaissie, Eli, MD AU - Lee, Jeanette, PhD Y1 - 2002/01/24/ PY - 2002 DA - 2002 Jan 24 SP - 225 EP - 34 CY - Boston PB - Massachusetts Medical Society VL - 346 IS - 4 SN - 00284793 KW - Medical Sciences KW - Anti-Bacterial Agents KW - Antifungal Agents KW - Pyrimidines KW - Triazoles KW - voriconazole KW - Amphotericin B KW - Fungi KW - Drug therapy KW - Fever KW - Colleges & universities KW - Fungal infections KW - Leukemia KW - Patients KW - Mortality KW - Patient safety KW - Stratigraphy KW - Pyrimidines -- adverse effects KW - Anti-Bacterial Agents -- therapeutic use KW - Antifungal Agents -- adverse effects KW - Antifungal Agents -- pharmacokinetics KW - Neutropenia -- etiology KW - Humans KW - Aged KW - Aged, 80 & over KW - Child KW - Triazoles -- adverse effects KW - Pyrimidines -- pharmacokinetics KW - Neoplasms -- therapy KW - Triazoles -- pharmacokinetics KW - Infusions, Intravenous -- adverse effects KW - Drug-Induced Liver Injury KW - Fever -- etiology KW - Prospective Studies KW - Neoplasms -- complications KW - Adult KW - Middle Aged KW - Chronic Disease KW - Adolescent KW - Male KW - Female KW - Pyrimidines -- therapeutic use KW - Mycoses -- prevention & control KW - Triazoles -- therapeutic use KW - Fever -- drug therapy KW - Neutropenia -- drug therapy KW - Amphotericin B -- therapeutic use KW - Antifungal Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/223944912?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+Journal+of+Medicine&rft.atitle=Voriconazole+compared+with+liposomal+amphotericin+B+for+empirical+antifungal+therapy+in+patients+with+neutropenia+and+persistent+fever&rft.au=Walsh%2C+Thomas+J%2C+MD%3BPappas%2C+Peter%2C+MD%3BWinston%2C+Drew+J%2C+MD%3BLazarus%2C+Hillard+M%2C+MD%3BPetersen%2C+Finn%2C+MD%3BRaffalli%2C+John%2C+MD%3BYanovich%2C+Saul%2C+MD%3BStiff%2C+Patrick%2C+MD%3BGreenberg%2C+Richard%2C+MD%3BDonowitz%2C+Gerald%2C+MD%3BSchuster%2C+Mindy%2C+MD%3BReboli%2C+Annette%2C+MD%3BWingard%2C+John%2C+MD%3BArndt%2C+Carola%2C+MD%3BReinhardt%2C+John%2C+MD%3BHadley%2C+Susan%2C+MD%3BFinberg%2C+Robert%2C+MD%3BLaverdi%C3%A8re%2C+Mich%C3%A9l%2C+MD%3BPerfect%2C+John%2C+MD%3BGarber%2C+Gary%2C+MD%3BFioritoni%2C+Giuseppe%2C+MD%3BAnaissie%2C+Eli%2C+MD%3BLee%2C+Jeanette%2C+PhD&rft.aulast=Walsh&rft.aufirst=Thomas&rft.date=2002-01-24&rft.volume=346&rft.issue=4&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=The+New+England+Journal+of+Medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright © 2002 Massachusetts Medical Society. All rights reserved. N1 - Last updated - 2014-02-15 N1 - CODEN - NEJMAG ER - TY - JOUR T1 - Phenotypic consequences of mutations in the conserved motifs of the putative helicase domain of the human Cockayne syndrome group B gene. AN - 71494295; 11867210 AB - Cockayne syndrome (CS) is a human genetic disorder characterized by several neurological and developmental abnormalities. Two genetic complementation groups, CS-A and CS-B, have been identified. The CSB protein belongs to helicase superfamily 2, and to the SWI/SNF family of proteins. The CSB protein is implicated in transcription-coupled repair (TCR), basal transcription and chromatin remodeling. In addition, CS cells undergo UV-induced apoptosis at much lower doses than normal cells. However, the molecular function of the CSB protein in these biological pathways has remained unclear. Evidence indicates that the integrity of the Walker A and B boxes (motifs I and II) are important for CSB function, but the functional significance of the helicase motifs Ia, III--IV has not been previously examined. In this study, single amino acid changes in highly conserved residues of helicase motifs Ia, III, V, VI and a second putative nucleotide-binding motif (NTB) of the CSB protein were generated by site-directed mutagenesis to analyze the genetic function of the CSB protein in survival, RNA synthesis recovery and apoptosis after UV treatment. The survival analysis of these CS-B mutant cell lines was also performed after treatment with the chemical carcinogen, 4-nitroquinoline-1-oxide (4-NQO). The lesions induced by UV light, cyclobutane pyrimidine dimers, are known to be repaired by TCR whereas the lesions induced by 4-NQO are repaired by global genome repair. The results of this study demonstrate that the point mutations in highly conserved residues of helicase motifs Ia, III, V and VI abolished the genetic function of the CSB protein in survival, RNA synthesis recovery and apoptosis after UV treatment. Similarly, the same mutants failed to complement the sensitivity toward 4-NQO. Thus, the integrity of these helicase motifs is important for the biological function of the CSB protein. On the contrary, a point mutation in a C-terminal, second, NTB motif of the CSB protein showed full complementation in the ability to repair damage induced by UV light or 4-NQO, suggesting that this motif is not important for the CSB repair function. JF - Gene AU - Muftuoglu, Meltem AU - Selzer, Rebecca AU - Tuo, Jingsheng AU - Brosh, Robert M AU - Bohr, Vilhelm A AD - Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2002/01/23/ PY - 2002 DA - 2002 Jan 23 SP - 27 EP - 40 VL - 283 IS - 1-2 SN - 0378-1119, 0378-1119 KW - 4-nitroquinolone-1-oxide KW - 0 KW - Quinolones KW - 4-Nitroquinoline-1-oxide KW - 56-57-5 KW - RNA KW - 63231-63-0 KW - DNA Helicases KW - EC 3.6.4.- KW - ERCC6 protein, human KW - EC 3.6.4.12 KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Immunoblotting KW - Ultraviolet Rays KW - Cell Survival -- genetics KW - Dose-Response Relationship, Drug KW - Humans KW - Transcription, Genetic KW - Amino Acid Sequence KW - Dose-Response Relationship, Radiation KW - Phenotype KW - 4-Nitroquinoline-1-oxide -- pharmacology KW - Conserved Sequence -- genetics KW - Gene Expression Regulation -- radiation effects KW - Cell Survival -- drug effects KW - Transfection KW - RNA -- metabolism KW - Gene Expression Regulation -- drug effects KW - Cell Survival -- radiation effects KW - Sequence Homology, Amino Acid KW - Mutation KW - RNA -- genetics KW - Quinolones -- pharmacology KW - DNA Helicases -- metabolism KW - Amino Acid Motifs -- genetics KW - DNA Helicases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71494295?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene&rft.atitle=Phenotypic+consequences+of+mutations+in+the+conserved+motifs+of+the+putative+helicase+domain+of+the+human+Cockayne+syndrome+group+B+gene.&rft.au=Muftuoglu%2C+Meltem%3BSelzer%2C+Rebecca%3BTuo%2C+Jingsheng%3BBrosh%2C+Robert+M%3BBohr%2C+Vilhelm+A&rft.aulast=Muftuoglu&rft.aufirst=Meltem&rft.date=2002-01-23&rft.volume=283&rft.issue=1-2&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-13 N1 - Date created - 2002-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MOSC domains: ancient, predicted sulfur-carrier domains, present in diverse metal-sulfur cluster biosynthesis proteins including molybdenum cofactor sulfurases AN - 18287138; 5340365 AB - Using computational analysis, a novel superfamily of beta -strand-rich domains was identified in the Molybdenum cofactor sulfurase and several other proteins from both prokaryotes and eukaryotes. These MOSC domains contain an absolutely conserved cysteine and occur either as stand-alone forms such as the bacterial YiiM proteins, or fused to other domains such as a NifS-like catalytic domain in Molybdenum cofactor sulfurase. The MOSC domain is predicted to be a sulfur-carrier domain that receives sulfur abstracted by the pyridoxal phosphate-dependent NifS-like enzymes, on its conserved cysteine, and delivers it for the formation of diverse sulfur-metal clusters. The identification of this domain may clarify the mechanism of biogenesis of various metallo-enzymes including Molybdenum cofactor-containing enzymes that are compromised in human type II xanthinuria. JF - FEMS Microbiology Letters AU - Anantharaman, V AU - Aravind, L AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, 20894 Bethesda, MD USA Y1 - 2002/01/22/ PY - 2002 DA - 2002 Jan 22 SP - 55 EP - 61 PB - Elsevier Science VL - 207 IS - 1 SN - 0378-1097, 0378-1097 KW - Molybdenum cofactor sulfurase KW - YiiM protein KW - Microbiology Abstracts B: Bacteriology KW - Xanthines KW - Domains KW - Iron-sulfur centers KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18287138?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEMS+Microbiology+Letters&rft.atitle=MOSC+domains%3A+ancient%2C+predicted+sulfur-carrier+domains%2C+present+in+diverse+metal-sulfur+cluster+biosynthesis+proteins+including+molybdenum+cofactor+sulfurases&rft.au=Anantharaman%2C+V%3BAravind%2C+L&rft.aulast=Anantharaman&rft.aufirst=V&rft.date=2002-01-22&rft.volume=207&rft.issue=1&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=FEMS+Microbiology+Letters&rft.issn=03781097&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Xanthines; Iron-sulfur centers; Domains ER - TY - JOUR T1 - Interdomain Interaction and Substrate Coupling Effects on Dimerization and Conformational Stability of Enzyme I of the Escherichia coli Phosphoenolpyruvate:Sugar Phosphotransferase System AN - 17959951; 5888791 AB - The bacterial PEP:sugar phosphotransferase system couples the phosphorylation and translocation of specific sugars across the membrane. The activity of the first protein in this pathway, enzyme I (EI), is regulated by a monomer-dimer equilibrium where a Mg super(2+)-dependent autophosphorylation by PEP requires the dimer. Dimerization constants for dephospho- and phospho-EI and inactive mutants EI(H189E) and EI(H189A) (in which Glu or Ala is substituted for the active site His189) have been measured under a variety of conditions by sedimentation equilibrium at pH 7.5 and 4 and 20 degree C. Concurrently, thermal unfolding of these forms of EI has been monitored by differential scanning calorimetry and by changes in the intrinsic tryptophanyl residue fluorescence. Phosphorylated EI and EI(H189E) have 10-fold increased dimerization constants [ similar to 2 x 10 super(6) (M monomer) super(-1)] compared to those of dephospho-EI and EI(H189A) at 20 degree C. Dimerization is strongly promoted by 1 mM PEP with 2 mM MgCl sub(2) [K sub(A)' greater than or equal to 10 super(8) M super(-1) at 4 or 20 degree C], as demonstrated with EI(H189A) which cannot undergo autophosphorylation. Together, 1 mM PEP and 2 mM Mg super(2+) also markedly stabilize and couple the unfolding of C- and N-terminal domains of EI(H189A), increasing the transition temperature (T sub(m)) for unfolding the C-terminal domain by similar to 18 degree C and that for the N-terminal domain by similar to 9 degree C to T sub(max) approximately equal to 63 degree C, giving a value of K sub(D)' approximately equal to 3 mu M PEP at 45 degree C. PEP alone also promotes the dimerization of EI(H189A) but only increases T sub(m) similar to 5 degree C for C-terminal domain unfolding without affecting N-terminal domain unfolding, giving an estimated value of K sub(D)' approximately equal to 0.2 mM for PEP dissociation in the absence of Mg super(2+) at 45 degree C. In contrast, the dimerization constant of phospho-EI at 20 degree C is the same in the absence and presence of 5 mM PEP and 2 mM MgCl sub(2). Thus, the separation of substrate binding effects from those of phosphorylation by studies with the inactive EI(H189A) has shown that intracellular concentrations of PEP and Mg super(2+) are important determinants of both the conformational stability and dimerization of dephospho-EI. JF - Biochemistry (Washington) AU - Dimitrova, M N AU - Szczepanowski, R H AU - Ruvinov, S B AU - Peterkofsky, A AU - Ginsburg, A AD - Section of Protein Chemistry, Laboratory of Biochemistry, and Laboratory of Biochemical Genetics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-8012, USA Y1 - 2002/01/22/ PY - 2002 DA - 2002 Jan 22 SP - 906 EP - 913 VL - 41 IS - 3 SN - 0006-2960, 0006-2960 KW - Microbiology Abstracts B: Bacteriology KW - Temperature effects KW - Sugar KW - Fluorescence KW - Phosphorylation KW - Enzyme I KW - Escherichia coli KW - phosphotransferase KW - Sedimentation KW - Magnesium KW - Translocation KW - Differential scanning calorimetry KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17959951?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Interdomain+Interaction+and+Substrate+Coupling+Effects+on+Dimerization+and+Conformational+Stability+of+Enzyme+I+of+the+Escherichia+coli+Phosphoenolpyruvate%3ASugar+Phosphotransferase+System&rft.au=Dimitrova%2C+M+N%3BSzczepanowski%2C+R+H%3BRuvinov%2C+S+B%3BPeterkofsky%2C+A%3BGinsburg%2C+A&rft.aulast=Dimitrova&rft.aufirst=M&rft.date=2002-01-22&rft.volume=41&rft.issue=3&rft.spage=906&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/10.1021%2Fbi011801x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Magnesium; Enzyme I; phosphotransferase; Phosphorylation; Temperature effects; Translocation; Sugar; Sedimentation; Differential scanning calorimetry; Fluorescence DO - http://dx.doi.org/10.1021/bi011801x ER - TY - JOUR T1 - In Vitro-Packaged SV40 Pseudovirions as Highly Efficient Vectors for Gene Transfer AN - 18283341; 5334701 AB - A procedure for in vitro packaging of plasmid DNA in recombinant SV40 capsid proteins was developed by Sandalon et al. (1997). Here, we report the highly efficient transduction into different human, murine and monkey cell lines using a scaled-up protocol for producing SV40 pseudovirions, packaged in vitro, carrying the human multidrug-resistance gene MDR1 encoding P-glycoprotein (P-gp) or the green fluorescent protein reporter gene (GFP) under control of SV40 and cytomegalovirus (CMV) promoters. The percentage of expressing cells was proportional to the number of transducing particles, with close to 100% of cells transduced at optimal ratios of transducing particles to cells. The ability to confer multidrug resistance was evaluated by measuring dye efflux and cell-surface expression in infected cells. The relative level of expression of P-gp driven by the different promoters varied among different cell lines. In human lymphoblastoid cells, which express high levels of major histocompatibility complex (MHC) class I (a surface receptor for SV40), constructs that carry an intron yield the highest expression. Our experiments further demonstrate that MDR1 and GFP expression driven by these promoters is transient; however, transduced cells remain MDR1-positive if selected in colchicine. Thus, the SV40 vectors are well suited to situations in which only short-term expression is required or expression is selected, such as for bone marrow protection during chemotherapy. JF - Human Gene Therapy AU - Kimchi-Sarfaty, C AU - Ben-Nun-Shaul, O AU - Rund, D AU - Oppenheim, A AU - Gottesman, M M AD - Laboratory of Cell Biology, Building 37, Room 1A09, National Cancer Institute, NIH, 37 Convent Drive MSC 4255, Bethesda, MD 20892-4255, USA, mgottesman@nih.gov Y1 - 2002/01/20/ PY - 2002 DA - 2002 Jan 20 SP - 299 EP - 310 VL - 13 IS - 2 SN - 1043-0342, 1043-0342 KW - mice KW - man KW - MDR1 gene KW - green fluorescent protein KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Gene therapy KW - Reporter gene KW - Gene transfer KW - Simian virus 40 KW - Major histocompatibility complex KW - Multidrug resistance KW - Cytomegalovirus KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18283341?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=In+Vitro-Packaged+SV40+Pseudovirions+as+Highly+Efficient+Vectors+for+Gene+Transfer&rft.au=Kimchi-Sarfaty%2C+C%3BBen-Nun-Shaul%2C+O%3BRund%2C+D%3BOppenheim%2C+A%3BGottesman%2C+M+M&rft.aulast=Kimchi-Sarfaty&rft.aufirst=C&rft.date=2002-01-20&rft.volume=13&rft.issue=2&rft.spage=299&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cytomegalovirus; Simian virus 40; Gene therapy; Gene transfer; Multidrug resistance; Major histocompatibility complex; Expression vectors; Reporter gene ER - TY - JOUR T1 - Recombinant Adeno-Associated Virus Serotype 2 Vectors Mediate Stable Interleukin 10 Secretion from Salivary Glands into the Bloodstream AN - 18277635; 5334700 AB - We have constructed a recombinant adeno-associated virus serotype 2 vector encoding human interleukin 10 (rAAVhIL10). IL-10 is a potent antiinflammatory/immune cytokine, which has received growing attention for its therapeutic potential. Human IL-10 (hIL-10) production was virus dose dependent after in vitro infection of HSG cells, a human submandibular gland cell line. The vector-derived hIL-10 produced was biologically active, as the medium from rAAVhIL10-infected HSG cells caused a dose-dependent blockade of IL-12 secretion from spleen cells of IL-10 knockout mice challenged with heat-killed Brucella abortus. Administration of rAAVhIL10 (10 super(10) genomes per gland) to both mouse submandibular glands led to hIL-10 secretion into the bloodstream ( similar to 1-5 pg/ml), that is, in an endocrine manner, which was stable for similar to 2 months. Salivary gland administration of rAAVhIL10 under experimental conditions was more efficacious than intravenous administration ( similar to 0.5-0.7 pg/ml). Also, hIL-10 was readily secreted in vitro from organ cultures of minced submandibular glands infected with rAAVhIL10, 6 or 8 weeks earlier. Consistent with these results, hIL-10 mRNA was detected by reverse transcription-polymerase chain reaction in submandibular glands of mice infected with rAAVhIL10 but not from control mice. At these doses, little to no hIL-10 was detected in mouse saliva. Using a rAAV serotype 2 vector encoding beta -galactosidase, we observed that the primary parenchymal target cells were ductal. These findings represent the first report of rAAV use to target exocrine glands for systemic secretion of a therapeutic protein, and support the notion that rAAV serotype 2 vectors may be useful in salivary glands for local (periglandular) and systemic gene-based protein therapeutics. JF - Human Gene Therapy AU - Yamano, S AU - Huang, L-Y AU - Ding, C AU - Chiorini, JA AU - Goldsmith, C M AU - Wellner, R B AU - Golding, B AU - Kotin, R M AU - Scott, DE AU - Baum, B J AD - GTTB/NIDCR/NIH, 10 Center Drive, MSC 1190, Building 10, Room 1N113, Bethesda, MD 20892, USA, bbaum@dir.nidcr.nih.gov Y1 - 2002/01/20/ PY - 2002 DA - 2002 Jan 20 SP - 287 EP - 298 VL - 13 IS - 2 SN - 1043-0342, 1043-0342 KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Adeno-associated virus 2 KW - Gene therapy KW - Brucella abortus KW - Submandibular gland KW - Salivary gland KW - ^a-Galactosidase KW - Interleukin 10 KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18277635?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Recombinant+Adeno-Associated+Virus+Serotype+2+Vectors+Mediate+Stable+Interleukin+10+Secretion+from+Salivary+Glands+into+the+Bloodstream&rft.au=Yamano%2C+S%3BHuang%2C+L-Y%3BDing%2C+C%3BChiorini%2C+JA%3BGoldsmith%2C+C+M%3BWellner%2C+R+B%3BGolding%2C+B%3BKotin%2C+R+M%3BScott%2C+DE%3BBaum%2C+B+J&rft.aulast=Yamano&rft.aufirst=S&rft.date=2002-01-20&rft.volume=13&rft.issue=2&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adeno-associated virus 2; Brucella abortus; Salivary gland; Interleukin 10; Expression vectors; Gene therapy; ^a-Galactosidase; Submandibular gland ER - TY - JOUR T1 - Conformational changes that occur during M3 muscarinic acetylcholine receptor activation probed by the use of an in situ disulfide cross-linking strategy. AN - 71369399; 11698401 AB - The structural changes involved in ligand-dependent activation of G protein-coupled receptors are not well understood at present. To address this issue, we developed an in situ disulfide cross-linking strategy using the rat M(3) muscarinic receptor, a prototypical G(q)-coupled receptor, as a model system. It is known that a tyrosine residue (Tyr(254)) located at the C terminus of transmembrane domain (TM) V and several primarily hydrophobic amino acids present within the cytoplasmic portion of TM VI play key roles in determining the G protein coupling selectivity of the M(3) receptor subtype. To examine whether M3 receptor activation involves changes in the relative orientations of these functionally critical residues, pairs of cysteine residues were substituted into a modified version of the M(3) receptor that contained a factor Xa cleavage site within the third intracellular loop and lacked most endogenous cysteine residues. All analyzed mutant receptors contained a Y254C point mutation and a second cysteine substitution within the segment Lys(484)-Ser(493) at the intracellular end of TM VI. Following their transient expression in COS-7 cells, mutant receptors present in their native membrane environment (in situ) were subjected to mild oxidizing conditions, either in the absence or in the presence of the muscarinic agonist, carbachol. The successful formation of disulfide cross-links was monitored by studying changes in the electrophoretic mobility of oxidized, factor Xa-treated receptors on SDS gels. The observed cross-linking patterns indicated that M(3) receptor activation leads to structural changes that allow the cytoplasmic ends of TM V and TM VI to move closer to each other and that also appear to involve a major change in secondary structure at the cytoplasmic end of TM VI. This is the first study employing an in situ disulfide cross-linking strategy to examine agonist-dependent dynamic structural changes in a G protein-coupled receptor. JF - The Journal of biological chemistry AU - Ward, Stuart D C AU - Hamdan, Fadi F AU - Bloodworth, Lanh M AU - Wess, Jürgen AD - Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/01/18/ PY - 2002 DA - 2002 Jan 18 SP - 2247 EP - 2257 VL - 277 IS - 3 SN - 0021-9258, 0021-9258 KW - Disulfides KW - 0 KW - Ligands KW - Molecular Probes KW - Receptor, Muscarinic M3 KW - Receptors, Muscarinic KW - Biotin KW - 6SO6U10H04 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Animals KW - COS Cells KW - Amino Acid Sequence KW - Radioligand Assay KW - Mutagenesis, Site-Directed KW - Blotting, Western KW - GTP-Binding Proteins -- metabolism KW - Molecular Sequence Data KW - Biotin -- metabolism KW - Protein Conformation KW - Receptors, Muscarinic -- genetics KW - Disulfides -- chemistry KW - Receptors, Muscarinic -- chemistry KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71369399?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Conformational+changes+that+occur+during+M3+muscarinic+acetylcholine+receptor+activation+probed+by+the+use+of+an+in+situ+disulfide+cross-linking+strategy.&rft.au=Ward%2C+Stuart+D+C%3BHamdan%2C+Fadi+F%3BBloodworth%2C+Lanh+M%3BWess%2C+J%C3%BCrgen&rft.aulast=Ward&rft.aufirst=Stuart+D&rft.date=2002-01-18&rft.volume=277&rft.issue=3&rft.spage=2247&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-13 N1 - Date created - 2002-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fluorescence in situ hybridization analysis of HER-2/neu in brushings of normal oral mucosa. AN - 71446782; 11850076 AB - Oncogene alterations have been clearly demonstrated to be related to the carcinogenesis and progression of oral squamous cell carcinoma (OSCC). However, the analysis of these alterations for screening and early diagnostic purposes generally requires invasive techniques for surgical removal of pathological epithelium. The aim of the present study was to assess the feasibility of fluorescence in situ hybridization (FISH) analysis of HER-2/neu amplification in oral mucosa brushings and to compare the HER-2/neu status with the history and smoking and drinking habits of healthy subjects. Cells obtained by centrifugation of oral brushings from 21 subjects (overall no. of cells: 5125) were suspended in physiological saline and fixed onto two slides for cytological evaluation and FISH analysis (dual-target, dual-color fluorescence assay) of the HER-2/neu gene and CEP17 centromere. A mean of 89.8% of the cells showed two HER-2/neu signals and a mean of 94% had two CEP17 signals at fluorescent microscopy. Finally, a mean of 96% of cells with HER-2/neu / CEP17 had a ratio equal to 1. No association between smoking and drinking habits, age and the HER-2/neu and CEP17 characteristics evaluated by FISH was found. JF - Cancer genetics and cytogenetics AU - Paradiso, Angelo AU - Abatangelo, Marta AU - Piepoli, Sandra AU - Tommasi, Stefania AU - Xu, Jian Ming AU - Caponio, Maria Angela AU - Marzullo, Franco AU - D'Auria, Carlo AU - Achille, Gaetano AU - Grammatica, Luciano AD - Clinical Experimental Oncology Laboratory, National Cancer Institute, Via Amendola 209, Bari, Italy. anpara@tin.it Y1 - 2002/01/15/ PY - 2002 DA - 2002 Jan 15 SP - 141 EP - 144 VL - 132 IS - 2 SN - 0165-4608, 0165-4608 KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Index Medicus KW - Microscopy, Fluorescence KW - Humans KW - In Situ Hybridization, Fluorescence KW - Receptor, ErbB-2 -- genetics KW - Mouth Mucosa -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71446782?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+genetics+and+cytogenetics&rft.atitle=Fluorescence+in+situ+hybridization+analysis+of+HER-2%2Fneu+in+brushings+of+normal+oral+mucosa.&rft.au=Paradiso%2C+Angelo%3BAbatangelo%2C+Marta%3BPiepoli%2C+Sandra%3BTommasi%2C+Stefania%3BXu%2C+Jian+Ming%3BCaponio%2C+Maria+Angela%3BMarzullo%2C+Franco%3BD%27Auria%2C+Carlo%3BAchille%2C+Gaetano%3BGrammatica%2C+Luciano&rft.aulast=Paradiso&rft.aufirst=Angelo&rft.date=2002-01-15&rft.volume=132&rft.issue=2&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Cancer+genetics+and+cytogenetics&rft.issn=01654608&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-20 N1 - Date created - 2002-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Degradation of L-glutamate dehydrogenase from Escherichia coli: allosteric regulation of enzyme stability. AN - 71414440; 11795873 AB - L-glutamate dehydrogenase (GDH) is stable in exponentially growing Escherichia coli cells but is degraded at a rate of 20-30% per hour in cells starved for either nitrogen or carbon. GDH degradation is energy-dependent, and mutations in ATP-dependent proteases, ClpAP or Lon lead to partial stabilization. Degradation is inhibited by chloramphenicol and is completely blocked in relA mutant cells, suggesting that ribosome-mediated signaling may facilitate GDH degradation. Purified GDH has a single tight site for NADPH binding. Binding of NADPH in the absence of other ligands leads to destabilization of the enzyme. NADPH-induced instability and sensitivity to proteolysis is reversed by tri- and dicarboxylic acids or nucleoside di- and triphosphates. GTP and ppGpp bind to GDH at an allosteric site and reverse the destabilizing effects of NADPH. Native GDH is resistant to degradation by several purified ATP-dependent proteases: ClpAP, ClpXP, Lon, and ClpYQ, but denatured GDH is degraded by ClpAP. Our results suggest that, in vivo, GDH is sensitized to proteases by loss of a stabilizing ligand or interaction with an destabilizing metabolite that accumulates in starving cells, and that any of several ATP-dependent proteases degrade the sensitized protein. (c)2002 Elsevier Science. JF - Archives of biochemistry and biophysics AU - Maurizi, Michael R AU - Rasulova, Fatima AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. mmaurizi@helix.nih.gov Y1 - 2002/01/15/ PY - 2002 DA - 2002 Jan 15 SP - 206 EP - 216 VL - 397 IS - 2 SN - 0003-9861, 0003-9861 KW - Carboxylic Acids KW - 0 KW - ClpYQ protease, E coli KW - Escherichia coli Proteins KW - Heat-Shock Proteins KW - NF-kappa B KW - Nucleotides KW - Transcription Factor RelA KW - NADP KW - 53-59-8 KW - Phenylmethylsulfonyl Fluoride KW - 57KD15003I KW - Chloramphenicol KW - 66974FR9Q1 KW - Ammonia KW - 7664-41-7 KW - Glutamate Dehydrogenase KW - EC 1.4.1.2 KW - Aspartate Kinase KW - EC 2.7.2.4 KW - ATP-Dependent Proteases KW - EC 3.4.21.- KW - Serine Endopeptidases KW - Lon protein, E coli KW - EC 3.4.21.53 KW - Protease La KW - ClpXP protease, E coli KW - EC 3.4.21.92 KW - Endopeptidase Clp KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Glucose KW - IY9XDZ35W2 KW - Cysteine KW - K848JZ4886 KW - Potassium Cyanide KW - MQD255M2ZO KW - Index Medicus KW - Heat-Shock Proteins -- metabolism KW - Protein Processing, Post-Translational -- drug effects KW - Models, Molecular KW - Aspartate Kinase -- metabolism KW - Adenosine Triphosphatases -- metabolism KW - NADP -- metabolism KW - Protein Conformation -- drug effects KW - NADP -- pharmacology KW - Glucose -- deficiency KW - Potassium Cyanide -- pharmacology KW - Phenylmethylsulfonyl Fluoride -- pharmacology KW - NF-kappa B -- genetics KW - Chloramphenicol -- pharmacology KW - Ammonia -- metabolism KW - Serine Endopeptidases -- metabolism KW - Enzyme Stability KW - Carboxylic Acids -- pharmacology KW - Allosteric Regulation KW - Nucleotides -- pharmacology KW - NF-kappa B -- metabolism KW - Glutamate Dehydrogenase -- metabolism KW - Escherichia coli -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71414440?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+biochemistry+and+biophysics&rft.atitle=Degradation+of+L-glutamate+dehydrogenase+from+Escherichia+coli%3A+allosteric+regulation+of+enzyme+stability.&rft.au=Maurizi%2C+Michael+R%3BRasulova%2C+Fatima&rft.aulast=Maurizi&rft.aufirst=Michael&rft.date=2002-01-15&rft.volume=397&rft.issue=2&rft.spage=206&rft.isbn=&rft.btitle=&rft.title=Archives+of+biochemistry+and+biophysics&rft.issn=00039861&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-25 N1 - Date created - 2002-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein kinase Cepsilon mediates PMA-induced growth inhibition of low population density NIH 3T3 fibroblasts. AN - 71403352; 11795874 AB - Phorbol 12-myristate-13-acetate (PMA), a potent tumor promoter and activator of most protein kinase C (PKC) isotypes, was found to significantly inhibit the growth of low population density (1-5% confluency) NIH 3T3 cells. Higher cell population density (above 10% confluency) provided protection from this growth inhibitory effect of PMA. PMA-induced growth arrest is accompanied by an elevation in the level of p21(Cip1) protein, along with cell cycle arrest at the G1/S transition. Activation of PKC is required for this growth inhibitory response since the pan PKC inhibitor GF109203 blocked this effect of PMA. However, the classical PKC inhibitor Gö6976 had no effect, strongly suggesting the involvement of novel PKC isotypes (delta and/or epsilon). Overexpression of PKCepsilon, but not PKCdelta, was found to potentiate PMA-induced growth inhibition. Overexpression of a kinase-inactive dominant-negative mutant of PKCepsilon (K437R) decreased the growth inhibitory effect of PMA and also blocked the PMA-induced increase in the level of p21(Cip1) protein. Taken together, these results indicate that PMA has a cell population density-dependent effect on the growth of NIH 3T3 cells and that the PMA growth inhibitory effect at low cell population density is mediated through activation of PKCepsilon. (c)2001 Elsevier Science. JF - Archives of biochemistry and biophysics AU - Petrovics, Gyorgy AU - Bird, Terry AU - Lehel, Csaba AU - Oravecz, Tamas AU - Anderson, Wayne B AD - Laboratory of Cellular Oncology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 2002/01/15/ PY - 2002 DA - 2002 Jan 15 SP - 217 EP - 223 VL - 397 IS - 2 SN - 0003-9861, 0003-9861 KW - Cdkn1a protein, mouse KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Growth Inhibitors KW - Isoenzymes KW - Prkce protein, mouse KW - EC 2.7.1.- KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-epsilon KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - 3T3 Cells KW - S Phase -- drug effects KW - Cyclins -- biosynthesis KW - Cell Count KW - Cell Division -- drug effects KW - Mice KW - G1 Phase -- drug effects KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Growth Inhibitors -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71403352?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+biochemistry+and+biophysics&rft.atitle=Protein+kinase+Cepsilon+mediates+PMA-induced+growth+inhibition+of+low+population+density+NIH+3T3+fibroblasts.&rft.au=Petrovics%2C+Gyorgy%3BBird%2C+Terry%3BLehel%2C+Csaba%3BOravecz%2C+Tamas%3BAnderson%2C+Wayne+B&rft.aulast=Petrovics&rft.aufirst=Gyorgy&rft.date=2002-01-15&rft.volume=397&rft.issue=2&rft.spage=217&rft.isbn=&rft.btitle=&rft.title=Archives+of+biochemistry+and+biophysics&rft.issn=00039861&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-25 N1 - Date created - 2002-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rescue of polyglutamine-mediated cytotoxicity by double-stranded RNA-mediated RNA interference. AN - 71392386; 11809726 AB - RNA interference (RNAi) is a mechanism that appears to control unwanted gene expression in a wide range of species. In Drosophila, RNAi is most effectively induced by double-stranded RNAs (dsRNAs) of over approximately 80 nucleotides (nt) and in mammalian cells an RNAi-like inhibition of gene expression has been shown to be mediated by dsRNAs of approximately 21-23 nt. To test if RNAi can be used to specifically down-regulate a human disease-related transcript we have used Drosophila and human tissue culture models of the dominant genetic disorder spinobulbar muscular atrophy (SBMA). A variety of different dsRNAs were assessed for the ability to inhibit expression of transcripts that included a truncated human androgen receptor (ar) gene containing different CAG repeat lengths (16-112 repeats). In Drosophila cells, dsRNAs corresponding to non-repetitive sequences mediated a high degree of sequence-specific inhibition, whereas RNA duplexes containing CAG repeat tracts only induced gene-specific inhibition when flanking ar sequences were included; dsRNAs containing various lengths of CAG repeats plus ar sequences were unable to induce allele-specific interference. In mammalian cells we tested sequence-specific small dsRNAs of 22 nt; these rescued the toxicity and caspase-3 activation induced by plasmids expressing a transcript encoding an expanded polyglutamine tract. This study demonstrates the feasibility of targeting a transcript associated with an important group of genetic diseases by RNAi. JF - Human molecular genetics AU - Caplen, Natasha J AU - Taylor, J Paul AU - Statham, Victoria S AU - Tanaka, Fumiaki AU - Fire, Andrew AU - Morgan, Richard A AD - Medical Genetics Branch, National Human Genome Research Institute and Neurogenetics Branch, National Institute of Neurological Diseases, National Institutes of Health, Bethesda, MD 20892, USA. ncaplen@nhgri.nih.gov Y1 - 2002/01/15/ PY - 2002 DA - 2002 Jan 15 SP - 175 EP - 184 VL - 11 IS - 2 SN - 0964-6906, 0964-6906 KW - Luminescent Proteins KW - 0 KW - Peptides KW - RNA, Double-Stranded KW - Receptors, Androgen KW - Recombinant Fusion Proteins KW - Green Fluorescent Proteins KW - 147336-22-9 KW - polyglutamine KW - 26700-71-0 KW - RNA KW - 63231-63-0 KW - CASP3 protein, human KW - EC 3.4.22.- KW - Caspase 3 KW - Caspases KW - Index Medicus KW - Animals KW - Apoptosis KW - Gene Silencing KW - Trinucleotide Repeats KW - Receptors, Androgen -- genetics KW - Humans KW - Disease Models, Animal KW - Luminescent Proteins -- metabolism KW - Genetic Therapy KW - Caspases -- metabolism KW - Feasibility Studies KW - RNA -- metabolism KW - Recombinant Fusion Proteins -- genetics KW - Drosophila KW - Cell Line KW - Muscular Disorders, Atrophic -- genetics KW - Down-Regulation KW - Peptides -- genetics KW - RNA, Double-Stranded -- metabolism KW - Peptides -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71392386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+molecular+genetics&rft.atitle=Rescue+of+polyglutamine-mediated+cytotoxicity+by+double-stranded+RNA-mediated+RNA+interference.&rft.au=Caplen%2C+Natasha+J%3BTaylor%2C+J+Paul%3BStatham%2C+Victoria+S%3BTanaka%2C+Fumiaki%3BFire%2C+Andrew%3BMorgan%2C+Richard+A&rft.aulast=Caplen&rft.aufirst=Natasha&rft.date=2002-01-15&rft.volume=11&rft.issue=2&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Human+molecular+genetics&rft.issn=09646906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-07 N1 - Date created - 2002-01-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nonmyeloablative conditioning followed by transplantation of genetically modified HLA-matched peripheral blood progenitor cells for hematologic malignancies in patients with acquired immunodeficiency syndrome. AN - 71361863; 11781257 AB - To assess the safety and efficacy of nonmyeloablative allogeneic transplantation in patients with HIV infection, a clinical protocol was initiated in patients with refractory hematologic malignancies and concomitant HIV infection. The results from the first 2 patients are reported. The indications for transplantation were treatment-related acute myelogenous leukemia and primary refractory Hodgkin disease in patients 1 and 2, respectively. Only patient 1 received genetically modified cells. Both patients tolerated the procedure well with minimal toxicity, and complete remissions were achieved in both patients, but patient 2 died of relapsed Hodgkin disease 12 months after transplantation. Patient 1 continues in complete remission with undetectable HIV levels and rising CD4 counts, and with both the therapeutic and control gene transfer vectors remaining detectable at low levels more than 2 years after transplantation. These results suggest that nonmyeloablative allogeneic transplantation in the context of highly active antiretroviral therapy is feasible in patients with treatment-sensitive HIV infection. JF - Blood AU - Kang, Elizabeth M AU - de Witte, Moniek AU - Malech, Harry AU - Morgan, Richard A AU - Phang, Sheila AU - Carter, Charles AU - Leitman, Susan F AU - Childs, Richard AU - Barrett, A John AU - Little, Richard AU - Tisdale, John F AD - Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/01/15/ PY - 2002 DA - 2002 Jan 15 SP - 698 EP - 701 VL - 99 IS - 2 SN - 0006-4971, 0006-4971 KW - Anti-Bacterial Agents KW - 0 KW - Cyclosporine KW - 83HN0GTJ6D KW - Cyclophosphamide KW - 8N3DW7272P KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Ganciclovir KW - P9G3CKZ4P5 KW - Prednisone KW - VB0R961HZT KW - Abridged Index Medicus KW - Index Medicus KW - Acute Disease KW - Anti-Bacterial Agents -- therapeutic use KW - Ganciclovir -- therapeutic use KW - Prednisone -- therapeutic use KW - Cyclosporine -- therapeutic use KW - Humans KW - Graft vs Host Disease -- drug therapy KW - Graft vs Host Disease -- etiology KW - Recurrence KW - Viral Load KW - Feasibility Studies KW - Premedication KW - Adult KW - Treatment Outcome KW - Antiretroviral Therapy, Highly Active KW - Infection Control KW - Remission Induction KW - Cyclophosphamide -- pharmacology KW - Vidarabine -- analogs & derivatives KW - Acquired Immunodeficiency Syndrome -- therapy KW - Acquired Immunodeficiency Syndrome -- complications KW - Transplantation Conditioning KW - Hematopoietic Stem Cell Transplantation KW - Leukemia, Myeloid -- therapy KW - Leukemia, Myeloid -- complications KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Vidarabine -- pharmacology KW - Hodgkin Disease -- therapy KW - Hodgkin Disease -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71361863?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Nonmyeloablative+conditioning+followed+by+transplantation+of+genetically+modified+HLA-matched+peripheral+blood+progenitor+cells+for+hematologic+malignancies+in+patients+with+acquired+immunodeficiency+syndrome.&rft.au=Kang%2C+Elizabeth+M%3Bde+Witte%2C+Moniek%3BMalech%2C+Harry%3BMorgan%2C+Richard+A%3BPhang%2C+Sheila%3BCarter%2C+Charles%3BLeitman%2C+Susan+F%3BChilds%2C+Richard%3BBarrett%2C+A+John%3BLittle%2C+Richard%3BTisdale%2C+John+F&rft.aulast=Kang&rft.aufirst=Elizabeth&rft.date=2002-01-15&rft.volume=99&rft.issue=2&rft.spage=698&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-13 N1 - Date created - 2002-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Urocortin, but not urocortin II, protects cultured hippocampal neurons from oxidative and excitotoxic cell death via corticotropin-releasing hormone receptor type I. AN - 71356530; 11784785 AB - Urocortin and urocortin II are members of the corticotropin-releasing hormone (CRH) family of neuropeptides that function to regulate stress responses. Two high-affinity G-protein-coupled receptors have been identified that bind CRH and/or urocortin I and II, designated CRHR1 and CRHR2, both of which are present in hippocampal regions of mammalian brain. The hippocampus plays an important role in regulating stress responses and is a brain region in which neurons are vulnerable during disease and stress conditions, including cerebral ischemia, Alzheimer's disease, and anxiety disorders. Here we report that urocortin exerts a potent protective action in cultured rat hippocampal neurons with concentrations in the range of 0.5-5.0 pm, increasing the resistance of the cells to oxidative (amyloid beta-peptide, 4-hydroxynonenal, ferrous sulfate) and excitotoxic (glutamate) insults. We observed that urocortin is 10-fold more potent than CRH in protecting hippocampal neurons from insult, whereas urocortin II is ineffective. RT-PCR and sequencing analyses revealed the presence of both CRHR1 and CRHR2 in the hippocampal cultures, with CRHR1 being expressed at much higher levels than CRHR2. Using subtype-selective CRH receptor antagonists, we provide evidence that the neuroprotective effect of exogenously added urocortin is mediated by CRHR1. Furthermore, we provide evidence that the signaling pathway that mediates the neuroprotective effect of urocortin involves cAMP-dependent protein kinase, protein kinase C, and mitogen-activated protein kinase. This is the first demonstration of a biological activity of urocortin in hippocampal neurons, suggesting a role for the peptide in adaptive responses of hippocampal neurons to potentially lethal oxidative and excitotoxic insults. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Pedersen, Ward A AU - Wan, Ruiqian AU - Zhang, Peisu AU - Mattson, Mark P AD - Laboratory of Neurosciences, Gerontology Research Center, National Institute on Aging, Baltimore, Maryland 21224, USA. Y1 - 2002/01/15/ PY - 2002 DA - 2002 Jan 15 SP - 404 EP - 412 VL - 22 IS - 2 KW - Aldehydes KW - 0 KW - Amyloid beta-Peptides KW - CRF receptor type 1 KW - Enzyme Inhibitors KW - Ferrous Compounds KW - Neuroprotective Agents KW - Receptors, Corticotropin-Releasing Hormone KW - Urocortins KW - ferrous sulfate KW - 39R4TAN1VT KW - Glutamic Acid KW - 3KX376GY7L KW - Corticotropin-Releasing Hormone KW - 9015-71-8 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - 4-hydroxy-2-nonenal KW - K1CVM13F96 KW - Index Medicus KW - Aldehydes -- toxicity KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Animals KW - Ferrous Compounds -- toxicity KW - Mitogen-Activated Protein Kinases -- metabolism KW - Hippocampus -- metabolism KW - Lipid Peroxidation -- drug effects KW - Neuroprotective Agents -- pharmacology KW - Hippocampus -- drug effects KW - Rats KW - Protein Kinase C -- metabolism KW - Signal Transduction -- physiology KW - Rats, Sprague-Dawley KW - Glutamic Acid -- toxicity KW - Cells, Cultured KW - Amyloid beta-Peptides -- toxicity KW - Signal Transduction -- drug effects KW - Hippocampus -- cytology KW - Enzyme Inhibitors -- pharmacology KW - Cytoprotection -- physiology KW - Oxidative Stress -- physiology KW - Neurons -- metabolism KW - Receptors, Corticotropin-Releasing Hormone -- metabolism KW - Neurons -- drug effects KW - Neurons -- cytology KW - Oxidative Stress -- drug effects KW - Corticotropin-Releasing Hormone -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71356530?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Urocortin%2C+but+not+urocortin+II%2C+protects+cultured+hippocampal+neurons+from+oxidative+and+excitotoxic+cell+death+via+corticotropin-releasing+hormone+receptor+type+I.&rft.au=Pedersen%2C+Ward+A%3BWan%2C+Ruiqian%3BZhang%2C+Peisu%3BMattson%2C+Mark+P&rft.aulast=Pedersen&rft.aufirst=Ward&rft.date=2002-01-15&rft.volume=22&rft.issue=2&rft.spage=404&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-30 N1 - Date created - 2002-01-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The interrelated roles of TGF-beta and IL-10 in the regulation of experimental colitis. AN - 71355268; 11777988 AB - In the present study, we define the relation between TGF-beta and IL-10 in the regulation of the Th1-mediated inflammation occurring in trinitrobenzene sulfonic acid (TNBS)-colitis. In initial studies, we showed that the feeding of trinitrophenol-haptenated colonic protein to SJL/J mice induces CD4(+) regulatory T cells that transfer protection from induction of TNBS-colitis, and that such protection correlates with cells producing TGF-beta, not IL-10. Further studies in which SJL/J mice were fed haptenated colonic protein, and then administered either anti-TGF-beta or anti-IL-10 at the time of subsequent TNBS administration per rectum, showed that while both Abs abolished protection, anti-TGF-beta administration prevented TGF-beta secretion, but left IL-10 secretion intact; whereas anti-IL-10 administration prevented both TGF-beta secretion and IL-10 secretion. Thus, it appeared that the protective effect of IL-10 was an indirect consequence of its effect on TGF-beta secretion. To establish this point further, we conducted adoptive transfer studies and showed that anti-IL-10 administration had no effect on induction of TGF-beta producing T cells in donor mice. However, it did inhibit their subsequent expansion in recipient mice, probably by regulating the magnitude of the Th1 T cell response which would otherwise inhibit the TGF-beta response. Therefore, these studies suggest that TGF-beta production is a primary mechanism of counter-regulation of Th1 T cell-mediated mucosal inflammation, and that IL-10 is necessary as a secondary factor that facilitates TGF-beta production. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Fuss, Ivan J AU - Boirivant, Monica AU - Lacy, Brian AU - Strober, Warren AD - Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. ifuss@niaid.nih Y1 - 2002/01/15/ PY - 2002 DA - 2002 Jan 15 SP - 900 EP - 908 VL - 168 IS - 2 SN - 0022-1767, 0022-1767 KW - Adjuvants, Immunologic KW - 0 KW - Antibodies, Monoclonal KW - Haptens KW - Picrates KW - Transforming Growth Factor beta KW - Interleukin-10 KW - 130068-27-8 KW - Trinitrobenzenesulfonic Acid KW - 8T3HQG2ZC4 KW - picric acid KW - A49OS0F91S KW - Abridged Index Medicus KW - Index Medicus KW - Administration, Oral KW - Animals KW - Picrates -- administration & dosage KW - Haptens -- administration & dosage KW - CD4-Positive T-Lymphocytes -- immunology KW - Mice KW - Administration, Rectal KW - Down-Regulation -- immunology KW - Colon -- immunology KW - Antibodies, Monoclonal -- administration & dosage KW - Mice, Inbred Strains KW - Adoptive Transfer KW - Trinitrobenzenesulfonic Acid -- administration & dosage KW - Lymphocyte Activation -- immunology KW - T-Lymphocyte Subsets -- transplantation KW - Colon -- metabolism KW - T-Lymphocyte Subsets -- immunology KW - Male KW - Transforming Growth Factor beta -- biosynthesis KW - Colitis -- prevention & control KW - Colitis -- etiology KW - Transforming Growth Factor beta -- physiology KW - Adjuvants, Immunologic -- physiology KW - Colitis -- immunology KW - Interleukin-10 -- immunology KW - Colitis -- chemically induced KW - Transforming Growth Factor beta -- immunology KW - Interleukin-10 -- physiology KW - Adjuvants, Immunologic -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71355268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=The+interrelated+roles+of+TGF-beta+and+IL-10+in+the+regulation+of+experimental+colitis.&rft.au=Fuss%2C+Ivan+J%3BBoirivant%2C+Monica%3BLacy%2C+Brian%3BStrober%2C+Warren&rft.aulast=Fuss&rft.aufirst=Ivan&rft.date=2002-01-15&rft.volume=168&rft.issue=2&rft.spage=900&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-31 N1 - Date created - 2002-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multidrug-resistance mdr1a/1b double knockout mice are more sensitive than wild type mice to acute arsenic toxicity, with higher arsenic accumulation in tissues. AN - 71352796; 11750083 AB - Arsenic is an environmental toxicant. Active extrusion via the ArsAB pump is a mechanism for arsenic detoxication in bacteria. However, how arsenic is effluxed from mammalian cells is not completely known. Our recent work shows that acquired arsenic resistance is associated with overexpression of P-glycoprotein and can be reversed by PSC833, an inhibitor for P-glycoprotein. This study utilized the mdr1a/1b(-/-) mice, which lack mdr1-type P-glycoproteins, to examine whether these mice are sensitive to arsenic toxicity and have higher arsenic accumulation in their tissues. The mdr1a/1b(-/-) and wild-type FVB mice were given arsenic as sodium arsenite (12-19 mg/kg, sc) and toxicity was examined 24 h later. The mdr1a/1b(-/-) mice were more sensitive than wild-type mice to arsenite-induced lethality, with LD(50) of 14.5 and 17 mg/kg, respectively. Histologically, arsenite produced more frequent and more severe lesions in the liver and kidney of the mdr1a/1b(-/-) mice than in wild-type mice. Serum alanine aminotransferase activity and blood urea nitrogen levels, indicative of hepatic and renal damage respectively, were increased 4 to 6-fold in the mdr1a/1b(-/-) mice as compared with 1-2-fold increases in wild-type mice. The mdr1a/1b(-/-) mice accumulated more arsenic in the liver (15.3 vs. 5.2 microg/g), kidney (7.23 vs. 3.22 microg/g), small intestine (3.98 vs. 1.57 microg/g) and brain (0.45 vs. 0.17 microg/g), as compared with wild-type mice 24 h after sodium arsenite (14 mg/kg, s.c.) administration. In summary, this study demonstrated that the mdr1a/1b(-/-) mice were more sensitive to acute arsenic toxicity and accumulated more arsenic than wild-type mice, suggesting that P-glycoproteins are involved, at least in part, in arsenic efflux in mammalians. JF - Toxicology AU - Liu, Jie AU - Liu, Yaping AU - Powell, Douglas A AU - Waalkes, Michael P AU - Klaassen, Curtis D AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, Mail Drop F0-09, NCI at NIEHS, 111, Alexander Drive, Research Triangle Park, NC 27709, USA. liu6@niehs.nih.gov Y1 - 2002/01/15/ PY - 2002 DA - 2002 Jan 15 SP - 55 EP - 62 VL - 170 IS - 1-2 SN - 0300-483X, 0300-483X KW - Arsenites KW - 0 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Arsenic KW - N712M78A8G KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Alanine Transaminase -- blood KW - Kidney -- pathology KW - Arsenites -- metabolism KW - Mice KW - Tissue Distribution KW - Blood Urea Nitrogen KW - Mice, Knockout KW - Arsenic -- pharmacokinetics KW - Genes, MDR -- genetics KW - Arsenic -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71352796?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Multidrug-resistance+mdr1a%2F1b+double+knockout+mice+are+more+sensitive+than+wild+type+mice+to+acute+arsenic+toxicity%2C+with+higher+arsenic+accumulation+in+tissues.&rft.au=Liu%2C+Jie%3BLiu%2C+Yaping%3BPowell%2C+Douglas+A%3BWaalkes%2C+Michael+P%3BKlaassen%2C+Curtis+D&rft.aulast=Liu&rft.aufirst=Jie&rft.date=2002-01-15&rft.volume=170&rft.issue=1-2&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-31 N1 - Date created - 2001-12-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of garlic supplements on the pharmacokinetics of saquinavir. AN - 71347156; 11740713 AB - Herbal therapies are widely used, but there are few data on their interactions with conventional medications. This study evaluated the effect of garlic supplements on the pharmacokinetics of saquinavir. Ten healthy volunteers received 10 doses of saquinavir (Fortovase) at a dosage of 1200 mg 3 times daily with meals for 4 days on study days 1-4, 22-25, and 36-39, and they received a total of 41 doses of garlic caplets taken 2 times daily on study days 5-25. Blood samples were obtained on study days 4, 25, and 39 for determination of saquinavir plasma pharmacokinetic parameters. In the presence of garlic, the mean saquinavir area under the curve (AUC) during the 8-h dosing interval decreased by 51%, trough levels at 8 h after dosing decreased by 49%, and the mean maximum concentrations (Cmax) decreased by 54%. After the 10-day washout period, the AUC, trough, and Cmax values returned to 60%-70% of their values at baseline. Patients should use caution when combining garlic supplements with saquinavir when it is used as a sole protease inhibitor. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Piscitelli, Stephen C AU - Burstein, Aaron H AU - Welden, Nada AU - Gallicano, Keith D AU - Falloon, Judith AD - Pharmacy Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892-1880, USA. Y1 - 2002/01/15/ PY - 2002 DA - 2002 Jan 15 SP - 234 EP - 238 VL - 34 IS - 2 KW - Drug Combinations KW - 0 KW - Plant Extracts KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Saquinavir KW - L3JE09KZ2F KW - Index Medicus KW - Plant Extracts -- blood KW - Administration, Oral KW - Drug Administration Schedule KW - Humans KW - Enterocytes -- drug effects KW - Cytochrome P-450 Enzyme System -- metabolism KW - HIV Infections -- enzymology KW - HIV-1 -- enzymology KW - Longitudinal Studies KW - Plant Extracts -- adverse effects KW - Plant Extracts -- pharmacology KW - Adult KW - HIV Infections -- drug therapy KW - Intestine, Small -- drug effects KW - HIV-1 -- drug effects KW - Plant Extracts -- administration & dosage KW - Male KW - Enterocytes -- enzymology KW - Female KW - Intestine, Small -- enzymology KW - Saquinavir -- blood KW - Dietary Supplements -- adverse effects KW - Saquinavir -- adverse effects KW - Garlic -- adverse effects KW - Saquinavir -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71347156?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.atitle=The+effect+of+garlic+supplements+on+the+pharmacokinetics+of+saquinavir.&rft.au=Piscitelli%2C+Stephen+C%3BBurstein%2C+Aaron+H%3BWelden%2C+Nada%3BGallicano%2C+Keith+D%3BFalloon%2C+Judith&rft.aulast=Piscitelli&rft.aufirst=Stephen&rft.date=2002-01-15&rft.volume=34&rft.issue=2&rft.spage=234&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=1537-6591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-04 N1 - Date created - 2001-12-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Clin Infect Dis. 2002 Aug 1;35(3):343 [12115105] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The enantioselective determination of chlorpheniramine and its major metabolites in human plasma using chiral chromatography on a beta -cyclodextrin chiral stationary phase and mass spectrometric detection AN - 18323082; 5372838 AB - A sensitive enantioselective high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of plasma concentrations of (-)(R)- and (+)(S)-chlorpheniramine (CP) and their metabolites, desmethyl-chlorpheniramine (DCP), didesmethyl-chorpheniramine (DDCP) and chlorpheniramine N-oxide (CPNO). Enantioselective separations were achieved on a beta -cyclodextrin chiral stationary phase (CYCLOBOND I 2000) with a mobile phase consisting of diethylamine acetate (0.25%, pH 4.4):methanol:acetonitrile {85:7.5:7.5, (v/v/v)} and a flow-rate of 0.5 ml/min. For CP, the enantioselectivity ( alpha ) of the separation was 1.12 with a resolution factor (R sub(s)) of 1.17. The method was validated for CP by using mass spectroscopy detection (MSD). Concentrations of each enantiomer could be measured down to 125 pg/ml from a 1-ml plasma sample. Extracted calibration curves were linear from 0.13 to 50.00 ng/ml for each enantiomer. The method was applied to samples from two clinical studies. JF - Journal of Pharmaceutical and Biomedical Analysis AU - Fried, K M AU - Young, A E AU - Yasuda, SU AU - Wainer, I W AD - Bioanalytical and Drug Discovery Unit, Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825, USA, wainerir@grc.nia.nih.gov Y1 - 2002/01/15/ PY - 2002 DA - 2002 Jan 15 SP - 479 EP - 488 VL - 27 IS - 3-4 SN - 0731-7085, 0731-7085 KW - man KW - determination KW - metabolites KW - chlorpheniramine KW - Toxicology Abstracts KW - High-performance liquid chromatography KW - Plasma KW - Mass spectroscopy KW - X 24222:Analytical procedures UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18323082?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Pharmaceutical+and+Biomedical+Analysis&rft.atitle=The+enantioselective+determination+of+chlorpheniramine+and+its+major+metabolites+in+human+plasma+using+chiral+chromatography+on+a+beta+-cyclodextrin+chiral+stationary+phase+and+mass+spectrometric+detection&rft.au=Fried%2C+K+M%3BYoung%2C+A+E%3BYasuda%2C+SU%3BWainer%2C+I+W&rft.aulast=Fried&rft.aufirst=K&rft.date=2002-01-15&rft.volume=27&rft.issue=3-4&rft.spage=479&rft.isbn=&rft.btitle=&rft.title=Journal+of+Pharmaceutical+and+Biomedical+Analysis&rft.issn=07317085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special Issue: The Impact of Enantioseparation Techniques on the Development and use of Chiral Drugs. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - High-performance liquid chromatography; Mass spectroscopy; Plasma ER - TY - JOUR T1 - Protein kinase C-induced disorganization and endocytosis of photosensitive membrane in Limulus ventral photoreceptors. AN - 71359767; 11774337 AB - Protein kinase C (PKC) desensitizes the light response in photoreceptors from the ventral optic nerve of the horseshoe crab Limulus. Photoisomerization of Limulus rhodopsin leads to phosphoinositide hydrolysis, resulting in the production of inositol trisphosphate and diacylglycerol (DAG). Inositol trisphosphate mobilizes intracellular stores of Ca(2+), resulting in photoreceptor excitation in Limulus, while DAG may activate PKC. We investigated whether PKC-mediated desensitization of the photoresponse is accompanied by ultrastructural changes in the rhodopsin-bearing photosensitive membrane (rhabdom) in Limulus ventral photoreceptors. PKC activation by (-)-indolactam V in darkness induces disorganization and swelling of the rhodopsin-containing microvilli and endocytosis of rhabdomeral membrane. The effects of (-)-indolactam V on dark-adapted photoreceptor ultrastructure are reversible, are stereospecific, are blocked by coapplication of PKC inhibitors, and closely match those induced by continuous, bright light. Rhabdom disorganization and endocytosis via PKC activation may, therefore, contribute to desensitization of the light-adapted photoreceptor. Copyright 2001 Wiley-Liss, Inc. JF - The Journal of comparative neurology AU - Dabdoub, Alain AU - Payne, Richard AU - Jinks, Robert N AD - National Institutes of Health, NIDCD, Rockville, Maryland 20850, USA. Y1 - 2002/01/14/ PY - 2002 DA - 2002 Jan 14 SP - 217 EP - 225 VL - 442 IS - 3 SN - 0021-9967, 0021-9967 KW - Carcinogens KW - 0 KW - Enzyme Inhibitors KW - Indoles KW - Lactams KW - indolactam V KW - 8CIY9O1323 KW - Rhodopsin KW - 9009-81-8 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Carcinogens -- pharmacology KW - Animals KW - Photic Stimulation KW - Circadian Rhythm -- physiology KW - Dose-Response Relationship, Drug KW - Enzyme Inhibitors -- pharmacology KW - Microscopy, Electron KW - Indoles -- pharmacology KW - Male KW - Lactams -- pharmacology KW - Photoreceptor Cells, Invertebrate -- drug effects KW - Horseshoe Crabs -- drug effects KW - Intracellular Membranes -- drug effects KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Horseshoe Crabs -- enzymology KW - Photoreceptor Cells, Invertebrate -- ultrastructure KW - Light Signal Transduction -- drug effects KW - Endocytosis -- drug effects KW - Rhodopsin -- metabolism KW - Endocytosis -- physiology KW - Intracellular Membranes -- ultrastructure KW - Horseshoe Crabs -- ultrastructure KW - Intracellular Membranes -- enzymology KW - Light Signal Transduction -- physiology KW - Photoreceptor Cells, Invertebrate -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71359767?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+comparative+neurology&rft.atitle=Protein+kinase+C-induced+disorganization+and+endocytosis+of+photosensitive+membrane+in+Limulus+ventral+photoreceptors.&rft.au=Dabdoub%2C+Alain%3BPayne%2C+Richard%3BJinks%2C+Robert+N&rft.aulast=Dabdoub&rft.aufirst=Alain&rft.date=2002-01-14&rft.volume=442&rft.issue=3&rft.spage=217&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+comparative+neurology&rft.issn=00219967&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-25 N1 - Date created - 2002-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of adenylyl cyclases by a region outside the minimally functional cytoplasmic domains. AN - 71360346; 11694527 AB - The highly conserved topological structure of G protein-activated adenylyl cyclases seems unnecessary because the soluble cytoplasmic domains retain regulatory and catalytic properties. Yet, we previously isolated a constitutively active mutant of the Dictyostelium discoideum adenylyl cyclase harboring a single point mutation in the region linking the cytoplasmic and membrane domains (Leu-394). We show here that multiple amino acid substitutions at Leu-394 also display constitutive activity. The constitutive activity of these mutants is not dependent on G proteins or cytosolic regulators, although some of the mutants can be activated to higher levels than wild type. Combining a constitutive mutation such as L394T with K482N, a point mutation that renders the enzyme insensitive to regulators, restores an enzyme with wild type properties of low basal activity and the capacity to be activated by G proteins. Thus regions located outside the cytoplasmic loops of adenylyl cyclases are not only important in the acquisition of an activated conformation, they also have impact on other regions within the catalytic core of the enzyme. JF - The Journal of biological chemistry AU - Parent, Carole A AU - Borleis, Jane AU - Devreotes, Peter N AD - Department of Biological Chemistry, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA. parentc@helix.nih.gov Y1 - 2002/01/11/ PY - 2002 DA - 2002 Jan 11 SP - 1354 EP - 1360 VL - 277 IS - 2 SN - 0021-9258, 0021-9258 KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Index Medicus KW - Phenotype KW - Mutagenesis, Site-Directed KW - Animals KW - Protein Structure, Secondary KW - Sequence Alignment KW - Molecular Sequence Data KW - Guanosine 5'-O-(3-Thiotriphosphate) -- metabolism KW - Amino Acid Sequence KW - Protein Structure, Tertiary KW - Dictyostelium -- genetics KW - Adenylyl Cyclases -- chemistry KW - Adenylyl Cyclases -- metabolism KW - Adenylyl Cyclases -- genetics KW - Dictyostelium -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71360346?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Regulation+of+adenylyl+cyclases+by+a+region+outside+the+minimally+functional+cytoplasmic+domains.&rft.au=Parent%2C+Carole+A%3BBorleis%2C+Jane%3BDevreotes%2C+Peter+N&rft.aulast=Parent&rft.aufirst=Carole&rft.date=2002-01-11&rft.volume=277&rft.issue=2&rft.spage=1354&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-07 N1 - Date created - 2002-01-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Binding of the natural killer cell inhibitory receptor Ly49A to its major histocompatibility complex class I ligand. Crucial contacts include both H-2Dd AND beta 2-microglobulin. AN - 71355822; 11696552 AB - Ly49A, an inhibitory C-type lectin-like mouse natural killer cell receptor, functions through interaction with the major histocompatibility complex class I molecule, H-2D(d). The x-ray crystal structure of the Ly49A.H-2D(d) complex revealed that homodimeric Ly49A interacts at two distinct sites of H-2D(d): Site 1, spanning one side of the alpha1 and alpha2 helices, and Site 2, involving the alpha1, alpha2, alpha3, and beta(2)m domains. Mutants of Ly49A, H-2D(d), and beta(2)-microglobulin at intermolecular contacts and the Ly49A dimer interface were examined for binding affinity and kinetics. Although mutations at Site 1 had little affect, several at Site 2 and at the dimer interface hampered the Ly49A.H-2D(d) interaction, with no effect on gross structure or T cell receptor interaction. The region surrounding the most critical residues (in H-2D(d), Asp(122); in Ly49A, Asp(229), Ser(236), Thr(238), Arg(239), and Asp(241); and in beta(2)-microglobulin, Gln(29) and Lys(58)) of the Ly49A.H-2D(d) interface at Site 2 includes a network of water molecules, suggesting a molecular basis for allelic specificity in natural killer cell recognition. JF - The Journal of biological chemistry AU - Wang, Jian AU - Whitman, Mary C AU - Natarajan, Kannan AU - Tormo, Jose AU - Mariuzza, Roy A AU - Margulies, David H AD - Molecular Biology Section, Laboratory of Immunology, NIAID, National Institutes of Health, Bethesda, Maryland 20892-1892, USA. Y1 - 2002/01/11/ PY - 2002 DA - 2002 Jan 11 SP - 1433 EP - 1442 VL - 277 IS - 2 SN - 0021-9258, 0021-9258 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, Ly KW - Antigens, Surface KW - Carrier Proteins KW - H-2 Antigens KW - Histocompatibility Antigen H-2D KW - Klra1 protein, mouse KW - Lectins, C-Type KW - Ligands KW - Membrane Proteins KW - NK Cell Lectin-Like Receptor Subfamily A KW - Receptors, Immunologic KW - Receptors, NK Cell Lectin-Like KW - Recombinant Proteins KW - beta 2-Microglobulin KW - Index Medicus KW - Animals KW - Models, Molecular KW - Antibodies, Monoclonal -- metabolism KW - Dimerization KW - Surface Plasmon Resonance KW - Mice KW - Amino Acid Sequence KW - Recombinant Proteins -- genetics KW - Protein Binding KW - Antigens, Surface -- genetics KW - Binding Sites KW - Receptors, Immunologic -- genetics KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - Receptors, Immunologic -- metabolism KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Antigens, Surface -- metabolism KW - Killer Cells, Natural -- physiology KW - Major Histocompatibility Complex -- physiology KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry KW - Membrane Proteins -- chemistry KW - beta 2-Microglobulin -- metabolism KW - Carrier Proteins -- genetics KW - Membrane Proteins -- metabolism KW - Membrane Proteins -- genetics KW - beta 2-Microglobulin -- genetics KW - Protein Structure, Quaternary KW - H-2 Antigens -- genetics KW - H-2 Antigens -- chemistry KW - H-2 Antigens -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71355822?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Binding+of+the+natural+killer+cell+inhibitory+receptor+Ly49A+to+its+major+histocompatibility+complex+class+I+ligand.+Crucial+contacts+include+both+H-2Dd+AND+beta+2-microglobulin.&rft.au=Wang%2C+Jian%3BWhitman%2C+Mary+C%3BNatarajan%2C+Kannan%3BTormo%2C+Jose%3BMariuzza%2C+Roy+A%3BMargulies%2C+David+H&rft.aulast=Wang&rft.aufirst=Jian&rft.date=2002-01-11&rft.volume=277&rft.issue=2&rft.spage=1433&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-07 N1 - Date created - 2002-01-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Purification and Characterization of Methionine Sulfoxide Reductases from Mouse and Staphylococcus aureus and Their Substrate Stereospecificity AN - 18235108; 5295045 AB - Many organisms have been shown to possess a methionine sulfoxide reductase (MsrA), exhibiting high specificity for reduction the S form of free and protein-bound methionine sulfoxide to methionine. Recently, a different form of the reductase (referred to as MsrB) has been detected in several organisms. We show here that MsrB is a selenoprotein that exhibits high specificity for reduction of the R forms of free and protein-bound methionine sulfoxide. The enzyme was partially purified from mouse liver and a derivative of the mouse MsrB gene, in which the codon specifying selenocystein incorporation was replaced by the cystein codon, was prepared, cloned, and overexpressed in Escherichia coli. The properties of the modified MsrB protein were compared directly with those of MsrA. Also, we have shown that in Staphylococcus aureus there are two MsrA and one nonselenoprotein MsrB, which demonstrates the same substrate stereospecificity as the mouse MsrB. JF - Biochemical and Biophysical Research Communications AU - Moskovitz, J AU - Singh, V K AU - Requena, J AU - Wilkinson, B J AU - Jayaswal, R K AU - Stadtman, E R AD - Laboratory of Biochemistry, National Institute of Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, moskovij@nhlbi.nih.gov Y1 - 2002/01/11/ PY - 2002 DA - 2002 Jan 11 SP - 62 EP - 65 PB - Academic Press VL - 290 IS - 1 SN - 0006-291X, 0006-291X KW - mice KW - MsrA protein KW - MsrB gene KW - MsrB protein KW - methionine sulfoxide KW - methyl sulfoxide reductase I KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Stereospecificity KW - Substrate specificity KW - Staphylococcus aureus KW - J 02728:Enzymes KW - G 07397:Rodentia (mice) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18235108?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+Biophysical+Research+Communications&rft.atitle=Purification+and+Characterization+of+Methionine+Sulfoxide+Reductases+from+Mouse+and+Staphylococcus+aureus+and+Their+Substrate+Stereospecificity&rft.au=Moskovitz%2C+J%3BSingh%2C+V+K%3BRequena%2C+J%3BWilkinson%2C+B+J%3BJayaswal%2C+R+K%3BStadtman%2C+E+R&rft.aulast=Moskovitz&rft.aufirst=J&rft.date=2002-01-11&rft.volume=290&rft.issue=1&rft.spage=62&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+Biophysical+Research+Communications&rft.issn=0006291X&rft_id=info:doi/10.1006%2Fbbrc.2001.6171 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Staphylococcus aureus; Substrate specificity; Stereospecificity DO - http://dx.doi.org/10.1006/bbrc.2001.6171 ER - TY - JOUR T1 - The beta -Hairpin Motif of UvrB Is Essential for DNA Binding, Damage Processing, and UvrC-mediated Incisions AN - 18223792; 5292312 AB - UvrB plays a major role in recognition and processing of DNA lesions during nucleotide excision repair. The crystal structure of UvrB revealed a similar fold as found in monomeric DNA helicases. Homology modeling suggested that the beta -hairpin motif of UvrB might be involved in DNA binding (Theis, K., Chen, P. J., Skorvaga, M., Van Houten, B., and Kisker, C. (1999) EMBO J. 18, 6899-6907). To determine a role of the beta -hairpin of Bacillus caldotenax UvrB, we have constructed a deletion mutant, Delta beta h UvrB, which lacks residues Gln-97-Asp-112 of the beta -hairpin. Delta beta h UvrB does not form a stable UvrB-DNA pre-incision complex and is inactive in UvrABC-mediated incision. However, Delta beta h UvrB is able to bind to UvrA and form a complex with UvrA and damaged DNA, competing with wild type UvrB. In addition, Delta beta h UvrB shows wild type-like ATPase activity in complex with UvrA that is stimulated by damaged DNA. In contrast to wild type UvrB, the ATPase activity of mutant UvrB does not lead to a destabilization of the damaged duplex. These results indicate that the conserved beta -hairpin motif is a major factor in DNA binding. JF - Journal of Biological Chemistry AU - Skorvaga, M AU - Theis, K AU - Mandavilli, B S AU - Kisker, C AU - van Houten, B AD - Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA, vanhout1@niehs.nih.gov Y1 - 2002/01/11/ PY - 2002 DA - 2002 Jan 11 SP - 1553 EP - 1559 VL - 277 IS - 2 SN - 0021-9258, 0021-9258 KW - b-hairpin KW - UvrA protein KW - UvrB protein KW - UvrC protein KW - beta -hairpin KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Bacillus caldotenax KW - Adenosinetriphosphatase KW - DNA-binding protein KW - DNA repair KW - DNA helicase KW - J 02725:DNA KW - N 14731:DNA-unwinding enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18223792?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=The+beta+-Hairpin+Motif+of+UvrB+Is+Essential+for+DNA+Binding%2C+Damage+Processing%2C+and+UvrC-mediated+Incisions&rft.au=Skorvaga%2C+M%3BTheis%2C+K%3BMandavilli%2C+B+S%3BKisker%2C+C%3Bvan+Houten%2C+B&rft.aulast=Skorvaga&rft.aufirst=M&rft.date=2002-01-11&rft.volume=277&rft.issue=2&rft.spage=1553&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bacillus caldotenax; DNA helicase; DNA-binding protein; DNA repair; Adenosinetriphosphatase ER - TY - JOUR T1 - Rac1 and RhoG promote cell survival by the activation of PI3K and Akt, independently of their ability to stimulate JNK and NF-kappaB. AN - 71415689; 11803464 AB - Small GTPases of the Rho family play a central role in cellular processes that involve the reorganization of the actin-based cytoskeleton. Rho-related GTPases, which include Rac and Cdc42, can also regulate gene expression often through the activation of kinase cascades leading to enhanced activity of stress activated protein kinases (SAPKs), including JNK and p38 MAP kinases. As SAPKs are implicated in programmed cell death, these observations suggest that Rho GTPases may promote the initiation of the apoptotic process. However, recent reports suggest that Rho GTPases can have either a protective or a pro-apoptotic role, depending on the particular cellular context. In an effort to explore the molecular mechanisms underlying these divergent biological activities, we asked whether there was indeed a correlation between the ability to induce SAPKs and apoptosis by Rho family members. We found that although constitutively activated (Q61L) mutants of Rac1, Cdc42, and RhoG, a Rac1 related GTPase of unknown function, potently induce JNK in COS 7 cells, none of these GTPases could induce apoptosis, nor enhance uv-induced cell death. In contrast, Rac1 and RhoG efficiently protected cells from uv-induced apoptosis. Furthermore, we provide evidence that Rac1 and RhoG can activate both apoptotic and anti-apoptotic pathways. Whereas the former is mediated through JNK, the latter is independent on the transcriptional activation of NF-kappaB, a pro-survival pathway, but results from the direct interaction of these GTPases with phosphatidylinositol 3-kinase (PI3K) and the stimulation of Akt. Together, these findings indicate that members of the Rho family of small GTP-binding proteins can provoke the concomitant stimulation of two counteracting signaling pathways, and that their balance ultimately determines the ability of these GTPases to promote cell survival or death. JF - Oncogene AU - Murga, Cristina AU - Zohar, Muriel AU - Teramoto, Hidemi AU - Gutkind, J Silvio AD - Oral and Pharyngeal Cancer Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland, MD 20892-4330, USA. Y1 - 2002/01/10/ PY - 2002 DA - 2002 Jan 10 SP - 207 EP - 216 VL - 21 IS - 2 SN - 0950-9232, 0950-9232 KW - NF-kappa B KW - 0 KW - Proto-Oncogene Proteins KW - Recombinant Proteins KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-akt KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - GTP Phosphohydrolases KW - EC 3.6.1.- KW - rac1 GTP-Binding Protein KW - EC 3.6.5.2 KW - Index Medicus KW - Animals KW - COS Cells KW - Enzyme Activation KW - Protein-Tyrosine Kinases -- metabolism KW - Mutagenesis, Site-Directed KW - Transfection KW - Recombinant Proteins -- metabolism KW - Cercopithecus aethiops KW - Enzyme Induction KW - Amino Acid Substitution KW - Cell Line KW - Phosphatidylinositol 3-Kinases -- metabolism KW - GTP Phosphohydrolases -- genetics KW - Mitogen-Activated Protein Kinases -- metabolism KW - GTP Phosphohydrolases -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - rac1 GTP-Binding Protein -- metabolism KW - rac1 GTP-Binding Protein -- genetics KW - Mitogen-Activated Protein Kinases -- biosynthesis KW - NF-kappa B -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71415689?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Rac1+and+RhoG+promote+cell+survival+by+the+activation+of+PI3K+and+Akt%2C+independently+of+their+ability+to+stimulate+JNK+and+NF-kappaB.&rft.au=Murga%2C+Cristina%3BZohar%2C+Muriel%3BTeramoto%2C+Hidemi%3BGutkind%2C+J+Silvio&rft.aulast=Murga&rft.aufirst=Cristina&rft.date=2002-01-10&rft.volume=21&rft.issue=2&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-15 N1 - Date created - 2002-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rapid activation of G2/M checkpoint after hypertonic stress in renal inner medullary epithelial (IME) cells is protective and requires p38 kinase. AN - 71361888; 11756692 AB - Cells in the kidney medulla are subject to variable and often extreme osmotic stress during concentration of the urine. Previous studies showed that renal inner medullary epithelial (IME) cells respond to hypertonicity by G(2) arrest. The purpose of the present study was to investigate the mechanisms involved in initiation and maintenance of G(2) arrest. Rapid initiation of G(2) arrest after UV radiation is mediated by p38 kinase. Here we find that p38 kinase is responsible for rapid initiation of the G(2) delay in IME cells after the hypertonic stress created by adding NaCl. High NaCl, but not high urea, rapidly initiates G(2) arrest. Inhibition of p38 kinase by SB202190 (10 microM) blocks the rapid initiation of this checkpoint both in an immortalized cell line (mIMCD3) and in second-passage IME cells from mouse renal inner medulla. p38 inhibition does not affect exit from G(2) arrest. The rapid initiation of G(2) arrest is followed by inhibition of cdc2 kinase, which is also prevented by SB202190. To assess the possible protective role of G(2) arrest, we measured DNA strand breaks as reflected by immunostaining against phospho-histone H2AX, which becomes phosphorylated on Ser-139 associated with DNA breaks. Abrogation of rapid G(2)/M checkpoint activation by SB202190 increases the histone H2AX phosphorylation in G(2)/M cells. We propose that the rapid initiation of G(2) delay by p38 kinase after hypertonicity protects the cells by decreasing the level of DNA breaks caused by aberrant mitosis entry. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Dmitrieva, Natalia I AU - Bulavin, Dmitry V AU - Fornace, Albert J AU - Burg, Maurice B AD - Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institute, and Gene Response Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. dmitrien@nhlbi.nih.gov Y1 - 2002/01/08/ PY - 2002 DA - 2002 Jan 08 SP - 184 EP - 189 VL - 99 IS - 1 SN - 0027-8424, 0027-8424 KW - Central Nervous System Stimulants KW - 0 KW - Enzyme Inhibitors KW - Histones KW - Imidazoles KW - Pyridines KW - Caffeine KW - 3G6A5W338E KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole KW - PVX798P8GI KW - Index Medicus KW - Animals KW - Ultraviolet Rays KW - Central Nervous System Stimulants -- pharmacology KW - Imidazoles -- pharmacology KW - DNA Damage KW - Dose-Response Relationship, Drug KW - Caffeine -- pharmacology KW - Mice KW - Dose-Response Relationship, Radiation KW - Precipitin Tests KW - Blotting, Western KW - Phosphorylation KW - Cells, Cultured KW - Histones -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Time Factors KW - Pyridines -- pharmacology KW - Osmotic Pressure KW - Epithelial Cells -- pathology KW - Mitosis KW - Kidney Medulla -- cytology KW - G2 Phase KW - Mitogen-Activated Protein Kinases -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71361888?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Rapid+activation+of+G2%2FM+checkpoint+after+hypertonic+stress+in+renal+inner+medullary+epithelial+%28IME%29+cells+is+protective+and+requires+p38+kinase.&rft.au=Dmitrieva%2C+Natalia+I%3BBulavin%2C+Dmitry+V%3BFornace%2C+Albert+J%3BBurg%2C+Maurice+B&rft.aulast=Dmitrieva&rft.aufirst=Natalia&rft.date=2002-01-08&rft.volume=99&rft.issue=1&rft.spage=184&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-15 N1 - Date created - 2002-01-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1994 Dec 22-29;372(6508):739-46 [7997261] Science. 1982 Sep 24;217(4566):1214-22 [7112124] Annu Rev Physiol. 1997;59:437-55 [9074772] J Biol Chem. 1997 May 16;272(20):13165-70 [9148932] Science. 1997 Sep 5;277(5331):1495-7 [9278510] Science. 1997 Sep 5;277(5331):1501-5 [9278512] Biochem Mol Biol Int. 1997 Sep;43(1):63-72 [9315283] J Biol Chem. 1998 Jan 16;273(3):1832-7 [9430735] J Biol Chem. 1998 Mar 6;273(10):5858-68 [9488723] J Biol Chem. 1998 May 29;273(22):13645-51 [9593703] Physiol Rev. 1991 Oct;71(4):1081-115 [1924548] Science. 1993 Mar 19;259(5102):1760-3 [7681220] Am J Physiol. 1993 Sep;265(3 Pt 2):F416-24 [8214101] J Biol Chem. 1993 Nov 25;268(33):25009-14 [7693711] Science. 1994 Aug 5;265(5173):808-11 [7914033] Cell. 1994 Sep 23;78(6):1027-37 [7923353] J Biol Chem. 1996 Jul 26;271(30):17920-6 [8663524] Arch Biochem Biophys. 1998 Jun 1;354(1):172-80 [9633613] J Cell Biol. 1998 Jul 27;142(2):523-35 [9679149] Genes Dev. 1998 Oct 1;12(19):2973-83 [9765199] Am J Physiol. 1998 Jun;274(6 Pt 2):F1167-73 [9841510] J Clin Invest. 1998 Nov 15;102(10):1874-81 [9819374] EMBO J. 1999 Apr 1;18(7):1845-57 [10202148] J Biol Chem. 1999 Jul 16;274(29):20185-90 [10400634] Environ Health Perspect. 1999 Feb;107 Suppl 1:5-24 [10229703] Pharmacol Ther. 1999 May-Jun;82(2-3):389-97 [10454214] Cancer Res. 1999 Sep 1;59(17):4375-82 [10485486] Nat Cell Biol. 1999 Jul;1(3):E73-9 [10559915] Am J Physiol Renal Physiol. 2000 Feb;278(2):F209-18 [10662725] Cell Signal. 2000 Jan;12(1):1-13 [10676842] J Biol Chem. 2000 Feb 25;275(8):5600-5 [10681541] J Exp Med. 2000 Mar 6;191(5):859-70 [10704466] J Biol Chem. 2000 Mar 31;275(13):9390-5 [10734083] J Biol Chem. 2000 Apr 7;275(14):10342-8 [10744722] Mol Microbiol. 2000 Jun;36(6):1381-90 [10931288] Cell Prolif. 2000 Jun;33(3):147-66 [10959624] EMBO J. 2000 Dec 1;19(23):6517-26 [11101524] Mol Biol Cell. 2001 Jan;12(1):53-62 [11160822] Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1999-2004 [11172065] Physiol Rev. 2001 Apr;81(2):807-69 [11274345] Oncogene. 2001 Apr 5;20(15):1803-15 [11313928] Nature. 2001 May 3;411(6833):102-7 [11333986] Am J Physiol Renal Physiol. 2001 Sep;281(3):F522-30 [11502601] Cell. 1994 Sep 23;78(6):1039-49 [7923354] N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Molecular determinants of the pathogenesis of Mycobacterium tuberculosis AN - 39559545; 3647145 AU - Barry, C III Y1 - 2002/01/08/ PY - 2002 DA - 2002 Jan 08 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39559545?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Molecular+determinants+of+the+pathogenesis+of+Mycobacterium+tuberculosis&rft.au=Barry%2C+C+III&rft.aulast=Barry&rft.aufirst=C&rft.date=2002-01-08&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Australian Society for Microbiology, Unit 23, 20 Commercial Road, Melbourne Vic, 3004, Australia; URL: www.theasm.com.au. Paper No. SY28.1 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Identification of Plasmodium-responsive genes in Drosophila melanogaster AN - 39503337; 3656919 AU - Costero, A AU - Shahabuddin, M Y1 - 2002/01/08/ PY - 2002 DA - 2002 Jan 08 KW - CPI, Conference Papers Index KW - U 7000:Multidisciplinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39503337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Identification+of+Plasmodium-responsive+genes+in+Drosophila+melanogaster&rft.au=Costero%2C+A%3BShahabuddin%2C+M&rft.aulast=Costero&rft.aufirst=A&rft.date=2002-01-08&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Tropical Medicine, 60 Revere Dr., Suite 500, Northbrook, IL 60062, USA; phone: 847-480-9592; fax: 847-480-9282; email: astmh@astmh.org; URL: www.astmh.org. Paper No. 804 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Identification and characterization of histamine releasing recombinant antigen from Strongyloides stercoralis L3 cDNA library AN - 39498218; 3656462 AU - Ravi, V AU - Ramachandran, S AU - Thompson, R W AU - Neva, F A Y1 - 2002/01/08/ PY - 2002 DA - 2002 Jan 08 KW - CPI, Conference Papers Index KW - U 7000:Multidisciplinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39498218?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Identification+and+characterization+of+histamine+releasing+recombinant+antigen+from+Strongyloides+stercoralis+L3+cDNA+library&rft.au=Ravi%2C+V%3BRamachandran%2C+S%3BThompson%2C+R+W%3BNeva%2C+F+A&rft.aulast=Ravi&rft.aufirst=V&rft.date=2002-01-08&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Tropical Medicine, 60 Revere Dr., Suite 500, Northbrook, IL 60062, USA; phone: 847-480-9592; fax: 847-480-9282; email: astmh@astmh.org; URL: www.astmh.org. Paper No. 393 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Functional genomics and new approaches to TB drug development AN - 39491805; 3647042 AU - Barry, C III Y1 - 2002/01/08/ PY - 2002 DA - 2002 Jan 08 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39491805?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Functional+genomics+and+new+approaches+to+TB+drug+development&rft.au=Barry%2C+C+III&rft.aulast=Barry&rft.aufirst=C&rft.date=2002-01-08&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Australian Society for Microbiology, Unit 23, 20 Commercial Road, Melbourne Vic, 3004, Australia; URL: www.theasm.com.au. Paper No. SY10.3 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Comparison of two cDNA clones of HEV which are infectious for primates identifies a cis-reacting element AN - 39481453; 3656081 AU - Emerson, SU AU - Zhang, M AU - Meng, X-J AU - St Clair, M AU - Nguyen, H AU - Huang, Y AU - Purcell, R H Y1 - 2002/01/08/ PY - 2002 DA - 2002 Jan 08 KW - CPI, Conference Papers Index KW - U 7000:Multidisciplinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39481453?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Comparison+of+two+cDNA+clones+of+HEV+which+are+infectious+for+primates+identifies+a+cis-reacting+element&rft.au=Emerson%2C+SU%3BZhang%2C+M%3BMeng%2C+X-J%3BSt+Clair%2C+M%3BNguyen%2C+H%3BHuang%2C+Y%3BPurcell%2C+R+H&rft.aulast=Emerson&rft.aufirst=SU&rft.date=2002-01-08&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Tropical Medicine, 60 Revere Dr., Suite 500, Northbrook, IL 60062, USA; phone: 847-480-9592; fax: 847-480-9282; email: astmh@astmh.org; URL: www.astmh.org. Paper No. 57 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Recovery of hepatitis E virus (HEV)-like agents from rats in Los Angeles AN - 39481418; 3656080 AU - Purcell, R H AU - Rood, M AU - Kabrane-Lazizi, Y AU - Engle, R E AU - Shapiro, M AU - Emerson, SU Y1 - 2002/01/08/ PY - 2002 DA - 2002 Jan 08 KW - CPI, Conference Papers Index KW - U 7000:Multidisciplinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39481418?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Recovery+of+hepatitis+E+virus+%28HEV%29-like+agents+from+rats+in+Los+Angeles&rft.au=Purcell%2C+R+H%3BRood%2C+M%3BKabrane-Lazizi%2C+Y%3BEngle%2C+R+E%3BShapiro%2C+M%3BEmerson%2C+SU&rft.aulast=Purcell&rft.aufirst=R&rft.date=2002-01-08&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Tropical Medicine, 60 Revere Dr., Suite 500, Northbrook, IL 60062, USA; phone: 847-480-9592; fax: 847-480-9282; email: astmh@astmh.org; URL: www.astmh.org. Paper No. 56 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Evaluation of a clinically acceptable hepatitis E vaccine AN - 39479216; 3656084 AU - Purcell, R H AU - Shapiro, M AU - Nguyen, H AU - Prieels, J-P AU - Govindarajan, S AU - Emerson, SU Y1 - 2002/01/08/ PY - 2002 DA - 2002 Jan 08 KW - CPI, Conference Papers Index KW - U 7000:Multidisciplinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39479216?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Evaluation+of+a+clinically+acceptable+hepatitis+E+vaccine&rft.au=Purcell%2C+R+H%3BShapiro%2C+M%3BNguyen%2C+H%3BPrieels%2C+J-P%3BGovindarajan%2C+S%3BEmerson%2C+SU&rft.aulast=Purcell&rft.aufirst=R&rft.date=2002-01-08&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Tropical Medicine, 60 Revere Dr., Suite 500, Northbrook, IL 60062, USA; phone: 847-480-9592; fax: 847-480-9282; email: astmh@astmh.org; URL: www.astmh.org. Paper No. 60 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - In vivo site-directed mutagenesis using oligonucleotides: A versatile system for functional genomics AN - 39470436; 3646385 AU - Storici, F AU - Lewis, L K AU - Resnick, MA Y1 - 2002/01/08/ PY - 2002 DA - 2002 Jan 08 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39470436?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=In+vivo+site-directed+mutagenesis+using+oligonucleotides%3A+A+versatile+system+for+functional+genomics&rft.au=Storici%2C+F%3BLewis%2C+L+K%3BResnick%2C+MA&rft.aulast=Storici&rft.aufirst=F&rft.date=2002-01-08&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Yeast 2001, Academy of Sciences of the Czech Republic, Videnska 1083, CZ-142 20 Prague 4, Czech Republic; fax: 420-2-475-25-01; email: yeast@biomed.cas.cz. Paper No. 05-23 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Alternative activation of arginase-1/nos-2 in macrophages controls tissue fibrosis and granuloma formation in a murine model of schistosomiasis AN - 39468640; 3656959 AU - Hesse, M AU - Modolell, M AU - La Flamme, AC AU - Schito, M AU - Fuentes, J M AU - Cheever, A W AU - Pearce, E J AU - Wynn, T A Y1 - 2002/01/08/ PY - 2002 DA - 2002 Jan 08 KW - CPI, Conference Papers Index KW - U 7000:Multidisciplinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39468640?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Alternative+activation+of+arginase-1%2Fnos-2+in+macrophages+controls+tissue+fibrosis+and+granuloma+formation+in+a+murine+model+of+schistosomiasis&rft.au=Hesse%2C+M%3BModolell%2C+M%3BLa+Flamme%2C+AC%3BSchito%2C+M%3BFuentes%2C+J+M%3BCheever%2C+A+W%3BPearce%2C+E+J%3BWynn%2C+T+A&rft.aulast=Hesse&rft.aufirst=M&rft.date=2002-01-08&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Tropical Medicine, 60 Revere Dr., Suite 500, Northbrook, IL 60062, USA; phone: 847-480-9592; fax: 847-480-9282; email: astmh@astmh.org; URL: www.astmh.org. Paper No. 844 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Binding of GCN1 near the ribosomal A-site and to the N-terminus of GCN2 is required for activation of the kinase GCN2 in amino acid starved cells AN - 39457367; 3646550 AU - Sattlegger, E AU - Swanson, M AU - Hinnebusch, A Y1 - 2002/01/08/ PY - 2002 DA - 2002 Jan 08 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39457367?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Binding+of+GCN1+near+the+ribosomal+A-site+and+to+the+N-terminus+of+GCN2+is+required+for+activation+of+the+kinase+GCN2+in+amino+acid+starved+cells&rft.au=Sattlegger%2C+E%3BSwanson%2C+M%3BHinnebusch%2C+A&rft.aulast=Sattlegger&rft.aufirst=E&rft.date=2002-01-08&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Yeast 2001, Academy of Sciences of the Czech Republic, Videnska 1083, CZ-142 20 Prague 4, Czech Republic; fax: 420-2-475-25-01; email: yeast@biomed.cas.cz. Paper No. 10-55 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Optimization of the conformation and efficacy of transmission-blocking and asexual malaria vaccine candidates AN - 39450956; 3656014 AU - Stowers, A Y1 - 2002/01/08/ PY - 2002 DA - 2002 Jan 08 KW - CPI, Conference Papers Index KW - U 7000:Multidisciplinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39450956?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Optimization+of+the+conformation+and+efficacy+of+transmission-blocking+and+asexual+malaria+vaccine+candidates&rft.au=Stowers%2C+A&rft.aulast=Stowers&rft.aufirst=A&rft.date=2002-01-08&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Tropical Medicine, 60 Revere Dr., Suite 500, Northbrook, IL 60062, USA; phone: 847-480-9592; fax: 847-480-9282; email: astmh@astmh.org; URL: www.astmh.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Detection of IGM anti-HEV using class-capture enzyme immunoassay AN - 39433558; 3656375 AU - Yu, C AU - Purcell, R H AU - Emerson, SU AU - Engle, R E Y1 - 2002/01/08/ PY - 2002 DA - 2002 Jan 08 KW - CPI, Conference Papers Index KW - U 7000:Multidisciplinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39433558?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Detection+of+IGM+anti-HEV+using+class-capture+enzyme+immunoassay&rft.au=Yu%2C+C%3BPurcell%2C+R+H%3BEmerson%2C+SU%3BEngle%2C+R+E&rft.aulast=Yu&rft.aufirst=C&rft.date=2002-01-08&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Tropical Medicine, 60 Revere Dr., Suite 500, Northbrook, IL 60062, USA; phone: 847-480-9592; fax: 847-480-9282; email: astmh@astmh.org; URL: www.astmh.org. Poster Paper No. 311 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Peyer's patch dendritic cell subsets and the induction of mucosal immunity AN - 39414699; 3655998 AU - Kelsall, B Y1 - 2002/01/08/ PY - 2002 DA - 2002 Jan 08 KW - CPI, Conference Papers Index KW - U 7000:Multidisciplinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39414699?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Peyer%27s+patch+dendritic+cell+subsets+and+the+induction+of+mucosal+immunity&rft.au=Kelsall%2C+B&rft.aulast=Kelsall&rft.aufirst=B&rft.date=2002-01-08&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Tropical Medicine, 60 Revere Dr., Suite 500, Northbrook, IL 60062, USA; phone: 847-480-9592; fax: 847-480-9282; email: astmh@astmh.org; URL: www.astmh.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Global gene expression analysis in macrophages and dendritic cells in response to Brugia malayi AN - 39408231; 3656096 AU - Semnani, R T AU - Chaussabel, D AU - McDowell, MA AU - Kieser, P AU - Sher, A AU - Sacks, D AU - Nutman, T Y1 - 2002/01/08/ PY - 2002 DA - 2002 Jan 08 KW - CPI, Conference Papers Index KW - U 7000:Multidisciplinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39408231?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Global+gene+expression+analysis+in+macrophages+and+dendritic+cells+in+response+to+Brugia+malayi&rft.au=Semnani%2C+R+T%3BChaussabel%2C+D%3BMcDowell%2C+MA%3BKieser%2C+P%3BSher%2C+A%3BSacks%2C+D%3BNutman%2C+T&rft.aulast=Semnani&rft.aufirst=R&rft.date=2002-01-08&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Tropical Medicine, 60 Revere Dr., Suite 500, Northbrook, IL 60062, USA; phone: 847-480-9592; fax: 847-480-9282; email: astmh@astmh.org; URL: www.astmh.org. Paper No. 72 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Pre-clinical evaluation of a recombinant candidate vaccine for hepatitis E: Duration of protection AN - 39406743; 3656083 AU - Zhang, M AU - Emerson, SU AU - Shapiro, M AU - Govindarajan, S AU - Purcell, R H Y1 - 2002/01/08/ PY - 2002 DA - 2002 Jan 08 KW - CPI, Conference Papers Index KW - U 7000:Multidisciplinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39406743?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Pre-clinical+evaluation+of+a+recombinant+candidate+vaccine+for+hepatitis+E%3A+Duration+of+protection&rft.au=Zhang%2C+M%3BEmerson%2C+SU%3BShapiro%2C+M%3BGovindarajan%2C+S%3BPurcell%2C+R+H&rft.aulast=Zhang&rft.aufirst=M&rft.date=2002-01-08&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Tropical Medicine, 60 Revere Dr., Suite 500, Northbrook, IL 60062, USA; phone: 847-480-9592; fax: 847-480-9282; email: astmh@astmh.org; URL: www.astmh.org. Paper No. 59 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Hepatitis E virus (HEV) capsid antigens derived from viruses of human or swine origin are equally efficient for detecting anti-HEV by Elisa AN - 39386614; 3656082 AU - Engle, R E AU - Yu, C AU - Emerson, SU AU - Meng, X-J AU - Purcell, R H Y1 - 2002/01/08/ PY - 2002 DA - 2002 Jan 08 KW - CPI, Conference Papers Index KW - U 7000:Multidisciplinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39386614?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Hepatitis+E+virus+%28HEV%29+capsid+antigens+derived+from+viruses+of+human+or+swine+origin+are+equally+efficient+for+detecting+anti-HEV+by+Elisa&rft.au=Engle%2C+R+E%3BYu%2C+C%3BEmerson%2C+SU%3BMeng%2C+X-J%3BPurcell%2C+R+H&rft.aulast=Engle&rft.aufirst=R&rft.date=2002-01-08&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Tropical Medicine, 60 Revere Dr., Suite 500, Northbrook, IL 60062, USA; phone: 847-480-9592; fax: 847-480-9282; email: astmh@astmh.org; URL: www.astmh.org. Paper No. 58 N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - A recombinant vaccine expressed in the milk of transgenic mice protects Aotus monkeys from a lethal challenge with Plasmodium falciparum AN - 18359263; 5293574 AB - Two strains of transgenic mice have been generated that secrete into their milk a malaria vaccine candidate, the 42-kDa C-terminal portion of Plasmodium falciparum merozoite surface protein 1 (MSP1 sub(42)). One strain secretes an MSP1 sub(42) with an amino acid sequence homologous to that of the FVO parasite line, the other an MSP1 sub(42) where two putative N-linked glycosylation sites in the FVO sequence have been removed. Both forms of MSP1 sub(42) were purified from whole milk to greater than 91% homogeneity at high yields. Both proteins are recognized by a panel of monoclonal antibodies and have identical N termini, but are clearly distinguishable by some biochemical properties. These two antigens were each emulsified with Freund's adjuvant and used to vaccinate Aotus nancymai monkeys, before challenge with the homologous P. falciparum FVO parasite line. Vaccination with a positive control molecule, a glycosylated form of MSP1 sub(42) produced in the baculovirus expression system, successfully protected five of six monkeys. By contrast, vaccination with the glycosylated version of milk-derived MSP1 sub(42) conferred no protection compared with an adjuvant control. Vaccination with the nonglycosylated, milk-derived MSP1 sub(42) successfully protected the monkeys, with 4/5 animals able to control an otherwise lethal infection with P. falciparum compared with 1/7 control animals. Analysis of the different vaccines used suggested that the differing nature of the glycosylation patterns may have played a critical role in determining efficacy. This study demonstrates the potential for producing efficacious malarial vaccines in transgenic animals. JF - Proceedings of the National Academy of Sciences, USA AU - Stowers, A W AU - Chen, L AU - Zhang, Y AU - Kennedy, M C AU - Zou, L AU - Lambert, L AU - Rice, T J AU - Kaslow, D C AU - Saul, A AU - Long, CA AU - Meade, H AU - Miller, L H AD - Malaria Vaccine Development Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Rockville, MD 20852, USA, astowers@niaid.nih.gov Y1 - 2002/01/08/ PY - 2002 DA - 2002 Jan 08 SP - 339 EP - 344 VL - 99 IS - 1 SN - 0027-8424, 0027-8424 KW - Owl Monkeys KW - monkeys KW - MSP1 gene KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Malaria KW - Milk KW - Aotus KW - Immunity KW - Plasmodium falciparum KW - Transgenic mice KW - Immunization KW - Merozoites KW - Vaccines KW - W3 33365:Vaccines (other) KW - K 03086:Immunology & vaccination KW - F 06807:Active immunization KW - G 07120:Recombinant DNA/Genetic engineering KW - W 30965:Miscellaneous, Reviews KW - N 14800:Immunological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18359263?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=A+recombinant+vaccine+expressed+in+the+milk+of+transgenic+mice+protects+Aotus+monkeys+from+a+lethal+challenge+with+Plasmodium+falciparum&rft.au=Stowers%2C+A+W%3BChen%2C+L%3BZhang%2C+Y%3BKennedy%2C+M+C%3BZou%2C+L%3BLambert%2C+L%3BRice%2C+T+J%3BKaslow%2C+D+C%3BSaul%2C+A%3BLong%2C+CA%3BMeade%2C+H%3BMiller%2C+L+H&rft.aulast=Stowers&rft.aufirst=A&rft.date=2002-01-08&rft.volume=99&rft.issue=1&rft.spage=339&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.012590199 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Aotus; Plasmodium falciparum; Malaria; Milk; Vaccines; Transgenic mice; Immunity; Immunization; Merozoites DO - http://dx.doi.org/10.1073/pnas.012590199 ER - TY - JOUR T1 - Model for the Catalytic Domain of the Proofreading epsilon Subunit of Escherichia coli DNA Polymerase III Based on NMR Structural Data AN - 17940171; 5892512 AB - The DNA polymerase III holoenzyme (HE) is the primary replicative polymerase of Escherichia coli. The epsilon subunit of the HE complex provides the 3'-exonucleolytic proofreading activity for this enzyme complex. epsilon consists of two domains: an N-terminal domain containing the proofreading exonuclease activity (residues 1-186) and a C-terminal domain required for binding to the polymerase ( alpha ) subunit (residues 187-243). Multidimensional NMR studies of super(2)H-, super(13)C-, and super(15)N-labeled N-terminal domains ( epsilon 186) were performed to assign the backbone resonances and measure H super(N)-H super(N) nuclear Overhauser effects (NOEs). NMR studies were also performed on triple-labeled [U- super(2)H, super(13)C, super(15)N] epsilon 186 containing Val, Leu, and Ile residues with protonated methyl groups, which allowed for the assignment of H super(N)-CH sub(3) and CH sub(3)-CH sub(3) NOEs. Analysis of the super(13)C super( alpha ), super(13)C super( beta ), and super(13)CO shifts, using chemical shift indexing and the TALOS program, allowed for the identification of regions of the secondary structure. H super(N)-H super(N) NOEs provided information on the assembly of the extended strands into a beta -sheet structure and confirmed the assignment of the alpha helices. Measurement of H super(N)-CH sub(3) and CH sub(3)-CH sub(3) NOEs confirmed the beta -sheet structure and assisted in the positioning of the alpha helices. The resulting preliminary characterization of the three-dimensional structure of the protein indicated that significant structural homology exists with the active site of the Klenow proofreading exonuclease domain, despite the extremely limited sequence homology. On the basis of this analogy, molecular modeling studies of epsilon 186 were performed using as templates the crystal structures of the exonuclease domains of the Klenow fragment and the T4 DNA polymerase and the recently determined structure of the E. coli Exonuclease I. A multiple sequence alignment was constructed, with the initial alignment taken from the previously published hidden Markov model and NMR constraints. Because several of the published structures included complexed ssDNA, we were also able to incorporate an A-C-G trinucleotide into the epsilon 186 structure. Nearly all of the residues which have been identified as mutators are located in the portion of the molecule which binds the DNA, with most of these playing either a catalytic or structural role. JF - Biochemistry (Washington) AU - DeRose, E F AU - Li, D AU - Darden, T AU - Harvey, S AU - Perrino, F W AU - Schaaper, R M AU - London, R E AD - Laboratory of Structural Biology and Laboratory of Molecular Genetics, NIEHS, Box 12233, Research Triangle Park, North Carolina 27709, USA Y1 - 2002/01/08/ PY - 2002 DA - 2002 Jan 08 SP - 94 EP - 110 VL - 41 IS - 1 SN - 0006-2960, 0006-2960 KW - Microbiology Abstracts B: Bacteriology KW - Protein structure KW - hidden Markov models KW - Nucleotide sequence KW - DNA-directed DNA polymerase KW - Secondary structure KW - Crystal structure KW - Escherichia coli KW - exonuclease KW - N.M.R. KW - Nuclear Overhauser effect KW - Proofreading KW - J 02725:DNA UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17940171?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Model+for+the+Catalytic+Domain+of+the+Proofreading+epsilon+Subunit+of+Escherichia+coli+DNA+Polymerase+III+Based+on+NMR+Structural+Data&rft.au=DeRose%2C+E+F%3BLi%2C+D%3BDarden%2C+T%3BHarvey%2C+S%3BPerrino%2C+F+W%3BSchaaper%2C+R+M%3BLondon%2C+R+E&rft.aulast=DeRose&rft.aufirst=E&rft.date=2002-01-08&rft.volume=41&rft.issue=1&rft.spage=94&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/10.1021%2Fbi0114170 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA-directed DNA polymerase; N.M.R.; Proofreading; exonuclease; Nucleotide sequence; hidden Markov models; Crystal structure; Nuclear Overhauser effect; Protein structure; Secondary structure DO - http://dx.doi.org/10.1021/bi0114170 ER - TY - JOUR T1 - Structure and expression of the scallop Omega-crystallin gene. Evidence for convergent evolution of promoter sequences. AN - 71350227; 11682475 AB - Omega-crystallin of the scallop lens is an inactive aldehyde dehydrogenase (1A9). Here we have cloned the scallop Omega-crystallin gene. Except for an extra novel first exon, its 14-exon structure agrees well with that of mammalian aldehyde dehydrogenases 1, 2, and 6. The -2120/+63, -714/+63, and -156/+63 Omega-crystallin promoter fragments drive the luciferase reporter gene in transfected alphaTN4-1 lens cells and L929 fibroblasts but not in Cos7 cells. Putative binding sequences for cAMP-responsive element-binding protein (CREB)/Jun, alphaACRYBP1, AP-1, and PAX-6 in the Omega-crystallin promoter are surprisingly similar to the cis-elements used for lens promoter activity of the mouse and chicken alphaA-crystallin genes, which encode proteins homologous to small heat shock proteins. Site-specific mutations in the overlapping CREB/Jun and Pax-6 sites abolished activity of the Omega-crystallin promoter in transfected cells. Gel shift experiments utilizing extracts from the alphaTN4-1, L929, and Cos7 cells and the scallop stomach and oligonucleotides derived from the putative binding sites of the Omega-crystallin promoter showed complex formation. Gel shift experiments showed binding of recombinant Pax-6 and CREB to their respective sites. Our data suggest convergent evolutionary adaptations that underlie the preferential expression of crystallin genes in the lens of vertebrates and invertebrates. JF - The Journal of biological chemistry AU - Carosa, Eleonora AU - Kozmik, Zbynek AU - Rall, J Edward AU - Piatigorsky, Joram AD - Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-2730, USA. Y1 - 2002/01/04/ PY - 2002 DA - 2002 Jan 04 SP - 656 EP - 664 VL - 277 IS - 1 SN - 0021-9258, 0021-9258 KW - Crystallins KW - 0 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Base Sequence KW - Biological Evolution KW - Molecular Sequence Data KW - Mice KW - Mice, Transgenic KW - Cell Line KW - Promoter Regions, Genetic KW - Mollusca -- genetics KW - Crystallins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71350227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Structure+and+expression+of+the+scallop+Omega-crystallin+gene.+Evidence+for+convergent+evolution+of+promoter+sequences.&rft.au=Carosa%2C+Eleonora%3BKozmik%2C+Zbynek%3BRall%2C+J+Edward%3BPiatigorsky%2C+Joram&rft.aulast=Carosa&rft.aufirst=Eleonora&rft.date=2002-01-04&rft.volume=277&rft.issue=1&rft.spage=656&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-24 N1 - Date created - 2002-01-04 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF175578; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Elevated interleukin-6 during ethanol consumption acts as a potential endogenous protective cytokine against ethanol-induced apoptosis in the liver: involvement of induction of Bcl-2 and Bcl-x(L) proteins. AN - 71399995; 11791174 AB - Elevation of serum interleukin-6 (IL-6) levels is always associated with alcoholic liver disease (ALD), but the significance of such elevation is not clear. Here we show that chronic ethanol consumption induces significant apoptosis in the liver of IL-6 (-/-) mice but not IL-6 (+/+) mice. IL-6 (-/-) hepatocytes are more susceptible to ethanol- and tumor necrosis factor alpha- (TNFalpha-) induced apoptotic killing, which can be corrected by IL-6. Expression of both anti-apoptotic (such as Bcl-2 and Bcl-x(L)) and proapoptotic (such as Bax) proteins is markedly elevated in the liver of human ALD and chronically ethanol-fed IL-6 (+/+) mice. On the contrary, induction of Bcl-2 and Bcl-x(L) is not observed in the liver of chronically ethanol-fed IL-6 (-/-) mice, whereas expression of Bax protein remains elevated. Injection of IL-6 markedly induces expression of Bcl-2 and Bcl-x(L) but not Bax in the liver. Finally, high concentrations of ethanol inhibit IL-6-activated anti-apoptotic signal, but increasing the concentrations of IL-6 is able to overcome such inhibitory effect. These findings suggest that elevated serum IL-6 levels in ALD may overcome the inhibitory effect of ethanol on IL-6-mediated anti-apoptotic signals and prevent alcohol-induced hepatic apoptosis by induction of Bcl-2 and Bcl-x(L). JF - Oncogene AU - Hong, Feng AU - Kim, Won-Ho AU - Tian, Zhigang AU - Jaruga, Barbara AU - Ishac, Edward AU - Shen, Xuening AU - Gao, Bin AD - Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, MD 20892, USA. Y1 - 2002/01/03/ PY - 2002 DA - 2002 Jan 03 SP - 32 EP - 43 VL - 21 IS - 1 SN - 0950-9232, 0950-9232 KW - BCL2L1 protein, human KW - 0 KW - Bcl2l1 protein, mouse KW - Interleukin-6 KW - Proto-Oncogene Proteins c-bcl-2 KW - Tumor Necrosis Factor-alpha KW - bcl-X Protein KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Animals KW - Hepatocytes -- drug effects KW - Humans KW - Cells, Cultured -- drug effects KW - Mice KW - Mice, Knockout KW - Genotype KW - Tumor Necrosis Factor-alpha -- toxicity KW - Genes, bcl-2 KW - Body Weight -- drug effects KW - Gene Expression Regulation -- drug effects KW - Genetic Predisposition to Disease KW - Male KW - Organ Size -- drug effects KW - Proto-Oncogene Proteins c-bcl-2 -- biosynthesis KW - Liver -- pathology KW - Liver Diseases, Alcoholic -- pathology KW - Proto-Oncogene Proteins c-bcl-2 -- physiology KW - Alcoholism -- metabolism KW - Interleukin-6 -- blood KW - Liver Diseases, Alcoholic -- genetics KW - Interleukin-6 -- physiology KW - Liver -- drug effects KW - Apoptosis -- drug effects KW - Interleukin-6 -- genetics KW - Ethanol -- toxicity KW - Proto-Oncogene Proteins c-bcl-2 -- genetics KW - Liver Diseases, Alcoholic -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71399995?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Elevated+interleukin-6+during+ethanol+consumption+acts+as+a+potential+endogenous+protective+cytokine+against+ethanol-induced+apoptosis+in+the+liver%3A+involvement+of+induction+of+Bcl-2+and+Bcl-x%28L%29+proteins.&rft.au=Hong%2C+Feng%3BKim%2C+Won-Ho%3BTian%2C+Zhigang%3BJaruga%2C+Barbara%3BIshac%2C+Edward%3BShen%2C+Xuening%3BGao%2C+Bin&rft.aulast=Hong&rft.aufirst=Feng&rft.date=2002-01-03&rft.volume=21&rft.issue=1&rft.spage=32&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-19 N1 - Date created - 2002-01-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ECT IN NEUROLOGICAL COUNDITIONS AN - 858421107; 14231116 AB - It is a myth that electroconvulsive therapy (ECT) produces greater side effects and worsens the neurological condition when used in neurologically ill patients. With the advancement and sophistication in ECT practice standards and modification procedures, it can be safely administered either to treat selected neurological conditions or the co-morbid psychiatric illnesses without additional risks. However ECT should be administered only after thorough evaluation of risks and benefits in such individuals. JF - Indian Journal of Psychiatry AU - Girish, K AU - Gangadhar, B N AU - Janakiramaiah, N AD - K. GIRISH, M.D., D.N.B., Senior Resident, Department of Psychiatry, National Institute of Mental Health & Neuro Sciences, Bangalore-560029 Y1 - 2002 PY - 2002 DA - 2002 SP - 228 EP - 239 PB - Medknow Publications Pvt. Ltd., A-108/109 Kanara Business Center Mumbai 400075 India VL - 44 IS - 3 SN - 0019-5545, 0019-5545 KW - Risk Abstracts; CSA Neurosciences Abstracts KW - Risk assessment KW - Cost-benefit analysis KW - ECS KW - Medical treatment KW - Side effects KW - N3 11001:Behavioral and Cognitive Neuroscience KW - R2 23010:General: Models, forecasting UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/858421107?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Indian+Journal+of+Psychiatry&rft.atitle=ECT+IN+NEUROLOGICAL+COUNDITIONS&rft.au=Girish%2C+K%3BGangadhar%2C+B+N%3BJanakiramaiah%2C+N&rft.aulast=Girish&rft.aufirst=K&rft.date=2002-01-01&rft.volume=44&rft.issue=3&rft.spage=228&rft.isbn=&rft.btitle=&rft.title=Indian+Journal+of+Psychiatry&rft.issn=00195545&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-03-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - Cost-benefit analysis; ECS; Side effects; Risk assessment; Medical treatment ER - TY - JOUR T1 - Clinical presentation of DFNB12 and Usher syndrome type 1D. AN - 85371102; pmid-12408077 JF - Advances in oto-rhino-laryngology AU - Bork, Julie M AU - Morell, Robert J AU - Khan, Shaheen AU - Riazuddin, Sheikh AU - Wilcox, Edward R AU - Friedman, Thomas B AU - Griffith, Andrew J AD - Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Md., USA. borkj@nidcd.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 145 EP - 152 VL - 61 SN - 0065-3071, 0065-3071 KW - Index Medicus KW - National Library of Medicine KW - Adolescent KW - Adult KW - Aged KW - *Cadherins: genetics KW - Child KW - Child, Preschool KW - Female KW - Genetic Linkage KW - Hearing Loss, Sensorineural: diagnosis KW - *Hearing Loss, Sensorineural: genetics KW - Humans KW - Male KW - Middle Aged KW - Mutation, Missense KW - *Phenotype KW - Retinitis Pigmentosa: genetics KW - Syndrome KW - Vestibular Diseases: genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85371102?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+oto-rhino-laryngology&rft.atitle=Clinical+presentation+of+DFNB12+and+Usher+syndrome+type+1D.&rft.au=Bork%2C+Julie+M%3BMorell%2C+Robert+J%3BKhan%2C+Shaheen%3BRiazuddin%2C+Sheikh%3BWilcox%2C+Edward+R%3BFriedman%2C+Thomas+B%3BGriffith%2C+Andrew+J&rft.aulast=Bork&rft.aufirst=Julie&rft.date=2002-01-01&rft.volume=61&rft.issue=&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Advances+in+oto-rhino-laryngology&rft.issn=00653071&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Genetic modifiers of hereditary hearing loss. AN - 85370003; pmid-12408088 JF - Advances in oto-rhino-laryngology AU - Riazuddin, Saima AU - Ahmed, Zubair M AU - Friedman, Thomas B AU - Griffith, Andrew J AU - Riazuddin, Sheikh AU - Wilcox, Edward R AD - Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Md., USA. riazuddi@nidcd.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 224 EP - 229 VL - 61 SN - 0065-3071, 0065-3071 KW - Index Medicus KW - National Library of Medicine KW - Animals KW - Audiometry, Pure-Tone KW - Auditory Threshold KW - Hearing Loss, Sensorineural: diagnosis KW - *Hearing Loss, Sensorineural: genetics KW - Heterozygote KW - Homozygote KW - Humans KW - Multifactorial Inheritance KW - Pedigree KW - Phenotype UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85370003?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+oto-rhino-laryngology&rft.atitle=Genetic+modifiers+of+hereditary+hearing+loss.&rft.au=Riazuddin%2C+Saima%3BAhmed%2C+Zubair+M%3BFriedman%2C+Thomas+B%3BGriffith%2C+Andrew+J%3BRiazuddin%2C+Sheikh%3BWilcox%2C+Edward+R&rft.aulast=Riazuddin&rft.aufirst=Saima&rft.date=2002-01-01&rft.volume=61&rft.issue=&rft.spage=224&rft.isbn=&rft.btitle=&rft.title=Advances+in+oto-rhino-laryngology&rft.issn=00653071&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - DFNB3, spectrum of MYO15A recessive mutant alleles and an emerging genotype-phenotype correlation. AN - 85369976; pmid-12408074 AB - We have now identified seven MYO15A mutations that cause congenital profound neurosensory hearing loss and a possible hypomorphic allele of MYO15A associated with moderately-severe hearing loss in 1 of 8 SMS patients. Because myosin XVA is encoded by 66 exons, screening for mutations in hearing-impaired individuals is expensive and labor-intensive in comparison to a screen for mutations in GJB2 (Cx26), for example, which has only a single protein coding exon. Among consanguineous families segregating profound, congenital hearing loss from Pakistan, approximately 10% are consistent with linkage to DFNB3 (11 of 112 DFNB families). In one-half of these DFNB3 families, we found a homozygous mutation in 1 of the 66 exons of MYO15A [25]. This suggests that mutations of MYO15A are responsible for at least 5% of recessively inherited, profound hearing loss in Pakistan. However, without the benefit of a pre-screen for linkage to DFNB3, it will be a challenge to determine the extent to which mutations of MYO15A contribute to hereditary hearing loss among isolated cases and small families in other populations. JF - Advances in oto-rhino-laryngology AU - Friedman, Thomas B AU - Hinnant, John T AU - Ghosh, Manju AU - Boger, Erich T AU - Riazuddin, S AU - Lupski, James R AU - Potocki, Lorraine AU - Wilcox, Edward R AD - Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Md., USA. friedman@nidcd.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 124 EP - 130 VL - 61 SN - 0065-3071, 0065-3071 KW - Index Medicus KW - National Library of Medicine KW - Abnormalities, Multiple: genetics KW - Alleles KW - Auditory Threshold KW - Genotype KW - *Hearing Loss, Sensorineural: congenital KW - *Hearing Loss, Sensorineural: genetics KW - Humans KW - *Mutation KW - *Myosins: genetics KW - Phenotype UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85369976?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+oto-rhino-laryngology&rft.atitle=DFNB3%2C+spectrum+of+MYO15A+recessive+mutant+alleles+and+an+emerging+genotype-phenotype+correlation.&rft.au=Friedman%2C+Thomas+B%3BHinnant%2C+John+T%3BGhosh%2C+Manju%3BBoger%2C+Erich+T%3BRiazuddin%2C+S%3BLupski%2C+James+R%3BPotocki%2C+Lorraine%3BWilcox%2C+Edward+R&rft.aulast=Friedman&rft.aufirst=Thomas&rft.date=2002-01-01&rft.volume=61&rft.issue=&rft.spage=124&rft.isbn=&rft.btitle=&rft.title=Advances+in+oto-rhino-laryngology&rft.issn=00653071&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Progress in the prevention of otitis media through immunization. AN - 85365914; pmid-11773835 AB - To review the progress that has been made in developing effective vaccines against the major bacterial pathogens responsible for acute otitis media.Review of the literature with the aid of the MEDLINE database using the search terms otitis media and otitis media and vaccine.Data were collected from clinical trials and laboratory studies.The heptavalent pneumococcal conjugated vaccine, Prevnar, reduced the incidence of acute otitis media from all causes by 7% in one study and by 6% in another study. For culture-positive pneumococcal otitis media, the point estimate of efficacy was 66.7% in one study, and the reduction in incidence was 34% in another study. A Phase I clinical trial has been completed successfully for a conjugated vaccine against nontypeable Haemophilus influenzae (NTHi), which has high immunogenicity for mice and rabbits, induces complement-mediated bactericidal activity against NTHi in rabbits, and is protective against NTHi otitis media in chinchillas. A conjugated vaccine against Moraxella catarrhalis elicits strong immune responses in mice and rabbits and induces complement-mediated bactericidal activity in rabbits.The prevention of otitis media is likely to require multivalent pneumococcal, NTHi, and M. catarrhalis vaccines, and these vaccines likely can be developed within a decade. JF - Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology AU - Snow, James B AD - National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA. jsnow@crosslink.net Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 1 EP - 2 VL - 23 IS - 1 SN - 1531-7129, 1531-7129 KW - Index Medicus KW - National Library of Medicine KW - Acute Disease KW - *Haemophilus Infections: immunology KW - Humans KW - *Neisseriaceae Infections: immunology KW - Otitis Media: microbiology KW - *Otitis Media: prevention & control KW - *Respiratory Syncytial Virus Infections: immunology KW - *Streptococcal Infections: immunology KW - *Vaccination UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85365914?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Otology+%26+neurotology+%3A+official+publication+of+the+American+Otological+Society%2C+American+Neurotology+Society+%5Band%5D+European+Academy+of+Otology+and+Neurotology&rft.atitle=Progress+in+the+prevention+of+otitis+media+through+immunization.&rft.au=Snow%2C+James+B&rft.aulast=Snow&rft.aufirst=James&rft.date=2002-01-01&rft.volume=23&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Otology+%26+neurotology+%3A+official+publication+of+the+American+Otological+Society%2C+American+Neurotology+Society+%5Band%5D+European+Academy+of+Otology+and+Neurotology&rft.issn=15317129&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Cortical control of brainstem motor systems. AN - 85364274; pmid-11836748 JF - Movement disorders : official journal of the Movement Disorder Society AU - Hallett, Mark AD - Human Motor Control Section, NINDS, National Institutes of Health, Bethesda, Maryland 20892, USA. hallettm@ninds.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - S23 EP - S26 VL - 17 Suppl 2 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Animals KW - *Brain Stem: physiology KW - *Cerebral Cortex: physiology KW - Cranial Nerves: physiology KW - Humans KW - *Motor Neurons: physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85364274?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Cortical+control+of+brainstem+motor+systems.&rft.au=Hallett%2C+Mark&rft.aulast=Hallett&rft.aufirst=Mark&rft.date=2002-01-01&rft.volume=17+Suppl+2&rft.issue=&rft.spage=S23&rft.isbn=&rft.btitle=&rft.title=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.issn=08853185&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Effects of systematic bolus viscosity and volume changes on hyoid movement kinematics. AN - 85360807; pmid-12355143 AB - Using ultrasonography with head and transducer stabilization, this study examined the effects of maximally controlled, systematic changes in bolus viscosity (thin juice-like, 7 cP; nectar-like, 243-260 cP; honey-like, 724-759 cP; spoon-thick, 2760-2819 cP) and volume (5, 10, 20, 30 cc) on hyoid kinematics in 31 healthy subjects (16 male, 15 female) in three age groups (20-39, 40-59, 60-79 years). Frame-by-frame hyoid displacements were tracked from digitized images of 612 swallows. Measures of movement durations, maximal amplitudes, total distances, and peak velocities were subjected to repeated measures multivariate analyses of variance with viscosity, volume, age, and gender as factors. Results showed that (1) spoon-thick swallows had the greatest preswallow gesture and total movement durations; (2) larger-volume swallows had significantly greater maximal amplitudes, forward peak velocity, and total vertical distance; (3) older subjects had longer start-to-max duration (though shorter preswallow gesture and total movement durations), greater maximal vertical amplitude, longer total vertical distance, and greater backward peak velocity than younger subjects; (4) males had greater values for all kinematic parameters except preswallow gesture, hyoid-at-max, and max-to-end durations. The results illustrate the importance of examining the interrelations among kinematic variables to better understand task accommodation and motor control strategies. The evidence also supports the concept of suprahyoid-infrahyoid functional adaptation and compensation in the healthy elderly. JF - Dysphagia AU - Chi-Fishman, Gloria AU - Sonies, Barbara C AD - Ultrasound Imaging and Oral Pharyngeal Function Laboratory, Physical Disabilities Branch, Rehabilitation Medicine Department, W G Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. gcf@nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 278 EP - 287 VL - 17 IS - 4 SN - 0179-051X, 0179-051X KW - National Library of Medicine KW - Adult KW - Aged KW - *Biomechanics KW - *Deglutition: physiology KW - Female KW - Humans KW - *Hyoid Bone: physiology KW - Male KW - Middle Aged KW - *Movement: physiology KW - Reference Values KW - *Viscosity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85360807?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Dysphagia&rft.atitle=Effects+of+systematic+bolus+viscosity+and+volume+changes+on+hyoid+movement+kinematics.&rft.au=Chi-Fishman%2C+Gloria%3BSonies%2C+Barbara+C&rft.aulast=Chi-Fishman&rft.aufirst=Gloria&rft.date=2002-01-01&rft.volume=17&rft.issue=4&rft.spage=278&rft.isbn=&rft.btitle=&rft.title=Dysphagia&rft.issn=0179051X&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Carboplatin in elderly patients. AN - 85255807; pmid-11989919 JF - Tumori AU - Sorio Roberto AU - Talamini Renata AU - Toffoli Giuseppe AU - Lombardi Davide AU - Libra Massimo AU - Veronesi, Andrea AD - National Cancer Institute, Aviano (PN). PY - 2002 SP - S35 EP - S36 VL - 88 IS - 1 Suppl 1 SN - 0300-8916, 0300-8916 KW - Obesity KW - Age Factors KW - Drug Interactions KW - Ovarian Neoplasms KW - Area Under Curve KW - Antineoplastic Agents KW - Human KW - Aged KW - Middle Age KW - Carboplatin KW - Female KW - Frail Elderly UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85255807?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tumori&rft.atitle=Carboplatin+in+elderly+patients.&rft.au=Sorio+Roberto%3BTalamini+Renata%3BToffoli+Giuseppe%3BLombardi+Davide%3BLibra+Massimo%3BVeronesi%2C+Andrea&rft.aulast=Sorio+Roberto&rft.aufirst=&rft.date=2002-01-01&rft.volume=88&rft.issue=1+Suppl+1&rft.spage=S35&rft.isbn=&rft.btitle=&rft.title=Tumori&rft.issn=03008916&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Human neural systems for face recognition and social communication. AN - 85254966; pmid-11801231 AB - Face perception is mediated by a distributed neural system in humans that consists of multiple, bilateral regions. The functional organization of this system embodies a distinction between the representation of invariant aspects of faces, which is the basis for recognizing individuals, and the representation of changeable aspects, such as eye gaze, expression, and lip movement, which underlies the perception of information that facilitates social communication. The system also has a hierarchical organization. A core system, consisting of occipitotemporal regions in extrastriate visual cortex, mediates the visual analysis of faces. An extended system consists of regions from neural systems for other cognitive functions that can act in concert with the core system to extract meaning from faces. Of regions in the extended system for face perception, the amygdala plays a central role in processing the social relevance of information gleaned from faces, particularly when that information may signal a potential threat. JF - Biological Psychiatry AU - Haxby, James V AU - Hoffman, Elizabeth A AU - Ida, Gobbini M AD - Laboratory of Brain and Cognition, National Institute of Mental Health, Building 10, Room 4C104, 10 Center Drive-MSC 1366, Bethesda, MD 20892, USA. PY - 2002 SP - 59 EP - 67 VL - 51 IS - 1 SN - 0006-3223, 0006-3223 KW - Magnetic Resonance Imaging KW - Social Perception KW - Human KW - Interpersonal Relations KW - Brain KW - Space Perception KW - Attention KW - Visual Perception KW - Nerve Net KW - Facial Expression KW - Recognition (Psychology) KW - Social Behavior KW - Communication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85254966?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+Psychiatry&rft.atitle=Human+neural+systems+for+face+recognition+and+social+communication.&rft.au=Haxby%2C+James+V%3BHoffman%2C+Elizabeth+A%3BIda%2C+Gobbini+M&rft.aulast=Haxby&rft.aufirst=James&rft.date=2002-01-01&rft.volume=51&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Biological+Psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Periodicity, mixed-mode oscillations, and quasiperiodicity in a rhythm-generating neural network. AN - 85251690; pmid-11751309 AB - We studied patterns of oscillatory neural activity in the network that generates respiratory rhythm in mammals. When isolated in vitro, this network spontaneously generates an inspiratory-related motor rhythm, with stable amplitude from cycle to cycle. We show that progressively elevating neuronal excitability in vitro causes periodic modulation of this inspiratory rhythm, evoking (in order): mixed-mode oscillations, quasiperiodicity, and ultimately disorganized aperiodic activity. Thus, the respiratory network oscillator follows a well defined sequence of behavioral states characterized by dynamical systems theory, which includes discrete stages of periodic and quasiperiodic amplitude modulation and progresses (according to theory) to aperiodic chaos-like behavior. We also observed periodic, mixed-mode periodic, and quasiperiodic breathing patterns in neonatal rodents and human infants in vivo, suggesting that breathing patterns generated by the intact nervous system reflect deterministic neural activity patterns in the underlying rhythm-generating network. JF - Biophysical Journal AU - Del Negro Christopher A AU - Wilson, Christopher G AU - Butera, Robert J AU - Rigatto Henrique AU - Smith, Jeffrey C AD - Cellular and Systems Neurobiology Section, Laboratory of Neural Control, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. PY - 2002 SP - 206 EP - 214 VL - 82 IS - 1 Pt 1 SN - 0006-3495, 0006-3495 KW - Support, U.S. Gov't, P.H.S. KW - In Vitro KW - Vagotomy KW - Animal KW - Electromyography KW - Nerve Net KW - Neurophysiology KW - Rats KW - Animals, Newborn KW - Respiratory Mechanics KW - Medulla Oblongata KW - Brain Stem KW - Aspiration KW - Support, Non-U.S. Gov't KW - Models, Neurological KW - Periodicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85251690?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biophysical+Journal&rft.atitle=Periodicity%2C+mixed-mode+oscillations%2C+and+quasiperiodicity+in+a+rhythm-generating+neural+network.&rft.au=Del+Negro+Christopher+A%3BWilson%2C+Christopher+G%3BButera%2C+Robert+J%3BRigatto+Henrique%3BSmith%2C+Jeffrey+C&rft.aulast=Del+Negro+Christopher+A&rft.aufirst=&rft.date=2002-01-01&rft.volume=82&rft.issue=1+Pt+1&rft.spage=206&rft.isbn=&rft.btitle=&rft.title=Biophysical+Journal&rft.issn=00063495&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Comparative analysis of group II metabotropic glutamate receptor immunoreactivity in Brodmann's area 46 of the dorsolateral prefrontal cortex from patients with schizophrenia and normal subjects AN - 759315954; 13685981 AB - Glutamate is the primary excitatory neurotransmitter in the mammalian central nervous system, and a key neurotransmitter in prefrontal cortical function. Converging lines of evidence implicate prefrontal cortical dysfunction in the neurobiology of schizophrenia. Thus, aberrant glutamate neurotransmission may underlie schizophrenia and other complex disorders of behavior. Group II metabotropic receptors (mGluRs) are important modulators of glutamatergic and non-glutamatergic neurotransmission. Moreover, in an animal model, an agonist for group II mGluRs has been shown to reverse the behavioral, locomotor, and cognitive effects of the psychotomimetic drug phencyclidine. Accordingly, group II mGluRs constitute attractive targets for the pharmacotherapeutics and study of schizophrenia. Using immunocytochemistry and Western immunoblotting, we compared the localization and levels of group II mGluRs in Brodmann's area 46 of the dorsolateral prefrontal cortex from patients with schizophrenia and normal subjects. Consistent with previous reports, we found that immunolabeling of group II mGluRs is prominent in Brodmann's area 46. The majority of labeling was present on axon terminals distributed in a lamina-specific fashion. No apparent difference in the cellular localization or laminar distribution of immunoreactive group II mGluRs was noted between the two diagnostic groups. Similarly, the levels of receptor immunoreactivity determined by quantitative Western immunoblotting were comparable between schizophrenic patients and normal subjects. We conclude that while the function of group II mGluRs in Brodmann's area 46 of dorsolateral prefrontal cortex may be altered in patients with schizophrenia, this is not evident at the level of protein expression using an antibody against mGluR2 and mGluR3.MOLECULAR PSYCHIATRY: (2002) 7, 157-164. DOI: 10.1038/sj.mp.4000966 JF - Molecular Psychiatry AU - Crook, J M AU - Akil, M AU - Law, B C W AU - Hyde, T M AU - Kleinman, J E AD - Section on Neuropathology, Clinical Brain Disorders Branch, National Institute of Mental Health, Bethesda, MD 20892, USA Y1 - 2002 PY - 2002 DA - 2002 SP - 157 EP - 164 PB - Nature Publishing Group, The Macmillan Building London N1 9XW UK VL - 7 IS - 2 SN - 1359-4184, 1359-4184 KW - Toxicology Abstracts; CSA Neurosciences Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/759315954?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Psychiatry&rft.atitle=Comparative+analysis+of+group+II+metabotropic+glutamate+receptor+immunoreactivity+in+Brodmann%27s+area+46+of+the+dorsolateral+prefrontal+cortex+from+patients+with+schizophrenia+and+normal+subjects&rft.au=Crook%2C+J+M%3BAkil%2C+M%3BLaw%2C+B+C+W%3BHyde%2C+T+M%3BKleinman%2C+J+E&rft.aulast=Crook&rft.aufirst=J&rft.date=2002-01-01&rft.volume=7&rft.issue=2&rft.spage=157&rft.isbn=&rft.btitle=&rft.title=Molecular+Psychiatry&rft.issn=13594184&rft_id=info:doi/10.1038%2Fsj.mp.4000966 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2011-12-14 DO - http://dx.doi.org/10.1038/sj.mp.4000966 ER - TY - JOUR T1 - Chronic lithium downregulates cyclooxygenase-2 activity and prostaglandin E sub(2) concentration in rat brain AN - 759315611; 13686082 AB - Rats treated with lithium chloride for 6 weeks have been reported to demonstrate reduced turnover of arachidonic acid (AA) in brain phospholipids, and decreases in mRNA and protein levels, and enzyme activity, of AA-selective cytosolic phospholipase A sub(2)(cPLA sub(2)). We now report that chronic lithium administration to rats significantly reduced the brain protein level and enzyme activity of cyclooxygenase-2 (COX-2), without affecting COX-2 mRNA. Lithium also reduced the brain concentration of prostaglandin E sub(2) (PGE sub(2)), a bioactive product of AA formed via the COX reaction. COX-1 and the Ca super(2+)-independent iPLA sub(2) (type VI) were unaffected by lithium. These and prior results indicate that lithium targets a part of the AA cascade that involves cPLA sub(2) and COX-2. This effect may contribute to lithium's therapeutic action in bipolar disorder.MOLECULAR PSYCHIATRY: (2002) 7, 845-850. doi:10.1038/sj.mp.4001111 JF - Molecular Psychiatry AU - Bosetti, F AU - Rintala, J AU - Seemann, R AU - Rosenberger, T A AU - Contreras, M A AU - Rapoport, S I AU - Chang, M C AD - Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2002 PY - 2002 DA - 2002 SP - 845 EP - 850 PB - Nature Publishing Group, The Macmillan Building London N1 9XW UK VL - 7 IS - 8 SN - 1359-4184, 1359-4184 KW - Toxicology Abstracts; CSA Neurosciences Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/759315611?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Psychiatry&rft.atitle=Chronic+lithium+downregulates+cyclooxygenase-2+activity+and+prostaglandin+E+sub%282%29+concentration+in+rat+brain&rft.au=Bosetti%2C+F%3BRintala%2C+J%3BSeemann%2C+R%3BRosenberger%2C+T+A%3BContreras%2C+M+A%3BRapoport%2C+S+I%3BChang%2C+M+C&rft.aulast=Bosetti&rft.aufirst=F&rft.date=2002-01-01&rft.volume=7&rft.issue=8&rft.spage=845&rft.isbn=&rft.btitle=&rft.title=Molecular+Psychiatry&rft.issn=13594184&rft_id=info:doi/10.1038%2Fsj.mp.4001111 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2011-12-14 DO - http://dx.doi.org/10.1038/sj.mp.4001111 ER - TY - JOUR T1 - Management of protease inhibitor-associated hyperlipidemia. AN - 72913136; 14727985 AB - Dyslipidemia, characterized by elevated serum levels of triglycerides and reduced levels of total cholesterol, low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol, has been recognized in patients with human immunodeficiency virus (HIV) infection. It is thought that elevated levels of circulating cytokines, such as tumor necrosis factor-alpha and interferon-alpha, may alter lipid metabolism in patients with HIV infection. Protease inhibitors, such as saquinavir, indinavir and ritonavir, have been found to decrease mortality and improve quality of life in patients with HIV infection. However, these drugs have been associated with a syndrome of fat redistribution, insulin resistance, and hyperlipidemia. Elevations in serum total cholesterol and triglyceride levels, along with dyslipidemia that typically occurs in patients with HIV infection, may predispose patients to complications such as premature atherosclerosis and pancreatitis. It has been estimated that hypercholesterolemia and hypertriglyceridemia occur in greater than 50% of protease inhibitor recipients after 2 years of therapy, and that the risk of developing hyperlipidemia increases with the duration of treatment with protease inhibitors. In general, treatment of hyperlipidemia should follow National Cholesterol Education Program guidelines; efforts should be made to modify/control coronary heart disease risk factors (i.e. smoking; hypertension; diabetes mellitus) and maximize lifestyle modifications, primarily dietary intervention and exercise, in these patients. Where indicated, treatment usually consists of either pravastatin or atorvastatin for patients with elevated serum levels of LDL-C and/or total cholesterol. Atorvastatin is more potent in lowering serum total cholesterol and triglycerides compared with other hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, but it is also associated with more drug interactions compared with pravastatin. Simvastatin and lovastatin are significantly metabolized by cytochrome P450 enzymes (CYP3A4) and are therefore not recommended for coadministration with protease inhibitors. A fibric acid derivative (gemfibrozil or fenofibrate) should be used in patients with primary hypertriglyceridemia. However, it must be kept in mind that protease inhibitors, such as nelfinavir and ritonavir, induce enzymes involved in the metabolism of the fibric acid derivatives and may, therefore, reduce the lipid-lowering activity of coadministered gemfibrozil or fenofibrate. In certain patients HMG-CoA reductase inhibitors may be used in combination with fibric acid derivatives but patients should be carefully monitored for liver and skeletal muscle toxicity. Select patients may experience improvements in serum lipid levels when their offending protease inhibitor(s) is/are exchanged for efavirenz, nevirapine, or abacavir; however each patient's virologic and immunologic status must be taken closely into consideration. JF - American journal of cardiovascular drugs : drugs, devices, and other interventions AU - Penzak, Scott R AU - Chuck, Susan K AD - Clinical Pharmacokinetics Laboratory, Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, Maryland 20892, USA. SPenzak@mail.cc.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 91 EP - 106 VL - 2 IS - 2 SN - 1175-3277, 1175-3277 KW - HIV Protease Inhibitors KW - 0 KW - Hypolipidemic Agents KW - Index Medicus KW - Therapeutic Equivalency KW - Coronary Disease -- etiology KW - Coronary Disease -- prevention & control KW - Humans KW - HIV Infections -- drug therapy KW - Treatment Outcome KW - Clinical Trials as Topic KW - Male KW - Hypolipidemic Agents -- therapeutic use KW - Hyperlipidemias -- chemically induced KW - Hyperlipidemias -- drug therapy KW - Hyperlipidemias -- diagnosis KW - HIV Protease Inhibitors -- pharmacokinetics KW - HIV Protease Inhibitors -- therapeutic use KW - HIV Protease Inhibitors -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72913136?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+cardiovascular+drugs+%3A+drugs%2C+devices%2C+and+other+interventions&rft.atitle=Management+of+protease+inhibitor-associated+hyperlipidemia.&rft.au=Penzak%2C+Scott+R%3BChuck%2C+Susan+K&rft.aulast=Penzak&rft.aufirst=Scott&rft.date=2002-01-01&rft.volume=2&rft.issue=2&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=American+journal+of+cardiovascular+drugs+%3A+drugs%2C+devices%2C+and+other+interventions&rft.issn=11753277&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-14 N1 - Date created - 2004-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coemergence of insomnia and a shift in the Th1/Th2 balance toward Th2 dominance. AN - 72907540; 12907840 AB - Insomnia is associated with physical and mental disorders. We examined the effect of insomnia on immune functions, focusing on the T helper 1 (Th1)/ T helper 2 (Th2) balance, by a cross-sectional design. We provided a self-administered questionnaire to evaluate sleep habits, smoking and medical disorders to 578 men without any toxic exposure (20-64 years old), and measured natural killer (NK) cell activity in 324 men and production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) after stimulation with phytohemagglutinin in 254 men. According to the criteria of DSM-IV, in which insomnia is classified into primary and secondary insomnia, we assessed the effect of insomnia on immune functions, controlling for age and smoking in groups with and without medical disorders. The prevalence of insomnia in the present study was 9.2%. In the absence of medical disorders, insomniac men had a significantly lower IFN-gamma and ratio of IFN-gamma to IL-4 than noninsomniac men. Men with insufficient sleep or difficulty initiating sleep (DIS) had a significantly lower IFN-gamma to IL-4 ratio than those not suffering from insufficient sleep or DIS. In the presence of medical disorders, insomniac men had significantly higher IL-4 than noninsomniac men. Men with difficulty maintaining sleep (DMS) had a significantly lower IFN-gamma to IL-4 ratio than men without DMS. NK cell activity was independent of insomnia. The present results showed a link between insomnia unrelated to medical disorders and a shift in the Th1/Th2 balance toward Th2 dominance, indicating that the relationship between sleep quality and the etiology of immune-related diseases should be reconsidered. Copyright 2003 S. Karger AG, Basel JF - Neuroimmunomodulation AU - Sakami, Shotaro AU - Ishikawa, Toshio AU - Kawakami, Norito AU - Haratani, Takashi AU - Fukui, Akira AU - Kobayashi, Fumio AU - Fujita, Osamu AU - Araki, Shunichi AU - Kawamura, Noriyuki AD - Division of Psychosomatic Research, National Institute of Mental Health, Chiba, Japan. PY - 2002 SP - 337 EP - 343 VL - 10 IS - 6 SN - 1021-7401, 1021-7401 KW - Phytohemagglutinins KW - 0 KW - Interleukin-4 KW - 207137-56-2 KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Cross-Sectional Studies KW - Interferon-gamma -- drug effects KW - Interleukin-4 -- immunology KW - Humans KW - Adult KW - Surveys and Questionnaires KW - Smoking -- immunology KW - Middle Aged KW - Interferon-gamma -- immunology KW - Down-Regulation -- immunology KW - Phytohemagglutinins -- pharmacology KW - Male KW - Th1 Cells -- immunology KW - Th1 Cells -- drug effects KW - Lymphocyte Subsets -- drug effects KW - Th2 Cells -- drug effects KW - Lymphocyte Subsets -- immunology KW - Sleep Initiation and Maintenance Disorders -- physiopathology KW - Sleep Initiation and Maintenance Disorders -- immunology KW - Neuroimmunomodulation -- drug effects KW - Neuroimmunomodulation -- immunology KW - Th2 Cells -- immunology KW - Killer Cells, Natural -- immunology KW - Killer Cells, Natural -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72907540?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroimmunomodulation&rft.atitle=Coemergence+of+insomnia+and+a+shift+in+the+Th1%2FTh2+balance+toward+Th2+dominance.&rft.au=Sakami%2C+Shotaro%3BIshikawa%2C+Toshio%3BKawakami%2C+Norito%3BHaratani%2C+Takashi%3BFukui%2C+Akira%3BKobayashi%2C+Fumio%3BFujita%2C+Osamu%3BAraki%2C+Shunichi%3BKawamura%2C+Noriyuki&rft.aulast=Sakami&rft.aufirst=Shotaro&rft.date=2002-01-01&rft.volume=10&rft.issue=6&rft.spage=337&rft.isbn=&rft.btitle=&rft.title=Neuroimmunomodulation&rft.issn=10217401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-04 N1 - Date created - 2003-08-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Responses to methylphenidate in Attention-Deficit/Hyperactivity Disorder and normal children: update 2002. AN - 72880884; 12685519 AB - Since the positive effects of stimulants on disruptive behavior were described (Bradley & Bowen, 1941), further pediatric studyhas been limited almost exclusively to samples of hyperkinetic school-age children. Because these agents normally were viewed as arousing in their effects on the central nervous system, but were calming in their therapeutic effects on these children, stimulant effects on Attention Deficit Disorder (ADD) were interpreted as being 'paradoxical.' Investigation of effects in normal children and adolescents and in those with disorders unrelated to Attention-Deficit/Hyperactivity Disorder (ADHD), as well as in young adult samples, however, indicate that stimulants appear to have similar behavioral effects in normal and in hyperactive children. This brief report is an update (as of August 2002) on studies of stimulants in ADHD and normal children, with particular focus on MPH. JF - Journal of attention disorders AU - Rapoport, J L AU - Inoff-Germain, G AD - Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892-1600, USA. rapoport@helix.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - S57 EP - S60 VL - 6 Suppl 1 SN - 1087-0547, 1087-0547 KW - Central Nervous System Stimulants KW - 0 KW - Methylphenidate KW - 207ZZ9QZ49 KW - Index Medicus KW - Reference Values KW - Randomized Controlled Trials as Topic KW - Arousal -- drug effects KW - Humans KW - Adult KW - Child KW - Adolescent KW - Attention Deficit Disorder with Hyperactivity -- psychology KW - Attention Deficit Disorder with Hyperactivity -- diagnosis KW - Methylphenidate -- adverse effects KW - Methylphenidate -- therapeutic use KW - Central Nervous System Stimulants -- therapeutic use KW - Central Nervous System Stimulants -- adverse effects KW - Attention Deficit Disorder with Hyperactivity -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72880884?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+attention+disorders&rft.atitle=Responses+to+methylphenidate+in+Attention-Deficit%2FHyperactivity+Disorder+and+normal+children%3A+update+2002.&rft.au=Rapoport%2C+J+L%3BInoff-Germain%2C+G&rft.aulast=Rapoport&rft.aufirst=J&rft.date=2002-01-01&rft.volume=6+Suppl+1&rft.issue=&rft.spage=S57&rft.isbn=&rft.btitle=&rft.title=Journal+of+attention+disorders&rft.issn=10870547&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-22 N1 - Date created - 2003-04-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cyclin-dependent kinases as targets for cancer therapy. AN - 72873131; 12703205 AB - With the overwhelming evidence that the majority of human neoplasms are the result of 'cdk hyperactivation' leading to the abrogation of the Rb pathway, novel direct and indirect cdk inhibitors are being developed. The first 2 direct cdk inhibitors tested in clinical trials, flavopiridol and UCN-01, showed promising results with some evidence of antitumor activity reaching plasma concentrations effective to inhibit cdk-related functions. Other indirect cdk inhibitors such as PS-341, perifosine are also being tested in the clinic. The best schedule of administration, combination with standard chemotherapeutic agents, determination of predictive markers (using novel technologies such as cDNA arrays) for response/toxicity and demonstration of cdk modulation from tumor samples from patients in these trials are important issues that need to be answered in order to obtain the best possible results with these agents. JF - Cancer chemotherapy and biological response modifiers AU - Senderowicz, Adrian M AD - Molecular Therapeutics Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4340, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 169 EP - 196 VL - 20 SN - 0921-4410, 0921-4410 KW - Antineoplastic Agents KW - 0 KW - Enzyme Inhibitors KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Index Medicus KW - Animals KW - Humans KW - Apoptosis -- drug effects KW - Clinical Trials as Topic KW - Disease Models, Animal KW - Drug Evaluation, Preclinical KW - Cell Cycle -- drug effects KW - Neoplasms -- drug therapy KW - Neoplasms -- enzymology KW - Enzyme Inhibitors -- therapeutic use KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72873131?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+biological+response+modifiers&rft.atitle=Cyclin-dependent+kinases+as+targets+for+cancer+therapy.&rft.au=Senderowicz%2C+Adrian+M&rft.aulast=Senderowicz&rft.aufirst=Adrian&rft.date=2002-01-01&rft.volume=20&rft.issue=&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+biological+response+modifiers&rft.issn=09214410&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-27 N1 - Date created - 2003-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adverse selection and generosity of alcohol treatment benefits. AN - 72863208; 12638715 AB - Concerns about attracting disproportionate numbers of employees with alcohol problems limit employers' willingness to offer health plans with generous alcohol treatment benefits. This paper analyzes two potential avenues of adverse selection, namely biased enrollment into plans and biased exit from plans offered by 57 employers between 1991 and 1997. We compare alcohol treatment use rates and costs of new and old enrollees between more generous and less generous plans; we also analyze disenrollment rates and enrollment duration by plan generosity for users and nonusers of alcohol treatment services. To avoid confounding benefit generosity with other plan features, in particular the use of managed care mechanisms, we compare plans that were administered in the same way by a large managed behavioral health care organization. Overall, we find no evidence of adverse selection into more generous plans. Contrary to the selection hypothesis, treatment costs of new members compared to old members are lower in firms with more generous treatment benefits than in firms with more limited benefits. Also, users of alcohol treatment services do not remain disproportionately enrolled longer in plans with generous benefits. JF - Inquiry : a journal of medical care organization, provision and financing AU - Harris, Katherine M AU - Sturm, Roland AD - Division of Clinical and Prevention Research, National Institute on Alcohol Abuse and Alcoholism (NIAAA), Rockville, MD 20852, USA. PY - 2002 SP - 413 EP - 428 VL - 39 IS - 4 SN - 0046-9580, 0046-9580 KW - Index Medicus KW - United States KW - Insurance Benefits KW - Behavioral Medicine -- economics KW - Humans KW - Managed Care Programs -- economics KW - Employer Health Costs KW - Cost Sharing KW - Models, Econometric KW - Utilization Review KW - Insurance Coverage KW - Health Care Costs KW - Insurance Selection Bias KW - Insurance, Psychiatric KW - Health Benefit Plans, Employee -- economics KW - Alcoholism -- therapy KW - Mental Health Services -- economics KW - Alcoholism -- economics KW - Consumer Behavior -- economics KW - Health Benefit Plans, Employee -- utilization KW - Consumer Behavior -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72863208?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Inquiry+%3A+a+journal+of+medical+care+organization%2C+provision+and+financing&rft.atitle=Adverse+selection+and+generosity+of+alcohol+treatment+benefits.&rft.au=Harris%2C+Katherine+M%3BSturm%2C+Roland&rft.aulast=Harris&rft.aufirst=Katherine&rft.date=2002-01-01&rft.volume=39&rft.issue=4&rft.spage=413&rft.isbn=&rft.btitle=&rft.title=Inquiry+%3A+a+journal+of+medical+care+organization%2C+provision+and+financing&rft.issn=00469580&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-27 N1 - Date created - 2003-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of cyclooxygenase-2 expression by APC in HT-29 human colorectal carcinoma cells. AN - 72862293; 12664576 JF - Advances in experimental medicine and biology AU - Hsi, Linda C AU - Angerman-Stewart, Julie AU - Eling, Thomas E AD - National Institute of Environmental Health Sciences, Eicosanoid Biochemistry Section, Laboratory of Molecular Carcinogenesis, Research Triangle Park, NC 27709, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 127 EP - 131 VL - 507 SN - 0065-2598, 0065-2598 KW - Isoenzymes KW - 0 KW - Membrane Proteins KW - RNA, Neoplasm KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Index Medicus KW - Adenomatous Polyposis Coli -- genetics KW - Gene Expression Regulation, Enzymologic KW - Tumor Cells, Cultured KW - Humans KW - RNA, Neoplasm -- genetics KW - Adenomatous Polyposis Coli -- enzymology KW - Gene Expression Regulation, Neoplastic KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Colorectal Neoplasms -- genetics KW - Colorectal Neoplasms -- enzymology KW - Isoenzymes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72862293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=Modulation+of+cyclooxygenase-2+expression+by+APC+in+HT-29+human+colorectal+carcinoma+cells.&rft.au=Hsi%2C+Linda+C%3BAngerman-Stewart%2C+Julie%3BEling%2C+Thomas+E&rft.aulast=Hsi&rft.aufirst=Linda&rft.date=2002-01-01&rft.volume=507&rft.issue=&rft.spage=127&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-21 N1 - Date created - 2003-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - PTEN regulates Akt kinase activity in hippocampal neurons and increases their sensitivity to glutamate and apoptosis. AN - 72855235; 12622404 AB - The tumor suppressor phosphatase PTEN can promote apoptosis of mitotic cells by inhibiting activation of the cell survival kinase Akt. PTEN is essential for normal embryonic development, PTEN expression is associated with neuronal differentiation, and deletion of PTEN in the mouse brain results in seizures, ataxia, and other abnormalities. However, the possible roles of PTEN in regulating neuronal survival are not known. We provide evidence that PTEN sensitizes hippocampal neurons to excitotoxic death in culture and in vivo. Overexpression of wild-type PTEN decreased, while a dominant-negative PTEN increased, levels of activated Akt in cultured hippocampal neurons. Wild-type PTEN promoted, while dominant-negative PTEN prevented, apoptotic death of neurons exposed to the excitatory amino acid neurotransmitter glutamate. Hippocampal neurons of mice with reduced PTEN levels were more resistant to seizure-induced death compared to wild-type littermates. These findings demonstrate a cell death function of PTEN in hippocampal neurons and identify PTEN as a potential therapeutic target for neurodegenerative disorders that involve excitotoxicity and apoptosis. The ability of PTEN to modify neuronal sensitivity to glutamate also suggests possible roles for PTEN in regulating developmental and synaptic plasticity. JF - Neuromolecular medicine AU - Gary, Devin S AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 261 EP - 269 VL - 2 IS - 3 SN - 1535-1084, 1535-1084 KW - Luminescent Proteins KW - 0 KW - Neurotoxins KW - Proto-Oncogene Proteins KW - Recombinant Fusion Proteins KW - Tumor Suppressor Proteins KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Glutamic Acid KW - 3KX376GY7L KW - Akt1 protein, rat KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - PTEN Phosphohydrolase KW - EC 3.1.3.67 KW - Index Medicus KW - Animals KW - Fetus KW - Neurons -- drug effects KW - Mice KW - Hippocampus -- drug effects KW - Mice, Knockout KW - Rats KW - Cells, Cultured KW - Neurons -- enzymology KW - Hippocampus -- enzymology KW - Immunohistochemistry KW - Male KW - Tumor Suppressor Proteins -- deficiency KW - Neurodegenerative Diseases -- enzymology KW - Phosphoric Monoester Hydrolases -- deficiency KW - Glutamic Acid -- metabolism KW - Neurotoxins -- metabolism KW - Tumor Suppressor Proteins -- genetics KW - Proto-Oncogene Proteins -- metabolism KW - Neurotoxins -- pharmacology KW - Phosphoric Monoester Hydrolases -- genetics KW - Glutamic Acid -- pharmacology KW - Neurodegenerative Diseases -- genetics KW - Apoptosis -- genetics KW - Apoptosis -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72855235?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuromolecular+medicine&rft.atitle=PTEN+regulates+Akt+kinase+activity+in+hippocampal+neurons+and+increases+their+sensitivity+to+glutamate+and+apoptosis.&rft.au=Gary%2C+Devin+S%3BMattson%2C+Mark+P&rft.aulast=Gary&rft.aufirst=Devin&rft.date=2002-01-01&rft.volume=2&rft.issue=3&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Neuromolecular+medicine&rft.issn=15351084&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-09 N1 - Date created - 2003-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clozapine-induced akathisia in children with schizophrenia. AN - 72853396; 12625995 AB - Akathisia is a relatively rare side effect with the newer atypical antipsychotic agents, particularly clozapine, and is easily misdiagnosed in children. As children are often unable to describe their symptoms verbally, their akathisia can be misdiagnosed as worsening of their psychosis, prompting an unnecessary increase in their neuroleptic dose. Two cases of childhood-onset schizophrenia associated with clozapine-induced akathisia responsive to beta-blocker treatment are described. Akathisia should be considered in all cases of apparent nonresponse to atypical antipsychotics. JF - Journal of child and adolescent psychopharmacology AU - Gogtay, Nitin AU - Sporn, Alexandra AU - Alfaro, Cara L AU - Mulqueen, Ann AU - Rapoport, Judith L AD - Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 347 EP - 349 VL - 12 IS - 4 SN - 1044-5463, 1044-5463 KW - Adrenergic beta-Antagonists KW - 0 KW - Antipsychotic Agents KW - Clozapine KW - J60AR2IKIC KW - Index Medicus KW - Humans KW - Child KW - Adrenergic beta-Antagonists -- therapeutic use KW - Male KW - Female KW - Akathisia, Drug-Induced -- drug therapy KW - Clozapine -- therapeutic use KW - Akathisia, Drug-Induced -- diagnosis KW - Antipsychotic Agents -- therapeutic use KW - Schizophrenia, Childhood -- drug therapy KW - Akathisia, Drug-Induced -- psychology KW - Clozapine -- adverse effects KW - Antipsychotic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72853396?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+child+and+adolescent+psychopharmacology&rft.atitle=Clozapine-induced+akathisia+in+children+with+schizophrenia.&rft.au=Gogtay%2C+Nitin%3BSporn%2C+Alexandra%3BAlfaro%2C+Cara+L%3BMulqueen%2C+Ann%3BRapoport%2C+Judith+L&rft.aulast=Gogtay&rft.aufirst=Nitin&rft.date=2002-01-01&rft.volume=12&rft.issue=4&rft.spage=347&rft.isbn=&rft.btitle=&rft.title=Journal+of+child+and+adolescent+psychopharmacology&rft.issn=10445463&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-07 N1 - Date created - 2003-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemoprevention of prostate cancer: current status and future directions. AN - 72839838; 12549768 AB - Prostate cancer chemoprevention can be described as the administration of natural products and pharmaceutical agents that inhibit one or more steps in the natural history of prostatic carcinogenesis. The principle components of the chemoprevention strategy are closely connected to this natural history and include: (a) agents and their molecular targets; (b) strategic intermediate endpoint biomarkers (IEBs) and their critical pathways; (c) cohorts identified by genetic and acquired risk factors and (d) efficient designs that combine these elements into a cohesive clinical trial. The primary goal is to find effective noncytotoxic agents that modulate the promotion and progression from normal epithelium to dysplasia to high-grade prostatic intraepithelial neoplasia (HGPIN) to locally invasive cancer and metastatic disease. Another important target for chemoprevention is to modulate progression to clinically aggressive disease and to maintain an androgen-sensitive clinical state and delay the emergence of androgen resistance. There is a rationale for use of antiandrogens as the lead class, e.g., 5 alpha receptor inhibitors (5ARI), for chemoprevention of prostate cancer. Nevertheless, the desire to improve the therapeutic index, achieve synergy (5ARI may have only modest anticancer effects) and prevent the emergence of drug (androgen) resistance provide incentives for developing other effective agents and combinations. The availability of more than a dozen classes of noncytotoxic pharmaceutical and natural products already in clinical development create many opportunities for rational combination therapy. Several agent classes have a pharmacodynamic basis for combination with antiandrogens including antiproliferatives, selective estrogen receptor modulators (SERMs), proapoptotic antioxidant micronutrients and selective cyclo-oxygenase (COX)-2 inhibitors. Many other rational pharmacodynamic combinations without antiandrogens are feasible. It is anticipated that in the future, a selective COX-2 inhibitor may be combined with other agent classes such as proapoptotic antioxidant micronutrients, receptor tyrosine kinase modulators, antiangiogenic modulators, antiproliferative/differentiating agents, NFkappaB modulators, IGF-1 modulators and other novel proapototic nonsteroidal drugs. A novel target for rational combinations is the hypermethylation of GST-PI leading to functional silencing of this key anticarcinogen defense enzyme in precursors (HGPIN) and prostate cancer. Factorial designs are well suited for evaluating the individual and combined effects of each agent in a single trial design. There are a number of moderate to high-risk cohorts and clinical models of primary and secondary prevention that can be employed in both short-term developmental (translational) trials for proof of biologic activity and in intermediate sized longer-term chemoprevention trials for proof of efficacy against prostate cancer. Strategic IEBs are needed to more efficiently monitor short-term biologic activity and validate efficacy. The emergence of new powerful tools such as gene chip cDNA microarrays for multiplex gene expression profiling and proteomic analysis of tissue based and secreted proteins will accelerate the identification of new molecular targets, strategic endpoints, cohorts at risk and the design of rational combination trials. JF - Cancer metastasis reviews AU - Lieberman, Ronald AD - Prostate and Urologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD 20852, USA. rl39r@nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 297 EP - 309 VL - 21 IS - 3-4 SN - 0167-7659, 0167-7659 KW - Anticarcinogenic Agents KW - 0 KW - Index Medicus KW - Humans KW - Forecasting KW - Chemoprevention -- trends KW - Male KW - Anticarcinogenic Agents -- therapeutic use KW - Prostatic Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72839838?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+metastasis+reviews&rft.atitle=Chemoprevention+of+prostate+cancer%3A+current+status+and+future+directions.&rft.au=Lieberman%2C+Ronald&rft.aulast=Lieberman&rft.aufirst=Ronald&rft.date=2002-01-01&rft.volume=21&rft.issue=3-4&rft.spage=297&rft.isbn=&rft.btitle=&rft.title=Cancer+metastasis+reviews&rft.issn=01677659&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-07 N1 - Date created - 2003-01-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Micronutrients in cancer chemoprevention. AN - 72838957; 12549762 AB - The selection of micronutrients, defined as essential and nonessential dietary components consumed in minute quantities, for testing in clinical chemoprevention trials is based on the totality of evidence arising from epidemiologic, in vitro, animal, and clinical studies. Those micronutrients that surface with chemopreventive potential, in terms of high efficacy and low toxicity, in early-phase clinical studies are then candidates for large-scale, randomized clinical chemoprevention trials with cancer endpoints. Micronutrients currently being examined in National Cancer Institute (NCI)-sponsored phase I, II, or III chemoprevention trials for prostate, breast, and colon cancers include isoflavones, lycopene, selenized yeast, selenomethionine, selenium, vitamin E, perillyl alcohol, folic acid, vitamin D, calcium, and curcumin. The response to micronutrients may vary not only in magnitude but also in direction. This variation and response likely depend on individual genetic polymorphisms and/or interactions among dietary components that influence absorption, metabolism, or site of action. Research priorities include investigation of possible molecular targets for micronutrients and whether genetic and epigenetic events dictate direction and magnitude of the response. JF - Cancer metastasis reviews AU - Greenwald, Peter AU - Milner, John A AU - Anderson, Darrell E AU - McDonald, Sharon S AD - Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7309, USA. greenwap@mail.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 217 EP - 230 VL - 21 IS - 3-4 SN - 0167-7659, 0167-7659 KW - Anticarcinogenic Agents KW - 0 KW - Micronutrients KW - Index Medicus KW - Animals KW - Humans KW - Forecasting KW - Diet KW - Micronutrients -- therapeutic use KW - Anticarcinogenic Agents -- therapeutic use KW - Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72838957?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+metastasis+reviews&rft.atitle=Micronutrients+in+cancer+chemoprevention.&rft.au=Greenwald%2C+Peter%3BMilner%2C+John+A%3BAnderson%2C+Darrell+E%3BMcDonald%2C+Sharon+S&rft.aulast=Greenwald&rft.aufirst=Peter&rft.date=2002-01-01&rft.volume=21&rft.issue=3-4&rft.spage=217&rft.isbn=&rft.btitle=&rft.title=Cancer+metastasis+reviews&rft.issn=01677659&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-07 N1 - Date created - 2003-01-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tools for clinical toxicology on the World Wide Web: review and scenario. AN - 72803550; 12507059 AB - Clinical toxicologists are entrusted with the health and safety of humans and animals exposed to toxic substances. To do their jobs well they need a solid knowledge of toxicological principles, an ability to handle emergent situations, a "bedside" manner that results in a good rapport with patients, and the ability to access current and accurate information in order to properly care for the afflicted. An information armamentarium that is increasingly digital and Web-based is becoming a necessity. This article reviews Web resources that can assist the toxicologist. A case scenario is presented to provide a practical perspective to the information tools outlined. JF - Journal of toxicology. Clinical toxicology AU - Wexler, Philip AU - Phillips, Scott AD - Toxicology and Environmental Health Information Program, National Library of Medicine, 2 Democracy Plaza, Suite 510, 6707 Democracy Blvd., Bethesda, MD 20892-5467, USA. wexlerp@mail.nlm.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 893 EP - 902 VL - 40 IS - 7 SN - 0731-3810, 0731-3810 KW - Hazardous Substances KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Information Systems KW - United States Food and Drug Administration KW - United States Environmental Protection Agency KW - Chemistry KW - National Library of Medicine (U.S.) KW - Chemical Phenomena KW - Databases, Factual KW - Toxicology -- education KW - Internet UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72803550?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology.+Clinical+toxicology&rft.atitle=Tools+for+clinical+toxicology+on+the+World+Wide+Web%3A+review+and+scenario.&rft.au=Wexler%2C+Philip%3BPhillips%2C+Scott&rft.aulast=Wexler&rft.aufirst=Philip&rft.date=2002-01-01&rft.volume=40&rft.issue=7&rft.spage=893&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology.+Clinical+toxicology&rft.issn=07313810&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-14 N1 - Date created - 2002-12-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Meat cooking and cancer risk. AN - 72776563; 12484160 JF - IARC scientific publications AU - Sinha, R AU - Norat, T AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Executive Plaza North, Rm. 443, 6130 Executive Blvd., Rockville, MD 20892, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 181 EP - 186 VL - 156 SN - 0300-5038, 0300-5038 KW - Amines KW - 0 KW - Biomarkers KW - Carcinogens KW - Heterocyclic Compounds KW - Polycyclic Aromatic Hydrocarbons KW - Index Medicus KW - Heterocyclic Compounds -- metabolism KW - Animals KW - Risk Factors KW - Humans KW - Amines -- metabolism KW - Polycyclic Aromatic Hydrocarbons -- adverse effects KW - Polycyclic Aromatic Hydrocarbons -- metabolism KW - Heterocyclic Compounds -- adverse effects KW - Feeding Behavior KW - Amines -- adverse effects KW - Hot Temperature KW - Carcinogens -- metabolism KW - Meat -- adverse effects KW - Neoplasms -- chemically induced KW - Neoplasms -- epidemiology KW - Cooking -- methods KW - Meat -- analysis KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72776563?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IARC+scientific+publications&rft.atitle=Meat+cooking+and+cancer+risk.&rft.au=Sinha%2C+R%3BNorat%2C+T&rft.aulast=Sinha&rft.aufirst=R&rft.date=2002-01-01&rft.volume=156&rft.issue=&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=IARC+scientific+publications&rft.issn=03005038&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-30 N1 - Date created - 2002-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Optimized clinical-scale culture conditions for ex vivo selective depletion of host-reactive donor lymphocytes: a strategy for GvHD prophylaxis in allogeneic PBSC transplantation. AN - 72763601; 12473206 AB - Ex vivo selective depletion (SD) is a strategy to prevent GvHD, in which host-reactive donor lymphocytes are selectively eliminated from a PBSC allograft while conserving useful donor immune function. Prior to testing this strategy in patients, our goal was to develop a clinical-scale SD process, which involves co-culture of donor lymphocytes and irradiated recipient cells, followed by the addition of an immunotoxin (IT) directed against the alpha-chain of the IL-2 receptor (CD25), expressed on activated donor T cells. Stimulator cells were generated from immunomagnetically selected and expanded recipient T lymphocytes. Donor PBMCs from G-CSF-mobilized peripheral blood were co-cultured for 72 h with irradiated stimulator cells. Alloreactive T cells were targeted for elimination by the addition of the anti-CD25 IT, RFT5-SMPT-dgA, and the IT enhancer, NH(4)Cl. Stimulator-cell selection/expansion yielded > 2 x 10(10) highly enriched CD3(+) cells (98.9 +/- 2.2%). After SD, cell recovery was 68.5 +/- 23.3% and viability was 84.6 +/- 6.4%. This permitted a potential T-cell dose >/= 1 x 10(8) CD3(+) cells kg(-1) to transplant recipients. Although SD donor lymphocytes retained little proliferative capacity against the original stimulator cells (2.6 +/- 0.6%), responses were conserved against third party cells (107.6 +/- 18.6%), the bacterial superantigen staphylococcus enterotoxin B (108.2 +/- 4.2%), and CMV Ag (72.1 +/- 3.8%). We have demonstrated that ex vivo SD is feasible in clinical-scale culture conditions. The ability of this strategy to prevent GvHD is the subject of an ongoing clinical trial, in which the SD lymphocyte product is transplanted in conjunction with a T cell-depleted PBSC allograft. JF - Cytotherapy AU - Solomon, S R AU - Tran, T AU - Carter, C S AU - Donnelly, S AU - Hensel, N AU - Schindler, J AU - Bahceci, E AU - Ghetie, V AU - Michálek, J AU - Mavroudis, D AU - Read, E J AU - Vitetta, E S AU - Barrett, A J AD - Stem Cell Allotransplantation Section, Hematology Branch, NHLBI, National Institutes of Health, Bethesda, MD 20892-1652, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 395 EP - 406 VL - 4 IS - 5 SN - 1465-3249, 1465-3249 KW - Antigens, CD3 KW - 0 KW - Culture Media KW - Cytokines KW - Receptors, Interleukin-2 KW - Index Medicus KW - Coculture Techniques KW - Leukocytes, Mononuclear KW - Dose-Response Relationship, Drug KW - Humans KW - Receptors, Interleukin-2 -- biosynthesis KW - Cytokines -- immunology KW - Freezing KW - Cell Survival KW - Lymphocyte Activation KW - Receptors, Interleukin-2 -- metabolism KW - Antigens, CD3 -- biosynthesis KW - Cells, Cultured KW - Hematopoietic Stem Cell Transplantation KW - Flow Cytometry KW - Time Factors KW - Immunophenotyping KW - Cell Division KW - Lymphocyte Depletion KW - Cell Culture Techniques -- methods KW - Transplantation, Homologous -- methods KW - T-Lymphocytes -- physiology KW - Graft vs Host Disease -- prevention & control KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72763601?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytotherapy&rft.atitle=Optimized+clinical-scale+culture+conditions+for+ex+vivo+selective+depletion+of+host-reactive+donor+lymphocytes%3A+a+strategy+for+GvHD+prophylaxis+in+allogeneic+PBSC+transplantation.&rft.au=Solomon%2C+S+R%3BTran%2C+T%3BCarter%2C+C+S%3BDonnelly%2C+S%3BHensel%2C+N%3BSchindler%2C+J%3BBahceci%2C+E%3BGhetie%2C+V%3BMich%C3%A1lek%2C+J%3BMavroudis%2C+D%3BRead%2C+E+J%3BVitetta%2C+E+S%3BBarrett%2C+A+J&rft.aulast=Solomon&rft.aufirst=S&rft.date=2002-01-01&rft.volume=4&rft.issue=5&rft.spage=395&rft.isbn=&rft.btitle=&rft.title=Cytotherapy&rft.issn=14653249&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-28 N1 - Date created - 2002-12-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Systemic alteration induced in mice by ultraviolet light irradiation and its relationship to ultraviolet carcinogenesis. 1977. AN - 72761751; 12481215 AB - Chronic irradiation of mice with ultraviolet (UV) light produces a systemic alteration of an immunologic nature. This alteration is detectable in mice long before primary skin cancers induced by UV light begin to appear. The alteration results in the failure of UV-irradiated mice to reject highly antigenic, transplanted UV-induced tumors that are rejected by unirradiated syngeneic recipients. The immunologic aspect of this systemic alteration was demonstrated by transferring lymphoid cells from UV-irradiated mice to lethally x-irradiated recipients. These recipients were unable to resist a later challenge with a syngeneic UV-induced tumor, whereas those given lymphoid cells from normal donors were resistant to tumor growth. Parabiosis of normal mice with UV-irradiated mice, followed by tumor challenge of both parabionts with a UV-induced tumor, resulted in the growth of the challenge tumors in both WV-irradiated and unirradiated mice. Splenic lymphocytes from tumor-implanted UV-treated mice were not cytotoxic in vitro against UV-induced tumors, whereas under identical conditions cells from tumor-implanted, unirradiated mice were highly cytotoxic. Our findings suggest that repeated UV irradiation can circumvent an immunologic mechanism that might otherwise destroy nascent UV-induced primary tumors that are strongly antigenic. JF - Bulletin of the World Health Organization AU - Fisher, Michael S AU - Kripke, Margaret L AD - Basic Research Program, Cancer Research Center, National Cancer Institute Frederick, Frederick, Maryland 21701, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 908 EP - 912 VL - 80 IS - 11 SN - 0042-9686, 0042-9686 KW - Index Medicus KW - Fisher KW - Kripke KW - Mice, Inbred Strains KW - Animals KW - History, 20th Century KW - Skin Neoplasms -- etiology KW - Risk Factors KW - Parabiosis -- history KW - Mice KW - Skin Neoplasms -- history KW - Neoplasm Transplantation -- history KW - Ultraviolet Rays -- history KW - Immune Tolerance -- radiation effects KW - Ultraviolet Rays -- adverse effects KW - Neoplasms, Radiation-Induced -- history KW - Neoplasms, Radiation-Induced -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72761751?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bulletin+of+the+World+Health+Organization&rft.atitle=Systemic+alteration+induced+in+mice+by+ultraviolet+light+irradiation+and+its+relationship+to+ultraviolet+carcinogenesis.+1977.&rft.au=Fisher%2C+Michael+S%3BKripke%2C+Margaret+L&rft.aulast=Fisher&rft.aufirst=Michael&rft.date=2002-01-01&rft.volume=80&rft.issue=11&rft.spage=908&rft.isbn=&rft.btitle=&rft.title=Bulletin+of+the+World+Health+Organization&rft.issn=00429686&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-26 N1 - Date created - 2002-12-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Bull World Health Organ. 2002;80(11):906-7 [12481214] N1 - People - Fisher; Kripke N1 - Last updated - 2017-01-18 N1 - SubjectsTermNotLitGenreText - Fisher; Kripke ER - TY - JOUR T1 - Progesterone receptors--animal models and cell signalling in breast cancer. Implications for breast cancer of inclusion of progestins in hormone replacement therapies. AN - 72753344; 12473171 AB - Progestins are included in menopausal hormone replacement therapy to counteract the increased risk for endometrial cancer associated with estrogen replacement therapy. Studies of hormone replacement therapy and breast cancer risk and of changes in mammographic density according to different regimens of hormone replacement therapy suggest that, for the most part, estrogen-progestin replacement therapy has a more adverse effect on breast cancer risk than does estrogen replacement therapy. Many questions remain unresolved, however, including risk associated with different regimens of estrogen-progestin replacement therapy, and whether the effects vary according to tumor characteristics, such as histology, extent of disease, and hormone receptor status. JF - Breast cancer research : BCR AU - Schairer, Catherine AD - National Cancer Institute, Division of Cancer Epidemiology and Genetics, Rockville, Maryland 20852, USA. schairec@exchange.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 244 EP - 248 VL - 4 IS - 6 SN - 1465-5411, 1465-5411 KW - Estrogens KW - 0 KW - Progestins KW - Receptors, Progesterone KW - Index Medicus KW - Animals KW - Mammography KW - Humans KW - Breast -- cytology KW - Cell Division -- drug effects KW - Disease Models, Animal KW - Female KW - Hormone Replacement Therapy -- adverse effects KW - Receptors, Progesterone -- physiology KW - Progestins -- adverse effects KW - Breast Neoplasms -- etiology KW - Progestins -- administration & dosage KW - Estrogens -- adverse effects KW - Estrogens -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72753344?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Breast+cancer+research+%3A+BCR&rft.atitle=Progesterone+receptors--animal+models+and+cell+signalling+in+breast+cancer.+Implications+for+breast+cancer+of+inclusion+of+progestins+in+hormone+replacement+therapies.&rft.au=Schairer%2C+Catherine&rft.aulast=Schairer&rft.aufirst=Catherine&rft.date=2002-01-01&rft.volume=4&rft.issue=6&rft.spage=244&rft.isbn=&rft.btitle=&rft.title=Breast+cancer+research+%3A+BCR&rft.issn=14655411&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-02 N1 - Date created - 2002-12-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Drugs Aging. 1998 May;12(5):343-8 [9606612] Fertil Steril. 1998 May;69(5):963-9 [9591509] Ann Med. 1998 Dec;30(6):511-24 [9920352] Ann Intern Med. 1999 Feb 16;130(4 Pt 1):262-9 [10068383] Int J Cancer. 1999 May 5;81(3):339-44 [10209946] Lancet. 1997 Oct 11;350(9084):1047-59 [10213546] Am J Obstet Gynecol. 1999 Aug;181(2):348-52 [10454681] Cancer Causes Control. 1999 Aug;10(4):253-60 [10482483] Br J Cancer. 1998 Oct;78(7):945-9 [9764588] J Clin Endocrinol Metab. 1999 Dec;84(12):4559-65 [10599719] JAMA. 2000 Jan 26;283(4):485-91 [10659874] J Natl Cancer Inst. 2000 Feb 16;92(4):328-32 [10675382] Cancer. 2000 Jun 1;88(11):2570-7 [10861435] Am J Epidemiol. 2000 Nov 15;152(10):950-64 [11092437] Am J Obstet Gynecol. 2001 Feb;184(3):340-9 [11228484] Cancer Causes Control. 2001 Feb;12(2):111-5 [11246839] Curr Oncol Rep. 2001 Jul;3(4):314-21 [11389815] Am J Obstet Gynecol. 2001 Aug;185(2 Suppl):S38-46 [11521121] Fertil Steril. 2001 Sep;76(3):445-50 [11532462] Maturitas. 2001 Nov 30;40(2):151-7 [11716993] J Clin Oncol. 2002 Feb 1;20(3):699-706 [11821451] JAMA. 2002 Feb 13;287(6):734-41 [11851540] Am J Obstet Gynecol. 2002 Feb;186(2):325-34 [11854659] JAMA. 2002 Jul 3;288(1):58-66 [12090863] Cancer Epidemiol Biomarkers Prev. 2002 Jul;11(7):593-600 [12101105] JAMA. 2002 Jul 17;288(3):321-33 [12117397] Cancer Causes Control. 2002 Aug;13(6):583-90 [12195648] Epidemiol Rev. 1993;15(1):17-35 [8405201] N Engl J Med. 1995 Jun 15;332(24):1589-93 [7753136] Am J Epidemiol. 1995 Oct 15;142(8):788-95 [7572954] Am J Epidemiol. 1997 Mar 15;145(6):536-45 [9063344] J Psychosom Obstet Gynaecol. 1997 Jun;18(2):145-57 [9219111] J Clin Oncol. 1997 Oct;15(10):3201-7 [9336356] Comment In: Breast Cancer Res. 2002;4(6):222-3 [12473167] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Timing of supplementation with the antioxidant N-acetyl-L-cysteine reduces tumor multiplicity in novel, cancer-prone p53 haploinsufficient Tg.AC (v-Ha-ras) transgenic mice but has no impact on malignant progression. AN - 72738261; 12467136 AB - Epidemiological studies support the protective role of dietary antioxidants in preventing cancer. However, emerging evidence suggests that antioxidant supplements may actually exacerbate carcinogenesis. We explored this paradox in a model containing two common genotypic characteristics of human cancers. We selected p53 haploinsufficient Tg.AC (v-Ha-ras) mice as a model, because it contains an activated, carcinogen-inducible ras oncogene and an inactivated p53 tumor suppressor gene. These mice develop chemically induced benign and malignant skin tumors rapidly. Mice were fed basal diet with or without 3% N-acetyl-L-cysteine (NAC) before and after topical application of the carcinogen benzo[a]pyrene (64 micrograms twice per week for 7 wk) until 50% of mice within a group displayed at least one lesion. Half each of mice fed the basal and the NAC-supplemented diet were then switched to the alternate diet. Mice fed the NAC-supplemented diet or switched from the NAC-supplemented to the basal diet displayed 38% and 26% reductions, respectively, in tumor multiplicity and a 15% reduction if switched from the basal to the NAC-supplemented diet. Although latency was unaffected, NAC induced a lag in tumor incidence, which exceeded 90% at 10 wk for all groups. The timing of NAC supplementation did not affect malignant progression. Thus dietary NAC was chemoprotective by slowing tumorigenesis but did not affect malignant conversion. JF - Nutrition and cancer AU - Martin, Keith R AU - Saulnier, Muriel J AU - Kari, Frank W AU - Barrett, J Carl AU - French, John E AD - Transgenic Carcinogenesis Unit, Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. krm12@psu.edu Y1 - 2002 PY - 2002 DA - 2002 SP - 59 EP - 66 VL - 43 IS - 1 SN - 0163-5581, 0163-5581 KW - Antioxidants KW - 0 KW - Free Radical Scavengers KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Animals KW - Survival Rate KW - Linear Models KW - Cross-Over Studies KW - Disease Models, Animal KW - Mice KW - Mice, Transgenic KW - Time Factors KW - Male KW - Female KW - Acetylcysteine -- administration & dosage KW - Carcinoma, Squamous Cell -- mortality KW - Carcinoma, Squamous Cell -- chemically induced KW - Cell Transformation, Neoplastic -- drug effects KW - Free Radical Scavengers -- administration & dosage KW - Skin Neoplasms -- prevention & control KW - Sarcoma -- chemically induced KW - Genes, ras -- genetics KW - Sarcoma -- mortality KW - Skin Neoplasms -- chemically induced KW - Carcinoma, Squamous Cell -- prevention & control KW - Sarcoma -- prevention & control KW - Dietary Supplements KW - Skin Neoplasms -- mortality KW - Antioxidants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72738261?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+and+cancer&rft.atitle=Timing+of+supplementation+with+the+antioxidant+N-acetyl-L-cysteine+reduces+tumor+multiplicity+in+novel%2C+cancer-prone+p53+haploinsufficient+Tg.AC+%28v-Ha-ras%29+transgenic+mice+but+has+no+impact+on+malignant+progression.&rft.au=Martin%2C+Keith+R%3BSaulnier%2C+Muriel+J%3BKari%2C+Frank+W%3BBarrett%2C+J+Carl%3BFrench%2C+John+E&rft.aulast=Martin&rft.aufirst=Keith&rft.date=2002-01-01&rft.volume=43&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+cancer&rft.issn=01635581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-16 N1 - Date created - 2002-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reassignment of Mycs gene to mouse chromosome XA1.2-2 by radiation hybrid mapping and fluorescence in situ hybridization. AN - 72689594; 12438760 JF - Cytogenetic and genome research AU - Shan, Z H AU - Popescu, N C AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2002 PY - 2002 DA - 2002 VL - 97 IS - 1-2 SN - 1424-8581, 1424-8581 KW - DNA Primers KW - 0 KW - Index Medicus KW - Animals KW - Base Sequence KW - Radiation Hybrid Mapping KW - DNA Primers -- genetics KW - Molecular Sequence Data KW - In Situ Hybridization, Fluorescence KW - Chromosomes, Artificial, Bacterial -- genetics KW - Mice KW - Genes, myc KW - X Chromosome -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72689594?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytogenetic+and+genome+research&rft.atitle=Reassignment+of+Mycs+gene+to+mouse+chromosome+XA1.2-2+by+radiation+hybrid+mapping+and+fluorescence+in+situ+hybridization.&rft.au=Shan%2C+Z+H%3BPopescu%2C+N+C&rft.aulast=Shan&rft.aufirst=Z&rft.date=2002-01-01&rft.volume=97&rft.issue=1-2&rft.spage=140G&rft.isbn=&rft.btitle=&rft.title=Cytogenetic+and+genome+research&rft.issn=14248581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-16 N1 - Date created - 2002-11-19 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AB016289; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Numerous proteins in Mammalian cells are prone to iron-dependent oxidation and proteasomal degradation. AN - 72637722; 12401949 AB - The mechanisms that underlie iron toxicity in cells and organisms are poorly understood. Previous studies of regulation of the cytosolic iron sensor, iron-regulatory protein 2 (IRP2), indicate that iron-dependent oxidation triggers ubiquitination and proteasomal degradation of IRP2. To determine if oxidization by iron is involved in degradation of other proteins, we have used a carbonyl assay to identify oxidized proteins in lysates from RD4 cells treated with either an iron source or iron chelator. Protein lysates from iron-loaded or iron-depleted cells were resolved on two-dimensional gels and these iron manipulations were also repeated in the presence of proteasomal inhibitors. Eleven abundant proteins were identified as prone to iron-dependent oxidation and subsequent proteasomal degradation. These proteins included two putative iron-binding proteins, hNFU1 and calreticulin; two proteins involved in metabolism of hydrogen peroxide, peroxiredoxin 2 and superoxide dismutase 1; and several proteins identified in inclusions in neurodegenerative diseases, including HSP27, UCHL1, actin and tropomyosin. Our results indicate that cells can recognize and selectively eliminate iron-dependently oxidized proteins, but unlike IRP2, levels of these proteins do not significantly decrease in iron-treated cells. As iron overload is a feature of many human neurological diseases, further characterization of the process of degradation of iron-dependently oxidized proteins may yield insights into mechanisms of human disease. Copyright 2002 S. Karger AG, Basel JF - Developmental neuroscience AU - Drake, Steven K AU - Bourdon, Emmanuel AU - Wehr, Nancy B AU - Levine, Rodney L AU - Backlund, Peter S AU - Yergey, Alfred L AU - Rouault, Tracey A AD - National Institute of Child Health and Human Development, Bethesda, MD, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 114 EP - 124 VL - 24 IS - 2-3 SN - 0378-5866, 0378-5866 KW - Cysteine Proteinase Inhibitors KW - 0 KW - Ferric Compounds KW - Iron Chelating Agents KW - Multienzyme Complexes KW - Proteins KW - Quaternary Ammonium Compounds KW - lactacystin KW - 133343-34-7 KW - Iron KW - E1UOL152H7 KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Deferoxamine KW - J06Y7MXW4D KW - ferric ammonium citrate KW - UVP74NG1C5 KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Cysteine Proteinase Inhibitors -- pharmacology KW - Blotting, Western KW - Deferoxamine -- pharmacology KW - Tumor Cells, Cultured KW - Oxidation-Reduction -- drug effects KW - Humans KW - Ferric Compounds -- pharmacology KW - Quaternary Ammonium Compounds -- pharmacology KW - Iron Chelating Agents -- pharmacology KW - Proteins -- drug effects KW - Multienzyme Complexes -- metabolism KW - Acetylcysteine -- analogs & derivatives KW - Cysteine Endopeptidases -- metabolism KW - Proteins -- analysis KW - Acetylcysteine -- pharmacology KW - Proteins -- metabolism KW - Iron -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72637722?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+neuroscience&rft.atitle=Numerous+proteins+in+Mammalian+cells+are+prone+to+iron-dependent+oxidation+and+proteasomal+degradation.&rft.au=Drake%2C+Steven+K%3BBourdon%2C+Emmanuel%3BWehr%2C+Nancy+B%3BLevine%2C+Rodney+L%3BBacklund%2C+Peter+S%3BYergey%2C+Alfred+L%3BRouault%2C+Tracey+A&rft.aulast=Drake&rft.aufirst=Steven&rft.date=2002-01-01&rft.volume=24&rft.issue=2-3&rft.spage=114&rft.isbn=&rft.btitle=&rft.title=Developmental+neuroscience&rft.issn=03785866&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-07 N1 - Date created - 2002-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nicotinic receptors mediate increased GABA release in brain through a tetrodotoxin-insensitive mechanism during prolonged exposure to nicotine. AN - 72630834; 12401328 AB - The effects of nicotine on the spontaneous release of GABA from nerve terminals in the chick lateral spiriform nucleus were examined using whole cell patch-clamp recording in brain slices. Exposure to 1 microM nicotine produced an early immediate increase in the frequency of spontaneous postsynaptic GABAergic currents. This effect was blocked in the presence of 0.5 microM tetrodotoxin. However, a prolonged application of 0.1-1 microM nicotine (>3 min) caused a tetrodotoxin-insensitive increase in the frequency of spontaneous GABAergic currents. This late tetrodotoxin-insensitive effect was blocked by the nicotinic antagonists dihydro-beta-erythroidine (30 microM) and mecamylamine (10 microM), but not by methyllycaconitine (50-100 nM), indicating that activation of high affinity nicotine receptors was mainly responsible for this effect. This enhancement was inhibited by the high threshold Ca(2+) channel blocker Cd(2+) (100 microM), but not by dantrolene or ryanodine. The tetrodotoxin-insensitive enhancement of the frequency of GABA currents by nicotine was reduced by inhibition of cAMP-dependent protein kinase with HA1004 (30 microM), but not by inhibition of protein kinase C with staurosporine (1 microM), and was facilitated by forskolin (10 microM) or bromo-cAMP (50 microM). The results indicate that nicotine-enhanced GABA release can operate through both tetrodotoxin-sensitive and -insensitive mechanisms in a single brain region and that a second messenger cascade may be involved in the tetrodotoxin-insensitive enhancement by nicotine. JF - Neuroscience AU - Zhu, P J AU - Chiappinelli, V A AD - Department of Pharmacology, The George Washington University Medical Center, Washington, DC 20037, USA. pzhu@mail.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 137 EP - 144 VL - 115 IS - 1 SN - 0306-4522, 0306-4522 KW - Receptors, Nicotinic KW - 0 KW - Tetrodotoxin KW - 4368-28-9 KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Animals KW - Synaptic Transmission -- drug effects KW - Chick Embryo KW - In Vitro Techniques KW - Synaptic Transmission -- physiology KW - Nicotine -- toxicity KW - Brain -- drug effects KW - gamma-Aminobutyric Acid -- secretion KW - Brain -- metabolism KW - Receptors, Nicotinic -- physiology KW - Tetrodotoxin -- pharmacology KW - Brain -- secretion KW - gamma-Aminobutyric Acid -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72630834?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Nicotinic+receptors+mediate+increased+GABA+release+in+brain+through+a+tetrodotoxin-insensitive+mechanism+during+prolonged+exposure+to+nicotine.&rft.au=Zhu%2C+P+J%3BChiappinelli%2C+V+A&rft.aulast=Zhu&rft.aufirst=P&rft.date=2002-01-01&rft.volume=115&rft.issue=1&rft.spage=137&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-05 N1 - Date created - 2002-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical trial design for target-based therapy. AN - 72630273; 12401902 AB - Anticancer drug discovery has shifted from an empiric random screening directed approach to a more rational and mechanistic, target-based approach, which reflects our rapidly expanding knowledge of the pathogenesis of a variety of forms of cancer at the molecular level, providing new targets for drug discovery and development. The clinical development of target-based anticancer drugs will require fundamental changes to the traditional clinical trial design and end points that have been used for conventional cytotoxic drugs. In the phase I and II settings, traditional end points (toxicity and response) may not be suitable for more selective, cytostatic target-based agents, and these end points may be replaced by biological or pharmacokinetic end points to define the optimal doses and the therapeutic effects of these drugs on their targets. For phase III trials, measurable clinical benefit will continue to be the primary end point. As our understanding of the complex pathways and networks controlling cell signaling, proliferation, and cell death expands, we must learn how and when to use agents to target specific steps in malignant transformation and proliferation, and we must adapt clinical trial design to test the clinical utility of this promising new class of anticancer drugs. JF - The oncologist AU - Fox, Elizabeth AU - Curt, Gregory A AU - Balis, Frank M AD - Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA. foxb@mail.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 401 EP - 409 VL - 7 IS - 5 SN - 1083-7159, 1083-7159 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Drug Evaluation -- methods KW - Humans KW - Drug Therapy -- trends KW - Neoplasms -- drug therapy KW - Clinical Trials as Topic -- standards KW - Research Design KW - Drug Design KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72630273?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+oncologist&rft.atitle=Clinical+trial+design+for+target-based+therapy.&rft.au=Fox%2C+Elizabeth%3BCurt%2C+Gregory+A%3BBalis%2C+Frank+M&rft.aulast=Fox&rft.aufirst=Elizabeth&rft.date=2002-01-01&rft.volume=7&rft.issue=5&rft.spage=401&rft.isbn=&rft.btitle=&rft.title=The+oncologist&rft.issn=10837159&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-04 N1 - Date created - 2002-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Humane endpoints for laboratory animals used in regulatory testing. AN - 72190538; 12388849 AB - Laboratory animals are used for regulatory testing to assess the safety, efficacy, and/or potential adverse health effects of new chemicals and products such as vaccines, medicines, food additives, pesticides, and industrial chemicals. Testing results are used for risk assessment decisions intended to safeguard human and animal health. However, chemical toxicity and vaccine testing can cause injury, disease, and mortality involving significant pain and distress. Alleviation of pain and distress in animals during testing is problematic because regulations allow treatment only if the treatment does not interfere with the study. One approach to this problem has been to identify criteria that can serve as the basis for ending a test procedure sooner in an effort to terminate or avoid pain and distress while still allowing attainment of study objectives. These criteria are referred to as humane endpoints because they reduce the severity and/or duration of pain and distress experienced by an animal. New and revised test methods and approaches that incorporate humane endpoints are being considered and adopted by national and international regulatory testing authorities. The prerequisite for adoption of these methods is a determination that the methods have been adequately validated and that they provide equivalent or better information for risk assessment. Further progress in reducing animal pain and distress resulting from regulatory testing is expected as scientific and technological advances are incorporated into testing procedures and strategies. JF - ILAR journal AU - Stokes, William S AD - NTP Interagency Center for the Evaluation of Alternative Toxicological Methods, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - S31 EP - S38 VL - 43 Suppl SN - 1084-2020, 1084-2020 KW - Xenobiotics KW - 0 KW - Bioethics KW - Index Medicus KW - Biomedical and Behavioral Research KW - Animals KW - Animal Testing Alternatives KW - Pain -- prevention & control KW - Endpoint Determination -- methods KW - Xenobiotics -- classification KW - Animal Welfare KW - Toxicity Tests -- methods KW - Xenobiotics -- toxicity KW - Animals, Laboratory UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72190538?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ILAR+journal&rft.atitle=Humane+endpoints+for+laboratory+animals+used+in+regulatory+testing.&rft.au=Stokes%2C+William+S&rft.aulast=Stokes&rft.aufirst=William&rft.date=2002-01-01&rft.volume=43+Suppl&rft.issue=&rft.spage=S31&rft.isbn=&rft.btitle=&rft.title=ILAR+journal&rft.issn=10842020&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-25 N1 - Date created - 2002-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glow curve analysis applied to the discrimination of X ray versus proton irradiation. AN - 72185090; 12382714 AB - Three types of thermoluminescence dosemeters (TLDs): LiF:Mg,Ti (TLD-100), CaF2:Tm (TLD-300), and alpha-Al2O3:C (TLD-500), were investigated for their glow curve response to separate X ray and proton irradiations. The glow curve structure for each individual TLD's exposure to the X ray and proton irradiations was analysed and compared. Distinguishable differences between the glow curve structure characteristic of each type of radiation were observed. The proton TLD-100 glow curve has revealed a complex high-temperature peak structure that was used for the proton/X ray discrimination algorithm. Proton irradiation of TLD-300 resulted in an apparent switch in the relative heights of peaks 3 and 5 as compared to X ray. In TLD-500, proton irradiation produced a more subtle difference in the glow curve with an increase in the ratio between high- and low-temperature peaks. Results demonstrate promising differences in glow curve structure present allowing for discrimination between X ray and proton radiation field exposures. JF - Radiation protection dosimetry AU - Skopec, M AU - Price, J L AU - Guardala, N AU - Loew, M AU - Moscovitch, M AD - Department of Diagnostic Radiology, National Institutes of Health, Bethesda, Maryland, USA. marskopec@yahoo.com Y1 - 2002 PY - 2002 DA - 2002 SP - 99 EP - 102 VL - 101 IS - 1-4 SN - 0144-8420, 0144-8420 KW - Lithium Compounds KW - 0 KW - Protons KW - lithium fluoride KW - 1485XST65B KW - Titanium KW - D1JT611TNE KW - Magnesium KW - I38ZP9992A KW - Calcium Fluoride KW - O3B55K4YKI KW - Fluorides KW - Q80VPU408O KW - Index Medicus KW - Space life sciences KW - Non-programmatic KW - Thermodynamics KW - X-Rays KW - Thermoluminescent Dosimetry -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72185090?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+protection+dosimetry&rft.atitle=Glow+curve+analysis+applied+to+the+discrimination+of+X+ray+versus+proton+irradiation.&rft.au=Skopec%2C+M%3BPrice%2C+J+L%3BGuardala%2C+N%3BLoew%2C+M%3BMoscovitch%2C+M&rft.aulast=Skopec&rft.aufirst=M&rft.date=2002-01-01&rft.volume=101&rft.issue=1-4&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Radiation+protection+dosimetry&rft.issn=01448420&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-23 N1 - Date created - 2002-10-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interactions of antimitotic peptides and depsipeptides with tubulin. AN - 72183396; 12385035 AB - Tubulin is the target for an ever increasing number of structurally unusual peptides and depsipeptides isolated from a wide range of organisms. Since tubulin is the subunit protein of microtubules, the compounds are usually potently toxic to mammalian cells. Without exception, these (depsi)peptides disrupt cellular microtubules and prevent spindle formation. This causes cells to accumulate at the G2/M phase of the cell cycle through inhibition of mitosis. In biochemical assays, the compounds inhibit microtubule assembly from tubulin and suppress microtubule dynamics at low concentrations. Most of the (depsi)peptides inhibit the binding of Catharanthus alkaloids to tubulin in a noncompetitive manner, GTP hydrolysis by tubulin, and nucleotide turnover at the exchangeable GTP site on beta-tubulin. In general, the (depsi)peptides induce the formation of tubulin oligomers of aberrant morphology. In all cases tubulin rings appear to be formed, but these rings differ in diameter, depending on the (depsi)peptide present during their formation. Published 2002 Wiley Periodicals, Inc. JF - Biopolymers AU - Hamel, Ernest AD - Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute at Frederick, National Institutes of Health, MD 21702, USA. hamele@mail.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 142 EP - 160 VL - 66 IS - 3 SN - 0006-3525, 0006-3525 KW - Antineoplastic Agents KW - 0 KW - Biopolymers KW - Peptides KW - Tubulin KW - Index Medicus KW - Biopolymers -- metabolism KW - Biopolymers -- chemistry KW - Animals KW - Biopolymers -- pharmacology KW - Models, Molecular KW - Microtubules -- metabolism KW - Microtubules -- drug effects KW - Tubulin -- drug effects KW - Tubulin -- chemistry KW - Tubulin -- metabolism KW - Peptides -- chemistry KW - Peptides -- pharmacology KW - Antineoplastic Agents -- chemistry KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72183396?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biopolymers&rft.atitle=Interactions+of+antimitotic+peptides+and+depsipeptides+with+tubulin.&rft.au=Hamel%2C+Ernest&rft.aulast=Hamel&rft.aufirst=Ernest&rft.date=2002-01-01&rft.volume=66&rft.issue=3&rft.spage=142&rft.isbn=&rft.btitle=&rft.title=Biopolymers&rft.issn=00063525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-16 N1 - Date created - 2002-10-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deactivation of P-glycoprotein by a novel compound, oxalyl bis (N-phenyl) hydroxamic acid. AN - 72180049; 12382028 AB - A plasma membrane glycoprotein (P-gp) of 170 kd is over-expressed in most of the drug resistant cells. P-gp is encoded in humans by the gene mdrl and is thought to function as a broad substrate ATP-dependent drug efflux pump. P-gp is also present in many types of normal cells. A good number of chemicals inhibit or deactivate P-gp and thus reverse multidrug resistance (MDR). Most of the reported resistance modifying agents (RMAs) are effective in vitro and have adverse effect on the hosts. Hence, the development of nontoxic RMA is of immense importance in the field of cancer chemotherapy. With this end in view, a nontoxic resistance modifying agent, viz., oxalyl bis (N-phenyl) hydroxamic acid (OPHA) has been developed on the basis of the structural commonalities of the reported RMAs. We reported earlier that OPHA reverses doxorubicin resistance in vitro and also reduces glutathione and glutathione S-transferase in a non P-gp expressing cell line. In the present report, the inhibition of P-gp by the compound, OPHA in human cervical cancer cell line, HeLa, has been described by western blotting, study of immunofluorescence and enzyme linked immunofluorescence assay (ELISA). The inhibition of P-gp by OPHA is significantly higher than that of verapamil. The high IC50 values of OPHA against different cell lines indicate the non toxic nature of the compound. This work underscores the possibility of using the present hydroxamic acid derivative as the nontoxic modulator of the MDR phenotype. JF - Neoplasma AU - Choudhuri, S K AD - Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, Calcutta- 700 026 India. soumitra01@vsnl.net Y1 - 2002 PY - 2002 DA - 2002 SP - 272 EP - 277 VL - 49 IS - 4 SN - 0028-2685, 0028-2685 KW - Benzeneacetamides KW - 0 KW - Hydroxamic Acids KW - Oxalates KW - P-Glycoprotein KW - oxalyl bis(N-phenyl)hydroxamic acid KW - Verapamil KW - CJ0O37KU29 KW - Index Medicus KW - Blotting, Western KW - HeLa Cells KW - Humans KW - Enzyme-Linked Immunosorbent Assay KW - Drug Resistance, Neoplasm KW - Verapamil -- pharmacology KW - Fluorescent Antibody Technique KW - Cell Line KW - Drug Resistance, Multiple KW - Neoplasms -- drug therapy KW - Oxalates -- pharmacology KW - P-Glycoprotein -- metabolism KW - Oxalates -- toxicity KW - Hydroxamic Acids -- chemistry KW - Hydroxamic Acids -- toxicity KW - Hydroxamic Acids -- pharmacology KW - Oxalates -- chemistry KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72180049?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neoplasma&rft.atitle=Deactivation+of+P-glycoprotein+by+a+novel+compound%2C+oxalyl+bis+%28N-phenyl%29+hydroxamic+acid.&rft.au=Choudhuri%2C+S+K&rft.aulast=Choudhuri&rft.aufirst=S&rft.date=2002-01-01&rft.volume=49&rft.issue=4&rft.spage=272&rft.isbn=&rft.btitle=&rft.title=Neoplasma&rft.issn=00282685&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-13 N1 - Date created - 2002-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Parenteral busulfan: is therapeutic monitoring still warranted? AN - 72158493; 12374450 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation AU - Grochow, Louise B AD - Investigational Drug Branch, National Cancer Institute, Rockville, Maryland, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 465 EP - 467 VL - 8 IS - 9 SN - 1083-8791, 1083-8791 KW - Busulfan KW - G1LN9045DK KW - Index Medicus KW - Hepatic Veno-Occlusive Disease -- prevention & control KW - Bone Marrow Transplantation -- methods KW - Hepatic Veno-Occlusive Disease -- chemically induced KW - Humans KW - Drug Monitoring KW - Bone Marrow Transplantation -- adverse effects KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive -- therapy KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive -- complications KW - Infusions, Parenteral KW - Busulfan -- administration & dosage KW - Busulfan -- pharmacokinetics KW - Busulfan -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72158493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biology+of+blood+and+marrow+transplantation+%3A+journal+of+the+American+Society+for+Blood+and+Marrow+Transplantation&rft.atitle=Parenteral+busulfan%3A+is+therapeutic+monitoring+still+warranted%3F&rft.au=Grochow%2C+Louise+B&rft.aulast=Grochow&rft.aufirst=Louise&rft.date=2002-01-01&rft.volume=8&rft.issue=9&rft.spage=465&rft.isbn=&rft.btitle=&rft.title=Biology+of+blood+and+marrow+transplantation+%3A+journal+of+the+American+Society+for+Blood+and+Marrow+Transplantation&rft.issn=10838791&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-18 N1 - Date created - 2002-10-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Biol Blood Marrow Transplant. 2002;8(9):493-500 [12374454] Biol Blood Marrow Transplant. 2002;8(9):486-92 [12374453] Biol Blood Marrow Transplant. 2002;8(9):477-85 [12374452] Biol Blood Marrow Transplant. 2002;8(9):468-76 [12374451] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Levels of analysis in psychiatric research. AN - 72126722; 12349868 AB - Most of the major psychiatric disorders have been analyzed at each of several different levels. For example, at the broadest level, epidemiological studies have served to establish the incidence of disorders like schizophrenia and major depression in a number of different populations. Family and twin studies have been important in determining the heritability of certain mental illnesses, and chromosomal and linkage analyses have identified a number of discrete loci that appear to be implicated in disease susceptibility or, even directly, in the pathogenesis of some disorders. In a few cases, specific genes have been found to be mutated or polymorphic and proteins they encode are currently being analyzed. This article reviews how these different levels contribute to our understanding of a number of psychiatric disorders, including drug addiction, which has been the focus of much of our own work. JF - Development and psychopathology AU - Kopnisky, Kathy L AU - Cowan, W Maxwell AU - Hyman, Steven E AD - NIH, National Institute of Mental Health, Bethesda, MD 20892-9619, USA. kkopnisk@mail.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 437 EP - 461 VL - 14 IS - 3 SN - 0954-5794, 0954-5794 KW - Activating Transcription Factor 1 KW - 0 KW - DNA-Binding Proteins KW - Transcription Factors KW - Index Medicus KW - Substance-Related Disorders -- physiopathology KW - Environment KW - Transcription Factors -- physiology KW - Animals KW - Depressive Disorder, Major -- pathology KW - Humans KW - Adoption KW - Schizophrenia -- pathology KW - Schizophrenia -- physiopathology KW - Depressive Disorder, Major -- genetics KW - Phenotype KW - Genetic Linkage -- genetics KW - Gene Expression -- genetics KW - Chromosome Aberrations KW - Schizophrenia -- genetics KW - Twins -- psychology KW - Family -- psychology KW - Depressive Disorder, Major -- physiopathology KW - Brain -- physiopathology KW - Mental Disorders -- genetics KW - Brain -- pathology KW - Mental Disorders -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72126722?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Development+and+psychopathology&rft.atitle=Levels+of+analysis+in+psychiatric+research.&rft.au=Kopnisky%2C+Kathy+L%3BCowan%2C+W+Maxwell%3BHyman%2C+Steven+E&rft.aulast=Kopnisky&rft.aufirst=Kathy&rft.date=2002-01-01&rft.volume=14&rft.issue=3&rft.spage=437&rft.isbn=&rft.btitle=&rft.title=Development+and+psychopathology&rft.issn=09545794&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-13 N1 - Date created - 2002-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Therapy-associated solid tumors. AN - 72098979; 12234023 AB - As survival after a diagnosis of cancer improves, characterization of the late sequelae of treatment becomes critical. The development of second malignant neoplasms represents one of the most serious side effects of treatment with radiation and chemotherapy. Although secondary leukemia was the first reported carcinogenic effect resulting from cancer treatment, solid tumors now comprise the largest second tumor burden in some populations of survivors. It should be recognized, however, that solid cancers do not necessarily represent an adverse effect of therapy, but may also reflect the operation of shared etiologic factors, host determinants, gene-environment interactions, and other influences. Quantification of second cancer risk is important in terms of patient management, enabling clinicians to make informed decisions with regard to optimal treatment of the initial cancer, balancing efficacy against acute and chronic sequelae. This article focuses on selected highlights and recent developments in treatment-associated solid malignancies, with emphasis on radiotherapy and chemotherapy in adults, and summarizes areas for future research. Although cancer therapy represents a double-edged sword, it should always be recognized that it is advances in treatment that are largely responsible for the tremendous improvement in patient survival. Thus, the benefit derived from many cancer therapies far outweighs any risk of developing a second cancer. JF - Acta oncologica (Stockholm, Sweden) AU - Travis, Lois B AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. travisl@mail.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 323 EP - 333 VL - 41 IS - 4 SN - 0284-186X, 0284-186X KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Risk Factors KW - Humans KW - Clinical Trials as Topic KW - Neoplasms -- drug therapy KW - Neoplasms -- pathology KW - Neoplasms, Radiation-Induced -- etiology KW - Neoplasms -- radiotherapy KW - Neoplasms, Second Primary -- etiology KW - Radiotherapy -- adverse effects KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72098979?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+oncologica+%28Stockholm%2C+Sweden%29&rft.atitle=Therapy-associated+solid+tumors.&rft.au=Travis%2C+Lois+B&rft.aulast=Travis&rft.aufirst=Lois&rft.date=2002-01-01&rft.volume=41&rft.issue=4&rft.spage=323&rft.isbn=&rft.btitle=&rft.title=Acta+oncologica+%28Stockholm%2C+Sweden%29&rft.issn=0284186X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-30 N1 - Date created - 2002-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potential effects of certain persistent organic pollutants and endocrine disrupting chemicals on the health of children. AN - 72071505; 12216998 AB - Persistent organic pollutants are lipophilic, man-made chemicals that are highly resistant to degradation. Due to their persistence, they have become distributed in small quantities throughout the world. They bioaccumulate in thefood chain and are stored in fatty tissues. Biomagnifications up the food chain result in potential widespread human exposure to these chemicals. Exposure to persistent organic pollutants has been associated with many adverse human health effects, including impaired neurodevelopment, immune and reproductive function. Many persistent organic pollutants also possess the ability to disrupt the normal functioning of the endocrine system. There is an increasing concern that low-level exposure to these endocrine disrupting chemicals may have adverse health impacts, particularly during fetal, neonatal, and childhood development. Both the nature and severity of health outcomes may depend on the developmental time-period during which chemical exposure occurs. This report summarizes scientific evidence on health effects of low-level exposure to persistent organic pollutants and endocrine disrupting chemicals. JF - Journal of toxicology. Clinical toxicology AU - Damstra, Terri AD - World Health Organization, Research Triangle Park, North Carolina 27709, USA. damstra@niehs.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 457 EP - 465 VL - 40 IS - 4 SN - 0731-3810, 0731-3810 KW - Environmental Pollutants KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Immune System -- drug effects KW - Reproduction -- drug effects KW - Humans KW - Brain -- drug effects KW - Child KW - Neoplasms -- etiology KW - Environmental Pollutants -- toxicity KW - Endocrine Glands -- drug effects KW - Child Welfare UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72071505?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology.+Clinical+toxicology&rft.atitle=Potential+effects+of+certain+persistent+organic+pollutants+and+endocrine+disrupting+chemicals+on+the+health+of+children.&rft.au=Damstra%2C+Terri&rft.aulast=Damstra&rft.aufirst=Terri&rft.date=2002-01-01&rft.volume=40&rft.issue=4&rft.spage=457&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology.+Clinical+toxicology&rft.issn=07313810&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-19 N1 - Date created - 2002-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of glucose on cloning efficiency and mutagenesis of fetal rat cells. AN - 72055266; 12210495 AB - In a previous study, treatment of rats with 10% glucose in the drinking water, as fetuses during gestation and for 1.5 months after delivery, significantly enhanced tumor incidence that resulted from N-methyl-N-nitrosourea (MNU, 20 mg/kg) given transplacentally on gestation day 21, with a 1.6-fold increase in overall tumor incidence. We investigated whether glucose would have an effect on MNU-induced mutation in fetal F-344 rat somatic cells as measured in an in vivo/in vitro assay. Rat fetuses were exposed transplacentally to MNU on gestation day 16 and to a 10% glucose solution from gestation day 7 to day 17. Cells were isolated on gestation day 17 for determination of cloning efficiency and for selection of 6-thioguanine (6-TG)-resistant HGPRT mutants. Cloning efficiency of the fetal cells exposed to MNU alone was 22.6+/-2.3% S.E., while that for cells from fetuses exposed to MNU+glucose was 27.5+/-1.6% S.E., which was a significant difference (P=0.018). This indicates an effect of glucose on cell proliferation and survival. MNU treatment significantly increased the mutation frequency of fetal cells from a spontaneous value of 0.4 x 10(-6) per viable cell to (8.8+/-1.8 S.E.,) x 10(-6) (P=0.0087). The coexposure to MNU and glucose yielded a mutant frequency per plate of 0.62+/-0.05 S.E., which was a 1.5-fold increase compared to MNU alone (0.43+/-0.11 S.E., P=0.075. In summary, the data indicate that glucose during pregnancy increases proliferation/survival of fetal cells and possibly also mutation rate. JF - Teratogenesis, carcinogenesis, and mutagenesis AU - Donovan, Paul J AU - Smith, George T AU - Riggs, Charles W AU - Alexandrov, Valerii A AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland 21702-1201, USA. donovapa@mail.ncifcrf.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 329 EP - 334 VL - 22 IS - 5 SN - 0270-3211, 0270-3211 KW - Methylnitrosourea KW - 684-93-5 KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Cells, Cultured KW - Methylnitrosourea -- pharmacology KW - Time Factors KW - Mutation KW - Cell Division KW - Glucose -- pharmacology KW - Embryo, Mammalian -- cytology KW - Cloning, Organism KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72055266?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Teratogenesis%2C+carcinogenesis%2C+and+mutagenesis&rft.atitle=Effects+of+glucose+on+cloning+efficiency+and+mutagenesis+of+fetal+rat+cells.&rft.au=Donovan%2C+Paul+J%3BSmith%2C+George+T%3BRiggs%2C+Charles+W%3BAlexandrov%2C+Valerii+A&rft.aulast=Donovan&rft.aufirst=Paul&rft.date=2002-01-01&rft.volume=22&rft.issue=5&rft.spage=329&rft.isbn=&rft.btitle=&rft.title=Teratogenesis%2C+carcinogenesis%2C+and+mutagenesis&rft.issn=02703211&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-10 N1 - Date created - 2002-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Correlation of antipsychotic and prolactin concentrations in children and adolescents acutely treated with haloperidol, clozapine, or olanzapine. AN - 72019438; 12188977 AB - Patients with a Diagnostic and Statistical Manual of Mental Disorders (third edition, revised) diagnosis of schizophrenia or psychotic disorder not otherwise specified with onset of psychosis before the age of 13 participated in 6- to 8-week open or double-blind trials of haloperidol (n = 15, mean dose 15.4 +/- 8.1 mg/day [0.27 +/- 0.15 mg/kg/day]), clozapine (n = 30, mean dose 269.9 +/- 173.3 mg/day [4.4 +/- 2.6 mg/kg/day]), or olanzapine (n = 12, mean dose 17.5 +/- 2.8 mg/day [0.30 +/- 0.13 mg/kg/day]). Blood samples were obtained at 6 weeks for evaluation of haloperidol, reduced haloperidol, clozapine, desmethylclozapine, and olanzapine plasma concentrations and serum prolactin concentrations. No gender differences were noted for antipsychotic dose or concentration within each treatment group. Correlations between antipsychotic plasma concentration and serum prolactin concentration were significant only for the olanzapine treatment group (r = 0.80, p = 0.002). Separate correlations for gender were significant only for females receiving olanzapine (r = 0.91, p = 0.03); the patient with the highest serum prolactin experienced galactorrhea. Further studies evaluating the prolactin-elevating properties of antipsychotics are warranted in this population. JF - Journal of child and adolescent psychopharmacology AU - Alfaro, Cara L AU - Wudarsky, Marianne AU - Nicolson, Rob AU - Gochman, Peter AU - Sporn, Alexandra AU - Lenane, Marge AU - Rapoport, Judith L AD - National Institutes of Health, Clinical Center Pharmacy Department, Bethesda, Maryland 20892, USA. calfaro@nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 83 EP - 91 VL - 12 IS - 2 SN - 1044-5463, 1044-5463 KW - Antipsychotic Agents KW - 0 KW - Benzodiazepines KW - 12794-10-4 KW - Pirenzepine KW - 3G0285N20N KW - Prolactin KW - 9002-62-4 KW - Clozapine KW - J60AR2IKIC KW - Haloperidol KW - J6292F8L3D KW - olanzapine KW - N7U69T4SZR KW - Index Medicus KW - Schizophrenia -- blood KW - Psychotic Disorders -- blood KW - Double-Blind Method KW - Humans KW - Adult KW - Schizophrenia -- drug therapy KW - Child KW - Adolescent KW - Male KW - Female KW - Psychotic Disorders -- drug therapy KW - Clozapine -- blood KW - Haloperidol -- therapeutic use KW - Prolactin -- blood KW - Clozapine -- therapeutic use KW - Antipsychotic Agents -- blood KW - Pirenzepine -- analogs & derivatives KW - Antipsychotic Agents -- therapeutic use KW - Haloperidol -- blood KW - Pirenzepine -- blood KW - Pirenzepine -- therapeutic use KW - Pirenzepine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72019438?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+child+and+adolescent+psychopharmacology&rft.atitle=Correlation+of+antipsychotic+and+prolactin+concentrations+in+children+and+adolescents+acutely+treated+with+haloperidol%2C+clozapine%2C+or+olanzapine.&rft.au=Alfaro%2C+Cara+L%3BWudarsky%2C+Marianne%3BNicolson%2C+Rob%3BGochman%2C+Peter%3BSporn%2C+Alexandra%3BLenane%2C+Marge%3BRapoport%2C+Judith+L&rft.aulast=Alfaro&rft.aufirst=Cara&rft.date=2002-01-01&rft.volume=12&rft.issue=2&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Journal+of+child+and+adolescent+psychopharmacology&rft.issn=10445463&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-03 N1 - Date created - 2002-08-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Monoclonal antibody-based therapy strategies: providing options for the cancer patient. AN - 71991350; 12171546 AB - Treatment of patients with unconjugated MAb such as rituximab (Rituxan) the anti-CD20 MAb or trastuzumab (Herceptin) the anti-Her2 MAb, have shown efficacy in clinical trials and have gained approval from the Food and Drug Administration (FDA) has a result. Likewise, an anti-CD33 MAb conjugated with the antibiotic calicheamicin (Mylotarg) has proven efficacious in the treatment of patients with acute myeloid leukemia and has also been approved by the FDA. This overview presents some of the monoclonal antibody (MAb)-guided strategies with a focus on some of the experiences reported for MAb evaluated in clinical trials. JF - Current pharmaceutical design AU - Milenic, Diane E AD - Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, The National Institutes of Health, Bethesda, MD 20892, USA. esbl@helix.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 1749 EP - 1764 VL - 8 IS - 19 SN - 1381-6128, 1381-6128 KW - Antibodies, Monoclonal KW - 0 KW - Antineoplastic Agents KW - Immunoconjugates KW - Immunotoxins KW - Prodrugs KW - Index Medicus KW - Animals KW - Radioimmunotherapy KW - Prodrugs -- therapeutic use KW - Antineoplastic Agents -- administration & dosage KW - Humans KW - Cell Death KW - Clinical Trials as Topic KW - Immunotoxins -- therapeutic use KW - Immunoconjugates -- therapeutic use KW - Prodrugs -- administration & dosage KW - Neoplasms -- radiotherapy KW - Antibodies, Monoclonal -- pharmacology KW - Neoplasms -- therapy KW - Neoplasms -- immunology KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71991350?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+pharmaceutical+design&rft.atitle=Monoclonal+antibody-based+therapy+strategies%3A+providing+options+for+the+cancer+patient.&rft.au=Milenic%2C+Diane+E&rft.aulast=Milenic&rft.aufirst=Diane&rft.date=2002-01-01&rft.volume=8&rft.issue=19&rft.spage=1749&rft.isbn=&rft.btitle=&rft.title=Current+pharmaceutical+design&rft.issn=13816128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-24 N1 - Date created - 2002-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced metabolic activity coincides with survival and differentiation of cultured rat retinal ganglion cells exposed to glutamate. AN - 71979730; 12150775 AB - Neurotransmitters are prominent candidates for trans-cellular signals that influence the development of the CNS. The present study has examined the effect of glutamate on survival, differentiation and metabolic activity of cultured rat retinal ganglion cells at 3 days in vitro. Retinal cultures from neonatal Wistar rats were treated with glutamate for 48 h. The metabolic activity was markedly increased in the retinal ganglion cells exposed to 20 microM glutamate. This was accompanied by an enhanced survival of these neurons. The number of differentiated retinal ganglion cells as determined by microtubule-associated protein-2 labeling was significantly increased following exposure to low but not higher doses of glutamate. The effect of glutamate on the metabolic activity and differentiation was blocked by tetrodotoxin. The results of the present study shows that glutamate has a significant effect on survival, differentiation and metabolic activity. An increase in the metabolic activity indicates an enhancement in the electrical activity. Thus, our results are consistent with the hypothesis that glutamate is critically involved in the regulation of electrical activity in developing rat retinal ganglion cells. JF - Neuroscience AU - Govindaiah AU - Shankaranarayana Rao, B S AU - Raju, T R AD - Department of Neurophysiology, National Institute of Mental Health and Neurosciences, P.O. Box 2900, Hosur Road, 560029, Bangalore, India. Y1 - 2002 PY - 2002 DA - 2002 SP - 547 EP - 553 VL - 113 IS - 3 SN - 0306-4522, 0306-4522 KW - Microtubule-Associated Proteins KW - 0 KW - Glutamic Acid KW - 3KX376GY7L KW - Tetrodotoxin KW - 4368-28-9 KW - Electron Transport Complex IV KW - EC 1.9.3.1 KW - Index Medicus KW - Rats KW - Animals, Newborn KW - Animals KW - Cell Survival -- drug effects KW - Cell Count KW - Rats, Wistar KW - Cell Culture Techniques KW - Tetrodotoxin -- pharmacology KW - Cell Differentiation -- drug effects KW - Immunohistochemistry KW - Retinal Ganglion Cells -- metabolism KW - Microtubule-Associated Proteins -- metabolism KW - Retinal Ganglion Cells -- enzymology KW - Glutamic Acid -- metabolism KW - Retinal Ganglion Cells -- drug effects KW - Electron Transport Complex IV -- metabolism KW - Glutamic Acid -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71979730?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Enhanced+metabolic+activity+coincides+with+survival+and+differentiation+of+cultured+rat+retinal+ganglion+cells+exposed+to+glutamate.&rft.au=Govindaiah%3BShankaranarayana+Rao%2C+B+S%3BRaju%2C+T+R&rft.aulast=Govindaiah&rft.aufirst=&rft.date=2002-01-01&rft.volume=113&rft.issue=3&rft.spage=547&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-13 N1 - Date created - 2002-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A method to identify and simultaneously determine the relative quantities of proteins isolated by gel electrophoresis. AN - 71927314; 12125017 AB - Gel electrophoresis is often used for the primary analysis and purification of proteins, and peptide mapping by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a widely used technique for the rapid identification of unknown proteins. The identification is usually obtained by digesting the protein with an enzyme and matching the masses of the proteolytic peptides with those of each protein in a sequence database. Another important aspect in many proteomic experiments is the determination of the relative protein quantities (e.g. comparison between control and altered states). Usually, this is obtained by comparing the spot intensities of two independent gels. This procedure is time-consuming and not very accurate. Recently, several methodologies using isotope labeling of proteins for quantitative proteomic studies have been introduced (e.g. using ICAT reagents or growing cells in isotopically enriched nutrients). However, none of these methodologies is foolproof and there is still the need for simple and inexpensive alternatives for determining the relative quantities of proteins. Previously, we showed that a mixture of acrylamide and deuterated acrylamide could be used as cysteine alkylating reagent prior to electrophoresis, improving the coverage and the confidence of the protein identification procedure (Sechi S, Chait BT. Anal. Chem. 1998; 70: 5150). Here we show that a similar approach can be used to obtain relative quantitation at the femtomole level of proteins isolated by gel electrophoresis. Deuterated acrylamide is used to alkylate the cysteines in one sample and regular acrylamide is used to alkylate the cysteines in the second sample. The two samples are then mixed together in a 1:1 ratio and the relative protein quantities are determined from the ion intensity ratios of the two cysteine-containing peptides isotopic envelopes (regular/deuterated). The analysis of several proteins mixed in different ratios is reported showing that this approach can reliably be used for protein identification and quantification. Briefly, a simple and inexpensive method for quantifying and simultaneously identifying proteins isolated by gel electrophoresis using MALDI-MS is presented. JF - Rapid communications in mass spectrometry : RCM AU - Sechi, Salvatore AD - National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 6707 Democracy Blvd, Rm 611, Bethesda, MD 20892-5460, USA. Salvatore_Sechi@nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 1416 EP - 1424 VL - 16 IS - 15 SN - 0951-4198, 0951-4198 KW - Alkylating Agents KW - 0 KW - Indicators and Reagents KW - Protein Hydrolysates KW - Proteins KW - Trypsin KW - EC 3.4.21.4 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Trypsin -- chemistry KW - Cysteine -- chemistry KW - Electrophoresis, Polyacrylamide Gel KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Protein Hydrolysates -- chemistry KW - Alkylation KW - Proteins -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71927314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Rapid+communications+in+mass+spectrometry+%3A+RCM&rft.atitle=A+method+to+identify+and+simultaneously+determine+the+relative+quantities+of+proteins+isolated+by+gel+electrophoresis.&rft.au=Sechi%2C+Salvatore&rft.aulast=Sechi&rft.aufirst=Salvatore&rft.date=2002-01-01&rft.volume=16&rft.issue=15&rft.spage=1416&rft.isbn=&rft.btitle=&rft.title=Rapid+communications+in+mass+spectrometry+%3A+RCM&rft.issn=09514198&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-13 N1 - Date created - 2002-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Xenobiotic export pumps, endothelin signaling, and tubular nephrotoxicants--a case of molecular hijacking. AN - 71900039; 12112711 AB - This article is a review on recent studies in intact renal proximal tubules that link tubular nephrotoxicants with endothelin (ET) regulation of xenobiotic export pump function. The data show that transport on p-glycoprotein and Mrp2 decreases rapidly when ET signals through an ET(B) receptor, NO synthase (NOS), and protein kinase C (PKC). Surprisingly, nephrotoxicants, such as radiocontrast agents, aminoglycoside antibiotics, and heavy metal salts, "hijack" this signaling pathway, causing ET release from the tubules, hormone binding to its receptor, activation of NOS and PKC, and reduced xenobiotic transport. These findings suggest a new common mechanism by which nephrotoxicants may act to disrupt renal tubular function. Copyright 2002 Wiley Periodicals, Inc. JF - Journal of biochemical and molecular toxicology AU - Miller, David S AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. miller@niehs.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 121 EP - 127 VL - 16 IS - 3 SN - 1095-6670, 1095-6670 KW - Endothelins KW - 0 KW - Fluoresceins KW - Membrane Transport Proteins KW - Multidrug Resistance-Associated Proteins KW - P-Glycoprotein KW - Receptor, Endothelin B KW - Receptors, Endothelin KW - Xenobiotics KW - Nitric Oxide KW - 31C4KY9ESH KW - multidrug resistance-associated protein 2 KW - 4AF605U6JN KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcium KW - SY7Q814VUP KW - multidrug resistance-associated protein 1 KW - Y49M64GZ4Q KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Protein Kinase C -- metabolism KW - Calcium -- metabolism KW - Animals KW - P-Glycoprotein -- metabolism KW - Killifishes KW - Multidrug Resistance-Associated Proteins -- drug effects KW - Signal Transduction -- drug effects KW - Nitric Oxide -- metabolism KW - Xenobiotics -- pharmacokinetics KW - Endothelins -- metabolism KW - Methotrexate -- analogs & derivatives KW - Fluoresceins -- toxicity KW - Kidney Tubules, Proximal -- metabolism KW - Kidney Tubules, Proximal -- drug effects KW - Receptors, Endothelin -- drug effects KW - Biological Transport -- physiology KW - Methotrexate -- toxicity KW - Biological Transport -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71900039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+biochemical+and+molecular+toxicology&rft.atitle=Xenobiotic+export+pumps%2C+endothelin+signaling%2C+and+tubular+nephrotoxicants--a+case+of+molecular+hijacking.&rft.au=Miller%2C+David+S&rft.aulast=Miller&rft.aufirst=David&rft.date=2002-01-01&rft.volume=16&rft.issue=3&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Journal+of+biochemical+and+molecular+toxicology&rft.issn=10956670&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-03 N1 - Date created - 2002-07-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Administration of either anti-CD40 or interleukin-12 following lethal total body irradiation induces acute lethal toxicity affecting the gut. AN - 71885105; 12108917 AB - Interleukin (IL)-12 and antibodies against CD40 have demonstrated antitumor effects in a variety of in vivo model systems. However, both agents can also mediate significant toxicities either when used following lethal TBI or when administered in combination with other agents such as IL-2. In this study, we assessed the effects of anti-CD40 monoclonal antibody (MoAb) and IL-12 in lethally irradiated mice. Acute lethal toxicity was observed following the administration of either 10 microg anti-CD40 MoAb (FGK45) or 0.5 microg of recombinant murine (rm)IL-12 that resulted in 100% mortality of all mice within 4 to 6 days. Histological evaluation revealed destruction of the normal gut architecture in both anti-CD40 MoAb- and rmIL-12-treated mice. Analysis of serum cytokine levels in the lethally irradiated mice receiving anti-CD40 MoAb demonstrated a marked increase of interferon (IFN)-gamma and IL-12 p40, whereas mice receiving rmIL-12 demonstrated a marked increase of IFN-gamma. Lethally irradiated IL-12 p40 knock-out mice were resistant to anti-CD40-induced toxicity, suggesting that the lack of IL-12 p40 with no possibility of making functional IL- 12 p70 is key for this toxic reaction. Similarly, lethally irradiated IFN-gamma knock-out mice were completely resistant to rmIL-12-induced toxicity, suggesting that IFN-gamma is a major player in IL-12-mediated toxicity. These results suggest that both anti-CD40 MoAb and rmIL-12 induce an acute fatal toxicity characterized by similar intestinal pathology and mediated in part by IFN-gamma. JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation AU - Hixon, Julie A AU - Anver, Miriam R AU - Blazar, Bruce R AU - Panoskaltsis-Mortari, Angela AU - Wiltrout, Robert H AU - Murphy, William J AD - SAIC-Frederick, NCI-Frederick, Maryland 21702, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 316 EP - 325 VL - 8 IS - 6 SN - 1083-8791, 1083-8791 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD40 KW - Interleukin-12 Subunit p40 KW - Protein Subunits KW - Interleukin-12 KW - 187348-17-0 KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Acute Disease KW - Animals KW - Interferon-gamma -- genetics KW - Survival Rate KW - Combined Modality Therapy -- mortality KW - Protein Subunits -- physiology KW - Interferon-gamma -- pharmacology KW - Mice KW - Protein Subunits -- blood KW - Interferon-gamma -- blood KW - Female KW - Mice, Knockout KW - Whole-Body Irradiation -- mortality KW - Antibodies, Monoclonal -- toxicity KW - Intestinal Diseases -- chemically induced KW - Interleukin-12 -- physiology KW - Interleukin-12 -- blood KW - Interleukin-12 -- toxicity KW - Antigens, CD40 -- immunology KW - Antibodies, Monoclonal -- administration & dosage KW - Intestinal Diseases -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71885105?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biology+of+blood+and+marrow+transplantation+%3A+journal+of+the+American+Society+for+Blood+and+Marrow+Transplantation&rft.atitle=Administration+of+either+anti-CD40+or+interleukin-12+following+lethal+total+body+irradiation+induces+acute+lethal+toxicity+affecting+the+gut.&rft.au=Hixon%2C+Julie+A%3BAnver%2C+Miriam+R%3BBlazar%2C+Bruce+R%3BPanoskaltsis-Mortari%2C+Angela%3BWiltrout%2C+Robert+H%3BMurphy%2C+William+J&rft.aulast=Hixon&rft.aufirst=Julie&rft.date=2002-01-01&rft.volume=8&rft.issue=6&rft.spage=316&rft.isbn=&rft.btitle=&rft.title=Biology+of+blood+and+marrow+transplantation+%3A+journal+of+the+American+Society+for+Blood+and+Marrow+Transplantation&rft.issn=10838791&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-02 N1 - Date created - 2002-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mitochondrial DNA alterations in cancer. AN - 71877386; 12094550 AB - A number of studies have demonstrated the presence of mitochondrial DNA (mtDNA) mutations in cancer cells. In this article, we review mitochondrial genomic aberrations reported in solid tumors of the breast, colon, stomach, liver, kidney, bladder, head/neck, and lung. The tantalizing association of tumors with mtDNA mutations implicates these mutations in the process of carcinogenesis. Alterations in expression of mtDNA transcripts in a variety of cancer types are also reviewed. In solid tumors, elevated expression of mtDNA-genes coding for subunits of the mitochondrial electron respiratory chain may reflect mitochondrial adaptation to perturbations in cellular energy requirements. The role of mtDNA mutations and altered expression of mitochondrial genes in carcinogenesis is discussed. Mitochondrial DNA mutations can initiate a cascade of events leading to a continuous increase in the production of reactive oxygen species (persistent oxidative stress), a condition that probably favors tumor development. JF - Cancer investigation AU - Copeland, William C AU - Wachsman, Joseph T AU - Johnson, F M AU - Penta, John S AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA. copelan1@niehs.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 557 EP - 569 VL - 20 IS - 4 SN - 0735-7907, 0735-7907 KW - DNA, Mitochondrial KW - 0 KW - Reactive Oxygen Species KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Humans KW - Electron Transport -- genetics KW - Mutation KW - Neoplasms -- genetics KW - Neoplasms -- metabolism KW - DNA, Mitochondrial -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71877386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Crime%2C+Law+and+Social+Change&rft.atitle=From+dispersed+to+monopolized+violence%3A+expansion+and+consolidation+of+the+Primeiro+Comando+da+Capital%27s+Hegemony+in+S%C3%A3o+Paulo%27s+prisons&rft.au=Dias%2C+Camila+Nunes%3BDarke%2C+Sacha&rft.aulast=Dias&rft.aufirst=Camila&rft.date=2016-04-01&rft.volume=65&rft.issue=3&rft.spage=213&rft.isbn=&rft.btitle=&rft.title=Crime%2C+Law+and+Social+Change&rft.issn=09254994&rft_id=info:doi/10.1007%2Fs10611-015-9578-2 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-19 N1 - Date created - 2002-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Changes in basal and cocaine-evoked extracellular dopamine uptake and release in the rat nucleus accumbens during early abstinence from cocaine: quantitative determination under transient conditions. AN - 71871840; 12088750 AB - Despite an abundance of studies on mechanisms of behavioral sensitization, considerable uncertainty exists as to whether alterations in dopamine neurotransmission underlie the exacerbated behavioral effects of cocaine observed during the early stages of abstinence. One of the factors contributing to the uncertainty and controversy may be the limitations in utilized measurement techniques (mostly conventional microdialysis). The techniques of quantitative microdialysis under transient conditions and rotating disk electrode voltammetry were used to characterize basal dopamine dynamics as well as time-related changes in extracellular dopamine concentrations and dopamine uptake that occur in response to an acute drug challenge in control animals and animals with previous history of cocaine. Basal extracellular dopamine concentrations were unaltered on abstinence day 3 from repeated cocaine administration (5 days, 20 mg/kg, i.p.). The extraction fraction of dopamine, an indirect measure of dopamine uptake, was significantly lower in cocaine-sensitized animals relative to controls. These two facts, taken together, suggest that basal dopamine release is depressed in cocaine-sensitized animals on abstinence day 3. At the same time, a cocaine challenge decreased the extraction fraction and increased the extracellular dopamine concentration in both experimental groups. The magnitude of the increase in extracellular dopamine concentration was greater in cocaine-sensitized animals, while the ability of cocaine to decrease the extraction fraction was unaltered, suggesting that the increase in extracellular dopamine concentration reflects an increase in drug-evoked dopamine release. Moreover, cocaine-pretreated rats demonstrated greater depolarization-induced dopamine release and the ability of dopamine D(2) receptor agonist, quinpirole, to inhibit release was decreased in these animals. These data demonstrate that a cocaine treatment regimen resulting in behavioral sensitization is associated with a reduction in basal dopamine release, an enhancement in both cocaine and K(+)-evoked dopamine release, and a subsensitivity of dopamine D(2) autoreceptors that regulate dopamine release in the nucleus accumbens. JF - Neuroscience AU - Chefer, V I AU - Shippenberg, T S AD - Integrative Neuroscience Unit, Behavioral Neuroscience Laboratory, NIH/NIDA Intramural Research Program, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. vchefer@intra.nida.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 907 EP - 919 VL - 112 IS - 4 SN - 0306-4522, 0306-4522 KW - Dopamine Uptake Inhibitors KW - 0 KW - Street Drugs KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Microdialysis KW - Animals KW - Rats, Sprague-Dawley KW - Street Drugs -- pharmacology KW - Extracellular Space -- metabolism KW - Time Factors KW - Male KW - Substance Withdrawal Syndrome -- metabolism KW - Nucleus Accumbens -- drug effects KW - Nucleus Accumbens -- metabolism KW - Dopamine -- metabolism KW - Cocaine -- pharmacology KW - Cocaine -- metabolism KW - Dopamine Uptake Inhibitors -- metabolism KW - Dopamine Uptake Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71871840?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Changes+in+basal+and+cocaine-evoked+extracellular+dopamine+uptake+and+release+in+the+rat+nucleus+accumbens+during+early+abstinence+from+cocaine%3A+quantitative+determination+under+transient+conditions.&rft.au=Chefer%2C+V+I%3BShippenberg%2C+T+S&rft.aulast=Chefer&rft.aufirst=V&rft.date=2002-01-01&rft.volume=112&rft.issue=4&rft.spage=907&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-03 N1 - Date created - 2002-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transgenic shuttle vector assays for determining genetic differences in oxidative B cell mutagenesis in vivo. AN - 71844494; 12078516 JF - Methods in enzymology AU - Felix, Klaus AU - Rockwood, Lynne D AU - Janz, Siegfried AD - Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 434 EP - 448 VL - 353 SN - 0076-6879, 0076-6879 KW - Index Medicus KW - Animals KW - Plasmacytoma -- genetics KW - Plasmids -- genetics KW - Plasmacytoma -- pathology KW - Mice KW - Oxidative Stress KW - Transgenes -- genetics KW - Mutagenesis -- genetics KW - Genetic Vectors -- genetics KW - B-Lymphocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71844494?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=Transgenic+shuttle+vector+assays+for+determining+genetic+differences+in+oxidative+B+cell+mutagenesis+in+vivo.&rft.au=Felix%2C+Klaus%3BRockwood%2C+Lynne+D%3BJanz%2C+Siegfried&rft.aulast=Felix&rft.aufirst=Klaus&rft.date=2002-01-01&rft.volume=353&rft.issue=&rft.spage=434&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-13 N1 - Date created - 2002-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Detection and affinity purification of oxidant-sensitive proteins using biotinylated glutathione ethyl ester. AN - 71844347; 12078486 JF - Methods in enzymology AU - Sullivan, Daniel M AU - Levine, Rodney L AU - Finkel, Toren AD - Laboratory of Molecular Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 101 EP - 113 VL - 353 SN - 0076-6879, 0076-6879 KW - Annexin A2 KW - 0 KW - Neoplasm Proteins KW - Oxidants KW - Proteins KW - glutathione diethyl ester KW - 97451-40-6 KW - Peroxidases KW - EC 1.11.1.- KW - PRDX3 protein, human KW - EC 1.11.1.15 KW - Peroxiredoxin III KW - Peroxiredoxins KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Oxidation-Reduction KW - Peroxidases -- isolation & purification KW - Annexin A2 -- isolation & purification KW - HeLa Cells KW - Humans KW - Annexin A2 -- metabolism KW - Protein Binding KW - Peroxidases -- metabolism KW - Proteins -- isolation & purification KW - Glutathione -- metabolism KW - Glutathione -- chemistry KW - Oxidants -- metabolism KW - Proteins -- metabolism KW - Glutathione -- analogs & derivatives KW - Biotinylation KW - Chromatography, Affinity -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71844347?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=Detection+and+affinity+purification+of+oxidant-sensitive+proteins+using+biotinylated+glutathione+ethyl+ester.&rft.au=Sullivan%2C+Daniel+M%3BLevine%2C+Rodney+L%3BFinkel%2C+Toren&rft.aulast=Sullivan&rft.aufirst=Daniel&rft.date=2002-01-01&rft.volume=353&rft.issue=&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-13 N1 - Date created - 2002-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional analysis of cell adhesion: quantitation of cell-matrix attachment. AN - 71827570; 12070999 JF - Methods in cell biology AU - Akiyama, Steven K AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 281 EP - 296 VL - 69 SN - 0091-679X, 0091-679X KW - Extracellular Matrix Proteins KW - 0 KW - Index Medicus KW - Cells, Cultured KW - Protein Binding KW - Cytological Techniques KW - Extracellular Matrix Proteins -- metabolism KW - Extracellular Matrix -- metabolism KW - Cell Adhesion -- physiology KW - Cell Movement -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71827570?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+cell+biology&rft.atitle=Functional+analysis+of+cell+adhesion%3A+quantitation+of+cell-matrix+attachment.&rft.au=Akiyama%2C+Steven+K&rft.aulast=Akiyama&rft.aufirst=Steven&rft.date=2002-01-01&rft.volume=69&rft.issue=&rft.spage=281&rft.isbn=&rft.btitle=&rft.title=Methods+in+cell+biology&rft.issn=0091679X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-20 N1 - Date created - 2002-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene expression profiles derived from fine needle aspiration correlate with response to systemic chemotherapy in breast cancer. AN - 71794117; 12052255 AB - Drug resistance in breast cancer is a major obstacle to successful chemotherapy. In this study we used cDNA microarray technology to examine gene expression profiles obtained from fine needle aspiration (FNA) of primary breast tumors before and after systemic chemotherapy. Our goal was to determine the feasibility of obtaining representative expression array profiles from limited amounts of tissue and to identify those expression profiles that correlate with treatment response. Repeat presurgical FNA samples were taken from six patients who were to undergo primary surgical treatment. Additionally, a group of 10 patients who were to receive neoadjuvant chemotherapy underwent two FNAs before chemotherapy (adriamycin 60 mg/m2 and cyclophosphamide 600 mg/m2) followed by another FNA on day 21 after the first cycle. Total RNA was amplified with T7 Eberwine's procedure and labeled cDNA was hybridized onto a 7600-feature glass cDNA microarray. We identified candidate gene expression profiles that might distinguish tumors with complete response to chemotherapy from tumors that do not respond, and found that the number of genes that change after one cycle of chemotherapy was 10 times greater in the responding group than in the non-responding group. This study supports the suitability of FNA-derived cDNA microarray expression profiling of breast cancers as a comprehensive genomic approach for studying the mechanisms of drug resistance. Our findings also demonstrate the potential of monitoring post-chemotherapy changes in expression profiles as a measure of pharmacodynamic effect and suggests that these approaches might yield useful results when validated by larger studies. JF - Breast cancer research : BCR AU - Sotiriou, Christos AU - Powles, Trevor J AU - Dowsett, Mitch AU - Jazaeri, Amir A AU - Feldman, Andrew L AU - Assersohn, Laura AU - Gadisetti, Chandramouli AU - Libutti, Steven K AU - Liu, Edison T AD - Division of Clinical Sciences, Advanced Technology Center, National Cancer Institute, National Institutes of Health, Gaithersburg, USA. christos.sotiriou@bordet.be Y1 - 2002 PY - 2002 DA - 2002 SP - 1 VL - 4 IS - 3 SN - 1465-5411, 1465-5411 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Humans KW - Treatment Outcome KW - Predictive Value of Tests KW - Doxorubicin -- administration & dosage KW - Biopsy, Needle KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Female KW - Breast Neoplasms -- genetics KW - Breast Neoplasms -- drug therapy KW - Breast Neoplasms -- pathology KW - Drug Resistance, Neoplasm -- genetics KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Oligonucleotide Array Sequence Analysis -- standards KW - Gene Expression Profiling -- standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71794117?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Breast+cancer+research+%3A+BCR&rft.atitle=Gene+expression+profiles+derived+from+fine+needle+aspiration+correlate+with+response+to+systemic+chemotherapy+in+breast+cancer.&rft.au=Sotiriou%2C+Christos%3BPowles%2C+Trevor+J%3BDowsett%2C+Mitch%3BJazaeri%2C+Amir+A%3BFeldman%2C+Andrew+L%3BAssersohn%2C+Laura%3BGadisetti%2C+Chandramouli%3BLibutti%2C+Steven+K%3BLiu%2C+Edison+T&rft.aulast=Sotiriou&rft.aufirst=Christos&rft.date=2002-01-01&rft.volume=31&rft.issue=1&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=Journal+of+Housing+and+the+Built+Environment&rft.issn=15664910&rft_id=info:doi/10.1007%2Fs10901-015-9448-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-28 N1 - Date created - 2002-06-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nat Biotechnol. 2000 Apr;18(4):457-9 [10748532] Science. 1999 Oct 15;286(5439):531-7 [10521349] Trends Cell Biol. 2000 Sep;10(9):369-77 [10932094] Gynecol Oncol. 2001 Jan;80(1):67-73 [11136572] J Virol. 2001 Feb;75(3):1220-8 [11152495] Cancer. 2000 Dec 1;89(11):2145-52 [11147583] Cancer Res. 2001 Aug 15;61(16):5979-84 [11507038] Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10869-74 [11553815] J Mol Diagn. 2002 Feb;4(1):30-6 [11826185] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3010-4 [1557406] Control Clin Trials. 1993 Aug;14(4):266-85 [8365193] Lancet. 1997 Mar 22;349(9055):849 [9121265] Adv Cancer Res. 1997;71:241-319 [9111868] Leuk Res. 1998 Jul;22(7):619-24 [9680112] Lancet. 1998 Sep 19;352(9132):930-42 [9752815] Biochem Pharmacol. 1998 Aug 15;56(4):451-7 [9763220] Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8 [9843981] Int J Mol Med. 1998 Feb;1(2):491-4 [9852255] Jpn J Cancer Res. 1999 Jan;90(1):108-15 [10076573] Breast Cancer Res Treat. 1999 Apr;54(3):235-44 [10445422] J Clin Oncol. 1999 Oct;17(10):3058-63 [10506600] Proc Natl Acad Sci U S A. 2000 May 23;97(11):5768-72 [10811891] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Numb modifies neuronal vulnerability to amyloid beta-peptide in an isoform-specific manner by a mechanism involving altered calcium homeostasis: implications for neuronal death in Alzheimer's disease. AN - 71705770; 12025816 AB - Increased production of neurotoxic forms of amyloid beta-peptide (Abeta) and abnormalities in neuronal calcium homeostasis play central roles in the pathogenesis of Alzheimer's disease (AD). Notch, a membrane receptor that controls cell-fate decisions during development of the nervous system, has been linked to AD because it is a substrate for the gamma-secretase enzyme activity that involves the presenilin-1 (PS1) protein in which mutations cause early-onset inherited AD. The actions of Notch can be antagonized by Numb, an evolutionarily conserved protein that exists in four isoforms that differ in two functional domains: a phosphotyrosine-binding (PTB) domain and a proline-rich region (PRR). We now report that Numb isoforms containing a short PTB domain increase the vulnerability of PC12 cells to death induced by Abeta1-42 and by 4-hydroxynonenal, a lipid peroxidation product previously shown to mediate neurotoxic effects of Abeta. Dysregulation of cellular calcium homeostasis occurs in cells expressing Numb isoforms with a short PTB domain, and the death-promoting effect of Numb is abolished by pharmacological inhibition of calcium release. The levels of Numb are increased in cultured primary hippocampal neurons exposed to Abeta, suggesting a role for endogenous Numb in the neuronal death process. Furthermore, higher levels of Numb were detected in the cortex of mice expressing mutant amyloid precursor protein (APP) relative to age-matched wild-type mice. Our data identify a novel isoform-specific effect of Numb on neuronal life and death cell fate decisions potentially relevant to the pathogenesis of AD. Our findings also suggest that the effects of Numb on cell fate decisions, both during development of the nervous system and in neurodegenertive disorders, are mediated by changes in cellular calcium homeostasis. JF - Neuromolecular medicine AU - Chan, Sic L AU - Pedersen, Ward A AU - Zhu, Hiayan AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, MD 21224, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 55 EP - 67 VL - 1 IS - 1 SN - 1535-1084, 1535-1084 KW - Amyloid beta-Peptides KW - 0 KW - Membrane Proteins KW - Nerve Tissue Proteins KW - Numb protein, mouse KW - Protein Isoforms KW - Recombinant Proteins KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Alzheimer Disease -- genetics KW - Alzheimer Disease -- physiopathology KW - Disease Models, Animal KW - Mice KW - Protein Isoforms -- pharmacology KW - Mice, Transgenic KW - Homeostasis -- physiology KW - Homeostasis -- drug effects KW - Rats KW - Mice, Mutant Strains KW - Transfection KW - Recombinant Proteins -- metabolism KW - Cells, Cultured KW - Cell Death KW - Mice, Inbred C57BL KW - Male KW - PC12 Cells KW - Nerve Tissue Proteins -- physiology KW - Calcium -- metabolism KW - Hippocampus -- physiology KW - Neurons -- drug effects KW - Amyloid beta-Peptides -- pharmacology KW - Hippocampus -- pathology KW - Neurons -- pathology KW - Membrane Proteins -- physiology KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71705770?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Family+Violence&rft.atitle=Racial+Minority+Women+and+Criminal+Justice+Responses+to+Domestic+Violence&rft.au=Tam%2C+Dora+M%3B+Y%3BTutty%2C+Leslie+M%3BZhuang%2C+Ze+Hong%3BPaz%2C+Eva&rft.aulast=Tam&rft.aufirst=Dora+M%3B&rft.date=2016-05-01&rft.volume=31&rft.issue=4&rft.spage=527&rft.isbn=&rft.btitle=&rft.title=Journal+of+Family+Violence&rft.issn=08857482&rft_id=info:doi/10.1007%2Fs10896-015-9794-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-14 N1 - Date created - 2002-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disruption of neurogenesis in the subventricular zone of adult mice, and in human cortical neuronal precursor cells in culture, by amyloid beta-peptide: implications for the pathogenesis of Alzheimer's disease. AN - 71705422; 12025858 AB - The adult mammalian brain contains populations of stem cells that can proliferate and then differentiate into neurons or glia. The highest concentration of such neural progenitor cells (NPC) is located in the subventricular zone (SVZ) and these cells can produce new olfactory bulb and cerebral cortical neurons. NPC may provide a cellular reservoir for replacement of cells lost during normal cell turnover and after brain injury. However, neurogenesis does not compensate for neuronal loss in age-related neurodegenerative disorders such as Alzheimer's disease (AD), suggesting the possibility that impaired neurogenesis contributes to the pathogenesis of such disorders. We now report that amyloid beta-peptide (Abeta), a self-aggregating neurotoxic protein thought to cause AD, can impair neurogenesis in the SVZ/cerebral cortex of adult mice and in human cortical NPC in culture. The proliferation and migration of NPC in the SVZ of amyloid precursor protein (APP) mutant mice, and in mice receiving an intraventricular infusion of Abeta, were greatly decreased compared to control mice. Studies of NPC neurosphere cultures derived from human embryonic cerebral cortex showed that Abeta can suppress NPC proliferation and differentiation, and can induce apoptosis. The adverse effects of Abeta on neurogenesis were associated with a disruption of calcium regulation in the NPC. Our data show that Abeta can impair cortical neurogenesis, and suggest that this adverse effect of Abeta contributes to the depletion of neurons and the resulting olfactory and cognitive deficits in AD. JF - Neuromolecular medicine AU - Haughey, Norman J AU - Liu, Dong AU - Nath, Avi AU - Borchard, Amy C AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging, Gerontology Research Center, Baltimore, MD 21224, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 125 EP - 135 VL - 1 IS - 2 SN - 1535-1084, 1535-1084 KW - Amyloid beta-Peptides KW - 0 KW - Index Medicus KW - Animals KW - Stem Cells -- cytology KW - Apoptosis KW - Cells, Cultured KW - Humans KW - Cell Differentiation KW - Mice KW - Male KW - Cell Division KW - Cerebral Cortex -- cytology KW - Amyloid beta-Peptides -- genetics KW - Brain -- cytology KW - Neurons -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71705422?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuromolecular+medicine&rft.atitle=Disruption+of+neurogenesis+in+the+subventricular+zone+of+adult+mice%2C+and+in+human+cortical+neuronal+precursor+cells+in+culture%2C+by+amyloid+beta-peptide%3A+implications+for+the+pathogenesis+of+Alzheimer%27s+disease.&rft.au=Haughey%2C+Norman+J%3BLiu%2C+Dong%3BNath%2C+Avi%3BBorchard%2C+Amy+C%3BMattson%2C+Mark+P&rft.aulast=Haughey&rft.aufirst=Norman&rft.date=2002-01-01&rft.volume=81&rft.issue=6&rft.spage=891&rft.isbn=&rft.btitle=&rft.title=GeoJournal&rft.issn=03432521&rft_id=info:doi/10.1007%2Fs10708-016-9742-y LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-14 N1 - Date created - 2002-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of selected CD34+ cells in the treatment of relapsed/progressive HD: experiences from a single center. AN - 71702199; 12006213 AB - Treatment of HD using positively selected stem cells can achieve a durable CR in almost 80% patients, with a median follow-up of 24 months. We have found the use of positive selected CD34+ cells in the treatment of relapsed/progressive HD after high-dose chemotherapy to be a safe procedure with promising results. Positively selected (CD34+) stem cells were employed for autografting in the patients with HD after high-dose chemotherapy. Between April 1996 and February 2001, 28 patients with relapsed/progressive HD were autografted with positively selected CD34+ cells at our Institute. All patients are alive and we did not observe any deaths as a result of toxicity. From this group, 22 (78.6%) patients are in durable CR, with a median follow-up of 24 months (range 7-65 months). Six (21.4%) patients relapsed but are now in CR after radiotherapy and mini-allogeneic transplantation (one patient) or radiotherapy (five patients). Autologous transplantation with positively selected CD34+ cells in relapsed HD is a safe and effective procedure in the treatment of this disease. JF - Cytotherapy AU - Lakota, J AU - Ballová, V AU - Drgona, L' AU - Durkovic, P AU - Vranovský, A AD - BMT Unit, Department of Internal Medicine, National Cancer Institute, Bratislava, Slovakia. Y1 - 2002 PY - 2002 DA - 2002 SP - 177 EP - 180 VL - 4 IS - 2 SN - 1465-3249, 1465-3249 KW - Antigens, CD34 KW - 0 KW - Index Medicus KW - Humans KW - Adult KW - Middle Aged KW - Transplantation, Autologous KW - Male KW - Female KW - Antigens, CD34 -- immunology KW - Hematopoietic Stem Cells -- immunology KW - Hematopoietic Stem Cell Transplantation KW - Hodgkin Disease -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71702199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytotherapy&rft.atitle=Use+of+selected+CD34%2B+cells+in+the+treatment+of+relapsed%2Fprogressive+HD%3A+experiences+from+a+single+center.&rft.au=Lakota%2C+J%3BBallov%C3%A1%2C+V%3BDrgona%2C+L%27%3BDurkovic%2C+P%3BVranovsk%C3%BD%2C+A&rft.aulast=Lakota&rft.aufirst=J&rft.date=2002-01-01&rft.volume=4&rft.issue=2&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Cytotherapy&rft.issn=14653249&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-19 N1 - Date created - 2002-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Measuring oxidative mtDNA damage and repair using quantitative PCR. AN - 71698555; 12013794 JF - Methods in molecular biology (Clifton, N.J.) AU - Santos, Janine H AU - Mandavilli, Bhaskar S AU - Van Houten, Bennett AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 159 EP - 176 VL - 197 SN - 1064-3745, 1064-3745 KW - DNA Primers KW - 0 KW - DNA, Mitochondrial KW - Mutagens KW - Index Medicus KW - Animals KW - Base Sequence KW - Humans KW - Oxidative Phosphorylation KW - Mutagens -- toxicity KW - Templates, Genetic KW - DNA Repair KW - DNA Damage KW - Polymerase Chain Reaction -- methods KW - DNA, Mitochondrial -- isolation & purification KW - DNA, Mitochondrial -- chemistry KW - DNA, Mitochondrial -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71698555?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.atitle=making+feminist+sense+of+no-platforming&rft.au=O%27keefe%2C+Theresa&rft.aulast=O%27keefe&rft.aufirst=Theresa&rft.date=2016-07-01&rft.volume=&rft.issue=113&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Feminist+Review&rft.issn=01417789&rft_id=info:doi/10.1057%2Ffr.2016.7 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-20 N1 - Date created - 2002-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Measuring mtDNA mutation rates in Saccharomyces cerevisiae using the mtArg8 assay. AN - 71697791; 12013793 JF - Methods in molecular biology (Clifton, N.J.) AU - Strand, Micheline K AU - Copeland, William C AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 151 EP - 157 VL - 197 SN - 1064-3745, 1064-3745 KW - DNA, Fungal KW - 0 KW - DNA, Mitochondrial KW - Indicators and Reagents KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Gene Expression Regulation, Fungal KW - Base Sequence KW - DNA Repair KW - Point Mutation KW - DNA, Fungal -- genetics KW - Amino Acid Sequence KW - DNA Replication KW - Saccharomyces cerevisiae -- genetics KW - Saccharomyces cerevisiae -- growth & development KW - Mutation KW - DNA, Mitochondrial -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71697791?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.atitle=Measuring+mtDNA+mutation+rates+in+Saccharomyces+cerevisiae+using+the+mtArg8+assay.&rft.au=Strand%2C+Micheline+K%3BCopeland%2C+William+C&rft.aulast=Strand&rft.aufirst=Micheline&rft.date=2002-01-01&rft.volume=197&rft.issue=&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.issn=10643745&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-20 N1 - Date created - 2002-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term alpha-tocopherol supplementation is associated with lower serum vascular endothelial growth factor levels. AN - 71687764; 12017317 AB - We previously reported that daily supplementation with alpha-tocopherol reduced prostate cancer risk in a large, randomized trial, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. One potential mechanism explaining this is that alpha-tocopherol inhibited tumor angiogenesis, an effect demonstrated in animal models. We evaluated whether long-term supplementation with alpha-tocopherol modified serum vascular endothelial growth factor (VEGF) levels, a cytokine integrally involved in angiogenesis, in men who were not diagnosed with cancer and had baseline and follow-up blood available. One hundred of these men who received alpha-tocopherol (50 mg daily) were randomly selected and matched on age, study center and time between blood draws to 100 men who received placebo (median follow-up 3.7 years). VEGF levels were measured by enzyme-linked immunosorbent assay. The effect of alpha-tocopherol supplementation on serum VEGF was evaluated using a matched-paired t-test for differences in the change in VEGF over the intervention period between groups. There was an 11% reduction in VEGF levels in the alpha-tocopherol group as compared with a 10% increase in the placebo group (p=0.03). Our findings suggest that one of the mechanisms behind the inhibition of prostate carcinogenesis by alpha-tocopherol in the ATBC Study may have been through reduced VEGF concentrations and the suppression of tumor angiogenesis and therefore growth. JF - Anticancer research AU - Woodson, Karen AU - Triantos, Spyros AU - Hartman, Terryl AU - Taylor, Philip R AU - Virtamo, Jarmo AU - Albanes, Demetrius AD - Cancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. kw114v@nih.gov PY - 2002 SP - 375 EP - 378 VL - 22 IS - 1A SN - 0250-7005, 0250-7005 KW - Antioxidants KW - 0 KW - Endothelial Growth Factors KW - Lymphokines KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - alpha-Tocopherol KW - H4N855PNZ1 KW - Index Medicus KW - Randomized Controlled Trials as Topic KW - Drug Administration Schedule KW - Smoking -- blood KW - Humans KW - Cohort Studies KW - Alcohol Drinking -- blood KW - Aged KW - Middle Aged KW - Male KW - alpha-Tocopherol -- pharmacology KW - Lymphokines -- blood KW - alpha-Tocopherol -- administration & dosage KW - Antioxidants -- pharmacology KW - Dietary Supplements KW - Endothelial Growth Factors -- blood KW - Antioxidants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71687764?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Long-term+alpha-tocopherol+supplementation+is+associated+with+lower+serum+vascular+endothelial+growth+factor+levels.&rft.au=Woodson%2C+Karen%3BTriantos%2C+Spyros%3BHartman%2C+Terryl%3BTaylor%2C+Philip+R%3BVirtamo%2C+Jarmo%3BAlbanes%2C+Demetrius&rft.aulast=Woodson&rft.aufirst=Karen&rft.date=2002-01-01&rft.volume=22&rft.issue=1A&rft.spage=375&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-25 N1 - Date created - 2002-05-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reversal of multidrug resistance: lessons from clinical oncology. AN - 71652731; 11990784 AB - Modulation of P glycoprotein (Pgp) in clinical oncology has had limited success. Contributing factors have included the limitation in our understanding of the tumours in which Pgp overexpression is mechanistically important in clinical drug resistance; the failure to prove that concentrations of modulators achieved in patients were sufficient to inhibit Pgp; and the inability to conclusively prove that Pgp modulation was occurring in tumours in patients. New approaches are needed to determine the clinical settings in which Pgp overexpression plays a major role in resistance. (Clinical trials with third generation modulators are ongoing, including trials with the compounds LY335979, R101933 and XR9576. Using the Pgp substrate Tc-99m Sestamibi as an imaging agent, increased uptake has been seen in normal liver and kidney after administration of PSC 833, VX710 and XR9576. These studies confirm that the concentrations of modulator achieved in patients are able to increase uptake of a Pgp substrate. Furthermore, CD56+ cells obtained from patients treated with PSC 833 demonstrate enhanced rhodamine retention in an ex vivo assay after administration of the antagonist. Finally, a subset of patients treated with Pgp antagonists show enhanced Sestamibi retention in imaged tumours. These results suggest that Pgp modulators can increase drug accumulation in Pgp-expressing tumours and normal tissues in patients. Using third generation Pgp antagonists and properly designed clinical trials, it should be possible to determine the contribution of modulators to the reversal of clinical drug resistance. JF - Novartis Foundation symposium AU - Bates, Susan F AU - Chen, Clara AU - Robey, Robert AU - Kang, Min AU - Figg, William D AU - Fojo, Tito AD - Molecular Therapeutics Section, Medicine Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 83 EP - 96; discussion 96-102, 180-5 VL - 243 SN - 1528-2511, 1528-2511 KW - Antineoplastic Agents KW - 0 KW - Benzazepines KW - Cyclosporins KW - Dibenzocycloheptenes KW - Enzyme Inhibitors KW - Fluorescent Dyes KW - Neoplasm Proteins KW - P-Glycoprotein KW - Piperidines KW - Pyridines KW - Quinolines KW - Radiopharmaceuticals KW - Rhodamines KW - biricodar KW - 3KG76X4KJK KW - zosuquidar trihydrochloride KW - 813AGY3126 KW - Technetium Tc 99m Sestamibi KW - 971Z4W1S09 KW - tariquidar KW - J58862DTVD KW - laniquidar KW - K3FRN4DDOY KW - valspodar KW - Q7ZP55KF3X KW - Index Medicus KW - Radiopharmaceuticals -- pharmacokinetics KW - Animals KW - Drug Interactions KW - Benzazepines -- pharmacology KW - Tumor Cells, Cultured -- drug effects KW - Antineoplastic Agents -- pharmacokinetics KW - Humans KW - Cyclosporins -- therapeutic use KW - Pyridines -- therapeutic use KW - Tissue Distribution KW - Radionuclide Imaging KW - Genes, MDR KW - Mice, Knockout KW - Piperidines -- therapeutic use KW - Neoplasms -- diagnostic imaging KW - Fluorescent Dyes -- pharmacokinetics KW - Rhodamines -- pharmacokinetics KW - Neoplasms -- drug therapy KW - Tumor Cells, Cultured -- metabolism KW - Quinolines -- therapeutic use KW - Clinical Trials as Topic KW - Mice KW - Cyclosporins -- pharmacology KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Piperidines -- pharmacology KW - Quinolines -- pharmacology KW - Technetium Tc 99m Sestamibi -- pharmacokinetics KW - Dibenzocycloheptenes -- pharmacology KW - Benzazepines -- therapeutic use KW - Dibenzocycloheptenes -- therapeutic use KW - Pyridines -- pharmacology KW - Neoplasms -- metabolism KW - P-Glycoprotein -- physiology KW - Enzyme Inhibitors -- therapeutic use KW - Neoplasm Proteins -- physiology KW - Neoplasm Proteins -- antagonists & inhibitors KW - Drug Resistance, Multiple -- physiology KW - Neoplasm Proteins -- deficiency KW - Enzyme Inhibitors -- pharmacology KW - Drug Resistance, Neoplasm -- physiology KW - P-Glycoprotein -- deficiency KW - P-Glycoprotein -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71652731?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Novartis+Foundation+symposium&rft.atitle=Reversal+of+multidrug+resistance%3A+lessons+from+clinical+oncology.&rft.au=Bates%2C+Susan+F%3BChen%2C+Clara%3BRobey%2C+Robert%3BKang%2C+Min%3BFigg%2C+William+D%3BFojo%2C+Tito&rft.aulast=Bates&rft.aufirst=Susan&rft.date=2002-01-01&rft.volume=243&rft.issue=&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Novartis+Foundation+symposium&rft.issn=15282511&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-04 N1 - Date created - 2002-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of cyclooxygenase inhibitors in cancer prevention. AN - 71591075; 11945150 AB - Carcinogenesis results from the long-term accumulation of genetic and epigenetic aberrations at the molecular level, which are under constant selection pressure for growth advantage. Recognizing that cancer is the result of this long-term, multi-step process provides opportunities for molecularly targeted cancer prevention. Ideally, chemopreventive agents should be low in toxicity, morbidity, and cost. Several individual agents and agent combinations are currently under evaluation in the U.S. National Cancer Institute s (NCI) chemoprevention agent development program. Nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit cyclooxygenase (COX) -1 and -2 are among the most promising classes of agents for targeted molecular prevention. JF - Current pharmaceutical design AU - Anderson, William F AU - Umar, Asad AU - Viner, Jaye L AU - Hawk, Ernest T AD - Gastrointestinal & Other Cancers Research Group, National Cancer Institute, Division of Cancer Prevention, EPN, Room 2141, 6130 Executive Boulevard, Bethesda, MD 20892-7317, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 1035 EP - 1062 VL - 8 IS - 12 SN - 1381-6128, 1381-6128 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Anticarcinogenic Agents KW - Cyclooxygenase 2 Inhibitors KW - Cyclooxygenase Inhibitors KW - Isoenzymes KW - Membrane Proteins KW - Cyclooxygenase 1 KW - EC 1.14.99.1 KW - Cyclooxygenase 2 KW - PTGS1 protein, human KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Index Medicus KW - Isoenzymes -- antagonists & inhibitors KW - Animals KW - Isoenzymes -- biosynthesis KW - Humans KW - Treatment Outcome KW - Clinical Trials as Topic KW - Chemoprevention KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis KW - Cyclooxygenase Inhibitors -- therapeutic use KW - Anticarcinogenic Agents -- toxicity KW - Anticarcinogenic Agents -- therapeutic use KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Cyclooxygenase Inhibitors -- toxicity KW - Anticarcinogenic Agents -- pharmacology KW - Neoplasms -- prevention & control KW - Anti-Inflammatory Agents, Non-Steroidal -- toxicity KW - Neoplasms -- metabolism KW - Cyclooxygenase Inhibitors -- pharmacology KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71591075?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+pharmaceutical+design&rft.atitle=The+role+of+cyclooxygenase+inhibitors+in+cancer+prevention.&rft.au=Anderson%2C+William+F%3BUmar%2C+Asad%3BViner%2C+Jaye+L%3BHawk%2C+Ernest+T&rft.aulast=Anderson&rft.aufirst=William&rft.date=2002-01-01&rft.volume=8&rft.issue=12&rft.spage=1035&rft.isbn=&rft.btitle=&rft.title=Current+pharmaceutical+design&rft.issn=13816128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-26 N1 - Date created - 2002-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Safety and efficacy of high-dose interleukin-2 therapy in patients with brain metastases. AN - 71568466; 11924913 AB - The authors determined the safety and efficacy of recombinant high-dose interleukin-2 administration in patients with brain metastases. This retrospective review included 1,069 patients with metastatic melanoma or renal cell carcinoma who received high-dose interleukin-2 alone or in combination with other immunotherapy or chemotherapy from July 1985-July 2000. All patients were evaluated for both toxicity and response. Only the first exposure to interleukin-2 was considered. Parameters evaluated among the groups included toxicity profiles, reasons for stopping treatment, number of interleukin-2 doses per cycle, and response to therapy. Three patient groups were compared. Group I (n = 27) comprised patients with previously treated brain metastases (surgery or radiation), group 2 (n = 37) comprised patients with untreated brain metastases, and group 3 (n = 1,005) comprised patients without brain metastases. For most comparisons between patients with brain metastases and those without, no significant differences were noted in toxicity profiles or reasons for stopping interleukin-2 therapy. Patients with previously treated brain metastases received fewer interleukin-2 doses per cycle (median, 6.5) than patients with previously untreated brain metastases (median, 7.5) or patients without brain metastases (median, 7.5). Patients with previously treated brain metastases demonstrated an 18.5% overall clinical response to interleukin-2 treatment. However, patients with evaluable (previously untreated) brain metastases had an overall 5.6% response rate, which was less than the 19.8% response rate of patients without brain metastases. Two of thirty-six patients with evaluable brain metastases demonstrated objective regression of intracranial and extracranial disease after receiving interleukin-2. Carefully selected patients with brain metastases can safely receive high-dose interleukin-2, and some can experience a response to treatment at intracranial and extracranial disease sites. JF - Journal of immunotherapy (Hagerstown, Md. : 1997) AU - Guirguis, Lisa M AU - Yang, James C AU - White, Donald E AU - Steinberg, Seth M AU - Liewehr, David J AU - Rosenberg, Steven A AU - Schwartzentruber, Douglas J AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 2002 SP - 82 EP - 87 VL - 25 IS - 1 SN - 1524-9557, 1524-9557 KW - Interleukin-2 KW - 0 KW - Index Medicus KW - Kidney Neoplasms -- pathology KW - Melanoma -- secondary KW - Humans KW - Carcinoma, Renal Cell -- secondary KW - Adult KW - Retrospective Studies KW - Middle Aged KW - Melanoma -- therapy KW - Male KW - Female KW - Interleukin-2 -- adverse effects KW - Brain Neoplasms -- therapy KW - Interleukin-2 -- therapeutic use KW - Brain Neoplasms -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71568466?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.atitle=Safety+and+efficacy+of+high-dose+interleukin-2+therapy+in+patients+with+brain+metastases.&rft.au=Guirguis%2C+Lisa+M%3BYang%2C+James+C%3BWhite%2C+Donald+E%3BSteinberg%2C+Seth+M%3BLiewehr%2C+David+J%3BRosenberg%2C+Steven+A%3BSchwartzentruber%2C+Douglas+J&rft.aulast=Guirguis&rft.aufirst=Lisa&rft.date=2002-01-01&rft.volume=25&rft.issue=1&rft.spage=82&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.issn=15249557&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-18 N1 - Date created - 2002-04-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Clin Oncol. 1999 Mar;17(3):968-75 [10071291] J Immunother. 1999 Jul;22(4):356-62 [10404437] Ann Surg. 1998 Sep;228(3):307-19 [9742914] J Natl Cancer Inst. 1993 Apr 21;85(8):622-32 [8468720] JAMA. 1994 Mar 23-30;271(12):907-13 [8120958] J Natl Cancer Inst. 1994 Aug 3;86(15):1159-66 [8028037] J Clin Oncol. 1994 Dec;12(12):2714-22 [7989949] Acta Oncol. 1997;36(2):228 [9140444] Cancer. 1998 Aug 15;83(4):797-805 [9708948] Nat Med. 1998 Mar;4(3):321-7 [9500606] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The promise and peril of surrogate end points in cancer research. AN - 71566669; 11902582 AB - Both experimental and observational studies of cancer need to have an end point. Traditionally, in aetiological and prevention studies, that end point has been the incidence of cancer itself, whereas in therapeutic trials, the end point is usually time to cancer recurrence or death. But cancer takes a long time to develop in an individual and is rare in the population. Therefore, aetiological studies and prevention trials must be large and lengthy to be meaningful. Similarly, many therapeutic trials require a long follow-up of large numbers of patients. Surrogate end points--markers of preclinical cancer or of imminent recurrence--are therefore an attractive alternative. But how can we be sure that a study with a surrogate outcome gives us the right answer about the true end point? JF - Nature reviews. Cancer AU - Schatzkin, Arthur AU - Gail, Mitchell AD - Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892-7232, USA. schatzka@mail.nih.gov Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 19 EP - 27 VL - 2 IS - 1 SN - 1474-175X, 1474-175X KW - Antigens, Neoplasm KW - 0 KW - Biomarkers KW - Growth Substances KW - Hormones KW - Index Medicus KW - Colonic Polyps -- surgery KW - Humans KW - Models, Biological KW - Growth Substances -- analysis KW - Epithelium -- pathology KW - Adenoma -- pathology KW - Male KW - Uterine Cervical Neoplasms -- virology KW - Survival Analysis KW - Uterine Cervical Neoplasms -- prevention & control KW - Hormones -- analysis KW - Adenomatous Polyps -- surgery KW - Antigens, Neoplasm -- analysis KW - Adenomatous Polyps -- pathology KW - Papillomaviridae KW - Infection -- epidemiology KW - Neoplasm Recurrence, Local -- prevention & control KW - Hyperplasia KW - Papillomavirus Infections -- therapy KW - Environmental Exposure KW - Incidence KW - Adenoma -- surgery KW - Colorectal Neoplasms -- prevention & control KW - Female KW - Colonic Polyps -- pathology KW - Neoplasms -- pathology KW - Outcome Assessment (Health Care) -- methods KW - Outcome Assessment (Health Care) -- statistics & numerical data KW - Neoplasms -- epidemiology KW - Outcome Assessment (Health Care) -- standards KW - Clinical Trials as Topic -- standards KW - Neoplasms -- prevention & control KW - Neoplasms -- therapy KW - Neoplasms -- metabolism KW - Clinical Trials as Topic -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71566669?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+reviews.+Cancer&rft.atitle=The+promise+and+peril+of+surrogate+end+points+in+cancer+research.&rft.au=Schatzkin%2C+Arthur%3BGail%2C+Mitchell&rft.aulast=Schatzkin&rft.aufirst=Arthur&rft.date=2002-01-01&rft.volume=2&rft.issue=1&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Nature+reviews.+Cancer&rft.issn=1474175X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-16 N1 - Date created - 2002-03-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Complexities of cancer research: mouse genetic models. AN - 71559079; 11917159 AB - Cancer susceptibility is a complex interaction of an individual's genetic composition and environmental exposures. Huge strides have been made in understanding cancer over the past 100 yr, from recognition of cancer as a genetic disease, to identification of specific carcinogens, isolation of oncogenes, and recognition of tumor suppressors. A tremendous amount of knowledge has accumulated about the etiology of cancer. Cancer genetics has played a significant role in these discoveries. Analysis of high-risk familial cancers has led to the discovery of new tumor suppressor genes and important cancer pathways. These families, however, represent only a small fraction of cancer in the general population. Most cancer is instead probably the result of an intricate interaction of polymorphic susceptibility genes with the sea of environmental exposures that humans experience. Although the central cadre of cancer genes is known, little is understood about the peripheral genes that likely comprise the polymorphic susceptibility loci. The challenge for cancer genetics is therefore to move forward from the mendelian genetics of the rare familial cancer syndromes into the field of quantitative trait loci, susceptibility factors, and modifier genes. By identifying the genes that modulate an individual's susceptibility to cancer after an environmental exposure, researchers will be able to gain important insights into human biology, cancer prevention, and cancer treatment. This article summarizes the current state of quantitative trait genetic analysis and the tools, both proven and theoretical, that may be used to unravel one of the great challenges in cancer genetics. JF - ILAR journal AU - Hunter, Kent W AU - Williams, Robert W AD - Laboratory of Population Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 80 EP - 88 VL - 43 IS - 2 SN - 1084-2020, 1084-2020 KW - Index Medicus KW - Pedigree KW - Gene Expression Regulation, Neoplastic KW - Animals KW - Humans KW - Chromosome Mapping KW - Neoplasms -- physiopathology KW - Disease Models, Animal KW - Mice KW - Genetic Predisposition to Disease KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71559079?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ILAR+journal&rft.atitle=Complexities+of+cancer+research%3A+mouse+genetic+models.&rft.au=Hunter%2C+Kent+W%3BWilliams%2C+Robert+W&rft.aulast=Hunter&rft.aufirst=Kent&rft.date=2002-01-01&rft.volume=43&rft.issue=2&rft.spage=80&rft.isbn=&rft.btitle=&rft.title=ILAR+journal&rft.issn=10842020&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-16 N1 - Date created - 2002-03-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mammary gland carcinogenesis by food-derived heterocyclic amines: metabolism and additional factors influencing carcinogenesis by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). AN - 71556963; 11921185 AB - The heterocyclic amines (HCAs) are a family of mutagenic/carcinogenic compounds found in cooked meats. Several HCAs are mammary gland carcinogens in rats. Of these compounds, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the major one present in the human diet. This report reviews the studies on rat mammary gland carcinogenesis by HCAs; discusses what is currently known regarding mechanisms of mammary gland carcinogenesis of PhIP, especially the significance of metabolic processing; and further highlights the evidence for the possible role of PhIP in human breast cancer. JF - Environmental and molecular mutagenesis AU - Snyderwine, Elizabeth G AD - Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, National Cancer Institute Center for Cancer Research, Bethesda, Maryland 20892, USA. elizabeth_snyderwine@nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 165 EP - 170 VL - 39 IS - 2-3 SN - 0893-6692, 0893-6692 KW - Carcinogens KW - 0 KW - Imidazoles KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Humans KW - Diet KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Imidazoles -- toxicity KW - Carcinogens -- metabolism KW - Carcinogens -- toxicity KW - Mammary Neoplasms, Animal -- metabolism KW - Mammary Neoplasms, Animal -- chemically induced KW - Mammary Neoplasms, Experimental -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71556963?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+molecular+mutagenesis&rft.atitle=Mammary+gland+carcinogenesis+by+food-derived+heterocyclic+amines%3A+metabolism+and+additional+factors+influencing+carcinogenesis+by+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine+%28PhIP%29.&rft.au=Snyderwine%2C+Elizabeth+G&rft.aulast=Snyderwine&rft.aufirst=Elizabeth&rft.date=2002-01-01&rft.volume=39&rft.issue=2-3&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Environmental+and+molecular+mutagenesis&rft.issn=08936692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-18 N1 - Date created - 2002-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective estrogen receptor modulators (SERMs) and retinoids in breast cancer chemoprevention. AN - 71556012; 11921197 AB - Tamoxifen has been shown to decrease the risk of invasive breast cancer by 49% and noninvasive breast cancer by 50%. Tamoxifen is also associated with a threefold increased risk of endometrial cancer. Raloxifene, a second-generation selective estrogen receptor modulator (SERM), has not been associated with endometrial cancer risk, and is currently under study in a large, multi-institutional, randomized Study of Tamoxifen and Raloxifene (STAR) for breast cancer prevention in postmenopausal women. A pilot trial of raloxifene in premenopausal women to assess the safety, tolerability, effects on bone mineral density, mammographic density, and other biological endpoints is ongoing. The retinoids have been shown to decrease mammary tumors in rodent carcinogenesis models. The Italian trial of fenretinide (4-HPR) in women with stage I breast cancer randomized women to fenretinide or no intervention. This study did not show an overall effect of decreasing the risk of contralateral breast cancer. However, a protective effect was suggested in premenopausal women. It has been suggested that this effect may be related to insulin-like growth factor 1 (IGF-1), which has been shown to be modulated by fenretinide in premenopausal but not postmenopausal women. Pilot studies of SERMs alone and in combination with retinoids or other agents provide a model for testing the safety and tolerability, pharmacokinetics and pharmacodynamics, and biomarker modulation in high-risk women. These studies can provide information as to both the pathophysiology of carcinogenesis and the mechanism of action of chemopreventive agents, and help select agents and doses for testing in large randomized studies. JF - Environmental and molecular mutagenesis AU - Zujewski, JoAnne AD - Medical Oncology Clinical Research Unit, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. zujewski@nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 264 EP - 270 VL - 39 IS - 2-3 SN - 0893-6692, 0893-6692 KW - Antineoplastic Agents KW - 0 KW - Receptors, Estrogen KW - Selective Estrogen Receptor Modulators KW - Tamoxifen KW - 094ZI81Y45 KW - Fenretinide KW - 187EJ7QEXL KW - Raloxifene Hydrochloride KW - 4F86W47BR6 KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Index Medicus KW - Multicenter Studies as Topic KW - Randomized Controlled Trials as Topic KW - Receptors, Estrogen -- drug effects KW - Humans KW - Insulin-Like Growth Factor I -- metabolism KW - Incidence KW - Receptors, Estrogen -- physiology KW - Female KW - Risk Assessment KW - Fenretinide -- therapeutic use KW - Tamoxifen -- therapeutic use KW - Selective Estrogen Receptor Modulators -- therapeutic use KW - Raloxifene Hydrochloride -- therapeutic use KW - Breast Neoplasms -- prevention & control KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71556012?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+molecular+mutagenesis&rft.atitle=Selective+estrogen+receptor+modulators+%28SERMs%29+and+retinoids+in+breast+cancer+chemoprevention.&rft.au=Zujewski%2C+JoAnne&rft.aulast=Zujewski&rft.aufirst=JoAnne&rft.date=2002-01-01&rft.volume=39&rft.issue=2-3&rft.spage=264&rft.isbn=&rft.btitle=&rft.title=Environmental+and+molecular+mutagenesis&rft.issn=08936692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-18 N1 - Date created - 2002-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MMTV-associated transcription factor binding sites increase nm23-H1 metastasis suppressor gene expression in human breast carcinoma cell lines. AN - 71552207; 11918081 AB - We hypothesize that elevation of nm23-HI metastasis suppressor gene expression in micrometastatic tumor cells may reduce their subsequent colonization and invasion, and induce differentiation, with a clinical benefit. This report presents the first analysis of the nm23-HI promoter to identify sites which can increase its transcription. Deletion mapping of a 2.1 kb nm23-H1 promoter fragment tethered to a reporter gene identified three regions involved in its differential expression levels among a panel of human breast carcinoma cell lines: a 195 bp NheI-XbaI fragment responsible for basal expression levels, a 248 bp AvrII-Nhel fragment which contributed to the elevated nm23-H1 expression observed in the high expressing cell lines, and a 544 bp AvrII fragment containing an inhibitory element. Examination of the 248 bp AvrII-NheI fragment revealed the unexpected presence of three transcription factor binding sites (MAF/Ets, CTF/NF1 half site and ACAAAG enhancer) previously identified in the MMTV-LTR, and in WAP and milk gene promoters, proposed to mediate mammary-specific gene expression. Mutation of the three sites, individually or together, resulted in two-fold reductions in reporter gene expression. As controls, the same panel of mutations caused a different pattern of reporter gene expression in a non-mammary cell line, and mutation of another nearby site was without effect on nm23-HI. Our data identify a complex regulatory pattern for nm23-H1 transcription, and suggest that a mammary-specific cassette of transcription factors contribute to its elevated expression JF - Clinical & experimental metastasis AU - Ouatas, Taoufik AU - Clare, Susan E AU - Hartsough, Melanie T AU - De La Rosa, Abel AU - Steeg, Patricia S AD - Women's Cancers Section, Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA. taoufik@mail.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 35 EP - 42 VL - 19 IS - 1 SN - 0262-0898, 0262-0898 KW - CCAAT-Enhancer-Binding Proteins KW - 0 KW - CTF-1 transcription factor KW - DNA, Neoplasm KW - NFI Transcription Factors KW - NM23 Nucleoside Diphosphate Kinases KW - Neoplasm Proteins KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-ets KW - Recombinant Fusion Proteins KW - Transcription Factors KW - NME1 protein, human KW - EC 2.7.4.6 KW - Nme1 protein, mouse KW - Nucleoside-Diphosphate Kinase KW - Monomeric GTP-Binding Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Humans KW - Electrophoretic Mobility Shift Assay KW - Proto-Oncogene Proteins -- metabolism KW - Transcription, Genetic KW - Organ Specificity KW - Binding Sites KW - Mutagenesis KW - Tumor Cells, Cultured KW - Polymorphism, Restriction Fragment Length KW - CCAAT-Enhancer-Binding Proteins -- metabolism KW - Enhancer Elements, Genetic -- genetics KW - Genes, Reporter KW - Consensus Sequence KW - Female KW - Sequence Deletion KW - Breast Neoplasms -- genetics KW - Neoplasm Proteins -- biosynthesis KW - Transcription Factors -- metabolism KW - Genes, Tumor Suppressor KW - Breast Neoplasms -- metabolism KW - Transcription Factors -- genetics KW - Transcription Factors -- biosynthesis KW - Monomeric GTP-Binding Proteins -- genetics KW - Mammary Tumor Virus, Mouse -- genetics KW - Gene Expression Regulation, Neoplastic KW - Terminal Repeat Sequences -- genetics KW - Neoplasm Metastasis -- genetics KW - Breast Neoplasms -- pathology KW - Carcinoma -- pathology KW - Monomeric GTP-Binding Proteins -- biosynthesis KW - Neoplasm Proteins -- genetics KW - DNA, Neoplasm -- genetics KW - Promoter Regions, Genetic -- genetics KW - Carcinoma -- metabolism KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71552207?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+%26+experimental+metastasis&rft.atitle=MMTV-associated+transcription+factor+binding+sites+increase+nm23-H1+metastasis+suppressor+gene+expression+in+human+breast+carcinoma+cell+lines.&rft.au=Ouatas%2C+Taoufik%3BClare%2C+Susan+E%3BHartsough%2C+Melanie+T%3BDe+La+Rosa%2C+Abel%3BSteeg%2C+Patricia+S&rft.aulast=Ouatas&rft.aufirst=Taoufik&rft.date=2002-01-01&rft.volume=19&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Clinical+%26+experimental+metastasis&rft.issn=02620898&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-22 N1 - Date created - 2002-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicogenomics, drug discovery, and the pathologist. AN - 71536648; 11890469 AB - The field of toxicogenomics, which currently focuses on the application of large-scale differential gene expression (DGE) data to toxicology, is starting to influence drug discovery and development in the pharmaceutical industry. Toxicological pathologists, who play key roles in the development of therapeutic agents, have much to contribute to DGE studies, especially in the experimental design and interpretation phases. The intelligent application of DGE to drug discovery can reveal the potential for both desired (therapeutic) and undesired (toxic) responses. The pathologist's understanding of anatomic, physiologic, biochemical, immune, and other underlying factors that drive mechanisms of tissue responses to noxious agents turns a bewildering array of gene expression data into focused research programs. The latter process is critical for the successful application of DGE to toxicology. Pattern recognition is a useful first step, but mechanistically based DGE interpretation is where the long-term future of these new technologies lies. Pathologists trained to carry out such interpretations will become important members of the research teams needed to successfully apply these technologies to drug discovery and safety assessment. As a pathologist using DGE, you will need to learn to read DGE data in the same way you learned to read glass slides, patiently and with a desire to learn and, later, to teach. In return, you will gain a greater depth of understanding of cell and tissue function, both in health and disease. JF - Toxicologic pathology AU - Boorman, Gary A AU - Anderson, Steven P AU - Casey, Warren M AU - Brown, Roger H AU - Crosby, Lynn M AU - Gottschalk, K AU - Easton, Marilyn AU - Ni, Hong AU - Morgan, Kevin T AD - Laboratory for Experimental Pathology, Environmental Toxicology Program, NIEHS, Research Triangle Park, NC 27709, USA. PY - 2002 SP - 15 EP - 27 VL - 30 IS - 1 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Animals KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Gene Expression KW - Data Interpretation, Statistical KW - Pharmacology -- trends KW - Toxicology -- trends KW - Pathology -- trends KW - Genomics -- trends UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71536648?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Toxicogenomics%2C+drug+discovery%2C+and+the+pathologist.&rft.au=Boorman%2C+Gary+A%3BAnderson%2C+Steven+P%3BCasey%2C+Warren+M%3BBrown%2C+Roger+H%3BCrosby%2C+Lynn+M%3BGottschalk%2C+K%3BEaston%2C+Marilyn%3BNi%2C+Hong%3BMorgan%2C+Kevin+T&rft.aulast=Boorman&rft.aufirst=Gary&rft.date=2002-01-01&rft.volume=30&rft.issue=1&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-26 N1 - Date created - 2002-03-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quality review procedures necessary for rodent pathology databases and toxicogenomic studies: the National Toxicology Program experience. AN - 71510661; 11890481 AB - Accuracy of the pathology data is crucial since rodent studies often provide critical data used for setting human chemical exposure standards. Diagnoses represent a judgment on the expected biological behavior of a lesion and peer review can improve diagnostic accuracy and consistency. With the conduct of 500 2-year rodent studies, the National Toxicology Program (NTP) has refined its process for comprehensive review of the pathology data and diagnoses. We have found that careful judgment can improve and simplify the review, whereas simply applying a set review procedure may not assure study quality. The use of reviewing pathologists and pathology peer review groups is a very effective procedure to increase study quality with minimal time and cost. New genomic technology to assess differential gene expression is being used to predict morphological phenotypes such as necrosis, hyperplasia, and neoplasia. The challenge for pathologists is to provide uniform pathology phenotypes that can be correlated with the gene expression changes. The lessons learned in assuring data quality in standard rodent studies also applies to the emerging field of toxicogenomics. JF - Toxicologic pathology AU - Boorman, Gary A AU - Haseman, Joseph K AU - Waters, Michael D AU - Hardisty, Jerry F AU - Sills, Robert C AD - Laboratory for Experimental Pathology, Environmental Toxicology Program, National Center for Toxicogenomics, NIEHS, Research Triangle Park, NC 27709, USA. PY - 2002 SP - 88 EP - 92 VL - 30 IS - 1 SN - 0192-6233, 0192-6233 KW - Mutagens KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Databases, Factual KW - Rodentia -- physiology KW - Toxicology -- standards KW - Pathology -- standards KW - Mutagens -- toxicity KW - Genomics -- standards KW - Animals, Laboratory KW - Quality Control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71510661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Quality+review+procedures+necessary+for+rodent+pathology+databases+and+toxicogenomic+studies%3A+the+National+Toxicology+Program+experience.&rft.au=Boorman%2C+Gary+A%3BHaseman%2C+Joseph+K%3BWaters%2C+Michael+D%3BHardisty%2C+Jerry+F%3BSills%2C+Robert+C&rft.aulast=Boorman&rft.aufirst=Gary&rft.date=2002-01-01&rft.volume=30&rft.issue=1&rft.spage=88&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-26 N1 - Date created - 2002-03-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preparation of recombinant RNase single-chain antibody fusion proteins. AN - 71503156; 11876300 AB - This article describes the construction, expression, and purification of RNase single-chain antibody fusion proteins. To construct a fusion protein, the gene for each moiety, the RNase and the binding ligand, is modified separately to contain complementary DNA encoding a 13 amino acid spacer that separates the RNase from the binding moiety. Appropriate restriction enzyme sites for cloning into the vector are also added. The modified DNA is combined and fused using the PCR technique of splicing by overlap extension (1). The resulting DNA construct is expressed in inclusion bodies in BL21(DE3) bacteria that are specifically engineered for the expression of toxic proteins (2). After isolation and purification of the inclusion bodies, the fusion protein is solubilized, denatured, and renatured. The renatured RNase fusion protein mixture is purified to homogeneity by two chromatography steps. The first column, a CM-Sephadex C-50 or a heparin Sepharose column, eliminates the majority of contaminating proteins while the second column, an affinity column (Ni2+-NTA agarose), results in the final purification of the RNase fusion protein. JF - Molecular biotechnology AU - Newton, Dianne L AU - Rybak, Susanna M AD - SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 63 EP - 76 VL - 20 IS - 1 SN - 1073-6085, 1073-6085 KW - Antibodies KW - 0 KW - Immunoconjugates KW - Recombinant Fusion Proteins KW - Ribonucleases KW - EC 3.1.- KW - Index Medicus KW - Animals KW - Humans KW - Chromatography -- methods KW - Neoplasms -- therapy KW - Neoplasms -- immunology KW - Immunoconjugates -- genetics KW - Ribonucleases -- genetics KW - Recombinant Fusion Proteins -- isolation & purification KW - Recombinant Fusion Proteins -- genetics KW - Immunoconjugates -- metabolism KW - Antibodies -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71503156?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+biotechnology&rft.atitle=Preparation+of+recombinant+RNase+single-chain+antibody+fusion+proteins.&rft.au=Newton%2C+Dianne+L%3BRybak%2C+Susanna+M&rft.aulast=Newton&rft.aufirst=Dianne&rft.date=2002-01-01&rft.volume=20&rft.issue=1&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Molecular+biotechnology&rft.issn=10736085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-10 N1 - Date created - 2002-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Are Trp53 rescue of Brca1 embryonic lethality and Trp53/Brca1 breast cancer association related? AN - 71494786; 11879563 AB - Brca1 is involved in multiple biological pathways including DNA damage repair, transcriptional regulation, and cell-cycle progression. A complex pattern of interactions of Brca1 with Trp53 has also emerged. Xu and coworkers found that haploid loss of Trp53 significantly reduces the embryonic lethality observed in mice with a homozygous in-frame deletion of Brca1 exon 11. They report that widespread apoptosis correlates with the embryonic lethality resulting from this homozygous delta11 Brca1 mutation. A mechanism responsible for Brca1-associated carcinogenesis is proposed. These experiments extend our knowledge of a complex Brca1/Trp53 relationship. However, the precise mechanisms through which Brca1 interacts with Trp53 to suppress mammary tumor formation have yet to be elucidated. JF - Breast cancer research : BCR AU - McAllister, Kimberly A AU - Wiseman, Roger W AD - Laboratory of Women's Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. mcallis2@niehs.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 54 EP - 57 VL - 4 IS - 2 SN - 1465-5411, 1465-5411 KW - BRCA1 Protein KW - 0 KW - Index Medicus KW - Animals KW - Apoptosis -- genetics KW - Mice KW - Cell Cycle -- genetics KW - Mutation KW - Female KW - Mammary Neoplasms, Animal -- etiology KW - Mammary Neoplasms, Animal -- pathology KW - Genes, p53 KW - Mammary Neoplasms, Animal -- genetics KW - BRCA1 Protein -- physiology KW - BRCA1 Protein -- genetics KW - Genes, BRCA1 KW - Genes, Lethal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71494786?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Breast+cancer+research+%3A+BCR&rft.atitle=Are+Trp53+rescue+of+Brca1+embryonic+lethality+and+Trp53%2FBrca1+breast+cancer+association+related%3F&rft.au=McAllister%2C+Kimberly+A%3BWiseman%2C+Roger+W&rft.aulast=McAllister&rft.aufirst=Kimberly&rft.date=2002-01-01&rft.volume=4&rft.issue=2&rft.spage=54&rft.isbn=&rft.btitle=&rft.title=Breast+cancer+research+%3A+BCR&rft.issn=14655411&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-08 N1 - Date created - 2002-03-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell Growth Differ. 1997 Aug;8(8):829-38 [9269892] Mol Cell Biol. 1999 Oct;19(10):7061-75 [10490643] Nat Genet. 1997 Dec;17(4):423-30 [9398843] Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2302-6 [9482880] Cancer Res. 1998 Apr 1;58(7):1338-43 [9537225] Oncogene. 1998 Apr 2;16(13):1713-21 [9582019] Bioessays. 2000 Aug;22(8):728-37 [10918303] J Biol Chem. 2000 Oct 13;275(41):31869-75 [10884389] Am J Pathol. 2000 Dec;157(6):2151-9 [11106587] Cancer Res. 2001 May 15;61(10):4092-7 [11358831] Genes Dev. 2001 May 15;15(10):1188-93 [11358863] Nat Genet. 2001 Jul;28(3):266-71 [11431698] Oncogene. 2001 Nov 8;20(51):7514-23 [11709723] Cell. 1994 Aug 26;78(4):703-11 [8069917] Cell. 1996 Jun 28;85(7):1009-23 [8674108] Nature. 1997 Apr 24;386(6627):761, 763 [9126728] Genes Dev. 1997 May 15;11(10):1226-41 [9171368] Nat Genet. 1997 Jul;16(3):298-302 [9207798] Oncogene. 1998 Apr 30;16(17):2229-41 [9619832] Oncogene. 1998 Oct 1;17(13):1681-9 [9796697] Oncogene. 1999 Jan 7;18(1):263-8 [9926942] Cell Growth Differ. 1999 Jan;10(1):1-10 [9950212] Oncogene. 1999 Apr 15;18(15):2451-9 [10229196] Nat Genet. 1999 May;22(1):37-43 [10319859] J Pathol. 1999 Jan;187(1):43-60 [10341706] Nature. 1997 Sep 11;389(6647):187-90 [9296497] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of interactions of D1-like agonists, SKF 81297, SKF 82958 and A-77636, with cocaine: locomotor activity and drug discrimination studies in rodents. AN - 71480246; 11862342 AB - Recent data suggest that dopamine (DA) D1-like receptor full agonists may be potential pharmacotherapeutic agents for treating cocaine abuse. The structurally novel isochroman D1-like agonist, A-77636, has not been well characterized and may prove to be useful as such an agent. The interactions of cocaine and A-77636 were compared to those obtained with the better investigated benzazepine D1-like dopamine agonists, SKF 82958 and SKF 81297. The alterations in the locomotor stimulant and discriminative-stimulus effects of cocaine by the full D1-like dopamine receptor agonists were investigated across a full range of doses in order to characterize their interactions. Drug-naive Swiss-Webster mice were pretreated with SKF 81297, SKF 82958 or A-77636 (1-10 mg/kg) and cocaine (5-56 mg/kg) prior to a 30-min period in which locomotor activity was assessed. Rats were trained on a fixed ratio 20 (FR20) schedule to discriminate IP saline from cocaine (10 mg/kg) injections. Cocaine alone (1-10 mg/kg) and with either A-77636 (0.56-1.7 mg/kg), SKF 82958 (0.01-0.1 mg/kg) or SKF 81297 (0.1-0.56) were injected IP 5 min prior to a 15-min test session. Cocaine maximally stimulated activity at 20-40 mg/kg with higher and lower doses stimulating activity less. Each D1-like agonist produced a dose-related decrease in cocaine-induced locomotor activity and lowered its maximal rate. Each of the D1-like agonists partially substituted for cocaine, with maximal substitution approximating 49, 35, and 24% for SKF 81297, SKF 82958, and A-77636, respectively. SKF 82958 significantly shifted the cocaine dose-effect curve approximately 3-fold to the left. With SKF 81297, there was a trend towards a leftward shift of cocaine dose effects, however the change was not statistically significant. In contrast to the other two D1-like agonists, A-77636 either did not affect the cocaine dose-effect curve or shifted it to the right. All three agonists produced similar effects on cocaine-induced locomotor activity, however the discriminative-stimulus effects of cocaine were affected differently by the D1 agonists. These results suggest fundamental differences in the actions of these D1 agonists. Because A-77636 consistently attenuated the present effects of cocaine, it may prove more useful than the others as a pharmacotherapy to treat cocaine abuse. JF - Psychopharmacology AU - Chausmer, Allison L AU - Katz, Jonathan L AD - Medications Discovery Research Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 145 EP - 153 VL - 159 IS - 2 SN - 0033-3158, 0033-3158 KW - Benzazepines KW - 0 KW - Benzopyrans KW - Dopamine Agonists KW - Dopamine Uptake Inhibitors KW - Receptors, Dopamine D1 KW - A 77636 KW - 145307-34-2 KW - SK&F 81297 KW - 71636-61-8 KW - SK&F 82958 KW - 80751-65-1 KW - Cocaine KW - I5Y540LHVR KW - Adamantane KW - PJY633525U KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Benzazepines -- pharmacology KW - Dose-Response Relationship, Drug KW - Benzopyrans -- pharmacology KW - Mice KW - Male KW - Drug Interactions -- physiology KW - Adamantane -- pharmacology KW - Discrimination (Psychology) -- drug effects KW - Receptors, Dopamine D1 -- physiology KW - Receptors, Dopamine D1 -- agonists KW - Dopamine Agonists -- pharmacology KW - Discrimination (Psychology) -- physiology KW - Motor Activity -- physiology KW - Motor Activity -- drug effects KW - Cocaine -- pharmacology KW - Dopamine Uptake Inhibitors -- pharmacology KW - Adamantane -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71480246?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Comparison+of+interactions+of+D1-like+agonists%2C+SKF+81297%2C+SKF+82958+and+A-77636%2C+with+cocaine%3A+locomotor+activity+and+drug+discrimination+studies+in+rodents.&rft.au=Chausmer%2C+Allison+L%3BKatz%2C+Jonathan+L&rft.aulast=Chausmer&rft.aufirst=Allison&rft.date=2002-01-01&rft.volume=159&rft.issue=2&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-02 N1 - Date created - 2002-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Open-label pilot study of bupropion plus bromocriptine for treatment of cocaine dependence. AN - 71457328; 11853133 AB - Combinations of medications are often used in neuropsychiatry to enhance treatment efficacy. This 8-week, open-label study tested the combination of bupropion (< or =300 mg) and bromocriptine (< or =7.5 mg) daily in 34 cocaine-dependent (DSM-IIIR) outpatients also receiving weekly individual counseling. The first 18 subjects spent one week at maximum dose; the next 16 spent three weeks. Both groups showed significant reductions in self-reported cocaine use, with no significant change in proportion of urine toxicology tests positive for cocaine. There were no significant differences in outcome between groups. These results suggest that the combination of bupropion and bromocriptine is safe in cocaine addicts, but provide ambiguous evidence of its efficacy. JF - The American journal of drug and alcohol abuse AU - Montoya, Ivan D AU - Preston, Kenzie L AU - Rothman, Richard AU - Gorelick, David A AD - Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 189 EP - 196 VL - 28 IS - 1 SN - 0095-2990, 0095-2990 KW - Antidepressive Agents, Second-Generation KW - 0 KW - Dopamine Agonists KW - Bupropion KW - 01ZG3TPX31 KW - Bromocriptine KW - 3A64E3G5ZO KW - Index Medicus KW - Drug Therapy, Combination KW - Humans KW - Adult KW - Pilot Projects KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Bromocriptine -- administration & dosage KW - Dopamine Agonists -- therapeutic use KW - Bupropion -- therapeutic use KW - Antidepressive Agents, Second-Generation -- therapeutic use KW - Cocaine-Related Disorders -- drug therapy KW - Bromocriptine -- therapeutic use KW - Antidepressive Agents, Second-Generation -- administration & dosage KW - Dopamine Agonists -- administration & dosage KW - Bupropion -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71457328?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+drug+and+alcohol+abuse&rft.atitle=Open-label+pilot+study+of+bupropion+plus+bromocriptine+for+treatment+of+cocaine+dependence.&rft.au=Montoya%2C+Ivan+D%3BPreston%2C+Kenzie+L%3BRothman%2C+Richard%3BGorelick%2C+David+A&rft.aulast=Montoya&rft.aufirst=Ivan&rft.date=2002-01-01&rft.volume=28&rft.issue=1&rft.spage=189&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+drug+and+alcohol+abuse&rft.issn=00952990&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-20 N1 - Date created - 2002-02-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Arch Gen Psychiatry. 1991 Jan;48(1):87 [1898631] Med Clin North Am. 1999 Mar;83(2):415-43, vi-vii [10093586] J Gen Intern Med. 1993 Jan;8(1):1-4 [8419555] Am J Drug Alcohol Abuse. 1995 Feb;21(1):65-79 [7762545] J Clin Psychiatry. 1995 Sep;56(9):395-401 [7665537] Addiction. 1997 Jun;92(6):717-27 [9246799] J Clin Psychiatry. 1983 May;44(5 Pt 2):197-201 [6406457] Am J Drug Alcohol Abuse. 1985;11(3-4):171-91 [4091157] Drugs. 1993 Sep;46(3):384-93 [7693430] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Family growth: the eukaryotic DNA polymerase revolution. AN - 71454273; 11846034 JF - Cellular and molecular life sciences : CMLS AU - Bebenek, K AU - Kunkel, T A AD - Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. bebenek@niehs.nih.gov Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 54 EP - 57 VL - 59 IS - 1 SN - 1420-682X, 1420-682X KW - Escherichia coli Proteins KW - 0 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Animals KW - Escherichia coli Proteins -- metabolism KW - DNA Repair KW - DNA Damage KW - Humans KW - DNA Replication KW - Mutagenesis KW - Multigene Family KW - Eukaryotic Cells -- enzymology KW - DNA-Directed DNA Polymerase -- genetics KW - DNA-Directed DNA Polymerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71454273?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+and+molecular+life+sciences+%3A+CMLS&rft.atitle=Family+growth%3A+the+eukaryotic+DNA+polymerase+revolution.&rft.au=Bebenek%2C+K%3BKunkel%2C+T+A&rft.aulast=Bebenek&rft.aufirst=K&rft.date=2002-01-01&rft.volume=59&rft.issue=1&rft.spage=54&rft.isbn=&rft.btitle=&rft.title=Cellular+and+molecular+life+sciences+%3A+CMLS&rft.issn=1420682X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-05 N1 - Date created - 2002-02-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms of cancer drug resistance. AN - 71450225; 11818492 AB - The design of cancer chemotherapy has become increasingly sophisticated, yet there is no cancer treatment that is 100% effective against disseminated cancer. Resistance to treatment with anticancer drugs results from a variety of factors including individual variations in patients and somatic cell genetic differences in tumors, even those from the same tissue of origin. Frequently resistance is intrinsic to the cancer, but as therapy becomes more and more effective, acquired resistance has also become common. The most common reason for acquisition of resistance to a broad range of anticancer drugs is expression of one or more energy-dependent transporters that detect and eject anticancer drugs from cells, but other mechanisms of resistance including insensitivity to drug-induced apoptosis and induction of drug-detoxifying mechanisms probably play an important role in acquired anticancer drug resistance. Studies on mechanisms of cancer drug resistance have yielded important information about how to circumvent this resistance to improve cancer chemotherapy and have implications for pharmacokinetics of many commonly used drugs. JF - Annual review of medicine AU - Gottesman, Michael M AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, Maryland 20892-4255, USA. mgottesman@nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 615 EP - 627 VL - 53 SN - 0066-4219, 0066-4219 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Apoptosis -- drug effects KW - Inactivation, Metabolic -- physiology KW - Drug Resistance, Neoplasm KW - Neoplasms -- drug therapy KW - Cell Survival -- drug effects KW - Antineoplastic Agents -- pharmacokinetics KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71450225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+review+of+medicine&rft.atitle=Mechanisms+of+cancer+drug+resistance.&rft.au=Gottesman%2C+Michael+M&rft.aulast=Gottesman&rft.aufirst=Michael&rft.date=2002-01-01&rft.volume=53&rft.issue=&rft.spage=615&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+medicine&rft.issn=00664219&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-30 N1 - Date created - 2002-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic neurons in models of Parkinson's disease. AN - 71437329; 11796748 AB - Although the cause of Parkinson's disease (PD) is unknown, data suggest roles for environmental factors that may sensitize dopaminergic neurons to age-related dysfunction and death. Based upon epidemiological data suggesting roles for dietary factors in PD and other age-related neurodegenerative disorders, we tested the hypothesis that dietary folate can modify vulnerability of dopaminergic neurons to dysfunction and death in a mouse model of PD. We report that dietary folate deficiency sensitizes mice to MPTP-induced PD-like pathology and motor dysfunction. Mice on a folate-deficient diet exhibit elevated levels of plasma homocysteine. When infused directly into either the substantia nigra or striatum, homocysteine exacerbates MPTP-induced dopamine depletion, neuronal degeneration and motor dysfunction. Homocysteine exacerbates oxidative stress, mitochondrial dysfunction and apoptosis in human dopaminergic cells exposed to the pesticide rotenone or the pro-oxidant Fe(2+). The adverse effects of homocysteine on dopaminergic cells is ameliorated by administration of the antioxidant uric acid and by an inhibitor of poly (ADP-ribose) polymerase. The ability of folate deficiency and elevated homocysteine levels to sensitize dopaminergic neurons to environmental toxins suggests a mechanism whereby dietary folate may influence risk for PD. JF - Journal of neurochemistry AU - Duan, Wenzhen AU - Ladenheim, Bruce AU - Cutler, Roy G AU - Kruman, Inna I AU - Cadet, Jean Lud AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, Maryland 21224, USA. Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 101 EP - 110 VL - 80 IS - 1 SN - 0022-3042, 0022-3042 KW - Biomarkers KW - 0 KW - Rotenone KW - 03L9OT429T KW - Homocysteine KW - 0LVT1QZ0BA KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Iron KW - E1UOL152H7 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Parkinson Disease, Secondary -- chemically induced KW - Mitochondria -- physiology KW - Animals KW - Iron -- pharmacology KW - Corpus Striatum -- metabolism KW - Humans KW - Mice KW - Rotenone -- pharmacology KW - Tumor Cells, Cultured KW - Oxidative Stress KW - Mitochondria -- drug effects KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- pharmacology KW - Mice, Inbred C57BL KW - Corpus Striatum -- drug effects KW - Motor Activity -- drug effects KW - Drug Synergism KW - Hyperhomocysteinemia -- etiology KW - Cell Survival -- physiology KW - Male KW - Homocysteine -- blood KW - Folic Acid Deficiency -- complications KW - Dopamine -- metabolism KW - Parkinson Disease -- complications KW - Parkinson Disease -- physiopathology KW - Folic Acid Deficiency -- physiopathology KW - Parkinson Disease -- pathology KW - Neurons -- pathology KW - Brain -- physiopathology KW - Brain -- pathology KW - Neurons -- physiology KW - Homocysteine -- pharmacology KW - Diet UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71437329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Dietary+folate+deficiency+and+elevated+homocysteine+levels+endanger+dopaminergic+neurons+in+models+of+Parkinson%27s+disease.&rft.au=Duan%2C+Wenzhen%3BLadenheim%2C+Bruce%3BCutler%2C+Roy+G%3BKruman%2C+Inna+I%3BCadet%2C+Jean+Lud%3BMattson%2C+Mark+P&rft.aulast=Duan&rft.aufirst=Wenzhen&rft.date=2002-01-01&rft.volume=80&rft.issue=1&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-29 N1 - Date created - 2002-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reliability of reporting on life-style and agricultural factors by a sample of participants in the Agricultural Health Study from Iowa. AN - 71412658; 11805592 AB - Repeat interviews from 4,088 Iowa pesticide applicators participating in the Agricultural Health Study provided the opportunity to evaluate the reliability of self-reported information on pesticide use and various demographic and life-style factors. Self-completed questionnaires were administered 1 year apart when participants returned to county agricultural extension offices for pesticide certification or training. Percentage agreement for ever-/never-use of specific pesticides and application practices was quite high, generally ranging from 70% to more than 90%, and did not vary by age, educational level, or farm size. Agreement was lower (typically 50-60%) for duration, frequency, or decade of first use of specific pesticides. Level of agreement regarding pesticide use in this population is similar to that generally found for factors typically used in epidemiologic studies such as tobacco use and higher than typically reported for diet, physical activity, and medical conditions. JF - Epidemiology (Cambridge, Mass.) AU - Blair, Aaron AU - Tarone, Robert AU - Sandler, Dale AU - Lynch, Charles F AU - Rowland, Andrew AU - Wintersteen, Wendy AU - Steen, William C AU - Samanic, Claudine AU - Dosemeci, Mustafa AU - Alavanja, Michael C R AD - Division of Cancer Epidemiology and Gentics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. blaira@mail.nih.gov Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 94 EP - 99 VL - 13 IS - 1 SN - 1044-3983, 1044-3983 KW - Pesticides KW - 0 KW - Index Medicus KW - Reproducibility of Results KW - Humans KW - Cohort Studies KW - Surveys and Questionnaires KW - Iowa KW - Male KW - Female KW - Life Style KW - Agriculture UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71412658?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiology+%28Cambridge%2C+Mass.%29&rft.atitle=Reliability+of+reporting+on+life-style+and+agricultural+factors+by+a+sample+of+participants+in+the+Agricultural+Health+Study+from+Iowa.&rft.au=Blair%2C+Aaron%3BTarone%2C+Robert%3BSandler%2C+Dale%3BLynch%2C+Charles+F%3BRowland%2C+Andrew%3BWintersteen%2C+Wendy%3BSteen%2C+William+C%3BSamanic%2C+Claudine%3BDosemeci%2C+Mustafa%3BAlavanja%2C+Michael+C+R&rft.aulast=Blair&rft.aufirst=Aaron&rft.date=2002-01-01&rft.volume=13&rft.issue=1&rft.spage=94&rft.isbn=&rft.btitle=&rft.title=Epidemiology+%28Cambridge%2C+Mass.%29&rft.issn=10443983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-05 N1 - Date created - 2002-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Fagerstrom Test for Nicotine Dependence and the Diagnostic Interview Schedule: do they diagnose the same smokers? AN - 71409351; 11800217 AB - Two common assessment tools for nicotine dependence are the Fagerstrom Test for Nicotine Dependence (FTND) and the Nicotine Dependence section of the Diagnostic Interview Schedule [(DIS)-III-R or -IV based on the Diagnostic and Statistical Manual (DSM)-III-R and -IV, respectively]. The FTND emphasizes morning smoking and overall "heaviness" of smoking. The DSM emphasizes adverse consequences, desire to cut down, and mood changes during withdrawal. We tested (1) how the DSM-III-R diagnosis of Nicotine Dependence is related to FTND score; and (2) how the (a) DSM-III-R or (b) elevated FTND score is related to longer smoking histories, greater psychiatric symptomatology, and tobacco liking scores. Retrospective chart reviews were conducted on 370 smokers, the majority (55.9%) of whom had a current DSM-III-R diagnosis of Substance Dependence other than nicotine. All subjects had completed the FTND, the DIS-III-R, the Symptom Checklist-90-Revised (SCL-90-R), and a survey on drug liking. Agreement statistics were calculated between the DSM-II-R diagnosis of Nicotine Dependence and various cutoff scores values that were assigned as thresholds for nicotine dependence on the FTND. At no cutoff score did the two instruments reliably agree; the highest kappa (at a cutoff of FTND > or = 7) was 0.205. At cutoffs above 5, the FTND diagnosed fewer cases than the DSM-III-R. Multiple regression analysis showed that DSM diagnosis was associated with greater psychiatric symptomatology on the SCL-90-R, while FTND scores were associated with greater tobacco liking. The FTND and the DSM-III-R appear to measure different aspects of the tobacco dependence process. Specifically, the FTND may provide a stronger measure of physical dependence, while the DSM may tap other domains such as awareness of dependence, behaviors resulting from that awareness, and psychiatric symptomatology. Disagreements between the FTND and the DSM are likely to become greater with the changes in the DSM-IV. JF - Addictive behaviors AU - Moolchan, Eric T AU - Radzius, Aleksandras AU - Epstein, David H AU - Uhl, George AU - Gorelick, David A AU - Cadet, Jean Lud AU - Henningfield, Jack E AD - Clinical Pharmacology and Therapeutics Research Branch, National Institutes of Health, National Institute on Drug Abuse/Intramural Research Program, Baltimore MD, 21224, USA. emoolcha@intra.nida.nih.gov PY - 2002 SP - 101 EP - 113 VL - 27 IS - 1 SN - 0306-4603, 0306-4603 KW - Index Medicus KW - Humans KW - Adult KW - Retrospective Studies KW - Middle Aged KW - Statistics as Topic KW - Adolescent KW - Male KW - Female KW - Diagnostic and Statistical Manual of Mental Disorders KW - Substance-Related Disorders -- diagnosis KW - Tobacco Use Disorder -- psychology KW - Tobacco Use Disorder -- diagnosis KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71409351?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addictive+behaviors&rft.atitle=The+Fagerstrom+Test+for+Nicotine+Dependence+and+the+Diagnostic+Interview+Schedule%3A+do+they+diagnose+the+same+smokers%3F&rft.au=Moolchan%2C+Eric+T%3BRadzius%2C+Aleksandras%3BEpstein%2C+David+H%3BUhl%2C+George%3BGorelick%2C+David+A%3BCadet%2C+Jean+Lud%3BHenningfield%2C+Jack+E&rft.aulast=Moolchan&rft.aufirst=Eric&rft.date=2002-01-01&rft.volume=27&rft.issue=1&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Addictive+behaviors&rft.issn=03064603&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-27 N1 - Date created - 2002-01-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nonmyeloablative stem cell transplantation for solid tumors: expanding the application of allogeneic immunotherapy. AN - 71406735; 11799531 AB - In the arena of tumor immunology, there is a growing perception that the graft-versus-leukemia (GVL) reaction that follows allogeneic stem cell transplantation represents the most potent form of cancer immunotherapy currently in clinical use. While allogeneic stem cell transplantation has become an accepted form of "immunotherapy" for the treatment of hematological malignancies, its efficacy in inducing antitumor effects against nonhematological cancers has, until recently, been largely unexplored. The investigational application of nonmyeloablative allogeneic stem cell transplantation (NST) in solid tumors represents the logical consequence of almost 50 years of experimental and clinical research into the immunological basis for the cure of hematological malignancies following allogeneic bone marrow transplant (BMT). Here we review the historical background, development, and preliminary clinical results of allogeneic stem cell transplantation as immunotherapy for solid tumors. JF - Seminars in hematology AU - Childs, Richard AU - Barrett, John AD - Stem Cell Transplant Unit, Hematology Branch, National Heart, Lung and Blood Insitute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 63 EP - 71 VL - 39 IS - 1 SN - 0037-1963, 0037-1963 KW - Index Medicus KW - Animals KW - Graft vs Tumor Effect KW - Humans KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Transplantation, Homologous -- immunology KW - Antineoplastic Combined Chemotherapy Protocols -- toxicity KW - Antineoplastic Combined Chemotherapy Protocols -- standards KW - Clinical Protocols KW - Transplantation Conditioning -- methods KW - Transplantation Conditioning -- standards KW - Neoplasms -- therapy KW - Hematopoietic Stem Cell Transplantation -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71406735?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+hematology&rft.atitle=Nonmyeloablative+stem+cell+transplantation+for+solid+tumors%3A+expanding+the+application+of+allogeneic+immunotherapy.&rft.au=Childs%2C+Richard%3BBarrett%2C+John&rft.aulast=Childs&rft.aufirst=Richard&rft.date=2002-01-01&rft.volume=39&rft.issue=1&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Seminars+in+hematology&rft.issn=00371963&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-10 N1 - Date created - 2002-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cocaine, reward, movement and monoamine transporters. AN - 71384038; 11803442 AB - Recent evidence enriches our understanding of the molecular sites of action of cocaine reward and locomotor stimulation. Dopamine transporter blockade by cocaine appears a sufficient explanation for cocaine-induced locomotion. Variation in DAT appears to cause differences in locomotion without drug stimulation. However, previously-held views that DAT blockade was the sole site for cocaine reward have been replaced by a richer picture of multitransporter involvement with the rewarding and aversive actions of cocaine. These new insights, derived from studies of knockout mice with simultaneous deletions and/or blockade of multiple transporters, provide a novel model for the rewarding action of this heavily-abused substance and implicate multiple monoamine systems in cocaine's hedonic activities. JF - Molecular psychiatry AU - Uhl, G R AU - Hall, F S AU - Sora, I AD - Molecular Neurobiology Branch, NIDA-IRP, NIH, Baltimore, MD 21224, USA. guhl@intra.nida.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 21 EP - 26 VL - 7 IS - 1 SN - 1359-4184, 1359-4184 KW - Carrier Proteins KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Modulators KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Norepinephrine Plasma Membrane Transport Proteins KW - SLC6A2 protein, human KW - SLC6A3 protein, human KW - SLC6A4 protein, human KW - Serotonin Plasma Membrane Transport Proteins KW - Slc6a2 protein, mouse KW - Slc6a3 protein, mouse KW - Slc6a4 protein, mouse KW - Symporters KW - Serotonin KW - 333DO1RDJY KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Genetic Variation KW - Animals KW - Models, Psychological KW - Serotonin -- physiology KW - Carrier Proteins -- antagonists & inhibitors KW - Carrier Proteins -- genetics KW - Brain -- drug effects KW - Humans KW - Dopamine -- physiology KW - Symporters -- physiology KW - Symporters -- antagonists & inhibitors KW - Membrane Glycoproteins -- deficiency KW - Mice, Knockout KW - Carrier Proteins -- physiology KW - Genetic Predisposition to Disease KW - Models, Neurological KW - Cocaine-Related Disorders -- metabolism KW - Membrane Glycoproteins -- genetics KW - Symporters -- deficiency KW - Membrane Glycoproteins -- physiology KW - Membrane Glycoproteins -- antagonists & inhibitors KW - Symporters -- genetics KW - Mice KW - Norepinephrine -- physiology KW - Cocaine-Related Disorders -- genetics KW - Brain -- pathology KW - Nerve Tissue Proteins -- physiology KW - Nerve Tissue Proteins -- deficiency KW - Reward KW - Membrane Transport Proteins -- deficiency KW - Membrane Transport Proteins -- antagonists & inhibitors KW - Membrane Transport Proteins -- physiology KW - Motor Activity -- drug effects KW - Nerve Tissue Proteins -- antagonists & inhibitors KW - Nerve Tissue Proteins -- genetics KW - Cocaine -- pharmacology KW - Membrane Transport Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71384038?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+psychiatry&rft.atitle=Cocaine%2C+reward%2C+movement+and+monoamine+transporters.&rft.au=Uhl%2C+G+R%3BHall%2C+F+S%3BSora%2C+I&rft.aulast=Uhl&rft.aufirst=G&rft.date=2002-01-01&rft.volume=7&rft.issue=1&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Molecular+psychiatry&rft.issn=13594184&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-19 N1 - Date created - 2002-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transactivation of Fra-1 and consequent activation of AP-1 occur extracellular signal-regulated kinase dependently. AN - 71376655; 11756554 AB - Mitogen-activated protein (MAP) kinase, extracellular-signal-regulated kinases (ERKs) play an important role in activating AP-1-dependent transcription. Studies using the JB6 mouse epidermal model and a transgenic mouse model have established a requirement for AP-1-dependent transcription in tumor promotion. Tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor induce activator protein 1 (AP-1) activity and neoplastic transformation in JB6 transformation-sensitive (P(+)) cells, but not in transformation-resistant (P(-)) variants. The resistance in one of the P(-) variants can be attributed to the low levels of the MAP kinases, ERKs 1 and 2, and consequent nonresponsiveness to AP-1 activation. The resistant variant is not deficient in c-fos transcription. The purpose of these studies was to define the targets of activated ERK that lead to AP-1 transactivation. The results establish that the transactivation domain of Fra-1 can be activated, that activation of Fra-1 is ERK dependent, and that a putative ERK phosphorylation site must be intact for activation to occur. Fra-1 was activated by TPA in ERK-sufficient P(+) cells but not in ERK-deficient P(-) cells. A similar activation pattern was seen for c-Fos but not for Fra-2. Gel shift analysis identified Fra-1 as distinguishing mitogen-activated (P(+)) from nonactivated (P(-)) AP-1 complexes. A second AP-1-nonresponsive P(-) variant that underexpresses Fra-1 gained AP-1 response upon introduction of a Fra-1 expression construct. These observations suggest that ERK-dependent activation of Fra-1 is required for AP-1 transactivation in JB6 cells. JF - Molecular and cellular biology AU - Young, Matthew R AU - Nair, Rajalakshmi AU - Bucheimer, Natalie AU - Tulsian, Preety AU - Brown, Nicole AU - Chapp, Cristi AU - Hsu, Tin-Chen AU - Colburn, Nancy H AD - Basic Research Laboratory, National Cancer Institute-Frederick. Intramural Research Support Program, Science Applications International Corporation-Frederick, Frederick, Maryland 21702, USA. youngm@ncifcrf.gov Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 587 EP - 598 VL - 22 IS - 2 SN - 0270-7306, 0270-7306 KW - Carcinogens KW - 0 KW - Proto-Oncogene Proteins c-fos KW - RNA, Messenger KW - Transcription Factor AP-1 KW - fos-related antigen 1 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Tetradecanoylphorbol Acetate -- toxicity KW - Animals KW - Genetic Variation KW - Plasmids -- genetics KW - Carcinogens -- toxicity KW - Transcriptional Activation -- drug effects KW - Mice KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Binding Sites KW - Base Sequence KW - Genes, fos KW - Protein Structure, Tertiary KW - Cell Line KW - Cell Transformation, Neoplastic -- genetics KW - Proto-Oncogene Proteins c-fos -- metabolism KW - Transcription Factor AP-1 -- metabolism KW - Proto-Oncogene Proteins c-fos -- genetics KW - Mitogen-Activated Protein Kinases -- metabolism KW - Proto-Oncogene Proteins c-fos -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71376655?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Transactivation+of+Fra-1+and+consequent+activation+of+AP-1+occur+extracellular+signal-regulated+kinase+dependently.&rft.au=Young%2C+Matthew+R%3BNair%2C+Rajalakshmi%3BBucheimer%2C+Natalie%3BTulsian%2C+Preety%3BBrown%2C+Nicole%3BChapp%2C+Cristi%3BHsu%2C+Tin-Chen%3BColburn%2C+Nancy+H&rft.aulast=Young&rft.aufirst=Matthew&rft.date=2002-01-01&rft.volume=22&rft.issue=2&rft.spage=587&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-29 N1 - Date created - 2001-12-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):10952-6 [8248197] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):609-13 [8290571] J Am Soc Nephrol. 1993 Nov;4(5):1104-10 [8305637] Cell Growth Differ. 1994 Jan;5(1):9-16 [8123597] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3844-8 [8170999] Nature. 1994 May 12;369(6476):156-60 [8177321] Mol Cell Biol. 1999 Jan;19(1):330-41 [9858557] J Biol Chem. 1999 Jan 8;274(2):1124-30 [9873060] J Biol Chem. 1999 Feb 5;274(6):3385-95 [9920881] Oncogene. 1998 Dec 31;17(26):3493-8 [10030673] Oncogene. 1994 Jul;9(7):1855-60 [8208531] Curr Opin Cell Biol. 1994 Apr;6(2):230-8 [8024815] Oncogene. 1994 Sep;9(9):2537-47 [8058317] Nature. 1994 Sep 8;371(6493):171-5 [8072547] Oncogene. 1994 Nov;9(11):3305-11 [7936655] Cell. 1995 Jan 27;80(2):199-211 [7834740] Nature. 1979 Oct 18;281(5732):589-91 [492322] Proc Natl Acad Sci U S A. 1981 Nov;78(11):6912-6 [6947266] Cancer Res. 1982 Aug;42(8):3093-7 [6284358] Proc Natl Acad Sci U S A. 1987 Mar;84(5):1272-6 [3029776] Cell. 1988 Feb 12;52(3):471-80 [3125983] Science. 1988 May 20;240(4855):1010-6 [3130660] Mol Cell Biol. 1988 May;8(5):2063-9 [3133553] Trends Biochem Sci. 1994 Nov;19(11):470-3 [7855889] Cell Mol Biol Res. 1994;40(3):253-6 [7874203] Proc Natl Acad Sci U S A. 1995 May 23;92(11):4972-6 [7761434] Mol Cell Biol. 1995 Jul;15(7):3748-58 [7791782] Science. 1995 Jul 21;269(5222):403-7 [7618106] Cell. 1995 Sep 8;82(5):721-32 [7545543] FASEB J. 1995 Oct;9(13):1311-8 [7557021] Curr Biol. 1995 Jul 1;5(7):747-57 [7583121] Cancer Res. 1996 Feb 1;56(3):483-9 [8564958] Oncogene. 1996 Apr 4;12(7):1493-502 [8622865] Curr Opin Cell Biol. 1996 Apr;8(2):205-15 [8791420] J Mol Med (Berl). 1996 Oct;74(10):589-607 [8912180] Oncogene. 1997 Feb 20;14(7):837-47 [9047391] Curr Opin Cell Biol. 1997 Apr;9(2):240-6 [9069263] Biochem J. 1997 Jun 1;324 ( Pt 2):547-53 [9182717] Mol Carcinog. 1997 Jul;19(3):204-12 [9254887] Cancer Res. 1997 Aug 15;57(16):3569-76 [9270030] EMBO J. 1997 Sep 1;16(17):5310-21 [9311991] Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):156-61 [9419345] Mol Cell Biol. 1998 Jun;18(6):3310-20 [9584171] Oncogene. 1998 May 28;16(21):2711-21 [9652737] Mol Cell Biol. 1998 Dec;18(12):7095-105 [9819396] Mol Cell Biol. 1999 Jan;19(1):321-9 [9858556] Oncogene. 1999 May 20;18(20):3085-97 [10340380] Prog Biophys Mol Biol. 1999;71(3-4):479-500 [10354710] Cell Growth Differ. 1999 May;10(5):333-42 [10359014] Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9827-32 [10449779] Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):14037-42 [10570194] Nat Genet. 2000 Feb;24(2):184-7 [10655067] Biochim Biophys Acta. 1999 Dec 23;1489(2-3):263-80 [10673028] Genes Dev. 2000 Nov 1;14(21):2695-700 [11069886] Endocr Rev. 2001 Apr;22(2):153-83 [11294822] Cell. 1988 Nov 4;55(3):395-7 [3141060] Science. 1989 Mar 31;243(4899):1695-9 [2494702] Science. 1989 May 5;244(4904):566-9 [2541502] Science. 1990 Jul 6;249(4964):64-7 [2164259] Cell. 1991 May 17;65(4):663-75 [2032290] Biochim Biophys Acta. 1991 Dec 10;1072(2-3):129-57 [1751545] Oncogene. 1991 Dec;6(12):2179-85 [1766667] Mol Carcinog. 1992;5(1):62-74 [1543542] Mol Cell Biol. 1992 Mar;12(3):915-27 [1545823] Nature. 1992 Jul 30;358(6385):414-7 [1322499] Mol Carcinog. 1992;6(3):221-9 [1445622] Oncogene. 1993 Apr;8(4):877-86 [8455942] Cell. 1993 Apr 23;73(2):381-93 [8386592] J Cell Biol. 1993 Sep;122(5):1079-88 [8394845] Mol Cell Biol. 1993 Dec;13(12):7429-38 [7504176] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - BIG1 and BIG2: brefeldin A-inhibited guanine nucleotide-exchange proteins for ADP-ribosylation factors. AN - 71375471; 11665623 JF - Methods in enzymology AU - Pacheco-Rodriguez, Gustavo AU - Moss, Joel AU - Vaughan, Martha AD - Pulmonary-Critical Care Medicine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002 PY - 2002 DA - 2002 SP - 397 EP - 404 VL - 345 SN - 0076-6879, 0076-6879 KW - ARFGEF1 protein, human KW - 0 KW - ARFGEF2 protein, human KW - Guanine Nucleotide Exchange Factors KW - Recombinant Proteins KW - Brefeldin A KW - 20350-15-6 KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Cholera Toxin KW - 9012-63-9 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factor 1 KW - EC 3.6.5.2 KW - ADP-Ribosylation Factors KW - Index Medicus KW - Animals KW - Cattle KW - Recombinant Proteins -- metabolism KW - ADP-Ribosylation Factor 1 -- metabolism KW - Humans KW - In Vitro Techniques KW - Guanosine 5'-O-(3-Thiotriphosphate) -- metabolism KW - Brefeldin A -- pharmacology KW - Biological Transport, Active KW - ADP-Ribosylation Factors -- metabolism KW - Guanine Nucleotide Exchange Factors -- metabolism KW - GTP-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71375471?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=BIG1+and+BIG2%3A+brefeldin+A-inhibited+guanine+nucleotide-exchange+proteins+for+ADP-ribosylation+factors.&rft.au=Pacheco-Rodriguez%2C+Gustavo%3BMoss%2C+Joel%3BVaughan%2C+Martha&rft.aulast=Pacheco-Rodriguez&rft.aufirst=Gustavo&rft.date=2002-01-01&rft.volume=345&rft.issue=&rft.spage=397&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-08 N1 - Date created - 2001-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Paired charge-to-alanine mutagenesis of dengue virus type 4 NS5 generates mutants with temperature-sensitive, host range, and mouse attenuation phenotypes. AN - 71372946; 11752143 AB - Charge-to-alanine mutagenesis of dengue virus type 4 (DEN4) NS5 gene generated a collection of attenuating mutations for potential use in a recombinant live attenuated DEN vaccine. Codons for 80 contiguous pairs of charged amino acids in NS5 were individually mutagenized to create uncharged pairs of alanine residues, and 32 recombinant mutant viruses were recovered from the 80 full-length mutant DEN4 cDNA constructs. These mutant viruses were tested for temperature-sensitive (ts) replication in both Vero cells and HuH-7 human hepatoma cells. Of the 32 mutants, 13 were temperature sensitive (ts) in both cell lines, 11 were not ts in either cell line, and 8 exhibited a host range (tshr) phenotype. One tshr mutant was ts only in Vero cells, and seven were ts only in HuH-7 cells. Nineteen of the 32 mutants were 10-fold or more restricted in replication in the brains of suckling mice compared to that of wild-type DEN4, and three mutants were approximately 10,000-fold restricted in replication. The level of temperature sensitivity of replication in vitro did not correlate with attenuation in vivo. A virus bearing two pairs of charge-to-alanine mutations was constructed and demonstrated increased temperature sensitivity and attenuation relative to either parent virus. This large set of charge-to-alanine mutations specifying a wide range of attenuation for mouse brain should prove useful in fine-tuning recombinant live attenuated DEN vaccines. JF - Journal of virology AU - Hanley, Kathryn A AU - Lee, Jay J AU - Blaney, Joseph E AU - Murphy, Brian R AU - Whitehead, Stephen S AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. khanley@niaid.nih.gov Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 525 EP - 531 VL - 76 IS - 2 SN - 0022-538X, 0022-538X KW - NS5 protein, flavivirus KW - 0 KW - Vaccines, Attenuated KW - Viral Nonstructural Proteins KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Animals KW - Humans KW - Temperature KW - Amino Acid Sequence KW - Brain -- virology KW - Mice KW - Phenotype KW - Conserved Sequence -- genetics KW - Tumor Cells, Cultured KW - Animals, Suckling -- virology KW - Brain -- pathology KW - Cercopithecus aethiops KW - Vaccines, Attenuated -- genetics KW - Molecular Sequence Data KW - Mutation -- genetics KW - Vero Cells KW - Viral Nonstructural Proteins -- genetics KW - Amino Acid Substitution -- genetics KW - Alanine -- metabolism KW - Viral Nonstructural Proteins -- chemistry KW - Alanine -- genetics KW - Dengue Virus -- pathogenicity KW - Dengue Virus -- genetics KW - Viral Nonstructural Proteins -- metabolism KW - Dengue Virus -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71372946?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Paired+charge-to-alanine+mutagenesis+of+dengue+virus+type+4+NS5+generates+mutants+with+temperature-sensitive%2C+host+range%2C+and+mouse+attenuation+phenotypes.&rft.au=Hanley%2C+Kathryn+A%3BLee%2C+Jay+J%3BBlaney%2C+Joseph+E%3BMurphy%2C+Brian+R%3BWhitehead%2C+Stephen+S&rft.aulast=Hanley&rft.aufirst=Kathryn&rft.date=2002-01-01&rft.volume=76&rft.issue=2&rft.spage=525&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-11 N1 - Date created - 2001-12-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5139-43 [2052593] J Virol. 2001 Oct;75(20):9731-40 [11559806] Am J Trop Med Hyg. 2001 Nov;65(5):414-9 [11716092] Infect Immun. 1980 Jan;27(1):175-80 [6766902] Cancer Res. 1982 Sep;42(9):3858-63 [6286115] Am J Trop Med Hyg. 1984 Jul;33(4):684-9 [6476216] Proc Natl Acad Sci U S A. 1985 Jan;82(2):488-92 [3881765] Virology. 1989 Jul;171(1):302-5 [2525840] Annu Rev Biochem. 1989;58:765-98 [2673021] Am J Trop Med Hyg. 1992 Sep;47(3):265-70 [1355950] Arch Virol. 1993;128(1-2):111-21 [8418788] J Gen Virol. 1993 Apr;74 ( Pt 4):733-40 [8385698] Virology. 1993 Jun;194(2):769-80 [8389081] J Virol. 1994 Feb;68(2):863-76 [8289389] J Gen Virol. 1994 May;75 ( Pt 5):1183-7 [8176380] J Infect Dis. 1994 Dec;170(6):1448-55 [7995984] J Biol Chem. 1995 Aug 11;270(32):19100-6 [7642575] Virology. 1996 Feb 15;216(2):317-25 [8607261] J Virol. 1996 Jun;70(6):3930-7 [8648730] Vaccine. 1996 Mar;14(4):329-36 [8744561] J Virol. 1997 Jan;71(1):291-8 [8985349] J Infect Dis. 1997 Aug;176(2):313-21 [9237695] Vaccine. 1997 Aug-Sep;15(12-13):1372-8 [9302747] Am J Trop Med Hyg. 1998 Jan;58(1):90-5 [9452298] Virology. 1998 Jul 5;246(2):409-17 [9657959] Ann Acad Med Singapore. 1998 Mar;27(2):227-34 [9663316] Biochem Biophys Res Commun. 1999 Apr 21;257(3):731-7 [10208852] Virology. 1999 Jul 20;260(1):125-35 [10405364] Am J Trop Med Hyg. 2001 Nov;65(5):405-13 [11716091] J Infect Dis. 2000 Jan;181(1):2-9 [10608744] J Med Virol. 2000 Apr;60(4):432-8 [10686027] Vaccine. 2000 May 26;18 Suppl 2:44-7 [10821973] J Gen Virol. 2001 Apr;82(Pt 4):735-45 [11257177] Vaccine. 2001 Apr 30;19(23-24):3179-88 [11312014] J Gen Virol. 1991 Sep;72 ( Pt 9):2197-206 [1895057] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Subcutaneous Administration of a Replication-Competent Adenovirus Expressing HSV-tk to Cotton Rats: Dissemination, Persistence, Shedding, and Pathogenicity. AN - 71372389; 11779414 AB - Since human adenoviruses replicate only in human cells, toxicology studies with adenoviral vectors are hampered by the lack of a permissive nonhuman host. Before a replication-competent adenoviral vector expressing HSV-tk (Ad.OW34) can be used in clinical studies for intratumoral injections in patients with cutaneous lesions of head and neck cancer or intralesional injection for in situ vaccination strategy in advanced metastatic melanoma patients, risks have to be estimated in animal studies. In an attempt to assess potential toxicology, dissemination, persistence and shedding, we injected Ad.OW34 subcutaneously into cotton rats. (Sigmodon hispidus), which are considered a semi-permissive host for human adenoviruses. The animals underwent one or two subcutaneous injection cycles with 2.3 x 10(12) viral particles/kg each or a single course with 6.9 x 10(13) viral particles/kg and were analyzed at defined time points for histopathological changes in the brain, heart, lungs, spleen, liver, kidneys, ovaries, and skin. Additionally, these tissues as well as urine, feces, mouth, and skin swabs were analyzed at multiple time points by real-time quantitative polymerase chain reaction for the presence of vector sequences. The only significant treatment-related histopathologic finding was dermatitis with mild acanthosis at the site of vector injection. All other tissues evaluated were within normal limits or showed changes that were most likely incidental or spontaneous in nature. Vector sequences were detected in the skin at the injection site and to a lesser extent in the liver, spleen, and lungs. In addition, small amounts of vector DNA were detected in the ovaries. The vector sequences were rapidly cleared and the absence of viral sequences in the excreta and swabs of the majority of animals suggest that there was no significant replication of the vector in this host. The administration of Ad.OW34 was also associated with mild hyperamylasemia, lymphocytosis, and granulocytosis; however, we did not observe any clinical signs of illness or death in the experimental animals over the course of the study. JF - Human gene therapy AU - Wildner, Oliver AU - Morris, John C AD - Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. oliver.wildner@ruhr-uni-bochum.de Y1 - 2002/01/01/ PY - 2002 DA - 2002 Jan 01 SP - 101 EP - 112 VL - 13 IS - 1 SN - 1043-0342, 1043-0342 KW - Thymidine Kinase KW - EC 2.7.1.21 KW - Index Medicus KW - Virus Replication KW - Polymerase Chain Reaction KW - Animals KW - Gene Transfer Techniques KW - Humans KW - Injections, Subcutaneous KW - Genetic Therapy -- methods KW - Microscopy, Electron KW - Tissue Distribution KW - Virus Shedding KW - Leukocyte Count KW - Female KW - Genetic Vectors -- administration & dosage KW - Herpes Simplex -- enzymology KW - Adenoviruses, Human -- genetics KW - Sigmodontinae -- virology KW - Thymidine Kinase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71372389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+gene+therapy&rft.atitle=Subcutaneous+Administration+of+a+Replication-Competent+Adenovirus+Expressing+HSV-tk+to+Cotton+Rats%3A+Dissemination%2C+Persistence%2C+Shedding%2C+and+Pathogenicity.&rft.au=Wildner%2C+Oliver%3BMorris%2C+John+C&rft.aulast=Wildner&rft.aufirst=Oliver&rft.date=2002-01-01&rft.volume=13&rft.issue=1&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Human+gene+therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-12 N1 - Date created - 2002-01-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Hum Gene Ther 2002 Feb 10;13(3):484 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pilot study of the effects of intermittent interleukin-2 on human immunodeficiency virus (HIV)-specific immune responses in patients treated during recently acquired HIV infection. AN - 71371262; 11756982 AB - Highly active antiretroviral therapy (HAART) initiated during acute human immunodeficiency virus (HIV) infection may preserve HIV-specific CD4+ T cell responses that are thought to enhance HIV-specific CD8+ T cell function. The present pilot study was designed to determine whether preserved HIV-specific immune responses are augmented by the administration of the immunomodulatory agent interleukin (IL)-2. Nine persons recently (<6 months) infected with HIV were randomized to receive HAART alone or HAART plus 3 cycles of intermittent IL-2 during a 12-month period. Although HAART plus IL-2 significantly increased counts of total and naive CD4+ T cells, compared with HAART alone, there was no increase in CD4+ or CD8+ HIV-specific immune responses. In addition, adjuvant IL-2 therapy did not reduce the pool of HIV-infected resting CD4+ T cells. Thus, although intermittent IL-2 plus HAART quantitatively increased CD4+ T cells, this increase was not selective for HIV-specific CD4+ or CD8+ T cell responses in recently infected persons. JF - The Journal of infectious diseases AU - Dybul, Mark AU - Hidalgo, Bertha AU - Chun, Tae-Wook AU - Belson, Michael AU - Migueles, Stephen A AU - Justement, Jesse S AU - Herpin, Betsey AU - Perry, Cheryl AU - Hallahan, Claire W AU - Davey, Richard T AU - Metcalf, Julia A AU - Connors, Mark AU - Fauci, Anthony S AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. mdybul@nih.gov Y1 - 2002/01/01/ PY - 2002 DA - 2002 Jan 01 SP - 61 EP - 68 VL - 185 IS - 1 SN - 0022-1899, 0022-1899 KW - Anti-HIV Agents KW - 0 KW - Benzoxazines KW - HIV Protease Inhibitors KW - Interleukin-2 KW - Oxazines KW - Reverse Transcriptase Inhibitors KW - Lamivudine KW - 2T8Q726O95 KW - Indinavir KW - 5W6YA9PKKH KW - Interferon-gamma KW - 82115-62-6 KW - Stavudine KW - BO9LE4QFZF KW - efavirenz KW - JE6H2O27P8 KW - Abridged Index Medicus KW - Index Medicus KW - Coculture Techniques KW - Humans KW - CD4-Positive T-Lymphocytes -- immunology KW - Indinavir -- therapeutic use KW - Interferon-gamma -- biosynthesis KW - Pilot Projects KW - HIV Protease Inhibitors -- therapeutic use KW - Lamivudine -- therapeutic use KW - Lymphocyte Activation KW - Stavudine -- therapeutic use KW - CD8-Positive T-Lymphocytes -- immunology KW - Antiretroviral Therapy, Highly Active KW - Oxazines -- therapeutic use KW - Reverse Transcriptase Inhibitors -- therapeutic use KW - Drug Synergism KW - Lymphocyte Subsets KW - Interleukin-2 -- administration & dosage KW - Anti-HIV Agents -- therapeutic use KW - Interleukin-2 -- therapeutic use KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71371262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=Pilot+study+of+the+effects+of+intermittent+interleukin-2+on+human+immunodeficiency+virus+%28HIV%29-specific+immune+responses+in+patients+treated+during+recently+acquired+HIV+infection.&rft.au=Dybul%2C+Mark%3BHidalgo%2C+Bertha%3BChun%2C+Tae-Wook%3BBelson%2C+Michael%3BMigueles%2C+Stephen+A%3BJustement%2C+Jesse+S%3BHerpin%2C+Betsey%3BPerry%2C+Cheryl%3BHallahan%2C+Claire+W%3BDavey%2C+Richard+T%3BMetcalf%2C+Julia+A%3BConnors%2C+Mark%3BFauci%2C+Anthony+S&rft.aulast=Dybul&rft.aufirst=Mark&rft.date=2002-01-01&rft.volume=185&rft.issue=1&rft.spage=61&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-28 N1 - Date created - 2001-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity of a first-generation adenoviral vector in rhesus macaques. AN - 71362787; 11779415 AB - We constructed a first-generation adenovirus vector (AVC3FIX5) that we used to assess the rhesus macaque as a nonhuman primate model for preclinical testing of hemophilia B gene therapy vectors. Although we succeeded in our primary objective of demonstrating expression of human factor IX we encountered numerous toxic side effects that proved to be dose limiting. Following intravenous administration of AVC3FIX5 at doses of 3.4 x 10(11) vector particles/kg to 3.8 x 10(12) vector particles/kg, the animals in our study developed antibodies against human factor IX, and dose-dependent elevations of enzymes specific for liver, muscle, and lung injury. In addition, these animals showed dose-dependent prolongation of clotting times as well as acute, dose-dependent decreases in platelet counts and concomitant elevation of fibrinogen and von Willebrand factor. These abnormalities may be caused by the direct toxic effects of the adenovirus vector itself, or may result indirectly from the accompanying acute inflammatory response marked by elevations in IL-6, a key regulator of the acute inflammatory response. The rhesus macaque may be a useful animal model in which to evaluate mechanisms of adenovirus toxicities that have been encountered during clinical gene therapy trials. JF - Human gene therapy AU - Lozier, Jay N AU - Csako, Gyorgy AU - Mondoro, Traci H AU - Krizek, D M AU - Metzger, Mark E AU - Costello, Rene AU - Vostal, Jaroslav G AU - Rick, M E AU - Donahue, Robert E AU - Morgan, Richard A AD - National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. lozier@cber.fda.gov Y1 - 2002/01/01/ PY - 2002 DA - 2002 Jan 01 SP - 113 EP - 124 VL - 13 IS - 1 SN - 1043-0342, 1043-0342 KW - Interleukin-6 KW - 0 KW - Isoenzymes KW - von Willebrand Factor KW - Factor IX KW - 9001-28-9 KW - Fibrinogen KW - 9001-32-5 KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Creatine Kinase KW - EC 2.7.3.2 KW - Index Medicus KW - Muscle, Skeletal -- pathology KW - Animals KW - Dose-Response Relationship, Drug KW - Humans KW - Creatine Kinase -- metabolism KW - Interleukin-6 -- metabolism KW - Disease Models, Animal KW - Muscle, Skeletal -- drug effects KW - Blood Cell Count KW - Isoenzymes -- metabolism KW - Fibrinogen -- metabolism KW - Platelet Aggregation KW - von Willebrand Factor -- metabolism KW - Liver -- drug effects KW - Enzyme-Linked Immunosorbent Assay KW - Genetic Therapy -- methods KW - Macaca mulatta KW - Drug Evaluation, Preclinical KW - L-Lactate Dehydrogenase -- metabolism KW - Factor IX -- metabolism KW - Hemophilia B -- metabolism KW - Adenoviruses, Human -- genetics KW - Hemophilia B -- therapy KW - Genetic Vectors -- toxicity KW - Factor IX -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71362787?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+gene+therapy&rft.atitle=Toxicity+of+a+first-generation+adenoviral+vector+in+rhesus+macaques.&rft.au=Lozier%2C+Jay+N%3BCsako%2C+Gyorgy%3BMondoro%2C+Traci+H%3BKrizek%2C+D+M%3BMetzger%2C+Mark+E%3BCostello%2C+Rene%3BVostal%2C+Jaroslav+G%3BRick%2C+M+E%3BDonahue%2C+Robert+E%3BMorgan%2C+Richard+A&rft.aulast=Lozier&rft.aufirst=Jay&rft.date=2002-01-01&rft.volume=13&rft.issue=1&rft.spage=113&rft.isbn=&rft.btitle=&rft.title=Human+gene+therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-12 N1 - Date created - 2002-01-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cerebral blood flow pulsatility deficits in HIV+ poly substance abusers: differences associated with antiviral medications. AN - 71362017; 11772474 AB - This study examines the influence of HIV-seropositivity and antiviral medications on cerebral blood flow in cocaine abusers. Forty-five HIV negative (HIV-) cocaine abusers, 36 HIV positive (HIV+) cocaine abusers (CD4; mean 378, +/-229) and 27 control HIV- subjects were studied. Blood flow velocity and pulsatility were determined for the anterior and middle cerebral arteries using transcranial Doppler sonography (TCD). Psychological assessments, which included the psychiatric symptom checklist (SCL-90R), hopelessness (Beck) and well-being (Ellison) questionnaires revealed greater psychiatric distress in HIV+ cocaine abusers than the other groups. HIV- cocaine abusers and HIV+ cocaine abusers not receiving antiviral medications (n=25 of 36) had elevated pulsatility values, indicating increased resistance in the cerebral blood vessels in comparison to control subjects. HIV+ cocaine abusers using antiviral medications (n=11 of 36) had pulsatility values similar to HIV- control subjects. Interestingly, there was no significant relationship between intensity of psychiatric distress reported by HIV+ cocaine abusers and perfusion deficits. Our findings suggest that unmedicated HIV+ cocaine abusers have cerebrovascular deficits, which are similar to HIV- cocaine abusers. In addition, the use of antiviral medications appears to be associated with a reduction of these deficits in HIV+ cocaine abusers. Nevertheless, more studies will be needed before any conclusion can be reached regarding possible beneficial effects of these agents on the cerebral vasculature. JF - Drug and alcohol dependence AU - Herning, Ronald I AU - Tate, Kimberly AU - Better, Warren AU - Cadet, Jean Lud AD - Molecular Neuropsychiatry Section, Division of Intramural Research, National Institute on Drug Abuse, National Institutes of Health, PO Box 5180, Baltimore, MD 21224, USA. rherning@intra.nida.nih.gov Y1 - 2002/01/01/ PY - 2002 DA - 2002 Jan 01 SP - 129 EP - 135 VL - 65 IS - 2 SN - 0376-8716, 0376-8716 KW - Antiviral Agents KW - 0 KW - Index Medicus KW - Depressive Disorder, Major -- diagnosis KW - Heart Rate -- drug effects KW - Humans KW - Cerebrovascular Circulation -- physiology KW - Echoencephalography KW - Adult KW - Ultrasonography, Doppler, Transcranial KW - Male KW - Female KW - Brain -- physiopathology KW - Cerebrovascular Disorders -- physiopathology KW - Cerebrovascular Disorders -- chemically induced KW - Brain -- drug effects KW - Brain -- blood supply KW - Substance-Related Disorders -- complications KW - Antiviral Agents -- adverse effects KW - HIV Seropositivity -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71362017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=Cerebral+blood+flow+pulsatility+deficits+in+HIV%2B+poly+substance+abusers%3A+differences+associated+with+antiviral+medications.&rft.au=Herning%2C+Ronald+I%3BTate%2C+Kimberly%3BBetter%2C+Warren%3BCadet%2C+Jean+Lud&rft.aulast=Herning&rft.aufirst=Ronald&rft.date=2002-01-01&rft.volume=65&rft.issue=2&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=03768716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-07 N1 - Date created - 2002-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Infusional CDE with rituximab for the treatment of human immunodeficiency virus-associated non-Hodgkin's lymphoma: preliminary results of a phase I/II study. AN - 71361939; 11785839 AB - Infusional CDE (cyclophosphamide, doxorubicin, etoposide; iCDE) is one of the most effective chemotherapeutic regimen for human immunodeficiency virus (HIV)-associated non-Hodgkin's lymphoma (NHL), with a complete remission rate of 46% and a median overall survival of 8.2 months (Sparano JA, Blood 1993; 81:2810). Since the majority of HIV-associated NHL are CD20-positive we reasoned that the addition of rituximab to iCDE (R-iCDE) could also improve the poor outcome of these patients. As a first step we investigated the safety of R-iCDE in a phase I/II study. Thirty patients with aggressive HIV-associated NHL were enrolled between June 1998 and October 2000. Characteristics of 29 evaluable patients were: median age: 38 years (range 29-65 years); male sex 24/29; histology: DLCL 16 (55%), Burkitt 10 (35%), ALCL 2 (7%), unclassified 1 (3%); stage: I (35%), II (10%), III (10%), IV (45%); International Prognostic Index: 0, 1 (59%), 2 (24%), 3 (17%), 4, 5 (0); CD4 count: median 132/ mm3 (range 3-470/mm3). Patients received rituximab (375 mg/m2) in conjunction with iCDE (five or six cycles). All patients were treated with G-CSF and highly active antiretroviral therapy (HAART). Twenty-six of 29 patients received treatment as planned, while chemotherapy had to be discontinued in three patients (2 persistent thrombocytopenias, 1 cerebral hemorrhage). Grade 3 or 4 toxicity was observed as follows: neutropenia 79%, anemia 45%, thrombocytopenia 34%, bacterial infection 34%, opportunistic infection 7%, mucositis 17%. A dose reduction was necessary in 22%. Complete remission was achieved in 86% of the patients, partial remission in 4%. Ten percent had progressive disease. After a median follow-up of 9 months the median overall survival is not reached. The actuarial survival at 2 years is 80% and the actuarial progression-free survival is 79%. Four of 29 patients (14%) have died, three from NHL and one from cryptosporidiosis. These findings suggest that the combination of rituximab with iCDE in patients with HIV-associated NHL is safe and feasible and that the addition of the anti-CD20 antibody does not increase the risk for infections. The high complete remission rate also indicates a potential therapeutic benefit and warrants further randomized trials. JF - Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer AU - Tirelli, U AU - Spina, M AU - Jaeger, U AU - Nigra, E AU - Blanc, P L AU - Liberati, A M AU - Benci, A AU - Sparano, J A AD - National Cancer Institute, Aviano, Italy. Y1 - 2002 PY - 2002 DA - 2002 SP - 149 EP - 153 VL - 159 SN - 0080-0015, 0080-0015 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Murine-Derived KW - Rituximab KW - 4F4X42SYQ6 KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Drug Therapy, Combination KW - Disease-Free Survival KW - Infusions, Intravenous KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Male KW - Female KW - Lymphoma, AIDS-Related -- mortality KW - Cyclophosphamide -- therapeutic use KW - Etoposide -- therapeutic use KW - Lymphoma, AIDS-Related -- drug therapy KW - Doxorubicin -- therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71361939?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Recent+results+in+cancer+research.+Fortschritte+der+Krebsforschung.+Progres+dans+les+recherches+sur+le+cancer&rft.atitle=Infusional+CDE+with+rituximab+for+the+treatment+of+human+immunodeficiency+virus-associated+non-Hodgkin%27s+lymphoma%3A+preliminary+results+of+a+phase+I%2FII+study.&rft.au=Tirelli%2C+U%3BSpina%2C+M%3BJaeger%2C+U%3BNigra%2C+E%3BBlanc%2C+P+L%3BLiberati%2C+A+M%3BBenci%2C+A%3BSparano%2C+J+A&rft.aulast=Tirelli&rft.aufirst=U&rft.date=2002-01-01&rft.volume=159&rft.issue=&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=Recent+results+in+cancer+research.+Fortschritte+der+Krebsforschung.+Progres+dans+les+recherches+sur+le+cancer&rft.issn=00800015&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-03 N1 - Date created - 2002-01-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epidemiology of traumatic brain injuries: Indian scenario. AN - 71356454; 11783750 AB - Traumatic brain injuries (TBIs) are a leading cause of morbidity, mortality, disability and socioeconomic losses in India and other developing countries. Specific topics addressed in this paper include magnitude of the problem, causes, context of injury occurrence, risk factors, severity, outcome and impact of TBIs on rapidly transforming societies. It is estimated that nearly 1.5 to 2 million persons are injured and 1 million succumb to death every year in India. Road traffic injuries are the leading cause (60%) of TBIs followed by falls (20%-25%) and violence (10%). Alcohol involvement is known to be present among 15%-20% of TBIs at the time of injury. The rehabilitation needs of brain injured persons are significantly high and increasing from year to year. India and other developing countries face the major challenges of prevention, pre-hospital care and rehabilitation in their rapidly changing environments to reduce the burden of TBIs. JF - Neurological research AU - Gururaj, G AD - Department of Epidemiology, National Institute of Mental Health and Neuro Sciences, Bangalore, India. guru@nimhans.kar.nic.in Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 24 EP - 28 VL - 24 IS - 1 SN - 0161-6412, 0161-6412 KW - Index Medicus KW - India -- epidemiology KW - Age Factors KW - Sex Factors KW - Humans KW - Recovery of Function KW - Aged KW - Child KW - Accidents, Traffic -- statistics & numerical data KW - Accidental Falls -- statistics & numerical data KW - Adult KW - Safety -- standards KW - Disability Evaluation KW - Adolescent KW - Hospitalization -- statistics & numerical data KW - Alcoholism -- complications KW - Male KW - Female KW - Prevalence KW - Brain Injuries -- rehabilitation KW - Brain Injuries -- epidemiology KW - Brain Injuries -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71356454?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurological+research&rft.atitle=Epidemiology+of+traumatic+brain+injuries%3A+Indian+scenario.&rft.au=Gururaj%2C+G&rft.aulast=Gururaj&rft.aufirst=G&rft.date=2002-01-01&rft.volume=24&rft.issue=1&rft.spage=24&rft.isbn=&rft.btitle=&rft.title=Neurological+research&rft.issn=01616412&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-21 N1 - Date created - 2002-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 12-hydroxyeicosatetrenoate (12-HETE) attenuates AMPA receptor-mediated neurotoxicity: evidence for a G-protein-coupled HETE receptor. AN - 71355772; 11756509 AB - 12-hydroxyeicosatetraenoic acid (12-HETE) is a neuromodulator that is synthesized during ischemia. Its neuronal effects include attenuation of calcium influx and glutamate release as well as inhibition of AMPA receptor (AMPA-R) activation. Because 12-HETE reduces ischemic injury in the heart, we examined whether it can also reduce neuronal excitotoxicity. When treated with 12-(S)HETE, cortical neuron cultures subjected to AMPA-R-mediated glutamate toxicity suffered up to 40% less damage than untreated cultures. The protective effect of 12-(S)HETE was concentration-dependent (EC50 = 88 nm) and stereostructurally selective. Maximal protection was conferred by 300 nm 12-(S)HETE; 300 nm 15-(S)HETE was similarly protective, but 300 nm 5-(S)HETE was less effective. The chiral isomer 12-(R)HETE offered no protection; neither did arachidonic acid or 12-(S)hydroperoxyeicosatetraenoic acid. Excitotoxicity was calcium-dependent, and 12-(S)HETE was demonstrated to protect by inactivating N and L (but not P) calcium channels via a pertussis toxin-sensitive mechanism. Calcium imaging demonstrated that 12-(S)HETE also attenuates glutamate-induced calcium influx into neurons via a pertussis toxin-sensitive mechanism, suggesting that it acts via a G-protein-coupled receptor. In addition, 12-(S)HETE stimulates GTPgammaS binding (indicating G-protein activation) and inhibits adenylate cyclase in forskolin-stimulated cultures over the same concentration range as it exerts its anti-excitotoxic and calcium-influx attenuating effects. These studies demonstrate that 12-(S)HETE can protect neurons from excitotoxicity by activating a G(i/o)-protein-coupled receptor, which limits calcium influx through voltage-gated channels. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Hampson, Aidan J AU - Grimaldi, Maurizio AD - Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. ahampson@cortexpharm.com Y1 - 2002/01/01/ PY - 2002 DA - 2002 Jan 01 SP - 257 EP - 264 VL - 22 IS - 1 KW - 12-hydroxyeicosatetraenoic acid receptor KW - 0 KW - Adenylate Cyclase Toxin KW - Adenylyl Cyclase Inhibitors KW - Benzothiadiazines KW - Calcium Channels KW - Chelating Agents KW - Excitatory Amino Acid Antagonists KW - Neuroprotective Agents KW - Potassium Channel Blockers KW - Potassium Channels KW - Receptors, AMPA KW - Receptors, Eicosanoid KW - Receptors, Kainic Acid KW - Receptors, N-Methyl-D-Aspartate KW - Virulence Factors, Bordetella KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Glutamic Acid KW - 3KX376GY7L KW - 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid KW - 59985-28-3 KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Pertussis Toxin KW - EC 2.4.2.31 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - cyclothiazide KW - P71U09G5BW KW - Index Medicus KW - Animals KW - Calcium Channels -- metabolism KW - Benzothiadiazines -- pharmacology KW - Dose-Response Relationship, Drug KW - Receptors, Kainic Acid -- metabolism KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Models, Biological KW - Neuroprotective Agents -- pharmacology KW - Dizocilpine Maleate -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Rats KW - Virulence Factors, Bordetella -- pharmacology KW - Potassium Channels -- metabolism KW - Chelating Agents -- pharmacology KW - Glutamic Acid -- toxicity KW - Cells, Cultured KW - Calcium Channels -- drug effects KW - Potassium Channel Blockers -- pharmacology KW - Rats, Wistar KW - Guanosine 5'-O-(3-Thiotriphosphate) -- metabolism KW - L-Lactate Dehydrogenase -- metabolism KW - Receptors, Eicosanoid -- metabolism KW - 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid -- pharmacology KW - Neurons -- metabolism KW - Neurons -- drug effects KW - GTP-Binding Proteins -- metabolism KW - Neurons -- cytology KW - Receptors, AMPA -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71355772?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=12-hydroxyeicosatetrenoate+%2812-HETE%29+attenuates+AMPA+receptor-mediated+neurotoxicity%3A+evidence+for+a+G-protein-coupled+HETE+receptor.&rft.au=Hampson%2C+Aidan+J%3BGrimaldi%2C+Maurizio&rft.aulast=Hampson&rft.aufirst=Aidan&rft.date=2002-01-01&rft.volume=22&rft.issue=1&rft.spage=257&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-04 N1 - Date created - 2001-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I study of the intravenous administration of attenuated Salmonella typhimurium to patients with metastatic melanoma. AN - 71353469; 11773163 AB - A strain of Salmonella typhimurium (VNP20009), attenuated by chromosomal deletion of the purI and msbB genes, was found to target to tumor and inhibit tumor growth in mice. These findings led to the present phase I study of the intravenous infusion of VNP20009 to patients with metastatic cancer. In cohorts consisting of three to six patients, 24 patients with metastatic melanoma and one patient with metastatic renal cell carcinoma received 30-minute intravenous bolus infusions containing 10(6) to 10(9) cfu/m(2) of VNP20009. Patients were evaluated for dose-related toxicities, selective replication within tumors, and antitumor effects. The maximum-tolerated dose was 3 x 10(8) cfu/m(2). Dose-limiting toxicity was observed in patients receiving 1 x 10(9) cfu/m(2), which included thrombocytopenia, anemia, persistent bacteremia, hyperbilirubinemia, diarrhea, vomiting, nausea, elevated alkaline phosphatase, and hypophosphatemia. VNP20009 induced a dose-related increase in the circulation of proinflammatory cytokines, such as interleukin (IL)-1beta, tumor necrosis factor alpha, IL-6, and IL-12. Focal tumor colonization was observed in two patients receiving 1 x 10(9) cfu/m(2) and in one patient receiving 3 x 10(8) cfu/m(2). None of the patients experienced objective tumor regression, including those patients with colonized tumors. The VNP20009 strain of Salmonella typhimurium can be safely administered to patients, and at the highest tolerated dose, some tumor colonization was observed. No antitumor effects were seen, and additional studies are required to reduce dose-related toxicity and improve tumor localization. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Toso, John F AU - Gill, Vee J AU - Hwu, Patrick AU - Marincola, Francesco M AU - Restifo, Nicholas P AU - Schwartzentruber, Douglas J AU - Sherry, Richard M AU - Topalian, Suzanne L AU - Yang, James C AU - Stock, Frida AU - Freezer, Linda J AU - Morton, Kathleen E AU - Seipp, Claudia AU - Haworth, Leah AU - Mavroukakis, Sharon AU - White, Donald AU - MacDonald, Susan AU - Mao, John AU - Sznol, Mario AU - Rosenberg, Steven A AD - Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 2B42, Bethesda, MD 20892, USA. Y1 - 2002/01/01/ PY - 2002 DA - 2002 Jan 01 SP - 142 EP - 152 VL - 20 IS - 1 SN - 0732-183X, 0732-183X KW - Antibodies, Bacterial KW - 0 KW - Antineoplastic Agents KW - Cytokines KW - Index Medicus KW - Cytokines -- blood KW - Infusions, Intravenous KW - Genetic Engineering KW - Bacterial Translocation KW - Humans KW - Dose-Response Relationship, Immunologic KW - Adult KW - Antibodies, Bacterial -- blood KW - Colony Count, Microbial KW - Aged KW - Middle Aged KW - Maximum Tolerated Dose KW - Male KW - Female KW - Carcinoma, Renal Cell -- pathology KW - Melanoma -- pathology KW - Carcinoma, Renal Cell -- therapy KW - Melanoma -- secondary KW - Melanoma -- microbiology KW - Carcinoma, Renal Cell -- secondary KW - Carcinoma, Renal Cell -- microbiology KW - Melanoma -- therapy KW - Antineoplastic Agents -- therapeutic use KW - Salmonella typhimurium -- immunology KW - Salmonella typhimurium -- genetics KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71353469?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+I+study+of+the+intravenous+administration+of+attenuated+Salmonella+typhimurium+to+patients+with+metastatic+melanoma.&rft.au=Toso%2C+John+F%3BGill%2C+Vee+J%3BHwu%2C+Patrick%3BMarincola%2C+Francesco+M%3BRestifo%2C+Nicholas+P%3BSchwartzentruber%2C+Douglas+J%3BSherry%2C+Richard+M%3BTopalian%2C+Suzanne+L%3BYang%2C+James+C%3BStock%2C+Frida%3BFreezer%2C+Linda+J%3BMorton%2C+Kathleen+E%3BSeipp%2C+Claudia%3BHaworth%2C+Leah%3BMavroukakis%2C+Sharon%3BWhite%2C+Donald%3BMacDonald%2C+Susan%3BMao%2C+John%3BSznol%2C+Mario%3BRosenberg%2C+Steven+A&rft.aulast=Toso&rft.aufirst=John&rft.date=2002-01-01&rft.volume=20&rft.issue=1&rft.spage=142&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-01 N1 - Date created - 2002-01-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Infect Dis. 2000 Jun;181(6):1996-2002 [10837181] Chest. 2000 Aug;118(2):503-8 [10936147] J Exp Med. 2000 Oct 2;192(7):1035-46 [11015444] J Immunol. 2001 Jan 15;166(2):1248-60 [11145708] Rev Infect Dis. 1986 Jan-Feb;8(1):31-41 [3513285] J Infect. 1987 Jul;15(1):61-3 [2822812] Infect Immun. 1988 May;56(5):1352-7 [3356468] J Immunol. 1992 Feb 15;148(4):1176-81 [1737934] Eur J Cancer. 1996 Sep;32A(10):1712-8 [8983279] J Pediatr Surg. 1997 Feb;32(2):301-6 [9044141] Cancer Res. 1997 Oct 15;57(20):4537-44 [9377566] Scand J Gastroenterol. 1997 Nov;32(11):1180-2 [9399402] Chest. 1997 Dec;112(6 Suppl):321S-329S [9400897] Mol Microbiol. 1998 Jul;29(2):571-9 [9720873] Science. 1998 Nov 27;282(5394):1714-7 [9831564] Nat Biotechnol. 1999 Jan;17(1):37-41 [9920266] N Engl J Med. 1960 May 5;262:921-7 concl [13801168] Comment In: J Immunother. 2003 Mar-Apr;26(2):179-80 [12616110] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss in oxidative stress tolerance with aging linked to reduced extracellular signal-regulated kinase and Akt kinase activities. AN - 71352716; 11709495 AB - Oxidative stress is believed to be an important factor in the development of age-related diseases, and studies in lower organisms have established links between oxidative stress tolerance and longevity. We have hypothesized that aging is associated with a reduced ability to mount acute host defenses to oxidant injury, which increases the vulnerability of aged cells to stress. We tested this hypothesis by using primary hepatocytes from young (4-6 months) and aged (24-26 months) rats. Old hepatocytes were more sensitive to H2O2-induced apoptosis than were young cells. Lower survival is associated with reduced activations of extracellular signal-regulated kinase (ERK) and Akt kinase, both of which protect against oxidant injury. That reduced ERK and Akt activities contribute to lower survival of aged cells was supported by additional findings. First, pharmacologic inhibition of ERK and Akt activation in young cells markedly increased their sensitivity to H2O2. Second, caloric restriction, which increases rodent life span and delays the onset of many age-related declines in physiologic function, prevented loss in ERK and Akt activation by H2O2 and enhanced survival of old hepatocytes to levels similar to those of young cells. Strategies aimed at boosting these host responses to acute oxidant injury could have significant anti-aging benefits. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Ikeyama, Shizuo AU - Kokkonen, Gertrude AU - Shack, Sonsoles AU - Wang, Xian-Tao AU - Holbrook, Nikki J AD - Laboratory of Cellular and Molecular Biology, National Institute on Aging-IRP, Baltimore, Maryland 21224, USA. Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 114 EP - 116 VL - 16 IS - 1 KW - 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one KW - 0 KW - Chromones KW - Enzyme Inhibitors KW - Flavonoids KW - Morpholines KW - Oxidants KW - Proto-Oncogene Proteins KW - 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one KW - 31M2U1DVID KW - Hydrogen Peroxide KW - BBX060AN9V KW - Akt1 protein, rat KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Index Medicus KW - Animals KW - Hepatocytes -- drug effects KW - Oxidants -- pharmacology KW - Morpholines -- pharmacology KW - Hydrogen Peroxide -- pharmacology KW - Energy Intake KW - Hepatocytes -- enzymology KW - Models, Biological KW - Cell Survival KW - Rats KW - Chromones -- pharmacology KW - Cells, Cultured KW - Enzyme Inhibitors -- pharmacology KW - Flavonoids -- pharmacology KW - Drug Synergism KW - Proto-Oncogene Proteins -- antagonists & inhibitors KW - Mitogen-Activated Protein Kinases -- metabolism KW - Oxidative Stress KW - Aging KW - Proto-Oncogene Proteins -- metabolism KW - Mitogen-Activated Protein Kinases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71352716?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.atitle=Loss+in+oxidative+stress+tolerance+with+aging+linked+to+reduced+extracellular+signal-regulated+kinase+and+Akt+kinase+activities.&rft.au=Ikeyama%2C+Shizuo%3BKokkonen%2C+Gertrude%3BShack%2C+Sonsoles%3BWang%2C+Xian-Tao%3BHolbrook%2C+Nikki+J&rft.aulast=Ikeyama&rft.aufirst=Shizuo&rft.date=2002-01-01&rft.volume=16&rft.issue=1&rft.spage=114&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=1530-6860&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-31 N1 - Date created - 2002-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Survey of modalities of toxicity assessment and reporting in noncomparative prospective studies of chemotherapy in breast cancer. AN - 71351348; 11773153 AB - To review how toxicity, a main end point of phase II studies, is assessed and reported in published phase II chemotherapy trials in breast cancer. A survey was performed by hand-searching studies published in seven distinguished journals between 1995 and 1999. All selected articles were independently evaluated by two investigators using an ad hoc study report form. Descriptive statistics, contingency tables, and the chi(2) test were applied. Overall, 122 articles were found; 65.6% lacked a statistical study design. Planned modalities for assessment of toxicity were inadequately reported in 20.5% of the studies. The scheduling of assessment of hematologic toxicity varied greatly. Toxicity was predominantly summarized per patient (69.7%). Although overall the World Health Organization scale was adopted more frequently (45.9%), the Common Toxicity Criteria (in different versions) were used more frequently in studies published in journals with a high impact factor (P =.001), in more recently initiated studies (P =.03), in sponsored studies (P =.0006), and in studies with an identifiable statistical design (P =.006). The wide diversity in modalities of toxicity assessment and reporting observed in this study suggests that the reliability of the body of published data on the toxicity of chemotherapy in breast cancer may be questionable. Current standards should be revised and harmonized to improve the reliability of such data. A checklist is proposed to help editorial evaluation of assessment and reporting of toxicity in phase II studies. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Perrone, Francesco AU - De Maio, Ermelinda AU - Maione, Paolo AU - Di Maio, Massimo AU - Ottaiano, Alessandro AU - Pensabene, Matilde AU - Di Lorenzo, Giuseppe AU - Vernaglia Lombardi, Alessandra AU - Gallo, Ciro AD - Clinical Trials Office, National Cancer Institute, I-80131 Naples, Italy. fr.perrone@agora.it Y1 - 2002/01/01/ PY - 2002 DA - 2002 Jan 01 SP - 52 EP - 57 VL - 20 IS - 1 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Humans KW - Breast Neoplasms -- drug therapy KW - Antineoplastic Agents -- poisoning KW - Toxicity Tests -- methods KW - Clinical Trials, Phase II as Topic -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71351348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Survey+of+modalities+of+toxicity+assessment+and+reporting+in+noncomparative+prospective+studies+of+chemotherapy+in+breast+cancer.&rft.au=Perrone%2C+Francesco%3BDe+Maio%2C+Ermelinda%3BMaione%2C+Paolo%3BDi+Maio%2C+Massimo%3BOttaiano%2C+Alessandro%3BPensabene%2C+Matilde%3BDi+Lorenzo%2C+Giuseppe%3BVernaglia+Lombardi%2C+Alessandra%3BGallo%2C+Ciro&rft.aulast=Perrone&rft.aufirst=Francesco&rft.date=2002-01-01&rft.volume=20&rft.issue=1&rft.spage=52&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-01 N1 - Date created - 2002-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HPA axis and stimulant dependence: an enigmatic relationship. AN - 71351273; 11750767 AB - Clinical and preclinical evidence links stress to drug dependence. Stress is accompanied by the rapid modification of brain and body physiology which leads to release of neuroactive hormones, including biogenic amines and adrenal steroids, which activate the same brain circuitry, as stimulant drugs, such as cocaine and amphetamines. Some preclinical studies showed that stress and elevated plasma concentrations of glucocorticoids increase acquisition and maintenance of stimulant use in rats, whereas other studies revealed that animals with inherently hypoactive HPA axis are more vulnerable to stimulant "abuse". In humans cocaine acutely activates the HPA axis, and in chronic cocaine abusers early abstinence is accompanied by alterations of the HPA axis function, with distinct patterns of hormonal changes characteristic for different subgroups of addicts. Some of these changes correspond to psychiatric comorbidities, which may be predictive of propensity to relapse. Hemispheric laterality plays a role in the stress-induced activation of the HPA axis, with right prefrontal cortex (PFC) having mostly stimulatory effects and the left, inhibitory effects. Brain-imaging studies showed preferential alteration of structure and function of the right cerebral hemisphere in cocaine addicts. Activation of the right PFC and inhibition of the left was noted in typical depressive disorders, and right hemispheric hypoactivity was reported in attention deficit hyperactivity and antisocial personality disorders, which are highly comorbid with stimulant dependence. Distinct patterns of hemispheric predominance or hypofunction between individuals may contribute to vulnerability or resilience to stimulant dependence. The nature and significance of the link between stress and activity of HPA axis, and vulnerability to drug dependence is not clear and deserves further study. JF - Psychoneuroendocrinology AU - Majewska, Maria Dorota AD - Division of Treatment Research and Development, National Institute on Drug Abuse, National Institutes of Health, 6001 Executive Boulevard, Room 4123, MSC 9551, Bethesda, MD 20892-9551, USA. mrn158w@nih.gov PY - 2002 SP - 5 EP - 12 VL - 27 IS - 1-2 SN - 0306-4530, 0306-4530 KW - Central Nervous System Stimulants KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Prefrontal Cortex -- physiopathology KW - Substance-Related Disorders -- physiopathology KW - Hypothalamo-Hypophyseal System -- physiopathology KW - Pituitary-Adrenal System -- physiopathology KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71351273?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychoneuroendocrinology&rft.atitle=HPA+axis+and+stimulant+dependence%3A+an+enigmatic+relationship.&rft.au=Majewska%2C+Maria+Dorota&rft.aulast=Majewska&rft.aufirst=Maria&rft.date=2002-01-01&rft.volume=27&rft.issue=1-2&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=Psychoneuroendocrinology&rft.issn=03064530&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-18 N1 - Date created - 2001-12-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rituximab: clinical development and future directions. AN - 71349817; 11772344 AB - The availability of effective monoclonal antibodies (mAbs) has revolutionised the management of patients with B-cell malignancies. The most widely studied of these agents is rituximab (Rituxan, IDEC Pharmaceuticals, San Diego, CA), a chimeric anti-CD20 antibody. Using the standard 4-weekly administration schedule, rituximab induces responses in almost half of patients with relapsed follicular/low-grade (F/LG) non-Hodgkin's lymphoma (NHL) with complete remissions in 6%. Lower response rates (RRs) have been noted in chronic lymphocytic leukaemia (CLL) using the standard dose and schedule. The drug has been well tolerated in most patients with common adverse events including mild to moderate fevers and chills and rare occurrences of a serious syndrome related to cytokine release and rapid tumour clearance. This antibody is also active against aggressive NHL, mantle cell NHL, post-transplant lymphoproliferative disorder (PTLD), lymphoplasmacytic NHL and hairy cell leukaemia and is also being evaluated in autoimmune disorders. Combinations of rituximab with chemotherapy regimens such as CHOP (cyclophosphamide, adriamycin, vincristine, predinisone) may alter the therapeutic paradigm for these diseases. The future promise of this antibody is a foundation on which to develop new strategies to increase the cure of patients with lymphoid malignancies. JF - Expert opinion on biological therapy AU - Cheson, Bruce D AD - National Cancer Institute, Executive Plaza North, Room 741, Bethesda, MD 20892, USA. chesonb@ctep.nci.nih.gov Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 97 EP - 110 VL - 2 IS - 1 SN - 1471-2598, 1471-2598 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Murine-Derived KW - Antineoplastic Agents KW - Rituximab KW - 4F4X42SYQ6 KW - Index Medicus KW - Animals KW - Clinical Trials, Phase II as Topic KW - Dose-Response Relationship, Drug KW - Humans KW - Clinical Trials, Phase I as Topic KW - Clinical Trials as Topic KW - Neoplasms -- drug therapy KW - Antineoplastic Agents -- administration & dosage KW - Antibodies, Monoclonal -- toxicity KW - Antibodies, Monoclonal -- pharmacokinetics KW - Antineoplastic Agents -- pharmacokinetics KW - Antineoplastic Agents -- toxicity KW - Antineoplastic Agents -- therapeutic use KW - Antibodies, Monoclonal -- administration & dosage KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71349817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+opinion+on+biological+therapy&rft.atitle=Rituximab%3A+clinical+development+and+future+directions.&rft.au=Cheson%2C+Bruce+D&rft.aulast=Cheson&rft.aufirst=Bruce&rft.date=2002-01-01&rft.volume=2&rft.issue=1&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+biological+therapy&rft.issn=14712598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-27 N1 - Date created - 2002-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The late domain of human immunodeficiency virus type 1 p6 promotes virus release in a cell type-dependent manner. AN - 71349458; 11739676 AB - The p6 domain of human immunodeficiency virus type 1 (HIV-1) is located at the C terminus of the Gag precursor protein Pr55(Gag). Previous studies indicated that p6 plays a critical role in HIV-1 particle budding from virus-expressing HeLa cells. In this study, we performed a detailed mutational analysis of the N terminus of p6 to map the sequences required for efficient virus release. We observed that the highly conserved P-T/S-A-P motif located near the N terminus of p6 is remarkably sensitive to change; even conservative mutations in this sequence imposed profound virus release defects in HeLa cells. In contrast, single and double amino acid substitutions outside the P-T/S-A-P motif had no significant effect on particle release. The introduction of stop codons one or two residues beyond the P-T/S-A-P motif markedly impaired virion release, whereas truncation four residues beyond P-T/S-A-P had no effect on particle production in HeLa cells. By examining the effects of p6 mutation in biological and biochemical analyses and by electron microscopy, we defined the role of p6 in particle release and virus replication in a panel of T-cell and adherent cell lines and in primary lymphocytes and monocyte-derived macrophages. We demonstrated that the effects of p6 mutation on virus replication are markedly cell type dependent. Intriguingly, even in T-cell lines and primary lymphocytes in which p6 mutations block virus replication, these changes had little or no effect on particle release. However, p6-mutant particles produced in T-cell lines and primary lymphocytes exhibited a defect in virion-virion detachment, resulting in the production of tethered chains of virions. Virus release in monocyte-derived macrophages was markedly inhibited by p6 mutation. To examine further the cell type-specific virus release defect in HeLa versus T cells, transient heterokaryons were produced between HeLa cells and the Jurkat T-cell line. These heterokaryons display a T-cell-like phenotype with respect to the requirement for p6 in particle release. The results described here define the role of p6 in virus replication in a wide range of cell types and reveal a strong cell type-dependent requirement for p6 in virus particle budding. JF - Journal of virology AU - Demirov, Dimiter G AU - Orenstein, Jan M AU - Freed, Eric O AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0460, USA. Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 105 EP - 117 VL - 76 IS - 1 SN - 0022-538X, 0022-538X KW - Codon, Terminator KW - 0 KW - Gene Products, gag KW - gag Gene Products, Human Immunodeficiency Virus KW - p6 gag protein, Human immunodeficiency virus 1 KW - Index Medicus KW - Virus Replication KW - Mutagenesis, Site-Directed KW - HeLa Cells KW - Cells, Cultured KW - Humans KW - Molecular Sequence Data KW - Macrophages -- virology KW - Jurkat Cells -- virology KW - Amino Acid Sequence KW - Lymphocytes -- virology KW - Gene Products, gag -- genetics KW - HIV-1 -- chemistry KW - Gene Products, gag -- physiology KW - Gene Products, gag -- chemistry KW - Eukaryotic Cells -- virology KW - HIV-1 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71349458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=The+late+domain+of+human+immunodeficiency+virus+type+1+p6+promotes+virus+release+in+a+cell+type-dependent+manner.&rft.au=Demirov%2C+Dimiter+G%3BOrenstein%2C+Jan+M%3BFreed%2C+Eric+O&rft.aulast=Demirov&rft.aufirst=Dimiter&rft.date=2002-01-01&rft.volume=76&rft.issue=1&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-10 N1 - Date created - 2001-12-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1995 Sep;69(9):5455-60 [7636991] J Virol. 1995 Nov;69(11):6810-8 [7474093] Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11199-204 [11562473] Proc Natl Acad Sci U S A. 1985 Jan;82(2):488-92 [3881765] J Virol. 1986 Aug;59(2):284-91 [3016298] J Virol. 1988 Aug;62(8):2578-86 [3260631] J Virol. 1988 Oct;62(10):3874-8 [2843682] J Virol. 1988 Nov;62(11):3993-4002 [3262776] Virology. 1989 Jun;170(2):566-70 [2543131] J Med Virol. 1989 Aug;28(4):243-9 [2570823] Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3195-9 [2014240] Virology. 1991 Sep;184(1):417-22 [1871977] Science. 1995 Sep 29;269(5232):1872-5 [7569928] J Virol. 1996 Jan;70(1):341-51 [8523546] J Virol. 1998 Jun;72(6):4667-77 [9573230] J Virol. 1998 Dec;72(12):10218-21 [9811764] Virology. 1998 Nov 10;251(1):1-15 [9813197] J Virol. 1999 Mar;73(3):2309-20 [9971814] J Virol. 1999 Apr;73(4):2921-9 [10074141] J Virol. 1999 Apr;73(4):3359-65 [10074190] J Cell Sci. 1999 May;112 ( Pt 10):1417-23 [10212136] J Virol. 1999 Jun;73(6):4696-704 [10233929] EMBO J. 1999 Sep 1;18(17):4700-10 [10469649] J Gen Virol. 1995 Dec;76 ( Pt 12):3171-9 [8847526] Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):343-8 [10618420] J Virol. 2000 Apr;74(8):3548-54 [10729129] J Virol. 2000 Jun;74(12):5395-402 [10823843] J Virol. 2000 Aug;74(16):7250-60 [10906179] J Virol. 2000 Nov;74(21):9818-27 [11024108] Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):12945-7 [11087848] Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13057-62 [11087859] Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13063-8 [11087860] Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13069-74 [11087861] Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13871-6 [11095724] Virology. 2000 Dec 5;278(1):111-21 [11112487] Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1540-4 [8643668] Nature. 1996 Jun 27;381(6585):744-5 [8657277] J Virol. 1996 Aug;70(8):5695-700 [8764091] J Virol. 1997 Jun;71(6):4409-18 [9151831] J Virol. 1997 Aug;71(8):5841-8 [9223473] J Virol. 1997 Sep;71(9):6541-6 [9261374] J Virol. 1998 Apr;72(4):2962-8 [9525617] J Virol. 1998 Apr;72(4):3412-7 [9525672] J Virol. 1998 May;72(5):4095-103 [9557699] J Virol. 1998 May;72(5):4116-26 [9557701] Biopolymers. 1997;43(5):383-400 [9566119] Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7724-9 [11427703] J Gen Virol. 1991 Oct;72 ( Pt 10):2509-17 [1919528] Cell. 1992 Oct 30;71(3):359-62 [1423600] J Gen Virol. 1992 Dec;73 ( Pt 12):3079-86 [1469349] J Virol. 1993 Nov;67(11):6542-50 [8411357] J Virol. 1993 Dec;67(12):7229-37 [8230445] Annu Rev Cell Biol. 1993;9:129-61 [8280459] J Virol. 1994 Apr;68(4):2503-12 [8139032] J Virol. 1994 May;68(5):3232-42 [8151785] Nature. 1994 May 12;369(6476):107-8 [8192816] J Virol. 1994 Aug;68(8):5311-20 [8035531] J Virol. 1994 Oct;68(10):6605-18 [8083996] J Gen Virol. 1994 Nov;75 ( Pt 11):2985-97 [7964608] Virology. 1994 Dec;205(2):496-502 [7975251] Methods Cell Biol. 1994;43 Pt A:99-112 [7823872] Trends Biochem Sci. 1994 Dec;19(12):531-3 [7846762] J Virol. 1995 Mar;69(3):1984-9 [7853546] J Virol. 1995 May;69(5):2759-64 [7707498] J Virol. 1995 Jun;69(6):3949-54 [7745752] Curr Biol. 1995 Apr 1;5(4):364-7 [7542990] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antiapoptotic and cytotoxic properties of delta opioid peptide [D-Ala(2),D-Leu(5)]enkephalin in PC12 cells. AN - 71348545; 11746737 AB - The delta opioid peptide [D-Ala(2),D-Leu(5)]enkephalin (DADLE) has been shown to promote organ survival and to protect against methamphetamine-induced neurodegeneration. However, the cellular mechanisms of these actions of DADLE are not totally clear. We examined the action of DADLE in serum-deprived pheochromocytoma cells (PC12) and found that DADLE protected against cell death in those cells. However, the dose-response curves of the protective effects of DADLE are U-shaped as judged by three biochemical or morphological assays: the LDH release, the DNA laddering, and the apoptotic nuclei. It was found that femtomolar to picomolar concentrations of DADLE are antiapoptotic, whereas micormolar concentrations of DADLE are cytotoxic in PC12 cells. The protective effect of DADLE could be attenuated by a selective delta2 opioid antagonist and the cytotoxic action of DADLE was reduced by a selective mu opioid receptor antagonist. The treatment of cells with PD98059, a selective inhibitor of ERK kinase (MEK), or the transfection of cells with a dominant interfering form of MEK (MEK-KA97) blocked both the protective effect of DADLE and the ERK phosphorylation induced by DADLE. Cytotoxic concentrations of DADLE, on the other hand, caused an increase of Fas-ligand (FasL) in PC12 cells that was attenuated by a selective mu antagonist. Our results suggest, therefore, that endogenous opioid peptides may, at low concentrations, promote cell survival via the MEK-ERK pathway perhaps through delta2 opioid receptors, whereas they may kill cells at high concentrations via the activation of FasL through an as-yet unknown mechanism involving mu opioid receptors. Copyright 2001 Wiley-Liss, Inc. JF - Synapse (New York, N.Y.) AU - Hayashi, Teruo AU - Tsao, Li-I AU - Su, Tsung-Ping AD - Cellular Pathobiology Unit, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 86 EP - 94 VL - 43 IS - 1 SN - 0887-4476, 0887-4476 KW - Antigens, CD95 KW - 0 KW - Culture Media, Serum-Free KW - Cytotoxins KW - DNA, Single-Stranded KW - Enzyme Inhibitors KW - Fas Ligand Protein KW - Membrane Glycoproteins KW - Narcotic Antagonists KW - Neuroprotective Agents KW - Receptors, Opioid KW - Tnfsf6 protein, rat KW - Enkephalin, Leucine-2-Alanine KW - 63631-40-3 KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase Kinases KW - EC 2.7.12.2 KW - Index Medicus KW - Animals KW - DNA, Single-Stranded -- drug effects KW - Receptors, Opioid -- metabolism KW - DNA Fragmentation -- physiology KW - Mitogen-Activated Protein Kinase Kinases -- metabolism KW - Rats KW - Antigens, CD95 -- metabolism KW - Genetic Vectors KW - DNA Fragmentation -- drug effects KW - Antigens, CD95 -- drug effects KW - Mitogen-Activated Protein Kinase Kinases -- genetics KW - L-Lactate Dehydrogenase -- metabolism KW - DNA, Single-Stranded -- metabolism KW - Membrane Glycoproteins -- drug effects KW - Dose-Response Relationship, Drug KW - Mitogen-Activated Protein Kinases -- metabolism KW - Transfection KW - Enzyme Inhibitors -- pharmacology KW - Mitogen-Activated Protein Kinase Kinases -- antagonists & inhibitors KW - Mitogen-Activated Protein Kinases -- antagonists & inhibitors KW - Culture Media, Serum-Free -- pharmacology KW - Immunohistochemistry KW - Narcotic Antagonists -- pharmacology KW - Membrane Glycoproteins -- metabolism KW - PC12 Cells KW - Central Nervous System -- metabolism KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Apoptosis -- physiology KW - Apoptosis -- drug effects KW - Central Nervous System -- drug effects KW - Enkephalin, Leucine-2-Alanine -- pharmacology KW - Cytotoxins -- pharmacology KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71348545?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Synapse+%28New+York%2C+N.Y.%29&rft.atitle=Antiapoptotic+and+cytotoxic+properties+of+delta+opioid+peptide+%5BD-Ala%282%29%2CD-Leu%285%29%5Denkephalin+in+PC12+cells.&rft.au=Hayashi%2C+Teruo%3BTsao%2C+Li-I%3BSu%2C+Tsung-Ping&rft.aulast=Hayashi&rft.aufirst=Teruo&rft.date=2002-01-01&rft.volume=43&rft.issue=1&rft.spage=86&rft.isbn=&rft.btitle=&rft.title=Synapse+%28New+York%2C+N.Y.%29&rft.issn=08874476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-24 N1 - Date created - 2001-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of mutant thyroid hormone nuclear receptors is associated with human renal clear cell carcinoma. AN - 71348074; 11756220 AB - Thyroid hormone (T(3)) regulates proliferation and differentiation of cells, via its nuclear receptors (TRs). These processes have been shown to be abnormally regulated during carcinogenesis. We have previously found aberrant expression of TRalpha and TRbeta mRNAs in renal clear cell carcinoma (RCCC), suggesting possible involvement of TRs in the carcinogenesis of RCCC. To understand the molecular actions of TRs in RCCC, cDNAs for TRbeta1 and TRalpha1 were cloned from 22 RCCC tissues and 20 surrounding normal tissues. Mutations were found in seven TRbeta1 and three TRalpha1 cDNAs. Two TRbeta1 cDNAs had a single mutation, while five TRbeta1 and three TRalpha1 had two or three mutations. Most of the mutations were localized in the hormone-binding domain. Using the TRs prepared by in vitro transcription/translation, we found that these mutations led to a loss of T(3) binding activity and/or impairment in binding to thyroid hormone response elements (TREs). Furthermore, nuclear extracts from RCCC tissues also exhibited impairment in binding to TREs. These results indicate that the normal functions of TRs in RCCC tissues were impaired. Together with the aberrant expression patterns, these mutated TRs could contribute to the carcinogenesis of RCCC. JF - Carcinogenesis AU - Kamiya, Yuji AU - Puzianowska-Kuznicka, Monika AU - McPhie, Peter AU - Nauman, Janusz AU - Cheng, Sheue-yann AU - Nauman, Alicja AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, 37 Convent Drive MSC 4255, Bethesda, MD 20892-4255, USA. Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 25 EP - 33 VL - 23 IS - 1 SN - 0143-3334, 0143-3334 KW - DNA, Complementary KW - 0 KW - RNA, Messenger KW - Receptors, Thyroid Hormone KW - Triiodothyronine KW - 06LU7C9H1V KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - DNA, Complementary -- genetics KW - RNA, Messenger -- metabolism KW - Triiodothyronine -- metabolism KW - Humans KW - DNA Mutational Analysis KW - Electrophoretic Mobility Shift Assay KW - RNA, Messenger -- genetics KW - Protein Binding KW - Transcriptional Activation KW - Cloning, Molecular KW - Kidney Neoplasms -- genetics KW - Adenocarcinoma, Clear Cell -- genetics KW - Adenocarcinoma, Clear Cell -- metabolism KW - Kidney Neoplasms -- metabolism KW - Receptors, Thyroid Hormone -- metabolism KW - Receptors, Thyroid Hormone -- genetics KW - Receptors, Thyroid Hormone -- chemistry KW - Mutation -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71348074?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Expression+of+mutant+thyroid+hormone+nuclear+receptors+is+associated+with+human+renal+clear+cell+carcinoma.&rft.au=Kamiya%2C+Yuji%3BPuzianowska-Kuznicka%2C+Monika%3BMcPhie%2C+Peter%3BNauman%2C+Janusz%3BCheng%2C+Sheue-yann%3BNauman%2C+Alicja&rft.aulast=Kamiya&rft.aufirst=Yuji&rft.date=2002-01-01&rft.volume=23&rft.issue=1&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-14 N1 - Date created - 2001-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Binding of FADD and caspase-8 to molluscum contagiosum virus MC159 v-FLIP is not sufficient for its antiapoptotic function. AN - 71347888; 11752160 AB - Molluscum contagiosum virus (MCV), a member of the human poxvirus family, encodes the MC159 protein that inhibits Fas-, tumor necrosis factor (TNF)-, and TNF-related apoptosis-inducing ligant (TRAIL)-induced apoptosis. We used site-directed mutagenesis to change charged or hydrophobic amino acid residues to alanines to identify regions of MC159 that are critical for protection from apoptosis and for protein-protein interactions. Surprisingly, while MC159 is thought to block apoptosis by binding to Fas-associated death domain (FADD) or caspase-8, several mutants that lost apoptosis blocking activity still bound to both FADD and caspase-8. Mutations in the predicted hydrophobic patch 1 and alpha2 regions of both death effector domains (DEDs) within MC159 resulted in loss of the ability to bind to FADD or caspase-8 and to block apoptosis. Amino acid substitutions in the RXDL motif located in the alpha6 region of either DED resulted in loss of protection from apoptosis induced by Fas, TNF, and TRAIL and abolished the ability of MC159 to block death effector filament formation. Thus, charged or hydrophobic amino acids in three regions of the MC159 DEDs (hydrophobic patch 1, alpha2, and alpha6) are critical for the protein's ability to interact with cellular proteins and to block apoptosis. JF - Journal of virology AU - Garvey, Tara L AU - Bertin, John AU - Siegel, Richard M AU - Wang, G H AU - Lenardo, Michael J AU - Cohen, Jeffrey I AD - Medical Virology Section, Laboratory of Clinical Investigation, Molecular Development of the Immune System Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA. Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 697 EP - 706 VL - 76 IS - 2 SN - 0022-538X, 0022-538X KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Antigens, CD95 KW - Apoptosis Regulatory Proteins KW - Carrier Proteins KW - FADD protein, human KW - Fas-Associated Death Domain Protein KW - Membrane Glycoproteins KW - TNF-Related Apoptosis-Inducing Ligand KW - TNFSF10 protein, human KW - Tumor Necrosis Factor-alpha KW - Viral Proteins KW - CASP8 protein, human KW - EC 3.4.22.- KW - CASP9 protein, human KW - Caspase 8 KW - Caspase 9 KW - Caspases KW - Index Medicus KW - HeLa Cells KW - Humans KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Jurkat Cells KW - Amino Acid Sequence KW - Protein Binding KW - Structure-Activity Relationship KW - Protein Structure, Quaternary KW - Antigens, CD95 -- metabolism KW - Amino Acid Motifs KW - Conserved Sequence KW - Molecular Sequence Data KW - Mutation -- genetics KW - Membrane Glycoproteins -- pharmacology KW - Protein Structure, Tertiary KW - Cell Line KW - Viral Proteins -- genetics KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- antagonists & inhibitors KW - Apoptosis -- drug effects KW - Viral Proteins -- chemistry KW - Viral Proteins -- metabolism KW - Molluscum contagiosum virus -- metabolism KW - Caspases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71347888?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Binding+of+FADD+and+caspase-8+to+molluscum+contagiosum+virus+MC159+v-FLIP+is+not+sufficient+for+its+antiapoptotic+function.&rft.au=Garvey%2C+Tara+L%3BBertin%2C+John%3BSiegel%2C+Richard+M%3BWang%2C+G+H%3BLenardo%2C+Michael+J%3BCohen%2C+Jeffrey+I&rft.aulast=Garvey&rft.aufirst=Tara&rft.date=2002-01-01&rft.volume=76&rft.issue=2&rft.spage=697&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-11 N1 - Date created - 2001-12-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Virology. 2001 Mar 30;282(1):14-25 [11259186] Biotechniques. 1990 May;8(5):528-35 [2357375] Nat Cell Biol. 2000 Apr;2(4):241-3 [10783243] Science. 2000 Jun 30;288(5475):2351-4 [10875917] Science. 2000 Jun 30;288(5475):2354-7 [10875918] Immunity. 2000 Jun;12(6):611-20 [10894161] Cell. 2001 Feb 23;104(4):487-501 [11239407] Cell. 1995 May 19;81(4):495-504 [7758105] Cell. 1995 Jun 16;81(6):935-46 [7540117] Cell. 1996 Jan 26;84(2):299-308 [8565075] Cell. 1996 Jun 14;85(6):817-27 [8681377] Science. 1996 Aug 9;273(5276):813-6 [8670425] Science. 1996 Nov 8;274(5289):990-2 [8875942] Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1172-6 [9037025] Nature. 1997 Apr 3;386(6624):517-21 [9087414] J Biol Chem. 1997 Apr 11;272(15):9621-4 [9092488] EMBO J. 1997 May 15;16(10):2794-804 [9184224] J Virol. 1997 Nov;71(11):8928-32 [9343261] Science. 1998 Mar 20;279(5358):1954-8 [9506948] Nature. 1998 Mar 19;392(6673):296-300 [9521326] Nature. 1998 Apr 30;392(6679):941-5 [9582077] J Cell Biol. 1998 Jun 1;141(5):1243-53 [9606215] J Cell Biol. 1998 Jun 1;141(5):1255-66 [9606216] FEBS Lett. 1998 Jul 24;431(3):351-6 [9714541] Science. 1998 Aug 28;281(5381):1305-8 [9721089] Results Probl Cell Differ. 1999;23:25-63 [9950028] Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4552-7 [10200300] Cell. 1999 Jul 9;98(1):47-58 [10412980] Genes Cells. 1999 Sep;4(9):541-9 [10526240] Immunity. 2000 Jun;12(6):599-609 [10894160] Erratum In: J Virol. 2006 Feb;80(3):1615 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antifungal efficacy of caspofungin (MK-0991) in experimental pulmonary aspergillosis in persistently neutropenic rabbits: pharmacokinetics, drug disposition, and relationship to galactomannan antigenemia. AN - 71347066; 11751105 AB - The antifungal efficacy, pharmacokinetics, and safety of caspofungin (CAS) were investigated in the treatment and prophylaxis of invasive pulmonary aspergillosis due to Aspergillus fumigatus in persistently neutropenic rabbits. Antifungal therapy consisted of 1, 3, or 6 mg of CAS/kg of body weight/day (CAS1, CAS3, and CAS6, respectively) or 1 mg of deoxycholate amphotericin B (AMB)/kg/day intravenously for 12 days starting 24 h after endotracheal inoculation. Prophylaxis (CAS1) was initiated 4 days before endotracheal inoculation. Rabbits treated with CAS had significant improvement in survival and reduction in organism-mediated pulmonary injury (OMPI) measured by pulmonary infarct score and total lung weight (P or =3 mg/kg/day. As serial galactomannan antigen levels may be used for therapeutic monitoring, one should be aware that profoundly neutropenic patients receiving echinocandins for aspergillosis might have persistent galactomannan antigenemia despite clinical improvement. CAS improved survival, reduced pulmonary injury, and caused dose-dependent hyphal damage but with no reduction in residual fungal burden or galactomannan antigenemia in persistently neutropenic rabbits with invasive pulmonary aspergillosis. JF - Antimicrobial agents and chemotherapy AU - Petraitiene, Ruta AU - Petraitis, Vidmantas AU - Groll, Andreas H AU - Sein, Tin AU - Schaufele, Robert L AU - Francesconi, Andrea AU - Bacher, John AU - Avila, Nilo A AU - Walsh, Thomas J AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 12 EP - 23 VL - 46 IS - 1 SN - 0066-4804, 0066-4804 KW - Anti-Bacterial Agents KW - 0 KW - Antifungal Agents KW - Echinocandins KW - Lipopeptides KW - Mannans KW - Peptides KW - Peptides, Cyclic KW - galactomannan KW - 11078-30-1 KW - caspofungin KW - F0XDI6ZL63 KW - Index Medicus KW - Aspergillus -- drug effects KW - Animals KW - Neutropenia -- metabolism KW - Neutropenia -- complications KW - Treatment Outcome KW - Disease Models, Animal KW - Rabbits KW - Antibiotic Prophylaxis KW - Microbial Sensitivity Tests KW - Female KW - Aspergillosis -- metabolism KW - Antifungal Agents -- adverse effects KW - Antifungal Agents -- pharmacokinetics KW - Lung Diseases, Fungal -- drug therapy KW - Anti-Bacterial Agents -- adverse effects KW - Aspergillosis -- drug therapy KW - Anti-Bacterial Agents -- blood KW - Mannans -- metabolism KW - Anti-Bacterial Agents -- pharmacokinetics KW - Antifungal Agents -- blood KW - Aspergillosis -- complications KW - Lung Diseases, Fungal -- metabolism KW - Lung Diseases, Fungal -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71347066?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Antifungal+efficacy+of+caspofungin+%28MK-0991%29+in+experimental+pulmonary+aspergillosis+in+persistently+neutropenic+rabbits%3A+pharmacokinetics%2C+drug+disposition%2C+and+relationship+to+galactomannan+antigenemia.&rft.au=Petraitiene%2C+Ruta%3BPetraitis%2C+Vidmantas%3BGroll%2C+Andreas+H%3BSein%2C+Tin%3BSchaufele%2C+Robert+L%3BFrancesconi%2C+Andrea%3BBacher%2C+John%3BAvila%2C+Nilo+A%3BWalsh%2C+Thomas+J&rft.aulast=Petraitiene&rft.aufirst=Ruta&rft.date=2002-01-01&rft.volume=46&rft.issue=1&rft.spage=12&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-15 N1 - Date created - 2001-12-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mycoses. 1999;42(7-8):431-42 [10546484] J Clin Microbiol. 1997 Jan;35(1):139-43 [8968895] Medicine (Baltimore). 2000 Jul;79(4):250-60 [10941354] Antimicrob Agents Chemother. 2000 Sep;44(9):2310-8 [10952573] Antimicrob Agents Chemother. 2001 Jan;45(1):327-30 [11120990] J Clin Oncol. 2001 Jan 1;19(1):253-9 [11134220] Med Mycol. 2000;38 Suppl 1:335-47 [11204162] Antimicrob Agents Chemother. 2001 Feb;45(2):596-600 [11158761] Expert Opin Investig Drugs. 2001 Feb;10(2):269-80 [11178340] Diagn Microbiol Infect Dis. 2001 Feb;39(2):99-103 [11248522] Antimicrob Agents Chemother. 1998 Jan;42(1):151-3 [9449276] Adv Pharmacol. 1998;44:343-500 [9547888] Diagn Microbiol Infect Dis. 1998 Apr;30(4):251-5 [9582584] Antimicrob Agents Chemother. 1998 Aug;42(8):1985-9 [9687394] J Clin Microbiol. 1998 Oct;36(10):2950-6 [9738049] Diagn Microbiol Infect Dis. 1998 Sep;32(1):33-7 [9791755] J Clin Microbiol. 1999 May;37(5):1625-7 [10203542] J Antimicrob Chemother. 1999 Apr;43(4):491-6 [10350377] Eur J Clin Microbiol Infect Dis. 1999 Apr;18(4):302-4 [10385023] J Clin Microbiol. 1999 Oct;37(10):3223-8 [10488181] Antimicrob Agents Chemother. 2001 Oct;45(10):2845-55 [11557479] J Pharmacokinet Biopharm. 1978 Apr;6(2):165-75 [671222] J Infect Dis. 1985 Nov;152(5):938-45 [2413145] Radiology. 1985 Dec;157(3):611-4 [3864189] J Comput Assist Tomogr. 1987 May-Jun;11(3):534-6 [3571603] J Clin Microbiol. 1987 May;25(5):931-2 [3294892] Lab Anim Sci. 1988 Aug;38(4):467-71 [3184859] Rev Infect Dis. 1990 Mar-Apr;12(2):308-29 [2184499] Clin Infect Dis. 1992 Mar;14 Suppl 1:S43-53 [1562695] Cancer. 1992 Jun 1;69(11):2653-62 [1315207] Infect Immun. 1992 Jun;60(6):2237-45 [1375195] J Infect Dis. 1994 Feb;169(2):356-68 [8106769] Antimicrob Agents Chemother. 1994 Jul;38(7):1480-9 [7979276] Annu Rev Microbiol. 1994;48:471-97 [7826015] Bone Marrow Transplant. 1994;14 Suppl 5:S1-2 [7703924] J Clin Microbiol. 1995 Feb;33(2):497-500 [7714217] Trends Microbiol. 1995 Mar;3(3):98-104 [7773595] Antimicrob Agents Chemother. 1995 May;39(5):1065-9 [7625790] Am J Respir Crit Care Med. 1995 Sep;152(3):1079-86 [7663787] J Clin Microbiol. 1995 Jul;33(7):1912-4 [7665670] Infect Dis Clin North Am. 1996 Jun;10(2):365-400 [8803625] J Clin Oncol. 1997 Jan;15(1):139-47 [8996135] J Med Vet Mycol. 1997 Mar-Apr;35(2):79-86 [9147267] Antimicrob Agents Chemother. 1997 Jul;41(7):1612-4 [9210698] Antimicrob Agents Chemother. 1997 Aug;41(8):1775-7 [9257759] Antimicrob Agents Chemother. 1997 Aug;41(8):1835-6 [9257774] J Med Vet Mycol. 1997 Jul-Aug;35(4):285-7 [9292427] Antimicrob Agents Chemother. 1997 Sep;41(9):1937-9 [9303388] Antimicrob Agents Chemother. 1997 Sep;41(9):1957-60 [9303393] Antimicrob Agents Chemother. 1997 Nov;41(11):2326-32 [9371328] Antimicrob Agents Chemother. 1997 Nov;41(11):2333-8 [9371329] Antimicrob Agents Chemother. 1997 Nov;41(11):2339-44 [9371330] J Antimicrob Chemother. 1997 Nov;40(5):611-4 [9421307] Clin Infect Dis. 1996 Sep;23(3):608-15 [8879787] Antimicrob Agents Chemother. 2000 Feb;44(2):368-77 [10639364] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The zebrafish: a new model organism for integrative physiology. AN - 71344536; 11742817 AB - This brief review summarizes features of the zebrafish, Danio rerio, that make it a suitable model organism for studies of regulatory physiology. The review presents the argument that random mutagenesis screens are a valuable gene-finding strategy to identify genes of functional importance and that their utility, although well established for developmental issues, will extend to a variety of topics of interest to the regulatory physiologist. Particular attention is drawn to the range of functional responses amenable to mutagenesis screens in larval zebrafish. Other virtues of the organism, the range of genomic tools, the potential for innovative optical methods, and the tractability for genetic and other experimental manipulations, are also described. Finally, the review provides examples of functional studies in zebrafish, including studies in sensory neurons, cardiac rhythm disturbances, gastrointestinal function, and studies of the developing kidney, that illustrate potential applications. Because of the relative ease with which combinatorial studies can be performed, the zebrafish may eventually be particularly valuable in understanding the functional interaction between subtle gene defects that cause polygenic disorders. JF - American journal of physiology. Regulatory, integrative and comparative physiology AU - Briggs, Josephine P AD - National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-2560, USA. Jbriggs@nih.gov Y1 - 2002/01// PY - 2002 DA - January 2002 SP - R3 EP - R9 VL - 282 IS - 1 SN - 0363-6119, 0363-6119 KW - Index Medicus KW - Animals KW - Models, Animal KW - Physiology -- methods KW - Zebrafish UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71344536?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+physiology.+Regulatory%2C+integrative+and+comparative+physiology&rft.atitle=The+zebrafish%3A+a+new+model+organism+for+integrative+physiology.&rft.au=Briggs%2C+Josephine+P&rft.aulast=Briggs&rft.aufirst=Josephine&rft.date=2002-01-01&rft.volume=282&rft.issue=1&rft.spage=R3&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Regulatory%2C+integrative+and+comparative+physiology&rft.issn=03636119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-16 N1 - Date created - 2001-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interactions between cocaine and dopamine agonists on cardiovascular function in squirrel monkeys. AN - 71343259; 11752114 AB - Conscious squirrel monkeys were treated i.v. with cocaine and various dopamine agonist drugs. Cocaine produced a dose-dependent increase in blood pressure, heart rate, and the rate-pressure product (RPP). The dopamine D1 receptor agonist (+/-)-6-chloro-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF 82958) produced effects comparable to cocaine. The D1 agonist (+/-)-6-chloro-7, 8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF 81297) also produced increases in blood pressure and heart rate but was much less potent than either cocaine or SKF 82958. The partial D1 agonist (+/-)-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SKF 77434) did not significantly affect any cardiovascular parameters. The D2 agonist quinpirole slightly decreased blood pressure and increased heart rate. As such, the RPP only slightly increased. The selective dopamine uptake inhibitor 1-[2-[bis-(4-fluorphenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR 12909) produced increases in blood pressure, heart rate, and RPP, but again these effects were smaller and only seen at doses higher than cocaine. Effects similar to those with GBR 12909 were seen with the dopamine autoreceptor antagonist cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin (UH 232). The combination of GBR 12909, SKF 82958, or SKF 77434 with cocaine produced effects that were clearly subadditive. The effects of quinpirole in combination with cocaine were comparable to, or lower than, those of cocaine alone on blood pressure and RPP. The effects on heart rate were additive. Only UH 232 produced additive effects with cocaine for all three measures. As dopamine agonists have been proposed as potential treatments for cocaine abuse, these results suggest that dopamine D1 agonists and uptake inhibitors can be used safely in combination with cocaine. Caution may be warranted, however, with the use of dopamine autoreceptor antagonists in the treatment of cocaine abuse. JF - The Journal of pharmacology and experimental therapeutics AU - Schindler, C W AU - Gilman, J P AU - Bergman, J AU - Mello, N K AU - Woosley, R L AU - Goldberg, S R AD - Preclinical Pharmacology Section, Behavioral Neuroscience Branch, National Institutes of Health/National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland 21224, USA. cschindl@helix.nih.gov Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 180 EP - 187 VL - 300 IS - 1 SN - 0022-3565, 0022-3565 KW - Dopamine Agonists KW - 0 KW - Dopamine Antagonists KW - Dopamine Uptake Inhibitors KW - Receptors, Dopamine D1 KW - Receptors, Dopamine D2 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Saimiri KW - Animals KW - Heart Rate -- drug effects KW - Drug Interactions KW - Receptors, Dopamine D1 -- agonists KW - Dopamine Antagonists -- pharmacology KW - Receptors, Dopamine D2 -- agonists KW - Blood Pressure -- drug effects KW - Male KW - Hemodynamics -- drug effects KW - Dopamine Agonists -- pharmacology KW - Cocaine -- pharmacology KW - Dopamine Uptake Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71343259?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Interactions+between+cocaine+and+dopamine+agonists+on+cardiovascular+function+in+squirrel+monkeys.&rft.au=Schindler%2C+C+W%3BGilman%2C+J+P%3BBergman%2C+J%3BMello%2C+N+K%3BWoosley%2C+R+L%3BGoldberg%2C+S+R&rft.aulast=Schindler&rft.aufirst=C&rft.date=2002-01-01&rft.volume=300&rft.issue=1&rft.spage=180&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-24 N1 - Date created - 2001-12-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Xenobiotic efflux pumps in isolated fish brain capillaries. AN - 71343221; 11742838 AB - To identify specific transporters that drive xenobiotics from the central nervous system to blood, the accumulation of fluorescent drugs was studied in isolated capillaries from killifish and dogfish shark brain using confocal microscopy and quantitative image analysis. In killifish brain capillaries, luminal accumulation of fluorescent derivatives of cyclosporin A and verapamil was concentrative, specific, and energy dependent (inhibition by KCN). Transport was reduced by PSC-833, but not by leukotriene C4, indicating the involvement of P-glycoprotein. The ability of capillaries to transport the cyclosporin A derivative was unchanged over 20 h, demonstrating the long-term viability of the preparation. Luminal accumulation of the fluorescent organic anions sulforhodamine 101 and fluorescein-methotrexate was also concentrative, specific, and energy dependent. Transport of these compounds was reduced by leukotriene C4, but not by PSC-833, indicating the involvement of a multidrug resistance-associated protein (Mrp). Similar results were obtained for isolated capillaries from dogfish shark. Immunostaining localized P-glycoprotein and Mrp2 to the luminal surface of the killifish brain capillary endothelium. These findings validate a new and long-lived comparative model for studying drug transport across the blood-brain barrier and, as in mammals, implicate P-glycoprotein and Mrp2 in transport from the central nervous system to blood in fish. JF - American journal of physiology. Regulatory, integrative and comparative physiology AU - Miller, David S AU - Graeff, Claudia AU - Droulle, Lucy AU - Fricker, Stefanie AU - Fricker, Gert AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. miller@niehs.nih.gov Y1 - 2002/01// PY - 2002 DA - January 2002 SP - R191 EP - R198 VL - 282 IS - 1 SN - 0363-6119, 0363-6119 KW - 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene KW - 0 KW - Boron Compounds KW - Calcium Channel Blockers KW - Cyclosporins KW - Enzyme Inhibitors KW - Fluorescent Dyes KW - Indicators and Reagents KW - Membrane Transport Proteins KW - Multidrug Resistance-Associated Proteins KW - P-Glycoprotein KW - Xenobiotics KW - Leukotriene C4 KW - 2CU6TT9V48 KW - multidrug resistance-associated protein 2 KW - 4AF605U6JN KW - Cyclosporine KW - 83HN0GTJ6D KW - Verapamil KW - CJ0O37KU29 KW - 4-Chloro-7-nitrobenzofurazan KW - EQF2794IRE KW - Potassium Cyanide KW - MQD255M2ZO KW - valspodar KW - Q7ZP55KF3X KW - multidrug resistance-associated protein 1 KW - Y49M64GZ4Q KW - Index Medicus KW - Microscopy, Confocal KW - Animals KW - Leukotriene C4 -- pharmacology KW - Indicators and Reagents -- pharmacokinetics KW - Cyclosporins -- pharmacology KW - Potassium Cyanide -- pharmacology KW - Calcium Channel Blockers -- pharmacokinetics KW - Capillaries -- physiology KW - Boron Compounds -- pharmacokinetics KW - 4-Chloro-7-nitrobenzofurazan -- pharmacokinetics KW - Dogfish KW - P-Glycoprotein -- metabolism KW - Multidrug Resistance-Associated Proteins -- metabolism KW - In Vitro Techniques KW - Verapamil -- pharmacokinetics KW - Fundulidae KW - Enzyme Inhibitors -- pharmacokinetics KW - Fluorescent Dyes -- pharmacokinetics KW - Cyclosporine -- pharmacokinetics KW - Blood-Brain Barrier -- drug effects KW - Xenobiotics -- pharmacokinetics KW - Brain -- blood supply KW - Blood-Brain Barrier -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71343221?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+physiology.+Regulatory%2C+integrative+and+comparative+physiology&rft.atitle=Xenobiotic+efflux+pumps+in+isolated+fish+brain+capillaries.&rft.au=Miller%2C+David+S%3BGraeff%2C+Claudia%3BDroulle%2C+Lucy%3BFricker%2C+Stefanie%3BFricker%2C+Gert&rft.aulast=Miller&rft.aufirst=David&rft.date=2002-01-01&rft.volume=282&rft.issue=1&rft.spage=R191&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Regulatory%2C+integrative+and+comparative+physiology&rft.issn=03636119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-16 N1 - Date created - 2001-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - O(2)-Vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate protection against D-galactosamine/endotoxin-induced hepatotoxicity in mice: genomic analysis using microarrays. AN - 71341313; 11752092 AB - O(2)-Vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO), a liver-selective nitric oxide (NO)-donating prodrug, is metabolized by hepatic enzymes to release NO within the liver. This study was undertaken to examine the effects of V-PYRRO/NO on D-galactosamine/lipopolysaccharide (GlaN/LPS)-induced liver injury in mice. Mice were given injections of V-PYRRO/NO (10 mg/kg, s.c. at 2-h intervals) before and after GlaN/LPS (700 mg/30 microg/kg, i.p.). V-PYRRO/NO administration dramatically reduced GlaN/LPS-induced hepatotoxicity, as evidenced by reduced serum alanine aminotransferase activity and improved pathology. To examine the mechanisms of the protection, cDNA microarray was performed to profile the gene expression pattern in livers of mice treated with GlaN/LPS, GlaN/LPS plus V-PYRRO/NO, or controls. V-PYRRO/NO administration greatly ameliorated GlaN/LPS-induced alterations in the expression of genes encoding the stress response, DNA damage/repair response, and drug-metabolizing enzymes in accordance with hepatoprotection. Gel shift assay and Western blot analysis supported microarray results, showing that V-PYRRO/NO suppressed GlaN/LPS-induced activation of nuclear factor-kappaB and GlaN/LPS-induced increases in caspase-1, caspase-8, tumor necrosis factor receptor 1 (TNFR1)-associated death domain, and TNF-related apoptosis-inducing ligand. Immunohistochemical analysis further revealed that GlaN/LPS-induced activation of TNFR1, caspase-3, and hepatocellular apoptosis was ameliorated by V-PYRRO/NO treatment. GlaN/LPS-induced elevation of hepatic caspase-3 activity was diminished by V-PYRRO/NO treatment. In addition, V-PYRRO/NO alone suppressed the basal expression of genes encoding inducible NO synthase and TNF-alpha-related components, as revealed by mouse 1.2 array. In summary, this study demonstrates that the liver-selective NO donor, V-PYRRO/NO, is effective in blocking GlaN/LPS-induced hepatotoxicity in mice, and that this protection appears to involve, at least in part, the suppression of the TNF-alpha-mediated cell death pathways. JF - The Journal of pharmacology and experimental therapeutics AU - Liu, Jie AU - Saavedra, Joseph E AU - Lu, Tong AU - Song, Jian-Guo AU - Clark, James AU - Waalkes, Michael P AU - Keefer, Larry K AD - Inorganic Carcinogenesis Section, National Cancer Institute at National Institute of Environmental Health Sciences, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Liu6@niehs.nih.gov Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 18 EP - 25 VL - 300 IS - 1 SN - 0022-3565, 0022-3565 KW - Antigens, CD KW - 0 KW - Endotoxins KW - Lipopolysaccharides KW - NF-kappa B KW - O(2)-vinyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate KW - Pyrrolidines KW - Receptors, Tumor Necrosis Factor KW - Receptors, Tumor Necrosis Factor, Type I KW - Tumor Necrosis Factor-alpha KW - Galactosamine KW - 7535-00-4 KW - Casp3 protein, mouse KW - EC 3.4.22.- KW - Caspase 3 KW - Caspases KW - Index Medicus KW - Antigens, CD -- biosynthesis KW - Animals KW - Oligonucleotide Array Sequence Analysis KW - Lipopolysaccharides -- antagonists & inhibitors KW - Apoptosis -- physiology KW - Caspases -- biosynthesis KW - Tumor Necrosis Factor-alpha -- physiology KW - Mice KW - Genome KW - NF-kappa B -- biosynthesis KW - Blotting, Western KW - Receptors, Tumor Necrosis Factor -- biosynthesis KW - Signal Transduction -- drug effects KW - Lipopolysaccharides -- toxicity KW - Gene Expression Regulation -- drug effects KW - Tumor Necrosis Factor-alpha -- metabolism KW - Immunohistochemistry KW - Male KW - Chemical and Drug Induced Liver Injury -- prevention & control KW - Galactosamine -- toxicity KW - Pyrrolidines -- therapeutic use KW - Chemical and Drug Induced Liver Injury -- genetics KW - Endotoxins -- antagonists & inhibitors KW - Endotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71341313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=O%282%29-Vinyl+1-%28pyrrolidin-1-yl%29diazen-1-ium-1%2C2-diolate+protection+against+D-galactosamine%2Fendotoxin-induced+hepatotoxicity+in+mice%3A+genomic+analysis+using+microarrays.&rft.au=Liu%2C+Jie%3BSaavedra%2C+Joseph+E%3BLu%2C+Tong%3BSong%2C+Jian-Guo%3BClark%2C+James%3BWaalkes%2C+Michael+P%3BKeefer%2C+Larry+K&rft.aulast=Liu&rft.aufirst=Jie&rft.date=2002-01-01&rft.volume=300&rft.issue=1&rft.spage=18&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-24 N1 - Date created - 2001-12-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Early environmental stress and biological vulnerability to drug abuse. AN - 71341079; 11750773 AB - It has long been believed that stress and drug abuse are related. Studies using animal models have repeatedly demonstrated that stressed animals more readily self-administer alcohol or other drugs. Similarly, human patients consistently report in clinical interviews that stress is one reason for taking drugs. There are also studies that document neurophysiological, neuroanatomical, neurochemical, and physiological changes to animals and humans who are stressed. Many of these changes occur within biological systems that are also affected by psychoactive drugs. Early response to stress also modifies neurodevelopment in permanent ways, and these neuroadaptations occur within the same neuronal systems which comprise the drug-reward circuit. But absent are studies in humans that link early stress and modifications of neurodevelopment with increased vulnerability to drug abuse. This article provides a glimpse of research relating stress to alteration of brain functions and to drug abuse, and points to the work of others in this volume for more details. We hope this attempt to understand how early stress affects the developing brain and increases vulnerability to drug abuse will lead to a new program of research in this emerging area. JF - Psychoneuroendocrinology AU - Gordon, Harold W AD - Clinical Neurobiology Branch, Division of Treatment Research and Development, National Institute on Drug Abuse, The Neuroscience Center, 6001 Executive Boulevard, Room 4234, MSC 9559, Bethesda, MD 20892-9559, USA. hg23r@nih.gov PY - 2002 SP - 115 EP - 126 VL - 27 IS - 1-2 SN - 0306-4530, 0306-4530 KW - Index Medicus KW - Animals KW - Humans KW - Population KW - Social Environment KW - Substance-Related Disorders -- physiopathology KW - Stress, Psychological -- genetics KW - Stress, Psychological -- physiopathology KW - Stress, Psychological -- epidemiology KW - Substance-Related Disorders -- psychology KW - Substance-Related Disorders -- genetics KW - Substance-Related Disorders -- epidemiology KW - Stress, Psychological -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71341079?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychoneuroendocrinology&rft.atitle=Early+environmental+stress+and+biological+vulnerability+to+drug+abuse.&rft.au=Gordon%2C+Harold+W&rft.aulast=Gordon&rft.aufirst=Harold&rft.date=2002-01-01&rft.volume=27&rft.issue=1-2&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Psychoneuroendocrinology&rft.issn=03064530&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-18 N1 - Date created - 2001-12-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nonpeptidomimetic farnesyltransferase inhibitor RPR-115135 increases cytotoxicity of 5-fluorouracil: role of p53. AN - 71340590; 11752120 AB - A new nonpeptidic farnesyltransferase inhibitor, RPR-115135, in combination with 5-fluorouracil (5-FU) was studied in an isogenic cell line model system consisting of human colon cancer HCT-116 cells. HCT-116 cells were transfected with an empty control pCMV vector and with a dominant-negative mutated p53 transgene (248R/W). We found that, relative to control transfectants, there was a slight tendency for the p53 inactivated cells to be less sensitive to 5-FU after 6 days of continuous treatment. Simultaneous administration of RPR-115135 and 5-FU, at equitoxic concentrations, resulted in an enhancement of 5-FU cytotoxicity, especially in the CMV-2 clone. Growth inhibition could be accounted for on the basis of a specific cell cycle arrest phenotype (G(2)-M arrest in CMV-2 and S arrest in mutated clones), as assayed by flow cytometry. The combination RPR-115135 + 5-FU increases apoptotic events only in the CMV-2 clone. JF - The Journal of pharmacology and experimental therapeutics AU - Russo, Patrizia AU - Ottoboni, Cristina AU - Malacarne, Davide AU - Crippa, Alessandra AU - Riou, Jean-Francois AU - O'Connor, Patrick M AD - Laboratory of Molecular Pharmacology, Division Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. patrizia.russo@istge.it Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 220 EP - 226 VL - 300 IS - 1 SN - 0022-3565, 0022-3565 KW - Antimetabolites, Antineoplastic KW - 0 KW - Enzyme Inhibitors KW - Indoles KW - RPR115135 KW - Tumor Suppressor Protein p53 KW - Alkyl and Aryl Transferases KW - EC 2.5.- KW - Farnesyltranstransferase KW - EC 2.5.1.29 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Phenotype KW - Clone Cells KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Humans KW - DNA Fragmentation -- drug effects KW - Flow Cytometry KW - Cell Cycle -- drug effects KW - Tumor Suppressor Protein p53 -- physiology KW - Fluorouracil -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Alkyl and Aryl Transferases -- antagonists & inhibitors KW - Indoles -- pharmacology KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71340590?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Nonpeptidomimetic+farnesyltransferase+inhibitor+RPR-115135+increases+cytotoxicity+of+5-fluorouracil%3A+role+of+p53.&rft.au=Russo%2C+Patrizia%3BOttoboni%2C+Cristina%3BMalacarne%2C+Davide%3BCrippa%2C+Alessandra%3BRiou%2C+Jean-Francois%3BO%27Connor%2C+Patrick+M&rft.aulast=Russo&rft.aufirst=Patrizia&rft.date=2002-01-01&rft.volume=300&rft.issue=1&rft.spage=220&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-24 N1 - Date created - 2001-12-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alternative mutations at position 76 of the vacuolar transmembrane protein PfCRT are associated with chloroquine resistance and unique stereospecific quinine and quinidine responses in Plasmodium falciparum. AN - 71337540; 11752204 AB - Chloroquine resistance (CQR) in Plasmodium falciparum is associated with multiple mutations in the digestive vacuole membrane protein PfCRT. The chloroquine-sensitive (CQS) 106/1 line of P. falciparum has six of seven PfCRT mutations consistently found in CQR parasites from Asia and Africa. The missing mutation at position 76 (K76T in reported population surveys) may therefore be critical to CQR. To test this hypothesis, we exposed 106/1 populations (10(9)-10(10) parasites) to a chloroquine (CQ) concentration lethal to CQS parasites. In multiple independent experiments, surviving CQR parasites were detected in the cultures after 28 to 42 days. These parasites showed novel K76N or K76I PfCRT mutations and corresponding CQ IC(50) values that were approximately 8- and 12-fold higher than that of the original 106/1 IC(50). A distinctive feature of the K76I line relative to 106/1 parasites was their greatly increased sensitivity to quinine (QN) but reduced sensitivity to its enantiomer quinidine (QD), indicative of a unique stereospecific response not observed in other CQR lines. Furthermore, verapamil had the remarkable effect of antagonizing the QN response while potentiating the QD response of K76I parasites. In our single-step drug selection protocol, the probability of the simultaneous selection of two specific mutations required for CQR is extremely small. We conclude that the K76N or K76I change added to the other pre-existing mutations in the 106/1 PfCRT protein was responsible for CQR. The various mutations that have now been documented at PfCRT position 76 (K76T, K76N, K76I) suggest that the loss of lysine is central to the CQR mechanism. JF - Molecular pharmacology AU - Cooper, Roland A AU - Ferdig, Michael T AU - Su, Xin-Zhuan AU - Ursos, Lyann M B AU - Mu, Jianbing AU - Nomura, Takashi AU - Fujioka, Hisashi AU - Fidock, David A AU - Roepe, Paul D AU - Wellems, Thomas E AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 35 EP - 42 VL - 61 IS - 1 SN - 0026-895X, 0026-895X KW - Antimalarials KW - 0 KW - Calcium Channel Blockers KW - Membrane Proteins KW - Membrane Transport Proteins KW - PfCRT protein, Plasmodium falciparum KW - Protozoan Proteins KW - Chloroquine KW - 886U3H6UFF KW - Quinine KW - A7V27PHC7A KW - Verapamil KW - CJ0O37KU29 KW - Acridine Orange KW - F30N4O6XVV KW - Quinidine KW - ITX08688JL KW - Index Medicus KW - Animals KW - Drug Resistance -- physiology KW - Drug Interactions KW - Acridine Orange -- chemistry KW - Fluorescence KW - Parasitic Sensitivity Tests KW - Verapamil -- pharmacology KW - Antimalarials -- pharmacology KW - Calcium Channel Blockers -- pharmacology KW - Molecular Conformation KW - Mutation KW - Quinine -- pharmacology KW - Chloroquine -- pharmacology KW - Quinidine -- pharmacology KW - Membrane Proteins -- genetics KW - Plasmodium falciparum -- physiology KW - Plasmodium falciparum -- drug effects KW - Membrane Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71337540?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Alternative+mutations+at+position+76+of+the+vacuolar+transmembrane+protein+PfCRT+are+associated+with+chloroquine+resistance+and+unique+stereospecific+quinine+and+quinidine+responses+in+Plasmodium+falciparum.&rft.au=Cooper%2C+Roland+A%3BFerdig%2C+Michael+T%3BSu%2C+Xin-Zhuan%3BUrsos%2C+Lyann+M+B%3BMu%2C+Jianbing%3BNomura%2C+Takashi%3BFujioka%2C+Hisashi%3BFidock%2C+David+A%3BRoepe%2C+Paul+D%3BWellems%2C+Thomas+E&rft.aulast=Cooper&rft.aufirst=Roland&rft.date=2002-01-01&rft.volume=61&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-10 N1 - Date created - 2001-12-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The FANCG Fanconi anemia protein interacts with CYP2E1: possible role in protection against oxidative DNA damage. AN - 71335286; 11756225 AB - Fanconi anemia (FA) is a genetic disorder that leads to aplastic anemia and birth defects and predisposes to cancer. FA cells exhibit characteristic hypersensitivity to DNA cross-linking agents such as mitomycin C (MMC), and FANCG is one of six known FA gene products. By immunocytochemical analysis of transfected cells, we discovered that although FANCG localized to both the nucleus and cytoplasm, there was an increase in cells with predominantly cytoplasmic staining after treatment with MMC. Concurrently, while searching by two-hybrid analysis for proteins that associate with FANCG, we identified a novel interaction between FANCG and cytochrome P450 2E1 (CYP2E1). A member of the P450 superfamily, CYP2E1 is associated with the production of reactive oxygen intermediates and the bioactivation of carcinogens. High constitutive levels of CYP2E1 were found in a FA-G lymphoblast cell line, whereas complementation of the FA-G line with wild-type FANCG was associated with decreased CYP2E1. These findings suggested that the interaction of FANCG with CYP2E1 might alter redox metabolism and increase DNA oxidation. Using a fluorescent assay, we found a dose-dependent increase in the oxidized DNA base, 8-oxoguanine (8-oxoG), after treatment of mutant FA-G cells with H(2)O(2) or MMC. Conversely, significantly lower levels of 8-oxoG were detected in FANCG-complemented FA-G cells. We conclude that the unknown function of FANCG involves at least transient interaction with cytoplasmic components, possibly including CYP2E1, and propose a role for FANCG in protection against oxidative DNA damage. JF - Carcinogenesis AU - Futaki, Makoto AU - Igarashi, Takehito AU - Watanabe, Shinji AU - Kajigaya, Sachiko AU - Tatsuguchi, Atsushi AU - Wang, Jianxiang AU - Liu, Johnson M AD - Hematology Branch, NHLBI, NIH, Building 10, Room 7C103, Bethesda, MD 20892, USA. Y1 - 2002/01// PY - 2002 DA - January 2002 SP - 67 EP - 72 VL - 23 IS - 1 SN - 0143-3334, 0143-3334 KW - DNA-Binding Proteins KW - 0 KW - FANCG protein, human KW - Fanconi Anemia Complementation Group G Protein KW - RNA, Messenger KW - Guanosine KW - 12133JR80S KW - 8-hydroxyguanosine KW - 3868-31-3 KW - Mitomycin KW - 50SG953SK6 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Microscopy, Confocal KW - Oxidation-Reduction -- drug effects KW - HeLa Cells KW - Humans KW - Mitomycin -- pharmacology KW - Two-Hybrid System Techniques KW - Glutathione Transferase -- metabolism KW - Hydrogen Peroxide -- pharmacology KW - RNA, Messenger -- genetics KW - Protein Binding KW - Blotting, Western KW - RNA, Messenger -- metabolism KW - Flow Cytometry KW - Subcellular Fractions -- metabolism KW - Cell Line KW - Guanosine -- analogs & derivatives KW - Oxidative Stress -- drug effects KW - Cytochrome P-450 CYP2E1 -- metabolism KW - Guanosine -- metabolism KW - DNA-Binding Proteins -- metabolism KW - DNA Damage -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71335286?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=The+FANCG+Fanconi+anemia+protein+interacts+with+CYP2E1%3A+possible+role+in+protection+against+oxidative+DNA+damage.&rft.au=Futaki%2C+Makoto%3BIgarashi%2C+Takehito%3BWatanabe%2C+Shinji%3BKajigaya%2C+Sachiko%3BTatsuguchi%2C+Atsushi%3BWang%2C+Jianxiang%3BLiu%2C+Johnson+M&rft.aulast=Futaki&rft.aufirst=Makoto&rft.date=2002-01-01&rft.volume=23&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-14 N1 - Date created - 2001-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The intersection of stress, drug abuse and development. AN - 71331941; 11750780 AB - Use or abuse of licit and illicit substances is often associated with environmental stress. Current clinical evidence clearly demonstrates neurobehavioral, somatic growth and developmental deficits in children born to drug-using mothers. However, the effects of environmental stress and its interaction with prenatal drug exposure on a child's development is unknown. Studies in pregnant animals under controlled conditions show drug-induced long-term alterations in brain structures and functions of the offspring. These cytoarchitecture alterations in the brain are often associated with perturbations in neurotransmitter systems that are intimately involved in the regulation of the stress responses. Similar abnormalities have been observed in the brains of animals exposed to other adverse exogenous (e.g., environmental stress) and/or endogenous (e.g., glucocorticoids) experiences during early life. The goal of this article is to: (1) provide evidence and a perspective that common neural systems are influenced during development both by perinatal drug exposure and early stress exposure; and (2) identify gaps and encourage new research examining the effects of early stress and perinatal drug exposure, in animal models, that would elucidate how stress- and drug-induced perturbations in neural systems influence later vulnerability to abused drugs in adult offspring. JF - Psychoneuroendocrinology AU - Thadani, Pushpa V AD - Division of Neuroscience and Behavioral Research, National Institute on Drug Abuse, The Neuroscience Center, 6001 Executive Boulevard, Room 4282, MSC 9555, Bethesda, MD 20892-9555, USA. pt242@nih.gov PY - 2002 SP - 221 EP - 230 VL - 27 IS - 1-2 SN - 0306-4530, 0306-4530 KW - Index Medicus KW - Humans KW - Adult KW - Child KW - Brain -- physiology KW - Brain -- growth & development KW - Stress, Psychological -- physiopathology KW - Substance-Related Disorders -- etiology KW - Child Development -- physiology KW - Substance-Related Disorders -- psychology KW - Stress, Psychological -- psychology KW - Stress, Psychological -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71331941?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychoneuroendocrinology&rft.atitle=The+intersection+of+stress%2C+drug+abuse+and+development.&rft.au=Thadani%2C+Pushpa+V&rft.aulast=Thadani&rft.aufirst=Pushpa&rft.date=2002-01-01&rft.volume=27&rft.issue=1-2&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Psychoneuroendocrinology&rft.issn=03064530&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-18 N1 - Date created - 2001-12-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mandalas as a Therapeutic Technique for HIV-Infected Children and Adolescents: What Do They Reveal? AN - 61546855; 200304328 AB - HIV positive children need a safe outlet to express their feelings about living with the virus. Creative therapeutic techniques such as the creation of mandalas (circle drawings) can facilitate the development of an emotional outlet. Carl G. Jung used mandalas in his work & believed that they are the paths to our center, the voice of our unconscious. The content of 32 mandalas created by children & adolescents living with HIV during clinical sessions with their social worker was analyzed for the themes expressed & colors utilized. The most prominent themes within the artwork concerned the concrete aspects of living with HIV. However, negative themes were balanced by themes concerning happiness, optimism, social relationships, & the normalcy of everyday life. The artwork illustrates that HIV plays a prominent role in the lives of the participants. Their resiliency is evidenced by the fact that nearly half of the themes expressed were positive & life affirming. 3 Tables, 1 Figure, 19 References. Adapted from the source document. COPIES ARE AVAILABLE FROM: HAWORTH DOCUMENT DELIVERY CENTER, The Haworth Press, Inc., 10 Alice Street, Binghamton, NY 13904-1580 JF - Journal of HIV/AIDS & Social Services AU - Wiener, Lori S AU - Battles, Haven B AD - National Cancer Instit, National Instits Health, Bethesda, MD wienerl@mail.nih.gov Y1 - 2002///0, PY - 2002 DA - 0, 2002 SP - 27 EP - 39 VL - 1 IS - 3 SN - 1538-1501, 1538-1501 KW - mandalas KW - Art Works KW - Clinical Social Work KW - Psychotherapy KW - Acquired Immune Deficiency Syndrome KW - United States of America KW - Children KW - Unconscious (Psychology) KW - Treatment Methods KW - Adolescents KW - article KW - 6121: therapeutic interventions KW - 6126: acquired immune deficiency syndrome (AIDS) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61546855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+HIV%2FAIDS+%26+Social+Services&rft.atitle=Mandalas+as+a+Therapeutic+Technique+for+HIV-Infected+Children+and+Adolescents%3A+What+Do+They+Reveal%3F&rft.au=Wiener%2C+Lori+S%3BBattles%2C+Haven+B&rft.aulast=Wiener&rft.aufirst=Lori&rft.date=2002-01-01&rft.volume=1&rft.issue=3&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Journal+of+HIV%2FAIDS+%26+Social+Services&rft.issn=15381501&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Last updated - 2016-09-28 N1 - SubjectsTermNotLitGenreText - Children; Adolescents; Acquired Immune Deficiency Syndrome; Treatment Methods; Psychotherapy; Unconscious (Psychology); Clinical Social Work; Art Works; United States of America ER - TY - JOUR T1 - The Community Epidemiology Work Group Approach AN - 61500316; 200301834 AB - "Drug abuse" provides many unique challenges to the research community. Some of these involve fundamental epidemiologic issues, such as measuring the extent of the problem, identifying & assessing changes in patterns & trends, detecting emerging "drugs of abuse," characterizing vulnerable populations, & determining health & social consequences. A number of research methods are employed to address these issues. This paper describes one of these -- a model in which ongoing surveillance of "drug abuse" is maintained through a network of community-based researchers, local officials, academics, & other interested & qualified members of the community. Timely, accurate, & cost-effective data can be generated through systematic collection & analysis of indirect indicators of "drug abuse" that are often routinely produced by a variety of community sources. This information, in turn, can be used to make informed public health policy decisions. The community-based network model has been implemented at the city, state, national, regional, & international levels, & a case is made that this type of program could be useful, as well, in understanding the dynamics of "drug abuse" in rural areas of the country. 1 Table, 20 References. Adapted from the source document. JF - Substance Use & Misuse AU - Kozel, Nicholas J AU - Robertson, Elizabeth B AU - Falkowski, Carol L AD - National Instits Health, National Instit Drug Abuse, Division Epidemiology/Services/Prevention Research, Rockville, MD nkozel@ngmsmtp.nida.nih.gov Y1 - 2002///0, PY - 2002 DA - 0, 2002 SP - 783 EP - 803 VL - 37 IS - 5-7 SN - 1082-6084, 1082-6084 KW - Drug Addiction KW - Rural Communities KW - Rural Population KW - Research Methodology KW - Research Design KW - Drug Abuse KW - article KW - 6129: addiction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61500316?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Substance+Use+%26+Misuse&rft.atitle=The+Community+Epidemiology+Work+Group+Approach&rft.au=Kozel%2C+Nicholas+J%3BRobertson%2C+Elizabeth+B%3BFalkowski%2C+Carol+L&rft.aulast=Kozel&rft.aufirst=Nicholas&rft.date=2002-01-01&rft.volume=16&rft.issue=4&rft.spage=418&rft.isbn=&rft.btitle=&rft.title=Trauma%2C+Violence%2C+%26+Abuse&rft.issn=15248380&rft_id=info:doi/10.1177%2F1524838014537908 LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Last updated - 2016-09-28 N1 - CODEN - SUMIFL N1 - SubjectsTermNotLitGenreText - Drug Abuse; Drug Addiction; Rural Population; Rural Communities; Research Methodology; Research Design ER - TY - JOUR T1 - Palynology of the Cretaceous-Tertiary boundary in central Montana; evidence extraterrestrial impact as a cause of the terminal Cretaceous extinctions AN - 52032999; 2003-006860 AB - This report details a statistical analysis of palynological change across iridium-enriched claystones defining the Cretaceous-Tertiary (K-T) boundary in the Cretaceous Hell Creek Formation and Tertiary Tullock Member of the Fort Union Formation, eastern Montana, United States. The results strongly support the bolide impact model of terminal Cretaceous extinctions. Chi-square analysis of presence and abundance below and above the iridium datum was used to define characteristic Cretaceous and Tertiary palynomorph species. There is no statistical support for gradual decline in Cretaceous species below the iridium datum, although the presence and abundance of certain Cretaceous species decline somewhat, and the presence of Tertiary species increases slightly, 0-3 m below the iridium datum. An estimated 15%-30% of the Hell Creek palynoflora disappear 0-2 cm above the iridium datum, and another 20%-30% undergoes a significant decline in abundance. Palynoflorules directly overlying the iridium datum are characteristically depauperate. Partial recovery of the palynoflora occurs within 10-20 cm of the boundary, but species richness remains depressed throughout the lower Tullock Member compared to the Hell Creek Formation. Palynoflorules from rare Hell Creek coals contain significantly fewer Cretaceous and significantly more Tertiary species, relative to those of flood-plain deposits, suggesting that perhaps 30%-40% of affected Hell Creek species disappear or decline due to facies change. Greenhouse warming from impact-generated atmospheric CO (sub 2) and consequent increased soil water saturation, combined with still uncertain mass-kill mechanisms, best fit the available data to explain the pattern of change in vegetation at the K-T boundary throughout the Western Interior. JF - Special Paper - Geological Society of America AU - Hotton, Carol L A2 - Hartman, Joseph H. A2 - Johnson, Kirk R. A2 - Nichols, Douglas J. Y1 - 2002 PY - 2002 DA - 2002 SP - 473 EP - 501 PB - Geological Society of America (GSA), Boulder, CO VL - 361 SN - 0072-1077, 0072-1077 KW - United States KW - Northern Great Plains KW - lower Paleocene KW - Cretaceous KW - central Montana KW - Upper Cretaceous KW - Cenozoic KW - Western Interior KW - Paleocene KW - Garfield County Montana KW - Great Plains KW - Tullock Member KW - McCone County Montana KW - Fort Union Formation KW - North America KW - Hell Creek Formation KW - statistical analysis KW - Paleogene KW - paleogeography KW - Mesozoic KW - Montana KW - Tertiary KW - K-T boundary KW - palynomorphs KW - stratigraphic boundary KW - microfossils KW - 12:Stratigraphy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/52032999?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Special+Paper+-+Geological+Society+of+America&rft.atitle=Palynology+of+the+Cretaceous-Tertiary+boundary+in+central+Montana%3B+evidence+extraterrestrial+impact+as+a+cause+of+the+terminal+Cretaceous+extinctions&rft.au=Hotton%2C+Carol+L&rft.aulast=Hotton&rft.aufirst=Carol&rft.date=2002-01-01&rft.volume=361&rft.issue=&rft.spage=473&rft.isbn=0813723612&rft.btitle=&rft.title=Special+Paper+-+Geological+Society+of+America&rft.issn=00721077&rft_id=info:doi/ LA - English DB - GeoRef N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 2003-01-01 N1 - Number of references - 91 N1 - PubXState - CO N1 - Document feature - illus. incl. 20 tables, sketch map N1 - SuppNotes - Includes appendix N1 - Last updated - 2012-06-07 N1 - CODEN - GSAPAZ N1 - SubjectsTermNotLitGenreText - Cenozoic; central Montana; Cretaceous; Fort Union Formation; Garfield County Montana; Great Plains; Hell Creek Formation; K-T boundary; lower Paleocene; McCone County Montana; Mesozoic; microfossils; Montana; North America; Northern Great Plains; Paleocene; Paleogene; paleogeography; palynomorphs; statistical analysis; stratigraphic boundary; Tertiary; Tullock Member; United States; Upper Cretaceous; Western Interior ER - TY - JOUR T1 - HEPATITIS C VIRUS (HCV) AND HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1) INFECTIONS IN ALCOHOLICS AN - 21111113; 11140223 AB - Approximately 400,000 individuals in the United States are co-infected with hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) and it is likely that almost one in two of these subjects consumes alcohol. The majority of these patients suffer an accelerated course of liver disease as manifested by the onset of cirrhosis within 5 to 10 years of developing HCV infection, as well as an increased risk of developing hepatocellular carcinoma (HCC). It is thought that chronic alcohol abuse mediates liver damage as a result of increased production of free radicals and proinflammatory cytokines. In the setting of chronic HCV infection, alcohol ingestion has an additional effect of diminishing immune clearance and increasing viral burden to hasten the onset of cirrhosis and HCC. Likewise, chronic HCV and HIV-1 co-infection results in a net increase in HCV burden; higher prevalence rates of HCV transmission to sexual partners and offspring, as well as an accelerated progression to end stage liver disease as compared to individuals with HCV infection alone. Thus, the synergistic effects of alcohol abuse and HIV-1 greatly impact on the morbidity and mortality for patients with HCV coinfection. Ultimately, this cumulative disease process will require far more aggressive management with abstinence and counseling for alcohol abuse; highly active antiretrovirat therapy (HAART) for HIV infection and combination anti-viral therapy for HCV infection to stem the rapid progression to end stage liver disease. JF - Frontiers in Bioscience AU - Prakash, O AU - Mason, A AU - Luftig, R B AU - Bautista, A P AD - Laboratory of Molecular Oncology, National Institutes of Health, Bethesda, MD. USA Y1 - 2002 PY - 2002 DA - 2002 SP - 286 EP - 300 VL - 7 SN - 1093-9946, 1093-9946 KW - Virology & AIDS Abstracts; Toxicology Abstracts; Immunology Abstracts KW - Mortality KW - Cirrhosis KW - Liver diseases KW - Free radicals KW - Drug abuse KW - Alcoholics KW - Morbidity KW - Disease transmission KW - Inflammation KW - Sexual partners KW - Hepatitis C virus KW - Antiviral agents KW - highly active antiretroviral therapy KW - Human immunodeficiency virus 1 KW - Chronic infection KW - Cytokines KW - Progeny KW - Immune clearance KW - Hepatocellular carcinoma KW - Ethanol KW - V 22360:AIDS and HIV KW - X 24380:Social Poisons & Drug Abuse KW - F 06910:Microorganisms & Parasites UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21111113?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Frontiers+in+Bioscience&rft.atitle=HEPATITIS+C+VIRUS+%28HCV%29+AND+HUMAN+IMMUNODEFICIENCY+VIRUS+TYPE+1+%28HIV-1%29+INFECTIONS+IN+ALCOHOLICS&rft.au=Prakash%2C+O%3BMason%2C+A%3BLuftig%2C+R+B%3BBautista%2C+A+P&rft.aulast=Prakash&rft.aufirst=O&rft.date=2002-01-01&rft.volume=7&rft.issue=&rft.spage=286&rft.isbn=&rft.btitle=&rft.title=Frontiers+in+Bioscience&rft.issn=10939946&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-11-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Mortality; Liver diseases; Cirrhosis; Free radicals; Drug abuse; Morbidity; Alcoholics; Inflammation; Disease transmission; Sexual partners; Antiviral agents; highly active antiretroviral therapy; Chronic infection; Cytokines; Progeny; Immune clearance; Ethanol; Hepatocellular carcinoma; Hepatitis C virus; Human immunodeficiency virus 1 ER - TY - JOUR T1 - CHRONIC ALCOHOL INTOXICATION PRIMES KUPFFER CELLS AND ENDOTHELIAL CELLS FOR ENHANCED CC-CHEMOKINE PRODUCTION AND CONCOMITANTLY SUPPRESSES PHAGOCYTOSIS AND CHEMOTAXIS AN - 21104230; 11140096 AB - Chemokines are involved in the pathogenesis of alcoholic hepatitis and are considered to contribute to the migration of leukocytes into the liver during chronic ethanol intoxication. This work tests the hypothesis that chronic ethanol consumption selectively enhances chemokine release by Kupffer cells and hepatic sinusoidal endothelial cells and migration of inflammatory cells into the liver. Furthermore, enhanced hepatic chemokine secretion may induce an autocrine effect on the ability of Kupffer cells and endothelial cells to chemotax and ingest microbial particles. Male Wistar rats were fed with ethanol in agar block and water for 32 weeks, and were allowed free access to solid food. Results show that after 32 weeks of feeding, leukocyte infiltration and steatosis were observed in the livers of ethanol-fed rats. The majority of the infiltrated cells were CD8+ cells. Serum ALT, endotoxin, MIP-1 alpha , MCP-1 and RANTES, (but not CINC and MIP-2) were also increased in the ethanol-fed rats than in the pair-fed group. Isolated Kupffer cells from ethanol-fed rats were primed for enhanced MIP-1 alpha , MCP-1, and RANTES production in vitro, while the endothelial cells were primed for enhanced MIP-1 alpha release only. Chronic alcohol intoxication was also associated with increased basal H sub(2)O sub(2) formation, enhanced nuclear translocation and binding of NF-kB, AP-1 and MNP-1 in Kupffer Cells. Chronic ethanol feeding significantly enhanced MNP-1 binding, but not those of NF-kB and AP-1 in endothelial cells. Concomitantly, chemokine-induced chemotaxis, E.coli phagocytosis and f-met-leu-phe-induced superoxide anion production by Kupffer cells were downregulated in the ethanol-fed group. Taken together these data demonstrate that prolonged alcohol consumption may compromise the host to hepatitis as a result of increased chemokine production and at the same time may suppress the innate immune function of hepatic non-parenchymal cells. JF - Frontiers in Bioscience AU - Bautista, A P AD - Department of Physiology, NIAAA-Sponsored Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA Y1 - 2002 PY - 2002 DA - 2002 SP - 117 EP - 125 VL - 7 SN - 1093-9946, 1093-9946 KW - Toxicology Abstracts; Virology & AIDS Abstracts; Immunology Abstracts; Chemoreception Abstracts KW - Endotoxins KW - Intoxication KW - Agar KW - Chemokines KW - Hepatocytes KW - Food KW - Chemotaxis KW - NF- Kappa B protein KW - Leukocyte migration KW - Endothelial cells KW - Nuclear transport KW - Autocrine signalling KW - Hydrogen peroxide KW - Phagocytosis KW - Ethanol KW - Feeding KW - Monocyte chemoattractant protein 1 KW - Data processing KW - macrophage inflammatory protein 1 KW - steatosis KW - RANTES KW - CD8 antigen KW - Alcoholics KW - Inflammation KW - Hepatitis KW - Kupffer cells KW - Liver KW - superoxide anions KW - Immune response KW - R 18050:Chemoreception correlates of behavior KW - X 24380:Social Poisons & Drug Abuse KW - V 22320:Replication KW - F 06910:Microorganisms & Parasites UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21104230?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Frontiers+in+Bioscience&rft.atitle=CHRONIC+ALCOHOL+INTOXICATION+PRIMES+KUPFFER+CELLS+AND+ENDOTHELIAL+CELLS+FOR+ENHANCED+CC-CHEMOKINE+PRODUCTION+AND+CONCOMITANTLY+SUPPRESSES+PHAGOCYTOSIS+AND+CHEMOTAXIS&rft.au=Bautista%2C+A+P&rft.aulast=Bautista&rft.aufirst=A&rft.date=2002-01-01&rft.volume=7&rft.issue=&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=Frontiers+in+Bioscience&rft.issn=10939946&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-11-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Intoxication; Endotoxins; Agar; Chemokines; Hepatocytes; Food; Chemotaxis; NF- Kappa B protein; Endothelial cells; Leukocyte migration; Nuclear transport; Autocrine signalling; Hydrogen peroxide; Phagocytosis; Ethanol; Feeding; Data processing; Monocyte chemoattractant protein 1; macrophage inflammatory protein 1; steatosis; RANTES; CD8 antigen; Alcoholics; Inflammation; Hepatitis; Kupffer cells; Liver; superoxide anions; Immune response ER - TY - JOUR T1 - Preneoplastic and Precancerous Lesions in Rodents: Morphologic and Molecular Characteristics AN - 20269077; 7587265 AB - Cancer evolves through a sequential process from normal cells in many tissues of humans and animals. The natural history of tumor development can be seen histologically and by biochemical and molecular changes. There are two common basic pathways for the formation of malignant epithelial tumors; through preneoplastic foci and benign tumors (carcinoma developing in an adenoma) in parenchymal tissue or progression from intraepithelial neoplasia (IN) (atypical hyperplasia, noninvasive carcinoma, carcinoma in situ), a lesion in flat or lining epithelium. In epithelial-lining tissues of humans and rodents (e.g. cervix, mammary gland, prostate, skin), these lesions have been described as IN. In solid epithelial organs (liver, kidney, endocrine tissues) focal hyperplasia leads to adenomas. Adenomas develop foci of carcinoma, a process that is more common in rodents than in humans. These precancerous lesions in many rodent tissues often have multiple biochemical and molecular lesions which can be similar or different from those found in malignant tumors. The rodent molecular lesions include mutations in oncogenes (K-ras, H-ras) and tumor suppressor genes (p53, beta -catenin, apc) or loss of heterozygosity (LOH) in tumor suppressor genes of mutant mouse models. This manuscript will review specific sequential morphologic and molecular lesions in the histopathogenesis of cancer in several rodent tissues. The significance of molecular lesions for diagnosis of rodent lesions will be discussed. JF - Journal of Toxicologic Pathology AU - Ward, Jerrold M AD - Veterinary and Tumor Pathology Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health Y1 - 2002///0, PY - 2002 DA - 0, 2002 PB - Japanese Society of Toxicologic Pathology, 3-25-8 Nishi-Shinbashi Minato-ku Tokyo 105-0000 Japan VL - 15 IS - 2 SN - 0914-9198, 0914-9198 KW - Toxicology Abstracts KW - Key words : pathology of cancer KW - molecular lesions KW - preneoplastic KW - precancerous KW - Tumor suppressor genes KW - Molecular modelling KW - H-Ras protein KW - Animal models KW - Neoplasia KW - Oncogenes KW - adenomatous polyposis coli KW - Epithelium KW - Mammary gland KW - Tumors KW - Carcinoma KW - p53 protein KW - Loss of heterozygosity KW - K-Ras protein KW - Hyperplasia KW - catenin KW - Skin diseases KW - Reviews KW - Kidney KW - Liver KW - Cervix KW - Adenoma KW - Prostate KW - Mutation KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20269077?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Toxicologic+Pathology&rft.atitle=Preneoplastic+and+Precancerous+Lesions+in+Rodents%3A+Morphologic+and+Molecular+Characteristics&rft.au=Ward%2C+Jerrold+M&rft.aulast=Ward&rft.aufirst=Jerrold&rft.date=2002-01-01&rft.volume=15&rft.issue=2&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+Toxicologic+Pathology&rft.issn=09149198&rft_id=info:doi/10.1293%2Ftox.15.123 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-10-01 N1 - Last updated - 2016-05-27 N1 - SubjectsTermNotLitGenreText - Molecular modelling; Tumor suppressor genes; Mammary gland; H-Ras protein; Animal models; Tumors; Neoplasia; Loss of heterozygosity; p53 protein; Carcinoma; K-Ras protein; Hyperplasia; catenin; Oncogenes; Skin diseases; adenomatous polyposis coli; Reviews; Liver; Kidney; Epithelium; Cervix; Mutation; Prostate; Adenoma DO - http://dx.doi.org/10.1293/tox.15.123 ER - TY - JOUR T1 - A neurodevelopmental model of schizophrenia: Neonatal disconnection of the hippocampus AN - 20178389; 10262993 AB - In the context of our current knowledge about schizophrenia, heuristic models of psychiatric disorders may be used to test the plausibility of theories developed on the basis of new emerging biological findings, explore mechanisms of schizophrenia-like phenomena, and develop potential new treatments. In a series of studies, we have shown that neonatal excitotoxic lesions of the rat ventral hippocampus (VH) may serve as a heuristic model. The model appears to mimic a spectrum of neurobiological and behavioral features of schizophrenia, including functional pathology in presumably critical brain regions interconnected with the hippocampal formation and targeted by antipsychotic drugs--the striatum/nucleus accumbens and the prefrontal cortex, and leads in adolescence or early adulthood to the emergence of abnormalities in a number of dopamine related behaviors. Moreover, our data show that even transient inactivation of the VH during a critical period of development, that produces subtle, if any, anatomical changes in the hippocampus, may be sufficient to disrupt normal maturation of the prefrontal cortex (and perhaps, other interconnected late maturing regions) and trigger behavioral changes similar to those observed in animals with the permanent excitotoxic lesion. These results represent a potential new model of aspects of schizophrenia without a gross anatomical lesion. JF - Neurotoxicity Research AU - Lipska, Barbara K AU - Weinberger, Daniel R AD - Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, NIH, IRP, 10 Center Drive, Bldg. 10, Rm. 4N306, 20892-1385 Bethesda, MD, USA, lipskab@intra.nimh.nih.gov Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 469 EP - 475 PB - Taylor & Francis Group Ltd., 2 Park Square Milton Park, Abingdon Oxford OX14 4RN UK, [URL:http://www.taylorandfrancis.co.uk/] VL - 4 IS - 5-6 SN - 1029-8428, 1029-8428 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Nucleus accumbens KW - Data processing KW - Hippocampus KW - Adolescence KW - Brain KW - Schizophrenia KW - Mental disorders KW - Dopamine KW - Neuroleptics KW - Neostriatum KW - Neurotoxicity KW - Problem solving KW - Neonates KW - Critical period KW - Excitotoxicity KW - Cortex (prefrontal) KW - X 24310:Pharmaceuticals KW - N3 11001:Behavioral and Cognitive Neuroscience UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20178389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicity+Research&rft.atitle=A+neurodevelopmental+model+of+schizophrenia%3A+Neonatal+disconnection+of+the+hippocampus&rft.au=Lipska%2C+Barbara+K%3BWeinberger%2C+Daniel+R&rft.aulast=Lipska&rft.aufirst=Barbara&rft.date=2002-01-01&rft.volume=4&rft.issue=5-6&rft.spage=469&rft.isbn=&rft.btitle=&rft.title=Neurotoxicity+Research&rft.issn=10298428&rft_id=info:doi/10.1080%2F1029842021000022089 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-08-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Nucleus accumbens; Data processing; Hippocampus; Adolescence; Brain; Schizophrenia; Mental disorders; Dopamine; Neuroleptics; Neurotoxicity; Neostriatum; Problem solving; Neonates; Critical period; Cortex (prefrontal); Excitotoxicity DO - http://dx.doi.org/10.1080/1029842021000022089 ER - TY - JOUR T1 - Analysis of methamphetamine-induced changes in the expression of integrin family members in the cortex of wild-type and c-fos knockout mice AN - 20136814; 10263005 AB - Methamphetamine (METH) is an illicit drug that is also neurotoxic. Recent studies suggest that in addition to dopamine terminal degeneration in the striatum, METH causes apoptosis in cortical neurons. Earlier, we showed that c-fos knockout mice are more susceptible to the toxic effects of the drug. In order to identify possible pathways related to these differences, we have used cDNA array that provided us with a comprehensive catalog of METH affected genes. In the present study, we report on the effects of METH on the integrin family members that were shown to be involved in intracellular signaling cascades effecting cell survival. We found that, in comparison to wild type animals, c-fos knockout mice have lower baseline levels of the integrins in the cortex. Moreover, METH caused time-dependent decreases in their transcripts in both strains of mice. Quantitative RT-PCR confirmed the changes obtained in cDNA array. These findings are discussed in view of the possible role of integrins in METH-induced toxic effects on the cortical neurons. JF - Neurotoxicity Research AU - Betts, Elizabeth S AU - Krasnova, Irina N AU - McCoy, Michael T AU - Ladenheim, Bruce AU - Cadet, Jean Lud AD - Molecular Neuropsychiatry Section, National Institute on Drug Abuse, Intramural Research Program, 5500 Nathan Shock Drive, 21224 Baltimore, MD, USA, jcadet@intra.nida.nih.gov Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 617 EP - 623 PB - Taylor & Francis Group Ltd., 2 Park Square Milton Park, Abingdon Oxford OX14 4RN UK, [URL:http://www.taylorandfrancis.co.uk/] VL - 4 IS - 7-8 SN - 1029-8428, 1029-8428 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Cell survival KW - Intracellular signalling KW - Catalogs KW - Apoptosis KW - c-Fos protein KW - Drug abuse KW - Neurodegeneration KW - DNA microarrays KW - Methamphetamine KW - Dopamine KW - Cortex KW - Integrins KW - Neostriatum KW - Neurotoxicity KW - Polymerase chain reaction KW - X 24380:Social Poisons & Drug Abuse KW - N3 11028:Neuropharmacology & toxicology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20136814?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=Journal+of+Child+Custody%3A+Research%2C+Issues%2C+and+Practices&rft.atitle=The+chameleon+child%3A+Children+as+actors+in+the+high+conflict+divorce+drama&rft.au=Garber%2C+Benjamin+D.&rft.aulast=Garber&rft.aufirst=Benjamin&rft.date=2014-01-01&rft.volume=11&rft.issue=1&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Custody%3A+Research%2C+Issues%2C+and+Practices&rft.issn=15379418&rft_id=info:doi/10.1080%2F15379418.2014.892805 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-08-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Cell survival; Intracellular signalling; Apoptosis; Catalogs; c-Fos protein; Drug abuse; DNA microarrays; Neurodegeneration; Methamphetamine; Cortex; Dopamine; Integrins; Neurotoxicity; Neostriatum; Polymerase chain reaction DO - http://dx.doi.org/10.1080/1029842021000045453 ER - TY - JOUR T1 - Gene Therapy in Infants with Severe Combined Immunodeficiency AN - 20004164; 7478785 AB - Severe combined immunodeficiencies (SCID) are rare disorders that represent paediatric medical emergencies, as the outcome for affected patients can easily be fatal unless proper treatment is performed. The only curative treatment for SCID is reconstitution of the patients immunity. For more than 30 years, allogeneic bone marrow transplantation (BMT) has been extremely successful for SCID. However, BMT often results in only incomplete restoration of B cell function in treated patients, especially when haploidentical donors are used. In addition, BMT can be associated with severe complications such as graft-versus-host disease (GVHD). Alternative forms of therapy for SCID are therefore desirable. Genetic correction of peripheral T lymphocytes and/or haematopoietic stem cells (HSCs) by retrovirally mediated gene transfer has been attempted for patients with SCID due to adenosine deaminase deficiency, the first genetic disease targeted in clinical gene therapy trials with very limited success, overall. After these pioneer trials, recent progress has led to significant improvement of gene transfer techniques and better understanding of HSC biology which has culminated in the recent success of a gene therapy trial for patients affected with X-linked SCID (X-SCID). In this trial, patients with X-SCID received autologous bone marrow stem/progenitor cells which had been retrovirally transduced with a therapeutic gene. Based on the current follow-up, the overall efficacy of this gene therapy procedure is to be considered similar to or even better than that achievable by allogeneic BMT, because patients were not exposed to the risks of GVHD. Although these exciting results have clearly demonstrated that gene therapy is a feasible therapeutic option for X-SCID, they have also raised important questions regarding the long-term outcome of this experimental procedure and the possibility of translating this success into applications for other forms of SCID. JF - BioDrugs AU - Otsu, M AU - Candotti, F AD - Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA * Y1 - 2002 PY - 2002 DA - 2002 SP - 229 EP - 239 PB - Adis International Ltd., 41 Centorian Drive Private Bay 65901, Mairangi Bay Auckland 10 New Zealand, [mailto:sportsmed@adis.co.nz], [URL:http://www.adis.com] VL - 16 IS - 4 SN - 1173-8804, 1173-8804 KW - Virology & AIDS Abstracts; Genetics Abstracts; Biotechnology and Bioengineering Abstracts; Immunology Abstracts KW - Gene delivery systems KW - Gene therapies, therapeutic use KW - Immunodeficiency disorders, treatment KW - Infants KW - Autografts KW - Donors KW - Gene therapy KW - Lymphocytes B KW - Pediatrics KW - X chromosome KW - Bone marrow KW - Graft-versus-host reaction KW - Clinical trials KW - Stem cells KW - Lymphocytes T KW - Severe combined immunodeficiency KW - Bone marrow transplantation KW - Adenosine deaminase KW - W 30905:Medical Applications KW - V 22420:Plant Diseases KW - G 07730:Development & Cell Cycle KW - F 06920:Transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20004164?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BioDrugs&rft.atitle=Gene+Therapy+in+Infants+with+Severe+Combined+Immunodeficiency&rft.au=Otsu%2C+M%3BCandotti%2C+F&rft.aulast=Otsu&rft.aufirst=M&rft.date=2002-01-01&rft.volume=16&rft.issue=4&rft.spage=229&rft.isbn=&rft.btitle=&rft.title=BioDrugs&rft.issn=11738804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Autografts; Donors; Gene therapy; Pediatrics; Lymphocytes B; X chromosome; Bone marrow; Graft-versus-host reaction; Clinical trials; Stem cells; Lymphocytes T; Severe combined immunodeficiency; Bone marrow transplantation; Infants; Adenosine deaminase ER - TY - JOUR T1 - Development of a closed-system process for clinical-scale generation of DCs: evaluation of two monocyte-enrichment methods and two culture containers AN - 19856373; 7347502 AB - Background Clinical immunotherapy trials using DCs depend on large-scale methods for DC generation that fulfil current good manufacturing practice requirements. Our goal was to develop data on two variables, monocyte-enrichment method and culture container, which could be used to design a closed-system process for ex vivo generation of immature DCs. Methods Mononuclear cells were collected by leukapheresis and enriched for monocytes by either counterflow centrifugal elutriation, or immunomagnetic selection using Isolex, an automated closed-system device. Monocytes were cultured for 7 days in serum- free medium with GM-CSF and IL-4, using either plastic flasks or gas-permeable Stericell bags. Monocytes and cultured DCs were evaluated for yield, flow cytometric phenotype, and in vitro function in MLR, and autologous recall responses to tetanus toxoid and influenza virus. Results Enriched monocyte products from elutriation and immunomagnetic selection were equivalent in yield and purity, and were capable of generating immature DCs in either flasks or bags. DCs from all four culture conditions were equivalent in yield, phenotype, and in vitro function. Mean DC yield was 67-80% per seeding monocyte, and 11- 13% per starting mononuclear cell (MNC). A leukapheresis product containing 5 x 10 sub(9) MNCs processed by this method could therefore yield approximately 5 x 10 sub(8) immature DCs. Discussion In this manufacturing process, the Isolex system was equivalent to elutriation, and Stericell bags were equivalent to flasks. Together, the Isolex system and Stericell bags can be incorporated into a closed-system process to generate immature DCs. JF - Cytotherapy AU - Wong ECC AU - Lee, S M AU - Hines, K AU - Lee, J AU - Carter, C S AU - Kopp, W AU - Bender, J AU - Read, E J AD - Department of Transfusion Medicine, Warren G Magnusen Clinical Center, National Institutes of Health, Bethesda, MD, USA Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 65 EP - 76 PB - Taylor & Francis Ltd., 11 New Fetter Lane London EC4P 4EE UK, [mailto:info@tandf.co.uk], [URL:http://www.tandf.co.uk] VL - 4 IS - 1 SN - 1465-3249, 1465-3249 KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts; Biotechnology and Bioengineering Abstracts KW - DENDRITIC CELLS KW - CANCER IMMUNOTHERAPY KW - ELUTRIATION KW - IMMUNOMAGNETIC SELECTION KW - Leukocytes (mononuclear) KW - Interleukin 4 KW - Leukapheresis KW - Data processing KW - Immunotherapy KW - Granulocyte-macrophage colony-stimulating factor KW - Cell culture KW - Toxoids KW - Tetanus KW - Plasticity KW - Clinical trials KW - Flow cytometry KW - Influenza KW - Dendritic cells KW - Influenza virus KW - Monocytes KW - Vaccines KW - Plastics KW - V 22350:Immunology KW - W 30945:Fermentation & Cell Culture KW - J 02340:Antibiotics & Antimicrobials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19856373?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytotherapy&rft.atitle=Development+of+a+closed-system+process+for+clinical-scale+generation+of+DCs%3A+evaluation+of+two+monocyte-enrichment+methods+and+two+culture+containers&rft.au=Wong+ECC%3BLee%2C+S+M%3BHines%2C+K%3BLee%2C+J%3BCarter%2C+C+S%3BKopp%2C+W%3BBender%2C+J%3BRead%2C+E+J&rft.aulast=Wong+ECC&rft.aufirst=&rft.date=2002-01-01&rft.volume=4&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Cytotherapy&rft.issn=14653249&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Leukocytes (mononuclear); Leukapheresis; Interleukin 4; Data processing; Immunotherapy; Granulocyte-macrophage colony-stimulating factor; Cell culture; Toxoids; Plasticity; Tetanus; Clinical trials; Influenza; Flow cytometry; Dendritic cells; Plastics; Vaccines; Monocytes; Influenza virus ER - TY - JOUR T1 - Augmentation of the Activity of an Immunotoxin, Anti-Tac(Fv)-PE40KDEL, in T Cell Lines Infected with Human T Cell Leukemia Virus Type-I AN - 19844560; 7381453 AB - Therapy with an immunotoxin, anti-Tac(Fv)-PE38, which is a conjugate of the variable domains of an anti-Tac monoclonal antibody and Pseudomonas exotoxin, was reported to be useful for adult T cell leukemia (ATL) patients but a considerable amount of the immunotoxin is needed for the therapy and some side effects were also observed. We have previously demonstrated that an immunotoxin, anti-Tac(Fv)-PE40KDEL, showed strong cytotoxic effects on malignant cells from ATL patients. Therefore, we searched for agents that enhance the effects of the immunotoxin. PAK-200, FK-506, quinidine, cepharanthine and cyclosporine A (CsA) augmented the ability of the immunotoxin to inhibit protein synthesis in two human T cell leukemia virus type-I infected T cell lines, KUT-1 and KUT-2. CsA was the most potent agent in both the cell lines. Augmentation of the cytotoxic effect of the immunotoxin by these agents, especially CsA, may be useful in the immunotoxin therapy of ATL. JF - Leukemia & Lymphoma AU - Ohno, N AU - Kreitman, R J AU - Saito, T AU - Masamoto, I AU - Uozumi, K AU - Hanada, S AU - Takeuchi, S AU - Furukawa, T AU - Sumizawa, T AU - Arima, T AU - S-i, Akiyama AD - Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA Y1 - 2002 PY - 2002 DA - 2002 SP - 885 EP - 888 PB - Taylor & Francis Ltd., 11 New Fetter Lane London EC4P 4EE UK, [mailto:info@tandf.co.uk], [URL:http://www.tandf.co.uk] VL - 43 IS - 4 SN - 1042-8194, 1042-8194 KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts; Immunology Abstracts KW - Adult T cell leukemia (ATL) KW - Immunotoxin KW - Anti-Tac(Fv)-PE40KDEL KW - Augmentation KW - Cyclosporine A (CsA) KW - tacrolimus KW - Protein biosynthesis KW - Monoclonal antibodies KW - Pseudomonas KW - Tacrolimus KW - Cyclosporins KW - Exotoxins KW - Immunotoxins KW - Cytotoxicity KW - Quinidine KW - Lymphocytes T KW - Adult T cell leukemia KW - Lymphoma KW - Side effects KW - F 06915:Cancer Immunology KW - J 02400:Human Diseases KW - V 22370:Oncology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19844560?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia+%26+Lymphoma&rft.atitle=Children+resisting+contact+with+a+parent+postseparation%3A+Assessing+this+phenomenon+using+an+ecological+systems+framework&rft.au=Polak%2C+Shely%3B+Saini%2C+Michael&rft.aulast=Polak&rft.aufirst=Shely&rft.date=2015-04-01&rft.volume=56&rft.issue=3&rft.spage=220&rft.isbn=&rft.btitle=&rft.title=Journal+of+Divorce+%26+Remarriage&rft.issn=10502556&rft_id=info:doi/10.1080%2F10502556.2015.1012698 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-05-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - tacrolimus; Protein biosynthesis; Monoclonal antibodies; Tacrolimus; Cyclosporins; Immunotoxins; Exotoxins; Cytotoxicity; Quinidine; Lymphocytes T; Adult T cell leukemia; Lymphoma; Side effects; Pseudomonas ER - TY - JOUR T1 - The relationship of protein conservation and sequence length AN - 19816649; 6044828 AB - In general, the length of a protein sequence is determined by its function and the wide variance in the lengths of an organism's proteins reflects the diversity of specific functional roles for these proteins. However, additional evolutionary forces that affect the length of a protein may be revealed by studying the length distributions of proteins evolving under weaker functional constraints. We performed sequence comparisons to distinguish highly conserved and poorly conserved proteins from the bacterium Escherichia coli, the archaeon Archaeoglobus fulgidus, and the eukaryotes Saccharomyces cerevisiae, Drosophila melanogaster, and Homo sapiens. For all organisms studied, the conserved and nonconserved proteins have strikingly different length distributions. The conserved proteins are, on average, longer than the poorly conserved ones, and the length distributions for the poorly conserved proteins have a relatively narrow peak, in contrast to the conserved proteins whose lengths spread over a wider range of values. For the two prokaryotes studied, the poorly conserved proteins approximate the minimal length distribution expected for a diverse range of structural folds. There is a relationship between protein conservation and sequence length. For all the organisms studied, there seems to be a significant evolutionary trend favoring shorter proteins in the absence of other, more specific functional constraints. JF - BMC Evolutionary Biology AU - Lipman, David J AU - Souvorov, Alexander AU - Koonin, Eugene V AU - Panchenko, Anna R AU - Tatusova, Tatiana A AD - National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD 20894, USA, lipman@ncbi.nlm.nih.gov Y1 - 2002 PY - 2002 DA - 2002 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 2 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Microbiology Abstracts B: Bacteriology KW - Archaeoglobus fulgidus KW - Drosophila melanogaster KW - Escherichia coli KW - Conserved sequence KW - Prokaryotes KW - Evolution KW - Saccharomyces cerevisiae KW - Amino acid sequence KW - J 02410:Animal Diseases KW - K 03330:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19816649?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+Evolutionary+Biology&rft.atitle=The+relationship+of+protein+conservation+and+sequence+length&rft.au=Lipman%2C+David+J%3BSouvorov%2C+Alexander%3BKoonin%2C+Eugene+V%3BPanchenko%2C+Anna+R%3BTatusova%2C+Tatiana+A&rft.aulast=Lipman&rft.aufirst=David&rft.date=2002-01-01&rft.volume=2&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Evolutionary+Biology&rft.issn=1471-2148&rft_id=info:doi/10.1186%2F1471-2148-2-20 L2 - http://www.biomedcentral.com/content/pdf/1471-2148-2-20.pdf LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Conserved sequence; Prokaryotes; Evolution; Amino acid sequence; Drosophila melanogaster; Archaeoglobus fulgidus; Escherichia coli; Saccharomyces cerevisiae DO - http://dx.doi.org/10.1186/1471-2148-2-20 ER - TY - JOUR T1 - Respiratory symptoms and occupation: a cross-sectional study of the general population AN - 19786714; 7249817 AB - This study focused on respiratory symptoms due to occupational exposures in a contemporary general population cohort. Subjects were from the Dutch Monitoring Project on Risk Factors for Chronic Diseases (MORGEN). The composition of this population enabled estimation of respiratory risks due to occupation from the recent past for both men and women. Methods The study subjects (aged 20-59) were all inhabitants of Doetinchem, a small industrial town, and came from a survey of a random sample of 1104 persons conducted in 1993. A total of 274 cases with respiratory symptoms (subdivided in asthma and bronchitis symptoms) and 274 controls without symptoms were matched for age and sex. Relations between industry and occupation and respiratory symptoms were explored and adjusted for smoking habits and social economic status. Results Employment in the 'construction' (OR = 3.38; 95%CI 1.02 - 11.27), 'metal' (OR = 3.17; 95%CI 0. 98 - 10.28), 'rubber, plastics and synthetics' (OR = 6.52; 95%CI 1.26 - 53.80), and 'printing' industry (OR = 3.96; 95%CI 0.85 - 18.48) were positively associated with chronic bronchitis symptoms. In addition, the 'metal' industry was found to be weakly associated with asthma symptoms (OR = 2.59; 95%CI 0.87 - 7.69). Duration of employment within these industries was also positively associated with respiratory symptoms. Conclusion Respiratory symptoms in the general population are traceable to employment in particular industries even in a contemporary cohort with relatively young individuals. JF - Environmental Health AU - Vermeulen, Roel AU - Heederik, Dick AU - Kromhout, Hans AU - Smit, Henriette A AD - Environmental and Occupational Health Division, Institute for Risk Assessment Sciences, University Utrecht, Utrecht, PO Box 80176, 3503 TD Utrecht, The Netherlands, vermeulr@mail.nih.gov Y1 - 2002 PY - 2002 DA - 2002 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 1 SN - 1476-069X, 1476-069X KW - Pollution Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - Article No. 5 KW - Metals KW - Age KW - employment KW - Printing industry KW - Asthma KW - Employment KW - Respiratory diseases KW - Metal industry KW - Towns KW - Smoking KW - towns KW - Economics KW - Occupational exposure KW - R2 23080:Industrial and labor KW - H 1000:Occupational Safety and Health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19786714?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health&rft.atitle=Respiratory+symptoms+and+occupation%3A+a+cross-sectional+study+of+the+general+population&rft.au=Vermeulen%2C+Roel%3BHeederik%2C+Dick%3BKromhout%2C+Hans%3BSmit%2C+Henriette+A&rft.aulast=Vermeulen&rft.aufirst=Roel&rft.date=2002-01-01&rft.volume=1&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Environmental+Health&rft.issn=1476069X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-04-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Metals; Age; employment; Printing industry; Asthma; Respiratory diseases; Employment; Metal industry; Towns; Smoking; towns; Economics; Occupational exposure ER - TY - JOUR T1 - Genotoxicity and Carcinogenicity Studies of Soy Isoflavones AN - 18883300; 5734633 AB - The potential cancer preventive efficacy of soy isoflavones is being investigated in preclinical and phase 1 clinical studies sponsored by the U.S. National Cancer Institute. Although 90-day oral toxicity studies with PTI G-2535 (an investigational soy isoflavone drug product) in rats and dogs, as well as teratology studies, indicated no signs of toxicity, there remains a mechanistic concern associated with the ability of isoflavones (i.e., genistein) to inhibit topoisomerase, possibly leading to DNA strand breaks. The present report describes results from two in vitro genotoxicity studies, one in vivo genotoxicity study, and a single carcinogenicity study conducted in p53 knockout mice. Bacterial mutagenesis experiments using six tester strains without metabolic activation revealed no evidence that PTI G-2535 was mutagenic. In similar experiments with exogenous metabolic activation there were statistically significant increases in revertants, but less than twofold, in a single (Salmonella typhimurium TA100) tester strain. Mouse lymphoma cell mutagenesis experiments conducted with and without metabolic activation revealed statistically significant increases in mutation frequency at PTI G-2535 concentrations greater than or equal to 0.8 and 12 mu g/ml, respectively; such increases were dose related and increases in the frequency of both small and large colonies were observed. A statistically significant increase in the frequency of micronucleated polychromatic erythrocytes was also seen 24 hours after treatment in male, but not female, mice who received 500 and 1000 mg/kg body weight PTI G-2535; however, such increases were small, were not dose related, and were not observed 48 hours after treatment. In contrast, dietary genistein had no effect on survival, weight gain, or the incidence or types of tumors that developed in cancer-prone rodents lacking the p53 tumor suppressor gene, p53 knockout mice. The apparent risk/benefit of isoflavone ingestion may ultimately depend on the dose and developmental timing of exposure. JF - International Journal of Toxicology AU - Misra, R R AU - Hursting, S D AU - Perkins, S N AU - Sathyamoorthy, N AU - Mirsalis, J C AU - Riccio, E S AU - Crowell, JA AD - Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, EPN 2117, 6130 Executive Boulevard, Bethesda, MD 20892-7322, USA, jc94h@nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 277 EP - 285 VL - 21 IS - 4 SN - 1091-5818, 1091-5818 KW - dogs KW - isoflavones KW - rats KW - soy KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - X 24120:Food, additives & contaminants KW - H 14000:Toxicology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18883300?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=Journal+of+Human+Behavior+in+the+Social+Environment&rft.atitle=Seeing+the+forest+and+the+trees%3A+Using+dynamic+systems+theory+to+understand+%26quot%3Bstress+and+coping%26quot%3B+and+%26quot%3Btrauma+and+resilience.%26quot%3B&rft.au=Keenan%2C+Elizabeth+King&rft.aulast=Keenan&rft.aufirst=Elizabeth&rft.date=2010-12-01&rft.volume=20&rft.issue=8&rft.spage=1038&rft.isbn=&rft.btitle=&rft.title=Journal+of+Human+Behavior+in+the+Social+Environment&rft.issn=10911359&rft_id=info:doi/10.1080%2F10911359.2010.494947 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1080/10915810290096441 ER - TY - JOUR T1 - Complex formation between activator and RNA polymerase as the basis for transcriptional activation by MarA and SoxS in Escherichia coli AN - 18765739; 5634758 AB - Transcriptional activation in Escherichia coli is generally considered to proceed via the formation of an activator-DNA-RNA polymerase (RNP) ternary complex. Although the order of assembly of the three elements is thermodynamically irrelevant, a prevalent idea is that the activator-DNA complex is formed first, and recruitment of RNP to the binary complex occurs subsequently. We show here that the closely related activators, MarA, SoxS and Rob, which activate the same family of genes, are capable of forming complexes with RNP core or holoenzyme in the absence of DNA. In addition, we find that the ternary MarA-DNA-RNP and SoxS-DNA-RNP complexes are more stable than the corresponding Rob-DNA-RNP complex, although the binary Rob-DNA complex is often more stable than the corresponding MarA- or SoxS-DNA complexes. These results may help to explain certain puzzling aspects of the MarA/SoxS/Rob system. We suggest that activator-RNP complexes scan the chromosome and bind promoters of the regulon more efficiently than either RNP or the activators alone. JF - Molecular Microbiology AU - Martin, R G AU - Gillette, W K AU - Martin, NI AU - Rosner, J L AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 5, Room 333, Bethesda, MD 20892-0560, USA, rgmartin@helix.nih.gov Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 355 EP - 370 PB - Blackwell Science Ltd. VL - 43 IS - 2 SN - 0950-382X, 0950-382X KW - MarA protein KW - SoxS protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - J 02726:RNA and ribosomes KW - N 14662:Gene regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18765739?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Complex+formation+between+activator+and+RNA+polymerase+as+the+basis+for+transcriptional+activation+by+MarA+and+SoxS+in+Escherichia+coli&rft.au=Martin%2C+R+G%3BGillette%2C+W+K%3BMartin%2C+NI%3BRosner%2C+J+L&rft.aulast=Martin&rft.aufirst=R&rft.date=2002-01-01&rft.volume=43&rft.issue=2&rft.spage=355&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2002.02748.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1046/j.1365-2958.2002.02748.x ER - TY - JOUR T1 - A Continuous Tensor Field Approximation of Discrete DT-MRI Data for Extracting Microstructural and Architectural Features of Tissue AN - 18738871; 5615518 AB - The effective diffusion tensor of water, D, measured by diffusion tensor MRI (DT-MRI), is inherently a discrete, noisy, voxel-averaged sample of an underlying macroscopic effective diffusion tensor field, D(x). Within fibrous tissues this field is presumed to be continuous and smooth at a gross anatomical length scale. Here a new, general mathematical framework is proposed that uses measured DT-MRI data to produce a continuous approximation to D(x). One essential finding is that the continuous tensor field representation can be constructed by repeatedly performing one-dimensional B-spline transforms of the DT-MRI data. The fidelity and noise-immunity of this approximation are tested using a set of synthetically generated tensor fields to which background noise is added via Monte Carlo methods. Generally, these tensor field templates are reproduced faithfully except at boundaries where diffusion properties change discontinuously or where the tensor field is not microscopically homogeneous. Away from such regions, the tensor field approximation does not introduce bias in useful DT-MRI parameters, such as Trace(D(x)). It also facilitates the calculation of several new parameters, particularly differential quantities obtained from the tensor of spatial gradients of D(x). As an example, we show that they can identify tissue boundaries across which diffusion properties change rapidly using in vivo human brain data. One important application of this methodology is to improve the reliability and robustness of DT-MRI fiber tractography. JF - Journal of Magnetic Resonance AU - Pajevic, S AU - Aldroubi, A AU - Basser, P J AD - National Institue of Health, Building 13, Room 3W16, 13 South Drive, Bethesda, MD 20892-5772, USA, pjbasser@helix.nih.gov Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 85 EP - 100 VL - 154 IS - 1 SN - 1090-7807, 1090-7807 KW - Monte Carlo simulation KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18738871?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Magnetic+Resonance&rft.atitle=A+Continuous+Tensor+Field+Approximation+of+Discrete+DT-MRI+Data+for+Extracting+Microstructural+and+Architectural+Features+of+Tissue&rft.au=Pajevic%2C+S%3BAldroubi%2C+A%3BBasser%2C+P+J&rft.aulast=Pajevic&rft.aufirst=S&rft.date=2002-01-01&rft.volume=154&rft.issue=1&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Journal+of+Magnetic+Resonance&rft.issn=10907807&rft_id=info:doi/10.1006%2Fjmre.2001.2452 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1006/jmre.2001.2452 ER - TY - JOUR T1 - A Chemically Induced Rat Model of Hemolysis with Disseminated Thrombosis AN - 18673540; 5567582 AB - Although hemolytic anemia and thrombosis, which can be serious or even lethal, are often encountered in daily common practice, their pathogenesis has remained obscure, partially because of the absence of appropriate models. Here we present a unique chemically induced rat model of hemolytic anemia and disseminated thrombosis in which the organs developing infarction are comparable to those seen in humans. We exposed male and female Fischer F344 rats to two, three, or four daily doses of 2-butoxyethanol (BE) at 250 mg/kg body weight and examined for hemolysis and histopathological evidence of disseminated thrombosis on d 2, 3, 4, and 29. Time-course BE-related erythrocytic changes were statistically significant in both sexes. Evidence of thrombosis and infarction was seen mainly in females dosed more than once with widespread thrombotic crisis after two or three dosings, likely explicable by the more significant morphological changes in erythrocytes and hemolysis observed in this gender. We documented thrombosis and infarction in the heart, brain, lungs, eyes, and bones. Our model with its list of target organs similar to that observed in human diseases characterized by hemolysis and thrombosis [for example, thalassemia, sickle cell disease (SCD), paroxysmal nocturnal hemoglobinuria (PNF), disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), and hemolytic uremic syndrome (HUS)] suggests that it can be an excellent tool to study the pathogenesis of such complications. JF - Cardiovascular Toxicology AU - Ezov, N AU - Levin-Harrus, T AU - Mittelman, M AU - Redlich, M AU - Shabat, S AU - Ward, S M AU - Peddada, S AU - Nyska, M AU - Yedgar, S AU - Nyska, A AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, MD B3-06, P.O. Box 12233, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709-9998, USA, nyska@niehs.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 181 EP - 193 VL - 2 IS - 3 SN - 1530-7905, 1530-7905 KW - 2-butoxyethanol KW - rats KW - Toxicology Abstracts KW - X 24154:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18673540?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cardiovascular+Toxicology&rft.atitle=A+Chemically+Induced+Rat+Model+of+Hemolysis+with+Disseminated+Thrombosis&rft.au=Ezov%2C+N%3BLevin-Harrus%2C+T%3BMittelman%2C+M%3BRedlich%2C+M%3BShabat%2C+S%3BWard%2C+S+M%3BPeddada%2C+S%3BNyska%2C+M%3BYedgar%2C+S%3BNyska%2C+A&rft.aulast=Ezov&rft.aufirst=N&rft.date=2002-01-01&rft.volume=2&rft.issue=3&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=Cardiovascular+Toxicology&rft.issn=15307905&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The role of KasA and KasB in the biosynthesis of meromycolic acids and isoniazid resistance in Mycobacterium tuberculosis AN - 18662238; 5558836 AB - Mycobacterium tuberculosis has two discrete beta -ketoacyl synthases encoded by kasA and kasB that are located in tandem within a five-gene operon that has been implicated in isoniazid-sensitivity and mycolic acid synthesis. We have developed an in vitro meromycolic acid synthase assay to elucidate the anabolic role of these enzymes. Overproduction of KasA and KasB individually and together in M. smegmatis enabled cell-free incorporation of [ super(14)C] malonyl-CoA into lipids whose chain length was dependent upon the M. tuberculosis elongating enzyme used. KasA specifically elongated palmitoyl-CoA to monounsaturated fatty acids that averaged 40 carbons in length. KasB hyperproduction in the presence of KasA produced longer chain multiunsaturated hydrocarbons averaging 54 carbons in length. These products comigrated with a synthetic standard of meromycolic acid and their production was sensitive to isoniazid, thiolactomycin, and triclosan. KasA mutations associated with isoniazid resistance produced an enzyme that had a diminished overall catalytic activity but conferred enhanced resistance to isoniazid. In vivo analysis confirmed that overexpression of each of the four mutant KasAs enhanced isoniazid resistance when compared to overexpression of wild-type KasA. These results suggest discrete anabolic roles for both KasA and KasB in mycolic acid synthesis and substantiate the involvement of KasA mutations in isoniazid resistance. JF - Tuberculosis AU - Slayden, R A AU - Barry, CE III AD - Tuberculosis Research Section, Laboratory of Host Defenses, NIAID, NIH, 12441 Parklawn Dr, Rockville, MD 20852, USA, clifton_barry@nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 149 EP - 160 VL - 82 IS - 4-5 SN - 1472-9792, 1472-9792 KW - KasA protein KW - KasB protein KW - malonyl-CoA KW - meromycolic acids KW - Microbiology Abstracts B: Bacteriology KW - J 02814:Drug resistance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18662238?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tuberculosis&rft.atitle=The+role+of+KasA+and+KasB+in+the+biosynthesis+of+meromycolic+acids+and+isoniazid+resistance+in+Mycobacterium+tuberculosis&rft.au=Slayden%2C+R+A%3BBarry%2C+CE+III&rft.aulast=Slayden&rft.aufirst=R&rft.date=2002-01-01&rft.volume=82&rft.issue=4-5&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=Tuberculosis&rft.issn=14729792&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Raters' Objectivity in Using the Compendium of Physical Activities to Code Physical Activity Diaries AN - 18648430; 5534718 AB - The purpose of this study was to assess raters' agreement and objectivity in using the Compendium of Physical Activities to code physical activity diaries. This study assessed agreement in assigning metabolic equivalent (MET) codes and values and raters' objectivity in estimating energy expenditure were assessed. A secondary purpose of this study was to compare agreement and objectivity in coding English and Spanish physical activity diaries. In total, 48 diaries were coded by 4 trained raters. Generalizability theory was used to determine raters' objectivity. Agreement in assigning MET codes and MET values to individual activities ranged from 44% to 92%. The generalizability analyses indicated the raters' objectivity was high for the English and Spanish diaries (>.80). Objectivity in coding increased with 2 raters but remained adequate with just 1 rater. Therefore, using detailed diaries and trained raters may preclude the need for double coding physical activity diaries. Furthermore, eliminating codes from the Compendium of Physical Activities that are redundant or have overlapping descriptions may reduce disagreement in MET codes and values between raters. JF - Measurement in Physical Education and Exercise Science AU - Masse, L C AU - Heesch, K C AU - Fulton, JE AU - Watson, K B AD - National Cancer Institute, Health Promotion Research Branch, Division of Cancer Control and Population Sciences, 6130 Executive Boulevard, EPN 4076 MSC 7335, Rockville, MD 20892-7335, USA, massel@mail.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 207 EP - 224 VL - 6 IS - 4 SN - 1091-367X, 1091-367X KW - Physical Education Index KW - PE 070:Measurement & Evaluation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18648430?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Measurement+in+Physical+Education+and+Exercise+Science&rft.atitle=Raters%27+Objectivity+in+Using+the+Compendium+of+Physical+Activities+to+Code+Physical+Activity+Diaries&rft.au=Masse%2C+L+C%3BHeesch%2C+K+C%3BFulton%2C+JE%3BWatson%2C+K+B&rft.aulast=Masse&rft.aufirst=L&rft.date=2002-01-01&rft.volume=6&rft.issue=4&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=Measurement+in+Physical+Education+and+Exercise+Science&rft.issn=1091367X&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Radiation quality and tissue-specific microenvironments following exposure to 1 GeV/AMU Fe AN - 18646266; 5544307 AB - This paper summarizes quantitative in vivo laminin immunofluorescence analysis of mammary glands and skin epithelial structures from mice exposed to 1 GeV/amu Fe ions. Digital confocal microscopic images were quantified and linked to the rough 'core-penumbra' Fe track physical description. Comparison to [gamma]-ray sparsely ionizing radiation suggested the core of the Fe track being responsible for a biological response only seen with energetic Fe particles. Conclusions for modeling in vivo responses to radiation were then implied. JF - Advances in Space Research AU - Costes, S AU - Barcellos-Hoff, M H AD - National Cancer Institute, Ft. Detrick, Bldg 538, Frederick, MD 21702, USA Y1 - 2002 PY - 2002 DA - 2002 SP - 865 EP - 870 VL - 30 IS - 4 SN - 0273-1177, 0273-1177 KW - mice KW - Toxicology Abstracts KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18646266?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+Space+Research&rft.atitle=Radiation+quality+and+tissue-specific+microenvironments+following+exposure+to+1+GeV%2FAMU+Fe&rft.au=Costes%2C+S%3BBarcellos-Hoff%2C+M+H&rft.aulast=Costes&rft.aufirst=S&rft.date=2002-01-01&rft.volume=30&rft.issue=4&rft.spage=865&rft.isbn=&rft.btitle=&rft.title=Advances+in+Space+Research&rft.issn=02731177&rft_id=info:doi/10.1016%2FS0273-1177%2802%2900410-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0273-1177(02)00410-6 ER - TY - JOUR T1 - The US-Japan Cooperative Medical Science Program Tuberculosis and Leprosy Panel's 36th Annual Research Conference, New Orleans, Louisiana, USA, 15-17 July 2001 AN - 18621043; 5513591 AB - No AB. JF - Tuberculosis AU - Jacobs, G G AD - National Institutes of Health, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA Y1 - 2002 PY - 2002 DA - 2002 SP - 113 EP - 115 VL - 82 IS - 2-3 SN - 1472-9792, 1472-9792 KW - US-Japan cooperative Medical Science Program KW - Microbiology Abstracts B: Bacteriology KW - J 02930:Proceedings UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18621043?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tuberculosis&rft.atitle=The+US-Japan+Cooperative+Medical+Science+Program+Tuberculosis+and+Leprosy+Panel%27s+36th+Annual+Research+Conference%2C+New+Orleans%2C+Louisiana%2C+USA%2C+15-17+July+2001&rft.au=Jacobs%2C+G+G&rft.aulast=Jacobs&rft.aufirst=G&rft.date=2002-01-01&rft.volume=82&rft.issue=2-3&rft.spage=113&rft.isbn=&rft.btitle=&rft.title=Tuberculosis&rft.issn=14729792&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - PCB congeners and pesticides and female fecundity, New York State Angler Prospective Pregnancy Study AN - 18617546; 5523904 AB - Consumption of PCB-contaminated sport fish from Lake Ontario has been reported to be associated with diminished female fecundity. To identify Polychlorinated biphenyl (PCB) congeners and other pesticides that might be associated with reduced fecundity, we followed 102 women aged 20-34 years attempting pregnancy who completed daily diaries for 12 at risk menstrual cycles. Fecundity referred to time-to-pregnancy (TTP) or the number of at risk menstrual cycles required for pregnancy. Blood specimens were obtained for 88 (86%) women and were analyzed using gas chromatography and electron capture for 66 PCB congeners and seven pesticides. Laboratory values were recovery, background and fat corrected prior to natural log transformation. Using stepwise discriminant analysis, congeners IUPAC #205 and #206 and hexaclorobenzene were significantly and positively associated with increasing TTP when women were categorized as becoming pregnant in the first or first three at risk menstrual cycles, respectively. Congeners #205 and #206 are reported to have (anti) estrogenic structural activity. JF - Environmental Toxicology and Pharmacology AU - Buck, G M AU - Vena, JE AU - Greizerstein, H B AU - Weiner, J M AU - McGuinness, B AU - Mendola, P AU - Kostyniak, P J AU - Swanson, M AU - Bloom AU - Olson, J R AD - Epidemiology Branch, Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, 6100 Executive Blvd., Room 7B05, Rockville, MD 20852, USA, gb156i@nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 83 EP - 92 VL - 12 IS - 2 SN - 1382-6689, 1382-6689 KW - Toxicology Abstracts KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18617546?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Toxicology+and+Pharmacology&rft.atitle=PCB+congeners+and+pesticides+and+female+fecundity%2C+New+York+State+Angler+Prospective+Pregnancy+Study&rft.au=Buck%2C+G+M%3BVena%2C+JE%3BGreizerstein%2C+H+B%3BWeiner%2C+J+M%3BMcGuinness%2C+B%3BMendola%2C+P%3BKostyniak%2C+P+J%3BSwanson%2C+M%3BBloom%3BOlson%2C+J+R&rft.aulast=Buck&rft.aufirst=G&rft.date=2002-01-01&rft.volume=12&rft.issue=2&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Environmental+Toxicology+and+Pharmacology&rft.issn=13826689&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special Issue: Human and Animal Neurotoxicology from Exposure to Great Lakes Pollutants. N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Garlic - A Natural Source of Cancer Preventive Compounds. AN - 1859409569; 12716288 AB - Several epidemiological observations and a number of laboratory studies have indicated anticarcinogenic potential of garlic, which has been traditionally used from time immemorial for varied human ailments in different parts of the globe. The anticarcinogenic properties of garlic have been attributed to a wide variety of chemical compounds identified to be present in garlic but most studies have focused on specific thioallyl constituents. Garlic components have been found to block covalent binding of carcinogens to DNA, enhance degradation of carcinogens, have antioxidative and free radical scavenging properties and to regulate cell proliferation, apoptosis and immune responses. In view of the variety of effects produced by garlic and its chemical constituents, renewed interest has been generated in investigating its medicinal properties, particularly with reference to cancer prevention and prophylaxis. There are a number of mechanisms at work which jointly are responsible for eliciting the anticarcinogenic effects noted in laboratory studies in a wide range of experimental systems. This has opened up a new avenue for researchers in the field of cancer chemoprevention and merits further scrutiny to establish the role of garlic in prevention of human cancers. JF - Asian Pacific journal of cancer prevention : APJCP AU - Das, Sukta AD - Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata 700026 India. sukta2002@hotmail.com Y1 - 2002 PY - 2002 DA - 2002 SP - 305 EP - 311 VL - 3 IS - 4 SN - 1513-7368, 1513-7368 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859409569?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.atitle=Garlic+-+A+Natural+Source+of+Cancer+Preventive+Compounds.&rft.au=Das%2C+Sukta&rft.aulast=Das&rft.aufirst=Sukta&rft.date=2002-01-01&rft.volume=3&rft.issue=4&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.issn=15137368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2003-04-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Elimination of Deleterious Effects of Free Radicals in Murine Skin Carcinogenesis by Black Tea Infusion, Theaflavins & Epigallocatechin Gallate. AN - 1859396987; 12718579 AB - In recent years, numerous reports have been published on the identification of novel, naturally occurring antioxidants from plants, animals, microbial sources and processed food products. Most natural antioxidants are phenolic compounds, which have a modulatory role on physiological functions and biotransformation reactions involved in the detoxification process, thereby affording protection from cytotoxic, genotoxic and metabolic actions of environmental toxicants. As part of our program on evaluation of food, beverage and traditional medicinal plants for their anticarcinogenic activity, the present report deals with the evaluation of aqueous infusion of Black tea (Camellia sinensis), Black tea extract (80% Theaflavins) & EGCG on mice exposed to the chemical carcinogen DMBA. All the four detoxification enzymes studied viz, GST, GPx, SOD and CAT were found to be activated to different degrees following treatment with black tea and two of its active compounds. The activation of the enzymes was accompanied by significant reduction in lipid peroxidation. The effect on apoptosis and cell proliferation was also studied in mice skin following administration of DMBA. Theaflavins, and EGCG significantly inhibited cell proliferation and induced apoptosis. The observation suggests chemopreventive potential of black tea infusion, black tea extract Theaflavins and the compound EGCG. JF - Asian Pacific journal of cancer prevention : APJCP AU - Saha, Prosenjit AU - Das, Sukta AD - Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata 700026, India. sukta2002@hotmail.com Y1 - 2002 PY - 2002 DA - 2002 SP - 225 EP - 230 VL - 3 IS - 3 SN - 1513-7368, 1513-7368 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859396987?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.atitle=Elimination+of+Deleterious+Effects+of+Free+Radicals+in+Murine+Skin+Carcinogenesis+by+Black+Tea+Infusion%2C+Theaflavins+%26amp%3B+Epigallocatechin+Gallate.&rft.au=Saha%2C+Prosenjit%3BDas%2C+Sukta&rft.aulast=Saha&rft.aufirst=Prosenjit&rft.date=2002-01-01&rft.volume=3&rft.issue=3&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.issn=15137368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2003-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cervical Cancer: Etiology, Pathogenesis, Treatment, and Future Vaccines. AN - 1859396976; 12718577 AB - Cervical cancer is a sexually transmitted disease caused by the human papillomavirus (HPV), especially HPV-16 and -18. Of the half million new cases of cervical cancer reported yearly, 20% occur in India. Mass cancer screening programs to detect and treat cervical cancer and its precursor lesions are not available in India and most other developing countries because of the lack of resources. Curative and palliative treatments are not the same for all patients with cervical cancer because the result depends on the immunological response of the patient. This article describes the natural history of cervical carcinogenesis and the rational behind various modalities of prevention and treatment for the practising gynecological oncologist. Prophylactic vaccines against HPV-16 and -18 and therapeutic vaccines against cervical cancers should be able to overcome the logistical problems that now exist to screen, diagnose and treat cervical cancer and its precursor lesions. JF - Asian Pacific journal of cancer prevention : APJCP AU - Ghim, Shin-Je AU - Basu, Partha Sarathi AU - Jenson, AB AD - Chittaranjan National Cancer Institute, Kolkata 700026, India, ceds@vsnl.com Y1 - 2002 PY - 2002 DA - 2002 SP - 207 EP - 214 VL - 3 IS - 3 SN - 1513-7368, 1513-7368 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859396976?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.atitle=Cervical+Cancer%3A+Etiology%2C+Pathogenesis%2C+Treatment%2C+and+Future+Vaccines.&rft.au=Ghim%2C+Shin-Je%3BBasu%2C+Partha+Sarathi%3BJenson%2C+AB&rft.aulast=Ghim&rft.aufirst=Shin-Je&rft.date=2002-01-01&rft.volume=3&rft.issue=3&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.issn=15137368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2003-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of Apoptosis in Tumor Cells by Natural Phenolic Compounds. AN - 1859396199; 12718610 AB - Investigation has been conducted to delineate the action of some phenolic compounds of natural origin in four human tumor cell lines: acute myeloblastic leukemia (HL-60), chronic myelogenic leukemia (K-562), breast adenocarcinoma (MCF-7) and cervical epithelial carcinoma (HeLa). In cells grown in appropriate media the phenolics curcumin, yakuchinone B, resveratrol and capsaicin exhibited growth inhibition as assessed by trypan blue dye exclusion. It was evident from the results of the MTT reduction assay and [(3)H]thymidine incorporation into nuclear DNA that the phenolics were cytotoxic and inhibited cell proliferation. Dose response studies indicated curcumin to be most cytotoxic towards HL-60, K-562 and MCF-7 but did not show much activity in HeLa cells. On the other hand, yakuchinone B, although less active than curcumin, displayed cytotoxicity towards all four cell lines. Resveratrol was cytotoxic only in leukemic cells, while capsaicin was marginally cytotoxic. All these phenolics did not elicit any cytotoxic activity as judged by the above parameters towards lymphocytes purified from normal human blood. When cells treated with phenolics were stained with propidium iodide and examined under a fluorescent microscope, characteristic apoptotic features such as chromatin condensation and nuclear fragmentation were observed. Scoring of cells with apoptotic and non-apoptotic features showed positive correlation of apoptotic index with dose of phenolic, and fragmented DNA extracted free of genomic DNA displayed on gel electrophoresis a typical ladder pattern. These phenolics which have human exposure are known cancer chemopreventive agents and their action as inducers of apoptosis in tumor cells suggest their potential use in a strategy for cancer control. JF - Asian Pacific journal of cancer prevention : APJCP AU - Roy, Madhumita AU - Chakraborty, Sutapa AU - Siddiqi, Maqsood AU - Bhattacharya, Rathin K AD - Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, Kolkata 700 026, India cncinst@giasclo1.vsnl.net.in /rathin_b@yahoo.co.in Y1 - 2002 PY - 2002 DA - 2002 SP - 61 EP - 67 VL - 3 IS - 1 SN - 1513-7368, 1513-7368 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859396199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.atitle=Induction+of+Apoptosis+in+Tumor+Cells+by+Natural+Phenolic+Compounds.&rft.au=Roy%2C+Madhumita%3BChakraborty%2C+Sutapa%3BSiddiqi%2C+Maqsood%3BBhattacharya%2C+Rathin+K&rft.aulast=Roy&rft.aufirst=Madhumita&rft.date=2002-01-01&rft.volume=3&rft.issue=1&rft.spage=61&rft.isbn=&rft.btitle=&rft.title=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.issn=15137368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2003-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of Cell Proliferation and Induction of Apoptosis During Azoxymethane Induced Colon Carcinogenesis by Black Tea. AN - 1859395141; 12718607 AB - Tea (Camellia sinensis) is one of the most popular beverages, consumed worldwide. The health promoting properties of tea have been attributed to its antioxidative polyphenolic constituents and their oxidative products. The aim of the present study was to evaluate the chemopreventive efficacy of a black tea infusion on azoxymethane induced colonic preneoplastic lesions, the aberrant crypt foci in Sprague-Dawley rats. Rats were injected with azoxymethane (15mg/kg.b.w.) and received oral administration of 1% and 2% (w/v) tea infusions from the 1(st)day of carcinogen application. The treatment was continued for 12 weeks. The colons were then assessed for aberrant crypt foci and compared with the untreated carcinogen control group. In situ cell proliferation and in situ apoptosis were also estimated using Brdu incorporation and the TUNEL method, respectively. Aberrant crypt foci were reduced significantly (by 44% in the 1% tea-treated and by about 40% in 2% tea-treated group). Significant decrease in proliferation and increase in apoptosis suggest a possible interplay between the two processes resulting in inhibition of colon carcinogenesis by black tea. JF - Asian Pacific journal of cancer prevention : APJCP AU - Sengupta, Archana AU - Ghosh, Samit AU - Das, Sukta AD - Dept. of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata- 700026, India. archanadi1@rediffmail.com Y1 - 2002 PY - 2002 DA - 2002 SP - 41 EP - 46 VL - 3 IS - 1 SN - 1513-7368, 1513-7368 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859395141?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.atitle=Inhibition+of+Cell+Proliferation+and+Induction+of+Apoptosis+During+Azoxymethane+Induced+Colon+Carcinogenesis+by+Black+Tea.&rft.au=Sengupta%2C+Archana%3BGhosh%2C+Samit%3BDas%2C+Sukta&rft.aulast=Sengupta&rft.aufirst=Archana&rft.date=2002-01-01&rft.volume=3&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.issn=15137368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2003-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemopreventive Potential of Neem Flowers on Carcinogen-Induced Rat Mammary and Liver Carcinogenesis. AN - 1859395133; 12718580 AB - We have previously reported that dietary neem flowers (Azadirachta indica A. Juss var. siamensis Valeton) caused a marked increase in glutathione S-transferase (GST) activity in the liver, while resulting in a significant reduction in the activities of some hepatic P450-dependent monooxygenases. These results strongly indicate that neem flowers may have chemopreventive potential. In the present study, we examined the inhibitory effects of neem flowers on 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced mammary gland carcinogenesis in female Sprague Dawley rats and on aflatoxin B(1)(AFB(1))-induced hepatocarcinogenesis in male Wistar rats. Young animals were fed with AIN-76 purified diets containing either 10-12.5% ground freeze-dried neem flowers for 1 week prior to, during, and for 1 week after the administration of each carcinogen. Interestingly, it was found that neem flowers resulted in a marked reduction of the incidence of mammary gland (about 35.2%) and liver tumors (61.7% and 80.1% for benign and malignant tumors, respectively). Furthermore, the multiplicity of tumors per rats was also lower in the neem flower groups, i.e. those for mammary gland tumors and benign and malignant liver tumors were reduced to 44.0%, 87.9% and 88.9%, respectively. These results clearly demonstrated that neem flowers contain some chemopreventive agents capable of inhibiting AFB(1) and DMBA induced liver and mammary gland carcinogenesis in rats. JF - Asian Pacific journal of cancer prevention : APJCP AU - Tepsuwan, Anong AU - Kupradinun, Piengchai AU - Kusamran, Wannee R AD - Biochemistry and Chemical Carcinogenesis Section, Research Division, National Cancer Institute, Bangkok 10400, Thailand. waroran@health.moph.go.th Y1 - 2002 PY - 2002 DA - 2002 SP - 231 EP - 238 VL - 3 IS - 3 SN - 1513-7368, 1513-7368 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859395133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=Australian+Psychologist&rft.atitle=An+ecological+perspective%3A+Therapist+practices+with+children+who+experienced+abuse+and+trauma&rft.au=Edwards%2C+Claudia%3B+Karnilowicz%2C+Wally&rft.aulast=Edwards&rft.aufirst=Claudia&rft.date=2013-10-01&rft.volume=48&rft.issue=5&rft.spage=321&rft.isbn=&rft.btitle=&rft.title=Australian+Psychologist&rft.issn=00050067&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2003-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinogenicity Testing of the Cosmetic Dye: D&C Red No. 36. AN - 1859395120; 12718609 AB - D&C Red No. 36, a drug and cosmetic dye commonly used for coloring lipsticks, was evaluated for its carcinogenic potential in male and female Wistar rats. This dye has been shown to exhibit mutagenic activity towards Salmonella typhimurium TA 98 in the presence of S9 mix. In the present study, 50 male and 50 female rats in each group were given diets containing D&C Red No. 36 at 2 different concentrations, 1,000 ppm and 2,000 ppm, for 78 weeks and sacrificed at week 98. It was found that dye treatment had no significant effect on the survival of either male or female animals as well as the body weight gain in males. However, body weight gain of treated females was slightly lower than that of the control group. Histopathological assessment demonstrated a number of benign and malignant tumors to have developed in various organs of both dye treated and control groups. In male rats, benign liver tumors were found at incidences of 16.7% and 18.8% of the low (1,000 ppm) and high (2,000 ppm) dose groups, respectively, similar to the 20% for the control group. Malignant tumors of the thyroid gland were observed only in the low dose and control groups, at 4.2% and 2%, respectively. In the high dose group, the incidences of lung, liver, urinary bladder and soft tissue cancers were 4.2%, 2.1%, 2.1% and 2.1%, respectively, only one soft tissue cancer being observed in a control group animal. In females, benign tumors were observed in the liver and mammary glands. The incidences of liver tumors in the low and high dose groups were 12.8% and 16%, respectively, and 6% in the control group. Values for mammary gland tumors were 10.6%, 10%, and 18% respectively. Malignant tumors were also observed in various other organs, including the uterus, lung, kidney, thyroid, thymus and salivary gland, but the incidences were very low (about 2-4%) and in dye treated male and female rats were not statistically different from those in the control animals. The results of the present study thus demonstrated that D&C Red No. 36 at the concentrations of 1,000 ppm and 2,000 ppm in the diet is not carcinogenic either to male or female Wistar rats. While the occurrence of benign liver tumors in female rats may be related to dye treatment, the lack of any apparent dose-dependence or any statistically significant difference from the control group (P = 0.06) suggests that this is unlikely. JF - Asian Pacific journal of cancer prevention : APJCP AU - Kupradinun, Piengchai AU - Rienkijakarn, Mati AU - Tanyakaset, Manu AU - Tepsuwan, Anong AU - Kusamran, Wannee R AD - Laboratory Animal and Pathology Section, Research Division, National Cancer Institute, Bangkok 10400, Thailand pkupradi@health.moph.go.th Y1 - 2002 PY - 2002 DA - 2002 SP - 55 EP - 60 VL - 3 IS - 1 SN - 1513-7368, 1513-7368 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859395120?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.atitle=Carcinogenicity+Testing+of+the+Cosmetic+Dye%3A+D%26amp%3BC+Red+No.+36.&rft.au=Kupradinun%2C+Piengchai%3BRienkijakarn%2C+Mati%3BTanyakaset%2C+Manu%3BTepsuwan%2C+Anong%3BKusamran%2C+Wannee+R&rft.aulast=Kupradinun&rft.aufirst=Piengchai&rft.date=2002-01-01&rft.volume=3&rft.issue=1&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.issn=15137368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2003-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antimitotic Peptides and Depsipeptides AN - 18584340; 5333380 AB - Tubulin is the target for an ever increasing number of unusual peptides and depsipeptides that were originally isolated from a wide variety of organisms. Since tubulin is the major component of cellular microtubules, which maintain cell shape in interphase and form the mitotic spindle, most of these compounds are highly toxic to mammalian cells. These peptides and depsipeptides disrupt cellular microtubules and prevent formation of a functional spindle, resulting in the accumulation of cultured cells in the G2/M phase of the cell cycle through specific inhibition of mitosis. At the biochemical level, the compounds all inhibit the assembly of tubulin into polymer and, in the cases where it has been studied, strongly suppress microtubule dynamics at low concentrations. In most cases the peptides and depsipeptides inhibit the binding of vinblastine and vincristine to tubulin in a noncompetitive manner, inhibit tubulin-dependent GTP hydrolysis, and interfere with nucleotide turnover at the exchangeable GTP site on beta -tubulin. Most of the peptides and depsipeptides induce tubulin to form oligomers of aberrant morphology, including tubulin rings that vary in diameter depending on the (depsi) peptide under study. The purpose of this review is to give an overview of the cellular, biochemical, in vivo, and SAR aspects of this group of compounds. We also summarize initial efforts by computer modeling to decipher a pharmacophore among the diverse structures of these peptides and depsipeptides. JF - Current Medicinal Chemistry: Anti-Cancer Agents AU - Hamel, E AU - Covell, D G AD - Building 469, Room 104, NCI-Frederick Frederick, Maryland 21702, USA, hamele@mail.nih.gov Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 19 EP - 53 VL - 2 IS - 1 SN - 1568-0118, 1568-0118 KW - beta -tubulin KW - antimitotic agents KW - depsipeptides KW - vinblastine KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - ^b-tubulin KW - Reviews KW - Cell cycle KW - Antitumor agents KW - W3 33374:Antitumor agents KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18584340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Medicinal+Chemistry%3A+Anti-Cancer+Agents&rft.atitle=Antimitotic+Peptides+and+Depsipeptides&rft.au=Hamel%2C+E%3BCovell%2C+D+G&rft.aulast=Hamel&rft.aufirst=E&rft.date=2002-01-01&rft.volume=2&rft.issue=1&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Current+Medicinal+Chemistry%3A+Anti-Cancer+Agents&rft.issn=15680118&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cell cycle; Antitumor agents; Reviews ER - TY - JOUR T1 - The chlamydial inclusion: Escape from the endocytic pathway AN - 18554222; 5525456 AB - Chlamydiae, bacterial obligate intracellular pathogens, are the etiologic agents of several human diseases. A large part of the chlamydial intracellular survival strategy involves the formation of a unique organelle called the inclusion that provides a protected site within which they replicate. The chlamydial inclusion is effectively isolated from endocytic pathways but is fusogenic with a subset of exocytic vesicles that deliver sphingomyelin from the Golgi apparatus to the plasma membrane. A combination of host and parasite functions contribute to the biogenesis of this compartment. Establishment of the mature inclusion is accompanied by the insertion of multiple chlamydial proteins, suggesting that chlamydiae actively modify the inclusion to define its interactions with the eukaryotic host cell. Despite being sequestered within a membrane-bound vacuole, chlamydiae clearly communicate with and manipulate the host cell from within this privileged intracellular niche. JF - Annual Review of Cell and Developmental Biology AU - Fields, KA AU - Hackstadt, T AD - Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT 59840, USA, ted_hackstadt@nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 221 EP - 245 VL - 18 SN - 1081-0706, 1081-0706 KW - sphingomyelin KW - Microbiology Abstracts B: Bacteriology KW - J 02849:Sexually-transmitted diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18554222?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+Review+of+Cell+and+Developmental+Biology&rft.atitle=The+chlamydial+inclusion%3A+Escape+from+the+endocytic+pathway&rft.au=Fields%2C+KA%3BHackstadt%2C+T&rft.aulast=Fields&rft.aufirst=KA&rft.date=2002-01-01&rft.volume=18&rft.issue=&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Annual+Review+of+Cell+and+Developmental+Biology&rft.issn=10810706&rft_id=info:doi/10.1146%2Fannurev.cellbio.18.012502.105845 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1146/annurev.cellbio.18.012502.105845 ER - TY - JOUR T1 - Microarray analysis of altered gene expression in the TM4 Sertoli-like cell line exposed to chromium(III) chloride AN - 18507566; 5469365 AB - Chromium(III) chloride is a common human exposure metal that is a preconceptional carcinogen in mice, although it enters cells poorly, and is non-toxic and non-carcinogenic in most biologic systems. An indirect effect on sperm is postulated, and this effect might be mediated through the testicular Sertoli cells that influence spermatogenesis. To test this possibility, we exposed mouse TM4 Sertoli-like cultured cells to 1 mM CrCl sub(3) times 6H sub(2)O, a non-toxic dose, for 7 days and then extracted mRNA for microarray analysis. The chromium(III) chloride had modest effects on the expression of many genes, in the range of 1.5-2.3-fold. These effects provided an opportunity for development of statistical approaches for sifting microarray data in a situation where differences were small. Data were winnowed by screening for those ratios that fell outside the 99% confidence limits and/or represented a greater than or equal to 50% change in expression in the three comparison pairs. Fifty-two genes/clones were significant after the Bonferroni adjustment for multiple comparisons. The largest average increase was observed for the transcription factor Bach2, and this increase was confirmed by RT-PCR. The results show that Cr(III) has significant effects on gene expression in a Sertoli-like cell line. JF - Reproductive Toxicology AU - Cheng, RYS AU - Alvord, W G AU - Powell, D AU - Kasprzak, K S AU - Anderson, L M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Box B, Building 538, Fort Detrick, Frederick, MD 21702, USA, rcheng@ncifcrf.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 223 EP - 236 VL - 16 IS - 3 SN - 0890-6238, 0890-6238 KW - DNA microarrays KW - TM4 cells KW - Toxicology Abstracts KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18507566?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+Toxicology&rft.atitle=Microarray+analysis+of+altered+gene+expression+in+the+TM4+Sertoli-like+cell+line+exposed+to+chromium%28III%29+chloride&rft.au=Cheng%2C+RYS%3BAlvord%2C+W+G%3BPowell%2C+D%3BKasprzak%2C+K+S%3BAnderson%2C+L+M&rft.aulast=Cheng&rft.aufirst=RYS&rft.date=2002-01-01&rft.volume=16&rft.issue=3&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=Reproductive+Toxicology&rft.issn=08906238&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Assessing risk factors for obesity between childhood and adolescence: II. Energy metabolism and physical activity AN - 18488224; 5452515 AB - OBJECTIVE: To assess the effect of energy expenditure, including resting metabolic rate (RMR), total energy expenditure (TEE), and activity energy expenditure (AEE), as well as substrate oxidation (respiratory quotient [RQ]), on the development of obesity in a large cohort of Native American children with a high propensity for obesity. METHODS: During the summer months of 1992 to 1995 and again 5 years later, 138 (65 boys and 73 girls) 5-year-old Pima Indian children were studied. At baseline and follow-up, height and weight were measured; body composition was assessed with the use of 18O dilution; RMR and RQ were assessed with the use of indirect calorimetry; TEE was measured with the use of the doubly-labeled water method; and AEE was calculated (TEE - [RMR + 0.1 x TEE]). In addition, an activity questionnaire was used to assess participation in sporting activities as well as television viewing during the previous year. Linear regression models were used to assess the effects of the baseline variables on the development of obesity. RESULTS: Pima Indian children were markedly overweight at both 5 and 10 years of age. Cross-sectionally, percentage of body fat and body weight at 5 and 10 years of age were negatively correlated with sports participation and positively correlated with television viewing. Most important, there was a marked change in the correlation between body size and activity between 5 and 10 years of age: at age 5 years, weight was positively correlated with AEE and PAL, but at age 10 years, the correlation with AEE was lost and that with PAL was negative. However, prospectively, none of the variables measured at baseline was a predictor of percentage of body fat at age 10 years after adjustment for percentage of body fat at age 5 years. CONCLUSIONS: At age 5 years, obesity is associated with decreased participation in sports and increased television viewing but not with a decreased PAL. At age 10 years, obesity is associated with decreased participation in sports, increased television viewing, and a decreased PAL, suggesting that a decrease in PAL in free-living conditions seems to follow, not precede, the development of obesity. JF - Pediatrics AU - Salbe, AD AU - Weyer, C AU - Harper, I AU - Lindsay, R S AU - Ravussin, E AU - Tataranni, P A AD - Affiliation Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2002 PY - 2002 DA - 2002 SP - 307 EP - 314 VL - 110 IS - 2 Pt SN - 1098-4275, 1098-4275 KW - Physical Education Index KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18488224?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=Assessing+risk+factors+for+obesity+between+childhood+and+adolescence%3A+II.+Energy+metabolism+and+physical+activity&rft.au=Salbe%2C+AD%3BWeyer%2C+C%3BHarper%2C+I%3BLindsay%2C+R+S%3BRavussin%2C+E%3BTataranni%2C+P+A&rft.aulast=Salbe&rft.aufirst=AD&rft.date=2002-01-01&rft.volume=110&rft.issue=2+Pt&rft.spage=307&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=10984275&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - How many food additives are rodent carcinogens? AN - 18479549; 5453999 AB - One generally assumes that chemical agents added to foods are reasonably free of risks to human health, and practically everyone consumes some additives in his or her food daily throughout life. In the United States, the 1958 Food Additives Amendment to the Federal Food, Drug and Cosmetic Act of 1938 requires food manufacturers to demonstrate the safety of food additives to the Food and Drug Administration (FDA). The Amendment contains a provision that prohibits approval of an additive if it is found to cause cancer in humans or animals. In the present study, data from the National Toxicology Program rodent bioassay (NTPRB) were used to identify a sample of approximately 50 rodent-tested additives and other chemicals added to food that had been evaluated independently of the FDA/food industry. Surprisingly, the sample shows more than 40% of these food chemicals to be carcinogenic in one or more rodent groups. If this percentage is extrapolated to all substances added to food in the United States, it would imply that more than 1000 of such substances are potential rodent carcinogens. The NTP and FDA test guidelines use similar, though not necessarily identical, rodent test procedures, including near lifetime exposures to the maximum tolerated dose. The FDA specifies that test chemicals should be administered by the oral route. However, the oral route includes three methods of delivering chemicals, that is, mixed in the food or water or delivered by stomach tube (gavage). The NTP data show only 1 of 18 food chemicals mixed in the food are rodent carcinogens, but 16 of 23 gavage-administered food chemicals are carcinogenic to rodents. The distribution suggests that among orally delivered chemicals, those administered in the feed will more likely prove to be noncarcinogens than chemicals given by gavage. The rodent data also reveal that effects may vary according to dose and genotype, as well as by route of administration, to further complicate extrapolation to humans. Human experience with known carcinogens such as tobacco, asbestos, and benzidine convinces us that environmental carcinogens constitute a real threat to human health, although predicting human carcinogens from rodent tests involves a number of uncertainties. These uncertainties do not mean that we should simply ignore the presence of carcinogens. Rather, in the interests of public safety, a serious effort should be made to resolve the questions surrounding the presence of chemicals identified as rodent carcinogens in our food. JF - Environmental and Molecular Mutagenesis AU - Johnson, F M AD - MD EC-31 Toxicology Operations Branch, Environmental Toxicology Program, NIEHS, Research Triangle Park, NC 27709, USA, johnson1@niehs.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 69 EP - 80 VL - 39 IS - 1 SN - 0893-6692, 0893-6692 KW - mice KW - rats KW - Toxicology Abstracts KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18479549?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=Journal+of+Emotional+and+Behavioral+Disorders&rft.atitle=Special+educators+as+intervention+specialists%3A+Dynamic+systems+and+the+complexity+of+intensifying+intervention+for+students+with+emotional+and+behavioral+disorders&rft.au=Farmer%2C+Thomas+W.%3B+Sutherland%2C+Kevin+S.%3B+Talbott%2C+Elizabeth%3B+Brooks%2C+Debbie+S.%3B+Norwalk%2C+Kate%3B+Huneke%2C+Michelle&rft.aulast=Farmer&rft.aufirst=Thomas&rft.date=2016-09-01&rft.volume=24&rft.issue=3&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Journal+of+Emotional+and+Behavioral+Disorders&rft.issn=10634266&rft_id=info:doi/10.1177%2F1063426616650166 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/em.10037 ER - TY - JOUR T1 - Urothelial Cell DNA Adducts in Rubber Workers AN - 18474141; 5446471 AB - Workers employed in the rubber industry appear to have a significant excess cancer risk in a variety of sites, including cancer of the urinary bladder. In this cross-sectional study, we investigated the occurrence of DNA adducts in exfoliated bladder cells of currently exposed, nonsmoking rubber workers (n = 52) and their relationship with occupational exposure estimates and acetylation phenotype (NAT2). Four DNA adducts were identified, with the proportion of positive samples (e.g., DNA samples with quantifiable levels of a specific DNA adduct) ranging from 3.8 to 79%. The highest proportion of positive samples and the highest relative adduct labeling levels were in workers involved in the production functions "mixing" and "curing," areas with potential for substantial exposure to a wide range of chemical compounds used in rubber manufacturing [P < 0.05 for adducts 2 and/or 3, compared to all other departments). No statistically significant relationships were found between identified DNA adducts and urinary mutagenicity or personal inhalable and dermal exposure estimates. Interestingly, subjects with a fast NAT2 acetylation phenotype tended to have higher levels of DNA adducts. This study suggests that rubber workers engaged in mixing and curing may be exposed to compounds that can form DNA adducts in urothelial cells. Larger studies among rubber workers should be conducted to study in more detail the potential carcinogenicity of exposures encountered in these work areas. JF - Environmental and Molecular Mutagenesis AU - Vermeulen, R AU - Talaska, G AU - Schumann, B AU - Bos, R P AU - Rothman, N AU - Kromhout, H AD - Occupational Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., Rockville, MD 20852, USA, vermeulr@mail.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - 306 EP - 313 VL - 39 IS - 4 SN - 0893-6692, 0893-6692 KW - bladder cancer KW - urinary bladder KW - Health & Safety Science Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - N 14630:Chemical reactions & interactions, including effects of radiation KW - X 24155:Biochemistry KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18474141?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+Molecular+Mutagenesis&rft.atitle=Urothelial+Cell+DNA+Adducts+in+Rubber+Workers&rft.au=Vermeulen%2C+R%3BTalaska%2C+G%3BSchumann%2C+B%3BBos%2C+R+P%3BRothman%2C+N%3BKromhout%2C+H&rft.aulast=Vermeulen&rft.aufirst=R&rft.date=2002-01-01&rft.volume=39&rft.issue=4&rft.spage=306&rft.isbn=&rft.btitle=&rft.title=Environmental+and+Molecular+Mutagenesis&rft.issn=08936692&rft_id=info:doi/10.1002%2Fem.10078 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/em.10078 ER - TY - JOUR T1 - Maternal Serum Caffeine Metabolites and Small-for-Gestational Age Birth AN - 18472622; 5441467 AB - To determine whether the third-trimester maternal serum concentration of paraxanthine, caffeine's primary metabolite, is associated with delivery of a small-for-gestational age infant (birth weight less than the 10th percentile for gestational age, gender, and ethnicity) and whether this association differs by smoking, the authors studied 2,515 women who participated in the Collaborative Perinatal Project from 1959 to 1966. The women provided a third-trimester serum sample and had been controls for a nested case-control study of spontaneous abortion. The mean serum paraxanthine concentration was greater in women who gave birth to small-for-gestational age infants (754 ng/ml) than to appropriately grown infants (653 ng/ml, p = 0.02). However, the linear trend for increasing serum paraxanthine concentration to be associated with increasing risk of small-for-gestational age birth was confined to women who also smoked (p = 0.03). There was no association between paraxanthine and fetal growth in nonsmokers (p = 0.48). Adjustment for maternal age, prepregnant weight, education, parity, ethnicity, and the number of cigarettes smoked per day did not alter the results substantially, although the p value for trend among smokers increased to 0.07. The authors conclude that maternal third-trimester serum paraxanthine concentration, which reflects caffeine consumption, was associated with a higher risk of reduced fetal growth, particularly among women who smoked. JF - American Journal of Epidemiology AU - Klebanoff, MA AU - Levine, R J AU - Clemens, J D AU - Wilkins, D G AD - Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA Y1 - 2002/01/01/ PY - 2002 DA - 2002 Jan 01 SP - 32 EP - 37 VL - 155 IS - 1 SN - 0002-9262, 0002-9262 KW - man KW - paraxanthine KW - serum levels KW - Toxicology Abstracts KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18472622?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Epidemiology&rft.atitle=Maternal+Serum+Caffeine+Metabolites+and+Small-for-Gestational+Age+Birth&rft.au=Klebanoff%2C+MA%3BLevine%2C+R+J%3BClemens%2C+J+D%3BWilkins%2C+D+G&rft.aulast=Klebanoff&rft.aufirst=MA&rft.date=2002-01-01&rft.volume=155&rft.issue=1&rft.spage=32&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Immune Modulation by Ionizing Radiation and its Implications for Cancer Immunotherapy AN - 18459632; 5434318 AB - Ionizing radiation exhibits immunomodulatory properties, which could portend a future collaboration of cancer immunotherapy with radiation therapy. The "danger" model of immunity describes antigen-specific cellular immunity engendered by an inflammatory milieu. Dendritic cells (DCs) are attracted to this microenvironment, undergoing maturation after internalizing apoptotic and necrotic cellular debris. Mature DCs mediate antigen-specific cellular immunity via presentation of processed antigen to T cells. Administration of radiation has been utilized in vitro and in vivo to create an inflammatory setting, via induction of apoptosis, necrosis, cell surface molecules, and secretory molecules. Caspase-mediated cellular apoptosis is induced by radiation thro ugh multiple signaling pathways. Radiation upregulates expression of immunomodulatory surface molecules (MHC, costimulatory molecules, adhesion molecules, death receptors, heat shock proteins) and secretory molecules (cytokines, inflammatory mediators) in tumor, stromal, and vascular endothelial cells. Results of animal studies indicate possible radiation-mediated modulation of tumor antigen-specific immunity. Experimental data could indicate that the radiation-induced "danger" microenvironment engenders a DC-mediated antigen-specific immune response. Further enhancement of radiation-mediated inflammation and cell death can be achieved via administration of radiosensitizing pharmaceuticals. Radiation-mediated immune modulation currently remains unquantified and poorly understood. A major research effort will be required to elucidate mechanisms of action. With a thorough understanding of this phenomenon, we believe that ionizing radiation could be optimized for use with cancer vaccines and generate tumor antigen-specific cellular immunity. JF - Current Pharmaceutical Design AU - Friedman, E J AD - Building 10, Rm. B3B69, NIH/NCI, Bethesda, MD 20892, USA, EF68K@NIH.GOV Y1 - 2002 PY - 2002 DA - 2002 SP - 1765 EP - 1780 VL - 8 IS - 19 SN - 1381-6128, 1381-6128 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33190:Therapy: Other KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18459632?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Pharmaceutical+Design&rft.atitle=Immune+Modulation+by+Ionizing+Radiation+and+its+Implications+for+Cancer+Immunotherapy&rft.au=Friedman%2C+E+J&rft.aulast=Friedman&rft.aufirst=E&rft.date=2002-01-01&rft.volume=8&rft.issue=19&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Psychoanalytic+Association&rft.issn=00030651&rft_id=info:doi/10.1177%2F0003065114531044 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Acquisition of apoptotic resistance in arsenic-induced malignant transformation: role of the JNK signal transduction pathway AN - 18394771; 5387430 AB - This study examined the role of signal transduction and apoptosis in malignant transformation induced by arsenic. Prior study showed that chronic arsenite exposure (500 nM, ~18 weeks) induced malignant transformation in rat liver TRL 1215 cells. In the present work, these transformed cells were compared with passage-matched control cells. In addition, TRL 1215 cells were treated subchronically (up to 6 weeks) with arsenic (termed pre-transformed cells) to define events occurring prior to arsenic-induced transformation. Flow cytometry using annexin/FITC revealed that arsenic-induced apoptosis in transformed cells was markedly suppressed in comparison to control or pre-transformed cells. Ro318220, a strong activator of JNK, enhanced arsenite-induced apoptosis in transformed cells. Densitometric analysis of western blots revealed that the ratios of both Bcl-x sub(L)/Bax and Bcl-2/Bax were significantly increased (>2.5-fold) in arsenic-transformed cells. Transformed, pre-transformed and control cells were treated with arsenic and levels of phosphorylated extracellular signal-regulated kinases, ERK1/2, JNK1/2 and p38 were determined by western blot analysis. The three mitogen-activated protein kinases (MAPKs) were phosphorylated in a dose-dependent fashion in all cell types. However, the levels of phosphorylated JNK1/2 were markedly decreased in the arsenic-transformed cells, whereas in pre-transformed cells the levels of phosphorylated MAPKs remained the same as in control cells. JNK kinase activity was suppressed in transformed cells whereas Ro318220 enhanced this activity. Thus, during arsenic-induced malignant transformation resistance to apoptosis develops, possibly due to perturbation of the JNK pathway. JF - Carcinogenesis AU - Qu, W AU - Bortner, C D AU - Sakurai, T AU - Hobson, MJ AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, PO Box 12233, Mail Drop F0-09, 111 Alexander Drive, Research Triangle Park, NC 27709, USA Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 151 EP - 159 VL - 23 IS - 1 SN - 0143-3334, 0143-3334 KW - JNK protein KW - Toxicology Abstracts KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18394771?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Acquisition+of+apoptotic+resistance+in+arsenic-induced+malignant+transformation%3A+role+of+the+JNK+signal+transduction+pathway&rft.au=Qu%2C+W%3BBortner%2C+C+D%3BSakurai%2C+T%3BHobson%2C+MJ%3BWaalkes%2C+M+P&rft.aulast=Qu&rft.aufirst=W&rft.date=2002-01-01&rft.volume=23&rft.issue=1&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Hsp90 inhibitors as novel cancer chemotherapeutic agents AN - 18389715; 5382492 AB - Heat shock protein 90 (Hsp90) is a molecular chaperone whose association is required for the stability and function of multiple mutated, chimeric and over-expressed signaling proteins that promote the growth and/or survival of cancer cells. Hsp90 client proteins include mutated p53, Bcr-Abl, Raf-1, Akt, ErbB2 and hypoxia-inducible factor 1 alpha (HIF-1 alpha ). Hsp90 inhibitors, by interacting specifically with a single molecular target, cause the destabilization and eventual degradation of Hsp90 client proteins, and they have shown promising antitumor activity in preclinical model systems. One Hsp90 inhibitor, 17-allylaminogeldanamycin (17AAG), is currently in phase I clinical trial. Because of the chemoprotective activity of several proteins that are Hsp90 clients, the combination of an Hsp90 inhibitor with a standard chemotherapeutic agent could dramatically increase the in vivo efficacy of the therapeutic agent. JF - Trends in Molecular Medicine AU - Neckers, L AD - Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, 9610 Medical Center Drive, Suite 300, Rockville, MD 20850, USA, len@helix.nih.gov Y1 - 2002 PY - 2002 DA - 2002 SP - S55 EP - S61 VL - 8 IS - 4 SN - 1471-4914, 1471-4914 KW - Akt protein KW - ErbB2 protein KW - Hsp90 protein KW - Raf-1 protein KW - antitumor activity KW - clinical trials KW - hypoxia-inducible factor 1 alpha KW - man KW - p53 protein KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33374:Antitumor agents KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18389715?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+Molecular+Medicine&rft.atitle=Hsp90+inhibitors+as+novel+cancer+chemotherapeutic+agents&rft.au=Neckers%2C+L&rft.aulast=Neckers&rft.aufirst=L&rft.date=2002-01-01&rft.volume=8&rft.issue=4&rft.spage=S55&rft.isbn=&rft.btitle=&rft.title=Trends+in+Molecular+Medicine&rft.issn=14714914&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - A TRENDS Guide to Cancer Therapeutics N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - MALDI/MS-Based Epitope Mapping of Antigens Bound to Immobilized Antibodies AN - 18369656; 5337939 AB - Proteolytic digestion of proteins bound to immobilized antibodies, combined with matrix assisted laser desorption (MALDI) mass spectrometric identification of the affinity-bound peptides, can be a powerful technique for epitope determination. Binding of the protein to the antibody is done while the protein is in its native, folded state. A purified protein is not required for this procedure, because only proteins containing the antigenic determinant will bind to the antibody in the initial step. The method makes use of the resistance of the antibody to enzymatic digestion. Enzymatic cleavage products of the antigenic protein not containing the epitope are washed off the beads, leaving the epitope-containing fragments affinity bound to the immobilized antibody. Dissociation of the antigen-antibody complex prior to mass spectrometric analysis is unnecessary because the affinity-bound peptides are released by the MALDI matrix crystallization process, although the antibody remains covalently attached to the sepharose beads. This epitope-mapping protocol has been used in the determination of both continuous and discontinuous epitopes on both glycosylated and unglycosylated proteins. JF - Molecular Biotechnology AU - Parker, CE AU - Tomer, K B AD - Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA, parkerc@niehs.nih.gov Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 49 EP - 62 VL - 20 IS - 1 SN - 1073-6085, 1073-6085 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33375:Antibodies KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18369656?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=Anales+de+Psicolog%C3%ADa&rft.atitle=Harmonic+Scale+of+Development.+A+proposal+of+integration+by+which+to+assess+child+development&rft.au=Abell%C3%A1n%2C+Francisco+J.%3B+Calvo-Llena%2C+Mar%C3%ADa+T.%3B+Rabad%C3%A1n%2C+Rafael&rft.aulast=Abell%C3%A1n&rft.aufirst=Francisco&rft.date=2015-10-01&rft.volume=31&rft.issue=3&rft.spage=837&rft.isbn=&rft.btitle=&rft.title=Anales+de+Psicolog%C3%ADa&rft.issn=02129728&rft_id=info:doi/10.6018%2Fanalesps.31.3.199901 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Gene Expression Omnibus: NCBI gene expression and hybridization array data repository AN - 18363134; 5333897 AB - The Gene Expression Omnibus (GEO) project was initiated in response to the growing demand for a public repository for high-throughput gene expression data. GEO provides a flexible and open design that facilitates submission, storage and retrieval of heterogeneous data sets from high-throughput gene expression and genomic hybridization experiments. GEO is not intended to replace in house gene expression databases that benefit from coherent data sets, and which are constructed to facilitate a particular analytic method, but rather complement these by acting as a tertiary, central data distribution hub. The three central data entities of GEO are platforms, samples and series, and were designed with gene expression and genomic hybridization experiments in mind. A platform is, essentially, a list of probes that define what set of molecules may be detected. A sample describes the set of molecules that are being probed and references a single platform used to generate its molecular abundance data. A series organizes samples into the meaningful data sets which make up an experiment. The GEO repository is publicly accessible through the World Wide Web at http://www.ncbi.nlm.nih.gov/geo. JF - Nucleic Acids Research AU - Edgar, R AU - Domrachev, M AU - Lash, A E AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Lister Hill Center, 8600 Rockville Pike, Bethesda, MD 20894, USA, alash@nih.gov Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 207 EP - 210 VL - 30 IS - 1 SN - 0305-1048, 0305-1048 KW - Gene Expression Omnibus KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Gene expression KW - Databases KW - reviews KW - DNA probes KW - Bioinformatics KW - N 14100:Reviews KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18363134?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=Gene+Expression+Omnibus%3A+NCBI+gene+expression+and+hybridization+array+data+repository&rft.au=Edgar%2C+R%3BDomrachev%2C+M%3BLash%2C+A+E&rft.aulast=Edgar&rft.aufirst=R&rft.date=2002-01-01&rft.volume=30&rft.issue=1&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bioinformatics; DNA probes; Gene expression; reviews; Databases ER - TY - JOUR T1 - Genomic database resources for Dictyostelium discoideum AN - 18362755; 5333863 AB - Dictyostelium is an attractive model system for the study of mechanisms basic to cellular function or complex multicellular developmental processes. Recent advances in Dictyostelium genomics have generated a wide spectrum of resources. However, much of the current genomic sequence information is still not currently available through GenBank or related databases. Thus, many investigators are unaware that extensive sequence data from Dictyostelium has been compiled, or of its availability and access. Here, we discuss progress in Dictyostelium genomics and gene annotation, and highlight the primary portals for sequence access, manipulation and analysis (http://genome.imb-jena.de/dictyostelium/; http://dictygenome.bcm.tmc.edu/; http://www.sanger. ac.uk/Projects/D_discoideum/; http://www.csm.biol. tsukuba.ac.jp/cDNAproject.html). JF - Nucleic Acids Research AU - Kreppel, L AU - Kimmel, A R AD - Laboratory of Cellular and Developmental Biology (50/3351), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-8028, USA, ark1@helix.nih.gov Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 84 EP - 86 VL - 30 IS - 1 SN - 0305-1048, 0305-1048 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Agricultural and Environmental Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Dictyostelium discoideum KW - Nucleotide sequence KW - Genetic analysis KW - World Wide Web KW - Databases KW - Reviews KW - Bioinformatics KW - N 14100:Reviews KW - K 03076:Protozoa KW - W2 32080:Bioinformatics and computer applications KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18362755?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=Genomic+database+resources+for+Dictyostelium+discoideum&rft.au=Kreppel%2C+L%3BKimmel%2C+A+R&rft.aulast=Kreppel&rft.aufirst=L&rft.date=2002-01-01&rft.volume=30&rft.issue=1&rft.spage=84&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Dictyostelium discoideum; Genetic analysis; World Wide Web; Nucleotide sequence; Databases; Reviews; Bioinformatics ER - TY - JOUR T1 - CDD: a database of conserved domain alignments with links to domain three-dimensional structure AN - 18361841; 5333917 AB - The Conserved Domain Database (CDD) is a compilation of multiple sequence alignments representing protein domains conserved in molecular evolution. It has been populated with alignment data from the public collections Pfam and SMART, as well as with contributions from colleagues at NCBI. The current version of CDD (v.1.54) contains 3693 such models. CDD alignments are linked to protein sequence and structure data in Entrez. The molecular structure viewer Cn3D serves as a tool to interactively visualize alignments and three-dimensional structure, and to link three-dimensional residue coordinates to descriptions of evolutionary conservation. CDD can be accessed on the World Wide Web at http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml. Protein query sequences may be compared against databases of position-specific score matrices derived from alignments in CDD, using a service named CD-Search, which can be found at http://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi. CD-Search runs reverse-position-specific BLAST (RPS-BLAST), a variant of the widely used PSI-BLAST algorithm. CD-Search is run by default for protein-protein queries submitted to NCBI's BLAST service at http://www.ncbi.nlm.nih.gov/BLAST. JF - Nucleic Acids Research AU - Marchler-Bauer, A AU - Panchenko, A R AU - Shoemaker, BA AU - Thiessen, P A AU - Geer, L Y AU - Bryant, SH AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Building 38 A, Room 8N805, 8600 Rockville Pike, Bethesda, MD 20894, USA, bauer@ncbi.nlm.nih.gov Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 281 EP - 283 VL - 30 IS - 1 SN - 0305-1048, 0305-1048 KW - databases KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - reviews KW - Domains KW - World Wide Web KW - Databases KW - Proteins KW - Conserved sequence KW - Bioinformatics KW - N 14100:Reviews KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18361841?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=CDD%3A+a+database+of+conserved+domain+alignments+with+links+to+domain+three-dimensional+structure&rft.au=Marchler-Bauer%2C+A%3BPanchenko%2C+A+R%3BShoemaker%2C+BA%3BThiessen%2C+P+A%3BGeer%2C+L+Y%3BBryant%2C+SH&rft.aulast=Marchler-Bauer&rft.aufirst=A&rft.date=2002-01-01&rft.volume=30&rft.issue=1&rft.spage=281&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bioinformatics; World Wide Web; Conserved sequence; Proteins; Domains; reviews; Databases ER - TY - JOUR T1 - Database resources of the National Center for Biotechnology Information: 2002 update AN - 18361795; 5333844 AB - In addition to maintaining the GenBank nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data analysis and retrieval resources that operate on the data in GenBank and a variety of other biological data made available through NCBI's web site. NCBI data retrieval resources include Entrez, PubMed, LocusLink and the Taxonomy Browser. Data analysis resources include BLAST, Electronic PCR, OrfFinder, RefSeq, UniGene, HomoloGene, Database of Single Nucleotide Polymorphisms (dbSNP), Human Genome Sequencing, Human MapViewer, Human VMouse Homology Map, Cancer Chromosome Aberration Project (CCAP), Entrez Genomes, Clusters of Orthologous Groups (COGs) database, Retroviral Genotyping Tools, SAGEmap, Gene Expression Omnibus (GEO), Online Mendelian Inheritance in Man (OMIM), the Molecular Modeling Database (MMDB) and the Conserved Domain Database (CDD). Augmenting many of the web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of the resources can be accessed through the NCBI home page at http://www.ncbi.nlm.nih.gov. JF - Nucleic Acids Research AU - Wheeler, D L AU - Church, D M AU - Lash, A E AU - Leipe, D D AU - Madden, T L AU - Pontius, JU AU - Schuler, G D AU - Schriml, L M AU - Tatusova, T A AU - Wagner, L AU - Rapp, BA AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Building 38A, 8600 Rockville Pike, Bethesda, MD 20894, USA, wheeler@ncbi.nlm.nih.gov Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 13 EP - 16 VL - 30 IS - 1 SN - 0305-1048, 0305-1048 KW - National Center for Biotechnology Information KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Databases KW - Analysis KW - Nucleotide sequence KW - Bioinformatics KW - N 14100:Reviews KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18361795?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=Database+resources+of+the+National+Center+for+Biotechnology+Information%3A+2002+update&rft.au=Wheeler%2C+D+L%3BChurch%2C+D+M%3BLash%2C+A+E%3BLeipe%2C+D+D%3BMadden%2C+T+L%3BPontius%2C+JU%3BSchuler%2C+G+D%3BSchriml%2C+L+M%3BTatusova%2C+T+A%3BWagner%2C+L%3BRapp%2C+BA&rft.aulast=Wheeler&rft.aufirst=D&rft.date=2002-01-01&rft.volume=30&rft.issue=1&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Nucleotide sequence; Databases; Bioinformatics; Analysis ER - TY - JOUR T1 - Gene Expression Profile of Human Bone Marrow Stromal Cells: High-Throughput Expressed Sequence Tag Sequencing Analysis AN - 18357362; 5321059 AB - Human bone marrow stromal cells (HBMSC) are pluripotent cells with the potential to differentiate into osteoblasts, chondrocytes, myelosupportive stroma, and marrow adipocytes. We used high-throughput DNA sequencing analysis to generate 4258 single-pass sequencing reactions (known as expressed sequence tags, or ESTs) obtained from the 5' (97) and 3' (4161) ends of human cDNA clones from a HBMSC cDNA library. Our goal was to obtain tag sequences from the maximum number of possible genes and to deposit them in the publicly accessible database for ESTs (dbEST of the National Center for Biotechnology Information). Comparisons of our EST sequencing data with nonredundant human mRNA and protein databases showed that the ESTs represent 1860 gene clusters. The EST sequencing data analysis showed 60 novel genes found only in this cDNA library after BLAST analysis against 3.0 million ESTs in NCBI's dbEST database. The BLAST search also showed the identified ESTs that have close homology to known genes, which suggests that these may be newly recognized members of known gene families. The gene expression profile of this cell type is revealed by analyzing both the frequency with which a message is encountered and the functional categorization of expressed sequences. Comparing an EST sequence with the human genomic sequence database enables assignment of an EST to a specific chromosomal region (a process called digital gene localization) and often enables immediate partial determination of intron/exon boundaries within the genomic structure. It is expected that high-throughput EST sequencing and data mining analysis will greatly promote our understanding of gene expression in these cells and of growth and development of the skeleton. JF - Genomics AU - Jia, L AU - Young, M F AU - Powell, J AU - Yang, L AU - Ho, N C AU - Hotchkiss, R AU - Robey, P G AU - Francomano, CA AD - Laboratory of Genetics, National Institute of Aging, National Institutes of Health, Baltimore, Maryland, 21224, USA Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 7 EP - 17 PB - Academic Press VL - 79 IS - 1 SN - 0888-7543, 0888-7543 KW - man KW - Expressed sequence tags KW - Biotechnology and Bioengineering Abstracts; Calcium & Calcified Tissue Abstracts; Bioengineering Abstracts; Genetics Abstracts KW - Bone marrow KW - Gene expression KW - Differentiation KW - Stem cells KW - Gene clusters KW - Bioinformatics KW - Skeleton KW - T 200005:Molecular biology and genetics KW - G 07430:Chromosome studies/nucleotide sequence KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18357362?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genomics&rft.atitle=Gene+Expression+Profile+of+Human+Bone+Marrow+Stromal+Cells%3A+High-Throughput+Expressed+Sequence+Tag+Sequencing+Analysis&rft.au=Jia%2C+L%3BYoung%2C+M+F%3BPowell%2C+J%3BYang%2C+L%3BHo%2C+N+C%3BHotchkiss%2C+R%3BRobey%2C+P+G%3BFrancomano%2C+CA&rft.aulast=Jia&rft.aufirst=L&rft.date=2002-01-01&rft.volume=79&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Genomics&rft.issn=08887543&rft_id=info:doi/10.1006%2Fgeno.2001.6683 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bioinformatics; Skeleton; Stem cells; Gene clusters; Gene expression; Differentiation; Bone marrow DO - http://dx.doi.org/10.1006/geno.2001.6683 ER - TY - JOUR T1 - Oxidation of chlorophenols in soil at natural pH by catalyzed hydrogen peroxide: the effect of soil organic matter AN - 18355677; 5316852 AB - This investigation reports on the effects of soil organic matter (SOM) during the oxidation of chlorophenols with Fe super(2+)-catalyzed H sub(2)O sub(2) (Fenton oxidation) system. The soil pH was 7.1 and was not altered. Sorption experiments of soil pre-treated under various oxidation conditions were performed. Concentrations of organic matter in the liquid phase and soil before and after oxidation were analyzed. The results were correlated to the observation in batch Fenton oxidation tests. They showed that the oxidation of chlorophenols at natural soil pH depended on the dose of H sub(2)O sub(2) and Fe super(2+). The soil organic content did not vary significantly after various Fenton treatments, while the sorption of chlorophenols was 10-25% less by the oxidation. The concentration of chlorophenols in the liquid phase exhibited a "decrease and rebound" phenomenon in the batch Fenton oxidation tests. It appeared that the oxidation of SOM resulted in the release of sorbed chlorophenols which were then oxidized by the excess H sub(2)O sub(2). An "oxidation-desorption-oxidation" scheme was proposed to describe one of the interaction mechanisms among the oxidant, SOM, and chlorophenols during oxidation. JF - Chemosphere AU - Yeh, CK-J AU - Kao, Y-A AU - Cheng, C-P AD - Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, 1 Hseuh Fu Road, Nei Pu 91207, Pingtung, Taiwan, ROC, kjyeh@mail.npust.edu.tw Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 67 EP - 73 VL - 46 IS - 1 SN - 0045-6535, 0045-6535 KW - chlorophenols KW - hydrogen peroxide KW - Pollution Abstracts KW - Desorption KW - Organic matter KW - Oxidation KW - Soil contamination KW - P 5000:LAND POLLUTION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18355677?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemosphere&rft.atitle=Oxidation+of+chlorophenols+in+soil+at+natural+pH+by+catalyzed+hydrogen+peroxide%3A+the+effect+of+soil+organic+matter&rft.au=Yeh%2C+CK-J%3BKao%2C+Y-A%3BCheng%2C+C-P&rft.aulast=Yeh&rft.aufirst=CK-J&rft.date=2002-01-01&rft.volume=46&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Chemosphere&rft.issn=00456535&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Soil contamination; Oxidation; Organic matter; Desorption ER - TY - JOUR T1 - Cannabis (Marijuana) - Effects on Human Behavior and Performance AN - 18332123; 5380130 AB - Cannabis is one of the oldest and most commonly abused drugs in the world. Recently, tremendous advances have been made in our understanding of the endogenous cannabinoid system with the identification of cannabinoid receptors, cannabinoid receptor antagonists, endogenous neurotransmitters, metabolic enzymes, and reuptake mechanisms. These advances have helped us to elucidate the mechanisms of action of cannabis and the side effects and toxicities associated with its use. In addition, potential therapeutic applications are being investigated for the use of smoked cannabis and synthetic THC (dronabinol). Most workplace, military, and criminal justice positive urine drug tests are due to the use of cannabis. In addition, alternative matrices, including saliva, sweat, and hair, are being utilized for monitoring cannabis use in treatment, employment, and criminal justice settings. Experimental laboratory studies have identified cognitive, physiological, and psychomotor effects following cannabis. Epidemiological studies reveal that cannabis is the most common illicit drug world-wide in impaired drivers, and in motor vehicle injuries and fatalities. Driving simulator studies also indicate performance impairment following cannabis use; however, the results of open- and closed-road driving studies and of culpability studies do not consistently document increased driving risk. Clearly a combination of ethanol and cannabis use significantly increases risks. This article reviews the pharmacokinetics and pharmacodynamics of cannabis and places special emphasis on the effects of cannabis on complex tasks such as driving and flying. JF - Forensic Science Review AU - Huestis, MA AD - Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, United States of America Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 15 EP - 60 VL - 14 IS - 1-2 SN - 1042-7201, 1042-7201 KW - drug abuse KW - marijuana KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - u9-Tetrahydrocannabinol KW - Toxicity KW - Drug abuse KW - Driving ability KW - Cannabis KW - Neurotransmitters KW - Side effects KW - Ethanol KW - H 14000:Toxicology KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18332123?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Forensic+Science+Review&rft.atitle=Cannabis+%28Marijuana%29+-+Effects+on+Human+Behavior+and+Performance&rft.au=Huestis%2C+MA&rft.aulast=Huestis&rft.aufirst=MA&rft.date=2002-01-01&rft.volume=14&rft.issue=1-2&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=Forensic+Science+Review&rft.issn=10427201&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special Issue: The Effects of Drugs on Human Performance and Behavior. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cannabis; Toxicity; Side effects; Drug abuse; u9-Tetrahydrocannabinol; Neurotransmitters; Driving ability; Ethanol ER - TY - JOUR T1 - A DNA repair system specific for thermophilic Archaea and bacteria predicted by genomic context analysis AN - 18288380; 5334107 AB - During a systematic analysis of conserved gene context in prokaryotic genomes, a previously undetected, complex, partially conserved neighborhood consisting of more than 20 genes was discovered in most Archaea (with the exception of Thermoplasma acidophilum and Halobacterium NRC-1) and some bacteria, including the hyperthermophiles Thermotoga maritima and Aquifex aeolicus. The gene composition and gene order in this neighborhood vary greatly between species, but all versions have a stable, conserved core that consists of five genes. One of the core genes encodes a predicted DNA helicase, often fused to a predicted HD-superfamily hydrolase, and another encodes a RecB family exonuclease; three core genes remain uncharacterized, but one of these might encode a nuclease of a new family. Two more genes that belong to this neighborhood and are present in most of the genomes in which the neighborhood was detected encode, respectively, a predicted HD-superfamily hydrolase (possibly a nuclease) of a distinct family and a predicted, novel DNA polymerase. Another characteristic feature of this neighborhood is the expansion of a superfamily of paralogous, uncharacterized proteins, which are encoded by at least 20-30% of the genes in the neighborhood. The functional features of the proteins encoded in this neighborhood suggest that they comprise a previously undetected DNA repair system, which, to our knowledge, is the first repair system largely specific for thermophiles to be identified. This hypothetical repair system might be functionally analogous to the bacterial-eukaryotic system of translesion, mutagenic repair whose central components are DNA polymerases of the UmuC-DinB-Rad30-Rev1 superfamily, which typically are missing in thermophiles. JF - Nucleic Acids Research AU - Makarova, K S AU - Aravind, L AU - Grishin, N V AU - Rogozin, IB AU - Koonin, E V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Building 380, Bethesda, MD 20894, USA, koonin@ncbi.nlm.nih.gov Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 482 EP - 496 VL - 30 IS - 2 SN - 0305-1048, 0305-1048 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - DNA-directed DNA polymerase KW - Aquifex aeolicus KW - Thermophilic archaea KW - DNA repair KW - Thermotoga maritima KW - J 02725:DNA KW - N 14652:DNA repair UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18288380?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=A+DNA+repair+system+specific+for+thermophilic+Archaea+and+bacteria+predicted+by+genomic+context+analysis&rft.au=Samuelson%2C+Larissa+K.%3B+Jenkins%2C+Gavin+W.%3B+Spencer%2C+John+P.&rft.aulast=Samuelson&rft.aufirst=Larissa&rft.date=2015-04-01&rft.volume=7&rft.issue=2&rft.spage=191&rft.isbn=&rft.btitle=&rft.title=Topics+in+Cognitive+Science&rft.issn=17568757&rft_id=info:doi/10.1111%2Ftops.12129 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Thermotoga maritima; Aquifex aeolicus; DNA repair; Thermophilic archaea; DNA-directed DNA polymerase ER - TY - JOUR T1 - The Sm-like Hfq Protein Increases OxyS RNA Interaction with Target mRNAs AN - 18278213; 5334719 AB - The Escherichia coli host factor I, Hfq, binds to many small regulatory RNAs and is required for OxyS RNA repression of fhIA and rpoS mRNA translation. Here we report that Hfq is a bacterial homolog of the Sm and Sm-like proteins integral to RNA processing and mRNA degradation complexes in eukaryotic cells. Hfq exhibits the hallmark features of Sm and Sm-like proteins: the Sm1 sequence motif, a multisubunit ring structure (in this case a homomeric hexamer), and preferential binding to polyU. We also show that Hfq increases the OxyS RNA interaction with its target messages and propose that the enhancement of RNA-RNA pairing may be a general function of Hfq, Sm, and Sm-like proteins. JF - Molecular Cell AU - Zhang, A AU - Wassarman, K M AU - Ortega, J AU - Steven, A C AU - Storz, G AD - Cell Biology and Metabolism Branch National Institute of Child Health and Human Development National Institutes of Health Bethesda, Maryland 20892, USA, storz@helix.nih.gov Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 11 EP - 22 VL - 9 IS - 1 SN - 1097-2765, 1097-2765 KW - Hfq protein KW - OxyS protein KW - Sm proteins KW - double prime Sm proteins KW - rpoS gene KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - mRNA turnover KW - Escherichia coli KW - J 02726:RNA and ribosomes KW - N 14930:Transcription factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18278213?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Cell&rft.atitle=The+Sm-like+Hfq+Protein+Increases+OxyS+RNA+Interaction+with+Target+mRNAs&rft.au=Zhang%2C+A%3BWassarman%2C+K+M%3BOrtega%2C+J%3BSteven%2C+A+C%3BStorz%2C+G&rft.aulast=Zhang&rft.aufirst=A&rft.date=2002-01-01&rft.volume=9&rft.issue=1&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Molecular+Cell&rft.issn=10972765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; mRNA turnover ER - TY - JOUR T1 - Lipoxin-mediated inhibition of IL-12 production by DCs: a mechanism for regulation of microbial immunity AN - 18270483; 5329266 AB - Lipoxins are eicosanoid mediators that show potent inhibitory effects on the acute inflammatory process. We show here that the induction of lipoxin A sub(4) (LXA sub(4)) accompanied the in vivo suppression of interleukin 12 (IL-12) responsiveness of murine splenic dendritic cells (DCs) after microbial stimulation with an extract of Toxoplasma gondii. This paralysis of DC function could not be triggered in mice that were deficient in a key lipoxygenase involved in LXA sub(4) biosynthesis. In addition, DCs pre-treated with LXA sub(4) became refractory to microbial stimulation for IL-12 production in vitro and mice injected with a stable LXA sub(4) analog showed reduced splenic DC mobilization and IL-12 responses in vivo. Together, these findings indicate that the induction of lipoxins in response to microbial stimulation can provide a potent mechanism for regulating DC function during the innate response to pathogens. JF - Nature Immunology AU - Aliberti, J AU - Hieny, S AU - Reis e Sousa, C AU - Serhan, C N AU - Sher, A AD - Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 76 EP - 82 VL - 3 IS - 1 SN - 1529-2908, 1529-2908 KW - mice KW - lipoxin A4 KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Dendritic cells KW - Interleukin 12 KW - Toxoplasma gondii KW - Spleen KW - Inflammation KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18270483?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cliniques+m%C3%A9diterran%C3%A9ennes%3A+Psychanalyse+et+Psychopathologie+Freudiennes&rft.atitle=Violences+conjugales%2C+violences+th%C3%A9oriques+La+psychanalyse+%C3%A0+l%27%C3%A9preuve+du+genre&rft.au=Ayouch%2C+Thamy%3Bde+la+Plata+Cury+Tardivo%2C+Leila+Salom%C3%A3o&rft.aulast=Ayouch&rft.aufirst=Thamy&rft.date=2013-01-01&rft.volume=88&rft.issue=&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Cliniques+m%C3%A9diterran%C3%A9ennes%3A+Psychanalyse+et+Psychopathologie+Freudiennes&rft.issn=07627491&rft_id=info:doi/10.3917%2Fcm.088.0019 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Toxoplasma gondii; Interleukin 12; Inflammation; Dendritic cells; Spleen DO - http://dx.doi.org/10.1038/ni745 ER - TY - JOUR T1 - Adenoviral delivery of A-FOS, an AP-1 dominant negative, selectively inhibits drug resistance in two human cancer cell lines AN - 18268632; 5324171 AB - Activator protein-1 (AP-1) transcription factor has been linked to chemotherapeutic resistance. To assess the clinical efficacy of AP-1 inhibition toward reversing drug resistance, we have developed an adenovirus expressing a dominant negative that inhibits AP-1 DNA binding, named AdA-FOS. We examined the consequence of AdA-FOS infection on two paired human cancer cell lines, each pair consisting of a parental cell and the drug-resistant derivative. The first pair of cells is the parental human ovarian cancer cell line A2780 and the cisplatin-resistant A2780/CP70 cell line. The second pair of cells is the parental epidermal carcinoma cell line KB8 and the multidrug-resistant (mdr) KB85 cell line. Because of an association of up-regulated AP-1 activity with their drug resistance, these cell lines were considered good targets of AdA-FOS therapy. Following infection of the drug-sensitive and drug-resistant cells, we observed a significant decrease in cell viability of KB85 and A2780/CP70 cells at drug doses normally not lethal to the cell. The parental cell lines, A2780 and KB8 cells, were not similarly affected by AdA-FOS. This decrease in viability was specific to AdA-FOS as an adenovirus control (Advector) did not reverse drug resistance. Although the efficiency of AdA-FOS in therapy would need to be further analyzed with other cisplatin-resistant and mdr cell lines, these results suggest that AP-1 is a therapeutic molecular target and that inhibition of AP-1 DNA binding may be of clinical value in treating chemotherapeutic resistance. JF - Cancer Gene Therapy AU - Bonovich, M AU - Olive, M AU - Reed, E AU - O'Connell, B AU - Vinson, C AD - Building 37, Room 4D06, Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA, vinsonc@dc37a.nci.nih.gov Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 62 EP - 70 VL - 9 IS - 1 SN - 0929-1903, 0929-1903 KW - man KW - A-Fos protein KW - AP-1 protein KW - cisplatin KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Gene therapy KW - DNA-binding protein KW - Drug resistance KW - Transcription factors KW - Adenovirus KW - Multidrug resistance KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18268632?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Gene+Therapy&rft.atitle=Adenoviral+delivery+of+A-FOS%2C+an+AP-1+dominant+negative%2C+selectively+inhibits+drug+resistance+in+two+human+cancer+cell+lines&rft.au=Bonovich%2C+M%3BOlive%2C+M%3BReed%2C+E%3BO%27Connell%2C+B%3BVinson%2C+C&rft.aulast=Bonovich&rft.aufirst=M&rft.date=2002-01-01&rft.volume=9&rft.issue=1&rft.spage=62&rft.isbn=&rft.btitle=&rft.title=Cancer+Gene+Therapy&rft.issn=09291903&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adenovirus; Transcription factors; Multidrug resistance; Drug resistance; DNA-binding protein; Gene therapy; Expression vectors ER - TY - JOUR T1 - Radiochemical synthesis and biodistribution of a novel maxi-K potassium channel opener AN - 18255999; 5317495 AB - The racemate 1, ((+/-)-(5-Chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6-(trifluor omethyl)- 2H-indol-2-one), is a potent, specific and novel opener of cloned large-conductance, calcium-activated (maxi-K) potassium channels. One of its enantiomers, BMS-204352 (Maxi-Post), is undergoing clinical evaluation for efficacy in patients with suspected acute stroke. In the current study, we have prepared [ super(18)F]-labeled 1 using a silver assisted nucleophilic substitution to examine its distribution and disposition in the rat, with particular emphasis on the brain. Biodistribution studies in rats confirm that brain uptake is rapid and occurs at high levels, and indicate that a major fraction of the compound in the brain does not accumulate by a specific, saturable mechanism. JF - Nuclear Medicine and Biology AU - Kiesewetter, DO AU - Jagoda, E M AU - Starrett, JE Jr AU - Gribkoff, V K AU - Hewawasam, P AU - Srinivas, N AU - Salazar, D AU - Eckelman, W C AD - Positron Emission Tomography Department, Clinical Center, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892-1180, USA, dk7k@nih.gov Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 55 EP - 59 VL - 29 IS - 1 SN - 0969-8051, 0969-8051 KW - channels KW - distribution KW - rats KW - 1,-5-chloro-2-methoxyphenyl-1,3-dihydro-3-fluoro-6-trimethyl-2H-in dol-2one KW - Toxicology Abstracts KW - 1,-5-chloro-2-methoxyphenyl-1,3-dihydro-3-fluoro-6-trimethyl-2H-indol-2one KW - Potassium KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18255999?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nuclear+Medicine+and+Biology&rft.atitle=Radiochemical+synthesis+and+biodistribution+of+a+novel+maxi-K+potassium+channel+opener&rft.au=Kiesewetter%2C+DO%3BJagoda%2C+E+M%3BStarrett%2C+JE+Jr%3BGribkoff%2C+V+K%3BHewawasam%2C+P%3BSrinivas%2C+N%3BSalazar%2C+D%3BEckelman%2C+W+C&rft.aulast=Kiesewetter&rft.aufirst=DO&rft.date=2002-01-01&rft.volume=29&rft.issue=1&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Nuclear+Medicine+and+Biology&rft.issn=09698051&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Potassium ER - TY - JOUR T1 - Modulation of Cyclophilin Gene Expression by N-4-(Hydroxyphenyl)retinamide: Association With Reactive Oxygen Species Generation and Apoptosis AN - 18255368; 5317299 AB - To explore the mechanisms underlying the pro-apoptotic effects of the synthetic retinoid N-4-(hydroxyphenyl)retinamide (4-HPR) on LNCaP human prostate cancer cells, we used the differential display-polymerase chain reaction (DD-PCR) technique to identify 4-HPR-responsive genes. RNA extracted from LNCaP cells that had been treated for 24 h with 4-HPR at a dose (2.5 mu M) optimal for apoptosis induction was used for DD-PCR analysis using random primers. A differentially expressed 115 bp fragment was cloned and sequenced and then identified in GenBank as having a high degree of homology with several members of the cyclophilin gene family. Northern blot analyses using specific probes for cyclophilin A, cyclophilin D, and the cloned 115-bp fragment were performed on RNA extracted from LNCaP cells and MCF-7 human breast cancer cells treated with 4-HPR, N-acetylcysteine (NAC, an anti-oxidant), 4-HPR plus NAC, cyclosporin A, R-1881 (a synthetic androgen), dehydroepiandrosterone, all-trans retinoic acid, or prednisone. 4-HPR downregulated the transcript detected by the 115-bp fragment. Expression patterns detected by the 115-bp fragment and cyclophilin D probes were identical in response to each treatment; none of these treatments affected cyclophilin A expression. Furthermore, expression of mRNA transcripts detected by the 115-bp fragment and cyclophilin D probes correlated with the generation of reactive oxygen species (ROS), as detected by measurement of 2,7-dichlorofluorescein oxidation. Therefore, members of the cyclophilin gene family, such as cyclophilin D (a component of the mitochondrial permeability transition pore previously linked with oxidative stress and apoptosis), may play a role in the ROS-mediated apoptotic effects of 4-HPR. JF - Molecular Carcinogenesis AU - Hursting, S D AU - Shen, J-C AU - Sun, X-Y AU - Wang, TTY AU - Phang, J M AU - Perkins, S N AD - The Office of Preventive Oncology, National Cancer Institute, 6130 Executive Blvd., MSC 7105, Bethesda, MD 20892, USA Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 16 EP - 24 VL - 33 IS - 1 SN - 0899-1987, 0899-1987 KW - man KW - N-(4-Hydroxyphenyl)retinamide KW - LNCaP cells KW - N-4-(Hydroxyphenyl)retinamide KW - N-acetylcysteine KW - dehydroepiandrosterone KW - fenretinide KW - retinamide KW - Toxicology Abstracts; Genetics Abstracts KW - Gene expression KW - Prednisone KW - Apoptosis KW - Peptidylprolyl isomerase KW - Reactive oxygen species KW - Retinoic acid KW - Free radicals KW - Gene regulation KW - Androgens KW - G 07430:Chromosome studies/nucleotide sequence KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18255368?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aibss&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Public+money+and+management&rft.atitle=Defining+spending+reviews%3A+a+proposal+for+a+taxonomy%2C+with+applications+to+Italy+and+the+UK&rft.au=Agasisti%2C+Tommaso%3BArena%2C+Marika%3BCatalano%2C+Giuseppe%3BErbacci%2C+Angelo&rft.aulast=Agasisti&rft.aufirst=Tommaso&rft.date=2015-11-01&rft.volume=35&rft.issue=6&rft.spage=423&rft.isbn=&rft.btitle=&rft.title=Public+money+and+management&rft.issn=09540962&rft_id=info:doi/10.1080%2F09540962.2015.1083688 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reactive oxygen species; Apoptosis; Peptidylprolyl isomerase; Prednisone; Retinoic acid; Androgens; Gene regulation; Gene expression; Free radicals DO - http://dx.doi.org/10.1002/mc.10020 ER - TY - JOUR T1 - Protease Inhibitor-Induced Stabilization of p21 super(waf1/cip1) and Cell-Cycle Arrest in Chemical Carcinogen-Exposed Mammary and Lung Cells AN - 18254718; 5317297 AB - In previous studies, we have shown that human breast and lung carcinoma cells and mouse nontransformed type II lung cells fail to undergo cell-cycle arrest in G sub(1) phase in response to treatment with hydrocarbon carcinogens but rather accumulate in the S phase with damaged DNA. This situation may lead to replication of DNA on a damaged template and enhance frequency of mutations. The mechanism of this G sub(1) arrest failure was examined. Western immunoblot analyses of MCF7 human mammary cancer cells exposed to actinomycin D (used as a positive control for G sub(1) cell-cycle arrest) or hydrocarbon carcinogens revealed that while all of these chemicals caused an increase in p53, only trace levels of p21 super(waf1/cip1) protein were observed in the hydrocarbon carcinogen-treated samples. Similarly, in murine lung E10 type II cells, p53 but not p21 super(waf1/cip1) protein increased in response to benzo[a]pyrene dihydrodiol epoxide. Treatment of either MCF7 mammary of E10 lung cells with the protease inhibitor calpain I resulted in increased levels of p21 super(waf1/cip1) protein and enhancement of arrest of the cells in early phases of the cell cycle (G sub(1) and early S phase). The results suggest that failure of cell-cycle arrest in carcinogen-treated mammary and lung cells is related to increased protease-mediated degradation of p21 super(waf1/cip1) and/or related regulatory proteins. JF - Molecular Carcinogenesis AU - Khan, Q A AU - Dipple, A AU - Anderson, L M AD - Laboratory of Molecular Pharmacology, National Cancer Institute, Building 37, Bethesda, MD 20892, USA Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 1 EP - 8 VL - 33 IS - 1 SN - 0899-1987, 0899-1987 KW - inhibition KW - MCF7 cells KW - double prime p21 protein KW - actinomycin D KW - cip1 gene KW - p21 protein KW - waf1 gene KW - Toxicology Abstracts; Oncogenes & Growth Factors Abstracts KW - ^Ap21 protein KW - Hydrocarbons KW - Lung KW - Mammary gland KW - Proteinase inhibitors KW - Cell cycle KW - Proteinase KW - Chemical pollution KW - Carcinogens KW - Tumor cells KW - B 26242:Cyclins and cyclin-dependent kinases KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18254718?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Carcinogenesis&rft.atitle=Protease+Inhibitor-Induced+Stabilization+of+p21+super%28waf1%2Fcip1%29+and+Cell-Cycle+Arrest+in+Chemical+Carcinogen-Exposed+Mammary+and+Lung+Cells&rft.au=Khan%2C+Q+A%3BDipple%2C+A%3BAnderson%2C+L+M&rft.aulast=Khan&rft.aufirst=Q&rft.date=2002-01-01&rft.volume=33&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Molecular+Carcinogenesis&rft.issn=08991987&rft_id=info:doi/10.1002%2Fmc.10013 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mammary gland; Lung; Carcinogens; Cell cycle; Proteinase; Hydrocarbons; Chemical pollution; Proteinase inhibitors; Tumor cells DO - http://dx.doi.org/10.1002/mc.10013 ER - TY - JOUR T1 - Bacteriophage Therapy Rescues Mice Bacteremic from a Clinical Isolate of Vancomycin-Resistant Enterococcus faecium AN - 18218878; 5288626 AB - Colonization of the gastrointestinal tract with vancomycin-resistant Enterococcus faecium (VRE) has become endemic in many hospitals and nursing homes in the United States. Such colonization predisposes the individual to VRE bacteremia and/or endocarditis, and immunocompromised patients are at particular risk for these conditions. The emergence of antibiotic-resistant bacterial strains requires the exploration of alternative antibacterial therapies, which led our group to study the ability of bacterial viruses (bacteriophages, or phages) to rescue mice with VRE bacteremia. The phage strain used in this study has lytic activity against a wide range of clinical isolates of VRE. One of these VRE strains was used to induce bacteremia in mice by intraperitoneal (i.p.) injection of 10 CFU. The resulting bacteremia was fatal within 48 h. A single i.p. injection of 3 x 10 PFU of the phage strain, administered 45 min after the bacterial challenge, was sufficient to rescue 100% of the animals. Even when treatment was delayed to the point where all animals were moribund, approximately 50% of them were rescued by a single injection of this phage preparation. The ability of this phage to rescue bacteremic mice was demonstrated to be due to the functional capabilities of the phage and not to a nonspecific immune effect. The rescue of bacteremic mice could be effected only by phage strains able to grow in vitro on the bacterial host used to infect the animals, and when such strains are heat inactivated they lose their ability to rescue the infected mice. JF - Infection and Immunity AU - Biswas, B AU - Adhya, S AU - Washart, P AU - Paul, B AU - Trostel, AN AU - Powell, B AU - Carlton, R AU - Merril, C R AD - NIMH/NIH, 9000 Rockville Pike, Bldg 10, Room 2D54, Bethesda, MD 20892., merrilc@helix.nih.gov Y1 - 2002/01// PY - 2002 DA - Jan 2002 SP - 204 EP - 210 VL - 70 IS - 1 SN - 0019-9567, 0019-9567 KW - Microbiology Abstracts B: Bacteriology KW - Phages KW - Immunocompromised hosts KW - Gastrointestinal tract diseases KW - Bacteremia KW - Vancomycin KW - Predisposing factors KW - Antibiotic resistance KW - Endocarditis KW - Enterococcus faecium KW - J 02846:Gastrointestinal tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18218878?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft.genre=dissertations+%26+theses&rft.jtitle=&rft.atitle=&rft.au=Rumsey%2C+Bruce+David&rft.aulast=Rumsey&rft.aufirst=Bruce&rft.date=2003-01-01&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Self-reported+trauma+symptoms+among+male+and+female+domestic+violence+offenders&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Enterococcus faecium; Antibiotic resistance; Vancomycin; Bacteremia; Gastrointestinal tract diseases; Predisposing factors; Endocarditis; Immunocompromised hosts; Phages DO - http://dx.doi.org/10.1128/IAI.70.1.204-210.2002 ER - TY - JOUR T1 - Single or Group Housing Altered Hormonal Physiology and Affected Pituitary and Interstitial Cell Kinetics AN - 18056577; 5995796 AB - A significant negative correlation between testicular interstitial cell tumors and pituitary tumors in control male F344 rats has been reported associated with the number of animals per cage. Change in numbers of animals per cage may cause stress and increased serum corticosteroids that can impair testosterone synthesis by interstitial cells. Eventual atrophy of interstitial cells may result in pituitary hyperfunction and tumor development. For relevant risk assessments, understanding the effect husbandry has on cellular processes is necessary. Twenty-four 6-week-old male F344 rats were housed individually, as pairs, or as trios for 13 weeks. Measured parameters included feed consumption, body and organ weights, hemograms, hormonal levels, histopathology, and cellular kinetics in the pituitary and testicle. Several caging-related differences occurred, that, although not statistically different, could be biologically significant; these included increased serum levels of estradiol, progesterone, and corticosterone; increased spermatogonial proliferation; decreased apoptosis within seminiferous tubules; and increased BrdU immunoreactivity of the interstitial cells. The statistically significant decrease in lymphocyte numbers correlated with the associated increase in corticosterone levels. This study indicates that the number of animals in a cage is associated with hormonal and cellular kinetic changes in the pituitary and testes, which could influence the incidence of tumors in these organs. JF - Journal of Toxicological Sciences AU - Nyska, Abraham AU - Hester, Susan D AU - Cooper, Ralph L AU - Goldman, Jerome M AU - Stoker, Tammy E AU - House, Dennis AU - Wolf, Douglas C AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences Y1 - 2002///0, PY - 2002 DA - 0, 2002 SP - 449 EP - 457 PB - Japanese Society of Toxicology VL - 27 IS - 5 SN - 0388-1350, 0388-1350 KW - rats KW - Toxicology Abstracts KW - JOI: JST. JSTAGE/jts/27.449 KW - Rat KW - Testicle KW - Pituitary KW - Caging KW - Stress KW - Hormone KW - Testes KW - Apoptosis KW - Progesterone KW - Population density KW - Histopathology KW - Tumors KW - Hormones KW - Estradiol KW - Corticoids KW - Testosterone KW - Body weight KW - Interstitial cells KW - Kinetics KW - Glands KW - Immunoreactivity KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18056577?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Toxicological+Sciences&rft.atitle=Single+or+Group+Housing+Altered+Hormonal+Physiology+and+Affected+Pituitary+and+Interstitial+Cell+Kinetics&rft.au=Nyska%2C+Abraham%3BHester%2C+Susan+D%3BCooper%2C+Ralph+L%3BGoldman%2C+Jerome+M%3BStoker%2C+Tammy+E%3BHouse%2C+Dennis%3BWolf%2C+Douglas+C&rft.aulast=Nyska&rft.aufirst=Abraham&rft.date=2002-01-01&rft.volume=27&rft.issue=5&rft.spage=449&rft.isbn=&rft.btitle=&rft.title=Journal+of+Toxicological+Sciences&rft.issn=03881350&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2016-05-27 N1 - SubjectsTermNotLitGenreText - Testes; Apoptosis; Progesterone; Population density; Histopathology; Tumors; Hormones; Estradiol; Corticoids; Testosterone; Body weight; Interstitial cells; Glands; Kinetics; Immunoreactivity ER - TY - JOUR T1 - The catalytic domains of thiamine triphosphatase and CyaB-like adenylyl cyclase define a novel superfamily of domains that bind organic phosphates AN - 17700416; 6039557 AB - The CyaB protein from Aeromonas hydrophila has been shown to possess adenylyl cyclase activity. While orthologs of this enzyme have been found in some bacteria and archaea, it shows no detectable relationship to the classical nucleotide cyclases. Furthermore, the actual biological functions of these proteins are not clearly understood because they are also present in organisms in which there is no evidence for cyclic nucleotide signaling. We show that the CyaB like adenylyl cyclase and the mammalian thiamine triphosphatases define a novel superfamily of catalytic domains called the CYTH domain that is present in all three superkingdoms of life. Using multiple alignments and secondary structure predictions, we define the catalytic core of these enzymes to contain a novel alpha + beta scaffold with 6 conserved acidic residues and 4 basic residues. Using contextual information obtained from the analysis of gene neighborhoods and domain fusions, we predict that members of this superfamily may play a central role in the interface between nucleotide and polyphosphate metabolism. Additionally, based on contextual information, we identify a novel domain (called CHAD) that is predicted to functionally interact with the CYTH domain-containing enzymes in bacteria and archaea. The CHAD is predicted to be an alpha helical domain, and contains conserved histidines that may be critical for its function. The phyletic distribution of the CYTH domain suggests that it is an ancient enzymatic domain that was present in the Last Universal Common Ancestor and was involved in nucleotide or organic phosphate metabolism. Based on the conservation of catalytic residues, we predict that CYTH domains are likely to chelate two divalent cations, and exhibit a reaction mechanism that is dependent on two metal ions, analogous to nucleotide cyclases, polymerases and certain phosphoesterases. Our analysis also suggests that the experimentally characterized members of this superfamily, namely adenylyl cyclase and thiamine triphosphatase, are secondary derivatives of proteins that performed an ancient role in polyphosphate and nucleotide metabolism. JF - BMC Genomics AU - Iyer, Lakshminarayan M AU - Aravind, L AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA, lakshmin@ncbi.nlm.nih.gov Y1 - 2002 PY - 2002 DA - 2002 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 3 KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02310:Genetics & Taxonomy KW - G 07770:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17700416?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+Genomics&rft.atitle=The+catalytic+domains+of+thiamine+triphosphatase+and+CyaB-like+adenylyl+cyclase+define+a+novel+superfamily+of+domains+that+bind+organic+phosphates&rft.au=Iyer%2C+Lakshminarayan+M%3BAravind%2C+L&rft.aulast=Iyer&rft.aufirst=Lakshminarayan&rft.date=2002-01-01&rft.volume=3&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Genomics&rft.issn=1471-2164&rft_id=info:doi/10.1177%2F0891243211405653 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-12-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1186/1471-2164-3-33 ER - TY - JOUR T1 - Classification and evolutionary history of the single-strand annealing proteins, RecT, Red beta , ERF and RAD52 AN - 17698118; 6039484 AB - The DNA single-strand annealing proteins (SSAPs), such as RecT, Red beta , ERF and Rad52, function in RecA-dependent and RecA-independent DNA recombination pathways. Recently, they have been shown to form similar helical quaternary superstructures. However, despite the functional similarities between these diverse SSAPs, their actual evolutionary affinities are poorly understood. Using sensitive computational sequence analysis, we show that the RecT and Red beta proteins, along with several other bacterial proteins, form a distinct superfamily. The ERF and Rad52 families show no direct evolutionary relationship to these proteins and define novel superfamilies of their own. We identify several previously unknown members of each of these superfamilies and also report, for the first time, bacterial and viral homologs of Rad52. Additionally, we predict the presence of aberrant van den modules in RAD52 that are likely to be involved in DNA-binding. Using the contextual information obtained from the analysis of gene neighborhoods, we provide evidence of the interaction of the bacterial members of each of these SSAP superfamilies with a similar set of DNA repair/recombination protein. These include different nucleases or Holliday junction resolvases, the ABC ATPase SbcC and the single-strand-binding protein. We also present evidence of independent assembly of some of the predicted operons encoding SSAPs and in situ displacement of functionally similar genes. There are three evolutionarily distinct superfamilies of SSAPs, namely the RecT/Red beta , ERF, and RAD52, that have different sequence conservation patterns and predicted folds. All these SSAPs appear to be primarily of bacteriophage origin and have been acquired by numerous phylogenetically distant cellular genomes. They generally occur in predicted operons encoding one or more of a set of conserved DNA recombination proteins that appear to be the principal functional partners of the SSAPs. JF - BMC Genomics AU - Iyer, Lakshminarayan M AU - Koonin, Eugene V AU - Aravind, L AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA, lakshmin@ncbi.nlm.nih.gov Y1 - 2002 PY - 2002 DA - 2002 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 3 KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02310:Genetics & Taxonomy KW - G 07770:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17698118?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+Genomics&rft.atitle=Classification+and+evolutionary+history+of+the+single-strand+annealing+proteins%2C+RecT%2C+Red+beta+%2C+ERF+and+RAD52&rft.au=Iyer%2C+Lakshminarayan+M%3BKoonin%2C+Eugene+V%3BAravind%2C+L&rft.aulast=Iyer&rft.aufirst=Lakshminarayan&rft.date=2002-01-01&rft.volume=3&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Genomics&rft.issn=1471-2164&rft_id=info:doi/10.1186%2F1471-2164-3-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-12-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1186/1471-2164-3-8 ER - TY - JOUR T1 - Uptake of super(40)K and super(137)Cs in native plants of the Marshall Islands AN - 16134933; 5384802 AB - Uptake of super(137)Cs and super(40)K was studied in seven native plant species of the Marshall Islands. Plant and soil samples were obtained across a broad range of soil super(137)Cs concentrations (0.08-3900 Bq/kg) and a narrower range of super(40)K soil concentrations (2.3-55 Bq/kg), but with no systematic variation of super(40)K relative to super(137)Cs. Potassium-40 concentrations in plants varied little within the range of super(40)K soil concentrations observed. Unlike the case for super(40)K, super(137)Cs concentrations increased in plants with increasing super(137)Cs soil concentrations though not precisely in a proportionate manner. The best-fit relationship between soil and plant concentrations was P = aS super(b) where a and b are regression coefficients and P and S are plant and soil concentrations, respectively. The exponent b for super(40)K was zero, implying plant concentrations were a single value, while b for super(137)Cs varied between 0.51 and 0.82, depending on the species. For both super(40)K and super(137)Cs, we observed a decreasing concentration ratio (where concentration ratio = plant concentration/soil concentration) with increasing soil concentrations. For the CR values, the best-fit relationship was of the form CR = aS super(b) / S = aS super(b-1). For the super(40)K CR functions, the exponent b - 1 was close to -1 for all species. For the super(137)Cs CR functions, the exponent b - 1 varied from -0.19 to -0.48. The findings presented here, as well as those by other investigators, collectively argue against the usefulness of simplistic ratio models to accurately predict uptake of either super(40)K or super(137)Cs in plants over wide ranges of soil concentration. JF - Journal of Environmental Radioactivity AU - Simon, S L AU - Graham, J C AU - Terp, S D AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, MSC-7238, Executive Plaza South, National Institutes of Health, Betheseda, MD 20892, USA Y1 - 2002 PY - 2002 DA - 2002 SP - 223 EP - 243 VL - 59 IS - 2 SN - 0265-931X, 0265-931X KW - Pollution Abstracts; ASFA 3: Aquatic Pollution & Environmental Quality KW - Oceanic islands KW - Plantae KW - Cesium KW - Military operations KW - Caesium 137 KW - ISEW, Pacific, Marshall Is. KW - Potassium KW - Marshall Is. KW - Potassium isotopes KW - Soil contamination KW - Explosions KW - Bioaccumulation KW - Soils KW - Plants KW - Radioactive contamination KW - Radioisotopes KW - P 8000:RADIATION KW - Q5 08504:Effects on organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16134933?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Environmental+Radioactivity&rft.atitle=Uptake+of+super%2840%29K+and+super%28137%29Cs+in+native+plants+of+the+Marshall+Islands&rft.au=Simon%2C+S+L%3BGraham%2C+J+C%3BTerp%2C+S+D&rft.aulast=Simon&rft.aufirst=S&rft.date=2002-01-01&rft.volume=59&rft.issue=2&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=Journal+of+Environmental+Radioactivity&rft.issn=0265931X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2003-01-01 N1 - Last updated - 2014-05-07 N1 - SubjectsTermNotLitGenreText - Oceanic islands; Bioaccumulation; Soils; Caesium 137; Military operations; Radioisotopes; Radioactive contamination; Potassium isotopes; Explosions; Cesium; Plants; Potassium; Soil contamination; Plantae; ISEW, Pacific, Marshall Is.; Marshall Is. ER - TY - JOUR T1 - Inhibitor Complexes of the Pseudomonas Serine-Carboxyl Proteinase AN - 18667722; 5569461 AB - Crystal structures of the serine-carboxyl proteinase from Pseudomonas sp. 101 (PSCP), complexed with a number of inhibitors, have been solved and refined at high- to atomic-level resolution. All of these inhibitors (tyrostatin, pseudo-tyrostatin, AcIPF, AcIAF, and chymostatin, as well as previously studied iodotyrostatin and pseudo-iodotyrostatin) make covalent bonds to the active site Ser287 through their aldehyde moieties, while their side chains occupy subsites S1-S4 of the enzyme. The mode of binding of the inhibitors is almost identical for their P1 and P2 side chains, while significant differences are observed for P3 and P4 (if present). Kinetic parameters for the binding of these nanomolar inhibitors to PSCP have been established and correlated with the observed mode of binding. The preferences of this enzyme for a larger side chain in P2 as well as Tyr or Phe in P1 are explained by the size, shape, and characteristics of the S2 and S1 regions of the protein structure, respectively. Networks of hydrogen bonds involving glutamic and aspartic acids have been analyzed for the atomic-resolution structure of the native enzyme. PSCP contains a calcium-binding site that consists of Asp328, Asp348, three amide carbonyl groups, and a water molecule, in almost perfect octahedral coordination. The presence of Ca super(2+) cation is necessary for the activity of the enzyme. JF - Biochemistry (Washington) AU - Wlodawer, A AU - Li, Mi AU - Gustchina, A AU - Dauter, Z AU - Uchida, Kenichi AU - Oyama, Hiroshi AU - Goldfarb, N E AU - Dunn, B M AU - Oda, Kohei AD - Protein Structure Section, Macromolecular Crystallography Laboratory, and Intramural Research Support Program, SAIC Frederick, National Cancer Institute at Frederick, Frederick, MD 21702, USA Y1 - 2001/12/25/ PY - 2001 DA - 2001 Dec 25 SP - 15602 EP - 15611 VL - 40 IS - 51 SN - 0006-2960, 0006-2960 KW - kinetics KW - Microbiology Abstracts B: Bacteriology KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18667722?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Inhibitor+Complexes+of+the+Pseudomonas+Serine-Carboxyl+Proteinase&rft.au=Wlodawer%2C+A%3BLi%2C+Mi%3BGustchina%2C+A%3BDauter%2C+Z%3BUchida%2C+Kenichi%3BOyama%2C+Hiroshi%3BGoldfarb%2C+N+E%3BDunn%2C+B+M%3BOda%2C+Kohei&rft.aulast=Wlodawer&rft.aufirst=A&rft.date=2001-12-25&rft.volume=40&rft.issue=51&rft.spage=15602&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/10.1021%2Fbi011817n LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1021/bi011817n ER - TY - JOUR T1 - Initial ethanol exposure results in decreased heart rate variability in ethanol-naive rhesus monkeys. AN - 72378790; 11755149 AB - Ethanol's effects on heart rate variability may contribute to the increased cardiac disease and mortality observed in alcoholics. We assessed cardiac response to ethanol in seven previously ethanol-naive monkeys given a standard dose of ethanol, or saline. Ethanol exposure reduced cardiac signal complexity [mean+/-S.D. (ethanol: Hurst parameter=0.39+/-0.02; saline: Hurst parameter=0.32+/-0.06)] and increased the spectral exponent (ethanol: beta=1.36+/-0.35; saline: beta=1.12+/-0.35) when compared to saline, while heart rate itself was unaffected (saline: interbeat interval=303.57+/-24.57; ethanol: interbeat interval=308.14+/-20.45). Taken together with data that show autonomic disregulation in alcoholics, these findings provide further evidence of deleterious ethanol effects on cardiac signal dynamics. JF - European journal of pharmacology AU - Bennett, A J AU - Sponberg, A C AU - Graham, T AU - Suomi, S J AU - Higley, J D AU - DePetrillo, P B AD - Laboratory of Clinical Studies, Primate Unit, Division of Intramural Clinical and Biochemical Research, National Institute on Alcohol Abuse and Alcoholism, PO Box 529, Fisher Avenue, Poolesville, MD 20837, USA. ABENNETT@WFUBMC.EDU Y1 - 2001/12/21/ PY - 2001 DA - 2001 Dec 21 SP - 169 EP - 172 VL - 433 IS - 2-3 SN - 0014-2999, 0014-2999 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Animals KW - Autonomic Nervous System -- drug effects KW - Peripheral Nervous System -- drug effects KW - Macaca mulatta KW - Male KW - Female KW - Ethanol -- blood KW - Heart Rate -- drug effects KW - Ethanol -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72378790?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+pharmacology&rft.atitle=Initial+ethanol+exposure+results+in+decreased+heart+rate+variability+in+ethanol-naive+rhesus+monkeys.&rft.au=Bennett%2C+A+J%3BSponberg%2C+A+C%3BGraham%2C+T%3BSuomi%2C+S+J%3BHigley%2C+J+D%3BDePetrillo%2C+P+B&rft.aulast=Bennett&rft.aufirst=A&rft.date=2001-12-21&rft.volume=433&rft.issue=2-3&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-07 N1 - Date created - 2001-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Meeting report: signaling schemes for TGF-beta. AN - 72377627; 11752631 AB - The transforming growth factor-beta (TGF-beta) superfamily of signaling molecules regulates many developmental processes in a range of organisms from worms to humans. Understanding the mechanisms by which they exert their repertoire of effects has required identification of the components of signaling pathways that they control. Roberts and Derynck focus on this aspect of TGF-beta biology in their review of a recent Federation of American Societies for Experimental Biology (FASEB) meeting on TGF-beta signaling and development and summarize current signaling paradigms and future prospects in TGF-beta signaling from the cell surface to the nucleus. JF - Science's STKE : signal transduction knowledge environment AU - Roberts, A B AU - Derynck, R Y1 - 2001/12/18/ PY - 2001 DA - 2001 Dec 18 SP - 1 VL - 2001 IS - 113 KW - DNA-Binding Proteins KW - 0 KW - Ligands KW - Trans-Activators KW - Transforming Growth Factor beta KW - Index Medicus KW - Xenopus laevis KW - Animals KW - Humans KW - Drosophila melanogaster KW - Transcriptional Activation -- physiology KW - Mice KW - DNA-Binding Proteins -- physiology KW - Trans-Activators -- physiology KW - Signal Transduction -- physiology KW - Transforming Growth Factor beta -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72377627?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Science%27s+STKE+%3A+signal+transduction+knowledge+environment&rft.atitle=Meeting+report%3A+signaling+schemes+for+TGF-beta.&rft.au=Roberts%2C+A+B%3BDerynck%2C+R&rft.aulast=Roberts&rft.aufirst=A&rft.date=2001-12-18&rft.volume=2001&rft.issue=113&rft.spage=243&rft.isbn=&rft.btitle=&rft.title=Public+money+and+management&rft.issn=09540962&rft_id=info:doi/10.1080%2F09540962.2010.492188 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-11 N1 - Date created - 2001-12-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Short-cycle structured intermittent treatment of chronic HIV infection with highly active antiretroviral therapy: effects on virologic, immunologic, and toxicity parameters. AN - 72377090; 11734634 AB - Although continuous highly active antiretroviral therapy (HAART) is effective for many HIV-infected patients, it can be toxic and prohibitive in cost. By decreasing the total amount of time patients receive medications, intermittent HAART could reduce toxicity and cost. Therefore, we initiated a pilot study in which 10 HIV-infected individuals receiving effective therapy that resulted in levels of HIV RNA 300 cells per mm(3) of whole blood received repeated cycles of 7 days on HAART followed by 7 days off of HAART. Patients maintained suppression of plasma viremia for 32-68 weeks. There was no significant increase in HIV proviral DNA or replication-competent HIV in peripheral CD4(+) T cells or HIV RNA in peripheral blood or lymph node mononuclear cells. There was no significant change in CD4(+) T cell counts, no significant increase in CD4(+) or CD8(+) T cells expressing activation markers or producing IFN-gamma in response to HIV, no increase in CD4(+) T cell proliferation to p24 antigen, and no evidence for the development of resistance to HAART medications. There was a significant decrease in serum cholesterol and triglyceride levels. Thus, in this proof-of-concept study, short-cycle intermittent HAART maintained suppression of plasma viremia as well as HIV replication in reservoir sites while preserving CD4(+) T cell counts. In addition, there was a decrease in serum cholesterol and triglyceride levels. Intermittent therapy may be an important strategy to reduce cost and toxicity for HIV-infected individuals. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Dybul, M AU - Chun, T W AU - Yoder, C AU - Hidalgo, B AU - Belson, M AU - Hertogs, K AU - Larder, B AU - Dewar, R L AU - Fox, C H AU - Hallahan, C W AU - Justement, J S AU - Migueles, S A AU - Metcalf, J A AU - Davey, R T AU - Daucher, M AU - Pandya, P AU - Baseler, M AU - Ward, D J AU - Fauci, A S AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. mdybul@nih.gov Y1 - 2001/12/18/ PY - 2001 DA - 2001 Dec 18 SP - 15161 EP - 15166 VL - 98 IS - 26 SN - 0027-8424, 0027-8424 KW - Anti-HIV Agents KW - 0 KW - RNA, Viral KW - Index Medicus KW - Drug Administration Schedule KW - HIV-1 -- isolation & purification KW - Humans KW - Anti-HIV Agents -- adverse effects KW - Lymph Nodes -- pathology KW - Pilot Projects KW - CD4 Lymphocyte Count KW - Genotype KW - Phenotype KW - Anti-HIV Agents -- therapeutic use KW - Anti-HIV Agents -- pharmacology KW - HIV-1 -- drug effects KW - Microbial Sensitivity Tests KW - Antiretroviral Therapy, Highly Active -- adverse effects KW - HIV Infections -- virology KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72377090?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Short-cycle+structured+intermittent+treatment+of+chronic+HIV+infection+with+highly+active+antiretroviral+therapy%3A+effects+on+virologic%2C+immunologic%2C+and+toxicity+parameters.&rft.au=Dybul%2C+M%3BChun%2C+T+W%3BYoder%2C+C%3BHidalgo%2C+B%3BBelson%2C+M%3BHertogs%2C+K%3BLarder%2C+B%3BDewar%2C+R+L%3BFox%2C+C+H%3BHallahan%2C+C+W%3BJustement%2C+J+S%3BMigueles%2C+S+A%3BMetcalf%2C+J+A%3BDavey%2C+R+T%3BDaucher%2C+M%3BPandya%2C+P%3BBaseler%2C+M%3BWard%2C+D+J%3BFauci%2C+A+S&rft.aulast=Dybul&rft.aufirst=M&rft.date=2001-12-18&rft.volume=98&rft.issue=26&rft.spage=15161&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-22 N1 - Date created - 2001-12-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15109-14 [10611346] Circulation. 1999 Aug 17;100(7):700-5 [10449690] J Infect Dis. 2000 Apr;181(4):1273-9 [10836864] J Immunol. 2000 Jul 15;165(2):1082-92 [10878387] J Immunol. 2000 Aug 1;165(3):1685-91 [10903780] Int J STD AIDS. 2000 Sep;11(9):611-6 [10997508] Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10948-53 [11005867] Nature. 2000 Sep 28;407(6803):523-6 [11029005] Clin Infect Dis. 2000 Dec;31(6):1482-7 [11096016] AIDS. 2001 Jan 26;15(2):231-9 [11216932] J Infect Dis. 2001 May 1;183(9):1318-27 [11294662] Science. 2001 Apr 13;292(5515):221-3 [11305311] JAMA. 2001 Jul 11;286(2):171-9 [11448280] Nature. 1993 Oct 14;365(6447):671-3 [8413632] Am J Gastroenterol. 1995 Sep;90(9):1433-6 [7661164] Nature. 1997 May 8;387(6629):183-8 [9144289] Ann Intern Med. 1997 Jul 15;127(2):119-25 [9230000] Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13193-7 [9371822] J Infect Dis. 1998 Jan;177(1):235-8 [9419197] Antimicrob Agents Chemother. 1998 Feb;42(2):269-76 [9527771] Lancet. 1998 Mar 21;351(9106):871-5 [9525365] Lancet. 1999 Jan 9;353(9147):119-20 [10023903] J Acquir Immune Defic Syndr Hum Retrovirol. 1999 Mar 1;20(3):228-37 [10077170] JAMA. 1999 Mar 24-31;281(12):1069 [10188643] Nat Med. 1999 May;5(5):518-25 [10229228] N Engl J Med. 1999 May 27;340(21):1605-13 [10341272] N Engl J Med. 1999 May 27;340(21):1614-22 [10341273] Nat Med. 1999 Jun;5(6):651-5 [10371503] Lancet. 1999 Jun 19;353(9170):2093-9 [10382692] AIDS. 1999 Apr 16;13(6):F35-43 [10397555] AIDS. 1999 Apr 16;13(6):677-83 [10397562] Ann Intern Med. 1999 Jul 20;131(2):81-7 [10419445] AIDS. 1999 Jul 9;13(10):F63-70 [10416516] AIDS. 1999 Jul 30;13(11):F79-86 [10449278] J Acquir Immune Defic Syndr. 2000 Jan 1;23(1):35-43 [10708054] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Histone deacetylase inhibitors reduce polyglutamine toxicity. AN - 72373264; 11742087 AB - Polyglutamine diseases include at least nine neurodegenerative disorders, each caused by a CAG repeat expansion in a different gene. Accumulation of mutant polyglutamine-containing proteins occurs in patients, and evidence from cell culture and animal experiments suggests the nucleus as a site of pathogenesis. To understand the consequences of nuclear accumulation, we created a cell culture system with nuclear-targeted polyglutamine. In our system, cell death can be mitigated by overexpression of full-length cAMP response element binding protein (CREB)-binding protein (CBP) or its amino-terminal portion alone. CBP is one of several histone acetyltransferases sequestered by polyglutamine inclusions. We found histone acetylation to be reduced in cells expressing mutant polyglutamine. Reversal of this hypoacetylation, which can be achieved either by overexpression of CBP or its amino terminus or by treatment with deacetylase inhibitors, reduced cell loss. These findings suggest that nuclear accumulation of polyglutamine can lead to altered protein acetylation in neurons and indicate a novel therapeutic strategy for polyglutamine disease. JF - Proceedings of the National Academy of Sciences of the United States of America AU - McCampbell, A AU - Taye, A A AU - Whitty, L AU - Penney, E AU - Steffan, J S AU - Fischbeck, K H AD - Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 3B14, 10 Center Drive, Bethesda, MD 20892, USA. Y1 - 2001/12/18/ PY - 2001 DA - 2001 Dec 18 SP - 15179 EP - 15184 VL - 98 IS - 26 SN - 0027-8424, 0027-8424 KW - Enzyme Inhibitors KW - 0 KW - Histone Deacetylase Inhibitors KW - Nuclear Proteins KW - Peptides KW - Receptors, Androgen KW - Trans-Activators KW - polyglutamine KW - 26700-71-0 KW - CREB-Binding Protein KW - EC 2.3.1.48 KW - Crebbp protein, mouse KW - Index Medicus KW - Animals KW - Nuclear Proteins -- genetics KW - Transfection KW - Trans-Activators -- genetics KW - Receptors, Androgen -- genetics KW - Mice KW - Cell Death -- drug effects KW - Motor Neurons -- drug effects KW - Cell Line KW - Enzyme Inhibitors -- pharmacology KW - Peptides -- toxicity KW - Peptides -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72373264?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Histone+deacetylase+inhibitors+reduce+polyglutamine+toxicity.&rft.au=McCampbell%2C+A%3BTaye%2C+A+A%3BWhitty%2C+L%3BPenney%2C+E%3BSteffan%2C+J+S%3BFischbeck%2C+K+H&rft.aulast=McCampbell&rft.aufirst=A&rft.date=2001-12-18&rft.volume=98&rft.issue=26&rft.spage=15179&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-22 N1 - Date created - 2001-12-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1998 Nov 27;273(48):31853-9 [9822653] J Cell Biol. 1998 Dec 14;143(6):1457-70 [9852144] J Neurochem. 1999 Jan;72(1):185-95 [9886069] Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1585-90 [9990068] Neuron. 1999 Mar;22(3):623-33 [10197541] Hum Mol Genet. 1999 May;8(5):731-41 [10196362] EMBO J. 1999 Apr 1;18(7):1900-4 [10202153] Neuron. 1999 Apr;22(4):799-808 [10230799] Hum Mol Genet. 1999 Sep;8(9):1647-55 [10441327] Hum Mol Genet. 1999 Sep;8(9):1657-64 [10441328] Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11404-9 [10500189] Hum Mol Genet. 2000 Jan 1;9(1):69-78 [10587580] Anticancer Res. 1999 Nov-Dec;19(6B):4999-5005 [10697502] Cell. 2000 Mar 31;101(1):57-66 [10778856] Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6763-8 [10823891] J Biol Chem. 2000 Jul 7;275(27):20853-60 [10779504] Hum Mol Genet. 2000 Sep 1;9(14):2197-202 [10958659] Cancer Res. 2000 Aug 15;60(16):4561-72 [10969808] Nat Genet. 2000 Sep;26(1):29-36 [10973244] Nature. 2000 Nov 2;408(6808):101-6 [11081516] Expert Opin Investig Drugs. 2000 Dec;9(12):2923-34 [11093362] Mol Cell Biol. 2001 Jan;21(2):476-87 [11134336] Ann Neurol. 2001 Jan;49(1):14-23 [11198291] Hum Mol Genet. 2001 Jan 15;10(2):107-16 [11152658] Science. 2001 Mar 23;291(5512):2423-8 [11264541] Hum Mol Genet. 2001 Jul 1;10(14):1441-8 [11448935] Nature. 2001 Oct 18;413(6857):739-43 [11607033] Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13201-6 [11687606] Brain Res. 1983 Sep 19;275(1):75-82 [6626979] Nature. 1991 Jul 4;352(6330):77-9 [2062380] Neuroreport. 1991 Sep;2(9):505-8 [1751804] Cell. 1993 Mar 26;72(6):971-83 [8458085] Nat Genet. 1993 Jul;4(3):221-6 [8358429] Science. 1994 Feb 11;263(5148):808-11 [8303297] Nat Genet. 1994 Jan;6(1):14-8 [8136826] Nat Genet. 1994 Nov;8(3):221-8 [7874163] Nat Genet. 1996 Nov;14(3):269-76 [8896555] Genome Res. 1996 Oct;6(10):965-71 [8908515] Nat Genet. 1997 Jan;15(1):62-9 [8988170] Cell. 1997 Jun 27;89(7):1175-84 [9215639] Cell. 1997 Aug 8;90(3):537-48 [9267033] Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10215-20 [9294190] Nature. 1997 Oct 30;389(6654):971-4 [9353120] Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2122-7 [9482849] Hum Mol Genet. 1998 Apr;7(4):693-701 [9499423] Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3003-7 [9501205] J Biol Chem. 1998 Apr 10;273(15):9158-67 [9535906] Cell. 1998 Jun 12;93(6):939-49 [9635424] Curr Opin Cell Biol. 1998 Jun;10(3):373-83 [9640539] Biochem Biophys Res Commun. 1998 Aug 10;249(1):96-102 [9705838] Cell. 1998 Oct 2;95(1):41-53 [9778246] Biochem Biophys Res Commun. 1998 Nov 9;252(1):145-50 [9813160] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Constitutive nuclear factor kappaB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells. AN - 72360743; 11748286 AB - Gene expression profiling has revealed that diffuse large B cell lymphoma (DLBCL) consists of at least two distinct diseases. Patients with one DLBCL subtype, termed activated B cell-like (ABC) DLBCL, have a distinctly inferior prognosis. An untapped potential of gene expression profiling is its ability to identify pathogenic signaling pathways in cancer that are amenable to therapeutic attack. The gene expression profiles of ABC DLBCLs were notable for the high expression of target genes of the nuclear factor (NF)-kappaB transcription factors, raising the possibility that constitutive activity of the NF-kappaB pathway may contribute to the poor prognosis of these patients. Two cell line models of ABC DLBCL had high nuclear NF-kappaB DNA binding activity, constitutive IkappaB kinase (IKK) activity, and rapid IkappaB(alpha) degradation that was not seen in cell lines representing the other DLBCL subtype, germinal center B-like (GCB) DLBCL. Retroviral transduction of a super-repressor form of IkappaBalpha or dominant negative forms of IKKbeta was toxic to ABC DLBCL cells but not GCB DLBCL cells. DNA content analysis showed that NF-kappaB inhibition caused both cell death and G1-phase growth arrest. These findings establish the NF-kappaB pathway as a new molecular target for drug development in the most clinically intractable subtype of DLBCL and demonstrate that the two DLBCL subtypes defined by gene expression profiling utilize distinct pathogenetic mechanisms. JF - The Journal of experimental medicine AU - Davis, R E AU - Brown, K D AU - Siebenlist, U AU - Staudt, L M AD - Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1374, USA. Y1 - 2001/12/17/ PY - 2001 DA - 2001 Dec 17 SP - 1861 EP - 1874 VL - 194 IS - 12 SN - 0022-1007, 0022-1007 KW - NF-kappa B KW - 0 KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Gene Expression Profiling KW - Tumor Cells, Cultured KW - Cell Survival -- genetics KW - Humans KW - Prognosis KW - Signal Transduction KW - Lymphoma, Large B-Cell, Diffuse -- pathology KW - Lymphoma, B-Cell -- pathology KW - Lymphoma, B-Cell -- genetics KW - Lymphoma, B-Cell -- classification KW - Lymphoma, Large B-Cell, Diffuse -- genetics KW - NF-kappa B -- genetics KW - Lymphoma, Large B-Cell, Diffuse -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72360743?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+experimental+medicine&rft.atitle=Constitutive+nuclear+factor+kappaB+activity+is+required+for+survival+of+activated+B+cell-like+diffuse+large+B+cell+lymphoma+cells.&rft.au=Davis%2C+R+E%3BBrown%2C+K+D%3BSiebenlist%2C+U%3BStaudt%2C+L+M&rft.aulast=Davis&rft.aufirst=R&rft.date=2001-12-17&rft.volume=194&rft.issue=12&rft.spage=1861&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-14 N1 - Date created - 2001-12-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Blood. 1996 Feb 15;87(4):1571-8 [8608249] Blood. 1996 May 15;87(10):4340-7 [8639794] Annu Rev Immunol. 1996;14:649-83 [8717528] J Biol Chem. 1996 Nov 1;271(44):27201-4 [8910286] Science. 1997 Jan 24;275(5299):540-3 [8999800] J Biol Chem. 1997 Jan 31;272(5):2668-74 [9006902] J Exp Med. 1997 Mar 3;185(5):953-61 [9120401] Cold Spring Harb Symp Quant Biol. 1999;64:71-8 [11232339] J Biol Chem. 2001 Jan 19;276(3):1715-9 [11042193] Blood. 2001 May 1;97(9):2798-807 [11313274] J Biol Chem. 2001 May 25;276(21):18579-90 [11279141] J Biol Chem. 2001 Jun 8;276(23):20055-63 [11274146] Mol Cell Biol. 2001 Aug;21(16):5299-305 [11463813] Oncogene. 2001 Oct 25;20(48):7098-103 [11704834] EMBO J. 1999 Nov 15;18(22):6307-18 [10562543] Oncogene. 1999 Nov 22;18(49):6925-37 [10602467] Oncogene. 1999 Nov 22;18(49):6938-47 [10602468] J Exp Med. 2000 Jan 17;191(2):207-12 [10637266] J Biol Chem. 2000 Feb 4;275(5):3479-84 [10652342] Nature. 2000 Feb 3;403(6769):503-11 [10676951] Blood. 2000 Mar 15;95(6):2084-92 [10706878] Oncogene. 2000 Mar 2;19(10):1334-45 [10713675] Mol Cell Biol. 2000 Apr;20(8):2687-95 [10733571] J Exp Med. 2000 Apr 17;191(8):1281-92 [10770796] J Exp Med. 2000 May 15;191(10):1735-44 [10811866] J Exp Med. 2000 May 15;191(10):1745-54 [10811867] Proc Natl Acad Sci U S A. 2000 May 23;97(11):6055-60 [10811897] Annu Rev Immunol. 2000;18:621-63 [10837071] J Virol. 2000 Jul;74(14):6652-8 [10864681] Mol Cell Biol. 2000 Aug;20(15):5381-91 [10891479] Oncogene. 1991 Jul;6(7):1235-41 [1650444] Oncogene. 1997 Apr 17;14(15):1805-10 [9150386] J Biol Chem. 1997 Sep 26;272(39):24113-6 [9305854] Cell. 1997 Sep 19;90(6):1073-83 [9323135] Cell. 1997 Oct 17;91(2):243-52 [9346241] Science. 1997 Oct 31;278(5339):860-6 [9346484] J Clin Invest. 1997 Dec 15;100(12):2961-9 [9399941] J Exp Med. 1998 Mar 2;187(5):663-74 [9480976] Genes Dev. 1998 Apr 1;12(7):968-81 [9531535] Annu Rev Immunol. 1998;16:225-60 [9597130] Science. 1998 Sep 11;281(5383):1680-3 [9733516] Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8 [9843981] Bioorg Med Chem Lett. 1998 Feb 17;8(4):333-8 [9871680] Oncogene. 1999 Jan 28;18(4):943-53 [10023670] Genes Dev. 1999 Feb 15;13(4):382-7 [10049353] Genes Dev. 1999 Feb 15;13(4):400-11 [10049356] Science. 1999 Apr 9;284(5412):309-13 [10195894] Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9136-41 [10430908] Mol Cell Biol. 1999 Sep;19(9):5923-9 [10454539] Nature. 1999 Sep 2;401(6748):86-90 [10485711] Immunity. 2000 Aug;13(2):199-212 [10981963] Oncogene. 2000 Oct 5;19(42):4936-40 [11039911] Immunol Rev. 2000 Aug;176:134-40 [11043773] J Immunol. 2000 Nov 15;165(10):5462-71 [11067898] EMBO J. 2000 Dec 1;19(23):6351-60 [11101508] Anticancer Drug Des. 2000 Aug;15(4):239-44 [11200499] J Clin Invest. 2001 Feb;107(3):241-6 [11160144] Cell. 1991 Dec 20;67(6):1075-87 [1760839] Mol Cell Biol. 1992 Feb;12(2):685-95 [1531086] Cell. 1992 Apr 3;69(1):119-28 [1555236] Genes Dev. 1993 Jul;7(7A):1266-76 [8319912] Oncogene. 1993 Oct;8(10):2839-45 [8378093] Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):28-32 [8278379] Proc Natl Acad Sci U S A. 1994 May 24;91(11):5056-60 [8197184] Science. 1995 Mar 10;267(5203):1485-8 [7878466] Annu Rev Cell Biol. 1994;10:405-55 [7888182] Genes Dev. 1995 Aug 15;9(16):1965-77 [7649478] Mol Cell Biol. 1995 Sep;15(9):5180-7 [7651435] Blood. 1995 Oct 15;86(8):3160-72 [7579411] Blood. 1996 Jan 1;87(1):25-9 [8547649] EMBO J. 1996 Feb 15;15(4):873-87 [8631308] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Origin pairing ('handcuffing) as a mode of negative control of P1 plasmid copy number AN - 18204904; 5280453 AB - In one family of bacterial plasmids, multiple initiator binding sites, called iterons, are used for initiation of plasmid replication as well as for the control of plasmid copy number. Iterons can also pair in vitro via the bound initiators. This pairing, called handcuffing, has been suggested to cause steric hindrance to initiation and thereby control the copy number. To test this hypothesis, we have compared copy numbers of isogenic miniP1 plasmid monomer and dimer. The dimer copy number was only one-quarter that of the monomer, suggesting that the higher local concentration of origins in the dimer facilitated their pairing. Physical evidence consistent with iteron-mediated pairing of origins preferentially in the dimer was obtained in vivo. Thus, origin handcuffing can be a mechanism to control P1 plasmid replication. JF - EMBO Journal AU - Park, K AU - Han, E AU - Paulsson, J AU - Chattoraj, D K AD - Laboratory of Biochemistry, NCI, NIH, Bethesda, MD 20892-4255, USA, chattoraj@nih.gov Y1 - 2001/12/17/ PY - 2001 DA - 2001 Dec 17 SP - 7323 EP - 7332 VL - 20 IS - 24 SN - 0261-4189, 0261-4189 KW - bacteria KW - handcuffing KW - iterons KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Copy number control KW - Replication KW - Origin KW - Plasmids KW - J 02760:Plasmids KW - N 14650:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18204904?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=EMBO+Journal&rft.atitle=Origin+pairing+%28%27handcuffing%29+as+a+mode+of+negative+control+of+P1+plasmid+copy+number&rft.au=Park%2C+K%3BHan%2C+E%3BPaulsson%2C+J%3BChattoraj%2C+D+K&rft.aulast=Park&rft.aufirst=K&rft.date=2001-12-17&rft.volume=20&rft.issue=24&rft.spage=7323&rft.isbn=&rft.btitle=&rft.title=EMBO+Journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Replication; Origin; Plasmids; Copy number control ER - TY - JOUR T1 - Systemic cancer therapy with a tumor-selective vaccinia virus mutant lacking thymidine kinase and vaccinia growth factor genes. AN - 72369151; 11751395 AB - We have demonstrated previously the oncolytic effects of a systemically delivered, replicating vaccinia virus. To enhance the tumor specificity of this vector, we have developed a combined thymidine kinase-deleted (TK-) and vaccinia growth factor-deleted (VGF-) vaccinia virus and investigated its properties in vitro and in vivo. The gene for enhanced green fluorescent protein (EGFP) was inserted into the TK locus of a VGF- vaccinia virus by homologous recombination creating a double-deleted mutant vaccinia virus (vvDD-GFP). Infection of resting and dividing NIH3T3 cells with vvDD-GFP yielded reduced viral recovery compared with wild-type (WT), TK-, or VGF- viruses from resting cultures but equivalent virus recovery from dividing cultures. Eight days after nude mice were injected i.p. with 10(7) plaque-forming units (pfu) of WT, TK-, VGF-, or vvDD-GFP vaccinia virus, tissues and tumor were harvested for viral titer determination. No virus was recovered from the brains of mice injected with vvDD-GFP compared with the other viruses, which ranged from 130 to 28,000 pfu/mg protein; however, equivalent amounts were recovered from tumor. There was no toxicity from vvDD-GFP because nude mice receiving 10(8) pfu of IP vvDD-GFP lived >100 days, whereas mice receiving WT, VGF-, or TK- virus had median survivals of only 6, 17, and 29 days, respectively. Similar results were seen when 10(9) pfu of vvDD-GFP were given. Nude mice bearing s.c. murine colon adenocarcinoma (MC38) had significant tumor regression after treatment with 10(9) pfu of systemic (i.p.) vvDD-GFP compared with control (mean tumor size, 180.71 +/- 35.26 mm(3) versus 2796.79 +/- 573.20 mm(3) 12 days after injection of virus). Our data demonstrate that a TK- and VGF- mutant vaccinia virus is significantly attenuated in resting cells in vitro and demonstrates tumor-specific replication in vivo. It is a promising vector for use in tumor-directed gene therapy, given its enhanced safety profile, tumor selectivity, and the oncolytic effects after systemic delivery. JF - Cancer research AU - McCart, J A AU - Ward, J M AU - Lee, J AU - Hu, Y AU - Alexander, H R AU - Libutti, S K AU - Moss, B AU - Bartlett, D L AD - Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892-1502, USA. Y1 - 2001/12/15/ PY - 2001 DA - 2001 Dec 15 SP - 8751 EP - 8757 VL - 61 IS - 24 SN - 0008-5472, 0008-5472 KW - Luminescent Proteins KW - 0 KW - Peptides KW - vaccinia growth factor KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Thymidine Kinase KW - EC 2.7.1.21 KW - Index Medicus KW - Virus Replication KW - 3T3 Cells KW - Animals KW - HeLa Cells KW - Humans KW - Mice, Nude KW - Mice KW - Haplorhini KW - Tumor Cells, Cultured KW - Mice, Inbred C57BL KW - Cytopathogenic Effect, Viral KW - Genetic Vectors -- genetics KW - Poxviridae Infections -- virology KW - Luminescent Proteins -- biosynthesis KW - Luminescent Proteins -- genetics KW - Female KW - Vaccinia virus -- genetics KW - Vaccinia virus -- enzymology KW - Vaccinia virus -- physiology KW - Vaccinia virus -- pathogenicity KW - Genetic Therapy -- methods KW - Peptides -- genetics KW - Thymidine Kinase -- genetics KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72369151?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Systemic+cancer+therapy+with+a+tumor-selective+vaccinia+virus+mutant+lacking+thymidine+kinase+and+vaccinia+growth+factor+genes.&rft.au=McCart%2C+J+A%3BWard%2C+J+M%3BLee%2C+J%3BHu%2C+Y%3BAlexander%2C+H+R%3BLibutti%2C+S+K%3BMoss%2C+B%3BBartlett%2C+D+L&rft.aulast=McCart&rft.aufirst=J&rft.date=2001-12-15&rft.volume=61&rft.issue=24&rft.spage=8751&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-10 N1 - Date created - 2001-12-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Free radicals, chemokines, and cell injury in HIV-1 and SIV infections and alcoholic hepatitis. AN - 72356617; 11744325 AB - Oxidative stress has been observed in HIV-1 infection and alcoholic liver disease. The formation of reactive oxygen species (ROS) contributes to cell injury through apoptosis and/or necrosis and secretion of proinflammatory cytokines and chemokines. The major sources of ROS and chemokines are the Kupffer cells. During chronic ethanol consumption they are primed and activated for enhanced formation of pro-inflammatory factors, probably as a result of ethanol-induced translocation of gut-derived endotoxin into the circulation. Pro-inflammatory factors produced in the liver stimulate neutrophilic and/or lymphocytic infiltration to this organ. The presence of inflammatory cells in the liver may compromise the hepatocytes to injury by releasing cytotoxic factors, i.e., ROS, cytolytic proteases. Kupffer cells also interact with the glycoprotein 120 of SIV and HIV-1, which can induce oxidative stress and chemokine release. CD4+ lymphocytes that are infected with the virus generate intracellular ROS, which in turn leads to apoptosis and cell death. Downregulation of CD4+ cells contributes to immunodeficiency, while enhanced sequestration of inflammatory cells in the liver during chronic ethanol use with or without HIV-1/SIV may result in hepatocyte injury and exacerbation of alcoholic liver disease. JF - Free radical biology & medicine AU - Bautista, A P AD - Department of Physiology and NIAAA-Sponsored Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. abauti@lsuhsc.edu Y1 - 2001/12/15/ PY - 2001 DA - 2001 Dec 15 SP - 1527 EP - 1532 VL - 31 IS - 12 SN - 0891-5849, 0891-5849 KW - Alcohols KW - 0 KW - Chemokines KW - Free Radicals KW - Index Medicus KW - Animals KW - Necrosis KW - Humans KW - Apoptosis -- physiology KW - Kupffer Cells -- metabolism KW - Kupffer Cells -- drug effects KW - Macaca mulatta KW - Alcohols -- toxicity KW - Simian Acquired Immunodeficiency Syndrome -- metabolism KW - HIV Infections -- metabolism KW - Hepatitis, Alcoholic -- pathology KW - Hepatitis, Alcoholic -- metabolism KW - HIV Infections -- pathology KW - Chemokines -- secretion KW - Free Radicals -- metabolism KW - Simian Acquired Immunodeficiency Syndrome -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72356617?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Free+radicals%2C+chemokines%2C+and+cell+injury+in+HIV-1+and+SIV+infections+and+alcoholic+hepatitis.&rft.au=Bautista%2C+A+P&rft.aulast=Bautista&rft.aufirst=A&rft.date=2001-12-15&rft.volume=31&rft.issue=12&rft.spage=1527&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-22 N1 - Date created - 2001-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potentiation of simian immunodeficiency virus (SIV)-specific CD4(+) and CD8(+) T cell responses by a DNA-SIV and NYVAC-SIV prime/boost regimen. AN - 72344379; 11739541 AB - T cell-mediated immune responses play an important role in the containment of HIV-1 replication. Therefore, an effective vaccine against HIV-1 should be able to elicit high frequencies of virus-specific CD8(+) and CD4(+) T cells. The highly attenuated poxvirus-based vaccine candidate, NYVAC-SIV-gag-pol-env (NYVAC-SIV-gpe), has been shown to induce and/or expand SIV-specific CD4(+) and CD8(+) T cell responses in both naive and infected macaques. In this study, the immunogenicity of NYVAC-SIV-gpe alone was compared with a combination regimen where priming with an optimized DNA-SIV-gag-env vaccine candidate was followed by a NYVAC-SIV-gpe boost. In macaques immunized with the prime-boost regimen, the extent and durability of CD8(+) T cell response to an immunodominant SIV gag epitope was increased and these animals recognized a broader array of subdominant SIV epitopes in the cytolytic assay. In addition, the prime-boost regimen significantly enhanced the proliferative responses to both SIV gag and env proteins. Thus, the combination of these vaccine modalities may represent a valuable strategy in the development of a vaccine for HIV. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Hel, Z AU - Tsai, W P AU - Thornton, A AU - Nacsa, J AU - Giuliani, L AU - Tryniszewska, E AU - Poudyal, M AU - Venzon, D AU - Wang, X AU - Altman, J AU - Watkins, D I AU - Lu, W AU - von Gegerfelt, A AU - Felber, B K AU - Tartaglia, J AU - Pavlakis, G N AU - Franchini, G AD - Basic Research Laboratory and Biostatistics and Data Management Section, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2001/12/15/ PY - 2001 DA - 2001 Dec 15 SP - 7180 EP - 7191 VL - 167 IS - 12 SN - 0022-1767, 0022-1767 KW - Antibodies, Viral KW - 0 KW - Antigens, Viral KW - NYVAC vaccine KW - SAIDS Vaccines KW - Vaccines, Attenuated KW - Vaccines, DNA KW - Viral Vaccines KW - Interferon-gamma KW - 82115-62-6 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Vaccines, DNA -- immunology KW - Interferon-gamma -- biosynthesis KW - Immunization Schedule KW - Immunization, Secondary KW - Antibodies, Viral -- immunology KW - Antibodies, Viral -- biosynthesis KW - Lymphocyte Activation KW - Cells, Cultured KW - Antigens, Viral -- immunology KW - Kinetics KW - Vaccines, Attenuated -- immunology KW - Cytotoxicity Tests, Immunologic KW - Macaca mulatta KW - Simian Immunodeficiency Virus -- genetics KW - Simian Acquired Immunodeficiency Syndrome -- immunology KW - Simian Immunodeficiency Virus -- immunology KW - SAIDS Vaccines -- immunology KW - CD8-Positive T-Lymphocytes -- immunology KW - CD4-Positive T-Lymphocytes -- immunology KW - Viral Vaccines -- immunology KW - Simian Acquired Immunodeficiency Syndrome -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72344379?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Abuse+%26+Neglect&rft.atitle=Domestic+violence+and+immigration+status+among+latina+mothers+in+the+child+welfare+system%3A+Findings+from+the+National+Survey+of+Child+and+Adolescent+Well+well-being+II+%28NSCAW+II%29&rft.au=Ogbonnaya%2C+Ijeoma+Nwabuzor%3BFinno-Velasquez%2C+Megan%3BKohl%2C+Patricia+L.&rft.aulast=Ogbonnaya&rft.aufirst=Ijeoma&rft.date=2015-01-01&rft.volume=39&rft.issue=&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=Child+Abuse+%26+Neglect&rft.issn=01452134&rft_id=info:doi/10.1016%2Fj.chiabu.2014.10.009 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-27 N1 - Date created - 2001-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - RapA, a bacterial homolog of SWI2/SNF2, stimulates RNA polymerase recycling in transcription AN - 18278044; 5334512 AB - We report that RapA, an Escherichia coli RNA polymerase (RNAP)-associated homolog of SWI2/SNF2, is capable of dramatic activation of RNA synthesis. The RapA-mediated transcriptional activation in vitro depends on supercoiled DNA and high salt concentrations, a condition that is likely to render the DNA superhelix tightly compacted. Moreover, RapA activates transcription by stimulating RNAP recycling. Mutational analyses indicate that the ATPase activity of RapA is essential for its function as a transcriptional activator, and a rapA null mutant exhibits a growth defect on nutrient plates containing high salt concentrations in vivo. Thus, RapA acts as a general transcription factor and an integral component of the transcription machinery. The mode of action of RapA in remodeling posttranscription or posttermination complexes is discussed. JF - Genes & Development AU - Sukhodolets, M V AU - Cabrera, JE AU - Zhi, H AU - Jin, D J AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA, djjin@helix.nih.gov Y1 - 2001/12/15/ PY - 2001 DA - 2001 Dec 15 SP - 3330 EP - 3341 VL - 15 IS - 24 SN - 0890-9369, 0890-9369 KW - RapA protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - DNA-directed RNA polymerase KW - Adenosinetriphosphatase KW - Escherichia coli KW - Transcription KW - Mutants KW - J 02726:RNA and ribosomes KW - N 14553:Transcription initiation, elongation & termination UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18278044?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+%26+Development&rft.atitle=RapA%2C+a+bacterial+homolog+of+SWI2%2FSNF2%2C+stimulates+RNA+polymerase+recycling+in+transcription&rft.au=Sukhodolets%2C+M+V%3BCabrera%2C+JE%3BZhi%2C+H%3BJin%2C+D+J&rft.aulast=Sukhodolets&rft.aufirst=M&rft.date=2001-12-15&rft.volume=15&rft.issue=24&rft.spage=3330&rft.isbn=&rft.btitle=&rft.title=Genes+%26+Development&rft.issn=08909369&rft_id=info:doi/10.1101%2Fgad.936701 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA-directed RNA polymerase; Transcription; Adenosinetriphosphatase; Mutants DO - http://dx.doi.org/10.1101/gad.936701 ER - TY - JOUR T1 - Induction of apoptosis by Phenothiazine derivatives in V79 cells AN - 18254019; 5317437 AB - Phenothiazine derivatives chlorpromazine (cpz) and trifluoperazine (tfp) were found to induce apoptosis, abnormal cell cycle and expression of p53 in Chinese hamster lung fibroblast V79 cells. Both the drugs can induce apoptosis when cells are treated with drug at a concentration of 10 mu g/ml within 4 h, as detected by propidium iodide staining and DNA fragmentation analysis. Flow cytometric analysis revealed that the apoptotic response is mediated by a loss of G sub(1) population of cells. In Western blot analysis, p21 is induced and p53 is accompanied by additional bands. Also indirect immunolabeling of single cells revealed that p21 is accumulated from cytoplasm into nucleus after the drug treatment and the intensities of p53 increased. Our findings demonstrate for the first time that phenothiazine derivatives, in addition to their cytotoxic effects, could induce apoptosis, an observation that has important clinical implications. JF - Toxicology Letters AU - Karmakar, P AU - Natarajan, A T AU - Poddar, R K AU - Dasgupta, U B AD - Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA, karmakarp@grc.nia.nih.gov Y1 - 2001/12/15/ PY - 2001 DA - 2001 Dec 15 SP - 19 EP - 28 VL - 125 IS - 1-3 SN - 0378-4274, 0378-4274 KW - V79 cells KW - double prime p21 protein KW - phenothiazines KW - trifluoperazine KW - Toxicology Abstracts KW - ^Ap21 protein KW - Flow cytometry KW - Apoptosis KW - Cell cycle KW - Chlorpromazine KW - p53 protein KW - X 24111:Acute exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18254019?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+Letters&rft.atitle=Induction+of+apoptosis+by+Phenothiazine+derivatives+in+V79+cells&rft.au=Karmakar%2C+P%3BNatarajan%2C+A+T%3BPoddar%2C+R+K%3BDasgupta%2C+U+B&rft.aulast=Karmakar&rft.aufirst=P&rft.date=2001-12-15&rft.volume=125&rft.issue=1-3&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Toxicology+Letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Flow cytometry; Cell cycle; Chlorpromazine; Apoptosis; p53 protein ER - TY - JOUR T1 - Antagonism of the actions of peroxisome proliferator-activated receptor-alpha by bile acids. AN - 72343187; 11606578 AB - The peroxisome proliferator-activated receptor-alpha (PPARalpha) is a ligand-activated transcription factor that regulates the expression of a number of genes critical for fatty acid beta-oxidation. Because a number of substrates and intermediates of this metabolic pathway serve as ligand activators of this receptor, homeostatic control of fatty acid metabolism is achieved. Evidence also exists for PPARalpha-dependent regulation of genes encoding critical enzymes of bile acid biosynthesis. To determine whether the primary products of bile acid biosynthesis, cholic acid and chenodeoxycholic acid, were capable of modulating PPARalpha function, a variety of in vivo and in vitro approaches were utilized. Feeding a bile acid-enriched diet significantly reduced the degree of hepatomegaly and induction of target genes encoding enzymes of fatty acid beta-oxidation caused by treatment with the potent PPARalpha ligand Wyeth-14,643. Convergent data from mechanistic studies indicate that bile acids interfere with transactivation by PPARalpha at least in part by impairing the recruitment of transcriptional coactivators. The results of this study provide the first evidence in favor of the existence of compounds, normally found within the body, that are capable of antagonizing the physiological actions of PPARalpha. The impact of PPARalpha antagonism by endogenous bile acids is likely to be limited under normal conditions and to have only minimal effects on bile acid homeostasis. However, during certain pathophysiological states where intracellular bile acid concentrations are elevated, meaningful effects on PPARalpha-dependent target gene regulation are possible. JF - The Journal of biological chemistry AU - Sinal, C J AU - Yoon, M AU - Gonzalez, F J AD - Laboratory of Metabolism, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/12/14/ PY - 2001 DA - 2001 Dec 14 SP - 47154 EP - 47162 VL - 276 IS - 50 SN - 0021-9258, 0021-9258 KW - Bile Acids and Salts KW - 0 KW - DNA-Binding Proteins KW - Gastrointestinal Agents KW - Ligands KW - Mutagens KW - Pyrimidines KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - farnesoid X-activated receptor KW - Chenodeoxycholic Acid KW - 0GEI24LG0J KW - pirinixic acid KW - 86C4MRT55A KW - Cholic Acid KW - G1JO7801AE KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Pyrimidines -- chemistry KW - Protein Biosynthesis KW - Animals KW - Dose-Response Relationship, Drug KW - Oxygen -- metabolism KW - Chenodeoxycholic Acid -- chemistry KW - DNA-Binding Proteins -- genetics KW - Pyrimidines -- pharmacology KW - Mice KW - Cholic Acid -- chemistry KW - Gastrointestinal Agents -- chemistry KW - Plasmids KW - Mutagens -- pharmacology KW - Mice, Transgenic KW - Transcriptional Activation KW - Gastrointestinal Agents -- pharmacology KW - Transfection KW - Gene Expression Regulation -- drug effects KW - Chenodeoxycholic Acid -- pharmacology KW - Cholic Acid -- pharmacology KW - Mutagens -- chemistry KW - Cell Line KW - Receptors, Cytoplasmic and Nuclear -- antagonists & inhibitors KW - Transcription Factors -- antagonists & inhibitors KW - Transcription Factors -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Transcription Factors -- genetics KW - Bile Acids and Salts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72343187?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Antagonism+of+the+actions+of+peroxisome+proliferator-activated+receptor-alpha+by+bile+acids.&rft.au=Davis%2C+Howard%3BGeddes%2C+Mike&rft.aulast=Davis&rft.aufirst=Howard&rft.date=2000-04-01&rft.volume=20&rft.issue=2&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=Public+money+and+management&rft.issn=09540962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-24 N1 - Date created - 2001-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antibodies to Plasmodium vivax transmission-blocking vaccine candidate antigens Pvs25 and Pvs28 do not show synergism. AN - 72354469; 11738740 AB - Transmission-blocking vaccines against malaria parasites target molecules expressed by sexual stage parasites to elicit antibodies that prevent the infection of the mosquito vector. Pvs25 and Pvs28, expressed on the surface of ookinetes, are potential candidates for such a vaccine and induce antibodies that block the infectivity of Plasmodium vivax in immunized animals. To improve the ability to induce transmission-blocking antibodies, Pvs25 and Pvs28 were produced as a single fusion protein by the yeast Saccharomyces cerevisiae. Mice immunized with a low dose of the chimeric molecule (Pvs25-28) developed higher antibody responses compared with mice immunized with either Pvs25 or Pvs28. In membrane feeding assays, both anti-Pvs25-28 and anti-Pvs25 antisera had similarly potent transmission-blocking activities (and both were much greater than anti-Pvs28). Furthermore, serum from mice simultaneously immunized with both Pvs25 and Pvs28, or serum mixtures of anti-Pvs25 alone and anti-Pvs28 alone did not enhance the efficacy over anti-Pvs25 serum alone, demonstrating that there is no synergism in the ability to block transmission of P. vivax between anti-Pvs25 and anti-Pvs28 antibodies. JF - Vaccine AU - Hisaeda, H AU - Collins, W E AU - Saul, A AU - Stowers, A W AD - Malaria Vaccine Development Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5640 Fishers Lane, Rockville, MD 20852, USA. Y1 - 2001/12/12/ PY - 2001 DA - 2001 Dec 12 SP - 763 EP - 770 VL - 20 IS - 5-6 SN - 0264-410X, 0264-410X KW - Antibodies, Protozoan KW - 0 KW - Antigens, Protozoan KW - DNA, Protozoan KW - Malaria Vaccines KW - Recombinant Fusion Proteins KW - Vaccines, Synthetic KW - Index Medicus KW - Insect Vectors -- parasitology KW - Animals KW - Recombinant Fusion Proteins -- immunology KW - DNA, Protozoan -- genetics KW - Mice KW - Malaria, Vivax -- immunology KW - Recombinant Fusion Proteins -- administration & dosage KW - Immunization KW - Base Sequence KW - Malaria, Vivax -- prevention & control KW - Recombinant Fusion Proteins -- genetics KW - Culicidae -- parasitology KW - Malaria, Vivax -- transmission KW - Vaccines, Synthetic -- administration & dosage KW - Vaccines, Synthetic -- genetics KW - Drug Synergism KW - Female KW - Antigens, Protozoan -- genetics KW - Malaria Vaccines -- genetics KW - Antigens, Protozoan -- administration & dosage KW - Antibodies, Protozoan -- biosynthesis KW - Plasmodium vivax -- genetics KW - Plasmodium vivax -- immunology KW - Malaria Vaccines -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72354469?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Antibodies+to+Plasmodium+vivax+transmission-blocking+vaccine+candidate+antigens+Pvs25+and+Pvs28+do+not+show+synergism.&rft.au=Hisaeda%2C+H%3BCollins%2C+W+E%3BSaul%2C+A%3BStowers%2C+A+W&rft.aulast=Hisaeda&rft.aufirst=H&rft.date=2001-12-12&rft.volume=20&rft.issue=5-6&rft.spage=763&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-12 N1 - Date created - 2001-12-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - One-time gene gun or intramuscular rabies DNA vaccination of non-human primates: comparison of neutralizing antibody responses and protection against rabies virus 1 year after vaccination AN - 18252963; 5310823 AB - We have previously shown that Macaca fascicularis (Cynomologus) monkeys receiving a primary and either one or two booster rabies DNA vaccinations are protected against rabies virus. In this study, we determined whether monkeys that had been vaccinated only once via gene gun or intramuscularly (i.m.) with different concentrations of DNA would be protected against rabies virus challenge. Neutralizing antibody responses were assayed for 1 year before the monkeys were challenged. Neutralizing antibody was detected at least 50 days earlier in gene gun vaccinated as compared to i.m. vaccinated animals. Prior to viral challenge, all (6/6, 100%) gene gun vaccinated animals, but only 3/6 (50%) i.m. vaccinated animals seroconverted. In general, antibody titers of the gene gun vaccinated animals were higher than the titers of the i.m. vaccinated animals. There was no correlation between the concentration of DNA used for vaccination, the neutralizing antibody responses elicited and protection against viral challenge. Seven days after viral challenge, a rapid and strong anamnestic antibody response was elicited in 100% of the gene gun vaccinated monkeys and in four i.m. vaccinated monkeys. Neutralizing antibody remained undetectable in two i.m. vaccinated monkeys. Overall, 60% (3/5) of the gene gun vaccinated animals and 87% (5/6) of the i.m. vaccinated monkeys survived viral challenge. This study is the first, to our knowledge, to show long-term protection of non-human primates against a human viral pathogen using a DNA vaccination protocol that did not include a booster immunization. JF - Vaccine AU - Lodmell, D L AU - Parnell, MJ AU - Bailey, J R AU - Ewalt, L C AU - Hanlon, CA AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, MT 59840, USA, dlodmell@nih.gov Y1 - 2001/12/12/ PY - 2001 DA - 2001 Dec 12 SP - 838 EP - 844 VL - 20 IS - 5-6 SN - 0264-410X, 0264-410X KW - Crab-eating macaque KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts; Immunology Abstracts KW - Macaca fascicularis KW - Antibody response KW - DNA vaccines KW - Rabies KW - Rabies virus KW - Vaccines KW - F 06807:Active immunization KW - V 22098:Immunization: Vaccines & vaccination: Animal KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18252963?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=One-time+gene+gun+or+intramuscular+rabies+DNA+vaccination+of+non-human+primates%3A+comparison+of+neutralizing+antibody+responses+and+protection+against+rabies+virus+1+year+after+vaccination&rft.au=Lodmell%2C+D+L%3BParnell%2C+MJ%3BBailey%2C+J+R%3BEwalt%2C+L+C%3BHanlon%2C+CA&rft.aulast=Lodmell&rft.aufirst=D&rft.date=2001-12-12&rft.volume=20&rft.issue=5-6&rft.spage=838&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Rabies virus; Macaca fascicularis; DNA vaccines; Vaccines; Rabies; Antibody response ER - TY - JOUR T1 - Thrombolysis in patients with transient neurologic deficits. AN - 72343900; 11739841 AB - What is the risk of thrombolysis in patients with acute stroke who might recover without treatment? In the National Institute of Neurological Disorders and Stroke rt-PA for Acute Stroke Trial, 2.6% of patients taking placebo showed spontaneous 24-hour recovery, compared to 11.5% of recombinant tissue-type plasminogen activator (rt-PA)-treated patients (p < 0.001). There were no symptomatic ICH in the patients taking placebo; one hypertensive, rt-PA-treated patient hemorrhaged. Assuming the National Institute of Neurological Disorders and Stroke protocol is followed rigorously, patients with acute stroke rarely recover spontaneously and the thrombolytic risk is low. JF - Neurology AU - Lyden, P AU - Lu, M AU - Kwiatkowski, T AU - Frankel, M AU - Levine, S AU - Broderick, J AU - Brott, T AU - NINDS rt-PA Stroke Study Group AD - Department of Neurosciences, UCSD School of Medicine, San Diego, CA, USA. plyden@ucsd.edu ; NINDS rt-PA Stroke Study Group Y1 - 2001/12/11/ PY - 2001 DA - 2001 Dec 11 SP - 2125 EP - 2128 VL - 57 IS - 11 SN - 0028-3878, 0028-3878 KW - Tissue Plasminogen Activator KW - EC 3.4.21.68 KW - Abridged Index Medicus KW - Index Medicus KW - Cerebral Hemorrhage -- chemically induced KW - Humans KW - Treatment Outcome KW - Neurologic Examination -- drug effects KW - Aged KW - Middle Aged KW - Remission, Spontaneous KW - Male KW - Female KW - Thrombolytic Therapy KW - Tissue Plasminogen Activator -- adverse effects KW - Tissue Plasminogen Activator -- administration & dosage KW - Ischemic Attack, Transient -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72343900?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Thrombolysis+in+patients+with+transient+neurologic+deficits.&rft.au=Lyden%2C+P%3BLu%2C+M%3BKwiatkowski%2C+T%3BFrankel%2C+M%3BLevine%2C+S%3BBroderick%2C+J%3BBrott%2C+T%3BNINDS+rt-PA+Stroke+Study+Group&rft.aulast=Lyden&rft.aufirst=P&rft.date=2001-12-11&rft.volume=57&rft.issue=11&rft.spage=2125&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-15 N1 - Date created - 2001-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - GFRalpha-1 mRNA in dopaminergic and nondopaminergic neurons in the substantia nigra and ventral tegmental area. AN - 72365212; 11745638 AB - Glial cell line-derived neurotrophic factor (GDNF) is a survival factor for several types of neurons, including dopaminergic (DAergic) neurons. GDNF binds with high affinity to the GDNF family receptor alpha-1 (GFRalpha-1), which is highly expressed in the midbrain. Using anatomical and lesion techniques, we demonstrated that GFRalpha-1 was expressed in DAergic and non-DAergic neurons in the rat midbrain. Immunohistochemical characterization of GFRalpha-1-expressing neurons indicated that most of the neurons that were immunopositive for the DAergic marker tyrosine hydroxylase (TH) expressed GFRalpha-1 in the substantia nigra pars compacta (SNC). In contrast, fewer TH-containing neurons expressed GFRalpha-1 in the substantia nigra pars reticulata (SNR) and the ventral tegmental area (VTA). Depletion of GFRalpha-1/TH neurons was observed in the SNC following treatment with the neurotoxin 6-hydroxydopamine (6-OHDA); however, GFRalpha-1 expression remained in some neurons located in the SNR. The gamma-aminobutyric acid (GABA)ergic nature of GFRalpha-1-expressing neurons located in the SNR, which were resistant to (6-hydroxydopamine) 6-OHDA, was established by their expression of glutamic acid decarboxylase (GAD; the synthesizing enzyme for GABA). Further analysis indicated that coexpression of GFRalpha-1 and GAD varied in a rostrocaudal gradient in the SNR, substantia nigra pars lateralis (SNL), and VTA. Midbrain DAergic and GABAergic neurons have been previously classified according to their Ca(2+) binding protein (CaBP) content; thus, we also sought to investigate the proportion of midbrain GFRalpha-1-expressing neurons containing parvalbumin (PV), calbindin (CB), and calretinin (CR) in the midbrain. Although GFRalpha-1 expression was found mainly in CB- and CR-immunoreactive neurons, it was rarely observed in PV-immunolabeled neurons. Analysis of the proportion of GFRalpha-1-expressing neurons for each CaBP subpopulation indicated the coexistence of GFRalpha-1 with CR in the VTA and all subdivisions of the SN; double-labeled GFRalpha-1/CR neurons were distributed in the SNC, SNR, SNL, and VTA. GFRalpha-1/CB neurons were also detected in the SNC, SNL, and VTA. Expression of GFRalpha-1 in DAergic and non-DAergic neurons in the rat SN and VTA suggests that GDNF, via GFRalpha-1, might modulate DAergic and GABAergic functions in the nigrostriatal, mesolimbic, and nigrothalamic circuits of the adult rat. Published 2001 Wiley-Liss, Inc. JF - The Journal of comparative neurology AU - Sarabi, A AU - Hoffer, B J AU - Olson, L AU - Morales, M AD - Cellular Neurophysiology, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2001/12/10/ PY - 2001 DA - 2001 Dec 10 SP - 106 EP - 117 VL - 441 IS - 2 SN - 0021-9967, 0021-9967 KW - Calcium-Binding Proteins KW - 0 KW - Drosophila Proteins KW - Gfra1 protein, rat KW - Glial Cell Line-Derived Neurotrophic Factor Receptors KW - Proto-Oncogene Proteins KW - RNA, Messenger KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Proto-Oncogene Proteins c-ret KW - EC 2.7.10.1 KW - Receptor Protein-Tyrosine Kinases KW - Ret oncogene protein, Drosophila KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - Tyrosine 3-Monooxygenase -- metabolism KW - Rats, Sprague-Dawley KW - gamma-Aminobutyric Acid -- metabolism KW - Calcium-Binding Proteins -- metabolism KW - Male KW - Substantia Nigra -- metabolism KW - Neurons -- metabolism KW - RNA, Messenger -- metabolism KW - Receptor Protein-Tyrosine Kinases -- genetics KW - Dopamine -- metabolism KW - Ventral Tegmental Area -- metabolism KW - Ventral Tegmental Area -- cytology KW - Proto-Oncogene Proteins -- genetics KW - Substantia Nigra -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72365212?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+Journal+of+Criminology&rft.atitle=Similar+punishment%3F%3A+Comparing+sentencing+outcomes+in+domestic+and+non-domestic+violence+cases&rft.au=Bond%2C+Christine+E.+W.%3BJeffries%2C+Samantha&rft.aulast=Bond&rft.aufirst=Christine+E.&rft.date=2014-09-01&rft.volume=18&rft.issue=3&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Public+money+and+management&rft.issn=09540962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-22 N1 - Date created - 2001-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of Salivary Gland Acinar and Ductal Cell-Specific Promoters In Vivo with Recombinant Adenoviral Vectors AN - 18254393; 5312481 AB - Adenoviral vectors efficiently deliver exogenous genes to salivary glands. There are two general epithelial cell types, with very different functions, in salivary glands--acinar and ductal. To determine if gene expression can be restricted in vivo to either general cell type using a relatively cell/tissue-specific promoter in conjunction with adenovirus-mediated gene transfer, we tested the human amylase and kallikrein promoters. For initial studies the sensitive reporter gene luciferase was used in two adenoviral constructs. The adenovirus AdAMY-luc contains the human salivary gland amylase promoter (-1003 to +2)(AMY1C) and AdKALL-luc contains the human tissue kallikein promoter (-315 to -1)(KLK1). The adenovirus AdKALL-hAQP1 was also used to test a therapeutic gene, human aquaporin-1 (hAQP1), potentially of importance in treating surviving ductal cells in irradiation-damaged glands. Luciferase expression after AdAMY-luc delivery in vivo directly to the parotid, submandibular, and sublingual glands, as well as to the lungs, and intravenously via the femoral vein, was restricted to the three salivary glands and the pancreas. AdKALL-luc delivery via the same routes resulted in a more general distribution of luciferase expression, although greatest luciferase activity was seen in salivary glands and lung. Luciferase activity after AdAMY-luc delivery was proportionally greater ( similar to 14-fold) in acinar cells, whereas luciferase activity after AdKALL-luc delivery was proportionally greater ( similar to 9-fold) in ductal cells. The expression of hAQP1 after AdKALL-hAQP1 gene transfer was mainly observed in ductal cells in vivo. AdKALL-hAQP1 was as useful as AdCMV-hAQP1 in increasing salivary flow rates of irradiated rats. This study demonstrates that adenoviral vectors containing the relatively cell/tissue-specific AMY1C or KLK1 promoters may be useful for targeting therapeutic gene expression in salivary glands. JF - Human Gene Therapy AU - Zheng, C AU - Hoque, ATMS AU - Braddon, V R AU - Baum, B J AU - O'Connell, B C AD - GTTB/NIDCR/NIH, 9000 Rockvile Pike, Bldg. 10, 1N113, MSC 1190, Bethesda, MD 20892-1190, USA, changyu.zheng@nih.gov Y1 - 2001/12/10/ PY - 2001 DA - 2001 Dec 10 SP - 2215 EP - 2223 VL - 12 IS - 18 SN - 1043-0342, 1043-0342 KW - man KW - kallikrein KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts KW - ^a-Amylase KW - Gene therapy KW - Adenovirus KW - Salivary gland KW - Acinar cells KW - Expression vectors KW - Lung KW - Reporter gene KW - a-Amylase KW - N 14682:Cloning vectors KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18254393?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Evaluation+of+Salivary+Gland+Acinar+and+Ductal+Cell-Specific+Promoters+In+Vivo+with+Recombinant+Adenoviral+Vectors&rft.au=Zheng%2C+C%3BHoque%2C+ATMS%3BBraddon%2C+V+R%3BBaum%2C+B+J%3BO%27Connell%2C+B+C&rft.aulast=Zheng&rft.aufirst=C&rft.date=2001-12-10&rft.volume=12&rft.issue=18&rft.spage=2215&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adenovirus; Expression vectors; Acinar cells; Salivary gland; Gene therapy; Reporter gene; a-Amylase; Lung; ^a-Amylase ER - TY - JOUR T1 - The Cockayne Syndrome group B gene product is involved in general genome base excision repair of 8-hydroxyguanine in DNA. AN - 72320937; 11581270 AB - Cockayne Syndrome (CS) is a human genetic disorder with two complementation groups, CS-A and CS-B. The CSB gene product is involved in transcription-coupled repair of DNA damage but may participate in other pathways of DNA metabolism. The present study investigated the role of different conserved helicase motifs of CSB in base excision repair. Stably transformed human cell lines with site-directed CSB mutations in different motifs within its putative helicase domain were established. We find that CSB null and helicase motif V and VI mutants had greater sensitivity than wild type cells to gamma-radiation. Whole cell extracts from CSB null and motif V/VI mutants had lower activity of 8-hydroxyguanine incision in DNA than wild type cells. Also, 8-hydroxyguanine accumulated more in CSB null and motif VI mutant cells than in wild type cells after exposure to gamma-radiation. We conclude that a deficiency in general genome base excision repair of selective modified DNA base(s) might contribute to CS pathogenesis. Furthermore, whereas the disruption of helicase motifs V or VI results in a CSB phenotype, mutations in other helicase motifs do not cause this effect. The biological functions of CSB in different DNA repair pathways may be mediated by distinct functional motifs of the protein. JF - The Journal of biological chemistry AU - Tuo, J AU - Müftüoglu, M AU - Chen, C AU - Jaruga, P AU - Selzer, R R AU - Brosh, R M AU - Rodriguez, H AU - Dizdaroglu, M AU - Bohr, V A AD - Laboratory of Molecular Gerontology, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2001/12/07/ PY - 2001 DA - 2001 Dec 07 SP - 45772 EP - 45779 VL - 276 IS - 49 SN - 0021-9258, 0021-9258 KW - 8-hydroxyguanine KW - 5614-64-2 KW - Guanine KW - 5Z93L87A1R KW - DNA KW - 9007-49-2 KW - DNA Helicases KW - EC 3.6.4.- KW - ERCC6 protein, human KW - EC 3.6.4.12 KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Humans KW - Oxidative Stress KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Cell Line, Transformed KW - DNA Repair -- physiology KW - DNA Helicases -- chemistry KW - Guanine -- chemistry KW - DNA Helicases -- physiology KW - Cockayne Syndrome -- genetics KW - DNA -- genetics KW - DNA Helicases -- genetics KW - Guanine -- analogs & derivatives KW - Genome UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72320937?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+Cockayne+Syndrome+group+B+gene+product+is+involved+in+general+genome+base+excision+repair+of+8-hydroxyguanine+in+DNA.&rft.au=Tuo%2C+J%3BM%C3%BCft%C3%BCoglu%2C+M%3BChen%2C+C%3BJaruga%2C+P%3BSelzer%2C+R+R%3BBrosh%2C+R+M%3BRodriguez%2C+H%3BDizdaroglu%2C+M%3BBohr%2C+V+A&rft.aulast=Tuo&rft.aufirst=J&rft.date=2001-12-07&rft.volume=276&rft.issue=49&rft.spage=45772&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-10 N1 - Date created - 2001-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - SNIP1 inhibits NF-kappa B signaling by competing for its binding to the C/H1 domain of CBP/p300 transcriptional co-activators. AN - 72318961; 11567019 AB - SNIP1 is a 396-amino acid nuclear protein shown to be an inhibitor of the TGF-beta signal transduction pathway and to be important in suppressing transcriptional activation dependent on the co-activators CBP and p300. In this report we show that SNIP1 potently inhibits the activity of NF-kappa B, which binds the C/H1 domain of CBP/p300, but does not interfere with the activity of transcription factors such as p53, which bind to other domains of p300, or factors such as VP16, which are independent of these co-activators. Inhibition of NF-kappa B activity is a function of the N-terminal domain of SNIP1 and involves competition of SNIP1 and the NF-kappa B subunit, RelA/p65, for binding to p300, similar to the mechanism of inhibition of Smad signaling by SNIP1. Immunohistochemical staining shows that expression of SNIP1 is strictly regulated in development and that it colocalizes, in certain tissues, with nuclear staining for RelA/p65 and for p300, suggesting that they may regulate NF-kappa B activity in vivo in a spatially and temporally controlled manner. These data led us to suggest that SNIP1 may be an inhibitor of multiple transcriptional pathways that require the C/H1 domain of CBP/p300. JF - The Journal of biological chemistry AU - Kim, R H AU - Flanders, K C AU - Birkey Reffey, S AU - Anderson, L A AU - Duckett, C S AU - Perkins, N D AU - Roberts, A B AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-5055, USA. Y1 - 2001/12/07/ PY - 2001 DA - 2001 Dec 07 SP - 46297 EP - 46304 VL - 276 IS - 49 SN - 0021-9258, 0021-9258 KW - Carrier Proteins KW - 0 KW - Intracellular Signaling Peptides and Proteins KW - NF-kappa B KW - Nuclear Proteins KW - Repressor Proteins KW - SNIP1 protein, human KW - Snip1 protein, mouse KW - Trans-Activators KW - E1A-Associated p300 Protein KW - EC 2.3.1.48 KW - Ep300 protein, mouse KW - Index Medicus KW - Animals KW - Gene Expression Regulation -- physiology KW - Humans KW - Binding, Competitive KW - Embryonic and Fetal Development -- physiology KW - Mice KW - Transcriptional Activation KW - Cell Line KW - NF-kappa B -- chemistry KW - Trans-Activators -- metabolism KW - Carrier Proteins -- metabolism KW - Repressor Proteins -- physiology KW - Repressor Proteins -- metabolism KW - Trans-Activators -- chemistry KW - Carrier Proteins -- physiology KW - Nuclear Proteins -- chemistry KW - Nuclear Proteins -- metabolism KW - Signal Transduction KW - NF-kappa B -- metabolism KW - NF-kappa B -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72318961?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Public+money+and+management&rft.atitle=Value+for+money+in+urban+transport+public+expenditure+-+the+case+of+light+rail&rft.au=Lesley%2C+Lewis&rft.aulast=Lesley&rft.aufirst=Lewis&rft.date=1993-01-01&rft.volume=13&rft.issue=1&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Public+money+and+management&rft.issn=09540962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-10 N1 - Date created - 2001-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Phe-X-Glu DNA Binding Motif of MutS: The Role of Hydrogen Bonding in Mismatch Recognition AN - 18204640; 5273309 AB - The crystal structures of MutS protein from Thermus aquaticus and Escherichia coli in a complex with a mismatch-containing DNA duplex reveal that the Glu residue in a conserved Phe-X-Glu motif participates in a hydrogen-bonded contact with either an unpaired thymidine or the thymidine of a G-T base-base mismatch. Here, the role of hydrogen bonding in mismatch recognition by MutS is assessed. The relative affinities of MutS for DNA duplexes containing nonpolar shape mimics of A and T, 4-methylbenzimidazole (Z), and difluorotoluene (F), respectively, that lack hydrogen bonding donors and acceptors, are determined in gel mobility shift assays. The results provide support for an induced fit mode of mismatch binding in which duplexes destabilized by mismatches are preferred substrates for kinking by MutS. Hydrogen bonding between the O epsilon 2 group of Glu and the mismatched base contributes only marginally to mismatch recognition and is significantly less important than the aromatic ring stack with the conserved Phe residue. A MutS protein in which Ala is substituted for Glu super(38) is shown to be defective for mismatch repair in vivo. DNA binding studies reveal a novel role for the conserved Glu residue in the establishment of mismatch discrimination by MutS. JF - Journal of Biological Chemistry AU - Schofield, MJ AU - Brownewell, F E AU - Nayak, S AU - Du, C AU - Kool, E T AU - Hsieh, P AD - Genetics & Biochemistry Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA, ph52x@nih.gov Y1 - 2001/12/07/ PY - 2001 DA - 2001 Dec 07 SP - 45505 EP - 45508 VL - 276 IS - 49 SN - 0021-9258, 0021-9258 KW - DNA repair KW - MutS protein KW - Phe KW - adenine KW - glutamine KW - hydrogen bonds KW - mismatch repair KW - thymine KW - ASFA 1: Biological Sciences & Living Resources; Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Molecular structure KW - Escherichia coli KW - Crystal structure KW - DNA KW - Thermus aquaticus KW - Hydrogen KW - Nucleic acids KW - Q1 08205:Genetics and evolution KW - N 14652:DNA repair KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18204640?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=The+Phe-X-Glu+DNA+Binding+Motif+of+MutS%3A+The+Role+of+Hydrogen+Bonding+in+Mismatch+Recognition&rft.au=Schofield%2C+MJ%3BBrownewell%2C+F+E%3BNayak%2C+S%3BDu%2C+C%3BKool%2C+E+T%3BHsieh%2C+P&rft.aulast=Schofield&rft.aufirst=MJ&rft.date=2001-12-07&rft.volume=276&rft.issue=49&rft.spage=45505&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2014-05-07 N1 - SubjectsTermNotLitGenreText - Molecular structure; DNA; Hydrogen; Nucleic acids; Crystal structure; DNA repair; Escherichia coli; Thermus aquaticus ER - TY - JOUR T1 - AID is required to initiate Nbs1/gamma-H2AX focus formation and mutations at sites of class switching. AN - 72344791; 11740565 AB - Class switch recombination (CSR) is a region-specific DNA recombination reaction that replaces one immunoglobulin heavy-chain constant region (Ch) gene with another. This enables a single variable (V) region gene to be used in conjunction with different downstream Ch genes, each having a unique biological activity. The molecular mechanisms that mediate CSR have not been defined, but activation-induced cytidine deaminase (AID), a putative RNA-editing enzyme, is required for this reaction. Here we report that the Nijmegen breakage syndrome protein (Nbs1) and phosphorylated H2A histone family member X (gamma-H2AX, also known as gamma-H2afx), which facilitate DNA double-strand break (DSB) repair, form nuclear foci at the Ch region in the G1 phase of the cell cycle in cells undergoing CSR, and that switching is impaired in H2AX-/- mice. Localization of Nbs1 and gamma-H2AX to the Igh locus during CSR is dependent on AID. In addition, AID is required for induction of switch region (S mu)-specific DNA lesions that precede CSR. These results place AID function upstream of the DNA modifications that initiate CSR. JF - Nature AU - Petersen, S AU - Casellas, R AU - Reina-San-Martin, B AU - Chen, H T AU - Difilippantonio, M J AU - Wilson, P C AU - Hanitsch, L AU - Celeste, A AU - Muramatsu, M AU - Pilch, D R AU - Redon, C AU - Ried, T AU - Bonner, W M AU - Honjo, T AU - Nussenzweig, M C AU - Nussenzweig, A AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/12/06/ PY - 2001 DA - 2001 Dec 06 SP - 660 EP - 665 VL - 414 IS - 6864 SN - 0028-0836, 0028-0836 KW - BRCA1 Protein KW - 0 KW - DNA-Binding Proteins KW - Histones KW - Immunoglobulin Heavy Chains KW - Nuclear Proteins KW - DNA KW - 9007-49-2 KW - Rad51 Recombinase KW - EC 2.7.7.- KW - Rad51 protein, mouse KW - AICDA (activation-induced cytidine deaminase) KW - EC 3.5.4.- KW - Cytidine Deaminase KW - EC 3.5.4.5 KW - Index Medicus KW - Animals KW - DNA Repair KW - Mice KW - B-Lymphocytes -- immunology KW - Immunoglobulin Heavy Chains -- genetics KW - Cloning, Molecular KW - Lymphocyte Activation KW - Base Sequence KW - Cells, Cultured KW - BRCA1 Protein -- physiology KW - Recombination, Genetic KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - DNA-Binding Proteins -- physiology KW - B-Lymphocytes -- physiology KW - Cell Cycle KW - Immunoglobulin Class Switching -- physiology KW - Cytidine Deaminase -- physiology KW - Cytidine Deaminase -- genetics KW - Nuclear Proteins -- physiology KW - Histones -- physiology KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72344791?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=AID+is+required+to+initiate+Nbs1%2Fgamma-H2AX+focus+formation+and+mutations+at+sites+of+class+switching.&rft.au=Petersen%2C+S%3BCasellas%2C+R%3BReina-San-Martin%2C+B%3BChen%2C+H+T%3BDifilippantonio%2C+M+J%3BWilson%2C+P+C%3BHanitsch%2C+L%3BCeleste%2C+A%3BMuramatsu%2C+M%3BPilch%2C+D+R%3BRedon%2C+C%3BRied%2C+T%3BBonner%2C+W+M%3BHonjo%2C+T%3BNussenzweig%2C+M+C%3BNussenzweig%2C+A&rft.aulast=Petersen&rft.aufirst=S&rft.date=2001-12-06&rft.volume=414&rft.issue=6864&rft.spage=660&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-25 N1 - Date created - 2001-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Histone tails modulate nucleosome mobility and regulate ATP-dependent nucleosome sliding by NURF. AN - 72332795; 11724935 AB - Nucleosome Remodeling Factor (NURF) is an ATP-dependent nucleosome remodeling complex that alters chromatin structure by catalyzing nucleosome sliding, thereby exposing DNA sequences previously associated with nucleosomes. We systematically studied how the unstructured N-terminal residues of core histones (the N-terminal histone tails) influence nucleosome sliding. We used bacterially expressed Drosophila histones to reconstitute hybrid nucleosomes lacking one or more histone N-terminal tails. Unexpectedly, we found that removal of the N-terminal tail of histone H2B promoted uncatalyzed nucleosome sliding during native gel electrophoresis. Uncatalyzed nucleosome mobility was enhanced by additional removal of other histone tails but was not affected by hyperacetylation of core histones by p300. In addition, we found that the N-terminal tail of the histone H4 is specifically required for ATP-dependent catalysis of nucleosome sliding by NURF. Alanine scanning mutagenesis demonstrated that H4 residues 16-KRHR-19 are critical for the induction of nucleosome mobility, revealing a histone tail motif that regulates NURF activity. An exchange of histone tails between H4 and H3 impaired NURF-induced sliding of the mutant nucleosome, indicating that the location of the KRHR motif in relation to global nucleosome structure is functionally important. Our results provide functions for the N-terminal histone tails in regulating the mobility of nucleosomes. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Hamiche, A AU - Kang, J G AU - Dennis, C AU - Xiao, H AU - Wu, C AD - Laboratory of Molecular Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 2001/12/04/ PY - 2001 DA - 2001 Dec 04 SP - 14316 EP - 14321 VL - 98 IS - 25 SN - 0027-8424, 0027-8424 KW - Histones KW - 0 KW - Insect Proteins KW - Nucleosomes KW - Recombinant Proteins KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Index Medicus KW - Animals KW - Insect Proteins -- genetics KW - Insect Proteins -- chemistry KW - Recombinant Proteins -- metabolism KW - Drosophila melanogaster -- genetics KW - Drosophila melanogaster -- metabolism KW - Recombinant Proteins -- chemistry KW - Recombinant Proteins -- genetics KW - Movement KW - Mutagenesis KW - Insect Proteins -- metabolism KW - Histones -- metabolism KW - Nucleosomes -- metabolism KW - Histones -- chemistry KW - Adenosine Triphosphate -- metabolism KW - Nucleosomes -- chemistry KW - Histones -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72332795?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Histone+tails+modulate+nucleosome+mobility+and+regulate+ATP-dependent+nucleosome+sliding+by+NURF.&rft.au=Hamiche%2C+A%3BKang%2C+J+G%3BDennis%2C+C%3BXiao%2C+H%3BWu%2C+C&rft.aulast=Hamiche&rft.aufirst=A&rft.date=2001-12-04&rft.volume=98&rft.issue=25&rft.spage=14316&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-10 N1 - Date created - 2001-12-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3364-9 [10725359] J Mol Biol. 2000 Apr 28;298(2):211-23 [10764592] J Biol Chem. 2000 May 19;275(20):14787-90 [10747848] Mol Cell. 2000 Feb;5(2):355-65 [10882076] EMBO J. 2000 Jul 3;19(13):3377-87 [10880450] FEBS Lett. 2000 Jun 30;476(1-2):68-72 [10878253] Nature. 2000 Aug 3;406(6795):541-4 [10952318] Science. 2000 Sep 29;289(5488):2360-2 [11009424] J Biol Chem. 2000 Nov 10;275(45):35248-55 [10942776] Cell. 2000 Oct 27;103(3):423-33 [11081629] J Biol Chem. 2000 Nov 24;275(47):37285-90 [10970897] Trends Biochem Sci. 2000 Dec;25(12):619-23 [11116189] Mol Cell Biol. 2001 Feb;21(3):875-83 [11154274] Cell. 2000 Dec 22;103(7):1133-42 [11163188] Mol Cell. 2001 Jan;7(1):97-104 [11172715] J Mol Biol. 2001 Apr 6;307(4):977-85 [11286549] J Biol Chem. 2001 Apr 20;276(16):12764-8 [11279082] J Biol Chem. 2001 May 4;276(18):14773-83 [11279013] Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6599-604 [11381129] Mol Cell. 2001 Sep;8(3):531-43 [11583616] J Mol Biol. 1979 May 15;130(2):103-34 [469938] Eur J Biochem. 1979 Oct;100(1):225-35 [488093] Anal Biochem. 1981 Nov 15;118(1):197-203 [6175245] Proc Natl Acad Sci U S A. 1983 Jan;80(1):51-5 [6572008] J Biol Chem. 1984 Apr 10;259(7):4212-22 [6707002] Biosci Rep. 1984 May;4(5):365-86 [6375755] Cell. 1985 Oct;42(3):799-808 [2996776] J Mol Biol. 1989 Apr 5;206(3):451-63 [2716057] Curr Opin Cell Biol. 1990 Jun;2(3):437-45 [2198896] J Mol Biol. 1992 Apr 20;224(4):981-1001 [1314907] EMBO J. 1992 Aug;11(8):2951-9 [1639066] J Biol Chem. 1992 Sep 25;267(27):19587-95 [1527076] Cell. 1993 Jan 15;72(1):73-84 [8422685] J Biol Chem. 1995 Jul 28;270(30):17923-8 [7629098] EMBO J. 1995 Aug 1;14(15):3752-65 [7641694] J Biol Chem. 1995 Oct 27;270(43):25359-62 [7592700] Nucleic Acids Res. 1995 Nov 25;23(22):4557-64 [8524642] Cell. 1995 Dec 15;83(6):1011-20 [8521501] Cell. 1995 Dec 15;83(6):1021-6 [8521502] J Mol Biol. 1996 Mar 22;257(1):30-42 [8632457] EMBO J. 1996 May 15;15(10):2508-18 [8665858] Biochemistry. 1996 Apr 2;35(13):4009-15 [8672434] Nature. 1996 Jul 25;382(6589):319-24 [8684459] Biochem Biophys Res Commun. 1997 Jan 3;230(1):136-9 [9020030] Cell. 1997 Jul 11;90(1):145-55 [9230310] Nature. 1997 Aug 7;388(6642):598-602 [9252192] Semin Cell Dev Biol. 1999 Apr;10(2):189-95 [10441072] Cell. 1999 Aug 6;98(3):285-94 [10458604] Nature. 1999 Aug 19;400(6746):784-7 [10466730] Genes Dev. 1999 Sep 15;13(18):2339-52 [10500090] Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):8959-64 [9256417] Biochemistry. 1997 Sep 23;36(38):11381-8 [9298957] EMBO J. 1997 Aug 1;16(15):4717-26 [9303316] Nature. 1997 Sep 18;389(6648):251-60 [9305837] J Mol Biol. 1997 Sep 26;272(3):301-11 [9325091] Cell. 1998 Oct 2;95(1):93-104 [9778250] Mol Cell Biol. 1998 Nov;18(11):6293-304 [9774646] Bioessays. 1998 Aug;20(8):615-26 [9780836] Bioessays. 1998 Aug;20(8):634-41 [9780838] Science. 1998 Dec 4;282(5395):1900-4 [9836642] EMBO J. 1999 Jan 4;18(1):229-40 [9878065] J Biol Chem. 1999 Jan 15;274(3):1189-92 [9880483] Mol Cell Biol. 1999 Feb;19(2):1470-8 [9891080] Biochemistry. 1998 Dec 22;37(51):17637-41 [9922128] Cell. 1999 Feb 5;96(3):389-92 [10025404] Genes Dev. 1999 Mar 15;13(6):686-97 [10090725] Methods Enzymol. 1999;304:757-65 [10372395] Cell. 1999 Jun 25;97(7):833-42 [10399912] Cell. 1999 Jun 25;97(7):843-52 [10399913] Curr Biol. 1999 Oct 7;9(19):R742-6 [10530996] Biotechniques. 2000 Jan;28(1):38-40, 42, 46 [10649766] Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1038-43 [10655480] J Mol Biol. 1997 Oct 31;273(3):503-8 [9356240] Cell. 1998 Feb 6;92(3):307-13 [9476891] Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4947-52 [9560208] Mol Cell Biol. 1998 Aug;18(8):4629-38 [9671473] Cell. 1998 Jul 10;94(1):17-27 [9674423] Annu Rev Biochem. 1998;67:545-79 [9759497] Mol Cell Biol. 2000 Mar;20(6):1899-910 [10688638] Mol Cell Biol. 2000 Mar;20(6):2167-75 [10688663] Biochemistry. 2000 Apr 4;39(13):3835-41 [10736184] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence for a novel GTPase priming step in the SRP protein targeting pathway AN - 18143039; 5273237 AB - Protein targeting by the signal recognition particle (SRP) pathway requires the interaction of two homologous GTPases that reciprocally regulate each others GTPase activity, the SRP signal peptide- binding subunit (SRP54) and the SRP receptor alpha -subunit (SR alpha ). The GTPase domain of both proteins abuts a unique 'N domain that appears to facilitate external ligand binding. To examine the relationship between the unusual regulation and unique architecture of the SRP pathway GTPases, we mutated an invariant glycine in Escherichia coli SRP54 and SR alpha orthologs ('Ffh and 'FtsY, respectively) that resides at the N-GTPase domain interface. A G257A mutation in Ffh produced a lethal phenotype. The mutation did not significantly affect Ffh function, but severely reduced interaction with FtsY. Likewise, mutation of FtsY Gly455 produced growth defects and inhibited interaction with Ffh. The data suggest that Ffh and FtsY interact only in a 'primed conformation which requires interdomain communication. Based on these results, we propose that the distinctive features of the SRP pathway GTPases evolved to ensure that SRP and the SR engage external ligands before interacting with each other. JF - EMBO Journal AU - Lu, Y AU - Qi, H AU - Hyndman, J B AU - Ulbrandt, N D AU - Teplyakov, A AU - Tomasevic, N AU - Bernstein, H D AD - Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 10, Room 9D-20, Bethesda, MD 20892-1810, USA, harris_bernstein@nih.gov Y1 - 2001/12/03/ PY - 2001 DA - 2001 Dec 03 SP - 6724 EP - 6734 VL - 20 IS - 23 SN - 0261-4189, 0261-4189 KW - Ffh protein KW - FtsY protein KW - SRP protein KW - SRP54 protein KW - Microbiology Abstracts B: Bacteriology KW - Escherichia coli KW - Signals KW - Mutation KW - Ligands KW - Guanosinetriphosphatase KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18143039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=EMBO+Journal&rft.atitle=Evidence+for+a+novel+GTPase+priming+step+in+the+SRP+protein+targeting+pathway&rft.au=Lu%2C+Y%3BQi%2C+H%3BHyndman%2C+J+B%3BUlbrandt%2C+N+D%3BTeplyakov%2C+A%3BTomasevic%2C+N%3BBernstein%2C+H+D&rft.aulast=Lu&rft.aufirst=Y&rft.date=2001-12-03&rft.volume=20&rft.issue=23&rft.spage=6724&rft.isbn=&rft.btitle=&rft.title=EMBO+Journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Guanosinetriphosphatase; Mutation; Ligands; Signals ER - TY - JOUR T1 - Human Dendritic Cells as Targets of Dengue Virus Infection AN - 902345361; 14934892 AB - Dengue virus infections are an emerging global threat. Severe dengue infection is manifested as dengue hemorrhagic fever and dengue shock syndrome, both of which can be fatal complications. Factors predisposing to complicated disease and pathogenesis of severe infections are discussed. Using immunohistochemistry, immunofluorescence, flow cytometry, and ELISA techniques, we studied the cellular targets of dengue virus infection, at both the clinical (in vivo) and the laboratory (in vitro) level. Resident skin dendritic cells are targets of dengue virus infection as demonstrated in a skin biopsy from a dengue vaccine recipient. We show that factors influencing infection of monocytes/macrophages and dendritic cells are different. Immature dendritic cells were found to be the cells most permissive for dengue infection and maybe early targets for infection. Immature dendritic cells exposed to dengue virus produce TNF- alpha protein. Some of these immature dendritic cells undergo TNF- alpha mediated maturation as a consequence of exposure to the dengue virus.Journal of Investigative Dermatology Symposium Proceedings (2001) 6, 219-224; doi:10.1046/j.0022-202x.2001.00037.x JF - Journal of Investigative Dermatology Symposium Proceedings AU - Marovich, Mary AU - Grouard-Vogel, Geraldine AU - Louder, Mark AU - Eller, Michael AU - Sun, Wellington AU - Wu, Shuenn-Ju AU - Putvatana, Ravithat AU - Murphy, Gerald AU - Tassaneetrithep, Boonrat AU - Burgess, Timothy AU - Birx, Deborah AU - Hayes, Curtis AU - Schlesinger-Frankel, Sarah AU - Mascola, John AD - Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, U.S.A. Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 219 EP - 224 PB - Nature Publishing Group, The Macmillan Building London N1 9XW UK VL - 6 IS - 3 SN - 1087-0024, 1087-0024 KW - ASFA 3: Aquatic Pollution & Environmental Quality; ASFA 1: Biological Sciences & Living Resources; Virology & AIDS Abstracts KW - Dengue virus KW - Macrophages KW - Symptoms KW - Human diseases KW - Disease control KW - Biopsy KW - Infection KW - Public health KW - Flow cytometry KW - Dendritic cells KW - Dengue KW - ELISA KW - Monocytes KW - Enzyme-linked immunosorbent assay KW - Skin KW - Dermatology KW - Immunofluorescence KW - Dengue hemorrhagic fever KW - Shock KW - Tumor necrosis factor- alpha KW - Vaccines KW - Immunohistochemistry KW - V 22320:Replication KW - Q1 08485:Species interactions: pests and control KW - Q5 08524:Public health, medicines, dangerous organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/902345361?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Investigative+Dermatology+Symposium+Proceedings&rft.atitle=Human+Dendritic+Cells+as+Targets+of+Dengue+Virus+Infection&rft.au=Marovich%2C+Mary%3BGrouard-Vogel%2C+Geraldine%3BLouder%2C+Mark%3BEller%2C+Michael%3BSun%2C+Wellington%3BWu%2C+Shuenn-Ju%3BPutvatana%2C+Ravithat%3BMurphy%2C+Gerald%3BTassaneetrithep%2C+Boonrat%3BBurgess%2C+Timothy%3BBirx%2C+Deborah%3BHayes%2C+Curtis%3BSchlesinger-Frankel%2C+Sarah%3BMascola%2C+John&rft.aulast=Marovich&rft.aufirst=Mary&rft.date=2001-12-01&rft.volume=6&rft.issue=3&rft.spage=219&rft.isbn=&rft.btitle=&rft.title=Journal+of+Investigative+Dermatology+Symposium+Proceedings&rft.issn=10870024&rft_id=info:doi/10.1046%2Fj.0022-202x.2001.00037.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-11-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Macrophages; Flow cytometry; Symptoms; Human diseases; Disease control; ELISA; Vaccines; Immunofluorescence; Public health; Enzyme-linked immunosorbent assay; Skin; Dermatology; Biopsy; Infection; Dendritic cells; Dengue hemorrhagic fever; Shock; Dengue; Tumor necrosis factor- alpha; Monocytes; Immunohistochemistry; Dengue virus DO - http://dx.doi.org/10.1046/j.0022-202x.2001.00037.x ER - TY - JOUR T1 - Effects of levodopa on laryngeal muscle activity for voice onset and offset in Parkinson disease. AN - 85368210; pmid-11776365 AB - The laryngeal pathophysiology underlying the speech disorder in idiopathic Parkinson disease (IPD) was addressed in this electromyographic study of laryngeal muscle activity. This muscle activity was examined during voice onset and offset gestures in 6 persons in the early stages of IPD who were not receiving medication. The purpose was to determine (a) if impaired voice onset and offset control for speech and vocal fold bowing were related to abnormalities in laryngeal muscle activity in the nonmedicated state and (b) if these attributes change with levodopa. Blinded listeners rated the IPD participants' voice onset and offset control before and after levodopa was administered. In the nonmedicated state, the IPD participants' vocal fold bowing was examined on nasoendoscopy, and laryngeal muscle activity levels were compared with normal research volunteers. The IPD participants were then administered a therapeutic dose of levodopa, and changes in laryngeal muscle activity for voice onset and offset gestures were measured during the same session. Significant differences were found between IPD participants in the nonmedicated state: those with higher levels of muscle activation had vocal fold bowing and greater impairment in voice onset and offset control for speech. Similarly, following levodopa administration, those with thyroarytenoid muscle activity reductions had greater improvements in voice onset and offset control for speech. In this study, voice onset and offset control difficulties and vocal fold bowing were associated with increased levels of laryngeal muscle activity in the absence of medication. JF - Journal of speech, language, and hearing research : JSLHR AU - Gallena, S AU - Smith, P J AU - Zeffiro, T AU - Ludlow, C L AD - Laryngeal and Speech Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA. Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 1284 EP - 1299 VL - 44 IS - 6 SN - 1092-4388, 1092-4388 KW - Index Medicus KW - National Library of Medicine KW - Adult KW - *Antiparkinson Agents: administration & dosage KW - *Antiparkinson Agents: therapeutic use KW - Electromyography KW - Female KW - Humans KW - *Larynx: physiology KW - *Levodopa: pharmacology KW - *Levodopa: therapeutic use KW - Male KW - Middle Aged KW - *Muscle, Skeletal: drug effects KW - *Parkinson Disease: drug therapy KW - *Phonation: drug effects KW - Sound Spectrography KW - *Voice Quality: drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85368210?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+speech%2C+language%2C+and+hearing+research+%3A+JSLHR&rft.atitle=Effects+of+levodopa+on+laryngeal+muscle+activity+for+voice+onset+and+offset+in+Parkinson+disease.&rft.au=Gallena%2C+S%3BSmith%2C+P+J%3BZeffiro%2C+T%3BLudlow%2C+C+L&rft.aulast=Gallena&rft.aufirst=S&rft.date=2001-12-01&rft.volume=44&rft.issue=6&rft.spage=1284&rft.isbn=&rft.btitle=&rft.title=Journal+of+speech%2C+language%2C+and+hearing+research+%3A+JSLHR&rft.issn=10924388&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Immune responses and immunity in hepatitis C virus infection. AN - 85365230; pmid-11777207 JF - Journal of gastroenterology AU - Mizukoshi, E AU - Rehermann, B AD - Liver Diseases Section, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 799 EP - 808 VL - 36 IS - 12 SN - 0944-1174, 0944-1174 KW - Index Medicus KW - National Library of Medicine KW - *Hepacivirus: immunology KW - *Hepatitis C: immunology KW - Hepatitis C: prevention & control KW - Humans KW - *Immunity: immunology KW - Vaccines: immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85365230?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Public+money+and+management&rft.atitle=Debate%3A+Origins%2C+ambivalence+and+relevance+in+comparative+public+management+research&rft.au=Zhu%2C+Zhichang&rft.aulast=Zhu&rft.aufirst=Zhichang&rft.date=2014-11-01&rft.volume=34&rft.issue=6&rft.spage=407&rft.isbn=&rft.btitle=&rft.title=Public+money+and+management&rft.issn=09540962&rft_id=info:doi/10.1080%2F09540962.2014.962366 LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - What's new in the biology and treatment of undifferentiated carcinoma of nasopharyngeal type? AN - 85361970; pmid-11813890 JF - Acta oto-laryngologica AU - Carbone, A AU - Dolcetti, R AU - Shaha, A R AU - Gloghini, A AU - Molinari, R AU - Rinaldo, A AU - Boiocchi, M AU - Wei, W I AU - Ferlito, A AD - Division of Pathology, National Cancer Institute, IRCCS, Aviano, Italy. Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 884 EP - 895 VL - 121 IS - 8 SN - 0001-6489, 0001-6489 KW - Index Medicus KW - National Library of Medicine KW - Antineoplastic Combined Chemotherapy Protocols: therapeutic use KW - *Biology: methods KW - Carcinoma: pathology KW - *Carcinoma: therapy KW - Carcinoma: virology KW - Carcinoma, Squamous Cell: pathology KW - *Carcinoma, Squamous Cell: therapy KW - Carcinoma, Squamous Cell: virology KW - Combined Modality Therapy KW - DNA, Viral: genetics KW - Disease Progression KW - Epstein-Barr Virus Infections: immunology KW - Epstein-Barr Virus Infections: virology KW - Epstein-Barr Virus Nuclear Antigens: immunology KW - Humans KW - Intercellular Adhesion Molecule-1: immunology KW - Nasopharyngeal Neoplasms: etiology KW - Nasopharyngeal Neoplasms: pathology KW - *Nasopharyngeal Neoplasms: therapy KW - Viral Matrix Proteins: immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85361970?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+oto-laryngologica&rft.atitle=What%27s+new+in+the+biology+and+treatment+of+undifferentiated+carcinoma+of+nasopharyngeal+type%3F&rft.au=Carbone%2C+A%3BDolcetti%2C+R%3BShaha%2C+A+R%3BGloghini%2C+A%3BMolinari%2C+R%3BRinaldo%2C+A%3BBoiocchi%2C+M%3BWei%2C+W+I%3BFerlito%2C+A&rft.aulast=Carbone&rft.aufirst=A&rft.date=2001-12-01&rft.volume=121&rft.issue=8&rft.spage=884&rft.isbn=&rft.btitle=&rft.title=Acta+oto-laryngologica&rft.issn=00016489&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Genes required for ionizing radiation resistance in yeast AN - 839672263; 13746308 AB - The ability of Saccharomyces cerevisiae to tolerate ionizing radiation damage requires many DNA-repair and checkpoint genes, most having human orthologs. A genome-wide screen of diploid mutants homozygous with respect to deletions of 3,670 nonessential genes revealed 107 new loci that influence g-ray sensitivity. Many affect replication, recombination and checkpoint functions. Nearly 90% were sensitive to other agents, and most new genes could be assigned to the following functional groups: chromatin remodeling, chromosome segregation, nuclear pore formation, transcription, Golgi/vacuolar activities, ubiquitin-mediated protein degradation, cytokinesis, mitochondrial activity and cell wall maintenance. Over 50% share homology with human genes, including 17 implicated in cancer, indicating that a large set of newly identified human genes may have related roles in the toleration of radiation damage. JF - Nature Genetics AU - Bennett, Craig B AU - Lewis, LKevin AU - Karthikeyan, Gopalakrishnan AU - Lobachev, Kirill S AU - Jin, Yong H AU - Sterling, Joan F AU - Snipe, Joyce R AU - Resnick, Michael A AD - [1] Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. [2] Present addresses: Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA (C.B.B.); Department of Chemistry and Biochemistry, Southwest Texas State University, San Marcos, Texas 78666, USA (L.K.L.). Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 426 EP - 434 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 29 IS - 4 SN - 1061-4036, 1061-4036 KW - Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts C: Algology, Mycology & Protozoology; Toxicology Abstracts KW - Golgi apparatus KW - Chromatin remodeling KW - Diploids KW - Replication KW - Transcription KW - Mitochondria KW - Cancer KW - Saccharomyces cerevisiae KW - Recombination KW - Chromosomes KW - Homology KW - g Radiation KW - Cytokinesis KW - Ionizing radiation KW - Nuclear pores KW - gamma Radiation KW - Cell walls KW - X 24390:Radioactive Materials KW - N 14820:DNA Metabolism & Structure KW - K 03320:Cell Biology KW - G 07780:Fungi UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/839672263?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Genetics&rft.atitle=Genes+required+for+ionizing+radiation+resistance+in+yeast&rft.au=Bennett%2C+Craig+B%3BLewis%2C+LKevin%3BKarthikeyan%2C+Gopalakrishnan%3BLobachev%2C+Kirill+S%3BJin%2C+Yong+H%3BSterling%2C+Joan+F%3BSnipe%2C+Joyce+R%3BResnick%2C+Michael+A&rft.aulast=Bennett&rft.aufirst=Craig&rft.date=2001-12-01&rft.volume=29&rft.issue=4&rft.spage=426&rft.isbn=&rft.btitle=&rft.title=Nature+Genetics&rft.issn=10614036&rft_id=info:doi/10.1038%2Fng778 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-01-01 N1 - Last updated - 2016-02-04 N1 - SubjectsTermNotLitGenreText - Golgi apparatus; Diploids; Chromatin remodeling; Replication; Mitochondria; Transcription; Cancer; Recombination; Chromosomes; Homology; g Radiation; Ionizing radiation; Cytokinesis; Nuclear pores; gamma Radiation; Cell walls; Saccharomyces cerevisiae DO - http://dx.doi.org/10.1038/ng778 ER - TY - JOUR T1 - Exaggerated levothyroxine malabsorption due to calcium carbonate supplementation in gastrointestinal disorders. AN - 72405730; 11793625 AB - To describe a patient with primary hypothyroidism in whom ingestion of levothyroxine with calcium carbonate led to markedly elevated serum thyrotropin concentrations. A 61-year-old white woman with primary hypothyroidism, systemic lupus erythematosus, celiac disease, and history of Whipple resection for pancreatic cancer was euthyroid with levothyroxine 175-188 micrograms/d. After taking a high dose of calcium carbonate (1250 mg three times daily) with levothyroxine, she developed biochemical evidence of hypothyroidism (thyrotropin up to 41.4 mU/L) while remaining clinically euthyroid. Delaying calcium carbonate administration by four hours returned her serum thyrotropin to a borderline high concentration (5.7 mU/L) within a month. Serum concentrations of unbound and total thyroxine and triiodothyronine tended to decrease, but remained borderline low to normal while the patient concomitantly received levothyroxine and calcium carbonate. Concomitant administration of levothyroxine and calcium carbonate often results in levothyroxine malabsorption. While in most patients the clinical consequences of this interaction, even with prolonged exposure, are relatively small, overt hypothyrodism may develop in patients with preexisting malabsorption disorders. However, as the current case illustrates, the clinical manifestations of the initial levothyroxine deficit may not always be apparent and, of all usual laboratory thyroid function tests, only thyrotropin measurement will reliably uncover the exaggerated levothyroxine malabsorption. Decreased absorption of levothyroxine when given with calcium carbonate may be particularly pronounced in patients with preexisting malabsorption disorders. Once recognized, a change in drug administration schedule usually minimizes or eliminates this interaction. JF - The Annals of pharmacotherapy AU - Csako, G AU - McGriff, N J AU - Rotman-Pikielny, P AU - Sarlis, N J AU - Pucino, F AD - Department of Laboratory Medicine, Warren G Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, USA. gcsako@nih.gov Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 1578 EP - 1583 VL - 35 IS - 12 SN - 1060-0280, 1060-0280 KW - Antacids KW - 0 KW - Thyrotropin KW - 9002-71-5 KW - Calcium Carbonate KW - H0G9379FGK KW - Thyroxine KW - Q51BO43MG4 KW - Index Medicus KW - Lupus Erythematosus, Systemic -- complications KW - Thyrotropin -- blood KW - Celiac Disease -- complications KW - Humans KW - Middle Aged KW - Intestinal Absorption -- drug effects KW - Female KW - Thyroxine -- metabolism KW - Hypothyroidism -- drug therapy KW - Calcium Carbonate -- adverse effects KW - Thyroxine -- therapeutic use KW - Malabsorption Syndromes -- chemically induced KW - Hypothyroidism -- complications KW - Antacids -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72405730?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Abuse+%26+Neglect&rft.atitle=Self-reported+disciplinary+practices+among+women+in+the+child+welfare+system%3A+Association+with+domestic+violence+victimization&rft.au=Kelleher%2C+Kelly+J.%3BHazen%2C+Andrea+L.%3BCoben%2C+Jeffrey+H.%3BWang%2C+Yun%3BMcGeehan%2C+Jennifer%3BKohl%2C+Patricia+L.%3BGardner%2C+William+P.&rft.aulast=Kelleher&rft.aufirst=Kelly&rft.date=2008-08-01&rft.volume=32&rft.issue=8&rft.spage=811&rft.isbn=&rft.btitle=&rft.title=Child+Abuse+%26+Neglect&rft.issn=01452134&rft_id=info:doi/10.1016%2Fj.chiabu.2007.12.004 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-11 N1 - Date created - 2002-01-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The estimation and use of absolute risk for weighing the risks and benefits of selective estrogen receptor modulators for preventing breast cancer. AN - 72399639; 11795364 AB - In order to weigh the risks and benefits of intervention with selective estrogen response modifiers for preventing breast cancer, one needs to consider the effects of intervention on several health outcomes. For example, tamoxifen was shown to reduce the risks of breast cancer and hip fracture while increasing the risks of endometrial cancer and cardiovascular end points, including stroke. One approach to weighing risks and benefits is to estimate the net effect of the intervention on the absolute risk of each of the relevant health outcomes. To estimate this net effect, one needs to know not only the relative risk from the intervention, but also the absolute risk of the health outcome in the absence of intervention. Intervention trials yield unbiased estimates of intervention relative risks, but data are usually too limited to estimate these relative risks precisely for subgroups or for rare health outcomes. Moreover, intervention trials are usually too small to provide data for developing a model for estimating the individualized absolute risk of various health outcomes in the absence of intervention. The model of Gail et al. for projecting the individualized risk of breast cancer, as modified for use in the Breast Cancer Prevention Trial, has been validated. To weigh various risks and benefits of interventions, there is a need for research to develop such models for a range of health outcomes. JF - Annals of the New York Academy of Sciences AU - Gail, M H AD - National Cancer Institute, Bethesda, Maryland 20892, USA. Gailm@exchange.nih.gov Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 286 EP - 291 VL - 949 SN - 0077-8923, 0077-8923 KW - Selective Estrogen Receptor Modulators KW - 0 KW - Tamoxifen KW - 094ZI81Y45 KW - Index Medicus KW - Risk KW - Tamoxifen -- therapeutic use KW - Humans KW - Tamoxifen -- adverse effects KW - Female KW - Selective Estrogen Receptor Modulators -- adverse effects KW - Selective Estrogen Receptor Modulators -- therapeutic use KW - Breast Neoplasms -- prevention & control KW - Risk Assessment -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72399639?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=The+estimation+and+use+of+absolute+risk+for+weighing+the+risks+and+benefits+of+selective+estrogen+receptor+modulators+for+preventing+breast+cancer.&rft.au=Gail%2C+M+H&rft.aulast=Gail&rft.aufirst=M&rft.date=2001-12-01&rft.volume=949&rft.issue=&rft.spage=286&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-21 N1 - Date created - 2002-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The future of prostate cancer prevention. AN - 72398025; 11795434 AB - The dramatic international variation in prostate cancer mortality rates suggest an environmental influence. This combined with a building understanding of the genetic mechanisms of carcinogenesis encourages a search for ways to prevent it. Androgenic stimulation over a period of time has been suggested a cause of prostate cancer. The corollary to this hypothesis is that lowering androgenic stimulation over time will prevent prostate cancer. Decreasing androgenic stimulation of the prostate with 5-alpha-reductase inhibitors such as finasteride has been shown to decrease prostate size and may prevent prostate cancer. A large, long-term clinical trial is underway using finasteride to determine if it can prevent prostate cancer. Results are expected in 2004. Epidemiologic and laboratory studies also suggest that high selenium and vitamin E intake lowers risk of prostate cancer. Recent serendipitous findings of two randomized clinical trials support the hypothesis that selenium and vitamin administration will decrease prostate cancer risk. A study to assess these compounds is beginning. Other promising, but less developed, interventions in chemoprevention of prostate cancer include vitamin D supplementation and diet modification. All will need to be rigorously evaluated before they can be advocated for prostate cancer prevention. JF - Annals of the New York Academy of Sciences AU - Brawley, O W AU - Barnes, S AU - Parnes, H AD - Office of the Director, National Cancer Institute, Bethesda, Maryland 20852, USA. Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 145 EP - 152 VL - 952 SN - 0077-8923, 0077-8923 KW - 5-alpha Reductase Inhibitors KW - 0 KW - Androgen Antagonists KW - Androgens KW - Anticarcinogenic Agents KW - Antioxidants KW - Enzyme Inhibitors KW - Soybean Proteins KW - Vitamin A KW - 11103-57-4 KW - Vitamin D KW - 1406-16-2 KW - Vitamin E KW - 1406-18-4 KW - Finasteride KW - 57GNO57U7G KW - Selenium KW - H6241UJ22B KW - Index Medicus KW - Vitamin A -- therapeutic use KW - Multicenter Studies as Topic KW - Anticarcinogenic Agents -- therapeutic use KW - Androgen Antagonists -- therapeutic use KW - Humans KW - Finasteride -- therapeutic use KW - Vitamin E -- therapeutic use KW - Aged KW - Vitamin D -- therapeutic use KW - Adult KW - Treatment Outcome KW - Forecasting KW - Male KW - Prostatic Intraepithelial Neoplasia -- drug therapy KW - Randomized Controlled Trials as Topic KW - Enzyme Inhibitors -- therapeutic use KW - Double-Blind Method KW - Clinical Trials, Phase II as Topic KW - Clinical Trials, Phase III as Topic KW - Clinical Trials as Topic KW - Risk KW - Selenium -- therapeutic use KW - Soybean Proteins -- therapeutic use KW - Antioxidants -- therapeutic use KW - Middle Aged KW - Diet KW - Prostatic Neoplasms -- mortality KW - Adenocarcinoma -- mortality KW - Prostatic Neoplasms -- genetics KW - Neoplasms, Hormone-Dependent -- prevention & control KW - Prostatic Neoplasms -- prevention & control KW - Adenocarcinoma -- genetics KW - Adenocarcinoma -- prevention & control KW - Neoplasms, Hormone-Dependent -- mortality KW - Neoplasms, Hormone-Dependent -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72398025?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=The+future+of+prostate+cancer+prevention.&rft.au=Brawley%2C+O+W%3BBarnes%2C+S%3BParnes%2C+H&rft.aulast=Brawley&rft.aufirst=O&rft.date=2001-12-01&rft.volume=952&rft.issue=&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-13 N1 - Date created - 2002-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The future of colon cancer prevention. AN - 72395269; 11795446 AB - Chemoprevention science is in flux owing to rapid advances in postgenomic technology. We have witnessed enormous advances in the areas of early detection and molecular profiling of colorectal carcinogenesis; however, unique interpretive and technologic challenges persist. Neoplastic hallmarks must be iteratively tested and validated as markers of risk, targets for intervention, and/or markers of response in order to expedite the development of preventive interventions. In this review, we highlight several of the technologies that are revolutionizing our understanding of carcinogenesis and our approach to colorectal cancer prevention. JF - Annals of the New York Academy of Sciences AU - Umar, A AU - Viner, J L AU - Hawk, E T AD - Gastrointestinal & Other Cancers Research Group, National Cancer Institute, Division of Cancer Prevention, EPN, Bethesda, Maryland 20892-7317, USA. Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 88 EP - 108 VL - 952 SN - 0077-8923, 0077-8923 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Anticarcinogenic Agents KW - Biomarkers KW - Cyclooxygenase 2 Inhibitors KW - Cyclooxygenase Inhibitors KW - Enzyme Inhibitors KW - Isoenzymes KW - Membrane Proteins KW - Ornithine Decarboxylase Inhibitors KW - Proteome KW - Folic Acid KW - 935E97BOY8 KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Calcium KW - SY7Q814VUP KW - Eflornithine KW - ZQN1G5V6SR KW - Index Medicus KW - Animals KW - Receptor, Epidermal Growth Factor -- antagonists & inhibitors KW - Oligonucleotide Array Sequence Analysis KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Humans KW - Disease Progression KW - Folic Acid -- therapeutic use KW - Calcium -- therapeutic use KW - Models, Biological KW - Drug Design KW - Genes, APC KW - Adenoma -- prevention & control KW - Adenoma -- etiology KW - Forecasting KW - Drug Synergism KW - Eflornithine -- therapeutic use KW - Colonic Neoplasms -- genetics KW - Enzyme Inhibitors -- therapeutic use KW - Diagnostic Imaging KW - Clinical Trials as Topic KW - Mice KW - Colonic Neoplasms -- diagnosis KW - Isoenzymes -- antagonists & inhibitors KW - Cyclooxygenase Inhibitors -- therapeutic use KW - Risk KW - Colonic Neoplasms -- etiology KW - Colonic Neoplasms -- prevention & control KW - Adenoma -- genetics KW - Adenocarcinoma -- diagnosis KW - Colorectal Neoplasms -- diagnosis KW - Anticarcinogenic Agents -- therapeutic use KW - Adenocarcinoma -- etiology KW - Colorectal Neoplasms -- etiology KW - Adenocarcinoma -- genetics KW - Colorectal Neoplasms -- genetics KW - Adenocarcinoma -- prevention & control KW - Colorectal Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72395269?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=The+future+of+colon+cancer+prevention.&rft.au=Umar%2C+A%3BViner%2C+J+L%3BHawk%2C+E+T&rft.aulast=Umar&rft.aufirst=A&rft.date=2001-12-01&rft.volume=952&rft.issue=&rft.spage=88&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-13 N1 - Date created - 2002-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conclusions: Considerations regarding SERMs. AN - 72393695; 11795376 AB - The "considerations" addressed in this section consist of a number of thought-provoking issues and unresolved questions that emerge from the papers in this volume. The evidence for tamoxifen carcinogenicity in animal models and, to a more restricted extent, in humans has led some investigators to question whether SERMs are ready or appropriate for clinical testing--specifically, in a disease prevention setting involving healthy but high-risk individuals. There is, however, inconsistency in both efficacy and toxicity--specifically, carcinogenicity--between animal models and humans, leading others to question the value of basing the decision to proceed with clinical studies on preclinical results in animals. Although the molecular basis for SERM action is rapidly being clarified, the cellular activity of these agents is still elusive. We discuss the view that the efficacy of tamoxifen in breast cancer is based on its treatment of "occult cancers," or small collections of cancer cells that are not clinically apparent, not only in the context of prevention but also in the treatment setting. As part of our approach that assumes estrogen activity to be the foundation upon which SERM development is being modeled, we discuss the inconsistency between the epidemiologic data and prospective randomized data with respect to the relationship between estrogen use and cardiovascular disease. The need to validate surrogate markers of SERM action is discussed in relation to bone but is clearly relevant to all disease sites. The semantics used in describing SERM action as agonistic or antagonistic in relation to estrogen at various target sites has been inconsistent, especially in the clinical context. We attempt to dissect out some of the inconsistencies in semantics in the hope that this will contribute to improved communication of data resulting from SERM research. In the clinical arena, we begin with the premise that the large, simple randomized trial offers the optimal design for the testing of SERMs. In view of limited resources, however, we counter this position with alternative, if less desirable, approaches to the clinical format for SERM testing. Finally, we explore the process by which statistically meaningful results from clinical trials are extrapolated into the specific drug indications that apply to clinical practice. JF - Annals of the New York Academy of Sciences AU - Dunn, B K AU - Anthony, M AU - Sherman, S AU - Costantino, J P AD - Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20852, USA. dunnb@mail.nih.gov Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 352 EP - 365 VL - 949 SN - 0077-8923, 0077-8923 KW - Selective Estrogen Receptor Modulators KW - 0 KW - Index Medicus KW - Models, Animal KW - Osteoporosis -- prevention & control KW - Neoplasms -- drug therapy KW - Animals KW - Neoplasms -- pathology KW - Neoplasms -- classification KW - Humans KW - Osteoporosis -- classification KW - Clinical Trials as Topic -- standards KW - Research Design KW - Selective Estrogen Receptor Modulators -- standards KW - Selective Estrogen Receptor Modulators -- adverse effects KW - Selective Estrogen Receptor Modulators -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72393695?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Conclusions%3A+Considerations+regarding+SERMs.&rft.au=Dunn%2C+B+K%3BAnthony%2C+M%3BSherman%2C+S%3BCostantino%2C+J+P&rft.aulast=Dunn&rft.aufirst=B&rft.date=2001-12-01&rft.volume=949&rft.issue=&rft.spage=352&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-21 N1 - Date created - 2002-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. AN - 72393548; 11780065 AB - Inappropriate or prolonged inflammation is the main cause of many diseases; for this reason it is important to understand the physiological mechanisms that terminate inflammation in vivo. Agonists for several Gs-protein-coupled receptors, including cell-surface adenosine purinergic receptors, can increase levels of immunosuppressive cyclic AMP in immune cells; however, it was unknown whether any of these receptors regulates inflammation in vivo. Here we show that A2a adenosine receptors have a non-redundant role in the attenuation of inflammation and tissue damage in vivo. Sub-threshold doses of an inflammatory stimulus that caused minimal tissue damage in wild-type mice were sufficient to induce extensive tissue damage, more prolonged and higher levels of pro-inflammatory cytokines, and death of male animals deficient in the A2a adenosine receptor. Similar observations were made in studies of three different models of inflammation and liver damage as well as during bacterial endotoxin-induced septic shock. We suggest that A2a adenosine receptors are a critical part of the physiological negative feedback mechanism for limitation and termination of both tissue-specific and systemic inflammatory responses. JF - Nature AU - Ohta, A AU - Sitkovsky, M AD - Laboratory of Immunology, National Institute of Allegy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Bethesa, MD 20892-1892, USA. PY - 2001 SP - 916 EP - 920 VL - 414 IS - 6866 SN - 0028-0836, 0028-0836 KW - Cytokines KW - 0 KW - Inflammation Mediators KW - Receptors, Purinergic P1 KW - Concanavalin A KW - 11028-71-0 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Adenosine KW - K72T3FS567 KW - Index Medicus KW - Shock, Septic -- pathology KW - Animals KW - Liver -- pathology KW - Chemical and Drug Induced Liver Injury KW - Cytokines -- metabolism KW - Mice KW - Shock, Septic -- metabolism KW - Liver Diseases -- metabolism KW - Phenotype KW - GTP-Binding Proteins -- metabolism KW - Liver Diseases -- pathology KW - Mice, Inbred C57BL KW - T-Lymphocytes -- immunology KW - Male KW - Adenosine -- metabolism KW - Receptors, Purinergic P1 -- genetics KW - Receptors, Purinergic P1 -- physiology KW - Inflammation -- etiology KW - Inflammation -- metabolism KW - Inflammation Mediators -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72393548?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Public+money+and+management&rft.atitle=Meeting+in+the+middle%3A+joining+reflection+and+action+in+complex+public+sector+projects&rft.au=Duijn%2C+Michael%3BRijnveld%2C+Marc%3BHulst%2C+Merlijn+van&rft.aulast=Duijn&rft.aufirst=Michael&rft.date=2010-07-01&rft.volume=30&rft.issue=4&rft.spage=227&rft.isbn=&rft.btitle=&rft.title=Public+money+and+management&rft.issn=09540962&rft_id=info:doi/10.1080%2F09540962.2010.492183 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-31 N1 - Date created - 2002-01-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacologic advances in orofacial pain: from molecules to medicine. AN - 72392757; 11780658 AB - The management of chronic orofacial pain often follows a pattern of claims of efficacy based on clinical observations superseded by equivocal findings of effectiveness or belated recognition of toxicity. While therapeutic innovation spurred by genomics and proteomics is likely to result in new drugs for pain, inflammation, and neuropathic pain, the process of drug development and approval takes five to ten years and is often unsuccessful. Therapeutic strategies for improving treatment for chronic orofacial pain are proposed, but recognition of impediments to changing clinical practices suggest the need for interim measures. Greater understanding of the molecular and genetic events that contribute to pain chronicity and interindividual variations in pain responsiveness may eventually result in individualized molecular pain medicine to prevent and treat chronic orofacial pain. JF - Journal of dental education AU - Dionne, R A AD - National Institute of Dental and Craniofacial Research, NIH, USA. dionnera@yahoo.com Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 1393 EP - 1403 VL - 65 IS - 12 SN - 0022-0337, 0022-0337 KW - Analgesics KW - 0 KW - Analgesics, Opioid KW - Anti-Inflammatory Agents KW - Sensory System Agents KW - Dentistry KW - Index Medicus KW - Humans KW - Anti-Inflammatory Agents -- therapeutic use KW - Drug Design KW - Anti-Inflammatory Agents -- chemical synthesis KW - Molecular Biology KW - Analgesics -- chemical synthesis KW - Drug Approval KW - Sensory System Agents -- chemical synthesis KW - Analgesics, Opioid -- therapeutic use KW - Neuronal Plasticity -- drug effects KW - Chronic Disease KW - Sensory System Agents -- therapeutic use KW - Analgesics -- therapeutic use KW - Facial Pain -- prevention & control KW - Facial Pain -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72392757?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+dental+education&rft.atitle=Pharmacologic+advances+in+orofacial+pain%3A+from+molecules+to+medicine.&rft.au=Dionne%2C+R+A&rft.aulast=Dionne&rft.aufirst=R&rft.date=2001-12-01&rft.volume=65&rft.issue=12&rft.spage=1393&rft.isbn=&rft.btitle=&rft.title=Journal+of+dental+education&rft.issn=00220337&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-22 N1 - Date created - 2002-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ICCVAM evaluation of the murine local lymph node assay. Data analyses completed by the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods. AN - 72381116; 11754531 AB - To evaluate the reliability of the murine local lymph node assay (LLNA), a test for allergic contact dermatitis activity, the inter- and intralaboratory consistency statistics (h and k, respectively) were calculated for validation studies testing multiple chemicals. The analysis indicated the absence of excessive variability in the dose calculated to induce a threefold or greater increase in the stimulation index (SI). To assess the appropriateness of using an SI of 3 as the decision criteria for identifying a sensitizing compound, LLNA results based on SI values of 2.0, 2.5, 3.0, 3.5, and 4.0 were compared with guinea pig or human results. The results supported the use of an SI of 3 as the decision criteria. Assay performance was determined by comparing LLNA results to results obtained for guinea pigs or humans. The accuracy of the LLNA was 89% when compared with results from the guinea pig maximization test (GPMT)/Buehler assay (BA). The performance of the LLNA and the GPMT/BA was similar when each was compared to human maximization test results plus substances included as human patch test allergens. The LLNA offered advantages over the GPMT in respect to both the time required to conduct the test and the assay cost. JF - Regulatory toxicology and pharmacology : RTP AU - Haneke, K E AU - Tice, R R AU - Carson, B L AU - Margolin, B H AU - Stokes, W S AD - National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, National Institute of Environmental Health Sciences, MD EC-17, Research Triangle Park, NC 27709, USA. Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 274 EP - 286 VL - 34 IS - 3 SN - 0273-2300, 0273-2300 KW - Organic Chemicals KW - 0 KW - Index Medicus KW - United States KW - Sensitivity and Specificity KW - Animals KW - Reproducibility of Results KW - Guidelines as Topic -- standards KW - Environmental Exposure -- statistics & numerical data KW - Guideline Adherence KW - Guinea Pigs KW - Government Agencies -- economics KW - Humans KW - Environmental Exposure -- economics KW - Mice KW - Risk Assessment -- statistics & numerical data KW - Risk Assessment -- economics KW - Peer Review -- standards KW - Animal Welfare KW - Government Agencies -- statistics & numerical data KW - Lymph Nodes -- drug effects KW - Peer Review -- methods KW - Dermatitis, Allergic Contact -- etiology KW - Organic Chemicals -- toxicity KW - Interinstitutional Relations KW - Toxicity Tests -- statistics & numerical data KW - Dermatitis, Allergic Contact -- diagnosis KW - Toxicity Tests -- economics KW - Dermatitis, Allergic Contact -- economics KW - Toxicity Tests -- methods KW - Organic Chemicals -- analysis KW - Local Lymph Node Assay UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72381116?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.atitle=ICCVAM+evaluation+of+the+murine+local+lymph+node+assay.+Data+analyses+completed+by+the+National+Toxicology+Program+Interagency+Center+for+the+Evaluation+of+Alternative+Toxicological+Methods.&rft.au=Haneke%2C+K+E%3BTice%2C+R+R%3BCarson%2C+B+L%3BMargolin%2C+B+H%3BStokes%2C+W+S&rft.aulast=Haneke&rft.aufirst=K&rft.date=2001-12-01&rft.volume=34&rft.issue=3&rft.spage=274&rft.isbn=&rft.btitle=&rft.title=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.issn=02732300&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-26 N1 - Date created - 2001-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human immunodeficiency virus infection, aging, and cancer. AN - 72372851; 11750207 AB - HIV infection increases non-Hodgkin's lymphoma and Kaposi's sarcoma risk. Among HIV-uninfected persons, risk for these malignancies and others increases with age. As HIV-infected persons age, new patterns in cancer incidence may emerge. In this article, data from the AIDS-Cancer Registry Match study are presented on risk for Kaposi's sarcoma and lung cancer among persons with AIDS. For 132,346 homosexual men with AIDS, Kaposi's sarcoma incidence was highest for men 30-39 years old (5.0 cases/100 person-years) and declined with age (P(trend) <.0001). This trend likely arises from variation in Kaposi's sarcoma herpesvirus prevalence among homosexual men. For 239,257 adults with AIDS (all risk groups), lung cancer incidence increased with age, and was higher than in the general population (P <.0001), probably reflecting heavy smoking among HIV-infected adults. Identifying separate effects of HIV and aging on cancer risk will require detailed data on individuals' HIV infection status and exposures to known carcinogens. JF - Journal of clinical epidemiology AU - Engels, E A AD - Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., Room 8005, Rockville, MD 20852, USA. engelse@exchange.nih.gov Y1 - 2001/12// PY - 2001 DA - December 2001 SP - S29 EP - S34 VL - 54 Suppl 1 SN - 0895-4356, 0895-4356 KW - Index Medicus KW - Age Factors KW - Risk Factors KW - Humans KW - Incidence KW - Chronic Disease KW - United States -- epidemiology KW - Prevalence KW - Lymphoma, Non-Hodgkin -- epidemiology KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - HIV Infections -- complications KW - Lymphoma, Non-Hodgkin -- etiology KW - Sarcoma, Kaposi -- epidemiology KW - Sarcoma, Kaposi -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72372851?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+epidemiology&rft.atitle=Human+immunodeficiency+virus+infection%2C+aging%2C+and+cancer.&rft.au=Engels%2C+E+A&rft.aulast=Engels&rft.aufirst=E&rft.date=2001-12-01&rft.volume=54+Suppl+1&rft.issue=&rft.spage=S29&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+epidemiology&rft.issn=08954356&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-29 N1 - Date created - 2001-12-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) modulates lactogenic hormone-mediated differentiation and gene expression in HC11 mouse mammary epithelial cells. AN - 72368665; 11751460 AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mammary gland carcinogen in cooked meat. Using the HC11 mouse mammary epithelial cell line, a well-characterized model for hormone-mediated differentiation, we examined whether PhIP altered the expression of genes regulated by lactogenic hormones dexamethasone, insulin, and prolactin (DIP). When HC11-Lux cells (stably transfected with a beta-casein promoter luciferase construct) were cultured in DIP-containing medium, PhIP (100 microM) enhanced luciferase activity 11-fold over that observed in DIP medium alone. The effect of PhIP on augmenting luciferase activity was observed only when lactogenic hormones were included in the medium. Expression of the endogenous beta-casein gene was also higher in HC11 cells treated with PhIP in hormone-enriched medium. With the increased expression of beta-casein gene, the level of phospho-signal transducer and activator of transcription 5A (phospho-STAT5A), the transcription factor regulating beta-casein gene expression, was elevated in PhIP-exposed HC11 cells. AG490, a Janus kinase 2 (JAK2)-specific inhibitor, blocked the effect of PhIP on beta-casein gene expression. PhIP-treated cells also showed higher expression of Bcl-2 and lower expression of Bax, consistent with a possible antiapoptotic action of PhIP. The findings indicate that PhIP modulates lactogenic hormone-mediated gene expression in mammary epithelial cells, apparently via enhanced phosphorylation of STAT5A. The findings have implications for a novel mechanism of action of the mammary gland carcinogen PhIP. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Shan, L AU - Rouhani, S A AU - Schut, H A AU - Snyderwine, E G AD - Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 649 EP - 656 VL - 12 IS - 12 SN - 1044-9523, 1044-9523 KW - Bax protein, mouse KW - 0 KW - Carcinogens KW - Caseins KW - DNA Adducts KW - DNA-Binding Proteins KW - Enzyme Inhibitors KW - Imidazoles KW - Milk Proteins KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - STAT5 Transcription Factor KW - Stat5a protein, mouse KW - Trans-Activators KW - Tyrphostins KW - alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide KW - bcl-2-Associated X Protein KW - Prolactin KW - 9002-62-4 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Luciferases KW - EC 1.13.12.- KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Jak2 protein, mouse KW - EC 2.7.10.2 KW - Janus Kinase 2 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Index Medicus KW - Animals KW - Trans-Activators -- metabolism KW - Blotting, Northern KW - Proto-Oncogene Proteins -- metabolism KW - Promoter Regions, Genetic KW - Tumor Cells, Cultured KW - Phosphorylation KW - Tyrphostins -- pharmacology KW - Time Factors KW - Signal Transduction KW - DNA-Binding Proteins -- metabolism KW - Dose-Response Relationship, Drug KW - Luciferases -- metabolism KW - Mice KW - Protein-Tyrosine Kinases -- metabolism KW - DNA Adducts -- metabolism KW - Protein-Tyrosine Kinases -- antagonists & inhibitors KW - Caseins -- metabolism KW - Blotting, Western KW - Transfection KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Immunohistochemistry KW - Mammary Neoplasms, Animal -- metabolism KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Prolactin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72368665?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Public+money+and+management&rft.atitle=Will+practice-based+commissioning+in+the+English+NHS+resolve+the+problems+experienced+by+GP+fundholding%3F&rft.au=Greener%2C+Ian%3BMannion%2C+Russell&rft.aulast=Greener&rft.aufirst=Ian&rft.date=2008-08-01&rft.volume=28&rft.issue=4&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=Public+money+and+management&rft.issn=09540962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-04 N1 - Date created - 2001-12-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disruption of erythropoiesis by dioxin in the zebrafish. AN - 72366689; 11748828 AB - 2,3,7,8-Tetrachlorodibenzo-p- dioxin (TCDD, or dioxin) causes early life stage mortality in a variety of fish species. We have used the zebrafish (Danio rerio) to study the cardiovascular effects of TCDD treatment over the time course of zebrafish development. Early TCDD exposure (6 ng/ml) starting at 4 hr postfertilization (hpf) produced reductions in blood flow and in the number of circulating erythrocytes. These defects were consistently observable by 72 hpf. However, these responses were not observed when TCDD exposure was delayed until 96 hpf or later. These results suggest a model in which TCDD interferes with cardiovascular and erythropoietic developmental processes that are normally completed by 96 hpf. This model is strengthened by the finding that TCDD exposure blocks the step in hematopoiesis in which developing zebrafish switch from the primitive phase to the definitive phase of erythropoiesis. We observed no effect of TCDD on the levels of circulating primitive erythrocytes before 72 hpf and the expression of markers for early hematopoiesis, GATA-1 and GATA-2. However, early TCDD exposure prevented the appearance of definitive phase erythrocytes. TCDD produced a small delay in the migration of blood cells expressing SCL from the intermediate cell mass to the dorsal mesentery and dorsal aorta. Despite the decrease in blood flow produced by TCDD, confocal microscopy of the trunk vasculature by using a Tie2/green fluorescence protein endothelial marker at 48, 60, 72, and 96 hpf of TCDD-exposed (4 hpf) revealed no apparent defects in blood vessel structure. Copyright 2001 Wiley-Liss, Inc. JF - Developmental dynamics : an official publication of the American Association of Anatomists AU - Belair, C D AU - Peterson, R E AU - Heideman, W AD - NIEHS Developmental and Molecular Toxicology Center and School of Pharmacy, University of Wisconsin, Madison 53705, USA. Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 581 EP - 594 VL - 222 IS - 4 SN - 1058-8388, 1058-8388 KW - Environmental Pollutants KW - 0 KW - Polychlorinated Dibenzodioxins KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Embryo, Nonmammalian -- physiology KW - Blood Vessels -- embryology KW - Blood Circulation -- drug effects KW - Anemia -- chemically induced KW - Cardiovascular System -- embryology KW - Embryo, Nonmammalian -- drug effects KW - Hematopoiesis -- genetics KW - Erythropoiesis -- drug effects KW - Environmental Pollutants -- poisoning KW - Polychlorinated Dibenzodioxins -- poisoning KW - Zebrafish -- embryology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72366689?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Public+money+and+management&rft.atitle=New+development%3A+leading+Lean+action+to+transform+housing+services&rft.au=McQuade%2C+David&rft.aulast=McQuade&rft.aufirst=David&rft.date=2008-02-01&rft.volume=28&rft.issue=1&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=Public+money+and+management&rft.issn=09540962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-05 N1 - Date created - 2001-12-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rapid lipopolysaccharide-induced differentiation of CD14(+) monocytes into CD83(+) dendritic cells is modulated under serum-free conditions by exogenously added IFN-gamma and endogenously produced IL-10. AN - 72358770; 11745398 AB - We showed previously that about half of purified CD14(+) peripheral blood monocytes cultured under serum-free conditions and treated with GM-CSF and bacterial LPS rapidly (2 - 4 day) differentiate into CD83(+) dendritic cells (DC). The remaining cells retain the CD14(+)/CD83(-) monocyte/macrophage phenotype. In order to identify factors that influence whether monocytes differentiate into DC or remain on the monocyte/macrophage developmental pathway, we evaluated the effects of exogenously added IFN-gamma and endogenously produced IL-10 on the proportion and function of CD14(+) monocytes that adopt DC characteristics in response to LPS. IFN-gamma priming dramatically increased the proportion of monocytes that adopted stable DC characteristics in response to LPS, improved their T cell allosensitizing capacity, and enhanced levels of secreted IL-12 heterodimer. IFN-gamma priming also suppressed the production of IL-10, a cytokine known to have inhibitory effects on DC differentiation. When monocytes were treated with LPS plus IL-10-neutralizing antibodies, dramatically enhanced DC differentiation, IL-12 secretion, and T cell allosensitizing capacity were observed, mimicking in many respects the effects of IFN-gamma priming. IFN-gamma primed cells still displayed appreciable sensitivity to exogenously added IL-10, suggesting that attenuated IL-10 secretion is partially responsible for the enhancing effects of IFN-gamma. These studies therefore identify IFN-gamma as a DC differentiation co-factor for CD14(+) monocytes, and IL-10 as an autocrine/paracrine inhibitor of DC differentiation, linking these agents for the first time as mutually opposed regulators that govern whether CD14(+) cells differentiate into DC upon contact with LPS or remain on the monocyte/macrophage developmental pathway. JF - European journal of immunology AU - Koski, G K AU - Lyakh, L A AU - Rice, N R AD - Regulation of Cell Growth Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, USA. dendritic_cell@hotmail.com Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 3773 EP - 3781 VL - 31 IS - 12 SN - 0014-2980, 0014-2980 KW - Antigens, CD KW - 0 KW - Antigens, CD14 KW - CD83 antigen KW - Culture Media, Serum-Free KW - Immunoglobulins KW - Lipopolysaccharides KW - Membrane Glycoproteins KW - Proto-Oncogene Proteins KW - RELB protein, human KW - Transcription Factors KW - Interleukin-10 KW - 130068-27-8 KW - Transcription Factor RelB KW - 147337-75-5 KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Proto-Oncogene Proteins -- biosynthesis KW - Antigen-Presenting Cells -- physiology KW - Humans KW - Lymphocyte Culture Test, Mixed KW - Drug Synergism KW - Cell Differentiation -- drug effects KW - Transcription Factors -- biosynthesis KW - Immunophenotyping KW - Immunoglobulins -- analysis KW - Monocytes -- physiology KW - Lipopolysaccharides -- pharmacology KW - Antigens, CD14 -- analysis KW - Dendritic Cells -- drug effects KW - Monocytes -- drug effects KW - Membrane Glycoproteins -- analysis KW - Interferon-gamma -- pharmacology KW - Dendritic Cells -- physiology KW - Interleukin-10 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72358770?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Public+money+and+management&rft.atitle=Performance+strategy+and+accounting+in+local+government+and+higher+education+in+the+UK&rft.au=Broad%2C+Martin%3BGoddard%2C+Andrew%3BAlberti%2C+Larissa+Von&rft.aulast=Broad&rft.aufirst=Martin&rft.date=2007-04-01&rft.volume=13&rft.issue=4&rft.spage=312&rft.isbn=&rft.btitle=&rft.title=T%C3%BCrk+Psikiyatri+Dergisi&rft.issn=13002163&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-24 N1 - Date created - 2001-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Smoking and use of hair treatments in relation to risk of developing systemic lupus erythematosus. AN - 72354189; 11764212 AB - To examine the association between smoking and hair treatments (dyes, permanents) and risk of developing systemic lupus erythematosus (SLE). Patients (n = 265) diagnosed between January 1, 1995, and July 31, 1999, were recruited through 4 university based and 30 community based rheumatology practices in eastern North Carolina and South Carolina. Controls (n = 355) were identified through driver's license records and were frequency matched to patients by age, sex, and state. Data collection included a 60 min in-person interview. Analyses were limited to experiences that occurred before age at diagnosis (patients) or reference age (controls). Because the prevalence of use of hair treatments among men was very low, the analyses of those exposures were limited to women. There was no association with smoking history and risk of developing SLE when analyzed as status (current, former, or never-smoker) or measures of dose (duration or pack-years). Use of permanent hair dyes in women was associated with a small increased risk of developing SLE (OR 1.5, 95% CI 1.0, 2.2). This association increased with longer duration of use (compared with nonusers, OR 1.7, 95% CI 1.0, 2.7 for 6 or more years). There was little evidence of an association between SLE and use of temporary dyes or of permanents and straighteners. These results suggest at most a weak association between SLE risk and permanent hair dyes or smoking. Genetic variability in the metabolism of these products may be important to assess in future studies. JF - The Journal of rheumatology AU - Cooper, G S AU - Dooley, M A AU - Treadwell, E L AU - St Clair, E W AU - Gilkeson, G S AD - From the Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina 27709, USA. cooper1@niehs.nih.gov Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 2653 EP - 2656 VL - 28 IS - 12 SN - 0315-162X, 0315-162X KW - Hair Dyes KW - 0 KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Risk Factors KW - Humans KW - Case-Control Studies KW - North Carolina -- epidemiology KW - Male KW - Female KW - South Carolina -- epidemiology KW - Smoking -- adverse effects KW - Hair Dyes -- adverse effects KW - Lupus Erythematosus, Systemic -- epidemiology KW - Lupus Erythematosus, Systemic -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72354189?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+rheumatology&rft.atitle=Smoking+and+use+of+hair+treatments+in+relation+to+risk+of+developing+systemic+lupus+erythematosus.&rft.au=Cooper%2C+G+S%3BDooley%2C+M+A%3BTreadwell%2C+E+L%3BSt+Clair%2C+E+W%3BGilkeson%2C+G+S&rft.aulast=Cooper&rft.aufirst=G&rft.date=2001-12-01&rft.volume=&rft.issue=&rft.spage=312&rft.isbn=978-0-231-15180-1&rft.btitle=Child+welfare+for+the+twenty-first+century%3A+A+handbook+of+practices%2C+policies%2C+and+programs+%282nd+ed.%29&rft.title=Child+welfare+for+the+twenty-first+century%3A+A+handbook+of+practices%2C+policies%2C+and+programs+%282nd+ed.%29&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-02 N1 - Date created - 2001-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A protective role for cyclooxygenase-2 in drug-induced liver injury in mice. AN - 72350809; 11743745 AB - Despite the utility of cyclooxygenase (COX) inhibition as an antiinflammatory strategy, prostaglandin (PG) products of COX-1 and -2 provide important regulatory functions in some pathophysiological states. Scattered reports suggest that COX inhibition may also promote adverse drug events. Here we demonstrate a protective role for endogenous COX-derived products in a murine model of acetaminophen (APAP)-induced acute liver injury. A single hepatotoxic dose caused the selective induction of COX-2 mRNA and increased PGD2 and PGE2 levels within the livers of COX(+/+) male mice suggesting a role for COX-2 in this model of liver injury. APAP-induced hepatotoxicity and lethality were markedly greater in COX-2(-/-) and (-/+) mice in which normal PG responsiveness is altered. The significantly increased toxicity linked to COX-2 deficiency could be mimicked using the selective COX-2 inhibitory drug, celecoxib, in COX(+/+) mice and was not due to alterations in drug-protein adduct formation, a surrogate for bioactivation and toxicity. Microarray analyses indicated that increased injury associated with COX-2 deficiency coincided, most notably, with a profoundly impaired induction of heat shock proteins in COX-2(-/+) mice suggesting that PGs may act as critical endogenous stress signals following drug insult. These findings suggest that COX-2-derived mediators serve an important hepato-protective function and that COX inhibition may contribute to the risk of drug-induced liver injury, possibly through both nonimmunological and immunological pathways. JF - Chemical research in toxicology AU - Reilly, T P AU - Brady, J N AU - Marchick, M R AU - Bourdi, M AU - George, J W AU - Radonovich, M F AU - Pise-Masison, C A AU - Pohl, L R AD - Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, NHLBI, NIH, 9000 Rockville Pike, Building 10, Room 8N110, Bethesda, Maryland 20892-1760, USA. ReillyT@nhlbi.nih.gov Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 1620 EP - 1628 VL - 14 IS - 12 SN - 0893-228X, 0893-228X KW - Cyclooxygenase 2 Inhibitors KW - 0 KW - Cyclooxygenase Inhibitors KW - DNA Primers KW - Isoenzymes KW - Pyrazoles KW - RNA, Messenger KW - Sulfonamides KW - Acetaminophen KW - 362O9ITL9D KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - Prostaglandin-Endoperoxide Synthases KW - Celecoxib KW - JCX84Q7J1L KW - Dinoprostone KW - K7Q1JQR04M KW - Prostaglandin D2 KW - RXY07S6CZ2 KW - Index Medicus KW - Animals KW - Liver -- enzymology KW - Dinoprostone -- biosynthesis KW - Oligonucleotide Array Sequence Analysis KW - Disease Models, Animal KW - Sulfonamides -- pharmacology KW - Liver -- drug effects KW - Acetaminophen -- toxicity KW - Male KW - Immunoblotting KW - Liver -- pathology KW - Prostaglandin D2 -- biosynthesis KW - RNA, Messenger -- analysis KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Cyclooxygenase Inhibitors -- pharmacology KW - Gene Expression Profiling KW - Survival Rate KW - RNA, Messenger -- metabolism KW - Mice, Knockout -- genetics KW - Mice, Inbred C57BL KW - DNA Primers -- chemistry KW - Isoenzymes -- antagonists & inhibitors KW - Chemical and Drug Induced Liver Injury -- mortality KW - Chemical and Drug Induced Liver Injury -- pathology KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Isoenzymes -- genetics KW - Chemical and Drug Induced Liver Injury -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72350809?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=A+protective+role+for+cyclooxygenase-2+in+drug-induced+liver+injury+in+mice.&rft.au=Reilly%2C+T+P%3BBrady%2C+J+N%3BMarchick%2C+M+R%3BBourdi%2C+M%3BGeorge%2C+J+W%3BRadonovich%2C+M+F%3BPise-Masison%2C+C+A%3BPohl%2C+L+R&rft.aulast=Reilly&rft.aufirst=T&rft.date=2001-12-01&rft.volume=19&rft.issue=4&rft.spage=206&rft.isbn=&rft.btitle=&rft.title=Journal+of+Pediatric+Health+Care&rft.issn=08915245&rft_id=info:doi/10.1016%2Fj.pedhc.2005.02.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-28 N1 - Date created - 2001-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tests for order restrictions in binary data. AN - 72349286; 11764263 AB - In this article, a general procedure is presented for testing for equality of k independent binary response probabilities against any given ordered alternative. The proposed methodology is based on an estimation procedure developed in Hwang and Peddada (1994, Annals of Statistics 22, 67-93) and can be used for a very broad class of order restrictions. The procedure is illustrated through application to two data sets that correspond to three commonly encountered order restrictions: simple tree order, simple order, and down turn order. JF - Biometrics AU - Peddada, S D AU - Prescott, K E AU - Conaway, M AD - Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. peddada@niehs.nih.gov Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 1219 EP - 1227 VL - 57 IS - 4 SN - 0006-341X, 0006-341X KW - Index Medicus KW - Animals KW - Humans KW - Data Interpretation, Statistical KW - Models, Statistical KW - Likelihood Functions KW - Clinical Trials as Topic -- statistics & numerical data KW - Carcinogenicity Tests -- statistics & numerical data KW - Biometry -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72349286?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometrics&rft.atitle=Tests+for+order+restrictions+in+binary+data.&rft.au=Peddada%2C+S+D%3BPrescott%2C+K+E%3BConaway%2C+M&rft.aulast=Peddada&rft.aufirst=S&rft.date=2001-12-01&rft.volume=57&rft.issue=4&rft.spage=1219&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-03 N1 - Date created - 2001-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer genetics fundamentals. AN - 72346150; 11762507 AB - It is often said that cancer is genetic. What exactly does that mean? This article is our answer to that question at the turn of the millennium. We present models of carcinogenesis, review basic cancer genetics terminology, and explain some of the fundamental genetic changes common to all types of cancer. These are organized into 6 sections of (1) self-sufficiency in growth signals, (2) insensitivity to growth-inhibitory signals, (3) evasion of programmed cell death, (4) limitless replicative potential, (5) sustained angiogenesis, and (6) tissue invasion and metastases. Underlying all of these changes are the even more fundamental enabling factors of genetic instability on both the chromosomal and the gene level. Finally, we look toward the future in a field where the future is now! JF - Cancer nursing AU - Peters, J AU - Loud, J AU - Dimond, E AU - Jenkins, J AD - Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20852, USA. petersju@mail.nih.gov Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 446 EP - 61; quiz 462 VL - 24 IS - 6 SN - 0162-220X, 0162-220X KW - Index Medicus KW - Nursing KW - Gene Expression Regulation, Neoplastic KW - Neoplastic Processes KW - Humans KW - Terminology as Topic KW - Oncogenic Viruses KW - Neoplasms -- physiopathology KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72346150?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Social+Science+%26+Medicine&rft.atitle=Domestic+violence+and+child+nutrition+in+Liberia&rft.au=Sobkoviak%2C+Rudina+M.%3BYount%2C+Kathryn+M.%3BHalim%2C+Nafisa&rft.aulast=Sobkoviak&rft.aufirst=Rudina&rft.date=2012-01-01&rft.volume=74&rft.issue=2&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Social+Science+%26+Medicine&rft.issn=02779536&rft_id=info:doi/10.1016%2Fj.socscimed.2011.10.024 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-28 N1 - Date created - 2001-12-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury. AN - 72342184; 11737586 AB - Acute renal failure (ARF) is caused by ischemic and nephrotoxic insults acting alone or in combination. Anti-inflammatory agents have been shown to decrease renal ischemia-reperfusion and cisplatin-induced injury and leukocyte infiltration. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that inhibits inflammatory and cytotoxic pathways implicated in acute renal injury. Therefore, we sought to determine if IL-10 inhibits acute renal injury. The effects of IL-10 were studied in mice following cisplatin administration and bilateral renal ischemia-reperfusion, in a rat model of renal transplantation, and in cultured mouse cortical tubule cells. IL-10 significantly decreased renal injury following cisplatin administration and following renal ischemia/reperfusion. Delay of IL-10 treatment for one hour after cisplatin also significantly inhibited renal damage. IL-10 and alpha-melanocyte stimulating hormone (alpha-MSH) increased recovery following transplantation of a kidney subjected to warm ischemia. To explore the mechanism of action of IL-10, its effects were measured on mediators of leukocyte trafficking and inducible nitric oxide synthase (NOS-II). IL-10 inhibited cisplatin and ischemia-induced increases in mRNA for tumor necrosis factor-alpha (TNF-alpha), intercellular adhesion molecule-1 (ICAM-1), and NOS-II. IL-10 also inhibited staining for markers of apoptosis and cell cycle activity following cisplatin administration, and nitric oxide production in cultured mouse cortical tubules. IL-10 protects against renal ischemic and cisplatin-induced injury. IL-10 may act, in part, by inhibiting the maladaptive activation of genes that cause leukocyte activation and adhesion, and induction of iNOS. JF - Kidney international AU - Deng, J AU - Kohda, Y AU - Chiao, H AU - Wang, Y AU - Hu, X AU - Hewitt, S M AU - Miyaji, T AU - McLeroy, P AU - Nibhanupudy, B AU - Li, S AU - Star, R A AD - Renal Diagnostics and Therapeutics Unit, NIDDK, and Laboratory of Pathology, NCI, National Institutes of Health, Bethesda, Maryland 20892-1268, USA. Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 2118 EP - 2128 VL - 60 IS - 6 SN - 0085-2538, 0085-2538 KW - Interleukin-10 KW - 130068-27-8 KW - alpha-MSH KW - 581-05-5 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Animals KW - Rats, Inbred Lew KW - Kidney Transplantation KW - Mice KW - Mice, Inbred BALB C KW - alpha-MSH -- pharmacology KW - Rats KW - Kidney Tubules -- cytology KW - Cells, Cultured KW - Kidney Tubules -- drug effects KW - Preservation, Biological KW - Mice, Inbred C57BL KW - Time Factors KW - Reperfusion Injury -- pathology KW - Male KW - Renal Circulation KW - Kidney -- pathology KW - Interleukin-10 -- administration & dosage KW - Kidney -- drug effects KW - Cisplatin -- pharmacology KW - Interleukin-10 -- pharmacology KW - Ischemia -- pathology KW - Kidney -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72342184?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Kidney+international&rft.atitle=Interleukin-10+inhibits+ischemic+and+cisplatin-induced+acute+renal+injury.&rft.au=Deng%2C+J%3BKohda%2C+Y%3BChiao%2C+H%3BWang%2C+Y%3BHu%2C+X%3BHewitt%2C+S+M%3BMiyaji%2C+T%3BMcLeroy%2C+P%3BNibhanupudy%2C+B%3BLi%2C+S%3BStar%2C+R+A&rft.aulast=Deng&rft.aufirst=J&rft.date=2001-12-01&rft.volume=60&rft.issue=6&rft.spage=2118&rft.isbn=&rft.btitle=&rft.title=Kidney+international&rft.issn=00852538&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-29 N1 - Date created - 2001-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sudden cardiac death and antipsychotic drugs: do we know enough? AN - 72336382; 11735846 JF - Archives of general psychiatry AU - Zarate, C A AU - Patel, J AD - Mood Disorders Research Unit, National Institute of Mental Health Mood and Anxiety Disorders Program, National Institutes of Health, 9000 Rockville Pike, Bldg 10, Unit 3 West, Room 3s250, Bethesda, MD 20892, USA. zaratec@intra.nimh.nih.gov Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 1168 EP - 1171 VL - 58 IS - 12 SN - 0003-990X, 0003-990X KW - Antipsychotic Agents KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Risk KW - Dose-Response Relationship, Drug KW - Humans KW - Tennessee -- epidemiology KW - Adult KW - Retrospective Studies KW - Aged KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Cause of Death KW - Antipsychotic Agents -- administration & dosage KW - Death, Sudden, Cardiac -- epidemiology KW - Antipsychotic Agents -- adverse effects KW - Death, Sudden, Cardiac -- etiology KW - Psychotic Disorders -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72336382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+general+psychiatry&rft.atitle=Sudden+cardiac+death+and+antipsychotic+drugs%3A+do+we+know+enough%3F&rft.au=Zarate%2C+C+A%3BPatel%2C+J&rft.aulast=Zarate&rft.aufirst=C&rft.date=2001-12-01&rft.volume=58&rft.issue=12&rft.spage=1168&rft.isbn=&rft.btitle=&rft.title=Archives+of+general+psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-28 N1 - Date created - 2001-12-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Arch Gen Psychiatry. 2001 Dec;58(12):1161-7 [11735845] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxin-labeled monoclonal antibodies. AN - 72332217; 11762413 AB - To arm monoclonal antibodies (MAbs) with the power to kill malignant cells, they have been connected to toxins to create chimeric proteins called immunotoxins. Conventional immunotoxins contain a MAb chemically conjugated to a toxin which is mutated or chemically modified to minimize binding to normal cells. Examples include anti-B4-blocked ricin, targeting CD5, and RFB4-deglycosylated ricin A chain, targeting CD22. Conventional immunotoxins are capable of inducing responses in patients with hematologic malignancies, with dose-limiting toxicities being vascular leak syndrome, thrombocytopenia, and hepatic damage. Newer immunotoxins contain a recombinant ligand, either the variable domains (Fv) of a MAb, or a growth factor, fused to a truncated bacterial toxin. Bacterial toxins commonly used for this purpose include diphtheria toxin and Pseudomonas exotoxin. DAB389lL2 (Ontak) is a recently approved growth factor fusion toxin containing human interleukin-2 and diphtheria toxin and is effective in chemotherapy-resistant cutaneous T-cell lymphoma. Anti-Tac(Fv)-PE38 (LMB-2) and RFB4(dsFv)-PE38 (BL22) are two recombinant immunotoxins, targeting CD25 and CD22, respectively, in which Fvs of MAbs targeting these antigens are fused to truncated Pseudomonas exotoxin. Both LMB-2 and BL22 have exhibited clinical activity in patients with hematologic malignancies, with less vascular leak syndrome and probably less immunogenicity than the larger conventional immunotoxin conjugates. New recombinant immunotoxins are currently being engineered and developed to target other hematologic and solid tumor antigens. JF - Current pharmaceutical biotechnology AU - Kreitman, R J AD - Laboratory of Molecular Biology, Division of Cancer Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 313 EP - 325 VL - 2 IS - 4 SN - 1389-2010, 1389-2010 KW - Antibodies, Monoclonal KW - 0 KW - Immunotoxins KW - Index Medicus KW - Animals KW - Humans KW - Hematologic Neoplasms -- therapy KW - Immunotoxins -- adverse effects KW - Immunotoxins -- therapeutic use KW - Antibodies, Monoclonal -- adverse effects KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72332217?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+pharmaceutical+biotechnology&rft.atitle=Toxin-labeled+monoclonal+antibodies.&rft.au=Kreitman%2C+R+J&rft.aulast=Kreitman&rft.aufirst=R&rft.date=2001-12-01&rft.volume=2&rft.issue=4&rft.spage=313&rft.isbn=&rft.btitle=&rft.title=Current+pharmaceutical+biotechnology&rft.issn=13892010&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-13 N1 - Date created - 2001-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chromosomal breakage syndromes and the BRCA1 genome surveillance complex. AN - 72325916; 11733219 AB - Chromosomal instability can occur when the DNA damage response and repair process fails, resulting in syndromes characterized by growth abnormalities, hematopoietic defects, mutagen sensitivity, and cancer predisposition. Mutations in ATM, NBS1, MRE11, BLM, WRN, and FANCD2 are responsible for ataxia telangiectasia (AT), Nijmegen breakage syndrome, AT-like disorder, Bloom and Werner syndrome, and Fanconi anemia group D2, respectively. This diverse group of disorders is thought to be linked through protein interactions with the breast cancer tumor susceptibility gene product, BRCA1. BRCA1 forms a multi-subunit protein complex referred to as the BRCA1-associated genome surveillance complex (BASC), which includes DNA damage repair proteins such as MSH2-MSH6 and MLH1, as well as ATM, NBS1, MRE11, and BLM. Although still controversial, this finding suggests similarities in the pathogenesis of the human chromosome breakage syndromes and a complementary role for each protein in DNA structure surveillance or damage repair. JF - Trends in molecular medicine AU - Futaki, M AU - Liu, J M AD - Hematology Branch, NHLBI, National Institutes of Health, Building 10, Room 7C103, Bethesda, MD 20892, USA. Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 560 EP - 565 VL - 7 IS - 12 SN - 1471-4914, 1471-4914 KW - BRCA1 Protein KW - 0 KW - BRCA2 Protein KW - Macromolecular Substances KW - Protein Subunits KW - Index Medicus KW - Animals KW - Syndrome KW - Humans KW - BRCA2 Protein -- metabolism KW - Models, Biological KW - DNA Damage -- genetics KW - BRCA2 Protein -- genetics KW - DNA Repair -- genetics KW - Abnormalities, Multiple -- genetics KW - BRCA1 Protein -- genetics KW - BRCA1 Protein -- metabolism KW - Abnormalities, Multiple -- metabolism KW - Chromosome Breakage -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72325916?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Affilia%3A+Journal+of+Women+%26+Social+Work&rft.atitle=Graduating+social+work+students%27+perspectives+on+domestic+violence&rft.au=Black%2C+Beverly+M.%3BWeisz%2C+Arlene+N.%3BBennett%2C+Larry+W.&rft.aulast=Black&rft.aufirst=Beverly&rft.date=2010-05-01&rft.volume=25&rft.issue=2&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Affilia%3A+Journal+of+Women+%26+Social+Work&rft.issn=08861099&rft_id=info:doi/10.1177%2F0886109910364824 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-17 N1 - Date created - 2001-12-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Trends Mol Med 2002 Jan;8(1):49 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. AN - 72314716; 11729030 AB - This study determined if augmentation of neuroleptics with 3 g/day of ethyl eicosapentaenoic acid (EPA) improves symptoms and cognition in patients with schizophrenia or schizoaffective disorder. Eighty-seven patients meeting criteria for schizophrenia or schizoaffective disorder who had residual symptoms despite neuroleptic treatment were randomly assigned to receive either 3 g/day of ethyl EPA (N=43) or placebo (N=44) in a 16-week, double-blind supplementation trial. Assessments were performed at baseline and at weeks 1, 2, 4, 8, 12, and 16; a cognitive battery was administered at baseline and at week 16. No differences were found between groups in positive or negative symptoms, mood, cognition, or global impression ratings. Results were similar for the intention-to-treat (N=87) and completer (N=75) groups. For schizophrenia patients treated with 3 g/day of ethyl EPA, improvement in residual symptoms and cognitive impairment was no greater than for schizophrenia patients treated with placebo. JF - The American journal of psychiatry AU - Fenton, W S AU - Dickerson, F AU - Boronow, J AU - Hibbeln, J R AU - Knable, M AD - NIMH, NIH, Bethesda, MD 20892-9621, USA. wfenton@mail.nih.gov Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 2071 EP - 2074 VL - 158 IS - 12 SN - 0002-953X, 0002-953X KW - Antipsychotic Agents KW - 0 KW - eicosapentaenoic acid ethyl ester KW - 6GC8A4PAYH KW - Eicosapentaenoic Acid KW - AAN7QOV9EA KW - Abridged Index Medicus KW - Index Medicus KW - Drug Therapy, Combination KW - Antipsychotic Agents -- administration & dosage KW - Psychiatric Status Rating Scales KW - Double-Blind Method KW - Humans KW - Adult KW - Treatment Outcome KW - Neurologic Examination -- drug effects KW - Middle Aged KW - Antipsychotic Agents -- adverse effects KW - Male KW - Female KW - Cognition Disorders -- diagnosis KW - Psychotic Disorders -- psychology KW - Eicosapentaenoic Acid -- administration & dosage KW - Cognition Disorders -- drug therapy KW - Schizophrenia -- diagnosis KW - Eicosapentaenoic Acid -- analogs & derivatives KW - Schizophrenic Psychology KW - Schizophrenia -- drug therapy KW - Psychotic Disorders -- diagnosis KW - Cognition Disorders -- psychology KW - Psychotic Disorders -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72314716?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=A+placebo-controlled+trial+of+omega-3+fatty+acid+%28ethyl+eicosapentaenoic+acid%29+supplementation+for+residual+symptoms+and+cognitive+impairment+in+schizophrenia.&rft.au=Fenton%2C+W+S%3BDickerson%2C+F%3BBoronow%2C+J%3BHibbeln%2C+J+R%3BKnable%2C+M&rft.aulast=Fenton&rft.aufirst=W&rft.date=2001-12-01&rft.volume=158&rft.issue=12&rft.spage=2071&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-02 N1 - Date created - 2001-11-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Psychiatry. 2003 Jan;160(1):188-9; author reply 189 [12505833] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The CYP2D6 humanized mouse: effect of the human CYP2D6 transgene and HNF4alpha on the disposition of debrisoquine in the mouse. AN - 72307918; 11723233 AB - CYP2D6 is a highly polymorphic human gene responsible for a large variability in the disposition of more than 100 drugs to which humans may be exposed. Animal models are inadequate for preclinical pharmacological evaluation of CYP2D6 substrates because of marked species differences in CYP2D isoforms. To overcome this issue, a transgenic mouse line expressing the human CYP2D6 gene was generated. The complete wild-type CYP2D6 gene, including its regulatory sequence, was microinjected into a fertilized FVB/N mouse egg, and the resultant offspring were genotyped by both polymerase chain reaction and Southern blotting. CYP2D6-specific protein expression was detected in the liver, intestine, and kidney from only the CYP2D6 humanized mice. Pharmacokinetic analysis revealed that debrisoquine (DEB) clearance was markedly higher (94.1 +/- 22.3 l/h/kg), and its half-life significantly reduced (6.9 +/- 1.6 h), in CYP2D6 humanized mice compared with wild-type animals (15.2 +/- 0.9 l/h/kg and 16.5 +/- 4.5 h, respectively). Mutations in hepatic nuclear factor 4alpha (HNF4alpha), a hepatic transcription factor known to regulate in vitro expression of the CYP2D6 gene, could affect the disposition of CYP2D6 drug substrates. To determine whether the HNF4alpha gene modulates in vivo pharmacokinetics of CYP2D6 substrates, a mouse line carrying both the CYP2D6 gene and the HNF4alpha conditional mutation was generated and phenotyped using DEB. After deletion of HNF4alpha, DEB 4-hydroxylase activity in CYP2D6 humanized mice decreased more than 50%. The data presented in this study show that only CYP2D6 humanized mice but not wild-type mice display significant DEB 4-hydroxylase activity and that HNF4alpha regulates CYP2D6 activity in vivo. The CYP2D6 humanized mice represent an attractive model for future preclinical studies on the pharmacology, toxicology, and physiology of CYP2D6-mediated metabolism. JF - Molecular pharmacology AU - Corchero, J AU - Granvil, C P AU - Akiyama, T E AU - Hayhurst, G P AU - Pimprale, S AU - Feigenbaum, L AU - Idle, J R AU - Gonzalez, F J AD - Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 1260 EP - 1267 VL - 60 IS - 6 SN - 0026-895X, 0026-895X KW - Adrenergic Agents KW - 0 KW - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors KW - DNA-Binding Proteins KW - HNF4A protein, human KW - Hepatocyte Nuclear Factor 4 KW - Hnf4a protein, mouse KW - MLX protein, human KW - Phosphoproteins KW - Tcfl4 protein, mouse KW - Transcription Factors KW - Cytochrome P-450 CYP2D6 KW - EC 1.14.14.1 KW - Debrisoquin KW - X31CDK040E KW - Index Medicus KW - Animals KW - Alleles KW - Gene Transfer Techniques KW - Adrenergic Agents -- pharmacokinetics KW - Humans KW - Mice, Knockout -- metabolism KW - Mice KW - Gene Dosage KW - Male KW - Gene Deletion KW - Cytochrome P-450 CYP2D6 -- genetics KW - Mice, Transgenic -- metabolism KW - Phosphoproteins -- genetics KW - Cytochrome P-450 CYP2D6 -- metabolism KW - Transcription Factors -- metabolism KW - Debrisoquin -- pharmacokinetics KW - Transcription Factors -- genetics KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72307918?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=The+CYP2D6+humanized+mouse%3A+effect+of+the+human+CYP2D6+transgene+and+HNF4alpha+on+the+disposition+of+debrisoquine+in+the+mouse.&rft.au=Corchero%2C+J%3BGranvil%2C+C+P%3BAkiyama%2C+T+E%3BHayhurst%2C+G+P%3BPimprale%2C+S%3BFeigenbaum%2C+L%3BIdle%2C+J+R%3BGonzalez%2C+F+J&rft.aulast=Corchero&rft.aufirst=J&rft.date=2001-12-01&rft.volume=60&rft.issue=6&rft.spage=1260&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-21 N1 - Date created - 2001-11-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Mol Pharmacol 2002 Jan;61(1):248 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A bold new direction for environmental health research. AN - 72307730; 11726375 AB - The biotechnology revolution has opened new opportunities for addressing current inadequacies in decision making regarding environmental health. Strategic investments need to be made (1) to develop high-throughput technologies that could accelerate toxicity testing and generate a mechanistic understanding of toxicity, (2) to incorporate individual susceptibility into risk assessments, and (3) to establish a rational basis for testing and regulatory decision making. New initiatives of the National Institute of Environmental Health Sciences, including the Environmental Genome Project and the Toxicogenomics Center, are discussed. JF - American journal of public health AU - Olden, K AU - Guthrie, J AU - Newton, S AD - National Institute of Environmental Health Sciences and the National Toxicology Program, Research Triangle Park, NC, USA. olden@niehs.nih.gov Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 1964 EP - 1967 VL - 91 IS - 12 SN - 0090-0036, 0090-0036 KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Mutagenicity Tests -- methods KW - Humans KW - Health Policy KW - Decision Making KW - Research Design KW - Risk Assessment KW - Environmental Health -- trends UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72307730?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Interpersonal+Violence&rft.atitle=Coverage+of+domestic+violence+fatalities+by+newspapers+in+Washington+State&rft.au=Bullock%2C+Cathy+Ferrand%3BCubert%2C+Jason&rft.aulast=Bullock&rft.aufirst=Cathy&rft.date=2002-05-01&rft.volume=17&rft.issue=5&rft.spage=475&rft.isbn=&rft.btitle=&rft.title=Journal+of+Interpersonal+Violence&rft.issn=08862605&rft_id=info:doi/10.1177%2F0886260502017005001 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-21 N1 - Date created - 2001-11-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Epidemiology. 1998 Mar;9(2):211-2 [9504294] Science. 2000 Jul 28;289(5479):536-7 [10939962] N Engl J Med. 2000 Jul 13;343(2):78-85 [10891514] Environ Health Perspect. 1998 Jul;106(7):365-8 [9637792] Science. 1997 Oct 24;278(5338):569-70 [9381162] Nat Genet. 1998 Feb;18(2):91-3 [9462728] Nat Rev Genet. 2000 Nov;1(2):149-53 [11253655] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor suppressor genes: at the crossroads of molecular carcinogenesis, molecular epidemiology and human risk assessment. AN - 72299603; 11720736 AB - The p53 tumor suppressor gene is mutated in about half of all human cancer cases. The p53 protein modulates multiple cellular functions, such as gene transcription, DNA synthesis and repair, cell cycle arrest, senescence, and apoptosis. Mutations in the p53 gene can abrogate these functions and may lead to genetic instability and progress to cancer. The molecular archeology of the p53 mutation spectrum generates hypotheses concerning the etiology and molecular pathogenesis of cancer. The spectrum of somatic mutations in the p53 gene implicates environmental carcinogens and endogenous processes in the etiology of human cancer. The presence of a characteristic p53 mutation also can manifest a molecular link between exposure to a particular carcinogen and a specific type of human cancer, e.g. aflatoxin B1 (AFB1) exposure and codon 249ser mutations in hepatocellular carcinoma, ultraviolet (UV) exposure and CC to TT tandem mutations in skin cancer, and cigarette smoke and the prevalence of G to T transversions in lung cancer. Although several different exogenous carcinogens have been shown to selectively target p53, evidence supporting the endogenous insult of p53 from oxyradical and nitrogen-oxyradicals is accumulating. p53 mutations can be a biomarker of carcinogen effect. Determining the characteristic p53 mutation load in nontumorous tissue, with a highly sensitive mutation assay, can indicate a specific carcinogen exposure and also may help in identifying individuals at an increased risk of cancer. JF - Lung cancer (Amsterdam, Netherlands) AU - Hussain, S P AU - Hofseth, L J AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, 37 Convent Drive, MSC 4255, Bethesda, MD 20892, USA. Y1 - 2001/12// PY - 2001 DA - December 2001 SP - S7 EP - 15 VL - 34 Suppl 2 SN - 0169-5002, 0169-5002 KW - Carcinogens KW - 0 KW - Free Radical Scavengers KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Skin Neoplasms -- genetics KW - Nitric Oxide -- adverse effects KW - Skin Neoplasms -- etiology KW - Humans KW - Oxidative Stress KW - Point Mutation KW - Smoking -- adverse effects KW - Free Radical Scavengers -- adverse effects KW - Risk Assessment KW - Genetic Testing KW - Lung Neoplasms -- etiology KW - Genes, Tumor Suppressor KW - Genes, p53 -- genetics KW - Lung Neoplasms -- genetics KW - Genetic Predisposition to Disease KW - Cell Transformation, Neoplastic KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72299603?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3A&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Transcultural+Nursing&rft.atitle=Conceptualizing+partner+abuse+among+South+Asian+women+in+Hong+Kong&rft.au=Tonsing%2C+Jenny+Chingkhannem&rft.aulast=Tonsing&rft.aufirst=Jenny&rft.date=2014-07-01&rft.volume=25&rft.issue=3&rft.spage=281&rft.isbn=&rft.btitle=&rft.title=Journal+of+Transcultural+Nursing&rft.issn=10436596&rft_id=info:doi/10.1177%2F1043659614522650 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-05 N1 - Date created - 2001-11-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolism of (R)-(+)-pulegone in F344 rats. AN - 72294132; 11717176 AB - (R)-(+)-Pulegone, a monoterpene ketone, is a major component of pennyroyal oil. Ingestion of high doses of pennyroyal oil has caused severe toxicity and occasionally death. Studies have shown that metabolites of pulegone were responsible for the toxicity. Previous metabolism studies have used high, near lethal doses and isolation and analysis techniques that may cause degradation of some metabolites. To clarify these issues and further explore the metabolic pathways, a study of (14)C-labeled pulegone in F344 rats at doses from 0.8 to 80 mg/kg has been conducted. High-pressure liquid chromatography (HPLC) analysis of the collected urine showed the metabolism of pulegone to be extensive and complex. Fourteen metabolites were isolated by HPLC and characterized by NMR, UV, and mass spectroscopy. The results demonstrated that pulegone was metabolized by three major pathways: 1) hydroxylation to give monohydroxylated pulegones, followed by glucuronidation or further metabolism; 2) reduction of the carbon-carbon double bond to give diastereomeric menthone/isomenthone, followed by hydroxylation and glucuronidation; and 3) Michael addition of glutathione to pulegone, followed by further metabolism to give diastereomeric 8-(N-acetylcystein-S-yl)menthone/isomenthone. This 1,4-addition not only took place in vivo but also in vitro under catalysis of glutathione S-transferase or mild base. Several hydroxylated products of the two mercapturic acids were also observed. Contrary to the previous study, all but one of the major metabolites characterized in the present study are phase II metabolites, and most of the metabolites in free forms are structurally different from those previously identified phase I metabolites. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Chen, L J AU - Lebetkin, E H AU - Burka, L T AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. ferguso2@niehs.nih.gov Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 1567 EP - 1577 VL - 29 IS - 12 SN - 0090-9556, 0090-9556 KW - Monoterpenes KW - 0 KW - Menthol KW - 1490-04-6 KW - pulegone KW - 4LF2673R3G KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Animals KW - Stereoisomerism KW - Glutathione -- metabolism KW - Microsomes, Liver -- metabolism KW - Hydrolysis KW - Chromatography, High Pressure Liquid KW - Hydroxylation KW - Magnetic Resonance Spectroscopy KW - Rats KW - Rats, Inbred F344 KW - Biotransformation KW - Glutathione -- urine KW - Female KW - Male KW - Menthol -- pharmacokinetics KW - Menthol -- analogs & derivatives KW - Mentha -- chemistry KW - Menthol -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72294132?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.atitle=Metabolism+of+%28R%29-%28%2B%29-pulegone+in+F344+rats.&rft.au=Chen%2C+L+J%3BLebetkin%2C+E+H%3BBurka%2C+L+T&rft.aulast=Chen&rft.aufirst=L&rft.date=2001-12-01&rft.volume=29&rft.issue=12&rft.spage=1567&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.issn=00909556&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-31 N1 - Date created - 2001-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential effects of physiologically relevant hypoxic conditions on T lymphocyte development and effector functions. AN - 72292658; 11714773 AB - Direct measurements revealed low oxygen tensions (0.5-4.5% oxygen) in murine lymphoid organs in vivo. To test whether adaptation to changes in oxygen tension may have an effect on lymphocyte functions, T cell differentiation and functions at varying oxygen tensions were studied. These studies show: 1) differentiated CTL deliver Fas ligand- and perforin-dependent lethal hit equally well at all redox conditions; 2) CTL development is delayed at 2.5% oxygen as compared with 20% oxygen. Remarkably, development of CTL at 2.5% oxygen is more sustained and the CTL much more lytic; and 3) hypoxic exposure and TCR-mediated activation are additive in enhancing levels of hypoxia response element-containing gene products in lymphocyte supernatants. In contrast, hypoxia inhibited the accumulation of nonhypoxia response element-containing gene products (e.g., IL-2 and IFN-gamma) in the same cultures. This suggests that T cell activation in hypoxic conditions in vivo may lead to different patterns of lymphokine secretion and accumulation of cytokines (e.g., vascular endothelial growth factor) affecting endothelial cells and vascular permeabilization. Thus, although higher numbers of cells survive and are activated during 20% oxygen incubation in vitro, the CTL which develop at 2.5% oxygen are more lytic with higher levels of activation markers. It is concluded that the ambient 20% oxygen tension (plus 2-ME) is remarkably well suited for immunologic specificity and cytotoxicity studies, but oxygen dependence should be taken into account during the design and interpretation of results of in vitro T cell development assays and gene expression studies in vivo. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Caldwell, C C AU - Kojima, H AU - Lukashev, D AU - Armstrong, J AU - Farber, M AU - Apasov, S G AU - Sitkovsky, M V AD - Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA. Y1 - 2001/12/01/ PY - 2001 DA - 2001 Dec 01 SP - 6140 EP - 6149 VL - 167 IS - 11 SN - 0022-1767, 0022-1767 KW - Antigens, CD95 KW - 0 KW - Cytokines KW - DNA-Binding Proteins KW - Fas Ligand Protein KW - Fasl protein, mouse KW - Hif1a protein, mouse KW - Hypoxia-Inducible Factor 1 KW - Hypoxia-Inducible Factor 1, alpha Subunit KW - Ligands KW - Lymphocyte Function-Associated Antigen-1 KW - Membrane Glycoproteins KW - Nuclear Proteins KW - Pore Forming Cytotoxic Proteins KW - Receptor-CD3 Complex, Antigen, T-Cell KW - Receptors, Antigen, T-Cell KW - Transcription Factors KW - Perforin KW - 126465-35-8 KW - Oxygen KW - S88TT14065 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Nuclear Proteins -- genetics KW - CD8-Positive T-Lymphocytes -- metabolism KW - Oxygen -- metabolism KW - Cytokines -- secretion KW - Receptor-CD3 Complex, Antigen, T-Cell -- metabolism KW - DNA-Binding Proteins -- genetics KW - Response Elements -- immunology KW - Cell Differentiation -- genetics KW - Receptors, Antigen, T-Cell -- physiology KW - Cell Differentiation -- immunology KW - Lymphoid Tissue -- metabolism KW - Lymphocyte Count KW - Antigens, CD95 -- metabolism KW - Lymphoid Tissue -- cytology KW - Lymphocyte Function-Associated Antigen-1 -- metabolism KW - T-Lymphocytes, Cytotoxic -- cytology KW - Lymphocyte Culture Test, Mixed KW - Oxygen -- physiology KW - T-Lymphocytes, Cytotoxic -- immunology KW - Cytotoxicity, Immunologic -- genetics KW - Mice KW - T-Lymphocytes, Cytotoxic -- metabolism KW - Mice, Inbred DBA KW - CD8-Positive T-Lymphocytes -- cytology KW - Membrane Glycoproteins -- toxicity KW - Cells, Cultured KW - CD8-Positive T-Lymphocytes -- immunology KW - Mice, Inbred C57BL KW - T-Lymphocyte Subsets -- metabolism KW - T-Lymphocyte Subsets -- cytology KW - Cell Hypoxia -- genetics KW - T-Lymphocyte Subsets -- secretion KW - T-Lymphocyte Subsets -- immunology KW - Cell Hypoxia -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72292658?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Differential+effects+of+physiologically+relevant+hypoxic+conditions+on+T+lymphocyte+development+and+effector+functions.&rft.au=Caldwell%2C+C+C%3BKojima%2C+H%3BLukashev%2C+D%3BArmstrong%2C+J%3BFarber%2C+M%3BApasov%2C+S+G%3BSitkovsky%2C+M+V&rft.aulast=Caldwell&rft.aufirst=C&rft.date=2001-12-01&rft.volume=167&rft.issue=11&rft.spage=6140&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-02 N1 - Date created - 2001-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos. AN - 72291052; 11714865 AB - CYP3A4 is the most abundant isoform of cytochrome P450 (CYP) in adult human liver. It metabolizes numerous clinically, physiologically, and toxicologically important compounds. The expression of CYP3A4 varies 40-fold in individual human livers, and metabolism of CYP3A4 substrates varies at least 10-fold in vivo. Single nucleotide polymorphisms (SNPs) in CYP3A4 were identified by direct sequencing of genomic DNA in 72 individuals from three different ethnic groups, including Caucasians, Blacks (African-Americans and African pygmies), and Asians. A total of 28 SNPs were identified, including five which produced coding changes M445T (CYP3A4*3), R162Q (CYP3A4*15), F189S (CYP3A4*17), L293P (CYP3A4*18), and P467S (CYP3A4*19). The latter four represent new alleic variants. Racial variability was observed for the frequency of individual SNPs. CYP3A R162Q was identified only in Black populations with an allelic frequency of 4%. CYP3A4 F189S and CYP3A4 M445T were identified in Caucasians with allelic frequencies 2% and 4%, respectively. L293P and P467S were only observed in Asians at allelic frequencies of 2%. The cDNAs for the F189S, L293P, M445T, and P467S mutant alleles were constructed by site-directed mutagenesis and expressed in an Escherichia coli expression system. Testosterone and the insecticide chlorpyrifos were used to assess the catalytic activities of the most common CYP3A4 allele (CYP3A4*1) and its allelic variants. CYP3A4 F189S exhibited lower turnover numbers for testosterone and chlorpyrifos, while CYP3A4 L293P had higher turnover numbers for both substrates. The turnover numbers of the CYP3A4 M445T and P467S alleles to metabolize these compounds were not significantly different from those of wild-type CYP3A4. JF - The Journal of pharmacology and experimental therapeutics AU - Dai, D AU - Tang, J AU - Rose, R AU - Hodgson, E AU - Bienstock, R J AU - Mohrenweiser, H W AU - Goldstein, J A AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 825 EP - 831 VL - 299 IS - 3 SN - 0022-3565, 0022-3565 KW - Cholinesterase Inhibitors KW - 0 KW - Testosterone KW - 3XMK78S47O KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - CYP3A4 protein, human KW - EC 1.14.13.67 KW - CYP3A protein, human KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP3A KW - Chlorpyrifos KW - JCS58I644W KW - Index Medicus KW - Alleles KW - Genome, Human KW - Gene Frequency KW - Polymorphism, Genetic KW - Models, Molecular KW - Humans KW - Sequence Analysis, DNA KW - Cholinesterase Inhibitors -- metabolism KW - Mixed Function Oxygenases -- chemistry KW - Mixed Function Oxygenases -- metabolism KW - Testosterone -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- chemistry KW - Cytochrome P-450 Enzyme System -- metabolism KW - Mixed Function Oxygenases -- genetics KW - Chlorpyrifos -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72291052?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Identification+of+variants+of+CYP3A4+and+characterization+of+their+abilities+to+metabolize+testosterone+and+chlorpyrifos.&rft.au=Dai%2C+D%3BTang%2C+J%3BRose%2C+R%3BHodgson%2C+E%3BBienstock%2C+R+J%3BMohrenweiser%2C+H+W%3BGoldstein%2C+J+A&rft.aulast=Dai&rft.aufirst=D&rft.date=2001-12-01&rft.volume=299&rft.issue=3&rft.spage=825&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-20 N1 - Date created - 2001-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Absence of delta -9-tetrahydrocannabinol dysphoric effects in dynorphin-deficient mice. AN - 72290868; 11717384 AB - The involvement of dynorphin on Delta-9-tetrahydrocannabinol (THC) and morphine responses has been investigated by using mice with a targeted inactivation of the prodynorphin (Pdyn) gene. Dynorphin-deficient mice show specific changes in the behavioral effects of THC, including a reduction of spinal THC analgesia and the absence of THC-induced conditioned place aversion. In contrast, acute and chronic opioid effects were normal. The lack of negative motivational effects of THC in the absence of dynorphin demonstrates that this endogenous opioid peptide mediates the dysphoric effects of marijuana. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Zimmer, A AU - Valjent, E AU - Konig, M AU - Zimmer, A M AU - Robledo, P AU - Hahn, H AU - Valverde, O AU - Maldonado, R AD - Laboratory of Genetics, National Institute of Mental Health, Bethesda, Maryland 20892, USA. Y1 - 2001/12/01/ PY - 2001 DA - 2001 Dec 01 SP - 9499 EP - 9505 VL - 21 IS - 23 KW - Analgesics, Opioid KW - 0 KW - Enkephalins KW - Narcotics KW - Protein Precursors KW - Receptors, Opioid, kappa KW - Dynorphins KW - 74913-18-1 KW - Morphine KW - 76I7G6D29C KW - Dronabinol KW - 7J8897W37S KW - preproenkephalin KW - 93443-35-7 KW - Index Medicus KW - Animals KW - Enkephalins -- genetics KW - Receptors, Opioid, kappa -- genetics KW - Receptors, Opioid, kappa -- drug effects KW - Avoidance Learning -- drug effects KW - Receptors, Opioid, kappa -- deficiency KW - Narcotics -- pharmacology KW - Mice, Knockout KW - Morphine -- pharmacology KW - Analgesia KW - Spatial Behavior -- drug effects KW - Enkephalins -- deficiency KW - Analgesics, Opioid -- pharmacology KW - Motor Activity -- drug effects KW - Male KW - Motor Activity -- genetics KW - Motivation KW - Brain Chemistry KW - Protein Precursors -- genetics KW - Mice KW - Protein Precursors -- deficiency KW - Mice, Mutant Strains KW - Mice, Inbred C57BL KW - Pain Measurement -- drug effects KW - Gene Targeting KW - Female KW - Substance-Related Disorders -- physiopathology KW - Behavior, Animal -- drug effects KW - Dynorphins -- analysis KW - Dronabinol -- pharmacology KW - Dynorphins -- genetics KW - Dynorphins -- deficiency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72290868?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Absence+of+delta+-9-tetrahydrocannabinol+dysphoric+effects+in+dynorphin-deficient+mice.&rft.au=Zimmer%2C+A%3BValjent%2C+E%3BKonig%2C+M%3BZimmer%2C+A+M%3BRobledo%2C+P%3BHahn%2C+H%3BValverde%2C+O%3BMaldonado%2C+R&rft.aulast=Zimmer&rft.aufirst=A&rft.date=2001-12-01&rft.volume=21&rft.issue=23&rft.spage=9499&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-11 N1 - Date created - 2001-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Compartmental pharmacokinetics and tissue distribution of the antifungal echinocandin lipopeptide micafungin (FK463) in rabbits. AN - 72281259; 11709303 AB - The plasma pharmacokinetics and tissue distribution of the novel antifungal echinocandin-like lipopeptide micafungin (FK463) were investigated in healthy rabbits. Cohorts of three animals each received micafungin at 0.5, 1, and 2 mg/kg of body weight intravenously once daily for a total of 8 days. Serial plasma samples were collected on days 1 and 7, and tissue samples were obtained 30 min after the eighth dose. Drug concentrations were determined by validated high-performance liquid chromatographic methods. Plasma drug concentration data were fit to a two-compartment pharmacokinetic model, and pharmacokinetic parameters were estimated using weighted nonlinear least-square regression analysis. Micafungin demonstrated linear plasma pharmacokinetics without changes in total clearance and dose-normalized area under the concentration-time curve from 0 h to infinity. After administration of single doses to the rabbits, mean peak plasma drug concentrations ranged from 7.62 microg/ml at 0.5 mg/kg to 16.8 microg/ml at 2 mg/kg, the area under the concentration-time curve from 0 to 24 h ranged from 5.66 to 21.79 microg x h/ml, the apparent volume of distribution at steady state ranged from 0.296 to 0.343 liter/kg, and the elimination half-life ranged from 2.97 to 3.20 h, respectively. No significant changes in pharmacokinetic parameters and no accumulation was noted after multiple dosing. Mean tissue micafungin concentrations 30 min after the last of eight daily doses were highest in the lung (2.26 to 11.76 microg/g), liver (2.05 to 8.82 microg/g), spleen (1.87 to 9.05 microg/g), and kidney (1.40 to 6.12 microg/g). While micafungin was not detectable in cerebrospinal fluid, the concentration in brain tissue ranged from 0.08 to 0.18 microg/g. These findings indicate linear disposition of micafungin at dosages of 0.5 to 2 mg/kg and achievement of potentially therapeutic drug concentrations in plasma and tissues that are common sites of invasive fungal infections. JF - Antimicrobial agents and chemotherapy AU - Groll, A H AU - Mickiene, D AU - Petraitis, V AU - Petraitiene, R AU - Ibrahim, K H AU - Piscitelli, S C AU - Bekersky, I AU - Walsh, T J AD - Immunocompromised Host Section, Pediatric Oncology Branch National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 3322 EP - 3327 VL - 45 IS - 12 SN - 0066-4804, 0066-4804 KW - Antifungal Agents KW - 0 KW - Echinocandins KW - Lipopeptides KW - Lipoproteins KW - Peptides, Cyclic KW - micafungin KW - R10H71BSWG KW - Index Medicus KW - Animals KW - Area Under Curve KW - Spectrophotometry, Ultraviolet KW - Rabbits KW - Tissue Distribution KW - Female KW - Chromatography, High Pressure Liquid KW - Lipoproteins -- pharmacokinetics KW - Peptides, Cyclic -- administration & dosage KW - Lipoproteins -- administration & dosage KW - Antifungal Agents -- pharmacokinetics KW - Antifungal Agents -- adverse effects KW - Peptides, Cyclic -- adverse effects KW - Lipoproteins -- adverse effects KW - Antifungal Agents -- administration & dosage KW - Peptides, Cyclic -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72281259?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Compartmental+pharmacokinetics+and+tissue+distribution+of+the+antifungal+echinocandin+lipopeptide+micafungin+%28FK463%29+in+rabbits.&rft.au=Groll%2C+A+H%3BMickiene%2C+D%3BPetraitis%2C+V%3BPetraitiene%2C+R%3BIbrahim%2C+K+H%3BPiscitelli%2C+S+C%3BBekersky%2C+I%3BWalsh%2C+T+J&rft.aulast=Groll&rft.aufirst=A&rft.date=2001-12-01&rft.volume=45&rft.issue=12&rft.spage=3322&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-04 N1 - Date created - 2001-11-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Antimicrob Agents Chemother. 2000 Jan;44(1):57-62 [10602723] Annu Rev Microbiol. 1994;48:471-97 [7826015] Antimicrob Agents Chemother. 2000 Mar;44(3):619-21 [10681328] Antimicrob Agents Chemother. 2000 Apr;44(4):1108-11 [10722525] Antimicrob Agents Chemother. 2000 Jun;44(6):1728-30 [10817741] J Infect Dis. 2000 Jul;182(1):274-82 [10882607] J Antimicrob Chemother. 2000 Sep;46(3):485-7 [10980180] J Antibiot (Tokyo). 2000 Oct;53(10):1175-81 [11132964] Antimicrob Agents Chemother. 2001 Feb;45(2):596-600 [11158761] Antimicrob Agents Chemother. 2001 Oct;45(10):2845-55 [11557479] J Pharmacokinet Biopharm. 1978 Apr;6(2):165-75 [671222] Lab Anim Sci. 1988 Aug;38(4):467-71 [3184859] Scand J Infect Dis Suppl. 1990;74:23-33 [2097711] Antimicrob Agents Chemother. 1991 Jul;35(7):1321-8 [1929288] Diagn Microbiol Infect Dis. 1997 Dec;29(4):227-31 [9458979] Clin Infect Dis. 1996 May;22 Suppl 2:S166-78 [8722846] J Med Vet Mycol. 1997 Mar-Apr;35(2):79-86 [9147267] J Antimicrob Chemother. 1997 Nov;40(5):611-4 [9421307] Diagn Microbiol Infect Dis. 1999 Feb;33(2):75-80 [10091029] Antimicrob Agents Chemother. 1999 Apr;43(4):830-5 [10103187] Antimicrob Agents Chemother. 1999 Sep;43(9):2148-55 [10471556] J Antibiot (Tokyo). 1999 Jul;52(7):674-6 [10513849] Clin Microbiol Rev. 1993 Jan;6(1):1-21 [8457977] Antimicrob Agents Chemother. 2000 Mar;44(3):614-8 [10681327] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polysubstance abuse-vulnerability genes: genome scans for association, using 1,004 subjects and 1,494 single-nucleotide polymorphisms. AN - 72268670; 11704927 AB - Strong genetic contributions to drug abuse vulnerability are well documented, but few chromosomal locations for human drug-abuse vulnerability alleles have been confirmed. We now identify chromosomal markers whose alleles distinguish drug abusers from control individuals in each of two samples, on the basis of pooled-sample microarray and association analyses. Reproducibly positive chromosomal regions defined by these markers in conjunction with previous results were especially unlikely to have been identified by chance. Positive markers identify the alcohol dehydrogenase (ADH) locus, flank the brain-derived neurotropic factor (BDNF) locus, and mark seven other regions previously linked to vulnerability to nicotine or alcohol abuse. These data support polygenic contributions of common allelic variants to polysubstance abuse vulnerability. JF - American journal of human genetics AU - Uhl, G R AU - Liu, Q R AU - Walther, D AU - Hess, J AU - Naiman, D AD - Molecular Neurobiology Branch, National Institute of Drug Abuse, National Institutes of Health, Baltimore, MD, USA. guhl@intra.nida.nih.gov Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 1290 EP - 1300 VL - 69 IS - 6 SN - 0002-9297, 0002-9297 KW - Brain-Derived Neurotrophic Factor KW - 0 KW - Genetic Markers KW - Nicotine KW - 6M3C89ZY6R KW - Alcohol Dehydrogenase KW - EC 1.1.1.1 KW - Index Medicus KW - United States KW - Software KW - Radiation Hybrid Mapping KW - Multifactorial Inheritance -- genetics KW - Humans KW - Chromosome Mapping KW - European Continental Ancestry Group -- genetics KW - Brain-Derived Neurotrophic Factor -- genetics KW - Alleles KW - Genetic Markers -- genetics KW - Alcohol-Related Disorders -- genetics KW - African Continental Ancestry Group -- genetics KW - Nicotine -- pharmacology KW - Alcohol Dehydrogenase -- genetics KW - Adult KW - Africa -- ethnology KW - Europe -- ethnology KW - Substance-Related Disorders -- enzymology KW - Genetic Predisposition to Disease -- genetics KW - Polymorphism, Single Nucleotide -- genetics KW - Substance-Related Disorders -- genetics KW - Chromosomes, Human -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72268670?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+human+genetics&rft.atitle=Polysubstance+abuse-vulnerability+genes%3A+genome+scans+for+association%2C+using+1%2C004+subjects+and+1%2C494+single-nucleotide+polymorphisms.&rft.au=Uhl%2C+G+R%3BLiu%2C+Q+R%3BWalther%2C+D%3BHess%2C+J%3BNaiman%2C+D&rft.aulast=Uhl&rft.aufirst=G&rft.date=2001-12-01&rft.volume=69&rft.issue=6&rft.spage=1290&rft.isbn=&rft.btitle=&rft.title=American+journal+of+human+genetics&rft.issn=00029297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-10 N1 - Date created - 2001-11-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Med Genet. 1998 May 8;81(3):207-15 [9603606] Am J Hum Genet. 2000 Jul;67(1):120-32 [10841813] Biochem Pharmacol. 1998 Oct 1;56(7):831-9 [9774145] Arch Gen Psychiatry. 1998 Nov;55(11):967-72 [9819064] Arch Gen Psychiatry. 1998 Nov;55(11):973-9 [9819065] Neuropsychopharmacology. 1999 Jan;20(1):3-9 [9885780] Br J Psychiatry. 1998 Oct;173:345-50 [9926041] Am J Hum Genet. 1999 Apr;64(4):1147-57 [10090900] Mol Psychiatry. 1999 Mar;4(2):129-44 [10208445] J Neurosci. 1999 May 15;19(10):4110-22 [10234039] Nat Genet. 1999 Jun;22(2):164-7 [10369258] Arch Gen Psychiatry. 1999 Jul;56(7):655-61 [10401514] Am J Med Genet. 1999 Aug 20;88(4):391-7 [10402507] Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15239-44 [10611369] Am J Hum Genet. 2000 May;66(5):1616-30 [10762547] Behav Genet. 1999 Nov;29(6):409-21 [10857246] Behav Genet. 1999 Nov;29(6):473-9 [10857252] Alcohol Clin Exp Res. 2000 Jul;24(7):933-45 [10923994] Mol Psychiatry. 2000 Sep;5(5):558-62 [11032392] Am J Hum Genet. 2000 Nov;67(5):1208-18 [11032785] Am J Med Genet. 2000 Oct 9;96(5):665-70 [11054775] Arch Gen Psychiatry. 1986 Dec;43(12):1131-6 [3778110] Genomics. 1988 Apr;2(3):209-14 [3397059] Biol Psychiatry. 1990 Jun 15;27(12):1293-304 [2364118] Proc Natl Acad Sci U S A. 1990 Oct;87(20):8060-4 [2236018] Arch Gen Psychiatry. 1991 Jan;48(1):19-28 [1984758] Genomics. 1991 Jul;10(3):558-68 [1889806] Rev Environ Health. 1991;9(1):31-7 [1957048] Biochem Biophys Res Commun. 1992 Jan 15;182(1):325-32 [1339267] Arch Gen Psychiatry. 1992 Sep;49(9):723-7 [1355337] Neuron. 1993 Mar;10(3):475-89 [8461137] Arch Gen Psychiatry. 1995 Jan;52(1):42-52 [7811161] Nat Genet. 1995 Nov;11(3):241-7 [7581446] Psychiatry Res. 1995 Apr 28;56(3):213-20 [7568543] Science. 1996 Sep 13;273(5281):1516-7 [8801636] Am J Med Genet. 1996 Sep 20;67(5):473-7 [8886164] Biol Psychiatry. 1996 Oct 15;40(8):776-84 [8894071] Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):2785-6 [9096294] Am J Hum Genet. 1997 Sep;61(3):734-47 [9326338] Exp Neurol. 1999 Dec;160(2):500-7 [10619567] Genome Res. 2000 Feb;10(2):258-66 [10673283] EMBO J. 2000 Mar 15;19(6):1290-300 [10716929] Hepatology. 2000 Apr;31(4):984-9 [10733556] Br J Psychiatry. 1999 Oct;175:351-6 [10789303] Am J Med Genet. 1998 May 8;81(3):216-21 [9603607] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulatory mechanisms at the mouse Igf2/H19 locus. AN - 72252297; 11689707 AB - The closely linked H19 and Igf2 genes show highly similar patterns of gene expression but are reciprocally imprinted. H19 is expressed almost exclusively from the maternally inherited chromosome, while Igf2 expression is mostly from the paternal chromosome. In humans, loss of imprinting at this locus is associated with tumors and with developmental disorders. Monoallelic expression at the imprinted Igf2/H19 locus occurs by at least two distinct mechanisms: a developmentally regulated silencing of the paternal H19 promoter, and transcriptional insulation of the maternal Igf2 promoters. Both mechanisms of allele-specific silencing are ultimately dependent on a common cis-acting element located just upstream of the H19 promoter. The coordinated expression patterns and some experimental data support the idea that positive regulatory elements are also shared by the two genes. To clarify the organization and function of positive and negative regulatory elements at the H19/Igf2 locus, we analyzed two mouse mutations. First, we generated a deletion allele to localize enhancers used in vivo for expression of both H19 and Igf2 in mesodermal tissues to sequences downstream of the H19 gene. Coincidentally, we demonstrated that some expression of Igf2 is independent of the shared enhancer element. Second, we used this new information to further characterize an ectopic H19 differentially regulated region and the associated insulator. We demonstrated that its activity is parent-of-origin dependent. In contrast to recent results from Drosophila model systems; we showed that this duplication of a mammalian insulator does not interfere with its normal function. Implications of these findings for current models for monoallelic gene expression at this locus are discussed. JF - Molecular and cellular biology AU - Kaffer, C R AU - Grinberg, A AU - Pfeifer, K AD - Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 8189 EP - 8196 VL - 21 IS - 23 SN - 0270-7306, 0270-7306 KW - H19 long non-coding RNA KW - 0 KW - Mrpl23 protein, mouse KW - Proteins KW - RNA, Long Noncoding KW - RNA, Messenger KW - RNA, Untranslated KW - Troponin T KW - Insulin-Like Growth Factor II KW - 67763-97-7 KW - Index Medicus KW - Animals KW - Gene Silencing -- physiology KW - Troponin T -- metabolism KW - Troponin T -- genetics KW - Mutagenesis, Site-Directed KW - Alleles KW - DNA Methylation KW - Muscle, Skeletal -- metabolism KW - Sequence Deletion KW - Tongue -- embryology KW - Multigene Family KW - Mice KW - Organ Specificity KW - Proteins -- genetics KW - Proteins -- metabolism KW - Genomic Imprinting -- physiology KW - Muscle, Skeletal -- embryology KW - Mice, Mutant Strains KW - RNA, Messenger -- metabolism KW - Enhancer Elements, Genetic KW - Genes, Regulator -- physiology KW - Crosses, Genetic KW - Mesoderm -- metabolism KW - Tongue -- metabolism KW - Gene Expression Regulation, Developmental -- physiology KW - RNA, Untranslated -- metabolism KW - Insulin-Like Growth Factor II -- genetics KW - Insulin-Like Growth Factor II -- metabolism KW - RNA, Untranslated -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72252297?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Regulatory+mechanisms+at+the+mouse+Igf2%2FH19+locus.&rft.au=Kaffer%2C+C+R%3BGrinberg%2C+A%3BPfeifer%2C+K&rft.aulast=Kaffer&rft.aufirst=C&rft.date=2001-12-01&rft.volume=21&rft.issue=23&rft.spage=8189&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-05 N1 - Date created - 2001-11-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1999 Nov 24;99(5):459-62 [10589674] Nature. 1998 Feb 12;391(6668):711-5 [9490417] Hum Mol Genet. 1998 Jul;7(7):1149-59 [9618174] Mamm Genome. 1998 Sep;9(9):775-7 [9716667] Mamm Genome. 1998 Oct;9(10):846-8 [9745043] Mol Cell Biol. 1998 Nov;18(11):6767-76 [9774690] Hum Mol Genet. 1998 Nov;7(12):1979-85 [9811943] Genes Dev. 1998 Dec 1;12(23):3693-702 [9851976] Mol Cell Biol. 1999 Apr;19(4):2556-66 [10082521] Curr Opin Genet Dev. 1999 Apr;9(2):191-8 [10322134] Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9242-7 [10430927] Curr Opin Genet Dev. 1999 Oct;9(5):505-14 [10508687] Int J Dev Biol. 2000;44(1):145-50 [10761859] Curr Biol. 2000 Apr 20;10(8):449-57 [10801414] Genome Res. 2000 May;10(5):664-71 [10810089] Genes Dev. 2000 May 15;14(10):1186-95 [10817754] Nature. 2000 May 25;405(6785):408-9 [10839521] Nature. 2000 May 25;405(6785):482-5 [10839546] Nature. 2000 May 25;405(6785):486-9 [10839547] Curr Biol. 2000 May 18;10(10):607-10 [10837224] Science. 2000 Jun 23;288(5474):2145-6 [10896590] Curr Biol. 2000 Jul 13;10(14):853-6 [10899010] Genes Dev. 2000 Aug 1;14(15):1908-19 [10921905] Development. 2000 Sep;127(18):3923-30 [10952890] Nat Genet. 2000 Oct;26(2):203-6 [11017078] Genome Res. 2000 Nov;10(11):1697-710 [11076855] Science. 2001 Jan 19;291(5503):493-5 [11161205] Science. 2001 Jan 19;291(5503):495-8 [11161206] Science. 2001 Jan 19;291(5503):447-50 [11228144] Mol Cell Biol. 1988 Nov;8(11):4707-15 [2463463] Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1143-7 [1671714] Genes Dev. 1991 Jun;5(6):1092-101 [2044956] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10469-73 [1279680] Nature. 1993 Apr 22;362(6422):751-5 [8469285] Nat Genet. 1992 Sep;2(1):61-5 [1303252] Genes Dev. 1993 Sep;7(9):1663-73 [7690336] EMBO J. 1993 Sep;12(9):3669-77 [7504628] Nat Genet. 1995 Apr;9(4):407-13 [7795647] Genes Dev. 1995 Aug 1;9(15):1857-68 [7649473] Genes Dev. 1995 Sep 1;9(17):2079-89 [7544754] Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5860-5 [8650183] Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13876-83 [8943029] Hum Mol Genet. 1996 Dec;5(12):1931-7 [8968746] Mol Cell Biol. 1997 Aug;17(8):4322-9 [9234689] Development. 1997 Sep;124(18):3621-32 [9342054] Genomics. 1997 Oct 15;45(2):290-6 [9344651] Nat Genet. 1997 Nov;17(3):275-6 [9354788] Hum Mol Genet. 1998 Mar;7(3):483-7 [9467008] Mech Dev. 2000 Mar 1;91(1-2):365-8 [10704866] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional induction of MKP-1 in response to stress is associated with histone H3 phosphorylation-acetylation. AN - 72250435; 11689710 AB - Mitogen-activated protein (MAP) kinase phosphatase 1 (MKP-1) has been shown to play a critical role in mediating the feedback control of MAP kinase cascades in a variety of cellular processes, including proliferation and stress responsiveness. Although MKP-1 expression is induced by a broad array of extracellular stimuli, the mechanisms mediating its induction remain poorly understood. Here we show that MKP-1 mRNA was potently induced by arsenite and ultraviolet light and modestly increased by heat shock and hydrogen peroxide. Interestingly, arsenite also dramatically induces phosphorylation-acetylation of histone H3 at a global level which precedes the induction of MKP-1 mRNA. The transcriptional induction of MKP-1, histone H3 modification, and elevation in MKP-1 mRNA in response to arsenite are all partially prevented by the p38 MAP kinase inhibitor SB203580, suggesting that the p38 pathway is involved in these processes. Finally, analysis of the DNA brought down by chromatin immunoprecipitation (ChIP) reveals that arsenite induces phosphorylation-acetylation of histone H3 associated with the MKP-1 gene and enhances binding of RNA polymerase II to MKP-1 chromatin. ChIP assays following exposure to other stress agents reveal various degrees of histone H3 modification at the MKP-1 chromatin. The differential contribution of p38 and ERK MAP kinases in mediating MKP-1 induction by different stress agents further illustrates the complexity and versatility of stress-induced MKP-1 expression. Our results strongly suggest that chromatin remodeling after stress contributes to the transcriptional induction of MKP-1. JF - Molecular and cellular biology AU - Li, J AU - Gorospe, M AU - Hutter, D AU - Barnes, J AU - Keyse, S M AU - Liu, Y AD - Laboratory of Cellular and Molecular Biology, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 8213 EP - 8224 VL - 21 IS - 23 SN - 0270-7306, 0270-7306 KW - Arsenites KW - 0 KW - Cell Cycle Proteins KW - Chromatin KW - Enzyme Inhibitors KW - Histone Deacetylase Inhibitors KW - Histones KW - Immediate-Early Proteins KW - Oxidants KW - RNA, Messenger KW - Hydrogen Peroxide KW - BBX060AN9V KW - Ribosomal Protein S6 Kinases, 90-kDa KW - EC 2.7.11.1 KW - mitogen and stress-activated protein kinase 1 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - RNA Polymerase II KW - EC 2.7.7.- KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Protein Phosphatase 1 KW - DUSP1 protein, human KW - EC 3.1.3.48 KW - Dual Specificity Phosphatase 1 KW - Dusp1 protein, mouse KW - Protein Tyrosine Phosphatases KW - arsenite KW - N5509X556J KW - Index Medicus KW - RNA Polymerase II -- metabolism KW - Animals KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Ultraviolet Rays KW - Acetylation -- drug effects KW - Arsenites -- pharmacology KW - Chromatin -- metabolism KW - Oxidants -- pharmacology KW - Mitogen-Activated Protein Kinases -- metabolism KW - Humans KW - Hydrogen Peroxide -- pharmacology KW - Mice KW - Phosphorylation -- drug effects KW - RNA, Messenger -- metabolism KW - Phosphorylation -- radiation effects KW - Mice, Inbred C3H KW - Mitogen-Activated Protein Kinases -- antagonists & inhibitors KW - Enzyme Inhibitors -- pharmacology KW - Heat-Shock Response -- physiology KW - Acetylation -- radiation effects KW - Cell Line KW - Protein Tyrosine Phosphatases -- metabolism KW - Protein Tyrosine Phosphatases -- genetics KW - Immediate-Early Proteins -- metabolism KW - Histones -- chemistry KW - Fibroblasts -- cytology KW - Enzyme Induction -- radiation effects KW - Fibroblasts -- metabolism KW - Immediate-Early Proteins -- genetics KW - Stress, Physiological -- metabolism KW - Enzyme Induction -- drug effects KW - Histones -- metabolism KW - Enzyme Induction -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72250435?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Transcriptional+induction+of+MKP-1+in+response+to+stress+is+associated+with+histone+H3+phosphorylation-acetylation.&rft.au=Li%2C+J%3BGorospe%2C+M%3BHutter%2C+D%3BBarnes%2C+J%3BKeyse%2C+S+M%3BLiu%2C+Y&rft.aulast=Li&rft.aufirst=J&rft.date=2001-12-01&rft.volume=21&rft.issue=23&rft.spage=8213&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-05 N1 - Date created - 2001-11-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell. 2000 Dec;6(6):1343-54 [11163208] Leukemia. 1999 Sep;13(9):1316-24 [10482980] Cell. 2001 May 18;105(4):433-43 [11371341] J Biol Chem. 2001 Aug 3;276(31):29440-9 [11387337] Cell. 1979 Jun;17(2):241-54 [110462] Nature. 1986 Oct 23-29;323(6090):731-4 [3022151] Oncogene. 1987;2(1):79-84 [3325886] Biomed Biochim Acta. 1990;49(2-3):S5-10 [2117451] Oncogene. 1992 Jan;7(1):187-90 [1741163] Nature. 1992 Oct 15;359(6396):644-7 [1406996] Cell. 1992 Nov 13;71(4):587-97 [1423616] Science. 1993 Mar 19;259(5102):1763-6 [7681221] Oncogene. 1993 Jul;8(7):2015-20 [8390041] J Biol Chem. 1993 Jul 15;268(20):14553-6 [8325833] Mol Cell Biol. 1993 Sep;13(9):5195-205 [8355678] Science. 1999 Dec 24;286(5449):2514-7 [10617468] J Cell Biochem. 1999;Suppl 32-33:141-8 [10629113] FASEB J. 2000 Jan;14(1):6-16 [10627275] Curr Opin Cell Biol. 2000 Apr;12(2):186-92 [10712927] EMBO J. 2000 Mar 15;19(6):1176-9 [10716917] Br J Haematol. 2000 Mar;108(4):696-702 [10792271] FEBS Lett. 2000 Jun 2;474(2-3):146-50 [10838075] EMBO J. 2000 Jul 17;19(14):3714-26 [10899125] Haematologica. 1999 Jun;84 Suppl EHA-4:75-7 [10907475] Mol Cell. 2000 Jun;5(6):905-15 [10911985] Cell. 2000 Aug 4;102(3):279-91 [10975519] J Biol Chem. 1995 Mar 31;270(13):7420-6 [7535770] Cell. 2000 Aug 4;102(3):293-302 [10975520] Cell. 2000 Oct 13;103(2):263-71 [11057899] Biochem J. 2000 Nov 15;352 Pt 1:155-63 [11062068] Genes Dev. 2000 Dec 1;14(23):3003-13 [11114889] Curr Opin Oncol. 2001 Jan;13(1):8-13 [11148679] Cell. 1993 Nov 5;75(3):487-93 [8221888] J Biol Chem. 1994 Feb 4;269(5):3596-604 [8106404] Nature. 1994 Feb 17;367(6464):651-4 [8107850] Hum Genet. 1994 May;93(5):513-6 [8168826] Proc Natl Acad Sci U S A. 1994 May 24;91(11):4781-5 [8197135] EMBO J. 1994 Oct 3;13(19):4524-35 [7925294] Trends Biochem Sci. 1995 Mar;20(3):117-22 [7709430] J Biol Chem. 1995 Apr 14;270(15):8377-80 [7721728] J Cell Sci. 1995 Nov;108 ( Pt 11):3599-609 [8586671] Mol Reprod Dev. 1995 Dec;42(4):459-67 [8607977] Bioessays. 1996 Jul;18(7):567-77 [8757935] Curr Opin Cell Biol. 1996 Apr;8(2):205-15 [8791420] Curr Biol. 1996 Aug 1;6(8):1028-31 [8805335] Science. 1996 Oct 11;274(5285):174-5 [8927976] EMBO J. 1996 Nov 15;15(22):6269-79 [8947050] J Biol Chem. 1997 Jan 3;272(1):271-9 [8995258] Curr Opin Cell Biol. 1997 Apr;9(2):180-6 [9069255] J Biol Chem. 1997 Jul 18;272(29):17929-36 [9218417] Hypertension. 1997 Jul;30(1 Pt 1):106-11 [9231829] Nature. 1997 Sep 25;389(6649):349-52 [9311776] Gene. 1997 Dec 31;205(1-2):323-43 [9461407] EMBO J. 1998 Aug 3;17(15):4426-41 [9687510] Mol Cell Biol. 1998 Sep;18(9):5178-88 [9710602] EMBO J. 1999 Feb 1;18(3):664-74 [9927426] J Cell Biol. 1999 Apr 19;145(2):225-35 [10209020] J Biol Chem. 1999 Apr 30;274(18):12890-7 [10212278] Semin Cell Dev Biol. 1999 Apr;10(2):197-203 [10441073] Semin Cell Dev Biol. 1999 Apr;10(2):205-14 [10441074] J Biol Chem. 1999 Aug 27;274(35):24914-20 [10455166] EMBO J. 1999 Sep 1;18(17):4779-93 [10469656] Biochem J. 1999 Sep 15;342 Pt 3:481-96 [10477257] J Biol Chem. 2001 May 11;276(19):16491-500 [11278799] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural requirements for function of yeast GGAs in vacuolar protein sorting, alpha-factor maturation, and interactions with clathrin. AN - 72250395; 11689690 AB - The GGAs (Golgi-localized, gamma-ear-containing, ARF-binding proteins) are a family of multidomain adaptor proteins involved in protein sorting at the trans-Golgi network of eukaryotic cells. Here we present results from a functional characterization of the two Saccharomyces cerevisiae GGAs, Gga1p and Gga2p. We show that deletion of both GGA genes causes defects in sorting of carboxypeptidase Y (CPY) and proteinase A to the vacuole, vacuolar morphology, and maturation of alpha-factor. A structure-function analysis reveals a requirement of the VHS, GAT, and hinge for function, while the GAE domain is less important. We identify putative clathrin-binding motifs in the hinge domain of both yeast GGAs. These motifs are shown to mediate clathrin binding in vitro. While mutation of these motifs alone does not block function of the GGAs in vivo, combining these mutations with truncations of the hinge and GAE domains diminishes function, suggesting functional cooperation between different clathrin-binding elements. Thus, these observations demonstrate that the yeast GGAs play important roles in the CPY pathway, vacuole biogenesis, and alpha-factor maturation and identify structural determinants that are critical for these functions. JF - Molecular and cellular biology AU - Mullins, C AU - Bonifacino, J S AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-5430, USA. Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 7981 EP - 7994 VL - 21 IS - 23 SN - 0270-7306, 0270-7306 KW - Adaptor Proteins, Vesicular Transport KW - 0 KW - Carrier Proteins KW - Clathrin KW - GGA adaptor proteins KW - GGA2 protein, human KW - Peptides KW - Proteins KW - Saccharomyces cerevisiae Proteins KW - Mating Factor KW - 61194-02-3 KW - Carboxypeptidases KW - EC 3.4.- KW - Cathepsin A KW - EC 3.4.16.5 KW - Proprotein Convertases KW - EC 3.4.21.- KW - Subtilisins KW - KEX2 protein, S cerevisiae KW - EC 3.4.21.61 KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - Index Medicus KW - Proteins -- metabolism KW - Subtilisins -- metabolism KW - Structure-Activity Relationship KW - Saccharomyces cerevisiae KW - Mutagenesis, Site-Directed KW - Protein Binding -- physiology KW - Amino Acid Motifs -- physiology KW - Proteins -- chemistry KW - Molecular Sequence Data KW - Protein Structure, Tertiary -- physiology KW - Sequence Homology, Amino Acid KW - trans-Golgi Network -- metabolism KW - Clathrin -- metabolism KW - Vacuoles -- ultrastructure KW - Carrier Proteins -- metabolism KW - Protein Processing, Post-Translational -- physiology KW - Carrier Proteins -- chemistry KW - ADP-Ribosylation Factors -- metabolism KW - Peptides -- metabolism KW - Vacuoles -- metabolism KW - ADP-Ribosylation Factors -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72250395?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Structural+requirements+for+function+of+yeast+GGAs+in+vacuolar+protein+sorting%2C+alpha-factor+maturation%2C+and+interactions+with+clathrin.&rft.au=Mullins%2C+C%3BBonifacino%2C+J+S&rft.aulast=Mullins&rft.aufirst=C&rft.date=2001-12-01&rft.volume=21&rft.issue=23&rft.spage=7981&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-05 N1 - Date created - 2001-11-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochem Biophys Res Commun. 1988 Oct 14;156(1):246-54 [2845974] EMBO J. 1999 Aug 16;18(16):4383-93 [10449404] Science. 1989 Oct 27;246(4929):482-6 [2683070] Methods Enzymol. 1991;194:644-61 [1706462] J Cell Biol. 1991 Jul;114(2):207-18 [2071670] Mol Cell Biol. 1991 Dec;11(12):5813-24 [1840635] EMBO J. 1992 Aug;11(8):2811-8 [1639056] J Cell Biol. 1992 Nov;119(4):773-86 [1429836] Mol Biol Cell. 1992 Dec;3(12):1389-402 [1493335] EMBO J. 1993 Aug;12(8):3049-59 [8344247] Cell. 1994 May 20;77(4):579-86 [8187177] Mol Biol Cell. 1999 Nov;10(11):3643-59 [10564262] J Cell Biol. 1999 Dec 13;147(6):1223-36 [10601336] Genetics. 2000 Jan;154(1):83-97 [10628971] Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1096-100 [10655490] J Biol Chem. 2000 Mar 10;275(10):7176-83 [10702286] J Cell Biol. 2000 Apr 3;149(1):67-80 [10747088] J Cell Biol. 2000 Apr 3;149(1):81-94 [10747089] Mol Biol Cell. 2000 Apr;11(4):1241-55 [10749927] Biochem Biophys Res Commun. 2000 May 19;271(3):719-25 [10814529] Curr Opin Cell Biol. 2000 Aug;12(4):457-66 [10873832] Curr Opin Cell Biol. 2000 Aug;12(4):475-82 [10873831] EMBO J. 2000 Aug 15;19(16):4216-27 [10944104] Cell. 2001 Apr 6;105(1):93-102 [11301005] EMBO J. 2001 May 1;20(9):2180-90 [11331584] Science. 2001 Jun 1;292(5522):1712-6 [11387475] Science. 2001 Jun 1;292(5522):1716-8 [11387476] Mol Biol Cell. 2001 Jul;12(7):1925-35 [11451993] J Bacteriol. 1977 May;130(2):766-74 [400792] Annu Rev Physiol. 1988;50:345-62 [3288097] Annu Rev Biochem. 2000;69:699-727 [10966473] J Cell Biol. 2000 Oct 30;151(3):587-600 [11062260] Mol Cell Biol. 2000 Dec;20(24):9376-90 [11094088] Yeast. 2001 Jan 15;18(1):1-18 [11124697] Bioessays. 2001 Apr;23(4):333-43 [11268039] J Cell Biol. 1995 Mar;128(5):779-92 [7533169] J Cell Biol. 1995 Apr;129(1):35-46 [7698993] Trends Biochem Sci. 1995 Apr;20(4):147-50 [7770914] Mol Biol Cell. 1995 Sep;6(9):1089-102 [8534908] J Cell Biol. 1996 May;133(3):529-41 [8636229] J Cell Biol. 1997 Apr 7;137(1):79-92 [9105038] J Biol Chem. 1997 Apr 25;272(17):11344-9 [9111041] J Biol Chem. 1997 Jun 6;272(23):15011-6 [9169476] Cell. 1997 Oct 3;91(1):109-18 [9335339] J Cell Biol. 1997 Dec 29;139(7):1761-74 [9412470] Microbiol Mol Biol Rev. 1998 Mar;62(1):230-47 [9529893] J Cell Biol. 1998 Apr 6;141(1):71-84 [9531549] Science. 1998 Apr 17;280(5362):431-4 [9545220] J Cell Biol. 1998 Aug 10;142(3):651-63 [9700156] J Cell Biol. 1998 Aug 10;142(3):665-81 [9700157] Biochim Biophys Acta. 1998 Aug 14;1404(1-2):211-30 [9714809] Genetics. 1998 Oct;150(2):577-89 [9755191] Cell. 1998 Nov 13;95(4):443-6 [9827796] EMBO J. 1999 Jul 15;18(14):3897-908 [10406795] Science. 1989 Sep 22;245(4924):1358-65 [2675311] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Normal gonadal development in mice lacking GPBOX, a homeobox protein expressed in germ cells at the onset of sexual dimorphism. AN - 72250119; 11689708 AB - Gpbox is a paired-like homeobox gene that colocalizes with two other members of the family, PsxI and Pem, on the proximal portion of the mouse X chromosome. Gpbox is expressed in the extraembryonic placenta and within the germ cells of the embryonic gonad. Beginning with the onset of sexual dimorphism (embryonic day [E]11.5 to 12.5), GPBOX transcripts accumulate faster in female than in male germ cells but disappear later in embryogenesis (E16) and have not been reported in adult tissues. To investigate the function of Gpbox, mouse cell lines lacking GPBOX were established using targeted mutagenesis in embryonic stem cells. Both homozygous Gpbox null female and hemizygous Gpbox null male mice were fertile and reproduced normally. Additionally, the development of male and female gonads in the null background was indistinguishable from that observed in normal littermates. The lack of an obvious phenotype raises the possibility that another member of this homeobox gene family provides the absent Gpbox function. JF - Molecular and cellular biology AU - Takasaki, N AU - Rankin, T AU - Dean, J AD - Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 8197 EP - 8202 VL - 21 IS - 23 SN - 0270-7306, 0270-7306 KW - Homeodomain Proteins KW - 0 KW - Pregnancy Proteins KW - Psx1 protein, mouse KW - Psx2 protein, mouse KW - RNA, Messenger KW - Index Medicus KW - Animals KW - Ovary -- growth & development KW - Testis -- embryology KW - Homozygote KW - Mice KW - RNA, Messenger -- biosynthesis KW - Testis -- growth & development KW - Mice, Inbred Strains KW - Mice, Mutant Strains KW - Ovary -- cytology KW - Heterozygote KW - X Chromosome -- genetics KW - Placenta -- metabolism KW - Gene Targeting KW - Female KW - Male KW - Ovary -- embryology KW - Testis -- cytology KW - Homeodomain Proteins -- biosynthesis KW - Gonads -- growth & development KW - Homeodomain Proteins -- genetics KW - Gonads -- embryology KW - Gonads -- cytology KW - Sex Characteristics KW - Homeodomain Proteins -- metabolism KW - Germ Cells -- metabolism KW - Germ Cells -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72250119?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Normal+gonadal+development+in+mice+lacking+GPBOX%2C+a+homeobox+protein+expressed+in+germ+cells+at+the+onset+of+sexual+dimorphism.&rft.au=Takasaki%2C+N%3BRankin%2C+T%3BDean%2C+J&rft.aulast=Takasaki&rft.aufirst=N&rft.date=2001-12-01&rft.volume=21&rft.issue=23&rft.spage=8197&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-05 N1 - Date created - 2001-11-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Dev Biol. 1990 Oct;141(2):451-5 [2210045] Physiol Rev. 1986 Jan;66(1):71-117 [3511481] Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8424-8 [8378314] Dev Biol. 1994 Nov;166(1):170-9 [7958444] Annu Rev Biochem. 1994;63:487-526 [7979246] Development. 1996 Sep;122(9):2903-10 [8787763] Dev Biol. 1996 Nov 1;179(2):471-84 [8903361] Development. 1997 Jun;124(11):2275-84 [9187153] Genomics. 1997 Oct 15;45(2):447-50 [9344676] Gene. 1998 Jan 30;207(2):159-66 [9511757] Mech Dev. 1998 Feb;71(1-2):89-98 [9507072] Dev Biol. 1998 Oct 15;202(2):196-214 [9769172] Cell. 1998 Oct 30;95(3):379-91 [9814708] Genes Dev. 1999 Apr 1;13(7):755-67 [10197976] Dev Biol. 1999 Jun 15;210(2):481-96 [10357905] Dev Dyn. 1999 Nov;216(3):257-66 [10590477] Gene. 2000 Jan 4;241(1):149-55 [10607909] Dev Biol. 2000 Jul 1;223(1):181-93 [10864470] Mol Cell Endocrinol. 2000 May 25;163(1-2):3-9 [10963867] Development. 2000 Nov;127(21):4645-54 [11023867] J Exp Zool. 1983 Nov;228(2):173-93 [6663256] Cell. 1991 Jun 28;65(7):1153-63 [2065352] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bivalent disulfide-stabilized fragment variable immunotoxin directed against mesotheliomas and ovarian cancer. AN - 71339597; 12467225 AB - We have used protein engineering to generate a stable bivalent fragment variable (Fv) molecule from the antimesothelin antibody SS, in which the VH and VL domains of the Fv are linked to each other by a disulfide bond, and the two Fvs are connected by a flexible 15-amino acid (Gly4-Ser)3 linker. The SS (dsFv)2 molecule is fused to a M(r) 38,000 truncated form of Pseudomonas exotoxin to generate a bivalent, disulfide stabilized, (dsFv)2 immunotoxin. The immunotoxin was expressed in Escherichia coli, refolded in vitro, and purified to approximately 95% purity with a high yield of > 10%. Binding studies demonstrated that the (dsFv)2 molecule has 40 times higher apparent affinity for recombinant mesothelin than a monovalent dsFv molecule. The (dsFv)2 immunotoxin was 4-10-fold more cytotoxic to three mesothelin antigen-positive cell lines than the monovalent dsFv immunotoxin. However, when tested in mice bearing tumor cells expressing mesothelin, the antitumor activity of the bivalent immunotoxin is very similar to the activity of the lower affinity monovalent immunotoxin. Our data indicate that increasing affinity of an antibody fragment does not necessarily lead to higher antitumor activity of an immunotoxin in vivo. JF - Molecular cancer therapeutics AU - Bera, T K AU - Williams-Gould, J AU - Beers, R AU - Chowdhury, P AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 79 EP - 84 VL - 1 IS - 2 SN - 1535-7163, 1535-7163 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, Neoplasm KW - Bacterial Toxins KW - Disulfides KW - Exotoxins KW - GPI-Linked Proteins KW - Immunoglobulin Fragments KW - Immunotoxins KW - Membrane Glycoproteins KW - Virulence Factors KW - immunoglobulin Fv KW - mesothelin KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Escherichia coli -- metabolism KW - Tumor Cells, Cultured -- metabolism KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Gene Expression KW - Escherichia coli -- genetics KW - Neoplasms, Experimental -- metabolism KW - Mice, Nude KW - Mice KW - Plasmids KW - Mice, Inbred BALB C KW - Antigens, Neoplasm -- metabolism KW - Neoplasms, Experimental -- drug therapy KW - Immunoglobulin Fragments -- immunology KW - Female KW - Membrane Glycoproteins -- metabolism KW - Immunotoxins -- pharmacokinetics KW - Exotoxins -- genetics KW - Exotoxins -- pharmacology KW - ADP Ribose Transferases -- pharmacokinetics KW - Virulence Factors -- genetics KW - Bacterial Toxins -- pharmacology KW - ADP Ribose Transferases -- pharmacology KW - Mesothelioma -- immunology KW - ADP Ribose Transferases -- genetics KW - Exotoxins -- pharmacokinetics KW - Virulence Factors -- pharmacology KW - Bacterial Toxins -- genetics KW - Disulfides -- chemistry KW - Bacterial Toxins -- pharmacokinetics KW - Immunotoxins -- genetics KW - Immunotoxins -- pharmacology KW - Virulence Factors -- pharmacokinetics KW - Ovarian Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71339597?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+cancer+therapeutics&rft.atitle=Bivalent+disulfide-stabilized+fragment+variable+immunotoxin+directed+against+mesotheliomas+and+ovarian+cancer.&rft.au=Bera%2C+T+K%3BWilliams-Gould%2C+J%3BBeers%2C+R%3BChowdhury%2C+P%3BPastan%2C+I&rft.aulast=Bera&rft.aufirst=T&rft.date=2001-12-01&rft.volume=1&rft.issue=2&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Molecular+cancer+therapeutics&rft.issn=15357163&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-27 N1 - Date created - 2002-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diepoxybutane and mitomycin C toxicity is associated with the induction of oxidative DNA damage in sea urchin embryos. AN - 71313348; 11936580 AB - Diepoxybutane (DEB)- and mitomycin C (MMC)-associated toxicity was investigated in embryos from the sea urchin (SU) species Sphaerechinus granularis. DEB- and MMC-induced toxicity resulted in S. granularis embryos and larvae at concentrations ranging 10(-5) to 10(-4) M DEB, and 3 x 10(-6) to 3 x 10(-5) M MMC, in terms of larval malformations, developmental arrest and mortality. The formation of DNA oxidative damage, 8-hydroxy-2'-deoxyguanosine (8-OHdG) was measured in DEB- and in MMC-exposed embryos (at gastrula stage). A dose-dependent increase in 8-OHdG levels was observed that was significantly correlated with DEB- and MMC-induced developmental defects. The results lend further support to the body of evidence associating both DEB and MMC toxicity with oxidative stress, including DNA oxidative damage. JF - Human & experimental toxicology AU - Pagano, G AU - Degan, P AU - De Biase, A AU - Iaccarino, M AU - Warnau, M AD - G. Pascale Foundation, Italian National Cancer Institute, Naples. Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 651 EP - 655 VL - 20 IS - 12 SN - 0960-3271, 0960-3271 KW - Epoxy Compounds KW - 0 KW - Mutagens KW - Mitomycin KW - 50SG953SK6 KW - erythritol anhydride KW - 60OB65YNAB KW - 8-oxo-7-hydrodeoxyguanosine KW - 88847-89-6 KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Oxidation-Reduction KW - Animals KW - Abnormalities, Drug-Induced KW - Dose-Response Relationship, Drug KW - Oxidative Stress -- drug effects KW - Organ Culture Techniques KW - Deoxyguanosine -- metabolism KW - DNA Damage KW - Mutagens -- toxicity KW - Mitomycin -- toxicity KW - Epoxy Compounds -- toxicity KW - Sea Urchins KW - Embryo, Nonmammalian -- metabolism KW - Embryo, Nonmammalian -- drug effects KW - Deoxyguanosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71313348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+%26+experimental+toxicology&rft.atitle=Diepoxybutane+and+mitomycin+C+toxicity+is+associated+with+the+induction+of+oxidative+DNA+damage+in+sea+urchin+embryos.&rft.au=Pagano%2C+G%3BDegan%2C+P%3BDe+Biase%2C+A%3BIaccarino%2C+M%3BWarnau%2C+M&rft.aulast=Pagano&rft.aufirst=G&rft.date=2001-12-01&rft.volume=20&rft.issue=12&rft.spage=651&rft.isbn=&rft.btitle=&rft.title=Human+%26+experimental+toxicology&rft.issn=09603271&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-27 N1 - Date created - 2002-04-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Allogeneic transplantation using non-myeloablative transplant regimens. AN - 71304353; 11924917 AB - Reduced intensity (non-myeloablative) stem cell transplant (NST) preparative regimens are being increasingly used to exploit the curative potential of allogeneic stem cell transplantation without the morbidity and mortality associated with conventional transplantation. Growing confidence in the power of the allogeneic graft-versus-malignancy (GVM) effect makes such an approach attractive. Lower intensity transplants increase the degree of mixed chimerism, both in T cell and myeloid cell lineages. Currently a variety of NST treatment approaches are being developed and in this chapter their safety profile and the immunological characteristics of the mixed chimeric state are described. Results of NST in specific disease categories are still limited but the NST approach appears to have promise in the treatment of both haematological and non-haematological malignancies because of the benefit of low toxicity coupled with a strong graft-versus-malignancy effect. NST regimens are also being explored in high-risk patients with non-malignant disorders. However, at present, there is insufficient data to determine whether NST should replace standard myeloablative transplants in specific disease groups. With their low toxicity, NST are well placed as platforms for future developments in transplant immunology to avoid GVHD and enhance the allograft effect against malignant diseases. JF - Best practice & research. Clinical haematology AU - Battiwalla, M AU - Barrett, J AD - Stem Cell Allotransplantation Section, Haematology Branch, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA. Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 701 EP - 722 VL - 14 IS - 4 SN - 1521-6926, 1521-6926 KW - Index Medicus KW - Hematologic Neoplasms -- therapy KW - Hematologic Neoplasms -- pathology KW - Humans KW - Transplantation Chimera KW - Transplantation, Homologous -- methods KW - Graft vs Leukemia Effect KW - Transplantation, Homologous -- immunology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols -- toxicity KW - Stem Cell Transplantation -- methods KW - Transplantation Conditioning -- adverse effects KW - Transplantation Conditioning -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71304353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Best+practice+%26+research.+Clinical+haematology&rft.atitle=Allogeneic+transplantation+using+non-myeloablative+transplant+regimens.&rft.au=Battiwalla%2C+M%3BBarrett%2C+J&rft.aulast=Battiwalla&rft.aufirst=M&rft.date=2001-12-01&rft.volume=14&rft.issue=4&rft.spage=701&rft.isbn=&rft.btitle=&rft.title=Best+practice+%26+research.+Clinical+haematology&rft.issn=15216926&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-08 N1 - Date created - 2002-04-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Resolution of the early placental mammal radiation using Bayesian phylogenetics AN - 52133216; 2002-024708 AB - Molecular phylogenetic studies have resolved placental mammals into four major groups, but have not established the full hierarchy of interordinal relationships, including the position of the root. The latter is critical for understanding the early biogeographic history of placentals. We investigated placental phylogeny using Bayesian and maximum-likelihood methods and a 16.4-kilobase molecular data set. Interordinal relationships are almost entirely resolved. The basal split is between Afrotheria and other placentals, at about 103 million years, and may be accounted for by the separation of South America and Africa in the Cretaceous. Crown-group Eutheria may have their most recent common ancestry in the Southern Hemisphere (Gondwana). JF - Science AU - Murphy, William J AU - Eizirik, Eduardo AU - O'Brien, Stephen J AU - Madsen, Ole AU - Scally, Mark AU - Douady, Christophe J AU - Teeling, Emma AU - Ryder, Oliver A AU - Stanhope, Michael J AU - de Jong, Wilfried W AU - Springer, Mark S Y1 - 2001/12// PY - 2001 DA - December 2001 SP - 2348 EP - 2351 PB - American Association for the Advancement of Science, Washington, DC VL - 294 IS - 5550 SN - 0036-8075, 0036-8075 KW - Chordata KW - Cretaceous KW - Bayesian analysis KW - phylogeny KW - statistical analysis KW - Mammalia KW - biologic evolution KW - biogeography KW - paleogeography KW - Mesozoic KW - Boreoeutheria KW - Theria KW - South America KW - maximum likelihood KW - Gondwana KW - reconstruction KW - Vertebrata KW - Eutheria KW - adaptive radiation KW - Tetrapoda KW - 11:Vertebrate paleontology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/52133216?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science&rft.atitle=Resolution+of+the+early+placental+mammal+radiation+using+Bayesian+phylogenetics&rft.au=Murphy%2C+William+J%3BEizirik%2C+Eduardo%3BO%27Brien%2C+Stephen+J%3BMadsen%2C+Ole%3BScally%2C+Mark%3BDouady%2C+Christophe+J%3BTeeling%2C+Emma%3BRyder%2C+Oliver+A%3BStanhope%2C+Michael+J%3Bde+Jong%2C+Wilfried+W%3BSpringer%2C+Mark+S&rft.aulast=Murphy&rft.aufirst=William&rft.date=2001-12-01&rft.volume=294&rft.issue=5550&rft.spage=2348&rft.isbn=&rft.btitle=&rft.title=Science&rft.issn=00368075&rft_id=info:doi/10.1126%2Fscience.1067179 L2 - http://www.sciencemag.org/ LA - English DB - GeoRef N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 2002-01-01 N1 - Number of references - 33 N1 - PubXState - DC N1 - Document feature - illus. N1 - Last updated - 2012-06-07 N1 - CODEN - SCIEAS N1 - SubjectsTermNotLitGenreText - adaptive radiation; Bayesian analysis; biogeography; biologic evolution; Boreoeutheria; Chordata; Cretaceous; Eutheria; Gondwana; Mammalia; maximum likelihood; Mesozoic; paleogeography; phylogeny; reconstruction; South America; statistical analysis; Tetrapoda; Theria; Vertebrata DO - http://dx.doi.org/10.1126/science.1067179 ER - TY - JOUR T1 - Gene selection for sample classification based on gene expression data: study of sensitivity to choice of parameters of the GA/KNN method AN - 19885054; 7872916 AB - Motivation: We recently introduced a multivariate approach that selects a subset of predictive genes jointly for sample classification based on expression data. We tested the algorithm on colon and leukemia data sets. As an extension to our earlier work, we systematically examine the sensitivity, reproducibility and stability of gene selection/sample classification to the choice of parameters of the algorithm. Methods: Our approach combines a Genetic Algorithm (GA) and the k-Nearest Neighbor (KNN) method to identify genes that can jointly discriminate between different classes of samples (e.g. normal versus tumor). The GA/KNN method is a stochastic supervised pattern recognition method. The genes identified are subsequently used to classify independent test set samples. Results: The GA/KNN method is capable of selecting a subset of predictive genes from a large noisy data set for sample classification. It is a multivariate approach that can capture the correlated structure in the data. We find that for a given data set gene selection is highly repeatable in independent runs using the GA/KNN method. In general, however, gene selection may be less robust than classification. Availability: The method is available at http://dir.niehs.nih.gov/microarray/datamining. JF - Bioinformatics AU - Li, Leping AU - Weinberg, Clarice R AU - Darden, Thomas A AU - Pedersen, Lee G Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 1131 PB - Oxford University Press, Oxford Journals, Great Clarendon Street VL - 17 IS - 12 SN - 1367-4803, 1367-4803 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Gene expression KW - Leukemia KW - Pattern recognition KW - Data processing KW - Colon KW - Algorithms KW - Tumors KW - Bioinformatics KW - set gene KW - Stochasticity KW - W 30960:Bioinformatics & Computer Applications KW - G 07700:Molecular Genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19885054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioinformatics&rft.atitle=Gene+selection+for+sample+classification+based+on+gene+expression+data%3A+study+of+sensitivity+to+choice+of+parameters+of+the+GA%2FKNN+method&rft.au=Li%2C+Leping%3BWeinberg%2C+Clarice+R%3BDarden%2C+Thomas+A%3BPedersen%2C+Lee+G&rft.aulast=Li&rft.aufirst=Leping&rft.date=2001-12-01&rft.volume=17&rft.issue=12&rft.spage=1131&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-01-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Gene expression; Pattern recognition; Leukemia; Data processing; Colon; Algorithms; Bioinformatics; Tumors; set gene; Stochasticity ER - TY - JOUR T1 - Relationships Between Walk/Run Performance and Cardiorespiratory Fitness in Adolescents Who Are Overweight AN - 18705956; 5599706 AB - Background and Purpose. Little is known about the methods used to assess the physical fitness of adolescents who are overweight. We investigated the relationship between walk/run performance and cardiorespiratory fitness in adolescents who are overweight. Subjects. Eight African-American adolescents (5 female, 3 male) and 10 Caucasian adolescents (5 female, 5 male) who were overweight (mean age=14.5 years, SD=2.0, range=12-17; mean body mass index [BMI]=42.9 kg/m super(2), SD=11.5) participated in this study. Methods. Subjects performed a 12-minute walk/run test. The distances traveled at both 9 minutes (D sub(9)) and 12 minutes (D sub(12)) were recorded, and the distance traveled between 9 and 12 minutes (D sub(9-12)) was calculated. Subjects also completed a maximal cycle ergometry test, during which peak oxygen uptake O sub(2)peak), anaerobic threshold (AT), peak power (Wpeak), and power at the anaerobic threshold (WAT) were determined. Body composition was determined by air displacement plethysmography. Results. The mean percentage of body fat was 48.6% (SD=5.3%, range=40.3%-60.4%). Percentage of body fat and BMI were each inversely related to D sub(9), D sub(12), and O sub(2)peak (all P<.005). Peak oxygen uptake (r=.72, P=.0001), O sub(2)peak/kg lean body mass (r=.60, P<.005), Wpeak (r=.88, P<.0001), and WAT (r=.72, P=.0007) were all related to D sub(12), with greater r values than for D sub(9). If D sub(9-12) was included in regression analyses, D sub(9) did not account for additional variance in any of the cycle ergometry variables. Discussion and Conclusion. These results suggest that an easily obtained measurement of physical performance (distance traveled during a 12-minute walk/run test) is related to cardiorespiratory fitness and to body composition in adolescents who are overweight. The 12-minute walk/run distance is more predictive of cycle ergometry test results than the 9-minute distance. JF - Physical Therapy AU - Drinkard, B AU - McDuffie, J AU - McCann, S AU - Uwaifo, GI AU - Nicholson, J AU - Yanovski, JA AD - Rehabilitation Medicine Department, Warren Grant Magnuson Clinical Center, National Institutes of Health (NIH), Bethesda, MD 20892 (USA), bart_drinkard@nih.gov Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 1889 EP - 1896 VL - 81 IS - 12 SN - 0031-9023, 0031-9023 KW - Physical Education Index KW - PE 110:Physical Therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18705956?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Physical+Therapy&rft.atitle=Relationships+Between+Walk%2FRun+Performance+and+Cardiorespiratory+Fitness+in+Adolescents+Who+Are+Overweight&rft.au=Drinkard%2C+B%3BMcDuffie%2C+J%3BMcCann%2C+S%3BUwaifo%2C+GI%3BNicholson%2C+J%3BYanovski%2C+JA&rft.aulast=Drinkard&rft.aufirst=B&rft.date=2001-12-01&rft.volume=81&rft.issue=12&rft.spage=1889&rft.isbn=&rft.btitle=&rft.title=Physical+Therapy&rft.issn=00319023&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Improved binding of a bivalent single-chain immunotoxin results in increased efficacy for in vivo T-cell depletion AN - 18386431; 5351493 AB - Anti-CD3 immunotoxins exhibit considerable promise for the induction of transplantation tolerance in pre-clinical large animal models. Recently an anti-human anti-CD3 epsilon single-chain immunotoxin based on truncated diphtheria toxin has been described that can be expressed in CHO cells that have been mutated to diphtheria toxin resistance. After the two toxin glycosylation sites were removed, the bioactivity of the expressed immunotoxin was nearly equal to that of the chemically conjugated immunotoxin. This immunotoxin, A-dmDT390-sFv, contains diphtheria toxin to residue 390 at the N-terminus followed by VL and VH domains of antibody UCHT1 linked by a (G sub(4)S) sub(3) spacer (sFv). Surprisingly, we now report that this immunotoxin is severely compromised in its binding affinity toward CD3 super(+) cells as compared with the intact parental UCHT1 antibody, the UCHT1 Fab fragment or the engineered UCHT1 sFv domain alone. Binding was increased 7-fold by adding an additional identical sFv domain to the immunotoxin generating a divalent construct, A-dmDT390-bisFv (G sub(4)S). In vitro potency increased 10-fold over the chemically conjugated immunotoxin, UCHT1-CRM9 and the monovalent A-dmDT390-sFv. The in vivo potency of the genetically engineered immunotoxins was assayed in the transgenic heterozygote mouse, tg epsilon 600, in which the T-cells express human CD3 epsilon as well as murine CD3 epsilon . T-cell depletion in the spleen and lymph node observed with the divalent construct was increased 9- and 34-fold, respectively, compared with the monovalent construct. The additional sFv domain appears partially to compensate for steric hindrance of immunotoxin binding due to the large N-terminal toxin domain. JF - Protein Engineering AU - Thompson, J AU - Stavrou, S AU - Weetall, M AU - Hexham, J M AU - Digan, ME AU - Wang, Z AU - Woo, J H AU - Yu, Y AU - Mathias, A AU - Liu, Y Y AU - Ma, S AU - Gordienko, I AU - Lake, P AU - Neville, DM Jr AD - Section on Biophysical Chemistry, Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, MD 28092-4034, USA, davidn@helix.nih.gov Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 1035 EP - 1041 VL - 14 IS - 12 SN - 0269-2139, 0269-2139 KW - depletion KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33340:Other proteins, peptides, amino acids KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18386431?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+Engineering&rft.atitle=Improved+binding+of+a+bivalent+single-chain+immunotoxin+results+in+increased+efficacy+for+in+vivo+T-cell+depletion&rft.au=Thompson%2C+J%3BStavrou%2C+S%3BWeetall%2C+M%3BHexham%2C+J+M%3BDigan%2C+ME%3BWang%2C+Z%3BWoo%2C+J+H%3BYu%2C+Y%3BMathias%2C+A%3BLiu%2C+Y+Y%3BMa%2C+S%3BGordienko%2C+I%3BLake%2C+P%3BNeville%2C+DM+Jr&rft.aulast=Thompson&rft.aufirst=J&rft.date=2001-12-01&rft.volume=14&rft.issue=12&rft.spage=1035&rft.isbn=&rft.btitle=&rft.title=Protein+Engineering&rft.issn=02692139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Gordonia namibiensis sp. nov., a Novel Nitrile Metabolising Actinomycete Recovered from an African Sand AN - 18381722; 5348240 AB - A polyphasic approach was used to establish the taxonomic position of two actinomycetes isolated from a Namibian soil and shown to utilise nitrile compounds as growth substrates. The organisms, strains NAM-BN063A super(T) and NAM-BN063B, had chemical and morphological properties consistent with their assignment to the genus Gordonia. Direct 16S rRNA sequencing studies confirmed the taxonomic position of the strains following the generation of phylogenetic trees using four different algorithms. The strains consistently formed a distinct phylogenetic line within the evolutionary radiation occupied by gordoniae and were most closely related to Gordonia rubropertincta DSM 43197 super(T). DNA:DNA relatedness studies indicated that the two organisms belonged to a genomic species that was readily distinguished from G. rubropertincta. The unique phenotypic profile of the strains sharply separated them from representatives of all of the validly described species of Gordonia. The combination of genotypic and phenotypic data indicates that the two strains should be classified in the genus Gordonia as a new species. The name proposed for this taxon is Gordonia namibiensis, the type strain is NAM-BN063A super(T) (= DSM 44568 super(T) = NCIMB 13780 super(T)). JF - Systematic and Applied Microbiology AU - Brandao, PFB AU - Maldonado, LA AU - Ward, A C AU - Bull, A T AU - Goodfellow, M AD - Department of Agricultural and Environmental Science, University of Newcastle, Newcastle upon Tyne, NEI 7RU, United Kingdom, m.goodfellow@ncl.ac.uk Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 510 EP - 515 VL - 24 IS - 4 SN - 0723-2020, 0723-2020 KW - new species KW - nitrile compounds KW - Microbiology Abstracts B: Bacteriology KW - J 02710:Identification, taxonomy and typing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18381722?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Systematic+and+Applied+Microbiology&rft.atitle=Gordonia+namibiensis+sp.+nov.%2C+a+Novel+Nitrile+Metabolising+Actinomycete+Recovered+from+an+African+Sand&rft.au=Brandao%2C+PFB%3BMaldonado%2C+LA%3BWard%2C+A+C%3BBull%2C+A+T%3BGoodfellow%2C+M&rft.aulast=Brandao&rft.aufirst=PFB&rft.date=2001-12-01&rft.volume=24&rft.issue=4&rft.spage=510&rft.isbn=&rft.btitle=&rft.title=Systematic+and+Applied+Microbiology&rft.issn=07232020&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells AN - 18358386; 5324415 AB - Magnetic resonance (MR) tracking of magnetically labeled stem and progenitor cells is an emerging technology, leading to an urgent need for magnetic probes that can make cells highly magnetic during their normal expansion in culture. We have developed magnetodendrimers as a versatile class of magnetic tags that can efficiently label mammalian cells, including human neural stem cells (NSCs) and mesenchymal stem cells (MSCs), through a nonspecific membrane adsorption process with subsequent intracellular (non-nuclear) localization in endosomes. The superparamagnetic iron oxide nanocomposites have been optimized to exhibit superior magnetic properties and to induce sufficient MR cell contrast at incubated doses as low as 1 mu g iron/ml culture medium. When containing between 9 and 14 pg iron/cell, labeled cells exhibit an ex vivo nuclear magnetic resonance (NMR) relaxation rate (1/T2) as high as 24-39 s super(-1)/mM iron. Labeled cells are unaffected in their viability and proliferating capacity, and labeled human NSCs differentiate normally into neurons. Furthermore, we show here that NSC-derived (and LacZ-transfected), magnetically labeled oligodendroglial progenitors can be readily detected in vivo at least as long as six weeks after transplantation, with an excellent correlation between the obtained MR contrast and staining for beta -galactosidase expression. The availability of magnetodendrimers opens up the possibility of MR tracking of a wide variety of (stem) cell transplants. JF - Nature Biotechnology AU - Bulte, JWM AU - Douglas, T AU - Witwer, B AU - Zhang, S-C AU - Strable, E AU - Lewis, B K AU - Zywicke, H AU - Miller, B AU - van Gelderen, P AU - Moskowitz, B M AU - Duncan, I D AU - Frank, JA AD - Laboratory of Diagnostic Radiology Research (CC), National Institutes of Health, Bethesda, MD 20892, USA, jwmbulte@mri.jhu.edu Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 1141 EP - 1147 VL - 19 IS - 12 SN - 1087-0156, 1087-0156 KW - labelling KW - Magnetodendrimers KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Stem cells KW - Transplantation KW - Magnetic resonance imaging KW - Mesenchyme KW - Iron KW - W3 33120:Receptor based (antibodies, etc.) KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18358386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=Magnetodendrimers+allow+endosomal+magnetic+labeling+and+in+vivo+tracking+of+stem+cells&rft.au=Bulte%2C+JWM%3BDouglas%2C+T%3BWitwer%2C+B%3BZhang%2C+S-C%3BStrable%2C+E%3BLewis%2C+B+K%3BZywicke%2C+H%3BMiller%2C+B%3Bvan+Gelderen%2C+P%3BMoskowitz%2C+B+M%3BDuncan%2C+I+D%3BFrank%2C+JA&rft.aulast=Bulte&rft.aufirst=JWM&rft.date=2001-12-01&rft.volume=19&rft.issue=12&rft.spage=1141&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mesenchyme; Iron; Transplantation; Stem cells; Magnetic resonance imaging ER - TY - JOUR T1 - Gene Assessment and Sample Classification for Gene Expression Data Using a Genetic Algorithm/k-nearest Neighbor Method AN - 18355571; 5311320 AB - Recent tools that analyze microarray expression data have exploited correlation-based approaches such as clustering analysis. We describe a new method for assessing the importance of genes for sample classification based on expression data. Our approach combines a genetic algorithm (GA) and the k-nearest neighbor (KNN) method to identify genes that jointly can discriminate between two types of samples (e.g. normal vs. tumor). First, many such subsets of differentially expressed genes are obtained independently using the GA. Then, the overall frequency with which genes were selected is used to deduce the relative importance of genes for sample classification. Sample heterogeneity is accommodated; that is, the method should be robust against the existence of distinct subtypes. We applied GA/KNN to expression data from normal versus tumor tissue from human colon. Two distinct clusters were observed when the 50 most frequently selected genes were used to classify all of the samples in the data sets studied and the majority of samples were classified correctly. Identification of a set of differentially expressed genes could aid in tumor diagnosis and could also serve to identify disease subtypes that may benefit from distinct clinical approaches to treatment. JF - Combinatorial Chemistry & High Throughput Screening AU - Li, L AU - Darden, T A AU - Weinberg, C R AU - Levine, A J AU - Pedersen, L G AD - Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA, Li3@niehs.nih.gov Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 727 EP - 739 VL - 4 IS - 8 SN - 1386-2073, 1386-2073 KW - DNA microarrays KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene expression KW - Combinatorial chemistry KW - Algorithms KW - Bioinformatics KW - W3 33080:Bioinformatics and computer applications KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18355571?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Combinatorial+Chemistry+%26+High+Throughput+Screening&rft.atitle=Gene+Assessment+and+Sample+Classification+for+Gene+Expression+Data+Using+a+Genetic+Algorithm%2Fk-nearest+Neighbor+Method&rft.au=Li%2C+L%3BDarden%2C+T+A%3BWeinberg%2C+C+R%3BLevine%2C+A+J%3BPedersen%2C+L+G&rft.aulast=Li&rft.aufirst=L&rft.date=2001-12-01&rft.volume=4&rft.issue=8&rft.spage=727&rft.isbn=&rft.btitle=&rft.title=Combinatorial+Chemistry+%26+High+Throughput+Screening&rft.issn=13862073&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Algorithms; Gene expression; Bioinformatics; Combinatorial chemistry ER - TY - JOUR T1 - Crystallographic and Modeling Studies of RNase III Suggest a Mechanism for Double-Stranded RNA Cleavage AN - 18297830; 5346477 AB - Aquifex aeolicus Ribonuclease III (Aa-RNase III) belongs to the family of Mg super(2+)-dependent endonucleases that show specificity for double-stranded RNA (dsRNA). RNase III is conserved in all known bacteria and eukaryotes and has 1-2 copies of a 9-residue consensus sequence, known as the RNase III signature motif. The bacterial RNase III proteins are the simplest, consisting of two domains: an N-terminal endonuclease domain, followed by a double-stranded RNA binding domain (dsRBD). The three-dimensional structure of the dsRBD in Escherichia coli RNase III has been elucidated; no structural information is available for the endonuclease domain of any RNase III. We present the crystal structures of the Aa-RNase III endonuclease domain in its ligand-free form and in complex with Mn super(2+). The structures reveal a novel protein fold and suggest a mechanism for dsRNA cleavage. On the basis of structural, genetic, and biological data, we have constructed a hypothetical model of Aa-RNase III in complex with dsRNA and Mg super(2+) ion, which provides the first glimpse of RNase III in action. The functional Aa-RNase III dimer is formed via mainly hydrophobic interactions, including a "ball-and-socket" junction that ensures accurate alignment of the two monomers. The fold of the polypeptide chain and its dimerization create a valley with two compound active centers at each end of the valley. The valley can accommodate a dsRNA substrate. Mn super(2+) binding has significant impact on crystal packing, intermolecular interactions, thermal stability, and the formation of two RNA-cutting sites within each compound active center. JF - Structure AU - Blaszczyk, J AU - Tropea, JE AU - Bubunenko, M AU - Routzahn, K M AU - Waugh, D S AU - Court, D L AU - Ji, Xinhua AD - Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA, court@ncifcrf.gov Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 1225 EP - 1236 VL - 9 IS - 12 KW - RNA-binding domain KW - RNA KW - ribonuclease III KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Dimerization KW - Aquifex aeolicus KW - Crystal structure KW - Active sites KW - Magnesium KW - Manganese KW - J 02726:RNA and ribosomes KW - N 14711:RNases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18297830?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Structure&rft.atitle=Crystallographic+and+Modeling+Studies+of+RNase+III+Suggest+a+Mechanism+for+Double-Stranded+RNA+Cleavage&rft.au=Blaszczyk%2C+J%3BTropea%2C+JE%3BBubunenko%2C+M%3BRoutzahn%2C+K+M%3BWaugh%2C+D+S%3BCourt%2C+D+L%3BJi%2C+Xinhua&rft.aulast=Blaszczyk&rft.aufirst=J&rft.date=2001-12-01&rft.volume=9&rft.issue=12&rft.spage=1225&rft.isbn=&rft.btitle=&rft.title=Structure&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Aquifex aeolicus; Dimerization; Magnesium; Active sites; Crystal structure; Manganese ER - TY - JOUR T1 - Synergy, pharmacodynamics, and time-sequenced ultrastructural changes of the interaction between nikkomycin Z and the echinocandin FK463 against Aspergillus fumigatus AN - 18294013; 5346994 AB - We investigated the potential synergy between two cell wall-active agents, the echinocandin FK463 (FK) and the chitin synthase inhibitor nikkomycin Z (NZ), against 16 isolates of filamentous fungi. Susceptibility testing was performed with a broth macrodilution procedure by NCCLS methods. The median minimal effective concentration (MEC) of FK against all Aspergillus species was 0.25 mu g/ml (range, 0.05 to 0.5 mu g/ml). For Fusarium solani and Rhizopus oryzae, MECs of FK were >512 mu g/ml. The median MEC of NZ against Aspergillus fumigatus was 32 mu g/ml (range, 8 to 64 mu g/ml), and that against R. oryzae was 0.5 mu g/ml (range, 0.06 to 2 mu g/ml); however, for the other Aspergillus species, as well as F. solani, MECs were >512 mu g/ml. A checkerboard inhibitory assay demonstrated synergy against A. fumigatus (median fractional inhibitory concentration index = 0.312 [range, 0.15 to 0.475]). The effect was additive to indifferent against R. oryzae and indifferent against other Aspergillus spp. and F. solani. We further investigated the pharmacodynamics of hyphal damage by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and examined the time-sequenced changes in hyphal ultrastructure. Significant synergistic hyphal damage was demonstrated with the combination of NZ (2 to 32 mu g/ml) and FK (0.03 to 0.5 mu g/ml) over a wide range of concentrations (P < 0.001). The synergistic effect was most pronounced after 12 h of incubation and was sustained through 24 h. Time-sequenced light and electron microscopic studies demonstrated that structural alterations of hyphae were profound, with marked transformation of hyphae to blastospore-like structures, in the presence of FK plus NZ, while fungi treated with a single drug showed partial recovery at 24 h. The methods used in this study may be applicable to elucidating the activity and interaction of other cell wall-active agents. In summary, these two cell wall-targeted antifungal agents, FK and NZ, showed marked time-dependent in vitro synergistic activity against A. fumigatus. JF - Antimicrobial Agents & Chemotherapy AU - Chiou, C C AU - Mavrogiorgos, N AU - Tillem, E AU - Hector, R AU - Walsh, T J AD - Bldg. 10, Rm, 13N-240, Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA, walsht@mail.nih.gov Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 3310 EP - 3321 VL - 45 IS - 12 SN - 0066-4804, 0066-4804 KW - Time dependence KW - Echinocandin KW - FK463 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Antibiotic synergism KW - Hyphae KW - Aspergillosis KW - Minimum inhibitory concentration KW - Nikkomycin KW - Aspergillus fumigatus KW - Antibiotic sensitivity testing KW - Pharmacodynamics KW - A 01067:Antifungal & fungicidal KW - K 03063:Effects of physical & chemical factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18294013?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Synergy%2C+pharmacodynamics%2C+and+time-sequenced+ultrastructural+changes+of+the+interaction+between+nikkomycin+Z+and+the+echinocandin+FK463+against+Aspergillus+fumigatus&rft.au=Chiou%2C+C+C%3BMavrogiorgos%2C+N%3BTillem%2C+E%3BHector%2C+R%3BWalsh%2C+T+J&rft.aulast=Chiou&rft.aufirst=C&rft.date=2001-12-01&rft.volume=45&rft.issue=12&rft.spage=3310&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Aspergillus fumigatus; Aspergillosis; Nikkomycin; Antibiotic synergism; Pharmacodynamics; Antibiotic sensitivity testing; Minimum inhibitory concentration; Hyphae ER - TY - JOUR T1 - Safety, tolerance, and pharmacokinetics of high-dose liposomal amphotericin B (AmBisome) in patients infected with Aspergillus species and other filamentous fungi: Maximum tolerated dose study AN - 18288216; 5347020 AB - We conducted a phase I-II study of the safety, tolerance, and plasma pharmacokinetics of liposomal amphotericin B (L-AMB; AmBisome) in order to determine its maximally tolerated dosage (MTD) in patients with infections due to Aspergillus spp. and other filamentous fungi. Dosage cohorts consisted of 7.5, 10.0, 12.5, and 15.0 mg/kg of body weight/day; a total of 44 patients were enrolled, of which 21 had a proven or probable infection (13 aspergillosis, 5 zygomycosis, 3 fusariosis). The MTD of L-AMB was at least 15 mg/kg/day. Infusion-related reactions of fever occurred in 8 (19%) and chills and/or rigors occurred in 5 (12%) of 43 patients. Three patients developed a syndrome of substernal chest tightness, dyspnea, and flank pain, which was relieved by diphenhydramine. Serum creatinine increased two times above baseline in 32% of the patients, but this was not dose related. Hepatotoxicity developed in one patient. Steady-state plasma pharmacokinetics were achieved by day 7. The maximum concentration of drug in plasma (C sub(max)) of L-AMB in the dosage cohorts of 7.5, 10.0, 12.5, and 15.0 mg/kg/day changed to 76, 120, 116, and 105 mu g/ml, respectively, and the mean area under the concentration-time curve at 24 h (AUC sub(24)) changed to 692, 1,062, 860, and 554 mu g times h/ml, respectively, while mean CL changed to 23, 18, 16, and 25 ml/h/kg, respectively. These data indicate that L-AMB follows dose-related changes in disposition processing (e.g., clearance) at dosages of greater than or equal to 7.5 mg/kg/day. Because several extremely ill patients had early death, success was determined for both the modified intent-to-treat and evaluable (7 days of therapy) populations. Response rates (defined as complete response and partial response) were similar for proven and probable infections. Response and stabilization, respectively, were achieved in 36 and 16% of the patients in the modified intent-to-treat population (n = 43) and in 52 and 13% of the patients in the 7-day evaluable population (n = 31). These findings indicate that L-AMB at dosages as high as 15 mg/kg/day follows nonlinear saturation-like kinetics, is well tolerated, and can provide effective therapy for aspergillosis and other filamentous fungal infections. JF - Antimicrobial Agents & Chemotherapy AU - Walsh, T J AU - Goodman, J L AU - Pappas, P AU - Bekersky, I AU - Buell, D N AU - Roden, M AU - Barrett, J AU - Anaissie, E J AD - Immunocompromised Host Section, National Cancer Institute, Building 10, Rm. 13N240, Bethesda, MD 20892, USA, walsht@mail.nih.gov Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 3487 EP - 3496 VL - 45 IS - 12 SN - 0066-4804, 0066-4804 KW - man KW - pharmacokinetics KW - Toxicology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Amphotericin B KW - Safety KW - Drug tolerance KW - Aspergillosis KW - Aspergillus KW - Clinical trials KW - Pharmacokinetics KW - Zygomycosis KW - Antibiotic tolerance KW - Dose-response effects KW - Dosage KW - Side effects KW - X 24114:Metabolism KW - K 03087:Fungi: human UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18288216?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Safety%2C+tolerance%2C+and+pharmacokinetics+of+high-dose+liposomal+amphotericin+B+%28AmBisome%29+in+patients+infected+with+Aspergillus+species+and+other+filamentous+fungi%3A+Maximum+tolerated+dose+study&rft.au=Walsh%2C+T+J%3BGoodman%2C+J+L%3BPappas%2C+P%3BBekersky%2C+I%3BBuell%2C+D+N%3BRoden%2C+M%3BBarrett%2C+J%3BAnaissie%2C+E+J&rft.aulast=Walsh&rft.aufirst=T&rft.date=2001-12-01&rft.volume=45&rft.issue=12&rft.spage=3487&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Aspergillus; Side effects; Amphotericin B; Safety; Clinical trials; Drug tolerance; Aspergillosis; Zygomycosis; Pharmacokinetics; Dosage; Antibiotic tolerance; Dose-response effects ER - TY - JOUR T1 - Molecular Dynamics Simulations of the Denaturation and Refolding of an RNA Tetraloop AN - 18278864; 5334460 AB - Tetraloops are very abundant structural elements of RNA that are formed by four nucleotides in a hairpin loop which is closed by a double stranded helical stem with some Watson-Crick base pairs. A tetraloop r(GCGAAGGC) was identified from the crystal structure of the central domain of 16S rRNA (727-730) in the Thermus thermophilus 30S ribosomal complex. The crystal structure of the 30S complex includes a total of 104 nucleotides from the central domain of the 16S rRNA and three ribosomal proteins S6, S15 and S18. Independent biochemical experiments have demonstrated that protein S15 plays the role in initiating the formation of the central domain of this complex. In the crystal, the tetraloop interacts with the protein S15 at two sites: one of them is associated with hydrogen bond interactions between residue His50 and nucleotide G730, and the other is associated with the occurrence of residue Arg53 beside A728. This paper uses molecular dynamics (MD) simulations to investigate the protein-dependent structural stability of the tetraloop and demonstrates the folding pathway of this tetraloop via melting denaturation and its subsequent refolding. Three important results are derived from these simulations: (i) The stability of nucleotide A728 appears to be protein dependent. Without the interaction with S15, A728 flips away from stacking with A729. (ii) The melting temperature demonstrated by the simulations is analogous to the results of thermodynamic experiments. In addition, the simulated folding of the tetraloop is stepwise: the native shape of the backbone is formed first; this is then followed by the formation of the Watson-Crick base pairs in the stem; and finally the hydrogen bonds and base stacking in the loop are formed. (iii) The tetraloop structure is similar to the crystal structure at salt concentrations of 0.1 M and 1.0 M used for the simulations, but the refolded structure at 0.1 M salt is more comparable to the crystal structure than at 1.0 M. The results from the simulations using both the Generalized Born continuum model and explicit solvent model (Particle Mesh Ewald) generate a similar pathway for unfolding/refolding of the tetraloop. JF - Journal of Biomolecular Structure and Dynamics AU - Li, W AU - Ma, B AU - Shapiro, BA AD - Laboratory of Experimental and Computational Biology Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 469, Room 150 Frederick, MD USA 21702, bshapiro@ncifcrf.gov Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 381 EP - 396 VL - 19 IS - 3 SN - 0739-1102, 0739-1102 KW - tetraloops KW - molecular dynamics KW - ribosomal subunit 30S KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Ribosomal proteins KW - Crystal structure KW - Thermus thermophilus KW - rRNA 16S KW - J 02726:RNA and ribosomes KW - N 14414:Structure and sequence UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18278864?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biomolecular+Structure+and+Dynamics&rft.atitle=Molecular+Dynamics+Simulations+of+the+Denaturation+and+Refolding+of+an+RNA+Tetraloop&rft.au=Li%2C+W%3BMa%2C+B%3BShapiro%2C+BA&rft.aulast=Li&rft.aufirst=W&rft.date=2001-12-01&rft.volume=19&rft.issue=3&rft.spage=381&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomolecular+Structure+and+Dynamics&rft.issn=07391102&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Thermus thermophilus; Ribosomal proteins; Crystal structure; rRNA 16S ER - TY - JOUR T1 - Environmental Contaminants as Etiologic Factors for Diabetes AN - 18277289; 5326153 AB - For both type 1 and type 2 diabetes mellitus, the rates have been increasing in the United States and elsewhere; rates vary widely by country, and genetic factors account for less than half of new cases. These observations suggest environmental factors cause both type 1 and type 2 diabetes. Occupational exposures have been associated with increased risk of diabetes. In addition, recent data suggest that toxic substances in the environment, other than infectious agents or exposures that stimulate an immune response, are associated with the occurrence of these diseases. We reviewed the epidemiologic data that addressed whether environmental contaminants might cause type 1 or type 2 diabetes. For type 1 diabetes, higher intake of nitrates, nitrites, and N-nitroso compounds, as well as higher serum levels of polychlorinated biphenyls have been associated with increased risk. Overall, however, the data were limited or inconsistent. With respect to type 2 diabetes, data on arsenic and 2,3,7,8-tetrachlorodibenzo-p-dioxin relative to risk were suggestive of a direct association but were inconclusive. The occupational data suggested that more data on exposure to N-nitroso compounds, arsenic, dioxins, talc, and straight oil machining fluids in relation to diabetes would be useful. Although environmental factors other than contaminants may account for the majority of type 1 and type 2 diabetes, the etiologic role of several contaminants and occupational exposures deserves further study. JF - Environmental Health Perspectives AU - Longnecker, M P AU - Daniels, J L AD - NIEHS EB, PO Box 12233, MD A3-05, Research Triangle Park, NC 27709-2233, USA, longnecker@niehs.nih.gov Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 871 EP - 876 VL - 109 IS - 6 SN - 0091-6765, 0091-6765 KW - man KW - N-Nitroso compounds KW - diabetes mellitus KW - environmental factors KW - Toxicology Abstracts; Health & Safety Science Abstracts; Pollution Abstracts KW - Risk assessment KW - Environmental factors KW - Dioxins KW - Oil KW - PCB compounds KW - Occupational exposure KW - Arsenic KW - TCDD KW - Diabetes mellitus KW - Reviews KW - Dioxin KW - X 24240:Miscellaneous KW - H 11000:Diseases/Injuries/Trauma KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18277289?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Environmental+Contaminants+as+Etiologic+Factors+for+Diabetes&rft.au=Longnecker%2C+M+P%3BDaniels%2C+J+L&rft.aulast=Longnecker&rft.aufirst=M&rft.date=2001-12-01&rft.volume=109&rft.issue=6&rft.spage=871&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Risk assessment; Occupational exposure; Arsenic; Dioxins; Reviews; PCB compounds; TCDD; Diabetes mellitus; Oil; Dioxin; Environmental factors ER - TY - JOUR T1 - Bioterrorism: A clear and present danger AN - 18266315; 5323498 AB - The anthrax attacks in the United States, juxtaposed against the September 11 terrorist attacks on New York and Washington, DC, have transformed a theoretical threat to stark reality. The biomedical research community will be an integral part of the preparation for, defense against and response to bioterrorism. JF - Nature Medicine AU - Lane, H C AU - La Montagne, J AU - Fauci, A S AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA, clane@nih.gov Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 1271 EP - 1273 VL - 7 IS - 12 SN - 1078-8956, 1078-8956 KW - biological warfare agents KW - bioterrorism KW - Toxicology Abstracts; Microbiology Abstracts B: Bacteriology; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Anthrax KW - Bacillus anthracis KW - Toxins KW - J 02855:Human Bacteriology: Others KW - X 24171:Microbial KW - A 01023:Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18266315?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Medicine&rft.atitle=Bioterrorism%3A+A+clear+and+present+danger&rft.au=Lane%2C+H+C%3BLa+Montagne%2C+J%3BFauci%2C+A+S&rft.aulast=Lane&rft.aufirst=H&rft.date=2001-12-01&rft.volume=7&rft.issue=12&rft.spage=1271&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bacillus anthracis; Anthrax; Toxins ER - TY - JOUR T1 - Evasion of human innate and acquired immunity by a bacterial homolog of CD11b that inhibits opsonophagocytosis AN - 18266137; 5323488 AB - Microbial pathogens must evade the human immune system to survive, disseminate and cause disease. By proteome analysis of the bacterium Group A Streptococcus (GAS), we identified a secreted protein with homology to the alpha -subunit of Mac-1, a leukocyte beta sub(2) integrin required for innate immunity to invading microbes. The GAS Mac-1-like protein (Mac) was secreted by most pathogenic strains, produced in log-phase and controlled by the covR-covS two-component gene regulatory system, which also regulates transcription of other GAS virulence factors. Patients with GAS infection had titers of antibody specific to Mac that correlated with the course of disease, demonstrating that Mac was produced in vivo. Mac bound to CD16 (Fc gamma RIIIB) on the surface of human polymorphonuclear leukocytes and inhibited opsonophagocytosis and production of reactive oxygen species, which resulted in significantly decreased pathogen killing. Thus, by mimicking a host-cell receptor required for an innate immune response, the GAS Mac protein inhibits professional phagocyte function by a novel strategy that enhances pathogen survival, establishment of infection and dissemination. JF - Nature Medicine AU - Lei, B AU - DeLeo AU - Hoe, N P AU - Graham, M R AU - Mackie, S M AU - Cole, R L AU - Liu, M AU - Hill, H R AU - Low, DE AU - Federle, MJ AU - Scott, J R AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, USA, jmusser@niaid.nih.gov Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 1298 EP - 1305 VL - 7 IS - 12 SN - 1078-8956, 1078-8956 KW - man KW - CD11b antigen KW - CD16 antigen KW - Mac-1 antigen KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Phagocytes KW - Immune system KW - Phagocytosis KW - Streptococcus pyogenes KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18266137?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Medicine&rft.atitle=Evasion+of+human+innate+and+acquired+immunity+by+a+bacterial+homolog+of+CD11b+that+inhibits+opsonophagocytosis&rft.au=Lei%2C+B%3BDeLeo%3BHoe%2C+N+P%3BGraham%2C+M+R%3BMackie%2C+S+M%3BCole%2C+R+L%3BLiu%2C+M%3BHill%2C+H+R%3BLow%2C+DE%3BFederle%2C+MJ%3BScott%2C+J+R%3BMusser%2C+J+M&rft.aulast=Lei&rft.aufirst=B&rft.date=2001-12-01&rft.volume=7&rft.issue=12&rft.spage=1298&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus pyogenes; Phagocytosis; Immune system; Phagocytes ER - TY - JOUR T1 - Pairing of P1 plasmid partition sites by ParB AN - 18247521; 5308507 AB - The mechanisms by which bacterial plasmids and chromosomes are partitioned are largely obscure, but it has long been assumed that the molecules to be separated are initially paired, as are sister chromatids in mitosis. We offer in vivo evidence that the partition protein ParB encoded by the bacterial plasmid P1 can pair cis-acting partition sites of P1 inserted in a small, multicopy plasmid. ParB was shown previously to be capable of extensive spreading along DNA flanking the partition sites. Experiments in which ParB spreading was constrained by physical roadblocks suggest that extensive spreading is not required for the pairing process. JF - Molecular Microbiology AU - Edgar, R AU - Chattoraj, D K AU - Yarmolinsky, M AD - Laboratory of Biochemistry, National Cancer Institute, NIH, 37 Convent Drive, Bethesda, MD 20892-4255, USA., myarmo@helix.nih.gov Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 1363 EP - 1370 PB - Blackwell Science Ltd VL - 42 IS - 5 SN - 0950-382X, 0950-382X KW - pairing KW - ParB protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Chromosomes KW - Plasmids KW - J 02760:Plasmids KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18247521?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Pairing+of+P1+plasmid+partition+sites+by+ParB&rft.au=Edgar%2C+R%3BChattoraj%2C+D+K%3BYarmolinsky%2C+M&rft.aulast=Edgar&rft.aufirst=R&rft.date=2001-12-01&rft.volume=42&rft.issue=5&rft.spage=1363&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2001.02717.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chromosomes; Plasmids DO - http://dx.doi.org/10.1046/j.1365-2958.2001.02717.x ER - TY - JOUR T1 - Patterns of Genetic Diversity in Remaining Giant Panda Populations AN - 18245884; 5307901 AB - The giant panda (Ailuropoda melanoleuca) is among the more familiar symbols of species conservation. The protection of giant panda populations has been aided recently by the establishment of more and better-managed reserves in existing panda habitat located in six mountain ranges in western China. These remaining populations are becoming increasingly isolated from one another, however, leading to the concern that historic patterns of gene flow will be disrupted and that reduced population sizes will lead to diminished genetic variability. We analyzed four categories of molecular genetic markers (mtDNA restriction-fragment-length polymorphisms [RFLP], mtDNA control region sequences, nuclear multilocus DNA fingerprints, and microsatellite size variation) in giant pandas from three mountain populations (Qionglai, Minshan, and Qinling) to assess current levels of genetic diversity and to detect evidence of historic population subdivisions. The three populations had moderate levels of genetic diversity compared with similarly studied carnivores for all four gene measures, with a slight but consistent reduction in variability apparent in the smaller Qinling population. That population also showed significant differentiation consistent with its isolation since historic times. From a strictly genetic perspective, the giant panda species and the three populations look promising insofar as they have retained a large amount of genetic diversity in each population, although evidence of recent population reduction-likely from habitat loss-is apparent. Ecological management to increase habitat, population expansion, and gene flow would seem an effective strategy to stabilize the decline of this endangered species. JF - Conservation Biology AU - Lu, Z AU - Johnson, W E AU - Menotti-Raymond, M AU - Yuhki, N AU - Martenson, J S AU - Mainka, S AU - Shi-Qiang, H AU - Zhihe, Z AU - Li, G AU - Pan, W AU - Mao, X AU - O'Brien, S J AD - Laboratory of Genomic Diversity, National Cancer Institute, Frederick, MD 21702-1201, U.S.A., obrien@ncifcrf.gov Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 1596 EP - 1607 PB - Blackwell Science Ltd VL - 15 IS - 6 SN - 0888-8892, 0888-8892 KW - Giant Panda KW - Genetics Abstracts; Ecology Abstracts KW - Genetic diversity KW - Habitat KW - Ailuropoda melanoleuca KW - Population genetics KW - Mitochondrial DNA KW - Gene flow KW - China, People's Rep. KW - Conservation genetics KW - G 07381:General KW - G 07290:Population genetics KW - D 04705:Conservation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18245884?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Conservation+Biology&rft.atitle=Patterns+of+Genetic+Diversity+in+Remaining+Giant+Panda+Populations&rft.au=Lu%2C+Z%3BJohnson%2C+W+E%3BMenotti-Raymond%2C+M%3BYuhki%2C+N%3BMartenson%2C+J+S%3BMainka%2C+S%3BShi-Qiang%2C+H%3BZhihe%2C+Z%3BLi%2C+G%3BPan%2C+W%3BMao%2C+X%3BO%27Brien%2C+S+J&rft.aulast=Lu&rft.aufirst=Z&rft.date=2001-12-01&rft.volume=15&rft.issue=6&rft.spage=1596&rft.isbn=&rft.btitle=&rft.title=Conservation+Biology&rft.issn=08888892&rft_id=info:doi/10.1046%2Fj.1523-1739.2001.00086.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Ailuropoda melanoleuca; China, People's Rep.; Population genetics; Genetic diversity; Conservation genetics; Gene flow; Mitochondrial DNA; Habitat DO - http://dx.doi.org/10.1046/j.1523-1739.2001.00086.x ER - TY - JOUR T1 - Promoter CpG Methylation of Hox-a10 and Hox-a11 in Mouse Uterus Not Altered Upon Neonatal Diethylstilbestrol Exposure AN - 18238870; 5300693 AB - Mouse abdominal B-like Hoxa genes are expressed and functionally required in the developing reproductive tracts. Mice lacking either Hoxa-10 or Hoxa-11, two of the AbdB Hoxa genes, exhibit abnormal uterine development similar to that induced by in utero diethylstilbestrol (DES) exposure. Indeed, uterine Hoxa-10 and Hoxa-11 expression is potently repressed by perinatal DES exposure, providing a potential molecular mechanism for DES-induced reproductive tract malformations. We have shown previously that DES can permanently alter uterine lactoferrin gene expression through modulation of the lactoferrin promoter methylation pattern. Here we ask whether a similar mechanism also functions to deregulate uterine Hoxa-10 or Hoxa-11 expression during neonatal DES exposure. We mapped the Hoxa-10 promoter by cloning a 1.485 kb DNA fragment 5' of the Hoxa-10 exon1a, A 5' rapid amplification of cDNA ends (RACE) experiment revealed a transcription start site for the a10-1 transcript. Functional analysis of the proximal 200-bp sequences demonstrated significant promoter activity, confirming the location of the Hoxa-10 promoter. Moreover, methylation assays performed on eight CpGs in Hoxa-10 and 19 CpGs in Hoxa-11 proximal promoters demonstrated that all these CpGs were highly unmethylated in both control and DES-dosed mice from postnatal day 5 to day 30. Significant methylation around Hoxa-10 and Hoxa-11 promoters was only observed in DES-induced uterine carcinomas in 18-mo-old mice. Our results suggest that DES-induced downregulations of Hoxa-10 or Hoxa-11 gene expression are not associated with methylation changes in their proximal promoters and that gene imprinting by developmental DES exposure may be a gene-specific phenomenon. JF - Molecular Carcinogenesis AU - Li, Shuanfang AU - Ma, Liang AU - Chiang, Tung-chin AU - Burow, M AU - Newbold, R R AU - Negishi, Masahiko AU - Barrett, J C AU - Mclachlan, JA AD - LBC at NIEHS, C2-10, P.O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 213 EP - 219 VL - 32 IS - 4 SN - 0899-1987, 0899-1987 KW - mice KW - Hox-a10 gene KW - Hox-a11 gene KW - abdominal B gene KW - lactoferrin KW - Toxicology Abstracts; Genetics Abstracts KW - Uterus KW - Carcinogens KW - Gene regulation KW - DNA methylation KW - Reproduction KW - Diethylstilbestrol KW - X 24117:Biochemistry KW - G 07397:Rodentia (mice) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18238870?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Carcinogenesis&rft.atitle=Promoter+CpG+Methylation+of+Hox-a10+and+Hox-a11+in+Mouse+Uterus+Not+Altered+Upon+Neonatal+Diethylstilbestrol+Exposure&rft.au=Li%2C+Shuanfang%3BMa%2C+Liang%3BChiang%2C+Tung-chin%3BBurow%2C+M%3BNewbold%2C+R+R%3BNegishi%2C+Masahiko%3BBarrett%2C+J+C%3BMclachlan%2C+JA&rft.aulast=Li&rft.aufirst=Shuanfang&rft.date=2001-12-01&rft.volume=32&rft.issue=4&rft.spage=213&rft.isbn=&rft.btitle=&rft.title=Molecular+Carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Carcinogens; Gene regulation; DNA methylation; Uterus; Diethylstilbestrol; Reproduction ER - TY - JOUR T1 - Glutathione S-transferase Pi expression in forestomach carcinogenesis process induced by gavage-administered 2,4-hexadienal in the F344 rat AN - 18237892; 5302402 AB - 2,4-Hexadienal (2,4-Hx), an unsaturated aldehyde formed by in vivo and in vitro peroxidation of unsaturated lipid induced, in National Toxicology Program (NTP) gavage studies of F344 rats, forestomach hyperplasia in 13-week and 2-year exposures and squamous papilloma and carcinoma in 2-year studies. Hyperplasia was characterized by thickening of all layers of epithelium with particularly prominent proliferation of the basal cells. The present investigation describes the nature and potential significance of glutathione-S-transferase-Pi (GST-Pi) immunoexpression of normal forestomach epithelium, compared to that of 2,4-Hx-related basal cell hyperplasia and squamous cell papilloma and carcinoma. Paraffin-embedded forestomachs from these NTP studies were used to investigate possible correlations between the carcinogenic process and expression of GST-Pi, a physiological metabolic barrier and an inducible phase II detoxifying enzyme suggested to decrease the responsiveness of reactive oxygen species (ROS) and organic electrophilic compounds. The amount of immunopositive staining was graded on a scale of 0 (no staining) to 4 (marked staining). The simple basal epithelium of control rats showed strong immunopositivity. In cases of basal cell hyperplasia from the 13-week and 2-year studies, these cells usually expressed strong immunopositivity for GST-Pi (grade 3 to 4). In the 2-year treated animals only, occasional focal reduction (grade 0 to 2) in immunoreactivity for GST-Pi was noted. In papillomas and squamous cell carcinomas, a wide range of GST-Pi expression was observed, perhaps indicating irregularities in its induction or change in the phenotype of these cells compared to normal or hyperplastic ones. Reduced expression of GST-Pi by the foci of basal cell hyperplasia and in tumor cells may suggest changes in cellular protection from oxidative or electrophilic DNA damage; these changes may result in genetic alterations and be the precursor to clonal expansion. JF - Archives of Toxicology AU - Nyska, A AU - Moomaw, C I AU - Lomnitski, L AU - Chan, P F AD - Laboratory of Experimental Pathology, MD B3-06, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, PO Box 12233, Research Triangle Park, North Carolina 27709, USA, nyska@niehs.nih.gov Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 618 EP - 624 PB - Springer-Verlag, [URL:http://link.springer.de/link/service/journals/00204/bibs/1075 010/10750618.htm] VL - 75 IS - 10 SN - 0340-5761, 0340-5761 KW - glutathione S-transferase-Pi KW - rats KW - 2,4-Hexadienal KW - Toxicology Abstracts KW - Hyperplasia KW - Peroxidation KW - Carcinogenesis KW - Glutathione transferase KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18237892?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+Toxicology&rft.atitle=Glutathione+S-transferase+Pi+expression+in+forestomach+carcinogenesis+process+induced+by+gavage-administered+2%2C4-hexadienal+in+the+F344+rat&rft.au=Nyska%2C+A%3BMoomaw%2C+C+I%3BLomnitski%2C+L%3BChan%2C+P+F&rft.aulast=Nyska&rft.aufirst=A&rft.date=2001-12-01&rft.volume=75&rft.issue=10&rft.spage=618&rft.isbn=&rft.btitle=&rft.title=Archives+of+Toxicology&rft.issn=03405761&rft_id=info:doi/10.1007%2Fs002040100278 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Carcinogenesis; Glutathione transferase; Hyperplasia; Peroxidation DO - http://dx.doi.org/10.1007/s002040100278 ER - TY - JOUR T1 - Identification of Independent Streptococcus gordonii SspA and SspB Functions in Coaggregation with Actinomyces naeslundii AN - 18219545; 5288512 AB - The initial stages of dental plaque formation involve the adherence of early colonizing organisms such as Streptococcus gordonii and Actinomyces naeslundii to the saliva-coated tooth surface and to each other. The S. gordonii surface proteins SspA and SspB are known to play a role in adherence to salivary proteins and mediate coaggregation with other bacteria. Coaggregation is the adhesin receptor-mediated interaction between genetically distinct cell types and appears to be ubiquitous among oral isolates. To define the function of SspA and SspB separately on the surface of their natural host, we constructed and analyzed the coaggregation properties of an isogenic sspB mutant of S. gordonii DL1, an sspAB double mutant, and a previously described sspA mutant. A. naeslundii strains have been previously classified into six coaggregation groups based on the nature of their coaggregations with S. gordonii DL1 and other oral streptococci. Coaggregation assays with the sspA and sspB mutants showed that SspA and SspB are the streptococcal proteins primarily responsible for defining these coaggregation groups and, thus, are highly significant in the establishment of early dental plaque. SspA exhibited two coaggregation-specific functions. It participated in lactose-inhibitable and -noninhibitable interactions, while SspB mediated only lactose-noninhibitable coaggregations. Accordingly, the sspAB double mutant lacked these functions and allowed us to detect a third coaggregation interaction with one of these organisms. These proteins may play an important role in development of S. gordonii-A. naeslundii communities in early dental plaque. Understanding these adhesin proteins will aid investigations of complex microbial communities that characterize periodontal diseases. JF - Infection and Immunity AU - Egland, P G AU - Du, L D AU - Kolenbrander, P E AD - National Institutes of Health/NIDCR, Building 30, Room 310, 30 Convent Dr. MSC 4350, Bethesda, MD 20892-4350., pkolenbrander@dir.nidcr.nih.gov Y1 - 2001/12// PY - 2001 DA - Dec 2001 SP - 7512 EP - 7516 VL - 69 IS - 12 SN - 0019-9567, 0019-9567 KW - function KW - coaggregation KW - SspA protein KW - SspB protein KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Streptococcus gordonii KW - Dental plaque KW - Actinomyces naeslundii KW - Mutants KW - G 07320:Bacterial genetics KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18219545?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Identification+of+Independent+Streptococcus+gordonii+SspA+and+SspB+Functions+in+Coaggregation+with+Actinomyces+naeslundii&rft.au=Egland%2C+P+G%3BDu%2C+L+D%3BKolenbrander%2C+P+E&rft.aulast=Egland&rft.aufirst=P&rft.date=2001-12-01&rft.volume=69&rft.issue=12&rft.spage=7512&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.69.12.7512-7516.2001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus gordonii; Actinomyces naeslundii; Dental plaque; Mutants DO - http://dx.doi.org/10.1128/IAI.69.12.7512-7516.2001 ER - TY - JOUR T1 - A strategy for high throughput HLA-DQ typing AN - 18118375; 5210880 AB - We have developed a high throughput HLA typing methodology that is a modification of the standard sequence-specific primer method. This approach is distinct from other methods using an automated DNA analyzer, as more than one gene is typed in a single lane. We have optimized the method for use on an ABI 373 automated genotyping machine. Primers were designed to preferentially amplify DNA fragments of the generic allelic groups of the DQA1 and DQB1 loci. PCR products representing alleles at the DQA1 locus were amplified using a different fluorescent dye than the PCR products from the DQB1 locus. Only three PCR reactions are required for low resolution typing of DQA1 and DQB1. Use of different labeled primers enables genotyping for both loci in a single gel lane, allowing for 64 samples to be typed at low resolution for both DQA1 and DQB1 on a single gel. Automated allele assignments were determined based on DNA migration distance through a polyacrylamide gel using a standard genotype allele-calling program. Accuracy of this method is greater than 98% for both loci. The strategy described here may be adapted to include more loci or to produce higher resolution typing of alleles encoded by these loci. It can be readily optimized for use on other slab gel or capillary electrophoresis systems. JF - Journal of Immunological Methods AU - Feolo, M AU - Fuller, T C AU - Taylor, M AU - Zone, J J AU - Neuhausen, S L AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD USA Y1 - 2001/12/01/ PY - 2001 DA - 2001 Dec 01 SP - 65 EP - 71 PB - Elsevier Science VL - 258 IS - 1-2 SN - 0022-1759, 0022-1759 KW - DQA1 loci KW - man KW - DQB1 loci KW - high-throughput screening KW - histocompatibility locus HLA KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Capillary KW - Electrophoresis KW - Genotyping KW - Polymerase chain reaction KW - Gel electrophoresis KW - W3 33240:Immunology KW - F 06713:Physicochemical methods KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18118375?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunological+Methods&rft.atitle=A+strategy+for+high+throughput+HLA-DQ+typing&rft.au=Feolo%2C+M%3BFuller%2C+T+C%3BTaylor%2C+M%3BZone%2C+J+J%3BNeuhausen%2C+S+L&rft.aulast=Feolo&rft.aufirst=M&rft.date=2001-12-01&rft.volume=258&rft.issue=1-2&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Genotyping; Polymerase chain reaction; Gel electrophoresis; Capillary; Electrophoresis ER - TY - JOUR T1 - Neurotoxic properties of cerebrospinal fluid from behaviorally impaired autoimmune mice. AN - 72293917; 11716824 AB - The chronic, lupus-like autoimmune disease in MRL-lpr mice is associated with leucocyte infiltration into the choroid plexus, brain cell death, and deficits in motivated behavior. The presence of lymphoid cells in the ventricular lumen and the increased number of TUNEL-positive cells in periventricular areas led to the hypothesis that immune cells enter into the cerebrospinal fluid (CSF) and induce primary neuronal damage in regions bordering the cerebral ventricles. Using an in vitro approach, we presently examine the possibility that CSF from autoimmune mice is neurotoxic and/or gliotoxic. The CSF and serum from diseased MRL-lpr mice, less symptomatic MRL +/+ controls, and healthy Swiss/Webster mice (non-autoimmune controls) were frozen until their effects on the viability of pyramidal neurons and astrocytes were assessed in a two-color fluorescence assay. Significant reduction in neuronal viability (in some cases as low as 67%) was observed in the co-cultures of hippocampal neurons and astrocytes incubated for 24 h with CSF from autoimmune MRL-lpr mice. The viability of astrocytes did not differ among the groups, and the CSF from autoimmune mice appeared more toxic than the serum. The behavior of MRL-lpr mice differed significantly from the control groups, as indicated by impaired exploration, reduced intake of palatable food, and excessive immobility in the forced swim test. The present results suggest that CSF from the behaviorally impaired lupus-prone mice is neurotoxic and are consistent with the hypothesis that neuroactive metabolites are produced intrathecally in neuropsychiatric lupus erythematosus. JF - Brain research AU - Maric, D AU - Millward, J M AU - Ballok, D A AU - Szechtman, H AU - Denburg, J A AU - Barker, J L AU - Sakic, B AD - Laboratory of Neurophysiology, NINDS, National Institute of Health, Bethesda, MD, USA. Y1 - 2001/11/30/ PY - 2001 DA - 2001 Nov 30 SP - 183 EP - 193 VL - 920 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Index Medicus KW - Animals KW - Coculture Techniques KW - Eating -- physiology KW - Brain -- cytology KW - Brain -- drug effects KW - Astrocytes -- physiology KW - Motor Activity -- physiology KW - Mice KW - Swimming -- psychology KW - Pyramidal Cells -- physiology KW - Cell Survival -- drug effects KW - Drinking -- physiology KW - Neurons -- physiology KW - Mice, Inbred MRL lpr KW - Hippocampus -- pathology KW - Cell Survival -- physiology KW - Male KW - Neurotoxicity Syndromes -- psychology KW - Autoimmunity -- physiology KW - Behavior, Animal -- physiology KW - Cerebrospinal Fluid -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72293917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Neurotoxic+properties+of+cerebrospinal+fluid+from+behaviorally+impaired+autoimmune+mice.&rft.au=Maric%2C+D%3BMillward%2C+J+M%3BBallok%2C+D+A%3BSzechtman%2C+H%3BDenburg%2C+J+A%3BBarker%2C+J+L%3BSakic%2C+B&rft.aulast=Maric&rft.aufirst=D&rft.date=2001-11-30&rft.volume=920&rft.issue=1-2&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-07 N1 - Date created - 2001-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein kinase C regulates FADD recruitment and death-inducing signaling complex formation in Fas/CD95-induced apoptosis. AN - 72292076; 11581255 AB - Activation of protein kinase C (PKC) triggers cellular signals that inhibit Fas/CD95-induced cell death in Jurkat T-cells by poorly defined mechanisms. Previously, we have shown that one effect of PKC on Fas/CD95-dependent cell death occurs through inhibition of cell shrinkage and K(+) efflux (Gómez-Angelats, M., Bortner, C. D., and Cidlowski, J. A. (2000) J. Biol. Chem. 275, 19609-19619). Here we report that PKC alters Fas/CD95 signaling from the plasma membrane to the activation of caspases by exerting a profound action on survival/cell death decisions. Specific activation of PKC with 12-O-tetradecanoylphorbol-13-acetate or bryostatin-1 induced translocation of PKC from the cytosol to the membrane and effectively inhibited cell shrinkage and cell death triggered by anti-Fas antibody in Jurkat cells. In contrast, inhibition of classical PKC isotypes with Gö6976 exacerbated the effect of Fas activation on both apoptotic volume decrease and cell death. PKC activation/inhibition did not affect anti-Fas antibody binding to the cell surface, intracellular levels of FADD (Fas-associated protein with death domain), or c-FLIP (cellular FLICE-like inhibitory protein) expression. However, processing/activation of both caspase-8 and caspase-3 and BID cleavage were markedly blocked upon PKC activation and, conversely, were augmented during PKC inhibition, suggesting a role for PKC upstream of caspase-8 processing and activation. Analysis of death-inducing signaling complex (DISC) formation was carried out to examine the influence of PKC on recruitment of both FADD and procaspase-8 to the Fas receptor. PKC activation blocked FADD recruitment and caspase-8 activation and thus DISC formation in both type I and II cells. In contrast, inhibition of classical PKCs promoted the opposite effect on the Fas pathway by rapidly increasing FADD recruitment, caspase-8 activation, and DISC formation. Together, these data show that PKC finely modulates Fas/CD95 signaling by altering the efficiency of DISC formation. JF - The Journal of biological chemistry AU - Gómez-Angelats, M AU - Cidlowski, J A AD - Laboratory of Signal Transduction, Molecular Endocrinology Group, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/11/30/ PY - 2001 DA - 2001 Nov 30 SP - 44944 EP - 44952 VL - 276 IS - 48 SN - 0021-9258, 0021-9258 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Antigens, CD95 KW - Antineoplastic Agents KW - Bryostatins KW - Carbazoles KW - Carcinogens KW - Carrier Proteins KW - Enzyme Inhibitors KW - FADD protein, human KW - Fas-Associated Death Domain Protein KW - Indoles KW - Lactones KW - Macrolides KW - Mitogens KW - Go 6976 KW - 136194-77-9 KW - bryostatin 1 KW - 37O2X55Y9E KW - Protein Kinase C KW - EC 2.7.11.13 KW - CASP3 protein, human KW - EC 3.4.22.- KW - CASP8 protein, human KW - CASP9 protein, human KW - Caspase 3 KW - Caspase 8 KW - Caspase 9 KW - Caspases KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Humans KW - Jurkat Cells KW - Cell Separation KW - Caspases -- metabolism KW - Lactones -- pharmacology KW - Flow Cytometry KW - Signal Transduction KW - Cytosol -- metabolism KW - Subcellular Fractions KW - Precipitin Tests KW - Protein Binding KW - Blotting, Western KW - Carbazoles -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Indoles -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - Protein Transport KW - Protein Kinase C -- metabolism KW - Antigens, CD95 -- metabolism KW - Carrier Proteins -- metabolism KW - Apoptosis KW - Protein Kinase C -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72292076?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Protein+kinase+C+regulates+FADD+recruitment+and+death-inducing+signaling+complex+formation+in+Fas%2FCD95-induced+apoptosis.&rft.au=G%C3%B3mez-Angelats%2C+M%3BCidlowski%2C+J+A&rft.aulast=G%C3%B3mez-Angelats&rft.aufirst=M&rft.date=2001-11-30&rft.volume=276&rft.issue=48&rft.spage=44944&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-10 N1 - Date created - 2001-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Repeated cocaine administration into the rat ventral tegmental area produces behavioral sensitization to a systemic cocaine challenge. AN - 72270957; 11704265 AB - The aim of the present study was to investigate the capacity of repeated administration of cocaine (5 nmol/side) or the selective dopamine re-uptake inhibitor GBR 12909 (15 nmol/side) into the ventral tegmental area (VTA) to initiate behavioral sensitization to systemically administered cocaine (15 mg/kg, intraperitoneally). Following 1 week of withdrawal from intra-VTA treatment, cocaine or GBR 12909 pretreated animals displayed sensitized locomotor and rearing behavior to acute systemic cocaine administration. These data support the possibility that increased dopamine transmission in the VTA is involved in the cellular events that determine the initiation of behavioral sensitization to cocaine. JF - Behavioural brain research AU - Cornish, J L AU - Kalivas, P W AD - Department of Physiology and Neuroscience, Medical University of South Carolina, 29425, USA. jcornish@intra.nida.nih.gov Y1 - 2001/11/29/ PY - 2001 DA - 2001 Nov 29 SP - 205 EP - 209 VL - 126 IS - 1-2 SN - 0166-4328, 0166-4328 KW - Piperazines KW - 0 KW - vanoxerine KW - 90X28IKH43 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Rats KW - Injections, Intraperitoneal KW - Animals KW - Rats, Sprague-Dawley KW - Synaptic Transmission -- drug effects KW - Premedication KW - Microinjections KW - Piperazines -- pharmacology KW - Drug Synergism KW - Male KW - Arousal -- drug effects KW - Motor Activity -- drug effects KW - Ventral Tegmental Area -- drug effects KW - Cocaine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72270957?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Behavioural+brain+research&rft.atitle=Repeated+cocaine+administration+into+the+rat+ventral+tegmental+area+produces+behavioral+sensitization+to+a+systemic+cocaine+challenge.&rft.au=Cornish%2C+J+L%3BKalivas%2C+P+W&rft.aulast=Cornish&rft.aufirst=J&rft.date=2001-11-29&rft.volume=126&rft.issue=1-2&rft.spage=205&rft.isbn=&rft.btitle=&rft.title=Behavioural+brain+research&rft.issn=01664328&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-22 N1 - Date created - 2001-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A 28-year-old man addicted to cocaine. AN - 72308451; 11722273 JF - JAMA AU - Hyman, S E AD - National Institute of Mental Health, 6001 Executive Blvd, Room 8235, MSC 9669, Bethesda, MD 20892-9669, USA. shyman@mail.nih.gov Y1 - 2001/11/28/ PY - 2001 DA - 2001 Nov 28 SP - 2586 EP - 2594 VL - 286 IS - 20 SN - 0098-7484, 0098-7484 KW - Acetates KW - 0 KW - Amines KW - Crack Cocaine KW - Cyclohexanecarboxylic Acids KW - Excitatory Amino Acid Antagonists KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - gabapentin KW - 6CW7F3G59X KW - Abridged Index Medicus KW - Index Medicus KW - Cost of Illness KW - Risk Factors KW - Humans KW - Brain -- drug effects KW - Excitatory Amino Acid Antagonists -- therapeutic use KW - Adult KW - Acetates -- therapeutic use KW - Male KW - Cocaine-Related Disorders -- psychology KW - Cocaine-Related Disorders -- therapy KW - Cocaine-Related Disorders -- epidemiology KW - Crack Cocaine -- pharmacology KW - Cocaine-Related Disorders -- rehabilitation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72308451?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=proceeding&rft.jtitle=JAMA&rft.atitle=A+28-year-old+man+addicted+to+cocaine.&rft.au=Hyman%2C+S+E&rft.aulast=Hyman&rft.aufirst=S&rft.date=2001-11-28&rft.volume=286&rft.issue=20&rft.spage=2586&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-28 N1 - Date created - 2001-11-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 2002 Feb 27;287(8):988 [11866643] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Death due to bioterrorism-related inhalational anthrax: report of 2 patients. AN - 72305526; 11722269 AB - On October 9, 2001, a letter containing anthrax spores was mailed from New Jersey to Washington, DC. The letter was processed at a major postal facility in Washington, DC, and opened in the Senate's Hart Office Building on October 15. Between October 19 and October 26, there were 5 cases of inhalational anthrax among postal workers who were employed at that major facility or who handled bulk mail originating from that facility. The cases of 2 postal workers who died of inhalational anthrax are reported here. Both patients had nonspecific prodromal illnesses. One patient developed predominantly gastrointestinal symptoms, including nausea, vomiting, and abdominal pain. The other patient had a "flulike" illness associated with myalgias and malaise. Both patients ultimately developed dyspnea, retrosternal chest pressure, and respiratory failure requiring mechanical ventilation. Leukocytosis and hemoconcentration were noted in both cases prior to death. Both patients had evidence of mediastinitis and extensive pulmonary infiltrates late in their course of illness. The durations of illness were 7 days and 5 days from onset of symptoms to death; both patients died within 24 hours of hospitalization. Without a clinician's high index of suspicion, the diagnosis of inhalational anthrax is difficult during nonspecific prodromal illness. Clinicians have an urgent need for prompt communication of vital epidemiologic information that could focus their diagnostic evaluation. Rapid diagnostic assays to distinguish more common infectious processes from agents of bioterrorism also could improve management strategies. JF - JAMA AU - Borio, L AU - Frank, D AU - Mani, V AU - Chiriboga, C AU - Pollanen, M AU - Ripple, M AU - Ali, S AU - DiAngelo, C AU - Lee, J AU - Arden, J AU - Titus, J AU - Fowler, D AU - O'Toole, T AU - Masur, H AU - Bartlett, J AU - Inglesby, T AD - Johns Hopkins Center for Civilian Biodefense Studies, Johns Hopkins University, Candler Bldg, Suite 850, 111 Market Pl, Baltimore, MD 21202, USA. lborio@nih.gov Y1 - 2001/11/28/ PY - 2001 DA - 2001 Nov 28 SP - 2554 EP - 2559 VL - 286 IS - 20 SN - 0098-7484, 0098-7484 KW - Anti-Bacterial Agents KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Occupational Exposure KW - Anti-Bacterial Agents -- therapeutic use KW - Fatal Outcome KW - Mediastinitis -- diagnostic imaging KW - Dyspnea -- complications KW - Humans KW - Tomography, X-Ray Computed KW - Respiration, Artificial KW - Pleural Effusion -- diagnostic imaging KW - Tachycardia -- etiology KW - Abdominal Pain -- complications KW - Radiography, Thoracic KW - Heart Arrest -- etiology KW - Nausea -- complications KW - Bradycardia -- etiology KW - District of Columbia KW - Homicide KW - Leukocytosis KW - Blood -- microbiology KW - Fever -- complications KW - Middle Aged KW - Postal Service KW - Male KW - Bacillus anthracis -- isolation & purification KW - Anthrax -- diagnosis KW - Respiratory Tract Infections -- microbiology KW - Anthrax -- physiopathology KW - Respiratory Tract Infections -- physiopathology KW - Anthrax -- blood KW - Anthrax -- therapy KW - Respiratory Tract Infections -- blood KW - Respiratory Tract Infections -- therapy KW - Bioterrorism KW - Respiratory Tract Infections -- diagnosis KW - Spores, Bacterial -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72305526?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA&rft.atitle=Death+due+to+bioterrorism-related+inhalational+anthrax%3A+report+of+2+patients.&rft.au=Borio%2C+L%3BFrank%2C+D%3BMani%2C+V%3BChiriboga%2C+C%3BPollanen%2C+M%3BRipple%2C+M%3BAli%2C+S%3BDiAngelo%2C+C%3BLee%2C+J%3BArden%2C+J%3BTitus%2C+J%3BFowler%2C+D%3BO%27Toole%2C+T%3BMasur%2C+H%3BBartlett%2C+J%3BInglesby%2C+T&rft.aulast=Borio&rft.aufirst=L&rft.date=2001-11-28&rft.volume=286&rft.issue=20&rft.spage=2554&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-28 N1 - Date created - 2001-11-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 2002 Feb 27;287(8):984; author reply 985 [11866635] JAMA. 2002 Feb 27;287(8):984-5 [11866636] JAMA. 2001 Nov 28;286(20):2595-7 [11722275] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An in vivo ESR spin-trapping study: free radical generation in rats from formate intoxication--role of the Fenton reaction. AN - 72298764; 11717423 AB - Electron spin resonance spectroscopy has been used to study free radical generation in rats with acute sodium formate poisoning. The in vivo spin-trapping technique was used with alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone (POBN), which reacts with free radical metabolites to form radical adducts, which were detected in the bile and urine samples from Fischer rats. The use of [(13)C]-sodium formate and computer simulations of the spectra identified the 12-line spectrum as arising from the POBN/carbon dioxide anion radical adduct. The identification of POBN/*CO(2)(-) radical adduct provides direct electron spin resonance spectroscopy evidence for the formation of *CO(2)(-) radicals during acute intoxication by sodium formate, suggesting a free radical metabolic pathway. To study the mechanism of free radical generation by formate, we tested several known inhibitors. Both allopurinol, an inhibitor of xanthine oxidase, and aminobenzotriazole, a cytochrome P450 inhibitor, decreased free radical formation from formate, which may imply a dependence on hydrogen peroxide. In accord with this hypothesis, the catalase inhibitor 3-aminotriazole caused a significant increase in free radical formation. The iron chelator Desferal decreased the formation of free radicals up to 2-fold. Presumably, iron plays a role in the mechanism of free radical generation by formate via the Fenton reaction. The detection of formate free radical metabolites generated in vivo and the key role of the Fenton reaction in this process may be important for understanding the pathogenesis of both formate and methanol intoxication. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Dikalova, A E AU - Kadiiska, M B AU - Mason, R P AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2001/11/20/ PY - 2001 DA - 2001 Nov 20 SP - 13549 EP - 13553 VL - 98 IS - 24 SN - 0027-8424, 0027-8424 KW - Enzyme Inhibitors KW - 0 KW - Fenton's reagent KW - Formates KW - Free Radicals KW - Nitrogen Oxides KW - Pyridines KW - alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone KW - formic acid KW - 0YIW783RG1 KW - Carbon Dioxide KW - 142M471B3J KW - carboxyl radical KW - 14485-07-5 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Iron KW - E1UOL152H7 KW - Index Medicus KW - Rats KW - Electron Spin Resonance Spectroscopy -- methods KW - Animals KW - Rats, Inbred F344 KW - Spin Trapping -- methods KW - Enzyme Inhibitors -- pharmacology KW - Bile -- metabolism KW - Male KW - Iron -- physiology KW - Formates -- urine KW - Formates -- metabolism KW - Formates -- administration & dosage KW - Carbon Dioxide -- metabolism KW - Free Radicals -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72298764?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=An+in+vivo+ESR+spin-trapping+study%3A+free+radical+generation+in+rats+from+formate+intoxication--role+of+the+Fenton+reaction.&rft.au=Dikalova%2C+A+E%3BKadiiska%2C+M+B%3BMason%2C+R+P&rft.aulast=Dikalova&rft.aufirst=A&rft.date=2001-11-20&rft.volume=98&rft.issue=24&rft.spage=13549&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-08 N1 - Date created - 2001-11-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1957 Dec 13;126(3285):1241-2 [13495448] Helv Physiol Pharmacol Acta. 1957;15(1):150-67 [13428208] Toxicol Appl Pharmacol. 2000 Mar 1;163(2):141-8 [10698672] Free Radic Biol Med. 2000 Apr 15;28(8):1175-81 [10889446] Biochem Biophys Res Commun. 1968 Jan 25;30(2):111-7 [4384443] J Biol Chem. 1970 Jun 10;245(11):2837-44 [5467924] Toxicol Appl Pharmacol. 1975 Oct;34(1):49-61 [819] Biochem Med. 1975 Aug;13(4):319-33 [2163] Biochim Biophys Acta. 1976 Apr 9;430(1):13-29 [4141] Biochim Biophys Acta. 1977 Mar 29;497(1):225-33 [849479] Am J Med. 1980 Mar;68(3):414-8 [7361809] Environ Res. 1982 Dec;29(2):287-96 [7160348] Med Toxicol. 1986 Sep-Oct;1(5):309-34 [3537623] Br J Exp Pathol. 1987 Dec;68(6):853-61 [3426949] Arch Biochem Biophys. 1988 Jul;264(1):238-43 [2840026] Toxicol Appl Pharmacol. 1991 Jan;107(1):117-28 [1702908] Brain Res. 1991 Jan 18;539(1):175-7 [2015500] Pharmacol Toxicol. 1991 Sep;69(3):157-63 [1665561] Fundam Appl Toxicol. 1992 Jul;19(1):43-9 [1397800] Mol Pharmacol. 1992 Oct;42(4):723-9 [1331758] Arch Biochem Biophys. 1993 Jun;303(2):339-48 [8390220] J Magn Reson B. 1994 Jun;104(2):105-10 [8049862] Crit Rev Toxicol. 1995;25(1):25-65 [7734059] J Clin Invest. 1995 Sep;96(3):1653-7 [7657835] Free Radic Res. 1996 Sep;25(3):255-74 [8889492] Free Radic Biol Med. 1996;21(5):713-7 [8891675] J Toxicol Clin Toxicol. 1997;35(2):127-43 [9120880] J Pharmacol Exp Ther. 1964 Mar;143:292-300 [14161139] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chlamydia trachomatis cytotoxicity associated with complete and partial cytotoxin genes AN - 18192479; 5231840 AB - Chlamydia trachomatis is an obligate intracellular human bacterial pathogen that infects epithelial cells of the eye and genital tract. Infection can result in trachoma, the leading cause of preventable blindness worldwide, and sexually transmitted diseases. A common feature of infection is a chronic damaging inflammatory response for which the molecular pathogenesis is not understood. It has been proposed that chlamydiae have a cytotoxic activity that contributes to this pathology, but a toxin has not been identified. The C. trachomatis genome contains genes that encode proteins with significant homology to large clostridial cytotoxins. Here we show that C. trachomatis makes a replication-independent cytotoxic activity that produces morphological and cytoskeletal changes in epithelial cells that are indistinguishable from those mediated by clostridial toxin B. A mouse chlamydial strain that encodes a full-length cytotoxin caused pronounced cytotoxicity, as did a human strain that has a shorter ORF with homology to only the enzymatically active site of clostridial toxin B. Cytotoxin gene transcripts were detected in chlamydiae-infected cells, and a protein with the expected molecular mass was present in lysates of infected epithelial cells. The protein was present transiently in infected cells during the period of cytotoxicity. Together, these data provide compelling evidence for a chlamydial cytotoxin for epithelial cells and imply that the cytotoxin is present in the elementary body and delivered to host cells very early during infection. We hypothesize that the cytotoxin is a virulence factor that contributes to the pathogenesis of C. trachomatis diseases. JF - Proceedings of the National Academy of Sciences, USA AU - Belland, R J AU - Scidmore, MA AU - Crane, D D AU - Hogan, D M AU - Whitmire, W AU - McClarty, G AU - Caldwell, H D AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA, rbelland@niaid.nih.gov Y1 - 2001/11/20/ PY - 2001 DA - 2001 Nov 20 SP - 13984 EP - 13989 VL - 98 IS - 24 SN - 0027-8424, 0027-8424 KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Clostridium KW - Eye KW - Cytotoxins KW - Chlamydia trachomatis KW - Genitourinary tract KW - Blindness KW - Trachoma KW - Virulence KW - Cytotoxicity KW - Pathogenicity KW - Toxin b KW - Epithelium KW - G 07320:Bacterial genetics KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18192479?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Chlamydia+trachomatis+cytotoxicity+associated+with+complete+and+partial+cytotoxin+genes&rft.au=Belland%2C+R+J%3BScidmore%2C+MA%3BCrane%2C+D+D%3BHogan%2C+D+M%3BWhitmire%2C+W%3BMcClarty%2C+G%3BCaldwell%2C+H+D&rft.aulast=Belland&rft.aufirst=R&rft.date=2001-11-20&rft.volume=98&rft.issue=24&rft.spage=13984&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.241377698 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia trachomatis; Clostridium; Epithelium; Pathogenicity; Toxin b; Cytotoxicity; Virulence; Cytotoxins; Eye; Genitourinary tract; Trachoma; Blindness DO - http://dx.doi.org/10.1073/pnas.241377698 ER - TY - JOUR T1 - Proteasome-mediated glucocorticoid receptor degradation restricts transcriptional signaling by glucocorticoids. AN - 72272966; 11555652 AB - Ligand-dependent down-regulation of the glucocorticoid receptor (GR) has been shown to limit hormone responsiveness, but the mechanisms involved in this process are poorly understood. The glucocorticoid receptor is a phosphoprotein that upon ligand binding becomes hyperphosphorylated, and recent evidence indicates that phosphorylation status of the glucocorticoid receptor plays a prominent role in receptor protein turnover. Because phosphorylation is a key signal for ubiquitination and proteasomal catabolism of many proteins, we evaluated whether the ubiquitin-proteasomal pathway had a role in glucocorticoid receptor down-regulation and the subsequent transcriptional response to glucocorticoids. Pretreatment of COS-1 cells expressing mouse glucocorticoid receptor with the proteasome inhibitor MG-132 effectively blocks glucocorticoid receptor protein down-regulation by the glucocorticoid dexamethasone. Interestingly, both MG-132 and a second proteasome inhibitor beta-lactone significantly enhanced hormone response of transfected mouse glucocorticoid receptor toward transcriptional activation of glucocorticoid receptor-mediated reporter gene expression. The transcriptional activity of the endogenous human glucocorticoid receptor in HeLa cells was also enhanced by MG-132. Direct evidence for ubiquitination of the glucocorticoid receptor was obtained by immunoprecipitation of cellular extracts from proteasome-impaired cells. Examination of the primary sequence of mouse, human, and rat glucocorticoid receptor has identified a candidate PEST degradation motif. Mutation of Lys-426 within this PEST element both abrogated ligand-dependent down-regulation of glucocorticoid receptor protein and simultaneously enhanced glucocorticoid receptor-induced transcriptional activation of gene expression. Unlike wild type GR, proteasomal inhibition failed to enhance significantly transcriptional activity of K426A mutant GR. Together these findings suggest a major role of the ubiquitin-proteasome pathway in regulating glucocorticoid receptor protein turnover, thereby providing a mechanism to terminate glucocorticoid responses. JF - The Journal of biological chemistry AU - Wallace, A D AU - Cidlowski, J A AD - Molecular Endocrinology Group, Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/11/16/ PY - 2001 DA - 2001 Nov 16 SP - 42714 EP - 42721 VL - 276 IS - 46 SN - 0021-9258, 0021-9258 KW - Glucocorticoids KW - 0 KW - Ligands KW - Multienzyme Complexes KW - Receptors, Glucocorticoid KW - Dexamethasone KW - 7S5I7G3JQL KW - Luciferases KW - EC 1.13.12.- KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Multienzyme Complexes -- metabolism KW - Animals KW - Plasmids -- metabolism KW - Lysine -- chemistry KW - COS Cells KW - HeLa Cells KW - Dexamethasone -- pharmacology KW - Humans KW - Cysteine Endopeptidases -- chemistry KW - Luciferases -- metabolism KW - Precipitin Tests KW - Chloramphenicol O-Acetyltransferase -- metabolism KW - Transcriptional Activation KW - Mutagenesis, Site-Directed KW - Multienzyme Complexes -- chemistry KW - Blotting, Western KW - Phosphorylation KW - Amino Acid Motifs KW - Down-Regulation KW - Transfection KW - Cysteine Endopeptidases -- metabolism KW - Time Factors KW - Mutation KW - Signal Transduction KW - Receptors, Glucocorticoid -- chemistry KW - Glucocorticoids -- chemistry KW - Transcription, Genetic KW - Receptors, Glucocorticoid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72272966?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Proteasome-mediated+glucocorticoid+receptor+degradation+restricts+transcriptional+signaling+by+glucocorticoids.&rft.au=Wallace%2C+A+D%3BCidlowski%2C+J+A&rft.aulast=Wallace&rft.aufirst=A&rft.date=2001-11-16&rft.volume=276&rft.issue=46&rft.spage=42714&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-26 N1 - Date created - 2001-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NFkappaB activation is required for the neuroprotective effects of pigment epithelium-derived factor (PEDF) on cerebellar granule neurons. AN - 72272087; 11553640 AB - Pigment epithelium-derived factor (PEDF) protects immature cerebellar granule cells (1-3 days in vitro) against induced apoptosis and mature cells (5+ days in vitro) against glutamate toxicity, but its precise mechanism is still unknown. Because the transcription factor NFkappaB blocks cell death, including neuronal apoptosis, we have investigated the ability of PEDF to exert its effects via NFkappaB activation. PEDF induced an increased phosphorylation of IkappaBalpha, decreased levels of IkappaB proteins, and translocation of p65 (RelA) to the nucleus followed by a time-dependent increase of NFkappaB-DNA binding activity in both immature and mature neurons. The protective effects of PEDF against both induced apoptosis and glutamate toxicity were blocked by the addition of either the IkappaB kinase inhibitor BAY 11-7082, which inhibits the phosphorylation of IkappaB, or N-acetyl-Leu-Leu-norleucinal, which blocks proteosome degradation of IkappaB, demonstrating that NFkappaB is required for the neuroprotective effects of PEDF. Reverse transcription-polymerase chain reaction analysis revealed that up-regulation of the anti-apoptotic genes for Bcl-2, Bcl-x, and manganese superoxide dismutase was observed in PEDF-treated immature but not mature neurons. Up-regulation of nerve growth factor, brain-derived neurotrophic factor, and glial cell-derived neurotrophic factor mRNA was long-lasting in mature neurons. These results suggest that PEDF promotes neuronal survival through activation of NFkappaB, which in turn induces expression of anti-apoptotic and/or neurotrophic factor genes. JF - The Journal of biological chemistry AU - Yabe, T AU - Wilson, D AU - Schwartz, J P AD - Neurotrophic Factors Section, NINDS, National Institutes of Health, Bethesda, Maryland 20892-4126, USA. Y1 - 2001/11/16/ PY - 2001 DA - 2001 Nov 16 SP - 43313 EP - 43319 VL - 276 IS - 46 SN - 0021-9258, 0021-9258 KW - Culture Media, Serum-Free KW - 0 KW - Eye Proteins KW - NF-kappa B KW - Nerve Growth Factors KW - Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - RNA, Messenger KW - Serpins KW - pigment epithelium-derived factor KW - Glutamic Acid KW - 3KX376GY7L KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Ligases KW - EC 6.- KW - guanosine 3',5'-polyphosphate synthetases KW - Index Medicus KW - Animals KW - Apoptosis KW - Glutamic Acid -- metabolism KW - Cell Nucleus -- metabolism KW - Superoxide Dismutase -- metabolism KW - Transcription, Genetic KW - Reverse Transcriptase Polymerase Chain Reaction KW - Protein Binding KW - Rats KW - In Situ Nick-End Labeling KW - Rats, Sprague-Dawley KW - Blotting, Western KW - RNA, Messenger -- metabolism KW - Phosphorylation KW - Cells, Cultured KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - Ligases -- metabolism KW - Up-Regulation KW - Culture Media, Serum-Free -- pharmacology KW - Time Factors KW - Immunohistochemistry KW - Protein Transport KW - Proteins -- pharmacology KW - Neurons -- metabolism KW - Serpins -- pharmacology KW - NF-kappa B -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72272087?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=NFkappaB+activation+is+required+for+the+neuroprotective+effects+of+pigment+epithelium-derived+factor+%28PEDF%29+on+cerebellar+granule+neurons.&rft.au=Yabe%2C+T%3BWilson%2C+D%3BSchwartz%2C+J+P&rft.aulast=Yabe&rft.aufirst=T&rft.date=2001-11-16&rft.volume=276&rft.issue=46&rft.spage=43313&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-26 N1 - Date created - 2001-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The consequences of chromosomal aneuploidy on gene expression profiles in a cell line model for prostate carcinogenesis. AN - 72291056; 11719443 AB - Here we report the genetic characterization of immortalized prostate epithelial cells before and after conversion to tumorigenicity using molecular cytogenetics and microarray technology. We were particularly interested to analyze the consequences of acquired chromosomal aneuploidies with respect to modifications of gene expression profiles. Compared with nontumorigenic but immortalized prostate epithelium, prostate tumor cell lines showed high levels of chromosomal rearrangements that led to gains of 1p, 5, 11q, 12p, 16q, and 20q and losses of 1pter, 11p, 17, 20p, 21, 22, and Y. Of 5700 unique targets on a 6.5K cDNA microarray, approximately 3% were subject to modification in expression levels; these included GRO-1, -2, IAP-1,- 2, MMP-9, and cyclin D1, which showed increased expression, and TRAIL, BRCA1, and CTNNA, which showed decreased expression. Thirty % of expression changes occurred in regions the genomic copy number of which remained balanced. Of the remainder, 42% of down-regulated and 51% of up-regulated genes mapped to regions present in decreased or increased genomic copy numbers, respectively. A relative gain or loss of a chromosome or chromosomal arm usually resulted in a statistically significant increase or decrease, respectively, in the average expression level of all of the genes on the chromosome. However, of these genes, very few (e.g., 5 of 101 genes on chromosome 11q), and in some instances only two genes (MMP-9 and PROCR on chromosome 20q), were overexpressed by > or =1.7-fold when scored individually. Cluster analysis by gene function suggests that prostate tumorigenesis in these cell line models involves alterations in gene expression that may favor invasion, prevent apoptosis, and promote growth. JF - Cancer research AU - Phillips, J L AU - Hayward, S W AU - Wang, Y AU - Vasselli, J AU - Pavlovich, C AU - Padilla-Nash, H AU - Pezullo, J R AU - Ghadimi, B M AU - Grossfeld, G D AU - Rivera, A AU - Linehan, W M AU - Cunha, G R AU - Ried, T AD - Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 10 Center Drive, Bethesda, MD 20817, USA. phillipj@mail.nih.gov Y1 - 2001/11/15/ PY - 2001 DA - 2001 Nov 15 SP - 8143 EP - 8149 VL - 61 IS - 22 SN - 0008-5472, 0008-5472 KW - Index Medicus KW - Karyotyping KW - Cell Transformation, Neoplastic -- pathology KW - Tumor Cells, Cultured KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Nucleic Acid Hybridization KW - Translocation, Genetic KW - Male KW - Cell Transformation, Neoplastic -- genetics KW - Gene Expression Regulation, Neoplastic -- genetics KW - Prostatic Neoplasms -- pathology KW - Gene Expression Profiling KW - Aneuploidy KW - Prostatic Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72291056?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=The+consequences+of+chromosomal+aneuploidy+on+gene+expression+profiles+in+a+cell+line+model+for+prostate+carcinogenesis.&rft.au=Phillips%2C+J+L%3BHayward%2C+S+W%3BWang%2C+Y%3BVasselli%2C+J%3BPavlovich%2C+C%3BPadilla-Nash%2C+H%3BPezullo%2C+J+R%3BGhadimi%2C+B+M%3BGrossfeld%2C+G+D%3BRivera%2C+A%3BLinehan%2C+W+M%3BCunha%2C+G+R%3BRied%2C+T&rft.aulast=Phillips&rft.aufirst=J&rft.date=2001-11-15&rft.volume=61&rft.issue=22&rft.spage=8143&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-12 N1 - Date created - 2001-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4): an archaeal DinB-like DNA polymerase with lesion-bypass properties akin to eukaryotic poleta. AN - 72278760; 11713310 AB - Phylogenetic analysis of Y-family DNA polymerases suggests that it can be subdivided into several discrete branches consisting of UmuC/DinB/Rev1/Rad30/Rad30A and Rad30B. The most diverse is the DinB family that is found in all three kingdoms of life. Searches of the complete genome of the crenarchaeon Sulfolobus solfataricus P2 reveal that it possesses a DinB homolog that has been termed DNA polymerase IV (Dpo4). We have overproduced and purified native Dpo4 protein and report here its enzymatic characterization. Dpo4 is thermostable, but can also synthesize DNA at 37 degrees C. Under these conditions, the enzyme exhibits misinsertion fidelities in the range of 8 x 10(-3) to 3 x 10(-4). Dpo4 is distributive but at high enzyme to template ratios can synthesize long stretches of DNA and can substitute for Taq polymerase in PCR. On damaged DNA templates, Dpo4 can facilitate translesion replication of an abasic site, a cis-syn thymine-thymine dimer, as well as acetyl aminofluorene adducted- and cisplatinated-guanine residues. Thus, although phylogenetically related to DinB polymerases, our studies suggest that the archaeal Dpo4 enzyme exhibits lesion-bypass properties that are, in fact, more akin to those of eukaryotic poleta. JF - Nucleic acids research AU - Boudsocq, F AU - Iwai, S AU - Hanaoka, F AU - Woodgate, R AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, MD 20892-2725, USA. Y1 - 2001/11/15/ PY - 2001 DA - 2001 Nov 15 SP - 4607 EP - 4616 VL - 29 IS - 22 KW - Archaeal Proteins KW - 0 KW - Bacterial Proteins KW - DinB protein, E coli KW - Escherichia coli Proteins KW - Nucleotides KW - DNA Polymerase beta KW - EC 2.7.7.- KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Rad30 protein KW - Index Medicus KW - Nucleotides -- metabolism KW - Bacterial Proteins -- genetics KW - DNA Repair KW - Electrophoresis, Polyacrylamide Gel KW - Genes, Archaeal -- genetics KW - Archaeal Proteins -- metabolism KW - Bacterial Proteins -- metabolism KW - Eukaryotic Cells -- enzymology KW - Temperature KW - Sulfolobus KW - Genome, Archaeal KW - Polymerase Chain Reaction KW - Enzyme Stability KW - Archaeal Proteins -- genetics KW - DNA-Directed DNA Polymerase -- genetics KW - DNA-Directed DNA Polymerase -- metabolism KW - DNA Polymerase beta -- genetics KW - DNA Polymerase beta -- isolation & purification KW - DNA Polymerase beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72278760?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Sulfolobus+solfataricus+P2+DNA+polymerase+IV+%28Dpo4%29%3A+an+archaeal+DinB-like+DNA+polymerase+with+lesion-bypass+properties+akin+to+eukaryotic+poleta.&rft.au=Boudsocq%2C+F%3BIwai%2C+S%3BHanaoka%2C+F%3BWoodgate%2C+R&rft.aulast=Boudsocq&rft.aufirst=F&rft.date=2001-11-15&rft.volume=29&rft.issue=22&rft.spage=4607&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-11 N1 - Date created - 2001-11-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: EMBO J. 2000 Oct 2;19(19):5259-66 [11013228] Nucleic Acids Res. 2000 Nov 1;28(21):4147-56 [11058111] J Biol Chem. 2000 Dec 15;275(50):39678-84 [11006276] J Biol Chem. 2001 Jan 5;276(1):92-8 [11024016] Extremophiles. 2000 Dec;4(6):357-64 [11139078] Nat Rev Mol Cell Biol. 2000 Nov;1(2):101-9 [11253362] EMBO Rep. 2000 Dec;1(6):484-8 [11263491] Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7835-40 [11427726] Mol Cell. 2001 Jul;8(1):7-8 [11515498] Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12091-5 [7991589] Methods Enzymol. 1995;262:232-56 [8594351] J Biol Chem. 1996 May 3;271(18):10767-74 [8631887] Mutat Res. 1996 Oct 25;357(1-2):245-53 [8876701] Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1478-83 [9465040] J Biol Chem. 1998 Mar 6;273(10):5520-7 [9488676] Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9755-60 [9707548] Science. 1999 Feb 12;283(5404):1001-4 [9974380] J Biol Chem. 1999 Jun 4;274(23):15975-7 [10347143] EMBO J. 1999 Jun 15;18(12):3491-501 [10369688] Nature. 1999 Jun 17;399(6737):700-4 [10385124] Science. 1999 Jul 9;285(5425):263-5 [10398605] Genetics. 1999 Aug;152(4):1249-67 [10430556] Genomics. 1999 Aug 15;60(1):20-30 [10458907] Genes Dev. 1999 Sep 1;13(17):2191-5 [10485842] Mol Cell. 1999 Aug;4(2):281-6 [10488344] Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):11922-7 [10518552] Cell. 2001 Oct 5;107(1):91-102 [11595188] J Biol Chem. 1987 Oct 25;262(30):14689-96 [3667598] Methods Enzymol. 1990;185:60-89 [2199796] J Mol Biol. 1990 Oct 5;215(3):403-10 [2231712] Bioessays. 1991 Feb;13(2):79-84 [2029269] Nucleic Acids Res. 1991 Aug 11;19(15):4045-57 [1870963] Nucleic Acids Res. 1993 Feb 25;21(4):787-802 [8451181] Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12224-6 [10535901] J Biol Chem. 1999 Nov 5;274(45):31763-6 [10542196] Genes Cells. 1999 Nov;4(11):607-18 [10620008] Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):565-70 [10639119] Trends Biochem Sci. 2000 Mar;25(3):143-7 [10694886] J Biol Chem. 2000 Mar 17;275(11):7447-50 [10713043] Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):3838-43 [10760255] Nature. 2000 Apr 27;404(6781):1014-8 [10801133] Proc Natl Acad Sci U S A. 2000 May 23;97(11):5681-3 [10811923] EMBO J. 2000 Jun 15;19(12):3100-9 [10856253] Genes Dev. 2000 Jul 1;14(13):1589-94 [10887153] Genes Dev. 2000 Jul 1;14(13):1642-50 [10887158] Nature. 2000 Aug 31;406(6799):1015-9 [10984059] Mol Cell Biol. 2000 Oct;20(19):7099-108 [10982826] Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11227-31 [11016960] Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12176-81 [11016950] Nucleic Acids Res. 2000 Nov 1;28(21):4138-46 [11058110] EMBO J. 2000 Nov 15;19(22):6259-65 [11080171] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional and physical interactions of the adaptor protein complex AP-4 with ADP-ribosylation factors (ARFs). AN - 72275881; 11707398 AB - AP-4 is a member of the family of heterotetrameric adaptor protein (AP) complexes that mediate the sorting of integral membrane proteins in post-Golgi compartments. This complex consists of four subunits (epsilon, beta4, mu4 and sigma4) and localizes to the cytoplasmic face of the trans-Golgi network (TGN). Here, we show that the recruitment of endogenous AP-4 to the TGN in vivo is regulated by the small GTP-binding protein ARF1. In addition, we demonstrate a direct interaction of the epsilon and mu4 subunits of AP-4 with ARF1. epsilon binds only to ARF1-GTP and requires residues in the switch I and switch II regions of ARF1. In contrast, mu4 binds equally well to the GTP- and GDP-bound forms of ARF1 and is less dependent on switch I and switch II residues. These observations establish AP-4 as an ARF1 effector and suggest a novel mode of interaction between ARF1 and an AP complex involving both constitutive and regulated interactions. JF - The EMBO journal AU - Boehm, M AU - Aguilar, R C AU - Bonifacino, J S AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/11/15/ PY - 2001 DA - 2001 Nov 15 SP - 6265 EP - 6276 VL - 20 IS - 22 SN - 0261-4189, 0261-4189 KW - Adaptor Proteins, Vesicular Transport KW - 0 KW - Carrier Proteins KW - Membrane Proteins KW - Brefeldin A KW - 20350-15-6 KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - Index Medicus KW - Immunoblotting KW - HeLa Cells KW - Humans KW - Two-Hybrid System Techniques KW - Precipitin Tests KW - Protein Binding KW - Models, Biological KW - Binding Sites KW - Microscopy, Fluorescence KW - Mutagenesis, Site-Directed KW - Transfection KW - Brefeldin A -- pharmacology KW - Cell Membrane -- metabolism KW - Protein Structure, Tertiary KW - Mutation KW - Signal Transduction KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry KW - Membrane Proteins -- chemistry KW - ADP-Ribosylation Factors -- metabolism KW - Membrane Proteins -- metabolism KW - Golgi Apparatus -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72275881?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=Functional+and+physical+interactions+of+the+adaptor+protein+complex+AP-4+with+ADP-ribosylation+factors+%28ARFs%29.&rft.au=Boehm%2C+M%3BAguilar%2C+R+C%3BBonifacino%2C+J+S&rft.aulast=Boehm&rft.aufirst=M&rft.date=2001-11-15&rft.volume=20&rft.issue=22&rft.spage=6265&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-17 N1 - Date created - 2001-11-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Biol Cell. 1998 Jun;9(6):1323-37 [9614177] J Cell Biol. 1998 Jul 27;142(2):391-402 [9679139] FEBS Lett. 1998 Jul 3;430(3):231-5 [9688545] J Biol Chem. 1998 Aug 21;273(34):21431-4 [9705267] Cell. 1998 Oct 16;95(2):237-48 [9790530] Biochem J. 1998 Nov 1;335 ( Pt 3):567-72 [9794796] J Biol Chem. 1997 Oct 24;272(43):27160-6 [9341158] EMBO J. 1997 Dec 15;16(24):7305-16 [9405360] Science. 1998 Nov 13;282(5392):1327-32 [9812899] Infect Immun. 1999 Jan;67(1):259-65 [9864224] Cell. 1999 Feb 5;96(3):363-74 [10025402] J Biol Chem. 1999 Mar 12;274(11):7278-85 [10066790] Cell. 1999 Mar 19;96(6):893-902 [10102276] Mol Cell. 1999 Mar;3(3):275-85 [10198630] Cell. 1999 Nov 24;99(5):521-32 [10589680] J Biol Chem. 1999 Dec 17;274(51):36609-15 [10593962] Annu Rev Cell Dev Biol. 1999;15:705-32 [10611976] J Biol Chem. 2000 Feb 11;275(6):4022-32 [10660559] J Cell Biol. 2000 Apr 3;149(1):67-80 [10747088] J Cell Biol. 2000 Apr 3;149(1):81-94 [10747089] Mol Biol Cell. 2000 Apr;11(4):1241-55 [10749927] J Biol Chem. 2000 May 5;275(18):13962-6 [10747863] Curr Opin Cell Biol. 2000 Aug;12(4):475-82 [10873831] Nat Struct Biol. 2000 Jun;7(6):466-9 [10881192] J Biol Chem. 2000 Jul 21;275(29):21862-9 [10807927] EMBO J. 2000 Aug 1;19(15):3905-17 [10921873] EMBO J. 2000 Aug 15;19(16):4216-27 [10944104] Annu Rev Biochem. 2000;69:699-727 [10966473] Mol Biol Cell. 2000 Nov;11(11):3723-36 [11071902] EMBO J. 2000 Nov 15;19(22):6011-9 [11080148] FEBS Lett. 2000 Dec 29;487(2):252-6 [11150519] Yeast. 2001 Jan 15;18(1):1-18 [11124697] Gene. 2001 Jan 10;262(1-2):115-22 [11179674] Nat Rev Neurosci. 2000 Dec;1(3):161-72 [11257904] EMBO Rep. 2001 Mar;2(3):234-8 [11266366] Cell. 2001 Apr 6;105(1):93-102 [11301005] J Biol Chem. 2001 Apr 20;276(16):13145-52 [11139587] Curr Opin Cell Biol. 2001 Aug;13(4):444-53 [11454451] Mol Biol Cell. 2001 Oct;12(10):2907-20 [11598180] Cell. 1992 Apr 3;69(1):129-38 [1555237] Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6408-12 [1631136] Nature. 1992 Nov 26;360(6402):352-4 [1448152] J Biol Chem. 1993 Jun 5;268(16):12083-9 [8505331] Cell. 1993 Dec 17;75(6):1137-44 [8261513] J Biol Chem. 1994 Jan 14;269(2):1437-48 [8288610] Science. 1994 Jan 28;263(5146):523-6 [8290961] J Cell Biol. 1994 Feb;124(3):289-300 [8294513] J Biol Chem. 1994 Feb 4;269(5):3135-8 [8106346] J Biol Chem. 1994 Jul 8;269(27):17826-32 [8027036] Cell. 1994 Sep 9;78(5):751-60 [8087843] J Cell Biol. 1995 Mar;128(6):1003-17 [7896867] J Biol Chem. 1995 Jun 16;270(24):14809-15 [7782347] J Cell Biol. 1995 Nov;131(3):619-30 [7593184] Science. 1995 Dec 22;270(5244):1999-2002 [8533093] EMBO J. 1996 Aug 1;15(15):3778-86 [8670882] FEBS Lett. 1997 Jan 27;402(1):57-61 [9013859] J Biol Chem. 1997 Feb 14;272(7):4141-8 [9020126] J Biol Chem. 1997 Feb 28;272(9):5421-9 [9038142] EMBO J. 1997 Mar 3;16(5):917-28 [9118953] Biochemistry. 1997 Apr 15;36(15):4675-84 [9109679] Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4418-23 [9114004] Cell. 1999 Apr 16;97(2):149-52 [10219234] Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5013-8 [10220410] J Biol Chem. 1999 May 14;274(20):14198-203 [10318838] Cell. 1999 Jun 11;97(6):805-15 [10380931] Mol Biol Cell. 1999 Aug;10(8):2787-802 [10436028] Science. 1999 Aug 20;285(5431):1268-71 [10455054] J Cell Biol. 1999 Aug 23;146(4):755-64 [10459011] Cell Motil Cytoskeleton. 1999 Oct;44(2):119-32 [10506747] J Biol Chem. 1997 Aug 29;272(35):22221-6 [9268368] Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2140-5 [9482852] J Biol Chem. 1998 Apr 3;273(14):8344-50 [9525943] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Unique misinsertion specificity of poliota may decrease the mutagenic potential of deaminated cytosines. AN - 72271246; 11707422 AB - DNA polymerase iota (poliota) is a distributive error-prone enzyme that can incorporate nucleotides opposite a variety of DNA lesions. Further elongation is, however, either substantially inhibited or completely abolished. Here, we provide evidence that poliota can facilitate the efficient bypass of uracil and its derivatives as well as oxidized cytosine and guanine residues. The fidelity of translesion replication depends upon the lesion encountered. Correct nucleotides were inserted preferentially opposite 7,8-dihydro-8-oxoguanine (8-oxoG) and 5-hydroxycytosine (5-OHC). However, when bypassing uracil, 5-hydroxyuracil (5-OHU) or 5,6-dihydrouracil (5,6-DHU), poliota inserted T and G with a 4- to 26-fold preference over the Watson-Crick base, A. While the T:U, T:5-OHU and T:5,6-DHU mispairs were extended poorly, the G:U, G:5-OHU and G:5,6-DHU mispairs were extended with equal or greater efficiency than the correctly paired primer termini. Thus, poliota-dependent misinsertion of G opposite uracil and its derivatives may actually provide a mechanism whereby mammalian cells can decrease the mutagenic potential of lesions formed via the deamination of cytosine. JF - The EMBO journal AU - Vaisman, A AU - Woodgate, R AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2725, USA. Y1 - 2001/11/15/ PY - 2001 DA - 2001 Nov 15 SP - 6520 EP - 6529 VL - 20 IS - 22 SN - 0261-4189, 0261-4189 KW - DNA Primers KW - 0 KW - Guanosine KW - 12133JR80S KW - 8-hydroxyguanosine KW - 3868-31-3 KW - Uracil KW - 56HH86ZVCT KW - Guanine KW - 5Z93L87A1R KW - 5-hydroxycytosine KW - 75321-30-1 KW - Cytosine KW - 8J337D1HZY KW - DNA polymerase iota KW - EC 2.7.7.- KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Animals KW - Uracil -- chemistry KW - DNA Damage KW - Guanine -- chemistry KW - Humans KW - Oxygen -- metabolism KW - Mutagenesis, Site-Directed KW - Base Pairing KW - Base Pair Mismatch KW - Kinetics KW - Models, Chemical KW - DNA Primers -- metabolism KW - Time Factors KW - Guanosine -- analogs & derivatives KW - Cytosine -- chemistry KW - Guanosine -- genetics KW - Cytosine -- analogs & derivatives KW - DNA-Directed DNA Polymerase -- genetics KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72271246?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=Unique+misinsertion+specificity+of+poliota+may+decrease+the+mutagenic+potential+of+deaminated+cytosines.&rft.au=Vaisman%2C+A%3BWoodgate%2C+R&rft.aulast=Vaisman&rft.aufirst=A&rft.date=2001-11-15&rft.volume=20&rft.issue=22&rft.spage=6520&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-17 N1 - Date created - 2001-11-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Bacteriol. 1982 Aug;151(2):750-5 [7047496] Cold Spring Harb Symp Quant Biol. 2000;65:61-9 [12760021] Mol Cell Biol. 1985 Dec;5(12):3443-50 [3915777] Int J Radiat Biol Relat Stud Phys Chem Med. 1987 Apr;51(4):573-89 [3034813] J Biol Chem. 1987 Oct 25;262(30):14689-96 [3667598] J Biol Chem. 1990 Feb 5;265(4):2338-46 [1688852] Nature. 1991 Jan 31;349(6308):431-4 [1992344] J Bacteriol. 1991 Mar;173(6):1902-10 [2001994] Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3380-4 [1565630] Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):1122-6 [8430083] Nature. 1993 Apr 22;362(6422):709-15 [8469282] Mutat Res. 1993 Aug;288(2):249-55 [7688084] Biochemistry. 1993 Nov 16;32(45):12105-11 [8218289] Nucleic Acids Res. 1994 Jan 11;22(1):72-8 [8127657] Mol Cell Biol. 1995 Feb;15(2):989-96 [7823963] Mol Cell Biochem. 1994 Nov 9;140(1):1-22 [7877593] Carcinogenesis. 1995 Nov;16(11):2779-84 [7586199] Methods Enzymol. 1995;262:232-56 [8594351] Pathol Biol (Paris). 1996 Jan;44(1):14-24 [8734295] Nucleic Acids Res. 1998 Apr 1;26(7):1707-12 [9512542] Nature. 1999 Jun 17;399(6737):700-4 [10385124] Science. 1999 Jul 9;285(5425):263-5 [10398605] Genomics. 1999 Aug 15;60(1):20-30 [10458907] Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13300-5 [10557315] Science. 1999 Dec 3;286(5446):1897-905 [10583946] Carcinogenesis. 2000 Mar;21(3):361-70 [10688856] J Biol Chem. 2000 Mar 17;275(11):7447-50 [10713043] Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4156-61 [10725358] Genes Dev. 2000 Jul 1;14(13):1642-50 [10887158] Mol Cell. 2000 Jun;5(6):1059-65 [10912000] Mutat Res. 2000 Aug 30;460(3-4):165-81 [10946227] Nature. 2000 Aug 31;406(6799):1015-9 [10984059] Annu Rev Biochem. 2000;69:497-529 [10966467] Mol Cell Biol. 2000 Oct;20(19):7099-108 [10982826] EMBO J. 2000 Oct 2;19(19):5259-66 [11013228] J Exp Med. 2000 Nov 20;192(10):F27-30 [11085756] Philos Trans R Soc Lond B Biol Sci. 2001 Jan 29;356(1405):53-60 [11205331] Nucleic Acids Res. 2001 Feb 15;29(4):928-35 [11160925] Science. 2001 Mar 16;291(5511):2156-9 [11251121] J Biol Chem. 2001 May 4;276(18):15155-63 [11297519] Biochem Soc Trans. 2001 May;29(Pt 2):183-7 [11356150] EMBO J. 2001 Jun 1;20(11):2914-22 [11387224] Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7976-81 [11427727] EMBO J. 2001 Aug 1;20(15):4278-86 [11483530] J Biol Chem. 2001 Aug 17;276(33):30615-22 [11402031] Mol Cell. 2001 Jul;8(1):7-8 [11515498] Biochemistry. 1982 Dec 21;21(26):6746-51 [6760893] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mining the Melanosome for Tumor Vaccine Targets: P.polypeptide Is a Novel Tumor-associated Antigen AN - 18401994; 5386379 AB - To identify novel, tumor-specific target antigens for vaccine development, we studied immune responses to P.polypeptide, an M sub(r) 110,000 integral melanosomal membrane protein associated with the Prader-Willi syndrome. Together with expressed sequence tag (EST) and serial analyses of gene expression (SAGE) library analyses, reverse transcription-PCR and Northern blotting verified that P.polypeptide expression was limited to melanoma and melanocytes. A single dominant epitope corresponding to positions 427-435 (IMLCLIAAV) was identified using allele-specific epitope forecasting combined with work in HLA-A*0201/K super(b) transgenic mice. This epitope was then used to generate de novo human P.polypeptide-specific CD8 super(+) T cells capable of recognizing P.polypeptide expressing human tumor cell lines in an HLA-A*0201-restricted fashion. Thus, P.polypeptide may be valuable in the creation of novel therapeutic anticancer vaccines. JF - Cancer Research AU - Touloukian, CE AU - Leitner, W W AU - Robbins, P F AU - Rosenberg, SA AU - Restifo, N P AD - Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA Y1 - 2001/11/15/ PY - 2001 DA - 2001 Nov 15 SP - 8100 EP - 8104 VL - 61 IS - 22 SN - 0008-5472, 0008-5472 KW - CD8 antigen KW - histocompatibility antigen HLA KW - transgenic mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18401994?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Mining+the+Melanosome+for+Tumor+Vaccine+Targets%3A+P.polypeptide+Is+a+Novel+Tumor-associated+Antigen&rft.au=Touloukian%2C+CE%3BLeitner%2C+W+W%3BRobbins%2C+P+F%3BRosenberg%2C+SA%3BRestifo%2C+N+P&rft.aulast=Touloukian&rft.aufirst=CE&rft.date=2001-11-15&rft.volume=61&rft.issue=22&rft.spage=8100&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Stabilization of cortical actin induces internalization of transient receptor potential 3 (Trp3)-associated caveolar Ca2+ signaling complex and loss of Ca2+ influx without disruption of Trp3-inositol trisphosphate receptor association. AN - 72251616; 11524429 AB - Ca(2+) influx via plasma membrane Trp3 channels is proposed to be regulated by a reversible interaction with inositol trisphosphate receptor (IP(3)R) in the endoplasmic reticulum. Condensation of the cortical actin layer has been suggested to physically disrupt this interaction and inhibit Trp3-mediated Ca(2+) influx. This study examines the effect of cytoskeletal reorganization on the localization and function of Trp3 and key Ca(2+) signaling proteins. Calyculin-A treatment resulted in formation of condensed actin layer at the plasma membrane; internalization of Trp3, Galpha(q/11), phospholipase Cbeta, and caveolin-1; and attenuation of 1-oleoyl-2-acetyl-sn-glycerol- and ATP-stimulated Sr(2+) influx. Importantly, Trp3 and IP(3)R-3 remained co-localized inside the cell and were co-immunoprecipitated. Jasplakinolide also induced internalization of Trp3 and caveolin-1. Pretreatment of cells with cytochalasin D or staurosporine did not affect Trp3 but prevented calyculin-A-induced effects. Based on these data, we suggest that Trp3 is assembled in a caveolar Ca(2+) signaling complex with IP(3)R, SERCA, Galpha(q/11), phospholipase Cbeta, caveolin-1, and ezrin. Furthermore, our data demonstrate that conditions which stabilize cortical actin induce loss of Trp3 activity due to internalization of the Trp3-signaling complex, not disruption of IP(3)R-Trp3 interaction. This suggests that localization of the Trp3-associated signaling complex, rather than Trp3-IP(3)R coupling, depends on the status of the actin cytoskeleton. JF - The Journal of biological chemistry AU - Lockwich, T AU - Singh, B B AU - Liu, X AU - Ambudkar, I S AD - Secretory Physiology Section, Gene Therapy and Therapeutics Branch, NIDCR, National Institutes of Health Bethesda, Maryland 20892, USA. Y1 - 2001/11/09/ PY - 2001 DA - 2001 Nov 09 SP - 42401 EP - 42408 VL - 276 IS - 45 SN - 0021-9258, 0021-9258 KW - Actins KW - 0 KW - CAV1 protein, human KW - Calcium Channels KW - Caveolin 1 KW - Caveolins KW - ITPR1 protein, human KW - Inositol 1,4,5-Trisphosphate Receptors KW - Oxazoles KW - Receptors, Cytoplasmic and Nuclear KW - TRPC Cation Channels KW - TRPC3 cation channel KW - Potassium Iodide KW - 1C4QK22F9J KW - calyculin A KW - 7D07U14TK3 KW - Type C Phospholipases KW - EC 3.1.4.- KW - Calcium-Transporting ATPases KW - EC 3.6.3.8 KW - Sarcoplasmic Reticulum Calcium-Transporting ATPases KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Oxazoles -- pharmacology KW - Cells, Cultured KW - Humans KW - Calcium-Transporting ATPases -- analysis KW - Cytoskeleton -- physiology KW - Caveolins -- analysis KW - Type C Phospholipases -- physiology KW - Potassium Iodide -- pharmacology KW - Calcium -- metabolism KW - Actins -- physiology KW - Calcium Channels -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Caveolae -- chemistry KW - Receptors, Cytoplasmic and Nuclear -- analysis KW - Calcium Channels -- analysis KW - Calcium Signaling UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72251616?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Stabilization+of+cortical+actin+induces+internalization+of+transient+receptor+potential+3+%28Trp3%29-associated+caveolar+Ca2%2B+signaling+complex+and+loss+of+Ca2%2B+influx+without+disruption+of+Trp3-inositol+trisphosphate+receptor+association.&rft.au=Lockwich%2C+T%3BSingh%2C+B+B%3BLiu%2C+X%3BAmbudkar%2C+I+S&rft.aulast=Lockwich&rft.aufirst=T&rft.date=2001-11-09&rft.volume=276&rft.issue=45&rft.spage=42401&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-05 N1 - Date created - 2001-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiple genetic changes are associated with mammary tumorigenesis in Brca1 conditional knockout mice. AN - 72286708; 11709723 AB - Germline mutations in the tumor suppressor gene BRCA1 predispose women to breast cancer, however somatic mutations in the gene are rarely detected in sporadic cancers. To understand this phenomenon, we examined mouse models carrying conditional disruption of Brca1 in mammary epithelium in either p53 wild type (wt) or heterozygous backgrounds. Although a p53(+/-) mutation significantly accelerated tumorigenesis, both strains developed mammary tumors in a stochastic fashion, suggesting that multiple factors, in addition to p53 mutations, may be involved in Brca1 related tumorigenesis. A unique feature of Brca1 mammary tumors is their highly diverse histopathology accompanied by severe chromosome abnormalities. The tumors also display extensive genetic/molecular alterations, including overexpression of ErbB2, c-Myc, p27 and Cyclin D1 in the majority of tumors, while they were virtually ERalpha and p16 negative. Translocations involving p53 were also identified which lead to abnormal RNA and protein products. In addition, we generated cell lines from mammary tumors and found that the cells retained many of the genetic changes found in the primary tumors, suggesting that these genes may be players in Brca1-associated tumorigenesis. Despite their distinct morphology, all cultured tumor cells were Tamoxifen resistant but highly sensitive to Doxorubicin or gamma-irradiation, suggesting that these methods would be effective in treatment of this disease. JF - Oncogene AU - Brodie, S G AU - Xu, X AU - Qiao, W AU - Li, W M AU - Cao, L AU - Deng, C X AD - Genetics of Development and Disease Branch, 10/9N105, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/11/08/ PY - 2001 DA - 2001 Nov 08 SP - 7514 EP - 7523 VL - 20 IS - 51 SN - 0950-9232, 0950-9232 KW - Antineoplastic Agents KW - 0 KW - Antineoplastic Agents, Hormonal KW - Ccnb1 protein, mouse KW - Cyclin A KW - Cyclin B KW - Cyclin B1 KW - Cyclin E KW - Cyclin-Dependent Kinase Inhibitor p16 KW - Microfilament Proteins KW - Muscle Proteins KW - Proto-Oncogene Proteins c-myc KW - Tagln protein, mouse KW - Tamoxifen KW - 094ZI81Y45 KW - Cyclin D1 KW - 136601-57-5 KW - Doxorubicin KW - 80168379AG KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - CDC2 Protein Kinase KW - EC 2.7.11.22 KW - Proto-Oncogene Proteins p21(ras) KW - EC 3.6.5.2 KW - Index Medicus KW - Animals KW - Blotting, Northern KW - CDC2 Protein Kinase -- metabolism KW - Proto-Oncogene Proteins c-myc -- metabolism KW - Metaphase KW - Mice, Knockout KW - Cyclin A -- biosynthesis KW - Cyclin D1 -- metabolism KW - Tumor Cells, Cultured KW - Doxorubicin -- pharmacology KW - Heterozygote KW - Time Factors KW - Tamoxifen -- pharmacology KW - Proto-Oncogene Proteins p21(ras) -- biosynthesis KW - Gamma Rays KW - Receptor, ErbB-2 -- metabolism KW - Dose-Response Relationship, Drug KW - Microfilament Proteins -- biosynthesis KW - Antineoplastic Agents, Hormonal -- pharmacology KW - Mice KW - Dose-Response Relationship, Radiation KW - Cyclin E -- biosynthesis KW - Translocation, Genetic KW - Genotype KW - Cyclin-Dependent Kinase Inhibitor p16 -- biosynthesis KW - Blotting, Western KW - Cyclin B -- biosynthesis KW - Antineoplastic Agents -- pharmacology KW - Immunohistochemistry KW - Cell Line KW - Female KW - Mammary Neoplasms, Animal -- genetics KW - Genes, BRCA1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72286708?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Multiple+genetic+changes+are+associated+with+mammary+tumorigenesis+in+Brca1+conditional+knockout+mice.&rft.au=Brodie%2C+S+G%3BXu%2C+X%3BQiao%2C+W%3BLi%2C+W+M%3BCao%2C+L%3BDeng%2C+C+X&rft.aulast=Brodie&rft.aufirst=S&rft.date=2001-11-08&rft.volume=20&rft.issue=51&rft.spage=7514&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-07 N1 - Date created - 2001-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidative stress and p53 mutations in the carcinogenesis of iron overload-associated hepatocellular carcinoma. AN - 72262651; 11698570 JF - Journal of the National Cancer Institute AU - Marrogi, A J AU - Khan, M A AU - van Gijssel, H E AU - Welsh, J A AU - Rahim, H AU - Demetris, A J AU - Kowdley, K V AU - Hussain, S P AU - Nair, J AU - Bartsch, H AU - Okby, N AU - Poirier, M C AU - Ishak, K G AU - Harris, C C AD - Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/11/07/ PY - 2001 DA - 2001 Nov 07 SP - 1652 EP - 1655 VL - 93 IS - 21 SN - 0027-8874, 0027-8874 KW - NOS2 protein, human KW - EC 1.14.13.39 KW - Nitric Oxide Synthase KW - Nitric Oxide Synthase Type II KW - Index Medicus KW - DNA Repair KW - Humans KW - Nitric Oxide Synthase -- physiology KW - Liver Neoplasms -- metabolism KW - Iron Overload -- complications KW - Carcinoma, Hepatocellular -- metabolism KW - Genes, p53 KW - Carcinoma, Hepatocellular -- etiology KW - Carcinoma, Hepatocellular -- genetics KW - Oxidative Stress KW - Liver Neoplasms -- etiology KW - Mutation KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72262651?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Oxidative+stress+and+p53+mutations+in+the+carcinogenesis+of+iron+overload-associated+hepatocellular+carcinoma.&rft.au=Marrogi%2C+A+J%3BKhan%2C+M+A%3Bvan+Gijssel%2C+H+E%3BWelsh%2C+J+A%3BRahim%2C+H%3BDemetris%2C+A+J%3BKowdley%2C+K+V%3BHussain%2C+S+P%3BNair%2C+J%3BBartsch%2C+H%3BOkby%2C+N%3BPoirier%2C+M+C%3BIshak%2C+K+G%3BHarris%2C+C+C&rft.aulast=Marrogi&rft.aufirst=A&rft.date=2001-11-07&rft.volume=93&rft.issue=21&rft.spage=1652&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-07 N1 - Date created - 2001-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - AMPA and GABA(B) receptor antagonists and their interaction in rats with a genetic form of absence epilepsy. AN - 72281736; 11711038 AB - The effects of combined and single administration of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, 7,8-methylenedioxy-1-(4-aminophenyl)-4-methyl-3-acetyl-4,5-dihydro-2,3-benzodiazepine (LY 300164), and of the GABA(B) receptor antagonist gamma-aminopropyl-n-butyl-phosphinic acid (CGP 36742), on spontaneously occurring spike-wave discharges were investigated in WAG/Rij rats. LY 300164 had minor effects; only the highest dose (16 mg/kg) reduced the number of spike-wave discharges in a short time window. CGP 36742 was more effective as it significantly reduced the number of spike-wave discharges and shortened their duration at the doses of 25 and 100 mg/kg. The ED(50) values for the inhibition of spike-wave discharges by LY 300164 and CGP 36742 in a time window 30-60 min after injection were 15.5 and 16.6 mg/kg, respectively. The ED(50) of CGP 36742 was reduced to 8.0 mg/kg when this antagonist was administered in combination with LY 300164 (6 mg/kg). The interaction between the two antagonists appeared to be additive according to isobolographic analysis. Importantly, CGP 36742 and LY 300164 administered either alone or in combination had no apparent effects on behavior. These results may provide information for a rational approach to polytherapy for the treatment of generalized absence epilepsy. JF - European journal of pharmacology AU - Kamiński, R M AU - Van Rijn, C M AU - Turski, W A AU - Czuczwar, S J AU - Van Luijtelaar, G AD - Department of Comparative and Physiological Psychology, Nijmegen Institute for Cognition and Information, University of Nijmegen, P.O. Box 9104, 6500 HE, Nijmegen, The Netherlands. rkaminsk@intra.nida.nih.gov Y1 - 2001/11/02/ PY - 2001 DA - 2001 Nov 02 SP - 251 EP - 259 VL - 430 IS - 2-3 SN - 0014-2999, 0014-2999 KW - Excitatory Amino Acid Antagonists KW - 0 KW - GABA Antagonists KW - GABA-B Receptor Antagonists KW - Organophosphorus Compounds KW - Receptors, AMPA KW - Benzodiazepines KW - 12794-10-4 KW - GYKI 53405 KW - 143691-37-6 KW - (3-aminopropyl)(n-butyl)phosphinic acid KW - 145537-81-1 KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Behavior, Animal -- drug effects KW - Animals KW - Receptors, AMPA -- antagonists & inhibitors KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Electroencephalography -- drug effects KW - Time Factors KW - Male KW - Epilepsy, Absence -- genetics KW - Organophosphorus Compounds -- pharmacology KW - GABA Antagonists -- pharmacology KW - Benzodiazepines -- pharmacology KW - Epilepsy, Absence -- physiopathology KW - Excitatory Amino Acid Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72281736?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+pharmacology&rft.atitle=AMPA+and+GABA%28B%29+receptor+antagonists+and+their+interaction+in+rats+with+a+genetic+form+of+absence+epilepsy.&rft.au=Kami%C5%84ski%2C+R+M%3BVan+Rijn%2C+C+M%3BTurski%2C+W+A%3BCzuczwar%2C+S+J%3BVan+Luijtelaar%2C+G&rft.aulast=Kami%C5%84ski&rft.aufirst=R&rft.date=2001-11-02&rft.volume=430&rft.issue=2-3&rft.spage=251&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-14 N1 - Date created - 2001-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Involvement of corticotropin-releasing factor receptor subtype 1 in morphine withdrawal regulation of the brain noradrenergic system. AN - 72280794; 11711043 AB - Effects of pretreatment with the selective corticotropin-releasing factor (CRF) subtype 1 (CRF(1)) receptor antagonist, 2-(N-(2-methylthio-4-isopropylphenyl)-N-ethyl-amino-4-(4-(3-fluorophenyl)-1,2,3,6-tetrahydropyridin-1-yl)-6-methylpyrimidine (CRA1000) on the behavioral and biochemical changes after naloxone-precipitated morphine withdrawal were examined in ICR mice. Mice were chronically treated with morphine (8-45 mg/kg) for 5 days. Naloxone (3 mg/kg, s.c.) precipitated jumping, diarrhea, and body weight loss in morphine-dependent mice. In addition, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and noradrenaline turnover (MHPG/noradrenaline) levels in the cerebral cortex were increased following naloxone challenge in morphine-dependent mice. However, 5-hydroxytriptamine turnover did not alter the increase following naloxone challenge in morphine-dependent mice. Pretreatment with CRA1000 (20 mg/kg, i.p.) attenuated the incidence of withdrawal signs and naloxone-precipitated increases in noradrenaline turnover. These results suggest that the activation of CRF(1) receptor may play an important role in the elevation of noradrenaline transmission, but not in 5-hydroxytriptamine transmission, in the cerebral cortex, which projects from the locus coeruleus during morphine withdrawal. JF - European journal of pharmacology AU - Funada, M AU - Hara, C AU - Wada, K AD - Section of Addictive Drugs Research, Division of Drug Dependence, National Institute of Mental Health, National Center of Neurology and Psychiatry, 1-7-3 Kohnodai, Chiba 272-0827, Ichikawa, Japan. mfunada@ncnp-k.go.jp Y1 - 2001/11/02/ PY - 2001 DA - 2001 Nov 02 SP - 277 EP - 281 VL - 430 IS - 2-3 SN - 0014-2999, 0014-2999 KW - CRA1000 KW - 0 KW - CRF receptor type 1 KW - Narcotic Antagonists KW - Pyridines KW - Pyrimidines KW - Receptors, Corticotropin-Releasing Hormone KW - Naloxone KW - 36B82AMQ7N KW - Morphine KW - 76I7G6D29C KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Animals KW - Naloxone -- pharmacology KW - Cerebral Cortex -- drug effects KW - Mice, Inbred ICR KW - Cerebral Cortex -- metabolism KW - Morphine Dependence KW - Pyrimidines -- pharmacology KW - Mice KW - Behavior, Animal -- drug effects KW - Diarrhea -- chemically induced KW - Time Factors KW - Pyridines -- pharmacology KW - Narcotic Antagonists -- pharmacology KW - Diarrhea -- prevention & control KW - Male KW - Substance Withdrawal Syndrome -- physiopathology KW - Receptors, Corticotropin-Releasing Hormone -- physiology KW - Norepinephrine -- metabolism KW - Brain -- drug effects KW - Receptors, Corticotropin-Releasing Hormone -- antagonists & inhibitors KW - Brain -- metabolism KW - Morphine -- administration & dosage KW - Morphine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72280794?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+pharmacology&rft.atitle=Involvement+of+corticotropin-releasing+factor+receptor+subtype+1+in+morphine+withdrawal+regulation+of+the+brain+noradrenergic+system.&rft.au=Funada%2C+M%3BHara%2C+C%3BWada%2C+K&rft.aulast=Funada&rft.aufirst=M&rft.date=2001-11-02&rft.volume=430&rft.issue=2-3&rft.spage=277&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-14 N1 - Date created - 2001-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insulin receptor substrate-1 pleckstrin homology and phosphotyrosine-binding domains are both involved in plasma membrane targeting. AN - 72235895; 11526109 AB - The localization of insulin receptor substrate (IRS) molecules may be responsible for the differential biological activities of insulin and other peptides such as platelet-derived growth factor. The subcellular localization of IRS-1 is controversial, with some reports suggesting association with the cytoskeleton and other studies reporting membrane localization. In this study, we used immunofluorescence microscopy to define the localization of IRS-1. In the basal state, recombinant IRS-1 was localized predominantly in the cytoplasm. In response to insulin, recombinant IRS-1 translocated to the plasma membrane. We have also studied the localization of green fluorescent protein (GFP) fusion proteins. Unlike native IRS-1, a fusion protein containing GFP plus full-length IRS-1 appeared to localize in inclusion bodies. In contrast, when GFP was fused to the N terminus of IRS-1 (i.e. the pleckstrin homology and phosphotyrosine-binding domains), this fusion protein was targeted to the plasma membrane. Mutations of phosphoinositide-binding sites in both the pleckstrin homology and phosphotyrosine-binding domains significantly reduced the ability of Myc-tagged IRS-1 to translocate to the plasma membrane following insulin stimulation. However, these mutations did not cause a statistically significant impairment of tyrosine phosphorylation in response to insulin. This raises the possibility that IRS-1 tyrosine phosphorylation may occur prior to plasma membrane translocation. JF - The Journal of biological chemistry AU - Jacobs, A R AU - LeRoith, D AU - Taylor, S I AD - Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1758, USA. Y1 - 2001/11/02/ PY - 2001 DA - 2001 Nov 02 SP - 40795 EP - 40802 VL - 276 IS - 44 SN - 0021-9258, 0021-9258 KW - Blood Proteins KW - 0 KW - Insulin KW - Insulin Receptor Substrate Proteins KW - Luminescent Proteins KW - Phosphoproteins KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - platelet protein P47 KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Phosphotyrosine KW - 21820-51-9 KW - Index Medicus KW - Animals KW - COS Cells KW - Fluorescent Antibody Technique, Indirect KW - Insulin -- pharmacology KW - Luminescent Proteins -- metabolism KW - Recombinant Fusion Proteins -- chemistry KW - Binding Sites KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Phosphorylation KW - Recombinant Proteins -- metabolism KW - Cell Membrane -- metabolism KW - Protein Transport KW - Phosphoproteins -- genetics KW - Phosphoproteins -- chemistry KW - Phosphotyrosine -- metabolism KW - Blood Proteins -- chemistry KW - Blood Proteins -- metabolism KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72235895?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Insulin+receptor+substrate-1+pleckstrin+homology+and+phosphotyrosine-binding+domains+are+both+involved+in+plasma+membrane+targeting.&rft.au=Jacobs%2C+A+R%3BLeRoith%2C+D%3BTaylor%2C+S+I&rft.aulast=Jacobs&rft.aufirst=A&rft.date=2001-11-02&rft.volume=276&rft.issue=44&rft.spage=40795&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-07 N1 - Date created - 2001-10-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dissection of NT3 functions in vivo by gene replacement strategy. AN - 85280135; pmid-11684666 AB - The development of the peripheral nervous system is governed in part by a family of neurotrophic factors that signal through Trk tyrosine kinase receptors. Neurotrophin 3 (NT3) ablation in mice causes a more severe neuronal phenotype than deletion of its receptor TrkC, suggesting that NT3 acts also through other non-preferred Trk receptors. To study the role of low-affinity ligand receptor interactions in vivo, we have replaced the Nt3 gene with the gene for brain-derived neurotrophic factor (BDNF), a TrkB ligand. As in NT3 and TrkC null mice, the proprioception system of these mutants failed to assemble. However, sensory fiber projections in the embryonic spinal cord suggest chemotropic effects of BDNF in vivo. In the dorsal root ganglia, the developmental dynamic of neuron numbers demonstrates that NT3 is required for activation of TrkB during neurogenesis and that TrkA is required during target tissue innervation. In the inner ear, the ectopic BDNF rescued the severe neuronal deficits caused by NT3 absence, indicating that TrkB and TrkC activate equivalent pathways to promote survival of cochlear neurons. However, specific increased innervation densities suggest unique functions for BDNF and NT3 beyond promoting neuronal survival. This mouse model has allowed the dissection of specific spatiotemporal Trk receptor activation by NT3. Our analysis provides examples of how development can be orchestrated by complex high- and low-affinity interactions between ligand and receptor families. JF - Development (Cambridge, England) AU - Coppola, V AU - Kucera, J AU - Palko, M E AU - Martinez-De, Velasco J AU - Lyons, W E AU - Fritzsch, B AU - Tessarollo, L AD - Neural Development Group, Mouse Cancer Genetics Program, NCI, Frederick, MD 21701, USA. PY - 2001 SP - 4315 EP - 4327 VL - 128 IS - 21 SN - 0950-1991, 0950-1991 KW - Labyrinth KW - Support, U.S. Gov't, P.H.S. KW - Spinal Cord KW - Brain-Derived Neurotrophic Factor KW - Animal KW - Ganglia, Spinal KW - Mice KW - Neurons, Afferent KW - Mice, Mutant Strains KW - Genetic Techniques KW - Receptor, trkB KW - Support, U.S. Gov't, Non-P.H.S. KW - Support, Non-U.S. Gov't KW - Receptor, trkC KW - Neurotrophin 3 KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85280135?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Development+%28Cambridge%2C+England%29&rft.atitle=Dissection+of+NT3+functions+in+vivo+by+gene+replacement+strategy.&rft.au=Coppola%2C+V%3BKucera%2C+J%3BPalko%2C+M+E%3BMartinez-De%2C+Velasco+J%3BLyons%2C+W+E%3BFritzsch%2C+B%3BTessarollo%2C+L&rft.aulast=Coppola&rft.aufirst=V&rft.date=2001-11-01&rft.volume=128&rft.issue=21&rft.spage=4315&rft.isbn=&rft.btitle=&rft.title=Development+%28Cambridge%2C+England%29&rft.issn=09501991&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - A two-state piezoelectric model for outer hair cell motility. AN - 85252476; pmid-11606265 AB - Recent studies have revealed that voltage-dependent length changes of the outer hair cell are based on charge transfer across the membrane. Such a motility can be explained by an "area motor" model, which assumes two states in the motor and that conformational transitions involve transfer of motor charge across the membrane and mechanical displacements of the membrane. Here it is shown that the area motor is piezoelectric and that the hair cell that incorporates such a motor in its lateral membrane is also piezoelectric. Distinctive features of the outer hair cell are its exceptionally large piezoelectric coefficient, which exceeds the best known piezoelectric material by four orders of magnitude, and its prominent nonlinearity due to the discreteness of motor states. JF - Biophysical Journal AU - Iwasa, Kuni H AD - National Institute on Deafness and Other Communication Disorders PY - 2001 SP - 2495 EP - 2506 VL - 81 IS - 5 SN - 0006-3495, 0006-3495 KW - Cell Movement KW - Cochlea KW - Electrostatics KW - Reproducibility of Results KW - Hair Cells, Outer KW - Animal KW - Cell Membrane KW - Molecular Motors KW - Biomechanics KW - Protein Conformation KW - Models, Molecular UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85252476?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biophysical+Journal&rft.atitle=A+two-state+piezoelectric+model+for+outer+hair+cell+motility.&rft.au=Iwasa%2C+Kuni+H&rft.aulast=Iwasa&rft.aufirst=Kuni&rft.date=2001-11-01&rft.volume=81&rft.issue=5&rft.spage=2495&rft.isbn=&rft.btitle=&rft.title=Biophysical+Journal&rft.issn=00063495&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Cancers associated with Kaposi's sarcoma (KS) in AIDS: a link between KS herpesvirus and immunoblastic lymphoma AN - 759319730; 13758622 AB - Kaposi's sarcoma (KS), common among persons with acquired immunodeficiency syndrome (AIDS), is caused by KS herpesvirus (KSHV) but whether KSHV causes other malignancies is uncertain. Using linked United States AIDS and cancer registries, we measured the incidence of specific malignancies in persons with AIDS (4-27 months after AIDS onset). We identified associations with KSHV by calculating a relative risk: cancer incidence in persons with KS (all were KSHV-infected) divided by incidence in persons without KS. Using Poisson regression, relative risks were adjusted for human immunodeficiency virus risk group, gender, age, race, and calendar year. We included 189 159 subjects (26[puncsp]972 with KS). Immunoblastic lymphoma was significantly associated with KS (506 cases; relative risks: unadjusted 2.44, 95%CI 2.00-2.96, adjusted 1.58, 95%CI 1.29-1.93). Only one immunoblastic lymphoma had pleura as primary site. None of 37 other specified malignancies (other non-Hodgkin lymphomas, haematological malignancies, solid tumours) was significantly associated with KS. In summary, the association of immunoblastic lymphoma with KS was specific among examined malignancies and remained significant after statistical adjustment. Our findings, and the previously demonstrated presence of KSHV in the histologically related primary effusion lymphoma, suggest that KSHV is involved in the pathogenesis of some immunoblastic lymphomas. [copy 2001 Cancer Research Campaign JF - British Journal of Cancer AU - Engels, E A AU - Rosenberg, P S AU - Frisch, M AU - Goedert, J J AD - Viral Epidemiology Branch and Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., Rockville, MD, USA Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 1298 EP - 1303 PB - Nature Publishing Group, The Macmillan Building London N1 9XW UK VL - 85 IS - 9 SN - 0007-0920, 0007-0920 KW - Immunology Abstracts; Risk Abstracts; Health & Safety Science Abstracts; Virology & AIDS Abstracts KW - non-Hodgkin's lymphoma KW - Risk assessment KW - Age KW - Acquired immune deficiency syndrome KW - Herpesvirus KW - Kaposi's sarcoma-associated herpesvirus KW - Immunodeficiency KW - Statistical analysis KW - tumors KW - Tumors KW - Cancer KW - Pleura KW - USA KW - Malignancy KW - Kaposi's sarcoma KW - Human immunodeficiency virus KW - Gender KW - primary effusion lymphoma KW - Risk groups KW - Hematology KW - lymphoma KW - H 6000:Natural Disasters/Civil Defense/Emergency Management KW - V 22360:AIDS and HIV KW - F 06915:Cancer Immunology KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/759319730?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+Journal+of+Cancer&rft.atitle=Cancers+associated+with+Kaposi%27s+sarcoma+%28KS%29+in+AIDS%3A+a+link+between+KS+herpesvirus+and+immunoblastic+lymphoma&rft.au=Engels%2C+E+A%3BRosenberg%2C+P+S%3BFrisch%2C+M%3BGoedert%2C+J+J&rft.aulast=Engels&rft.aufirst=E&rft.date=2001-11-01&rft.volume=85&rft.issue=9&rft.spage=1298&rft.isbn=&rft.btitle=&rft.title=British+Journal+of+Cancer&rft.issn=00070920&rft_id=info:doi/10.1054%2Fbjoc.2001.2052 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2014-04-17 N1 - SubjectsTermNotLitGenreText - Risk assessment; Pleura; Acquired immune deficiency syndrome; Malignancy; Kaposi's sarcoma; primary effusion lymphoma; Statistical analysis; Immunodeficiency; Risk groups; Tumors; non-Hodgkin's lymphoma; Age; Gender; tumors; Hematology; lymphoma; Cancer; Human immunodeficiency virus; Herpesvirus; Kaposi's sarcoma-associated herpesvirus; USA DO - http://dx.doi.org/10.1054/bjoc.2001.2052 ER - TY - JOUR T1 - Biomarker assays in nipple aspirate fluid. AN - 72437975; 11843848 AB - The noninvasive technique of nipple aspiration as a potential source of biomarkers of breast cancer risk was evaluated. The feasibility of performing mutagenesis assays, amplifying DNA, and performing protein electrophoresis on nipple aspirate fluid was explored. A tool was developed to measure the level of discomfort, if any, from this procedure. Twenty-five healthy women (20 premenopausal and 5 postmenopausal) were enrolled. Fluid was obtained using a modified breast pump. Premenopausal women were scheduled for four to six weekly aspirations, and postmenopausal women were scheduled for one to two weekly aspirations. Mutagenesis assays were performed using the Salmonella (Ames) assay. DNA amplification of several microsatellite regions was carried out using polymerase chain reaction. Protein was quantified, and two-dimensional protein electrophoresis was performed. Overall, fluid was obtained from 80% of the women, and the level of discomfort was minimal. Acid hydrolysis of one sample resulted in mutagenicity; all six nonhydrolyzed samples were not mutagenic. The ability to amplify DNA ranged from 34% to 96%, depending on length of the microsatellite region examined. The average protein concentration was 71 microg/mL. Two-dimensional protein electrophoresis was successfully performed on samples from two subjects. Nipple aspiration is a simple technique and is easily learned and well tolerated, which yields a reagent useful for a variety of investigations. This technique may facilitate the identification and application of biomarkers for future breast cancer risk assessment and chemopreventive protocols. JF - The breast journal AU - Klein, P AU - Glaser, E AU - Grogan, L AU - Keane, M AU - Lipkowitz, S AU - Soballe, P AU - Brooks, L AU - Jenkins, J AU - Steinberg, S M AU - DeMarini, D M AU - Kirsch, I AD - Genetics Branch, CCR National Cancer Institute, Bethesda, MD 20889, USA. PY - 2001 SP - 378 EP - 387 VL - 7 IS - 6 SN - 1075-122X, 1075-122X KW - Biomarkers KW - 0 KW - Proteins KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Humans KW - Premenopause KW - Pain Measurement KW - Microsatellite Repeats KW - Feasibility Studies KW - Mutagenicity Tests KW - Postmenopause KW - Adult KW - Electrophoresis, Gel, Two-Dimensional KW - Proteins -- analysis KW - Middle Aged KW - Female KW - Exudates and Transudates -- cytology KW - Nipples -- secretion KW - Breast Neoplasms -- diagnosis KW - DNA -- analysis KW - Suction KW - Cytodiagnosis -- methods KW - Exudates and Transudates -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72437975?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+breast+journal&rft.atitle=Biomarker+assays+in+nipple+aspirate+fluid.&rft.au=Klein%2C+P%3BGlaser%2C+E%3BGrogan%2C+L%3BKeane%2C+M%3BLipkowitz%2C+S%3BSoballe%2C+P%3BBrooks%2C+L%3BJenkins%2C+J%3BSteinberg%2C+S+M%3BDeMarini%2C+D+M%3BKirsch%2C+I&rft.aulast=Klein&rft.aufirst=P&rft.date=2001-11-01&rft.volume=7&rft.issue=6&rft.spage=378&rft.isbn=&rft.btitle=&rft.title=The+breast+journal&rft.issn=1075122X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-07 N1 - Date created - 2002-02-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N-(phosphonacetyl)-L-aspartate and calcium leucovorin modulation of fluorouracil administered by constant rate and circadian pattern of infusion over 72 hours in metastatic gastrointestinal adenocarcinoma. AN - 72423142; 11822758 AB - We have reported that N-(phosphonacetyl)-L-aspartic acid (PALA) 1266 mg/m2 can safely be given 24 hours prior to the start of a 72-hour infusion of fluorouracil (FUra) and leucovorin (LV) at doses of 2000 and 500 mg/m2/day. Since inhibition of aspartate carbamoyltransferase (ACTase) activity was evident 4 hours post PALA, we wished to evaluate PALA given 1 hour prior to FUra. Further, we studied the toxicity and pharmacokinetics with FUra given by either fixed- or variable-rate infusion. Twenty-seven patients with gastrointestinal tract adenocarcinomas were treated with PALA 1266 mg/m2/15 min followed by a 72-hour infusion of FUra and LV (1750 & 500 mg/m2/day) given by fixed- or variable-rate (peak at 4:00 A.M.). Clinical toxicity was similar in two consecutive cycles in 17 patients receiving fixed- and variable-rate infusion at the same FUra dose. Overall, grade 3 stomatitis and hand-foot syndrome occurred in 12% and 4% patients receiving fixed- and in 16% and 10.5% of patients receiving variable-rate infusions. Six of 24 evaluable patients (25%) had a partial response. The profile of FUra plasma levels (Cp) over a 24-hour period during fixed- and variable-rate infusions were strikingly different, but the average Cp and area under the concentration-time curves were comparable. ACTase activity was significantly decreased at 4 and 24 hours after PALA (12% and 18% of baseline; P < 0.001), but enzyme activity had recovered to 40% by 72 hours. This regimen was active and well tolerated with similar toxicities with FUra given by either fixed- or variable rate infusion. PALA 1266 mg/m2 significantly inhibited ACTase activity for at least 24 hours. JF - Annals of oncology : official journal of the European Society for Medical Oncology AU - Grem, J L AU - Yee, L K AU - Schuler, B AU - Hamilton, J M AU - Chen, A P AU - Chabuk, C AU - Grollman, F AU - Grabenc, M AU - Allegra, C J AU - Takimoto, C H AD - NCI-Navy Medicine Branch, National Cancer Institute, National Naval Medical Center, Bethesda, Maryland 20889-5105, USA. gremj@mail.nih.gov Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 1581 EP - 1587 VL - 12 IS - 11 SN - 0923-7534, 0923-7534 KW - Aspartic Acid KW - 30KYC7MIAI KW - sparfosic acid KW - 78QVZ7RG8L KW - Aspartate Carbamoyltransferase KW - EC 2.1.3.2 KW - Phosphonoacetic Acid KW - N919E46723 KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Fluorouracil -- administration & dosage KW - Infusions, Intravenous KW - Leucovorin -- administration & dosage KW - Humans KW - Aspartate Carbamoyltransferase -- metabolism KW - Adult KW - Aspartate Carbamoyltransferase -- antagonists & inhibitors KW - Aged KW - Middle Aged KW - Chronotherapy KW - Fluorouracil -- pharmacokinetics KW - Male KW - Female KW - Aspartic Acid -- administration & dosage KW - Aspartic Acid -- analogs & derivatives KW - Phosphonoacetic Acid -- analogs & derivatives KW - Phosphonoacetic Acid -- administration & dosage KW - Adenocarcinoma -- secondary KW - Gastrointestinal Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Gastrointestinal Neoplasms -- pathology KW - Adenocarcinoma -- drug therapy KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72423142?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.atitle=N-%28phosphonacetyl%29-L-aspartate+and+calcium+leucovorin+modulation+of+fluorouracil+administered+by+constant+rate+and+circadian+pattern+of+infusion+over+72+hours+in+metastatic+gastrointestinal+adenocarcinoma.&rft.au=Grem%2C+J+L%3BYee%2C+L+K%3BSchuler%2C+B%3BHamilton%2C+J+M%3BChen%2C+A+P%3BChabuk%2C+C%3BGrollman%2C+F%3BGrabenc%2C+M%3BAllegra%2C+C+J%3BTakimoto%2C+C+H&rft.aulast=Grem&rft.aufirst=J&rft.date=2001-11-01&rft.volume=12&rft.issue=11&rft.spage=1581&rft.isbn=&rft.btitle=&rft.title=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.issn=09237534&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-16 N1 - Date created - 2002-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Current trends in screening and secondary prevention of colorectal cancer. AN - 72421965; 11813590 AB - Colorectal cancer is one of the most frequent neoplasms in Western countries with an estimated 400,000 deaths per year worldwide. Several randomized studies have demonstrated that screening programs with FOBT (Fecal Occult Blood Test) reduce mortality from 18 to 33%, whereas case-control and cohort studies with endoscopy have shown a mortality reduction ranging from 60 to 76%. The target population for secondary prevention is men and women aged more than 50 years and younger subjects in case first-degree relatives are affected or the family pedigree raises the suspicion of a genetic syndrome. This report summarizes the results of different screening strategies for average risk patients (FOBT, anamnestic risk questionnaire, sigmoidoscopy, colonoscopy and virtual colonoscopy) and the surveillance protocols applicable to high-risk patients, particularly for hereditary syndromes such as HNPCC and FAP. JF - Hepato-gastroenterology AU - Crespi, M AU - Stigliano, V AU - Assisi, D AD - Service of Environmental Carcinogenesis, Epidemiology and Prevention, Gastroenterology Section, National Cancer Institute Regina Elena, Viale Regina Elena, 291, 00161 Rome, Italy. mcrespi@uni.net PY - 2001 SP - 1635 EP - 1640 VL - 48 IS - 42 SN - 0172-6390, 0172-6390 KW - Index Medicus KW - Sensitivity and Specificity KW - Sigmoidoscopy KW - Occult Blood KW - Colonoscopy KW - Humans KW - Colonography, Computed Tomographic KW - Risk Assessment KW - Mass Screening -- trends KW - Colorectal Neoplasms -- genetics KW - Colorectal Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72421965?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepato-gastroenterology&rft.atitle=Current+trends+in+screening+and+secondary+prevention+of+colorectal+cancer.&rft.au=Crespi%2C+M%3BStigliano%2C+V%3BAssisi%2C+D&rft.aulast=Crespi&rft.aufirst=M&rft.date=2001-11-01&rft.volume=48&rft.issue=42&rft.spage=1635&rft.isbn=&rft.btitle=&rft.title=Hepato-gastroenterology&rft.issn=01726390&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-26 N1 - Date created - 2002-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein kinase activity is central to rat germ cell apoptosis induced by methoxyacetic acid. AN - 72404499; 11794376 AB - Methoxyacetic acid (MAA) is a major metabolite of ethylene glycol monomethyl ether (EGME). Previous investigations of the testicular lesion induced by EGME have found that dividing meiotic cells are the most sensitive, although several stages of spermatocytes are also vulnerable. Preliminary data from this lab suggested the involvement of protein kinase activity in the development of this lesion, a hypothesis explored in the present studies. We used cultured seminiferous tubules (STs) from juvenile rats (25-day-old), exposed in vitro to MAA and several inhibitors of protein kinases. Nineteen h following a 5-h exposure to 5 mM MAA (the plasma level in vivo after a toxic dose of EGME), apoptotic spermatocytes were seen in early- and late-stage STs. Cell death was prevented by cotreatment with broad-spectrum inhibitors of protein kinases such as H-7, H-8, K-252a, W-7, and genistein. In corroboration, immunocytochemistry with antibodies to various kinases (PKCmu, zeta, and gamma, AKAP220, CaMKII, MLCK, and Src) showed increased staining around dying spermatocytes following EGME treatment in vivo. 2D-PAGE, autoradiography, and nanospray mass spectrometry was used to separate and identify proteins whose phosphorylation status was most greatly changed following exposure to MAA. One protein was identified by sequence analysis as being glucose-regulated protein 94 (grp94). Westem blotting and immunocytochemistry confirmed this finding. The data we present implicate kinase activities in the pathogenesis of this lesion and suggest the involvement of Sertoli cells. JF - Toxicologic pathology AU - Jindo, T AU - Wine, R N AU - Li, L H AU - Chapin, R E AD - Reproductive Toxicology Group, National Toxicology Program, NIEHS, Research Triangle Park, North Carolina, USA. PY - 2001 SP - 607 EP - 616 VL - 29 IS - 6 SN - 0192-6233, 0192-6233 KW - Acetates KW - 0 KW - Enzyme Inhibitors KW - Immunosuppressive Agents KW - Protein Kinase Inhibitors KW - Protein Kinases KW - EC 2.7.- KW - methoxyacetic acid KW - F11T1H7Q7W KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Seminiferous Tubules -- drug effects KW - Cells, Cultured KW - In Vitro Techniques KW - Enzyme Inhibitors -- pharmacology KW - Male KW - Seminiferous Tubules -- pathology KW - Protein Kinases -- metabolism KW - Testis -- drug effects KW - Spermatozoa -- drug effects KW - Testis -- pathology KW - Spermatozoa -- pathology KW - Immunosuppressive Agents -- toxicity KW - Apoptosis -- drug effects KW - Acetates -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72404499?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Protein+kinase+activity+is+central+to+rat+germ+cell+apoptosis+induced+by+methoxyacetic+acid.&rft.au=Jindo%2C+T%3BWine%2C+R+N%3BLi%2C+L+H%3BChapin%2C+R+E&rft.aulast=Jindo&rft.aufirst=T&rft.date=2001-11-01&rft.volume=29&rft.issue=6&rft.spage=607&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-22 N1 - Date created - 2002-01-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Unexpected effects of FERM domain mutations on catalytic activity of Jak3: structural implication for Janus kinases. AN - 72368398; 11741532 AB - Janus kinases comprise carboxyterminal kinase, pseudokinase, SH2-like, and N-terminal FERM domains. We identified three patient-derived mutations in the FERM domain of Jak3 and investigated the functional consequences of these mutations. These mutations inhibited receptor binding and also abrogated kinase activity, suggesting interactions between the FERM and kinase domains. In fact, the domains were found to physically associate, and coexpression of the FERM domain enhanced activity of the isolated kinase domain. Conversely, staurosporine, which alters kinase domain structure, disrupted receptor binding, even though the catalytic activity of Jak3 is dispensable for receptor binding. Thus, the Jak FERM domain appears to have two critical functions: receptor interaction and maintenance of kinase integrity. JF - Molecular cell AU - Zhou, Y J AU - Chen, M AU - Cusack, N A AU - Kimmel, L H AU - Magnuson, K S AU - Boyd, J G AU - Lin, W AU - Roberts, J L AU - Lengi, A AU - Buckley, R H AU - Geahlen, R L AU - Candotti, F AU - Gadina, M AU - Changelian, P S AU - O'Shea, J J AD - Lymphocyte Cell Biology Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA. Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 959 EP - 969 VL - 8 IS - 5 SN - 1097-2765, 1097-2765 KW - AG 1879 KW - 0 KW - Enzyme Inhibitors KW - IL2RG protein, human KW - Interleukin Receptor Common gamma Subunit KW - Pyrimidines KW - Receptors, Interleukin-7 KW - Recombinant Fusion Proteins KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - JAK3 protein, human KW - EC 2.7.10.2 KW - Janus Kinase 3 KW - src-Family Kinases KW - Staurosporine KW - H88EPA0A3N KW - Index Medicus KW - Animals KW - COS Cells KW - Models, Molecular KW - Receptors, Interleukin-7 -- metabolism KW - Humans KW - Pyrimidines -- pharmacology KW - Amino Acid Sequence KW - src-Family Kinases -- antagonists & inhibitors KW - Recombinant Fusion Proteins -- chemistry KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Staurosporine -- pharmacology KW - Sequence Alignment KW - Adenosine Triphosphate -- analogs & derivatives KW - Adenosine Triphosphate -- metabolism KW - Receptors, Interleukin-7 -- genetics KW - Molecular Sequence Data KW - Enzyme Inhibitors -- pharmacology KW - Protein Structure, Tertiary KW - Mutation KW - Catalysis KW - Protein-Tyrosine Kinases -- genetics KW - Protein-Tyrosine Kinases -- metabolism KW - Protein-Tyrosine Kinases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72368398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+cell&rft.atitle=Unexpected+effects+of+FERM+domain+mutations+on+catalytic+activity+of+Jak3%3A+structural+implication+for+Janus+kinases.&rft.au=Zhou%2C+Y+J%3BChen%2C+M%3BCusack%2C+N+A%3BKimmel%2C+L+H%3BMagnuson%2C+K+S%3BBoyd%2C+J+G%3BLin%2C+W%3BRoberts%2C+J+L%3BLengi%2C+A%3BBuckley%2C+R+H%3BGeahlen%2C+R+L%3BCandotti%2C+F%3BGadina%2C+M%3BChangelian%2C+P+S%3BO%27Shea%2C+J+J&rft.aulast=Zhou&rft.aufirst=Y&rft.date=2001-11-01&rft.volume=8&rft.issue=5&rft.spage=959&rft.isbn=&rft.btitle=&rft.title=Molecular+cell&rft.issn=10972765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-22 N1 - Date created - 2001-12-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sensitizers and protectors of radiation and chemotherapy. AN - 72340188; 11740469 JF - Current problems in cancer AU - Poggi, M M AU - Coleman, C N AU - Mitchell, J B AD - Radiation Oncology Sciences Program, National Cancer Institute, Bethesda, Maryland, USA. PY - 2001 SP - 334 EP - 411 VL - 25 IS - 6 SN - 0147-0272, 0147-0272 KW - Prostaglandins, Synthetic KW - 0 KW - Radiation-Sensitizing Agents KW - Amifostine KW - M487QF2F4V KW - Index Medicus KW - Sensitivity and Specificity KW - Amifostine -- pharmacology KW - Radiation Dosage KW - Animals KW - Prostaglandins, Synthetic -- pharmacology KW - Humans KW - Clinical Trials as Topic KW - Chemotherapy, Adjuvant KW - Neoplasms -- drug therapy KW - Neoplasms -- radiotherapy KW - Radiation-Sensitizing Agents -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Radiation-Sensitizing Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72340188?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+problems+in+cancer&rft.atitle=Sensitizers+and+protectors+of+radiation+and+chemotherapy.&rft.au=Poggi%2C+M+M%3BColeman%2C+C+N%3BMitchell%2C+J+B&rft.aulast=Poggi&rft.aufirst=M&rft.date=2001-11-01&rft.volume=25&rft.issue=6&rft.spage=334&rft.isbn=&rft.btitle=&rft.title=Current+problems+in+cancer&rft.issn=01470272&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-29 N1 - Date created - 2001-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Abundance of siderophages in sputum: indicator of an adverse lung reaction to air pollution. AN - 72306242; 11726125 AB - To investigate the lung response to traffic-related air pollution by enumerating hemosiderin-laden alveolar macrophages (AM) in sputum. Sputum samples were collected from 103 urban adult males from Calcutta chronically exposed to automobile exhaust. Forty-nine rural individuals served as controls. AM were identified by nonspecific esterase staining. Perl's Prussian blue technique was employed for the detection of hemosiderin-laden AM (siderophages). The urban group, consisting of 31 traffic officers, 25 automobile service station workers and 47 street hawkers, had seven times more AM in their sputum than did the matched controls. Besides, a remarkable rise (27-fold) in the number of siderophages in sputum was observed in urban individuals. Smoking further elevated the AM count and number of siderophages. Abundant siderophages in the urban group may indicate the toxic effect of airborne pollutants on the lung, leading to phagocytosis of destroyed cells, including erythrocytes, and accumulation of iron in AM. Enumeration of siderophages in sputum appears to be a simple, noninvasive, inexpensive cytochemical technique well suited to preliminary assessment of the adverse effects of air pollution on the lungs in large, population-based studies, especially in developing countries. JF - Acta cytologica AU - Roy, S AU - Ray, M R AU - Basu, C AU - Lahiri, P AU - Lahiri, T AD - Chittaranjan National Cancer Institute and Environmental Biology Laboratory, Department of Zoology, University of Calcutta, India. PY - 2001 SP - 958 EP - 964 VL - 45 IS - 6 SN - 0001-5547, 0001-5547 KW - Vehicle Emissions KW - 0 KW - Hemosiderin KW - 9011-92-1 KW - Index Medicus KW - Hemosiderin -- analysis KW - Rural Health KW - Cell Count KW - Urban Health KW - Humans KW - Adult KW - Middle Aged KW - Male KW - Sputum -- chemistry KW - Sputum -- cytology KW - Lung -- drug effects KW - Occupational Exposure -- adverse effects KW - Macrophages, Alveolar -- chemistry KW - Lung -- pathology KW - Macrophages, Alveolar -- pathology KW - Vehicle Emissions -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72306242?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+cytologica&rft.atitle=Abundance+of+siderophages+in+sputum%3A+indicator+of+an+adverse+lung+reaction+to+air+pollution.&rft.au=Roy%2C+S%3BRay%2C+M+R%3BBasu%2C+C%3BLahiri%2C+P%3BLahiri%2C+T&rft.aulast=Roy&rft.aufirst=S&rft.date=2001-11-01&rft.volume=45&rft.issue=6&rft.spage=958&rft.isbn=&rft.btitle=&rft.title=Acta+cytologica&rft.issn=00015547&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-13 N1 - Date created - 2001-11-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Acta Cytol. 2003 Jul-Aug;47(4):695-6 [12920768] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New cytotoxic N-methylated beta-carboline alkaloids from the marine ascidian Eudistoma gilboverde. AN - 72299325; 11720532 AB - Bioassay-guided fractionation of an extract of the marine ascidian Eudistoma gilboverde provided three new beta-carboline alkaloids identified as 2-methyleudistomin D (1), 2-methyleudistomin J (2), and 14-methyleudistomidin C (3). Six known metabolites, eudistomins C, D (4), E, J (5), K, and L, were also isolated and characterized. The structures of the new metabolites were elucidated by spectroscopic analyses and by comparison of their spectral data with related literature values. Of the three new compounds, 14-methyleudistomidin C (3) exhibited the most potent cytotoxic activity with IC(50)'s of < 1.0 microg/mL against four different human tumor cell lines. JF - Journal of natural products AU - Rashid, M A AU - Gustafson, K R AU - Boyd, M R AD - Intramural Research Support Program, SAIC-Frederick, NCI-Frederick, Maryland 21702-1201, USA. Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 1454 EP - 1456 VL - 64 IS - 11 SN - 0163-3864, 0163-3864 KW - 14-methyleudistomidin C KW - 0 KW - 2-methyleudistomin D KW - 2-methyleudistomin J KW - Alkaloids KW - Antineoplastic Agents KW - Carbolines KW - eudistomin E KW - 88704-51-2 KW - Index Medicus KW - Molecular Structure KW - Animals KW - Drug Screening Assays, Antitumor KW - Stereoisomerism KW - Ovarian Neoplasms KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Spectrophotometry, Ultraviolet KW - Palau KW - Chromatography, High Pressure Liquid KW - Melanoma KW - Spectrophotometry, Infrared KW - Leukemia KW - Nuclear Magnetic Resonance, Biomolecular KW - Inhibitory Concentration 50 KW - Molecular Conformation KW - Colonic Neoplasms KW - Female KW - Alkaloids -- chemistry KW - Antineoplastic Agents -- isolation & purification KW - Alkaloids -- pharmacology KW - Alkaloids -- isolation & purification KW - Carbolines -- isolation & purification KW - Carbolines -- pharmacology KW - Antineoplastic Agents -- chemistry KW - Urochordata -- chemistry KW - Carbolines -- chemistry KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72299325?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+natural+products&rft.atitle=New+cytotoxic+N-methylated+beta-carboline+alkaloids+from+the+marine+ascidian+Eudistoma+gilboverde.&rft.au=Rashid%2C+M+A%3BGustafson%2C+K+R%3BBoyd%2C+M+R&rft.aulast=Rashid&rft.aufirst=M&rft.date=2001-11-01&rft.volume=64&rft.issue=11&rft.spage=1454&rft.isbn=&rft.btitle=&rft.title=Journal+of+natural+products&rft.issn=01633864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-14 N1 - Date created - 2001-11-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 10-Demethoxystegane, a new lignan from Steganotaenia araliacea. AN - 72296758; 11720541 AB - A new dibenzocyclooctadiene lactone lignan, 10-demethoxystegane (1), together with the known compounds steganone (2) and prestegane B (3), have been isolated from the organic extract of Steganotaenia araliacea(Apiaceae). Steganone (2) showed antiproliferative activity against an ovarian cancer cell line (OVCAR-3). JF - Journal of natural products AU - Meragelman, K M AU - McKee, T C AU - Boyd, M R AD - Molecular Targets Drug Discovery Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702-1201, USA. Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 1480 EP - 1482 VL - 64 IS - 11 SN - 0163-3864, 0163-3864 KW - 10-demethoxystegane KW - 0 KW - Antineoplastic Agents, Phytogenic KW - Lignans KW - steganone KW - prestegane B KW - 93376-04-6 KW - 4-Butyrolactone KW - OL659KIY4X KW - Index Medicus KW - Spectrophotometry, Infrared KW - Molecular Structure KW - Ovarian Neoplasms KW - Tumor Cells, Cultured -- drug effects KW - Nuclear Magnetic Resonance, Biomolecular KW - Humans KW - Spectrophotometry, Ultraviolet KW - Inhibitory Concentration 50 KW - Colonic Neoplasms KW - Female KW - Chromatography, High Pressure Liquid KW - Plants, Medicinal -- chemistry KW - Antineoplastic Agents, Phytogenic -- isolation & purification KW - Antineoplastic Agents, Phytogenic -- chemistry KW - Lignans -- isolation & purification KW - Apiaceae -- chemistry KW - Lignans -- pharmacology KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - 4-Butyrolactone -- pharmacology KW - 4-Butyrolactone -- isolation & purification KW - Lignans -- chemistry KW - 4-Butyrolactone -- chemistry KW - 4-Butyrolactone -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72296758?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+natural+products&rft.atitle=10-Demethoxystegane%2C+a+new+lignan+from+Steganotaenia+araliacea.&rft.au=Meragelman%2C+K+M%3BMcKee%2C+T+C%3BBoyd%2C+M+R&rft.aulast=Meragelman&rft.aufirst=K&rft.date=2001-11-01&rft.volume=64&rft.issue=11&rft.spage=1480&rft.isbn=&rft.btitle=&rft.title=Journal+of+natural+products&rft.issn=01633864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-14 N1 - Date created - 2001-11-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - X-deficient woodchuck hepatitis virus mutants behave like attenuated viruses and induce protective immunity in vivo. AN - 72294632; 11714744 AB - The X protein (HBX) of the hepatitis B virus (HBV) has been shown to be important for the establishment of HBV infection in vivo. Our previous studies suggested that interaction of HBX with the proteasome complex may underlie the pleiotropic functions of HBX. In this study, we generated a series of woodchuck hepatitis virus (WHV) X mutants, including mutants of the domain interacting with the proteasome, and studied their infectivity in woodchucks. Many of the mutants were defective in transactivation but none of them were completely replication defective in vitro. In vivo, all the wild-type and some X mutant-transfected animals demonstrated evidence of infection with anti-WHc and/or anti-WHs seroconversion. Most of the wild-type- and X mutant-transfected animals had transient viremia. Some animals were later challenged with infectious WHV. Animals inoculated with X mutants, including those with no serologic evidence of infection, were protected from the challenge, suggesting previous infection with resulting protective immunity. Our study demonstrates that the previously described functional domains of HBX are biologically important and the X-defective mutants, possibly as attenuated viruses, are not completely replication defective in vivo. JF - The Journal of clinical investigation AU - Zhang, Z AU - Torii, N AU - Hu, Z AU - Jacob, J AU - Liang, T J AD - Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1800, USA. Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 1523 EP - 1531 VL - 108 IS - 10 SN - 0021-9738, 0021-9738 KW - Antigens, Viral KW - 0 KW - DNA Primers KW - Trans-Activators KW - hepatitis B virus X protein KW - Abridged Index Medicus KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - DNA Replication -- genetics KW - Base Sequence KW - Marmota KW - Transcription, Genetic KW - Hepatitis B Virus, Woodchuck -- genetics KW - Trans-Activators -- genetics KW - Antigens, Viral -- immunology KW - Trans-Activators -- physiology KW - Hepatitis B Virus, Woodchuck -- immunology KW - Hepatitis B Virus, Woodchuck -- physiology KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72294632?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+investigation&rft.atitle=X-deficient+woodchuck+hepatitis+virus+mutants+behave+like+attenuated+viruses+and+induce+protective+immunity+in+vivo.&rft.au=Zhang%2C+Z%3BTorii%2C+N%3BHu%2C+Z%3BJacob%2C+J%3BLiang%2C+T+J&rft.aulast=Zhang&rft.aufirst=Z&rft.date=2001-11-01&rft.volume=108&rft.issue=10&rft.spage=1523&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-13 N1 - Date created - 2001-11-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1993 Mar;67(3):1218-26 [8437213] J Virol. 1992 Jul;66(7):4382-9 [1318408] J Virol. 1994 Mar;68(3):1651-9 [8107226] J Virol. 1994 Mar;68(3):2026-30 [8107266] J Clin Invest. 1994 Feb;93(2):550-5 [8113393] Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2230-4 [8134379] J Biol Chem. 1994 May 27;269(21):15118-23 [8195148] EMBO J. 1995 Jan 3;14(1):143-50 [7828586] J Virol. 1995 Mar;69(3):1851-9 [7853526] Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1003-7 [7862623] EMBO J. 1995 Oct 2;14(19):4747-57 [7588604] J Virol. 1996 Aug;70(8):4978-85 [8764004] J Virol. 1996 Aug;70(8):5582-91 [8764072] J Virol. 1997 Aug;71(8):6194-9 [9223516] Hepatology. 1998 Jan;27(1):228-39 [9425942] J Virol. 1999 Jan;73(1):281-9 [9847331] Hepatology. 1999 Jun;29(6):1863-9 [10347131] J Virol. 1999 Sep;73(9):7231-40 [10438810] J Virol. 2000 Jun;74(11):5257-65 [10799602] J Biol Chem. 2000 May 19;275(20):15157-65 [10748218] Oncogene. 2000 Sep 7;19(38):4427-31 [10980618] J Virol. 2001 Jan;75(1):161-70 [11119585] Gastroenterology. 2001 Mar;120(4):1000-8 [11231955] J Exp Med. 2001 Apr 2;193(7):847-54 [11283157] Nucleic Acids Res. 1984 Jan 25;12(2):857-72 [6694911] Proc Natl Acad Sci U S A. 1989 Mar;86(6):1846-9 [2928306] Nucleic Acids Res. 1989 Apr 11;17(7):2503-16 [2785681] J Virol. 1989 Sep;63(9):4019-26 [2788226] J Virol. 1990 Feb;64(2):613-20 [2153228] EMBO J. 1990 Feb;9(2):497-504 [2303039] Nature. 1990 Mar 1;344(6261):72-4 [2154703] J Virol. 1990 Nov;64(11):5553-8 [1698997] Science. 1991 May 10;252(5007):842-4 [1827531] Nature. 1991 May 23;351(6324):317-20 [2034275] Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8078-82 [8367466] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prospective study of tooth loss and incident esophageal and gastric cancers in China. AN - 72288657; 11714113 AB - To determine the association between tooth loss and the risk of developing esophageal squamous cell carcinoma, gastric cardia adenocarcinoma, or gastric non-cardia adenocarcinoma in a prospective study. Cox proportional hazards regression was used to examine these associations in a 28,868-person cohort followed prospectively for 5.25 years. The baseline questionnaire included questions regarding tooth loss, and individuals reporting lost teeth had their teeth counted by study personnel. The analytic cohort included 620 esophagus, 431 gastric cardia, and 102 gastric non-cardia cancer cases. Tooth loss was associated with a significantly elevated risk of developing all three cancers. When examined as median splits, tooth loss was associated with a relative risk (RR) (95% confidence interval, CI) of 1.3 (1.1-1.6) in the esophagus, 1.3 (1.0-1.6) in the gastric cardia, and 1.8 (1.1-3.0) in the gastric non-cardia. Further analysis demonstrated that this increased risk was most strongly associated with the loss of the first few teeth and was primarily confined to the younger members of our cohort. In this cohort tooth loss increased the risk of developing upper gastrointestinal cancer. We hypothesize that this may be related to alterations in oral bacterial flora and subsequent increases in the in-vivo production of carcinogens such as nitrosamines. JF - Cancer causes & control : CCC AU - Abnet, C C AU - Qiao, Y L AU - Mark, S D AU - Dong, Z W AU - Taylor, P R AU - Dawsey, S M AD - Cancer Prevention Studies Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892-7058, USA. abnetc@mail.nih.gov Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 847 EP - 854 VL - 12 IS - 9 SN - 0957-5243, 0957-5243 KW - Index Medicus KW - Risk KW - Prospective Studies KW - Humans KW - China -- epidemiology KW - Cohort Studies KW - Adult KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - Time Factors KW - Male KW - Female KW - Adenocarcinoma -- epidemiology KW - Carcinoma, Squamous Cell -- epidemiology KW - Tooth Loss -- epidemiology KW - Stomach Neoplasms -- epidemiology KW - Esophageal Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72288657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Prospective+study+of+tooth+loss+and+incident+esophageal+and+gastric+cancers+in+China.&rft.au=Abnet%2C+C+C%3BQiao%2C+Y+L%3BMark%2C+S+D%3BDong%2C+Z+W%3BTaylor%2C+P+R%3BDawsey%2C+S+M&rft.aulast=Abnet&rft.aufirst=C&rft.date=2001-11-01&rft.volume=12&rft.issue=9&rft.spage=847&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-13 N1 - Date created - 2001-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Incidence of squamous neoplasia of the cervix and vagina in women exposed prenatally to diethylstilbestrol (United States). AN - 72287895; 11714112 AB - Women exposed prenatally to diethylstibestrol (DES) have an excess risk of clear-cell adenocarcinoma of the vagina and cervix, but the effect on the incidence of squamous neoplasia is uncertain. The purpose of the current study was to evaluate the long-term risk of developing high-grade squamous neoplasia of the genital tract among women exposed prenatally to DES. A cohort comprising 3,899 DES-exposed and 1,374 unexposed daughters was followed for 13 years (1982 1995) for pathology-confirmed diagnoses of high-grade squamous intraepithelial neoplasia (HSIL) of the genital tract. Poisson regression analysis was used to compute relative risks (RR) and 95% confidence intervals (95% CI), adjusting for age, calendar year, and other covariates. The RR (95% CI) among DES-exposed versus unexposed, based on 111 cases of high-grade disease, was 2.1 (1.2-3.8). Adjustment for screening history estimated by the number of years since the last Pap smear had little effect. Risk estimates were higher with earlier intrauterine exposure; the RR (95% CI) for exposure within 7 weeks of the last menstrual period was 2.8 (1.4-5.5). Only two cases of invasive squamous cervical cancer occurred in total, precluding separate analysis. The findings support an association between in-utero DES exposure and high-grade squamous neoplasia, although a role for more intensive screening among DES-exposed women in the production of this excess could not be completely ruled out. JF - Cancer causes & control : CCC AU - Hatch, E E AU - Herbst, A L AU - Hoover, R N AU - Noller, K L AU - Adam, E AU - Kaufman, R H AU - Palmer, J R AU - Titus-Ernstoff, L AU - Hyer, M AU - Hartge, P AU - Robboy, S J AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. eehatch@bu.edu Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 837 EP - 845 VL - 12 IS - 9 SN - 0957-5243, 0957-5243 KW - Estrogens, Non-Steroidal KW - 0 KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Risk Factors KW - Humans KW - Cohort Studies KW - Incidence KW - Middle Aged KW - Follow-Up Studies KW - United States -- epidemiology KW - Time Factors KW - Female KW - Pregnancy KW - Diethylstilbestrol -- adverse effects KW - Carcinoma, Squamous Cell -- epidemiology KW - Uterine Cervical Neoplasms -- epidemiology KW - Vaginal Neoplasms -- chemically induced KW - Carcinoma, Squamous Cell -- chemically induced KW - Uterine Cervical Neoplasms -- chemically induced KW - Estrogens, Non-Steroidal -- adverse effects KW - Vaginal Neoplasms -- epidemiology KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72287895?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Incidence+of+squamous+neoplasia+of+the+cervix+and+vagina+in+women+exposed+prenatally+to+diethylstilbestrol+%28United+States%29.&rft.au=Hatch%2C+E+E%3BHerbst%2C+A+L%3BHoover%2C+R+N%3BNoller%2C+K+L%3BAdam%2C+E%3BKaufman%2C+R+H%3BPalmer%2C+J+R%3BTitus-Ernstoff%2C+L%3BHyer%2C+M%3BHartge%2C+P%3BRobboy%2C+S+J&rft.aulast=Hatch&rft.aufirst=E&rft.date=2001-11-01&rft.volume=12&rft.issue=9&rft.spage=837&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-13 N1 - Date created - 2001-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oral manifestations in patients with aplastic anemia. AN - 72287823; 11709685 AB - The aim of the present study was to characterize the prevalence and risks of oral complications in aplastic anemia (AA). Approximately 79 patients with AA (age, 37 +/- 17 years) and 66 control patients with schizophrenia (age, 33 +/- 12 years) were examined. Records were reviewed for demographic, clinical, and radiographic information. Prior medical therapy, laboratory values, disease duration, and medical treatment response were noted for patients with AA. Odds ratios (OR) and 95% CI were calculated for oral manifestations in cases and in control subjects. Univariate analysis identified important variables for logistic regression. Patients with AA presented more frequently with oral petechiae (OR = 49; 95% CI, 2.9-825), gingival hyperplasia (OR = 27; 95% CI, 1.6-463.5), spontaneous gingival bleeding (OR = 27; 95% CI, 1.6-463.5), and herpetic lesions (OR = 27; 95% CI, 1.6-463.5). Prior cyclosporine use was associated with gingival hyperplasia (P =.0001). No other predictors for oral manifestations or treatment outcomes were found. Oral soft tissue changes and infections were more common in patients with AA. Prior cyclosporine use was predictive of the presence of gingival hyperplasia. JF - Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics AU - Brennan, M T AU - Sankar, V AU - Baccaglini, L AU - Pillemer, S R AU - Kingman, A AU - Nunez, O AU - Young, N S AU - Atkinson, J C AD - Clinical Research Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Md, USA. Mike.Brennan@carolinashealthcare.org Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 503 EP - 508 VL - 92 IS - 5 SN - 1079-2104, 1079-2104 KW - Immunosuppressive Agents KW - 0 KW - Cyclosporine KW - 83HN0GTJ6D KW - Dentistry KW - Index Medicus KW - Gingival Hemorrhage -- etiology KW - Odds Ratio KW - Analysis of Variance KW - Oral Ulcer -- virology KW - Humans KW - Periodontal Diseases -- etiology KW - Oral Ulcer -- etiology KW - Gingival Hyperplasia -- etiology KW - Cyclosporine -- adverse effects KW - Purpura -- etiology KW - Logistic Models KW - Risk Factors KW - Adult KW - Treatment Outcome KW - Confidence Intervals KW - Follow-Up Studies KW - DMF Index KW - Male KW - Female KW - Stomatitis, Herpetic -- etiology KW - Immunosuppressive Agents -- adverse effects KW - Dental Care for Chronically Ill KW - Gingival Hyperplasia -- chemically induced KW - Anemia, Aplastic -- drug therapy KW - Anemia, Aplastic -- complications KW - Mouth Diseases -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72287823?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oral+surgery%2C+oral+medicine%2C+oral+pathology%2C+oral+radiology%2C+and+endodontics&rft.atitle=Oral+manifestations+in+patients+with+aplastic+anemia.&rft.au=Brennan%2C+M+T%3BSankar%2C+V%3BBaccaglini%2C+L%3BPillemer%2C+S+R%3BKingman%2C+A%3BNunez%2C+O%3BYoung%2C+N+S%3BAtkinson%2C+J+C&rft.aulast=Brennan&rft.aufirst=M&rft.date=2001-11-01&rft.volume=92&rft.issue=5&rft.spage=503&rft.isbn=&rft.btitle=&rft.title=Oral+surgery%2C+oral+medicine%2C+oral+pathology%2C+oral+radiology%2C+and+endodontics&rft.issn=10792104&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-22 N1 - Date created - 2001-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment options for a patient experiencing pruritic rash associated with transdermal testosterone: a review of the literature. AN - 72285183; 11714217 AB - A 22-year-old man with hypogonadotropic hypogonadism was receiving monthly intramuscular injections of testosterone replacement therapy. The patient refused to self-administer the injections because of discomfort, so the therapy was switched to testosterone patches. He experienced a pruritic, macular, erythematous rash underneath the reservoir area of two different transdermal formulations, which did not improve after pretreatment with topical corticosteroids. Eventually, he tolerated application of a testosterone gel and his serum testosterone levels returned to normal after 1 month of therapy. Commercially available and investigational testosterone products and therapeutic monitoring guidelines for androgen replacement are reviewed. JF - Pharmacotherapy AU - McGriff, N J AU - Csako, G AU - Kabbani, M AU - Diep, L AU - Chrousos, G P AU - Pucino, F AD - Pharmacy Department, Warren G. Magnuson Clinical Center, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, USA. n.mcgrif@usip.edu Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 1425 EP - 1435 VL - 21 IS - 11 SN - 0277-0008, 0277-0008 KW - Gels KW - 0 KW - Testosterone KW - 3XMK78S47O KW - Index Medicus KW - Injections, Intradermal KW - Administration, Cutaneous KW - Humans KW - Adult KW - Male KW - Testosterone -- administration & dosage KW - Testosterone -- adverse effects KW - Hormone Replacement Therapy -- statistics & numerical data KW - Pruritus -- chemically induced KW - Hormone Replacement Therapy -- methods KW - Testosterone -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72285183?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacotherapy&rft.atitle=Treatment+options+for+a+patient+experiencing+pruritic+rash+associated+with+transdermal+testosterone%3A+a+review+of+the+literature.&rft.au=McGriff%2C+N+J%3BCsako%2C+G%3BKabbani%2C+M%3BDiep%2C+L%3BChrousos%2C+G+P%3BPucino%2C+F&rft.aulast=McGriff&rft.aufirst=N&rft.date=2001-11-01&rft.volume=21&rft.issue=11&rft.spage=1425&rft.isbn=&rft.btitle=&rft.title=Pharmacotherapy&rft.issn=02770008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-02 N1 - Date created - 2001-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Photochemistry and photocytotoxicity of alkaloids from Goldenseal (Hydrastis canadensis L.) 1. Berberine. AN - 72284212; 11712911 AB - Goldenseal is an herb which is widely used for many medical applications such as in eyewashes and skin lotions and which is currently undergoing testing by the National Toxicology Program. The main alkaloid constituent of Goldenseal is berberine. The topical application of Goldenseal or berberine to the skin or eyes raises the possibility that an adverse phototoxic reaction may result from an interaction between the alkaloid and light. We have therefore studied the photochemistry of berberine in different solvents and its phototoxicty to HaCaT keratinocytes. Irradiation of berberine in aqueous solutions does not generate (1)O(2), but in CH(2)Cl(2), (1)O(2) is produced with a quantum yield phi = 0.34. With the aid of the electron paramagnetic resonance (EPR) spin trapping technique and 5,5-dimethyl-1-pyrroline N-oxide (DMPO), we have detected oxygen-centered radicals photogenerated by berberine in water and acetonitrile. In the latter solvent and in the absence of oxygen, the neutral berberine radical formed by one electron reduction was observed. Methanol radicals were detected by EPR in water/alcohol low-temperature glasses irradiated in the berberine long-wavelength absorption band. In such alcoholic glasses, we have also detected an EPR signal from the berberine triplet at 77 K, in contrast to aqueous glasses where neither triplet nor radicals were detectable. Our data show that, although a weak photosensitizer in water, berberine is able to produce both (1)O(2) and radical species in a nonpolar environment. UVA irradiation of HaCaT keratinocytes in the presence of 50 microM berberine resulted in an 80% decrease in cell viability and a 3-fold increase in DNA damage as measured by the Comet assay. These findings suggest that exposure to sunlight or artificial light sources emitting UVA should be avoided when topical preparations derived from Goldenseal or containing berberine are used. JF - Chemical research in toxicology AU - Inbaraj, J J AU - Kukielczak, B M AU - Bilski, P AU - Sandvik, S L AU - Chignell, C F AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 1529 EP - 1534 VL - 14 IS - 11 SN - 0893-228X, 0893-228X KW - Free Radicals KW - 0 KW - Photosensitizing Agents KW - Plant Extracts KW - Solvents KW - Berberine KW - 0I8Y3P32UF KW - Index Medicus KW - Photochemistry KW - Ultraviolet Rays KW - Humans KW - Cell Culture Techniques KW - Plant Extracts -- chemistry KW - Cell Survival KW - Oxidation-Reduction KW - Photosensitizing Agents -- chemistry KW - Electron Spin Resonance Spectroscopy KW - Plant Extracts -- toxicity KW - Keratinocytes -- pathology KW - Administration, Topical KW - Dermatitis, Phototoxic -- physiopathology KW - Berberine -- chemistry KW - Ranunculaceae -- chemistry KW - DNA Damage KW - Berberine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72284212?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Photochemistry+and+photocytotoxicity+of+alkaloids+from+Goldenseal+%28Hydrastis+canadensis+L.%29+1.+Berberine.&rft.au=Inbaraj%2C+J+J%3BKukielczak%2C+B+M%3BBilski%2C+P%3BSandvik%2C+S+L%3BChignell%2C+C+F&rft.aulast=Inbaraj&rft.aufirst=J&rft.date=2001-11-01&rft.volume=14&rft.issue=11&rft.spage=1529&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-26 N1 - Date created - 2001-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antiapoptotic effect of dipyrone on HL-60, Jurkat and Raji cell lines submitted to UV irradiation, arachidonic acid and cycloheximide treatments. AN - 72281623; 11710546 AB - The effect of dipyrone (metamizol) on cell viability was evaluated in human leukocyte cell lines upon different apoptotic treatments: arachidonic acid (AA), cycloheximide (CHX), tumor necrosis factor (TNF) and ultraviolet (UV) irradiation. Dipyrone had a dual effect: at high concentrations (beyond 300 microM), it was cytotoxic, leading to apoptosis, whereas at lower concentrations (37.5-300 microM), it was cytoprotective, delaying the loss of membrane integrity triggered by arachidonic acid (100-200 microM) and UV irradiation and the cytotoxicity of cycloheximide (25-50 microM). No effect of dipyrone was found on TNF-induced cytotoxicity (250 ng/ml). The cytoprotective effect of dipyrone is associated with a decrease in DNA fragmentation, as assessed by electrophoresis of genomic DNA and by flow cytometry; a reduction in the percentage of condensed nuclei, as evaluated by DNA staining with Hoescht 33342 and a decrease in poly(ADP)-ribose polymerase (PARP) cleavage, as assessed by Western blotting. The cytoprotective effect of dipyrone on leukocyte apoptosis occurs at concentrations usually found for the main active metabolite of the drug and may have implications on the therapeutic and side effects caused by this agent. JF - International immunopharmacology AU - Pompeia, C AU - Boaventura, M F AU - Curi, R AD - National Institute of Deafness and Other Communication Disorders, National Institutes of Health USA, Bethesda, MD 20892-4163. pompeiac@nidcd.nih.gov Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 2173 EP - 2182 VL - 1 IS - 12 SN - 1567-5769, 1567-5769 KW - Analgesics KW - 0 KW - Analgesics, Non-Narcotic KW - Cyclooxygenase Inhibitors KW - Neoplasm Proteins KW - Parasympatholytics KW - Protein Synthesis Inhibitors KW - Radiation-Protective Agents KW - Tumor Necrosis Factor-alpha KW - Arachidonic Acid KW - 27YG812J1I KW - Dipyrone KW - 6429L0L52Y KW - Cycloheximide KW - 98600C0908 KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - Aspirin KW - R16CO5Y76E KW - Index Medicus KW - Leukemia, B-Cell -- pathology KW - Tumor Cells, Cultured -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Apoptosis -- drug effects KW - DNA Fragmentation -- drug effects KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Neoplasm Proteins -- metabolism KW - Aspirin -- pharmacology KW - Tumor Cells, Cultured -- radiation effects KW - Cyclooxygenase Inhibitors -- pharmacology KW - Ultraviolet Rays KW - Analgesics, Non-Narcotic -- pharmacology KW - Jurkat Cells -- radiation effects KW - Parasympatholytics -- pharmacology KW - B-Lymphocytes -- radiation effects KW - Radiation-Protective Agents -- pharmacology KW - Parasympatholytics -- adverse effects KW - Analgesics -- adverse effects KW - Jurkat Cells -- drug effects KW - B-Lymphocytes -- drug effects KW - Analgesics, Non-Narcotic -- adverse effects KW - HL-60 Cells -- radiation effects KW - Radiation-Protective Agents -- administration & dosage KW - Cycloheximide -- pharmacology KW - Parasympatholytics -- administration & dosage KW - Radiation-Protective Agents -- adverse effects KW - Arachidonic Acid -- pharmacology KW - Analgesics -- pharmacology KW - Analgesics, Non-Narcotic -- administration & dosage KW - Dipyrone -- pharmacology KW - HL-60 Cells -- drug effects KW - Protein Synthesis Inhibitors -- pharmacology KW - Dipyrone -- adverse effects KW - Analgesics -- administration & dosage KW - Dipyrone -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72281623?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+immunopharmacology&rft.atitle=Antiapoptotic+effect+of+dipyrone+on+HL-60%2C+Jurkat+and+Raji+cell+lines+submitted+to+UV+irradiation%2C+arachidonic+acid+and+cycloheximide+treatments.&rft.au=Pompeia%2C+C%3BBoaventura%2C+M+F%3BCuri%2C+R&rft.aulast=Pompeia&rft.aufirst=C&rft.date=2001-11-01&rft.volume=1&rft.issue=12&rft.spage=2173&rft.isbn=&rft.btitle=&rft.title=International+immunopharmacology&rft.issn=15675769&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-29 N1 - Date created - 2001-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mitochondrial alterations with mitochondrial DNA depletion in the nerves of AIDS patients with peripheral neuropathy induced by 2'3'-dideoxycytidine (ddC). AN - 72272031; 11706061 AB - The 2'3'-dideoxycytidine (ddC), a nonazylated dideoxynucleoside analog used for the treatment of AIDS, causes a dose-dependent, painful, sensorimotor axonal peripheral neuropathy in up to 30% of the patients. To investigate the cause of the neuropathy, we performed morphological and molecular studies on nerve biopsy specimens from well-selected patients with ddC-neuropathy and from control subjects with disease, including patients with AIDS-related neuropathy never treated with ddC. Because ddC, in vitro, inhibits the replication of mitochondrial DNA (mtDNA), we counted the number of normal and abnormal mitochondria in a 0.04 mm(2) cross-sectional area of the nerves and quantified the copy numbers of mtDNA by competitive PCR in all specimens. A varying degree of axonal degeneration was present in all nerves. Abnormal mitochondria with enlarged size, excessive vacuolization, electron-dense concentric inclusions and degenerative myelin structures were prominent in the ddC-neuropathy and accounted for 55% +/- 2.5% of all counted mitochondria in the axon and Schwann cells, compared with 9% +/- 0.7% of the controls (p < 0.001). Significantly (p < 0.005) reduced copy numbers, with as high as 80% depletion, of the mtDNA was demonstrated in the nerves of the ddC-treated patients compared with the controls. We conclude that ddC induces a mitochondrial neuropathy with depletion of the nerve's mtDNA. The findings are consistent with the ability of ddC to selectively inhibit the gamma-DNA polymerase in neuronal cell lines. Toxicity to mitochondria of the peripheral nerve is a new cause of acquired neuropathy induced by exogenous toxins and may be the cause of neuropathy associated with the other neurotoxic antiretroviral drugs or toxic-metabolic conditions. JF - Laboratory investigation; a journal of technical methods and pathology AU - Dalakas, M C AU - Semino-Mora, C AU - Leon-Monzon, M AD - Neuromuscular Diseases SectionNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 1537 EP - 1544 VL - 81 IS - 11 SN - 0023-6837, 0023-6837 KW - Anti-HIV Agents KW - 0 KW - DNA, Mitochondrial KW - Zalcitabine KW - 6L3XT8CB3I KW - Index Medicus KW - Sural Nerve -- pathology KW - Mitochondria -- ultrastructure KW - Humans KW - Mitochondria -- drug effects KW - Adult KW - Middle Aged KW - Microscopy, Electron KW - Mitochondria -- genetics KW - Schwann Cells -- pathology KW - Peripheral Nervous System Diseases -- pathology KW - DNA, Mitochondrial -- metabolism KW - Anti-HIV Agents -- adverse effects KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Peripheral Nervous System Diseases -- virology KW - Zalcitabine -- adverse effects KW - Peripheral Nervous System Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72272031?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.atitle=Mitochondrial+alterations+with+mitochondrial+DNA+depletion+in+the+nerves+of+AIDS+patients+with+peripheral+neuropathy+induced+by+2%273%27-dideoxycytidine+%28ddC%29.&rft.au=Dalakas%2C+M+C%3BSemino-Mora%2C+C%3BLeon-Monzon%2C+M&rft.aulast=Dalakas&rft.aufirst=M&rft.date=2001-11-01&rft.volume=81&rft.issue=11&rft.spage=1537&rft.isbn=&rft.btitle=&rft.title=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.issn=00236837&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-07 N1 - Date created - 2001-11-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational exposure to wood, formaldehyde, and solvents and risk of nasopharyngeal carcinoma. AN - 72268145; 11700262 AB - Our objective was to evaluate the link between occupational exposures to wood dust, formaldehyde, and solvents and the development of nasopharyngeal carcinoma (NPC). A case-control study was conducted among 375 newly diagnosed cases of NPC in Taipei, Taiwan, and 325 community controls matched to cases on sex, age, and geographical residence (99 and 87% response rates, respectively). Most cases (>90%) were diagnosed with WHO Types 2 or 3 (nonkeratinizing and undifferentiated carcinomas), whereas the remaining cases were diagnosed with WHO Type 1 (squamous cell carcinomas). A complete occupational history was obtained via a personal interview and blindly assessed by an industrial hygienist for intensity and probability of exposure to wood dust, formaldehyde, and solvents. Information on socio-demographic characteristics, cigarette smoking, dietary consumption of nitrosamines, and other potential confounding factors was obtained via a personal interview. Blood specimens were tested for human leukocyte antigen class I/II genotypes, polymorphisms in cytochrome P450 2E1 genotype, and various anti-EBV antibodies known to be associated with NPC. Analysis was performed using logistic regression; relative risk (RR) estimates and 95% confidence intervals (CI) were calculated. Individuals exposed to wood dust had an adjusted RR of 1.7 (95% CI = 1.0-3.0). Those exposed to wood dust for >10 years had an adjusted RR of 2.4 (95% CI = 1.1-5.0; p(trend) = 0.02). Risk was strongest for those first exposed before the age of 25 years and those seropositive to EBV. Individuals exposed to formaldehyde were at a more modest and nonsignificant increased risk of NPC (RR = 1.4; 95% CI = 0.93-2.2). Those exposed to formaldehyde for >10 years had an adjusted RR of 1.6 (95% CI = 0.91-2.9). The association between formaldehyde and NPC was stronger in analyses restricted to EBV seropositive individuals (RR = 2.7; 95% CI = 1.2-5.9). However, no dose response was observed with increasing duration or cumulative use. No association was observed between solvent exposure and NPC (RR = 1.2; 95% CI = 0.86-1.7). Occupational exposure to wood dust is likely to be involved in the development of NPC, a finding that is consistent with the known link between wood exposure and nasal adenocarcinomas. Formaldehyde exposure is less clearly linked to NPC, whereas exposure to solvents is unlikely to be involved in NPC pathogenesis. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Hildesheim, A AU - Dosemeci, M AU - Chan, C C AU - Chen, C J AU - Cheng, Y J AU - Hsu, M M AU - Chen, I H AU - Mittl, B F AU - Sun, B AU - Levine, P H AU - Chen, J Y AU - Brinton, L A AU - Yang, C S AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. Hildesha@exchange.nih.gov Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 1145 EP - 1153 VL - 10 IS - 11 SN - 1055-9965, 1055-9965 KW - Dust KW - 0 KW - Solvents KW - Formaldehyde KW - 1HG84L3525 KW - Index Medicus KW - Logistic Models KW - Risk Factors KW - Humans KW - Taiwan -- epidemiology KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Occupational Exposure KW - Nasopharyngeal Neoplasms -- blood KW - Occupational Diseases -- blood KW - Nasopharyngeal Neoplasms -- epidemiology KW - Wood KW - Occupational Diseases -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72268145?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Occupational+exposure+to+wood%2C+formaldehyde%2C+and+solvents+and+risk+of+nasopharyngeal+carcinoma.&rft.au=Hildesheim%2C+A%3BDosemeci%2C+M%3BChan%2C+C+C%3BChen%2C+C+J%3BCheng%2C+Y+J%3BHsu%2C+M+M%3BChen%2C+I+H%3BMittl%2C+B+F%3BSun%2C+B%3BLevine%2C+P+H%3BChen%2C+J+Y%3BBrinton%2C+L+A%3BYang%2C+C+S&rft.aulast=Hildesheim&rft.aufirst=A&rft.date=2001-11-01&rft.volume=10&rft.issue=11&rft.spage=1145&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-18 N1 - Date created - 2001-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure and control of a cell-cell adhesion complex associated with spermiation in rat seminiferous epithelium. AN - 72265693; 11700851 AB - Spermiation, the release of late spermatids from the Sertoli cell, is disrupted by a number of toxicants. Control of the spermiation process, and the proteins that interact to adhere mature spermatids to Sertoli cells, is poorly understood. In these studies we used immunohistochemistry, coimmunoprecipitation/Western blotting, and mass spectrometry to refine an earlier model of sperm adhesion proposed by our laboratory. We have identified specific proteins linked together as part of a multiprotein complex, as well as several additional proteins (cortactin, ERK1/2, and 14-3-3 zeta) that may be functioning in both structural and signal transduction roles. The current and prior data suggest that protein phosphorylation is central to the control of spermiation. We also present and characterize an in vitro tubule culture system that allowed functional testing of the spermiation model by pharmacologic manipulation, and yielded data consistent with the importance of protein phosphorylation in spermiation. JF - Journal of andrology AU - Chapin, R E AU - Wine, R N AU - Harris, M W AU - Borchers, C H AU - Haseman, J K AD - Reproductive Toxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. robert.e.chapin@dupontpharma.com PY - 2001 SP - 1030 EP - 1052 VL - 22 IS - 6 SN - 0196-3635, 0196-3635 KW - Antigens KW - 0 KW - peroxovanadate KW - Bacitracin KW - 1405-87-4 KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Vanadates KW - 3WHH0066W5 KW - cdc42 GTP-Binding Protein KW - EC 3.6.5.2 KW - Staurosporine KW - H88EPA0A3N KW - Index Medicus KW - Animals KW - Epithelial Cells -- physiology KW - Vanadates -- pharmacology KW - Cell Division -- drug effects KW - Mice KW - Antigens -- analysis KW - Rats KW - Staurosporine -- pharmacology KW - Rats, Sprague-Dawley KW - Epithelial Cells -- cytology KW - Bacitracin -- pharmacology KW - Cell Death KW - Okadaic Acid -- pharmacology KW - Organ Culture Techniques -- methods KW - cdc42 GTP-Binding Protein -- analysis KW - Male KW - Spermatogenesis -- physiology KW - Cell Adhesion -- physiology KW - Seminiferous Tubules -- cytology KW - Spermatogenesis -- drug effects KW - Cell Adhesion -- drug effects KW - Seminiferous Tubules -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72265693?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+andrology&rft.atitle=Structure+and+control+of+a+cell-cell+adhesion+complex+associated+with+spermiation+in+rat+seminiferous+epithelium.&rft.au=Chapin%2C+R+E%3BWine%2C+R+N%3BHarris%2C+M+W%3BBorchers%2C+C+H%3BHaseman%2C+J+K&rft.aulast=Chapin&rft.aufirst=R&rft.date=2001-11-01&rft.volume=22&rft.issue=6&rft.spage=1030&rft.isbn=&rft.btitle=&rft.title=Journal+of+andrology&rft.issn=01963635&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-02 N1 - Date created - 2001-11-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Double-blind, placebo-controlled study of single-dose amphetamine formulations in ADHD. AN - 72265680; 11699800 AB - To compare the efficacy and time course of single morning doses of Adderall, extended-release, and immediate-release dextroamphetamine sulfate. Thirty-five children with attention-deficit/hyperactivity disorder, combined type, were given Adderall, immediate-release dextroamphetamine, dextroamphetamine Spansules, and placebo in a randomized, double-blind, crossover study. Behavior ratings, locomotor activity measurements, and academic measures were obtained over a period of 8 weeks. All three drugs exhibited robust efficacy versus placebo on nearly all measures. The effects of dextroamphetamine Spansules were less robust in the morning, particularly compared with Adderall, but they lasted 3 to 6 hours longer, depending on the measure. Although parent behavior ratings and locomotor activity showed improvements up to 12 hours after single doses of all three drugs, the number of math problems attempted and completed correctly 4 hours after dosing were only robustly increased by Spansules. Both immediate-release amphetamines demonstrated earlier onset of effects, but dextroamphetamine Spansules showed more sustained effects that were present on a wider range of measures. JF - Journal of the American Academy of Child and Adolescent Psychiatry AU - James, R S AU - Sharp, W S AU - Bastain, T M AU - Lee, P P AU - Walter, J M AU - Czarnolewski, M AU - Castellanos, F X AD - Child Psychiatry Branch, National Institute of Mental Health, Bethesda, MD, USA. Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 1268 EP - 1276 VL - 40 IS - 11 SN - 0890-8567, 0890-8567 KW - Adderall KW - 0 KW - Amphetamines KW - Central Nervous System Stimulants KW - Delayed-Action Preparations KW - Dextroamphetamine KW - TZ47U051FI KW - Index Medicus KW - Drug Administration Schedule KW - Double-Blind Method KW - Humans KW - Treatment Outcome KW - Child KW - Male KW - Female KW - Attention Deficit Disorder with Hyperactivity -- psychology KW - Attention Deficit Disorder with Hyperactivity -- diagnosis KW - Dextroamphetamine -- administration & dosage KW - Amphetamines -- administration & dosage KW - Amphetamines -- adverse effects KW - Central Nervous System Stimulants -- adverse effects KW - Central Nervous System Stimulants -- administration & dosage KW - Dextroamphetamine -- adverse effects KW - Attention Deficit Disorder with Hyperactivity -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72265680?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.atitle=Double-blind%2C+placebo-controlled+study+of+single-dose+amphetamine+formulations+in+ADHD.&rft.au=James%2C+R+S%3BSharp%2C+W+S%3BBastain%2C+T+M%3BLee%2C+P+P%3BWalter%2C+J+M%3BCzarnolewski%2C+M%3BCastellanos%2C+F+X&rft.aulast=James&rft.aufirst=R&rft.date=2001-11-01&rft.volume=40&rft.issue=11&rft.spage=1268&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.issn=08908567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-18 N1 - Date created - 2001-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Eosinophils, eosinophil ribonucleases, and their role in host defense against respiratory virus pathogens. AN - 72262447; 11698487 AB - Eosinophils remain among the most enigmatic of cells, as our appreciation of their detrimental activities--e.g., asthma and allergic disease--far outweighs our understanding of their beneficial effects. Among the major secretory effector proteins of eosinophils are the ribonucleases eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) in primates and their orthologs, the eosinophil-associated ribonucleases (EARs) in rodents. The rapid diversification observed among these ribonucleases suggested that the ultimate target(s) might be similarly efficient at generating sequence diversity while maintaining an unalterable susceptibility to ribonucleolytic cleavage. This has prompted us to consider a role for these proteins and by extension, for eosinophils, in host defense against single-stranded RNA virus pathogens. We detail our studies of the antiviral activity of eosinophils and eosinophil ribonucleases against respiratory syncytial virus (RSV) in vitro and the related, natural rodent pathogen, pneumonia virus of mice (PVM), in vivo, and consider the possibility that antiviral host defense and the dysregulated responses leading to asthma represent opposing sides of an eosinophil-mediated double-edged sword. JF - Journal of leukocyte biology AU - Rosenberg, H F AU - Domachowske, J B AD - Eosinophil Biology Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. hr2k@nih.gov Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 691 EP - 698 VL - 70 IS - 5 SN - 0741-5400, 0741-5400 KW - Blood Proteins KW - 0 KW - Eosinophil Granule Proteins KW - Recombinant Proteins KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Index Medicus KW - Cytoplasmic Granules -- enzymology KW - Animals KW - Asthma -- etiology KW - Recombinant Proteins -- pharmacology KW - Disease Susceptibility KW - Pneumovirus Infections -- virology KW - Humans KW - Murine pneumonia virus -- immunology KW - Mice KW - Child KW - Respiratory Syncytial Virus Infections -- immunology KW - Pneumovirus Infections -- immunology KW - Pulmonary Eosinophilia -- virology KW - Primates KW - Chemotaxis KW - Evolution, Molecular KW - Pulmonary Eosinophilia -- immunology KW - Infant KW - Rodentia KW - Species Specificity KW - Asthma -- immunology KW - Blood Proteins -- physiology KW - Eosinophils -- physiology KW - Virus Diseases -- immunology KW - Ribonucleases -- physiology KW - Ribonucleases -- pharmacology KW - Eosinophils -- enzymology KW - Ribonucleases -- genetics KW - Respiratory Tract Infections -- virology KW - Respiratory Tract Infections -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72262447?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+leukocyte+biology&rft.atitle=Eosinophils%2C+eosinophil+ribonucleases%2C+and+their+role+in+host+defense+against+respiratory+virus+pathogens.&rft.au=Rosenberg%2C+H+F%3BDomachowske%2C+J+B&rft.aulast=Rosenberg&rft.aufirst=H&rft.date=2001-11-01&rft.volume=70&rft.issue=5&rft.spage=691&rft.isbn=&rft.btitle=&rft.title=Journal+of+leukocyte+biology&rft.issn=07415400&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-07 N1 - Date created - 2001-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analgesia and COX-2 inhibition. AN - 72260139; 11695255 AB - While non-steroidal anti-inflammatory drugs (NSAIDs) are the mainstay of therapy for the management of acute pain and rheumatoid arthritis, toxicity associated with chronic administration limits their benefit-to-risk relationship in many patients. A series of studies is reviewed that assesses the relationship between cytokines released at the site of tissue injury and NSAID analgesia, and the in vivo selectivity of a selective cyclooxygenase (COX)-2 inhibitor (celecoxib) in comparison to a dual COX-1/COX-2 inhibitor (ketorolac). Three replicate studies in the oral surgery model of acute pain used submucosal microdialysis sample collection for the measurement of prostaglandin E2 (PGE2; a product of both COX-1 and COX-2) and thromboxane B2 (as a biomarker for COX-1 activity) with parallel assessments of pain. The time course of PGE2 production was consistent with early release due to COX-1 activity followed by increased production 2-3 hours after surgery, consistent with COX-2 expression. Ketorolac 30 mg at pain onset suppressed both pain and peripheral PGE2 levels. Ketorolac 1 mg either at the site of injury or intramuscularly also produced analgesia but without any effect on peripheral PGE2 levels. Celecoxib selectively suppressed PGE2 but not TxB2 at time points consistent with COX-2 activity, while producing analgesia. These studies demonstrate the ability to assess the time course and selective effects of COX-2 inhibitors in vivo and suggest that suppression of COX-2 mediated PGE2 is temporally related to NSAID analgesia. JF - Clinical and experimental rheumatology AU - Dionne, R A AU - Khan, A A AU - Gordon, S M AD - National Institute of Dental and Craniofacial Research, NIH, Washington, USA. dionnera@yahoo.com PY - 2001 SP - S63 EP - S70 VL - 19 IS - 6 Suppl 25 SN - 0392-856X, 0392-856X KW - Analgesics, Non-Narcotic KW - 0 KW - Anti-Inflammatory Agents, Non-Steroidal KW - Cyclooxygenase 2 Inhibitors KW - Cyclooxygenase Inhibitors KW - Isoenzymes KW - Membrane Proteins KW - Pyrazoles KW - Sulfonamides KW - Thromboxane B2 KW - 54397-85-2 KW - Dexamethasone KW - 7S5I7G3JQL KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Celecoxib KW - JCX84Q7J1L KW - Dinoprostone KW - K7Q1JQR04M KW - Ketorolac KW - YZI5105V0L KW - Index Medicus KW - Microdialysis KW - Drug Therapy, Combination KW - Acute Disease KW - Dinoprostone -- blood KW - Dexamethasone -- therapeutic use KW - Humans KW - Pain Measurement KW - Substrate Specificity KW - Thromboxane B2 -- blood KW - Cyclooxygenase Inhibitors -- therapeutic use KW - Analgesics, Non-Narcotic -- therapeutic use KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Anti-Inflammatory Agents, Non-Steroidal -- adverse effects KW - Facial Pain -- physiopathology KW - Facial Pain -- blood KW - Facial Pain -- drug therapy KW - Ketorolac -- therapeutic use KW - Sulfonamides -- therapeutic use KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72260139?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+and+experimental+rheumatology&rft.atitle=Analgesia+and+COX-2+inhibition.&rft.au=Dionne%2C+R+A%3BKhan%2C+A+A%3BGordon%2C+S+M&rft.aulast=Dionne&rft.aufirst=R&rft.date=2001-11-01&rft.volume=19&rft.issue=6+Suppl+25&rft.spage=S63&rft.isbn=&rft.btitle=&rft.title=Clinical+and+experimental+rheumatology&rft.issn=0392856X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-07 N1 - Date created - 2001-11-06 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 ER - TY - JOUR T1 - Testosterone and prostate specific antigen stimulate generation of reactive oxygen species in prostate cancer cells. AN - 72259966; 11698338 AB - Prostate specific antigen, the clinical marker for prostate cancer, is a neutral serine protease whose function is to lyse seminal proteins. Recent work by our laboratory has suggested that prostate specific antigen stimulates the generation of reactive oxygen species in prostate cancer cells. Using 2',7'-dichlorofluorescin diacetate, a dye that fluoresces in the presence of hydrogen peroxide or hydroxyl radicals, we found that prostate specific antigen markedly stimulated reactive oxygen species generation in LNCaP cells. The effect was concentration dependent and its specificity was supported by the fact that anti-prostate specific antigen antibodies abolished the response. Since testosterone stimulates the production of prostate specific antigen, we considered that the reactive oxygen species response to testosterone may be linked to prostate specific antigen. We found that the testosterone effect on reactive oxygen species was blocked by flutamide and by anti-prostate specific antigen antibody. Additionally, though PC3 and DU145 could not respond to testosterone, they readily increased reactive oxygen species in response to prostate specific antigen. Focusing on the mechanism of the prostate specific antigen effect, we tested two other serine proteases, trypsin and chymotrypsin, but found no effect on reactive oxygen species in LNCaP cells. Nevertheless, serine protease inhibitors, alpha(1)-antichymotrypsin, alpha(2)-macroglobulin and Bowman-Birk inhibitor, blocked reactive oxygen species generation stimulated by prostate specific antigen. This apparent paradox was investigated with the use of a specific anti-'prostate specific antigen' antibody which recognizes an epitope away from the catalytic site and which does not inhibit protease activity. Despite the lack of inhibition of proteolytic activity, this antibody blocked the effect of prostate specific antigen on reactive oxygen species generation. These findings suggest that although the integrity of the prostate specific antigen molecule is necessary for stimulating reactive oxygen species generation, its proteolytic activity is not. The underlying mechanism is currently under investigation. JF - Carcinogenesis AU - Sun, X Y AU - Donald, S P AU - Phang, J M AD - Metabolism and Cancer Susceptibility Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 1775 EP - 1780 VL - 22 IS - 11 SN - 0143-3334, 0143-3334 KW - Reactive Oxygen Species KW - 0 KW - Receptors, Androgen KW - Testosterone KW - 3XMK78S47O KW - Flutamide KW - 76W6J0943E KW - Peptide Hydrolases KW - EC 3.4.- KW - Prostate-Specific Antigen KW - EC 3.4.21.77 KW - Index Medicus KW - Oxidation-Reduction KW - Immunoblotting KW - Blotting, Western KW - Humans KW - Peptide Hydrolases -- metabolism KW - Receptors, Androgen -- metabolism KW - Flutamide -- pharmacology KW - Male KW - Prostatic Neoplasms -- metabolism KW - Reactive Oxygen Species -- metabolism KW - Testosterone -- pharmacology KW - Tumor Cells, Cultured -- metabolism KW - Tumor Cells, Cultured -- drug effects KW - Prostate-Specific Antigen -- pharmacology KW - Testosterone -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72259966?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Testosterone+and+prostate+specific+antigen+stimulate+generation+of+reactive+oxygen+species+in+prostate+cancer+cells.&rft.au=Sun%2C+X+Y%3BDonald%2C+S+P%3BPhang%2C+J+M&rft.aulast=Sun&rft.aufirst=X&rft.date=2001-11-01&rft.volume=22&rft.issue=11&rft.spage=1775&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-13 N1 - Date created - 2001-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diet and cancer prevention studies in p53-deficient mice. AN - 72259026; 11694654 AB - Progress in mechanism-based cancer prevention research may be facilitated by the use of animal models displaying specific genetic susceptibilities for cancer such as mice deficient in the p53 tumor suppressor gene, the most frequently altered gene in human cancer. We observed in p53-knockout (p53-/-) mice that calorie restriction (CR; 60% of the control group's intake of carbohydrate energy) increased the latency of spontaneous tumor development (mostly lymphomas) approximately 75%, decreased serum insulin-like growth factor (IGF)-1 and leptin levels, significantly slowed thymocyte cell cycle traverse and induced apoptosis in immature thymocytes. In heterozygous p53-deficient (p53+/-) mice, CR and 1 d/wk of food deprivation each significantly delayed spontaneous tumor development (a mix of lymphomas, sarcomas and epithelial tumors) and decreased serum IGF-1 and leptin levels even when begun late in life. We have also developed a rapid and relevant p53+/- mouse mammary tumor model by crossing p53-deficient mice with MMTV-Wnt-1 transgenic mice, and found that CR and 1 d/wk food deprivation significantly increased mammary tumor latency (greater than twofold) and reduced the mean serum IGF-1 and leptin levels to <50% of that of control mice (P < 0.0001). In addition, fluasterone, fenretinide and soy each delayed tumor development but had little effect on IGF-1 or leptin levels. We have capitalized on the susceptibility of p53+/- mice to chronic, low dose, aromatic amine-induced bladder carcinogenesis to develop a useful model for evaluating bladder cancer prevention approaches such as cyclooxygenase-2 inhibition. As demonstrated by these examples, mice with specific (and human-like) genetic susceptibilities for cancer provide powerful new tools for testing and characterizing interventions that may inhibit the process of carcinogenesis in humans. JF - The Journal of nutrition AU - Hursting, S D AU - Perkins, S N AU - Phang, J M AU - Barrett, J C AD - National Cancer Institute, Bethesda, MD 20892,USA. hursting@ncifcrf.gov Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 3092S EP - 4S VL - 131 IS - 11 Suppl SN - 0022-3166, 0022-3166 KW - Leptin KW - 0 KW - Tumor Suppressor Protein p53 KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Index Medicus KW - Animals KW - Humans KW - Mammary Neoplasms, Experimental -- physiopathology KW - Urinary Bladder Neoplasms -- genetics KW - Neoplasms -- physiopathology KW - Disease Models, Animal KW - Insulin-Like Growth Factor I -- metabolism KW - Mammary Neoplasms, Experimental -- genetics KW - Mice KW - Mice, Transgenic KW - Neoplasms -- genetics KW - Leptin -- blood KW - Mice, Knockout KW - Urinary Bladder Neoplasms -- physiopathology KW - Urinary Bladder Neoplasms -- prevention & control KW - Diet, Reducing KW - Crosses, Genetic KW - Neoplasms -- prevention & control KW - Mammary Neoplasms, Experimental -- prevention & control KW - Neoplasms, Experimental -- genetics KW - Neoplasms, Experimental -- prevention & control KW - Diet KW - Tumor Suppressor Protein p53 -- genetics KW - Neoplasms, Experimental -- physiopathology KW - Tumor Suppressor Protein p53 -- deficiency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72259026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+nutrition&rft.atitle=Diet+and+cancer+prevention+studies+in+p53-deficient+mice.&rft.au=Hursting%2C+S+D%3BPerkins%2C+S+N%3BPhang%2C+J+M%3BBarrett%2C+J+C&rft.aulast=Hursting&rft.aufirst=S&rft.date=2001-11-01&rft.volume=131&rft.issue=11+Suppl&rft.spage=3092S&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nutrition&rft.issn=00223166&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-19 N1 - Date created - 2001-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biopharmacologic and herbal therapies for cancer: research update from NCCAM. AN - 72257137; 11694644 AB - During the past decade, use of complementary and alternative medicine (CAM) by the American public increased from 34% in 1990 to 42% in 1995 with related out-of-pocket expenditures estimated at $27 billion. Among cancer patients, use of CAM ranges between 30 and 75% worldwide and includes dietary approaches, herbals and other biologically based treatments such as melatonin, mushrooms, shark cartilage and high dose vitamins and minerals. Concerns about herb-nutrient-drug interactions and product quality and standardization emphasize the need for rigorous research. In 1998, Congress mandated the creation of the National Center for Complementary and Alternative Medicine (NCCAM) to conduct and support such research of CAM therapies. The NCCAM portfolio for oncology is rapidly growing. As of July 2001, 26 projects are underway, two specialized centers are funded for cancer research and four botanical centers are cofunded with the Office of Dietary Supplements. Investigations are targeting herbals and complex herbal formulas; single dietary supplements and complex dietary regimens; biological agents; and mind-body, body-based and frontier approaches. Of these, biopharmacologic and herbal therapies are a major focus of research. The NCCAM portfolio illustrates how research of CAM, particularly studies of biopharmacologic and herbal approaches for cancer, is developing systematically and rigorously. JF - The Journal of nutrition AU - Richardson, M A AD - National Center for Complementary and Alternative Medicine (NCCAM), National Institutes of Health, Bethesda, MD, USA. marich@mail.nih.gov Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 3037S EP - 40S VL - 131 IS - 11 Suppl SN - 0022-3166, 0022-3166 KW - Index Medicus KW - Phytotherapy KW - Drug Interactions KW - Humans KW - Food-Drug Interactions KW - Treatment Outcome KW - Dietary Supplements -- standards KW - Plants, Medicinal -- adverse effects KW - Research Support as Topic -- trends KW - Quality Control KW - Research -- organization & administration KW - Complementary Therapies -- standards KW - Complementary Therapies -- adverse effects KW - Research -- trends KW - Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72257137?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+nutrition&rft.atitle=Biopharmacologic+and+herbal+therapies+for+cancer%3A+research+update+from+NCCAM.&rft.au=Richardson%2C+M+A&rft.aulast=Richardson&rft.aufirst=M&rft.date=2001-11-01&rft.volume=131&rft.issue=11+Suppl&rft.spage=3037S&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nutrition&rft.issn=00223166&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-19 N1 - Date created - 2001-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relative risk of neurological signs in siblings of patients with schizophrenia. AN - 72254753; 11691688 AB - First-degree relatives of patients with schizophrenia appear to have subtle neurological signs, suggesting that these measures could serve as intermediate phenotypes in genetic studies of schizophrenia. The strength of a possible genetic component is unknown, however, leaving it uncertain whether such traits could increase the power to find schizophrenia susceptibility loci. The authors' goal was to investigate the strength of this possible genetic component. They estimated the relative risk of neurological impairments in a large group of siblings of patients with schizophrenia. Two standard neurological scales (the Neurological Evaluation Scale and the Woods Scale) were used to examine 115 patients, 185 of their siblings, and 88 normal comparison subjects. There were significant differences between the siblings of patients with schizophrenia and the normal comparison subjects only on the Woods Scale. Relative risk of neurological impairment was significantly increased in the sibling group, but the significance was weak to moderate. Neurological impairment was not redundant with several other intermediate phenotypic measures based on cognitive impairment. These data suggest that neurological signs cluster in patients with schizophrenia and their families and could possibly identify a unique component of genetic variance for risk of schizophrenia. However, the fairly low relative risk and the uncertain pathophysiology of such signs may limit their usefulness. JF - The American journal of psychiatry AU - Egan, M F AU - Hyde, T M AU - Bonomo, J B AU - Mattay, V S AU - Bigelow, L B AU - Goldberg, T E AU - Weinberger, D R AD - Clinical Brain Disorders Branch, Intramural Research Program, NIMH, National Institutes of Health, Bethesda, MD, USA. eganm@intra.nimh.nih.gov Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 1827 EP - 1834 VL - 158 IS - 11 SN - 0002-953X, 0002-953X KW - Antipsychotic Agents KW - 0 KW - Serotonin Uptake Inhibitors KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Parkinsonian Disorders -- chemically induced KW - Dyskinesia, Drug-Induced -- epidemiology KW - Ethnic Groups -- statistics & numerical data KW - Serotonin Uptake Inhibitors -- adverse effects KW - Parkinsonian Disorders -- epidemiology KW - Cranial Nerves -- physiopathology KW - Risk Factors KW - Adult KW - Dyskinesia, Drug-Induced -- etiology KW - Genetic Predisposition to Disease KW - Antipsychotic Agents -- adverse effects KW - Female KW - Functional Laterality -- physiology KW - Male KW - Brain -- physiopathology KW - Schizophrenia -- drug therapy KW - Schizophrenia -- genetics KW - Schizophrenia -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72254753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=Relative+risk+of+neurological+signs+in+siblings+of+patients+with+schizophrenia.&rft.au=Egan%2C+M+F%3BHyde%2C+T+M%3BBonomo%2C+J+B%3BMattay%2C+V+S%3BBigelow%2C+L+B%3BGoldberg%2C+T+E%3BWeinberger%2C+D+R&rft.aulast=Egan&rft.aufirst=M&rft.date=2001-11-01&rft.volume=158&rft.issue=11&rft.spage=1827&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-13 N1 - Date created - 2001-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Beta amyloid peptide (Abeta42) is internalized via the G-protein-coupled receptor FPRL1 and forms fibrillar aggregates in macrophages. AN - 72254577; 11689470 AB - The 42 amino acid form of beta amyloid (Abeta42) plays a pivotal role in neurotoxicity and the activation of mononuclear phagocytes in Alzheimer's disease (AD). Our recent study revealed that FPRL1, a G-protein-coupled receptor, mediates the chemotactic and activating effect of Abeta42 on mononuclear phagocytes (monocytes and microglia), suggesting that FPRL1 may be involved in the proinflammatory responses in AD. We investigated the role of FPRL1 in cellular uptake and the subsequent fibrillar formation of Abeta42 by using fluorescence confocal microscopy. We found that upon incubation with macrophages or HEK293 cells genetically engineered to express FPRL1, Abeta42 associated with FPRL1 and the Abeta42/FPRL1 complexes were rapidly internalized into the cytoplasmic compartment. The maximal internalization of Abeta42/FPRL1 complexes occurred by 30 min after incubation. Removal of free Abeta42 from culture supernatants at 30 min resulted in a progressive recycling of FPRL1 to the cell surface and degradation of the internalized Abeta42. However, persistent exposure of the cells to Abeta42 over 24 h resulted in retention of Abeta42/FPRL1 complexes in the cytoplasmic compartment and the formation of Congo red positive fibrils in macrophages but not in HEK 293 cell transfected with FPRL1. These results suggest that besides mediating the proinflammatory activity of Abeta42, FPRL1 is also involved in the internalization of Abeta42, which culminates in the formation of fibrils only in macrophages. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Yazawa, H AU - Yu, Z X AU - Takeda AU - Le, Y AU - Gong, W AU - Ferrans, V J AU - Oppenheim, J J AU - Li, C C AU - Wang, J M AD - Laboratory of Molecular Immunoregulation, SAIC Frederick, Center for Cancer Research, National Cancer Institute at Frederick, Maryland 21702, USA. Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 2454 EP - 2462 VL - 15 IS - 13 KW - Amyloid beta-Peptides KW - 0 KW - FPR2 protein, human KW - Oligopeptides KW - Peptide Fragments KW - Receptors, Formyl Peptide KW - Receptors, Immunologic KW - Receptors, Lipoxin KW - Receptors, Peptide KW - Trp-Lys-Tyr-Met-Val-Met KW - amyloid beta-protein (1-42) KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Colchicine KW - SML2Y3J35T KW - Index Medicus KW - Microscopy, Confocal KW - Colchicine -- pharmacology KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Humans KW - Apoptosis -- drug effects KW - Endocytosis -- drug effects KW - Oligopeptides -- pharmacology KW - Time Factors KW - Cell Line KW - Protein Conformation KW - Peptide Fragments -- metabolism KW - Macrophages -- cytology KW - Peptide Fragments -- chemistry KW - Amyloid beta-Peptides -- metabolism KW - Receptors, Immunologic -- physiology KW - GTP-Binding Proteins -- metabolism KW - Peptide Fragments -- pharmacology KW - Amyloid beta-Peptides -- pharmacology KW - Amyloid beta-Peptides -- chemistry KW - Receptors, Peptide -- physiology KW - Macrophages -- drug effects KW - Macrophages -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72254577?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.atitle=Beta+amyloid+peptide+%28Abeta42%29+is+internalized+via+the+G-protein-coupled+receptor+FPRL1+and+forms+fibrillar+aggregates+in+macrophages.&rft.au=Yazawa%2C+H%3BYu%2C+Z+X%3BTakeda%3BLe%2C+Y%3BGong%2C+W%3BFerrans%2C+V+J%3BOppenheim%2C+J+J%3BLi%2C+C+C%3BWang%2C+J+M&rft.aulast=Yazawa&rft.aufirst=H&rft.date=2001-11-01&rft.volume=15&rft.issue=13&rft.spage=2454&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=1530-6860&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-05 N1 - Date created - 2001-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glutathione S-transferase genotypes and stomach cancer in a population-based case-control study in Warsaw, Poland. AN - 72253982; 11692073 AB - Glutathione S-transferases are important in the detoxification of a wide range of human carcinogens. Previous studies have shown inconsistent associations between the GSTT1 and GSTM1 null genotypes and stomach cancer risk. We investigated the relationship between these and related genotypes and stomach cancer risk in a population-based case-control study in Warsaw, Poland, where stomach cancer incidence and mortality rates are among the highest in Europe. DNA from blood samples was available for 304 stomach cancer patients and 427 control subjects. We observed a 1.48-fold increased risk for stomach cancer (95% confidence interval 0.97-2.25) in patients with the GSTT1 null genotype but no evidence of increased risk associated with the GSTM1, GSTM3 or GSTP1 genotypes. Furthermore, the stomach cancer risk associated with the GSTT1 null genotype varied by age at diagnosis, with odds ratios of 3.85, 1.91, 1.78 and 0.59 for those diagnosed at ages less than 50, 50-59, 60-69 and 70 years or older, respectively (P trend = 0.01). This was due to a shift in the GSTT1 genotype distribution across age groups among stomach cancer patients only. These results suggest that the GSTT1 null genotype may be associated with increased risk of stomach cancer. JF - Pharmacogenetics AU - Lan, Q AU - Chow, W H AU - Lissowska, J AU - Hein, D W AU - Buetow, K AU - Engel, L S AU - Ji, B AU - Zatonski, W AU - Rothman, N AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7240, USA. qingl@mail.nih.gov Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 655 EP - 661 VL - 11 IS - 8 SN - 0960-314X, 0960-314X KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Genotype KW - Genetics, Population KW - Poland -- epidemiology KW - Humans KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Smoking -- genetics KW - Smoking -- epidemiology KW - Male KW - Female KW - Stomach Neoplasms -- genetics KW - Glutathione Transferase -- genetics KW - Stomach Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72253982?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenetics&rft.atitle=Glutathione+S-transferase+genotypes+and+stomach+cancer+in+a+population-based+case-control+study+in+Warsaw%2C+Poland.&rft.au=Lan%2C+Q%3BChow%2C+W+H%3BLissowska%2C+J%3BHein%2C+D+W%3BBuetow%2C+K%3BEngel%2C+L+S%3BJi%2C+B%3BZatonski%2C+W%3BRothman%2C+N&rft.aulast=Lan&rft.aufirst=Q&rft.date=2001-11-01&rft.volume=11&rft.issue=8&rft.spage=655&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-28 N1 - Date created - 2001-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Agricultural risk factors for t(14;18) subtypes of non-Hodgkin's lymphoma. AN - 72229613; 11679800 AB - The t(14;18) translocation is a common somatic mutation in non-Hodgkin's lymphoma (NHL) that is associated with bcl-2 activation and inhibition of apoptosis. We hypothesized that some risk factors might act specifically along t(14;18)-dependent pathways, leading to stronger associations with t(14;18)-positive than t(14;18)-negative non-Hodgkin's lymphoma. Archival biopsies from 182 non-Hodgkin's lymphoma cases included in a case-control study of men in Iowa and Minnesota (the Factors Affecting Rural Men, or FARM study) were assayed for t(14;18) using polymerase chain reaction amplification; 68 (37%) were t(14;18)-positive. We estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) for various agricultural risk factors and t(14;18)-positive and -negative cases of non-Hodgkin's lymphoma, based on polytomous logistic regression models fit using the expectation-maximization (EM) algorithm. T(14;18)-positive non-Hodgkin's lymphoma was associated with farming (OR 1.4, 95% CI = 0.9-2.3), dieldrin (OR 3.7, 95% CI = 1.9-7.0), toxaphene (OR 3.0, 95% CI = 1.5-6.1), lindane (OR 2.3, 95% CI = 1.3-3.9), atrazine (OR 1.7, 95% CI = 1.0-2.8), and fungicides (OR 1.8, 95% CI = 0.9-3.6), in marked contrast to null or negative associations for the same self-reported exposures and t(14;18)-negative non-Hodgkin's lymphoma. Causal relations between agricultural exposures and t(14;18)-positive non-Hodgkin's lymphoma are plausible, but associations should be confirmed in a larger study. Results suggest that non-Hodgkin's lymphoma classification based on the t(14;18) translocation is of value in etiologic research. JF - Epidemiology (Cambridge, Mass.) AU - Schroeder, J C AU - Olshan, A F AU - Baric, R AU - Dent, G A AU - Weinberg, C R AU - Yount, B AU - Cerhan, J R AU - Lynch, C F AU - Schuman, L M AU - Tolbert, P E AU - Rothman, N AU - Cantor, K P AU - Blair, A AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 701 EP - 709 VL - 12 IS - 6 SN - 1044-3983, 1044-3983 KW - Agrochemicals KW - 0 KW - Hydrocarbons, Chlorinated KW - Index Medicus KW - Odds Ratio KW - Humans KW - Algorithms KW - Aged KW - Hydrocarbons, Chlorinated -- adverse effects KW - Apoptosis -- genetics KW - Risk Factors KW - Genes, bcl-2 -- genetics KW - Polymerase Chain Reaction -- methods KW - Adult KW - Case-Control Studies KW - Confidence Intervals KW - Middle Aged KW - Minnesota -- epidemiology KW - Iowa -- epidemiology KW - Male KW - Agrochemicals -- adverse effects KW - Lymphoma, Non-Hodgkin -- genetics KW - Translocation, Genetic -- genetics KW - Lymphoma, Non-Hodgkin -- epidemiology KW - Agricultural Workers' Diseases -- genetics KW - Agricultural Workers' Diseases -- epidemiology KW - Agricultural Workers' Diseases -- chemically induced KW - Chromosomes, Human, Pair 18 -- genetics KW - Chromosomes, Human, Pair 18 -- drug effects KW - Lymphoma, Non-Hodgkin -- chemically induced KW - Chromosomes, Human, Pair 14 -- drug effects KW - Chromosomes, Human, Pair 14 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72229613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiology+%28Cambridge%2C+Mass.%29&rft.atitle=Agricultural+risk+factors+for+t%2814%3B18%29+subtypes+of+non-Hodgkin%27s+lymphoma.&rft.au=Schroeder%2C+J+C%3BOlshan%2C+A+F%3BBaric%2C+R%3BDent%2C+G+A%3BWeinberg%2C+C+R%3BYount%2C+B%3BCerhan%2C+J+R%3BLynch%2C+C+F%3BSchuman%2C+L+M%3BTolbert%2C+P+E%3BRothman%2C+N%3BCantor%2C+K+P%3BBlair%2C+A&rft.aulast=Schroeder&rft.aufirst=J&rft.date=2001-11-01&rft.volume=12&rft.issue=6&rft.spage=701&rft.isbn=&rft.btitle=&rft.title=Epidemiology+%28Cambridge%2C+Mass.%29&rft.issn=10443983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-10-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A method for assessing occupational pesticide exposures of farmworkers. AN - 72225278; 11675625 AB - The health of farmworkers as related to pesticide exposure is of concern but assessing exposures for epidemiologic studies requires different techniques than approaches used for studies of industrial workers. A review of the literature identified possible factors that affect exposure intensity. A model was developed to estimate an exposure score. Exposures in the literature were estimated using the model and compared to the measurements in the literature. Three studies were found with information appropriate for evaluation of the model. There was a statistical difference between the means of the scores corresponding to above and below the median of the measurements. The correlation coefficient between the scores and the measurements from the literature was 0.77. Although the evaluation was limited, the model appeared to work well, but more testing is needed. More research is also needed to increase understanding of what affects the exposures of these workers. Published 2001 Wiley-Liss, Inc. JF - American journal of industrial medicine AU - Stewart, P A AU - Prince, J K AU - Colt, J S AU - Ward, M H AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7240, USA. Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 561 EP - 570 VL - 40 IS - 5 SN - 0271-3586, 0271-3586 KW - Pesticides KW - 0 KW - Index Medicus KW - Probability KW - Feasibility Studies KW - Humans KW - Epidemiologic Research Design KW - Statistics, Nonparametric KW - Transients and Migrants -- statistics & numerical data KW - Agriculture -- statistics & numerical data KW - Models, Statistical KW - Occupational Exposure -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72225278?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=A+method+for+assessing+occupational+pesticide+exposures+of+farmworkers.&rft.au=Stewart%2C+P+A%3BPrince%2C+J+K%3BColt%2C+J+S%3BWard%2C+M+H&rft.aulast=Stewart&rft.aufirst=P&rft.date=2001-11-01&rft.volume=40&rft.issue=5&rft.spage=561&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-07 N1 - Date created - 2001-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The alcohol use disorders identification test: an aid to recognition of alcohol problems in primary care patients. AN - 72224679; 11676584 AB - Misuse of alcohol is associated with a range of medical problems. Fortunately, a simple pencil-and-paper measure, the Alcohol Use Disorders Identification Test, can effectively and efficiently screen for early-stage alcohol abuse as well as provide the physician information that can assist in brief intervention. The objective of this article is to briefly summarize research published on the Alcohol Use Disorders Identification Test and suggest its potential role in brief intervention in primary care settings. Scientific literature on the Alcohol Use Disorders Identification Test though 2000 was reviewed and synthesized to address issues relevant to use of the test in primary health care settings. The Alcohol Use Disorders Identification Test is quite sensitive and specific and compares favorably with alternative self-report screens for alcohol problems. Copyright 2001 American Health Foundation and Academic Press. JF - Preventive medicine AU - Allen, J P AU - Reinert, D F AU - Volk, R J AD - National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20892, USA. jpallenphd@cs.com Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 428 EP - 433 VL - 33 IS - 5 SN - 0091-7435, 0091-7435 KW - Index Medicus KW - United States KW - Sensitivity and Specificity KW - Practice Patterns, Physicians' KW - Humans KW - Aged KW - Male KW - Female KW - Diagnostic Tests, Routine -- methods KW - Alcoholism -- diagnosis KW - Psychometrics KW - Primary Health Care -- organization & administration KW - Mass Screening -- methods KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72224679?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Preventive+medicine&rft.atitle=The+alcohol+use+disorders+identification+test%3A+an+aid+to+recognition+of+alcohol+problems+in+primary+care+patients.&rft.au=Allen%2C+J+P%3BReinert%2C+D+F%3BVolk%2C+R+J&rft.aulast=Allen&rft.aufirst=J&rft.date=2001-11-01&rft.volume=33&rft.issue=5&rft.spage=428&rft.isbn=&rft.btitle=&rft.title=Preventive+medicine&rft.issn=00917435&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-11 N1 - Date created - 2001-10-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assessing the feasibility of epidemiologic research on migrant and seasonal farmworkers: an overview. AN - 72223978; 11675617 JF - American journal of industrial medicine AU - Zahm, S H AU - Blair, A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20892-7242, USA. zahms@mail.nih.gov Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 487 EP - 489 VL - 40 IS - 5 SN - 0271-3586, 0271-3586 KW - Pesticides KW - 0 KW - Index Medicus KW - Feasibility Studies KW - Humans KW - Adult KW - Child KW - Pesticides -- adverse effects KW - Occupational Exposure -- analysis KW - Agriculture KW - Agricultural Workers' Diseases -- epidemiology KW - Transients and Migrants KW - Epidemiologic Research Design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72223978?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Assessing+the+feasibility+of+epidemiologic+research+on+migrant+and+seasonal+farmworkers%3A+an+overview.&rft.au=Zahm%2C+S+H%3BBlair%2C+A&rft.aulast=Zahm&rft.aufirst=S&rft.date=2001-11-01&rft.volume=40&rft.issue=5&rft.spage=487&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-07 N1 - Date created - 2001-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Direct stimulation of arginine vasopressin gene transcription by cAMP in parvocellular neurons of the paraventricular nucleus in organotypic cultures. AN - 72209706; 11606471 AB - The regulation of arginine vasopressin (AVP) gene transcription in the paraventricular nucleus (PVN) was studied in rat hypothalamic organotypic cultures using intronic in situ hybridization. While AVP heteronuclear (hn) RNA was not detected in the PVN under basal conditions, a marked induction of AVP hnRNA was observed after 2 and 3 h incubation of slices with forskolin. In contrast to the stimulatory effects of forskolin, phorbol 12-myristate 13-acetate (PMA) was completely ineffective in inducing AVP hnRNA in the PVN at any time examined (1-3 h). Forskolin-induced AVP hnRNA expression was unaffected by blockage of neurotransmission by the sodium channel inhibitor, tetrodotoxin, indicating that forskolin acts directly on AVP cells in the PVN. Dual staining in situ hybridization of forskolin-stimulated hypothalamic sections using both radio labeled AVP hnRNA and digoxigenin-labeled CRH mRNA probes revealed colocalization of both transcripts, indicating AVP hnRNA is expressed in the parvocellular neurons. The data demonstrate that cAMP directly activates AVP gene transcription in parvocellular neurons of the PVN. JF - Endocrinology AU - Arima, H AU - House, S B AU - Gainer, H AU - Aguilera, G AD - Section on Endocrine Physiology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892, USA. arima105@med.nagouya-u.ac.jp Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 5027 EP - 5030 VL - 142 IS - 11 SN - 0013-7227, 0013-7227 KW - RNA, Heterogeneous Nuclear KW - 0 KW - Arginine Vasopressin KW - 113-79-1 KW - Colforsin KW - 1F7A44V6OU KW - Tetrodotoxin KW - 4368-28-9 KW - Cyclic AMP KW - E0399OZS9N KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Colforsin -- pharmacology KW - RNA, Heterogeneous Nuclear -- metabolism KW - Tetrodotoxin -- pharmacology KW - Organ Culture Techniques KW - Arginine Vasopressin -- genetics KW - Paraventricular Hypothalamic Nucleus -- physiology KW - Neurons -- drug effects KW - Neurons -- physiology KW - Cyclic AMP -- physiology KW - Paraventricular Hypothalamic Nucleus -- cytology KW - Transcription, Genetic -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72209706?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology&rft.atitle=Direct+stimulation+of+arginine+vasopressin+gene+transcription+by+cAMP+in+parvocellular+neurons+of+the+paraventricular+nucleus+in+organotypic+cultures.&rft.au=Arima%2C+H%3BHouse%2C+S+B%3BGainer%2C+H%3BAguilera%2C+G&rft.aulast=Arima&rft.aufirst=H&rft.date=2001-11-01&rft.volume=142&rft.issue=11&rft.spage=5027&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-10-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional characterization of cyclooxygenase-2 polymorphisms. AN - 72203475; 11602656 AB - Cyclooxygenases (COX)-1 and -2 are the key enzymes in the conversion of arachidonic acid to prostaglandins. COX-2 appears to play an emerging role in inflammation and carcinogenesis. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used for the treatment of numerous diseases and reduce the risk of developing colorectal cancer. Polymorphisms in the COX-2 gene could alter enzyme expression, function, and/or the response to NSAIDs. Therefore, they could modify individual risks for developing cancer and other diseases or the occurrence of side effects or sensitivity toward selective or nonselective COX inhibitors. We sequenced the COX-2 gene of 72 individuals and identified rare polymorphisms in the promoter and the coding region. A COX-2 molecular model was used to locate the coding region polymorphisms relative to functional sites in the protein, and the COX-2 V511A polymorphism was very near to the active site. This variant protein was expressed, and function was evaluated, but no difference was detected in metabolism of the COX-2 substrates, arachidonic acid, linoleic acid, and 2-arachidonyl glycerol, compared with the wild type. The Km values for arachidonic acid showed no differences between the COX-2 wild type and V511A mutant. Inhibition with selective or nonselective COX inhibitors was essentially the same for the two enzymes. The absence of functionally important polymorphisms in the COX-2 gene may suggest that there has been selective pressure against those single nucleotide polymorphisms because of the critical role of this enzyme in maintenance of homeostasis. JF - The Journal of pharmacology and experimental therapeutics AU - Fritsche, E AU - Baek, S J AU - King, L M AU - Zeldin, D C AU - Eling, T E AU - Bell, D A AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 468 EP - 476 VL - 299 IS - 2 SN - 0022-3565, 0022-3565 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Isoenzymes KW - Membrane Proteins KW - Prostaglandins KW - DNA KW - 9007-49-2 KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Index Medicus KW - Polymorphism, Genetic KW - Models, Molecular KW - Humans KW - Prostaglandins -- biosynthesis KW - DNA -- analysis KW - Chromatography, High Pressure Liquid KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Asian Continental Ancestry Group KW - Blotting, Western KW - Cells, Cultured KW - European Continental Ancestry Group KW - DNA -- genetics KW - Isomerism KW - African Continental Ancestry Group KW - Cell Line KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Isoenzymes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72203475?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Functional+characterization+of+cyclooxygenase-2+polymorphisms.&rft.au=Fritsche%2C+E%3BBaek%2C+S+J%3BKing%2C+L+M%3BZeldin%2C+D+C%3BEling%2C+T+E%3BBell%2C+D+A&rft.aulast=Fritsche&rft.aufirst=E&rft.date=2001-11-01&rft.volume=299&rft.issue=2&rft.spage=468&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Monoclonal antibodies specific and inhibitory to human cytochromes P450 2C8, 2C9, and 2C19. AN - 72196745; 11602516 AB - Hybridomas were isolated that produce 13 monoclonal antibodies (mAbs) that are specific and highly inhibitory to members of the human P450 2C subfamily, 2C8, 2C9, 2C9*2, and 2C19. Many of the mAbs to P450 2C8, 2C9, and 2C19 are specific and exhibit potent inhibitory activity (85-95%). mAb 281-1-1 specifically binds, immunoblots, and strongly inhibits the activity of P450 2C8. mAb 763-15-5 specifically binds and strongly inhibits the activity of P450 2C9. mAb 1-7-4-8 specifically binds and strongly inhibits the activity of P450 2C19. The other mAbs bind and inhibit sets and subsets of the P450 2C family. The single and the combinatorial use of the mAbs can "reaction phenotype", i.e., determine the metabolic contribution and interindividual variation of a P450 isoform for the metabolism of a drug or nondrug xenobiotic in human liver microsomes. The utility of the mAb-based analytic system was examined with the model substrates Taxol (paclitaxel), diazepam, tolbutamide, diclofenac, mephenytoin, and imipramine. The mAb system can identify drugs metabolized by a common P450 or several P450s and polymorphic P450s. The mAb system identifies drugs or drug metabolic pathways that are catalyzed by a single P450 and thus may be used for in vivo phenotyping. The mAb system can identify whether a particular drug is metabolized by a single P450 that may exhibit polymorphic expression in humans. The mAb system offers large potential for studies of cytochrome P450 function useful in drug discovery and reduces the possibility of adverse drug reactions due to polymorphisms and drug interactions. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Krausz, K W AU - Goldfarb, I AU - Buters, J T AU - Yang, T J AU - Gonzalez, F J AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bldg. 37, Bethesda, MD 20892, USA. Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 1410 EP - 1423 VL - 29 IS - 11 SN - 0090-9556, 0090-9556 KW - Antibodies, Monoclonal KW - 0 KW - Cytochrome P-450 Enzyme Inhibitors KW - Enzyme Inhibitors KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Steroid Hydroxylases KW - EC 1.14.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP2C19 protein, human KW - Cytochrome P-450 CYP2C19 KW - Steroid 16-alpha-Hydroxylase KW - Index Medicus KW - Animals KW - Hybridomas KW - Microsomes, Liver -- metabolism KW - Humans KW - Microsomes, Liver -- enzymology KW - Mice KW - Microsomes, Liver -- immunology KW - Mice, Inbred BALB C KW - Binding Sites, Antibody KW - Antibodies, Monoclonal -- metabolism KW - Steroid Hydroxylases -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Antibodies, Monoclonal -- pharmacology KW - Steroid Hydroxylases -- antagonists & inhibitors KW - Steroid Hydroxylases -- immunology KW - Mixed Function Oxygenases -- immunology KW - Antibody Specificity KW - Mixed Function Oxygenases -- metabolism KW - Antibodies, Monoclonal -- isolation & purification KW - Mixed Function Oxygenases -- antagonists & inhibitors KW - Cytochrome P-450 Enzyme System -- immunology KW - Enzyme Inhibitors -- pharmacology KW - Enzyme Inhibitors -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72196745?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.atitle=Monoclonal+antibodies+specific+and+inhibitory+to+human+cytochromes+P450+2C8%2C+2C9%2C+and+2C19.&rft.au=Krausz%2C+K+W%3BGoldfarb%2C+I%3BButers%2C+J+T%3BYang%2C+T+J%3BGonzalez%2C+F+J%3BGelboin%2C+H+V&rft.aulast=Krausz&rft.aufirst=K&rft.date=2001-11-01&rft.volume=29&rft.issue=11&rft.spage=1410&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.issn=00909556&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-07 N1 - Date created - 2001-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinogenicity of bisphenol-A in Fischer rats and B6C3F1 mice. AN - 71379448; 14530916 AB - Bisphenol-A (BP-A; 4,4'-isopropylidenediphenol) is a monomer of plastics commonly used in various consumer products, and is used as an intermediate in the manufacture of epoxy, polycarbonate, and polyester-styrene resins. A National Toxicology Program carcinogenesis bioassay of BP-A (>98% pure) was conducted by feeding diets containing 0, 1000, or 2000 ppm BP-A to groups of 50 male and 50 female Fischer (F)344 rats; 0, 1000, or 5000 ppm to groups of 50 male B6C3F1 mice; and 0, 5000, or 10,000 ppm to groups of 50 female B6C3F1 mice for 103 weeks. The mean body weights of the low- and high-dose rats and of female mice and high-dose male mice were lower than those of the controls throughout much of the study. Lower body weight gains in rats were likely caused by reduced food consumption. Survivals were comparable among groups. Regarding neoplasia, leukemias occurred at increased incidences in BP-A-dosed rats of both sexes: male, 13/50 controls vs 12/50 low-dose and 23/50 high-dose (P < 0.03); in females, the respective findings were 7/50, 13/50, and 12/50. Interstitial-cell tumors of the testes were increased in BP-A-dosed male rats: 35/49 controls vs 48/50 (P < 0.01) and 46/49 (P < 0.01); and an increasing trend was observed for mammary gland fibroadenomas in male rats (P < 0.05, 0/50 controls vs 0/50 and 4/50). In male mice, lymphomas/leukemias were increased: 2/49 controls vs 9/50 (P < 0.05) and 5/50. Multinucleated giant hepatocytes were observed in male mice (1/49 controls vs 41/49 and 41/50), whereas there was no increase of liver tumors. In their BP-A bioassay report, the National Toxicology Program concluded that there was no convincing evidence that BP-A was carcinogenic for rats or mice. However, the marginal increases in leukemias in male and female rats, along with increases in the combined incidence of lymphomas and leukemias in male mice, suggest that BP-A may be associated with increased cancers of the hematopoietic system. Increases in interstitial-cell tumors of the testes in rats were also evidence of carcinogenesis, as was the unusual occurrence of mammary gland fibroadenomas in male rats. JF - Odontology AU - Huff, J AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. huff1@niehs.nih.gov Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 12 EP - 20 VL - 89 IS - 1 SN - 1618-1247, 1618-1247 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71379448?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Odontology&rft.atitle=Carcinogenicity+of+bisphenol-A+in+Fischer+rats+and+B6C3F1+mice.&rft.au=Huff%2C+J&rft.aulast=Huff&rft.aufirst=J&rft.date=2001-11-01&rft.volume=89&rft.issue=1&rft.spage=12&rft.isbn=&rft.btitle=&rft.title=Odontology&rft.issn=16181247&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-28 N1 - Date created - 2003-10-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic stavudine exposure induces hepatic mitochondrial toxicity in adult Erythrocebus patas monkeys. AN - 71329529; 12082400 AB - To understand the mitochondrial mechanisms underlying the lactic acidosis and hepatic steatosis seen in some HIV-1-infected individuals after long-term stavudine (d4T) exposure, we have explored mitochondrial integrity in adult monkeys (Erythrocebus patas) given a daily human equivalent dose of d4T for 78 days. Three Erythrocebus patas (patas) monkeys were given 3 mg d4T orally twice daily (total 6 mg d4T), or approximately 1.2 mg d4T/kg body weight per day, for 78 days and compared with 3 unexposed animals. Blood taken from controls and from treated monkeys before and after drug exposure was subjected to a complete clinical chemistry profile. Liver and skeletal muscles were examined for oxidative phosphorylation enzyme specific activities, mitochondrial deoxyribonucleic acid (mtDNA) quantity by slot blot, and mtDNA integrity by Southern blot. Clinical chemistry assays demonstrated few significant differences; however, one d4T-exposed monkey had a serum lactate of 8.1 mmol/L after 78 days of oral d4T ingestion. Specific activities of oxidative phosphorylation Complexes I, II, and IV were significantly altered in both livers and skeletal muscles from the d4T-exposed animals, compared with the controls (p < or = 0.05). Significant depletion of mitochondrial DNA was observed in livers of drug-exposed monkeys, but not in skeletal muscle (p < or = 0.05). Further examination of liver DNA by Southern blot confirmed hepatic mtDNA depletion in drug exposed animals. The data suggest that direct examination of the liver may be required to elucidate clinical d4T-induced hepatotoxicity related to mitochondrial damage. JF - Journal of human virology AU - Gerschenson, M AU - Nguyen, V T AU - St Claire, M C AU - Harbaugh, S W AU - Harbaugh, J W AU - Proia, L A AU - Poirier, M C AD - Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA. PY - 2001 SP - 335 EP - 342 VL - 4 IS - 6 SN - 1090-9508, 1090-9508 KW - Anti-HIV Agents KW - 0 KW - DNA, Mitochondrial KW - Multienzyme Complexes KW - Reverse Transcriptase Inhibitors KW - Stavudine KW - BO9LE4QFZF KW - Oxidoreductases KW - EC 1.- KW - Electron Transport Complex II KW - EC 1.3.5.1 KW - Succinate Dehydrogenase KW - EC 1.3.99.1 KW - Index Medicus KW - Multienzyme Complexes -- metabolism KW - Animals KW - DNA, Mitochondrial -- drug effects KW - Blood Chemical Analysis KW - Oxidoreductases -- metabolism KW - Humans KW - Mitochondria -- drug effects KW - Oxidative Phosphorylation KW - Mitochondria -- metabolism KW - Erythrocebus patas KW - Succinate Dehydrogenase -- metabolism KW - Reverse Transcriptase Inhibitors -- adverse effects KW - Mitochondria, Muscle -- metabolism KW - Mitochondria, Liver -- metabolism KW - Anti-HIV Agents -- adverse effects KW - Stavudine -- adverse effects KW - Mitochondria, Liver -- drug effects KW - Mitochondria, Muscle -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71329529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+human+virology&rft.atitle=Chronic+stavudine+exposure+induces+hepatic+mitochondrial+toxicity+in+adult+Erythrocebus+patas+monkeys.&rft.au=Gerschenson%2C+M%3BNguyen%2C+V+T%3BSt+Claire%2C+M+C%3BHarbaugh%2C+S+W%3BHarbaugh%2C+J+W%3BProia%2C+L+A%3BPoirier%2C+M+C&rft.aulast=Gerschenson&rft.aufirst=M&rft.date=2001-11-01&rft.volume=4&rft.issue=6&rft.spage=335&rft.isbn=&rft.btitle=&rft.title=Journal+of+human+virology&rft.issn=10909508&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-12 N1 - Date created - 2002-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitric oxide in CsA-induced hypertension: role of beta-adrenoceptor antagonist and thromboxane A2. AN - 71314203; 11993718 AB - Cyclosporine A (CsA) is an immunosuppressive agent, which also causes hypertension. The effect of CsA on vascular responses was determined in Sprague-Dawley rats and rat aortic rings. Male rats weighing 250-300 g were given either CsA (25 mg/kg/day) in olive oil or vehicle by intraperitoneal (ip) injection for 7 days. CsA administration produced a 42% increase (P < 0.001) in mean arterial pressure (MAP) which reached a plateau after 3 days. The level of both nitrate/nitrite (NO2/NO3), metabolites of nitric oxide (NO), decreased by 50% (P < 0.001), but the level of thromboxane A2 (TBXA2) increased by 75% (P < 0.001), in the urine. When 10(-9) M of CsAwas added acutely to intact aortic rings from untreated rats, NO2/NO3 production decreased by 83% (P < 0.011), but TBXA2 production increased by 86% (P < 0.001). The effects of CsA were reversed both in vivo and in vitro by pretreatment with propranolol (15 mg/kg/day ip), beta-adrenoceptor antagonist. There were no changes in MAP and tension in rats treated with prop alone. In addition, in aorta of rats that were treated with CsA ip for 7 days, CsA significantly activated protein kinase C (PKC) translocation. This suggests that PKC mediate, in part, CsA-induced hypertension. In summary, CsA inhibits endothelial NO formation, activate PKC, and increaseTBXA2 production, with resulting increase in MAP, and this changes can be overcome by pretreatment with propranolol. JF - Prostaglandins, leukotrienes, and essential fatty acids AU - Oriji, G K AU - Schanz, N AD - Hypertension-Endocrine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Orijig@wpunj.edu PY - 2001 SP - 259 EP - 263 VL - 65 IS - 5-6 SN - 0952-3278, 0952-3278 KW - Adrenergic beta-Antagonists KW - 0 KW - Immunosuppressive Agents KW - Nitric Oxide KW - 31C4KY9ESH KW - Thromboxane A2 KW - 57576-52-0 KW - Cyclosporine KW - 83HN0GTJ6D KW - Propranolol KW - 9Y8NXQ24VQ KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Rats KW - Protein Kinase C -- metabolism KW - Aorta -- metabolism KW - Protein Kinase C -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Aorta -- drug effects KW - Propranolol -- pharmacology KW - In Vitro Techniques KW - Male KW - Hypertension -- chemically induced KW - Cyclosporine -- adverse effects KW - Thromboxane A2 -- metabolism KW - Nitric Oxide -- metabolism KW - Adrenergic beta-Antagonists -- pharmacology KW - Hypertension -- metabolism KW - Immunosuppressive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71314203?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.atitle=Nitric+oxide+in+CsA-induced+hypertension%3A+role+of+beta-adrenoceptor+antagonist+and+thromboxane+A2.&rft.au=Oriji%2C+G+K%3BSchanz%2C+N&rft.aulast=Oriji&rft.aufirst=G&rft.date=2001-11-01&rft.volume=65&rft.issue=5-6&rft.spage=259&rft.isbn=&rft.btitle=&rft.title=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.issn=09523278&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-31 N1 - Date created - 2002-05-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Capecitabine: indications and future perspectives in the treatment of metastatic colorectal and breast cancer. AN - 71309680; 11989587 AB - Fluoropyrimidines remain the most important drugs in the treatment of breast and colorectal carcinoma, but response rates and survival time have been disappointing. Optimal administration is by continuous intravenous infusion, which makes it cumbersome to use and compromises patient independence. Recently, a number of new agents, including fluorouracil prodrugs and selective dihydropyrimidine dehydrogenase inhibitors, have been studied, with promising results. Capecitabine is the first in a new class of fluoropyrimidines. It is an oral, tumor-activated anticancer drug whose activity mimics that of continuously infused 5-fluorouracil. Capecitabine circumvents dihydropyrimidine dehydrogenase catabolism and appears to be at least as active against metastatic colorectal and breast cancer as conventionally administered intravenous 5-fluorouracil, with significantly less toxicity, an improved quality of life, and lesser cost. Capecitabine may ultimately provide enhanced antitumor activity to fluorouracil-containing regimes for advanced colorectal and breast cancer. JF - Tumori AU - Cassata, A AU - Procoplo, G AU - Alù, M AU - Ferrari, L AU - Ferrario, E AU - Beretta, E AU - Longarini, R AU - Busto, G AU - De Candis, D AU - Bajetta, E AD - Medical Oncology Unit B, National Cancer Institute, Milan, Italy. PY - 2001 SP - 364 EP - 371 VL - 87 IS - 6 SN - 0300-8916, 0300-8916 KW - Antimetabolites, Antineoplastic KW - 0 KW - Prodrugs KW - Deoxycytidine KW - 0W860991D6 KW - Capecitabine KW - 6804DJ8Z9U KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Fluorouracil -- therapeutic use KW - Animals KW - Radiotherapy, Adjuvant KW - Humans KW - Treatment Outcome KW - Clinical Trials as Topic KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Female KW - Survival Analysis KW - Breast Neoplasms -- drug therapy KW - Deoxycytidine -- metabolism KW - Prodrugs -- chemistry KW - Deoxycytidine -- analogs & derivatives KW - Deoxycytidine -- therapeutic use KW - Antimetabolites, Antineoplastic -- metabolism KW - Colorectal Neoplasms -- drug therapy KW - Antimetabolites, Antineoplastic -- pharmacology KW - Colorectal Neoplasms -- radiotherapy KW - Prodrugs -- therapeutic use KW - Prodrugs -- pharmacology KW - Antimetabolites, Antineoplastic -- chemistry KW - Prodrugs -- metabolism KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Deoxycytidine -- pharmacology KW - Deoxycytidine -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71309680?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tumori&rft.atitle=Capecitabine%3A+indications+and+future+perspectives+in+the+treatment+of+metastatic+colorectal+and+breast+cancer.&rft.au=Cassata%2C+A%3BProcoplo%2C+G%3BAl%C3%B9%2C+M%3BFerrari%2C+L%3BFerrario%2C+E%3BBeretta%2C+E%3BLongarini%2C+R%3BBusto%2C+G%3BDe+Candis%2C+D%3BBajetta%2C+E&rft.aulast=Cassata&rft.aufirst=A&rft.date=2001-11-01&rft.volume=87&rft.issue=6&rft.spage=364&rft.isbn=&rft.btitle=&rft.title=Tumori&rft.issn=03008916&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-17 N1 - Date created - 2002-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deletion of beta-strand and alpha-helix secondary structure in normal prion protein inhibits formation of its protease-resistant isoform. AN - 71214917; 11581371 AB - A fundamental event in the pathogenesis of transmissible spongiform encephalopathies (TSE) is the conversion of a normal, proteinase K-sensitive, host-encoded protein, PrP-sen, into its protease-resistant isoform, PrP-res. During the formation of PrP-res, PrP-sen undergoes conformational changes that involve an increase of beta-sheet secondary structure. While previous studies in which PrP-sen deletion mutants were expressed in transgenic mice or scrapie-infected cell cultures have identified regions in PrP-sen that are important in the formation of PrP-res, the exact role of PrP-sen secondary structures in the conformational transition of PrP-sen to PrP-res has not yet been defined. We constructed PrP-sen mutants with deletions of the first beta-strand, the second beta-strand, or the first alpha-helix and tested whether these mutants could be converted to PrP-res in both scrapie-infected neuroblastoma cells (Sc(+)-MNB cells) and a cell-free conversion assay. Removal of the second beta-strand or the first alpha-helix significantly altered both processing and the cellular localization of PrP-sen, while deletion of the first beta-strand had no effect on these events. However, all of the mutants significantly inhibited the formation of PrP-res in Sc(+)-MNB cells and had a greatly reduced ability to form protease-resistant PrP in a cell-free assay system. Thus, our results demonstrate that deletion of the beta-strands and the first alpha-helix of PrP-sen can fundamentally affect PrP-res formation and/or PrP-sen processing. JF - Journal of virology AU - Vorberg, I AU - Chan, K AU - Priola, S A AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA. Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 10024 EP - 10032 VL - 75 IS - 21 SN - 0022-538X, 0022-538X KW - Prions KW - 0 KW - Endopeptidase K KW - EC 3.4.21.64 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Tumor Cells, Cultured KW - Mice KW - Prions -- chemistry KW - Endopeptidase K -- pharmacology KW - Protein Structure, Secondary KW - Prions -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71214917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Deletion+of+beta-strand+and+alpha-helix+secondary+structure+in+normal+prion+protein+inhibits+formation+of+its+protease-resistant+isoform.&rft.au=Vorberg%2C+I%3BChan%2C+K%3BPriola%2C+S+A&rft.aulast=Vorberg&rft.aufirst=I&rft.date=2001-11-01&rft.volume=75&rft.issue=21&rft.spage=10024&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-25 N1 - Date created - 2001-10-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1997 Jul 17;388(6639):285-8 [9230438] EMBO J. 1999 Jun 15;18(12):3193-203 [10369660] Cell. 1990 Nov 16;63(4):673-86 [1977523] J Virol. 1991 Jul;65(7):3667-75 [1710287] Science. 1991 Jun 14;252(5012):1515-22 [1675487] Biochemistry. 1991 Aug 6;30(31):7672-80 [1678278] FASEB J. 1991 Oct;5(13):2799-807 [1916104] J Biol Chem. 1991 Sep 25;266(27):18217-23 [1680859] J Biol Chem. 1997 Aug 22;272(34):21479-87 [9261166] FEBS Lett. 1997 Aug 18;413(2):282-8 [9280298] Chem Biol. 1995 Dec;2(12):807-17 [8807814] Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13452-7 [9391046] Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13938-43 [9391131] J Virol. 1998 Feb;72(2):1153-9 [9445012] Cell. 1999 Mar 19;96(6):869-78 [10102274] Biochemistry. 1999 Apr 13;38(15):4885-95 [10200178] Biomed Pharmacother. 1999;53(1):27-33 [10221165] Nat Med. 1999 Nov;5(11):1308-12 [10545999] Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13044-9 [10557270] Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):145-50 [10618385] J Virol. 2000 Jan;74(2):828-33 [10623745] Proc Natl Acad Sci U S A. 2000 May 23;97(11):5836-41 [10811921] Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8334-9 [10899999] Biopolymers. 2000 Nov;54(6):406-15 [10951327] Science. 2000 Sep 15;289(5486):1925-8 [10988071] J Biol Chem. 2001 Sep 21;276(38):35265-71 [11466311] Science. 1982 Apr 9;216(4542):136-44 [6801762] Science. 1982 Dec 24;218(4579):1309-11 [6815801] Nature. 1983 Dec 1-7;306(5942):476-8 [6685822] Cell. 1984 Aug;38(1):127-34 [6432339] Cell. 1985 Apr;40(4):735-46 [2859120] J Gen Virol. 1986 Mar;67 ( Pt 3):463-73 [2419489] Proc Natl Acad Sci U S A. 1986 Apr;83(8):2310-4 [3085093] J Gen Virol. 1987 May;68 ( Pt 5):1391-9 [3106566] Cell. 1987 Oct 23;51(2):229-40 [2444340] J Virol. 1987 Dec;61(12):3688-93 [2446004] J Virol. 1988 Aug;62(8):2845-9 [2899175] J Virol. 1989 Jan;63(1):175-81 [2562814] J Virol. 1991 Nov;65(11):6292-5 [1681118] J Virol. 1991 Dec;65(12):6597-603 [1682507] Lab Invest. 1991 Dec;65(6):622-30 [1684401] J Biol Chem. 1992 Aug 15;267(23):16188-99 [1353761] Mol Biol Cell. 1992 Aug;3(8):851-63 [1356522] J Virol. 1993 Feb;67(2):643-50 [7678300] Biochemistry. 1993 Mar 2;32(8):1991-2002 [8448158] Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2793-7 [8464892] J Cell Biol. 1993 Apr;121(2):295-304 [8468348] Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3182-6 [8475059] Cell. 1993 Jun 4;73(5):979-88 [8098995] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5959-63 [8327467] J Biol Chem. 1993 Sep 25;268(27):20276-84 [8104185] J Cell Physiol. 1993 Nov;157(2):319-25 [7901226] Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):10962-6 [7902575] Dev Biol Stand. 1993;80:131-40 [8270103] Ann N Y Acad Sci. 1994 Jun 6;724:282-9 [8030948] J Virol. 1994 Aug;68(8):4873-8 [7913509] Nature. 1994 Aug 11;370(6489):471-4 [7913989] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9936-40 [7937921] J Cell Biol. 1995 Apr;129(1):121-32 [7698979] J Virol. 1995 Dec;69(12):7754-8 [7494285] EMBO J. 1996 Mar 15;15(6):1255-64 [8635458] Nature. 1996 Jul 11;382(6587):180-2 [8700211] Biophys Chem. 1996 Dec 10;63(1):A1-18 [8981746] Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15457-62 [8986833] J Virol. 1997 May;71(5):4107-10 [9094691] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - License to kill tumors: how much hope is justified for trail? AN - 71192162; 11562306 AB - In 1995, a new cytokine termed TRAIL (tumor necrosis factor--related apoptosis-inducing ligand) was discovered and demonstrated to selectively induce programmed cell death in transformed cell lines. Preclinical cytotoxicity studies in mice and nonhuman primates have produced promising results by demonstrating that TRAIL exerts potent tumoricidal activity but lacks severe toxicity towards normal tissues making it a potentially ideal candidate for cancer therapy. This article reviews aspects of our current understanding of TRAIL signaling pathways and summarizes how this knowledge is currently being translated into TRAIL-based tumor-selective therapeutic strategies. JF - Current pharmaceutical design AU - Frank, S AU - Ebert, A D AD - Biochemistry Section, Surgical Neurology Branch, NINDS, NIH, Bethesda 20892, USA. frankst@ninds.nih.gov Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 1689 EP - 1701 VL - 7 IS - 16 SN - 1381-6128, 1381-6128 KW - Antineoplastic Agents KW - 0 KW - Apoptosis Regulatory Proteins KW - Membrane Glycoproteins KW - TNF-Related Apoptosis-Inducing Ligand KW - TNFSF10 protein, human KW - Tumor Necrosis Factor-alpha KW - Index Medicus KW - Humans KW - Signal Transduction -- drug effects KW - Apoptosis -- drug effects KW - Neoplasms -- drug therapy KW - Neoplasms -- pathology KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Membrane Glycoproteins -- therapeutic use KW - Membrane Glycoproteins -- pharmacology KW - Tumor Necrosis Factor-alpha -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71192162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+pharmaceutical+design&rft.atitle=License+to+kill+tumors%3A+how+much+hope+is+justified+for+trail%3F&rft.au=Frank%2C+S%3BEbert%2C+A+D&rft.aulast=Frank&rft.aufirst=S&rft.date=2001-11-01&rft.volume=7&rft.issue=16&rft.spage=1689&rft.isbn=&rft.btitle=&rft.title=Current+pharmaceutical+design&rft.issn=13816128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-28 N1 - Date created - 2001-09-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment Service Patterns and Organizational Structures: An Analysis of Programs in DATOS-A AN - 61482549; 200203915 AB - The availability of a variety of treatment services was examined within a national sample of programs treating adolescent drug abuse patients. Treatment service delivery profiles were created & examined in the context of organizational variables such as program modality, program directors' academic credentials, program capacity, staff composition, accreditation, & patient problems. Results suggested that distinct profiles of services existed within residential & outpatient modalities & that these service profiles were related both to organizational factors & to patient problem profiles. 4 Tables, 41 References. [Copyright 2001 Sage Publications, Inc.] JF - Journal of Adolescent Research AU - Delany, Peter J AU - Broome, Kirk M AU - Flynn, Patrick M AU - Fletcher, Bennett W AD - Division Epidemilogy/Services/Prevention Research, National Instit Drug Abuse, Bethesda, MD pdelany@nida.nih.gov Y1 - 2001/11// PY - 2001 DA - November 2001 SP - 590 EP - 607 VL - 16 IS - 6 SN - 0743-5584, 0743-5584 KW - Treatment Outcomes KW - Treatment Programs KW - Delivery Systems KW - United States of America KW - Organizational Structure KW - Program Evaluation KW - Adolescents KW - Drug Abuse KW - Health Care Services KW - article KW - 6129: addiction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61482549?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Adolescent+Research&rft.atitle=Treatment+Service+Patterns+and+Organizational+Structures%3A+An+Analysis+of+Programs+in+DATOS-A&rft.au=Delany%2C+Peter+J%3BBroome%2C+Kirk+M%3BFlynn%2C+Patrick+M%3BFletcher%2C+Bennett+W&rft.aulast=Delany&rft.aufirst=Peter&rft.date=2001-11-01&rft.volume=16&rft.issue=6&rft.spage=590&rft.isbn=&rft.btitle=&rft.title=Journal+of+Adolescent+Research&rft.issn=07435584&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Last updated - 2016-09-28 N1 - CODEN - JADREZ N1 - SubjectsTermNotLitGenreText - Treatment Programs; Program Evaluation; Health Care Services; Drug Abuse; Adolescents; Organizational Structure; United States of America; Treatment Outcomes; Delivery Systems ER - TY - JOUR T1 - Child-care and family predictors of preschool attachment and stability from infancy AN - 38319667; 2297334 JF - Developmental psychology Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 847 EP - 862 VL - 37 IS - 6 SN - 0012-1649, 0012-1649 KW - Sociology KW - Early childhood KW - Psychology KW - Parent-child relations KW - Family relations KW - Child care KW - Developmental psychology KW - Affectivity KW - Infants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/38319667?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aibss&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+psychology&rft.atitle=Child-care+and+family+predictors+of+preschool+attachment+and+stability+from+infancy&rft.au=&rft.aulast=&rft.aufirst=&rft.date=2001-11-01&rft.volume=37&rft.issue=6&rft.spage=847&rft.isbn=&rft.btitle=&rft.title=Developmental+psychology&rft.issn=00121649&rft_id=info:doi/ LA - English DB - International Bibliography of the Social Sciences (IBSS) N1 - Date revised - 2013-06-12 N1 - Last updated - 2013-09-16 N1 - SubjectsTermNotLitGenreText - 3518 10404; 10404; 9178 4777 6093 6823; 617; 2192; 6495 2212; 3827 2211 652 5676 646 6091 2212; 4777 6093 ER - TY - JOUR T1 - Theophylline Revisited AN - 231738276; 11775391 AB - Theophylline was first isolated in 1888 and remains the most commonly used medication worldwide for the treatment of asthma. It decreases the need for asthma rescue medications by people who have asthma and is an effective steroid-sparing agent for patients who tolerate it. Recently, investigators have shown that theophylline decreases airway inflammation, accelerates eosinophil apoptosis, and decreases recruitment of lymphocytes and neutrophils to the lungs at low doses. It is classified as a phosphodiesterase (PDE) inhibitor, but its therapeutic mechanism of action remains undetermined. Theophylline should be reevaluated as a long-term medication for the treatment of asthma because of its ease of use, low cost, and recent evidence of its anti-inflammatory actions. [PUBLICATION ABSTRACT] JF - Allergy and Asthma Proceedings AU - Somerville, Laura L Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 347 EP - 51 CY - Providence PB - OceanSide Publications VL - 22 IS - 6 SN - 10885412 KW - Medical Sciences--Allergology And Immunology KW - Bronchodilator Agents KW - Phosphodiesterase Inhibitors KW - Theophylline KW - United States KW - Asthma -- drug therapy KW - Phosphodiesterase Inhibitors -- standards KW - Dose-Response Relationship, Drug KW - Humans KW - Bronchodilator Agents -- pharmacokinetics KW - United States Food & Drug Administration KW - Treatment Outcome KW - Theophylline -- pharmacokinetics KW - Practice Guidelines as Topic KW - Phosphodiesterase Inhibitors -- pharmacokinetics KW - Theophylline -- standards KW - Bronchodilator Agents -- standards KW - Bronchodilator Agents -- therapeutic use KW - Theophylline -- therapeutic use KW - Phosphodiesterase Inhibitors -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/231738276?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Allergy+and+Asthma+Proceedings&rft.atitle=Theophylline+Revisited&rft.au=Somerville%2C+Laura+L&rft.aulast=Somerville&rft.aufirst=Laura&rft.date=2001-11-01&rft.volume=22&rft.issue=6&rft.spage=347&rft.isbn=&rft.btitle=&rft.title=Allergy+and+Asthma+Proceedings&rft.issn=10885412&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright OceanSide Publications Nov 1, 2001 N1 - Last updated - 2011-04-29 ER - TY - JOUR T1 - Male Roles in Families 'at Risk': The Ecology of Child Maltreatment AN - 20698503; 10300967 AB - Research on child development has increasingly emphasized the complexity of developmental processes, and this reconceptualization is reflected in recent research on the effects of child maltreatment as well. The articles in this special issue illustrate the value of studying maltreatment in the context of children's relationships, not only with their biological mothers, but with biological fathers and father figures as well. Ambiguities remain, however, suggesting that we need to know much more about the quality and longevity of the relationships between these men and both their partners and surrogate children to understand their roles and impact more fully. JF - Child Maltreatment AU - Lamb, Michael E AD - National Institute of Child Health and Human Development Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 310 EP - 313 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 6 IS - 4 SN - 1077-5595, 1077-5595 KW - Risk Abstracts KW - child abuse KW - males KW - longevity KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20698503?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Maltreatment&rft.atitle=Male+Roles+in+Families+%27at+Risk%27%3A+The+Ecology+of+Child+Maltreatment&rft.au=Lamb%2C+Michael+E&rft.aulast=Lamb&rft.aufirst=Michael&rft.date=2001-11-01&rft.volume=6&rft.issue=4&rft.spage=310&rft.isbn=&rft.btitle=&rft.title=Child+Maltreatment&rft.issn=10775595&rft_id=info:doi/10.1177%2F1077559501006004004 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-09-01 N1 - Last updated - 2011-12-15 N1 - SubjectsTermNotLitGenreText - child abuse; males; longevity DO - http://dx.doi.org/10.1177/1077559501006004004 ER - TY - JOUR T1 - Antibody targeted therapeutics for lymphoma: new focus on the CD22 antigen and RNA AN - 20288634; 8934354 AB - The approval of antibodies for cancer treatment has provoked increased interest in the development of new and improved antibody-mediated therapies. This emerging approach centres on targeting CD22 on human B-cells with a monoclonal antibody (mAb). Anti-CD22 antibodies conjugated to a cytotoxic RNAse elicits potent and specific killing of the lymphoma cells in vitro and in human lymphoma models in severe combined immune deficiency (SCID) mice. RNA damage caused by RNAses could be an important alternative to standard DNA damaging chemotherapeutics. Moreover, targeted RNAses may overcome problems of toxicity and immunogenicity associated with plant- or bacterial toxin-containing immunotoxins. JF - Expert Opinion in Biological Therapy AU - Rybak, S M AU - Newton, D L AD - Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA,, rybak@ncifcrf Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 995 EP - 1003 PB - Ashley Publications Ltd., Unitec House, 3rd Floor 2 Albert Place, Finchley Central London, N3 1QB UK, [URL:http://ernesto.ashley-pub.com/] VL - 1 IS - 6 SN - 1471-2598, 1471-2598 KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts; Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - antibody KW - CD22 KW - immunotoxin KW - lymphoma KW - ribonuclease KW - Lymphocytes B KW - Monoclonal antibodies KW - Animal models KW - Toxicity KW - Cancer KW - Immunotoxins KW - ribonuclease A KW - DNA damage KW - CD22 antigen KW - Cytotoxicity KW - RNA KW - Immunogenicity KW - Ribonuclease KW - Lymphoma KW - W 30940:Products KW - F 06915:Cancer Immunology KW - J 02350:Immunology KW - N 14830:RNA UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20288634?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+Opinion+in+Biological+Therapy&rft.atitle=Antibody+targeted+therapeutics+for+lymphoma%3A+new+focus+on+the+CD22+antigen+and+RNA&rft.au=Rybak%2C+S+M%3BNewton%2C+D+L&rft.aulast=Rybak&rft.aufirst=S&rft.date=2001-11-01&rft.volume=1&rft.issue=6&rft.spage=995&rft.isbn=&rft.btitle=&rft.title=Expert+Opinion+in+Biological+Therapy&rft.issn=14712598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-02-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Monoclonal antibodies; Lymphocytes B; Animal models; Toxicity; Immunotoxins; Cancer; DNA damage; ribonuclease A; Cytotoxicity; CD22 antigen; RNA; Immunogenicity; Ribonuclease; Lymphoma ER - TY - JOUR T1 - Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal type 1 and type 2 cytokine-mediated inflammatory reactions AN - 20095398; 6724740 AB - In this study, we addressed the hypothesis that severe infection-induced liver disease can develop via two distinct but equally deleterious genetic programs depending on the dominant type 1 or type 2 immunological phenotype. By using murine cDNA microarrays, cytokine-deficient mice, and confirmatory biological assays, we identified gene expression profiles that associate with lethal type 1 and type 2 cytokine polarized immune responses and uncovered the contributions of previously unappreciated disease mechanisms to pathogenesis during infection with the parasitic trematode Schistosoma mansoni. JF - FASEB Journal AU - Hoffmann, Karl F AU - McCarty, Thomas C AU - Segal, David H AU - Chiaramonte, Monica AU - Hesse, Matthias AU - Davis, Eric M AU - Cheever, Allen W AU - Meltzer, Paul S AU - Morse, Herbert C AU - Wynn, Thomas A AD - National Institutes of Health, 9000 Rockville Pike, Bldg. 4, Room 126, Bethesda, MD 20892-0425, USA, twynn@niaid.nih.gov Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 2545 EP - 2547 PB - Federation of American Societies for Experimental Biology VL - 15 IS - 13 SN - 0892-6638, 0892-6638 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Schistosoma mansoni KW - Gene expression KW - DNA fingerprinting KW - Liver diseases KW - Cytokines KW - Immune response KW - Infection KW - DNA microarrays KW - Inflammation KW - G 07720:Immunogenetics KW - N 14025:RNA/DNA role in infection & immune response KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20095398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+Journal&rft.atitle=Disease+fingerprinting+with+cDNA+microarrays+reveals+distinct+gene+expression+profiles+in+lethal+type+1+and+type+2+cytokine-mediated+inflammatory+reactions&rft.au=Hoffmann%2C+Karl+F%3BMcCarty%2C+Thomas+C%3BSegal%2C+David+H%3BChiaramonte%2C+Monica%3BHesse%2C+Matthias%3BDavis%2C+Eric+M%3BCheever%2C+Allen+W%3BMeltzer%2C+Paul+S%3BMorse%2C+Herbert+C%3BWynn%2C+Thomas+A&rft.aulast=Hoffmann&rft.aufirst=Karl&rft.date=2001-11-01&rft.volume=15&rft.issue=13&rft.spage=2545&rft.isbn=&rft.btitle=&rft.title=FASEB+Journal&rft.issn=08926638&rft_id=info:doi/10.1096%2Ffj.01-0306fje LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-04-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Gene expression; DNA fingerprinting; Liver diseases; Cytokines; Immune response; Infection; DNA microarrays; Inflammation; Schistosoma mansoni DO - http://dx.doi.org/10.1096/fj.01-0306fje ER - TY - JOUR T1 - Phylogenetics, genome diversity and origin of modern leopard, Panthera pardus AN - 18766328; 5635748 AB - Leopards, Panthera pardus, are widely distributed across southern Asia and sub-Saharan Africa. The extent and phylogeographic patterns of molecular genetic diversity were addressed in a survey of 77 leopards from known geographical locales representing 13 of the 27 classical trinomial subspecies. Phylogenetic analysis of mitochondrial DNA sequences (727 bp of NADH5 and control region) and 25 polymorphic microsatellite loci revealed abundant diversity that could be partitioned into a minimum of nine discrete populations, tentatively named here as revised subspecies: P. pardus pardus, P. p. nimr, P. p. saxicolor, P. p. fusca, P. p. kotiya, P. p. delacouri, P. p. japonensis, P. p. orientalis and P. p. melas. However, because of limited sampling of African populations, this may be an underestimate of modern phylogeographic population structure. Combined phylogeographic and population diversity estimates support an origin for modern leopard lineages 470,000-825,000 years ago in Africa followed by their migration into and across Asia more recently (170,000-300,000 years ago). Recent demographic reductions likely have led to genetic impoverishment in P. p. orientalis and in the island subspecies P. p. kotiya. JF - Molecular Ecology AU - Uphyrkina, O AU - Johnson, W E AU - Quigley, H AU - Miquelle, D AU - Marker, L AU - Bush, M AU - O'Brien, S J AD - Laboratory of Genomic Diversity, National Cancer Institute, Frederick, MD 21702-1201, USA, obrien@ncifcrf.gov Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 2617 EP - 2633 PB - Blackwell Science Ltd. VL - 10 IS - 11 SN - 0962-1083, 0962-1083 KW - Leopard KW - subspecies KW - Ecology Abstracts; Genetics Abstracts KW - D 04672:Mammals KW - G 07405:Carnivora UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18766328?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Ecology&rft.atitle=Phylogenetics%2C+genome+diversity+and+origin+of+modern+leopard%2C+Panthera+pardus&rft.au=Uphyrkina%2C+O%3BJohnson%2C+W+E%3BQuigley%2C+H%3BMiquelle%2C+D%3BMarker%2C+L%3BBush%2C+M%3BO%27Brien%2C+S+J&rft.aulast=Uphyrkina&rft.aufirst=O&rft.date=2001-11-01&rft.volume=10&rft.issue=11&rft.spage=2617&rft.isbn=&rft.btitle=&rft.title=Molecular+Ecology&rft.issn=09621083&rft_id=info:doi/10.1046%2Fj.0962-1083.2001.01350.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1046/j.0962-1083.2001.01350.x ER - TY - JOUR T1 - Amphetamine-induced toxicity in dopamine terminals in CD-1 and C57BL/6J mice: Complex roles for oxygen-based species and temperature regulation AN - 18368657; 5337970 AB - In order to examine differential strain susceptibility to neurotoxic effects of amphetamine and to assess the potential role of superoxide radicals in amphetamine-induced dopaminergic damage, the drug was injected to mice with different levels of copper/zinc superoxide dismutase (Cu/Zn SOD) enzyme. Administration of amphetamine (10 mg/kg, i.p., given every 2 h, a total of four times) to wild-type CD-1 and C57BL/6J mice caused significant decreases in dopamine and 3,4-dihydroxyphenylacetic acid levels, in [ super(125)I]RTI-121-labeled dopamine transporters as well as a significant depletion in the concentration of dopamine transporter and vesicular monoamine transporter 2 proteins. The amphetamine-induced toxic effects were less prominent in CD-1 mice, which have much higher levels of Cu/Zn SOD activity (0.69 units/mg of protein) in their striata than C57BL/6J animals (0.007 units/mg of protein). Transgenic mice on CD-1 and C57BL/6J background, which had striatal levels of Cu/Zn SOD 2.57 and 1.67 units/mg of protein, respectively, showed significant protection against all the toxic effects of amphetamine. The attenuation of toxicity observed in transgenic mice was not caused by differences in amphetamine accumulation in wild-type and mutant animals. However, CD-1-SOD transgenic mice showed marked hypothermia to amphetamine whereas C57-SOD transgenic mice did not show a consistent thermic response to the drug. The data obtained demonstrate distinctions in the neurotoxic profile of amphetamine in CD-1 and C57BL/6J mice, which show some differences in Cu/Zn SOD activity and in their thermic responses to amphetamine administration. Thus, these observations provide evidence for possible complex interactions between thermoregulation and free radical load in the long-term neurotoxic effects of this illicit drug of abuse. JF - Neuroscience AU - Krasnova, IN AU - Ladenheim, B AU - Jayanthi, S AU - Oyler, J AU - Moran, TH AU - Huestis, MA AU - Cadet, J L AD - Molecular Neuropsychiatry Section, NIH/NIDA Intramural Research program, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, jcadet@intra.nida.nih.gov Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 265 EP - 274 VL - 107 IS - 2 SN - 0306-4522, 0306-4522 KW - 3,4-Dihydroxyphenylacetic acid KW - mice KW - strains KW - Toxicology Abstracts KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18368657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Amphetamine-induced+toxicity+in+dopamine+terminals+in+CD-1+and+C57BL%2F6J+mice%3A+Complex+roles+for+oxygen-based+species+and+temperature+regulation&rft.au=Krasnova%2C+IN%3BLadenheim%2C+B%3BJayanthi%2C+S%3BOyler%2C+J%3BMoran%2C+TH%3BHuestis%2C+MA%3BCadet%2C+J+L&rft.aulast=Krasnova&rft.aufirst=IN&rft.date=2001-11-01&rft.volume=107&rft.issue=2&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - N-terminal truncations in the FhlA protein result in formate- and MoeA-independent expression of the hyc (formate hydrogenlyase) operon of Escherichia coli AN - 18295311; 5347775 AB - The formate hydrogenlyase complex of Escherichia coli catalyses the cleavage of formate to CO sub(2) and H sub(2) and consists of a molybdoenzyme formate dehydrogenase-H, hydrogenase 3 and intermediate electron carriers. The structural genes of this enzyme complex are activated by the FhlA protein in the presence of both formate and molybdate; ModE-Mo serves as a secondary activator. Mutational analysis of the FhlA protein established that the unique N-terminal region of this protein was responsible for formate- and molybdenum-dependent transcriptional control of the hyc operon. Analysis of the N-terminal sequence of the FhlA protein revealed a unique motif (amino acids 7-37), which is also found in ATPases associated with several members of the ABC-type transporter family. A deletion derivative of FhlA lacking these amino acids (FhlA9-2) failed to activate the hyc operon in vivo, although the FhlA9-2 did bind to hyc promoter DNA in vitro. The ATPase activity of the FhlA9-2-DNA-formate complex was at least three times higher than that of the native protein-DNA-formate complex, and this degree of activity was achieved at a lower formate level. Extending the deletion to amino acid 117 (FhlA167) not only reversed the FhlA super(-) phenotype of FhlA9-2, but also led to both molybdenum- and formate-independence. Deleting the entire N-terminal domain (between amino acids 5 and 374 of the 692 amino acid protein) also led to an effector-independent transcriptional activator (FhlA165), which had a twofold higher level of hyc operon expression than the native protein. Both FhlA165 and FhlA167 still required ModE-Mo as a secondary activator for an optimal level of hyc-lac expression. The FhlA165 protein also had a twofold higher affinity to hyc promoter DNA than the native FhlA protein, while the FhlA167 protein had a significantly lower affinity for hyc promoter DNA in vitro. Although the ATPase activity of the native protein was increased by formate, the ATPase activity of neither FhlA165 or FhlA167 responded to formate. Removal of the first 117 amino acids of the FhlA protein appears to result in a constitutive, effector-independent activation of transcription of the genes encoding the components of the formate hydrogenlyase complex. The sequence similarity to ABC-ATPases, combined with the properties of the FhlA deletion proteins, led to the proposal that the N-terminal region of the native FhlA protein interacts with formate transport proteins, both as a formate transport facilitator and as a cytoplasmic acceptor. JF - Microbiology AU - Self, W T AU - Hasona, A AU - Shanmugam, K T AD - NHLBI, NIH, Bethesda, MD, USA, shan@ufl.edu Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 3093 EP - 3104 VL - 147 IS - 11 SN - 1350-0872, 1350-0872 KW - Fh1A protein KW - formate hydrogenlyase KW - hyc gene KW - Microbiology Abstracts B: Bacteriology KW - Gene expression KW - Escherichia coli KW - Amino acid sequence KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18295311?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Microbiology&rft.atitle=N-terminal+truncations+in+the+FhlA+protein+result+in+formate-+and+MoeA-independent+expression+of+the+hyc+%28formate+hydrogenlyase%29+operon+of+Escherichia+coli&rft.au=Self%2C+W+T%3BHasona%2C+A%3BShanmugam%2C+K+T&rft.aulast=Self&rft.aufirst=W&rft.date=2001-11-01&rft.volume=147&rft.issue=11&rft.spage=3093&rft.isbn=&rft.btitle=&rft.title=Microbiology&rft.issn=13500872&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Gene expression; Amino acid sequence ER - TY - JOUR T1 - Alcohol and Mortality from External Causes AN - 18294587; 5338298 AB - Objective: The aim of this study was to examine the relationship between alcohol consumption, considering both volume of intake and drinking pattern, and the risk of death from external causes. Method: A prospective study of mortality from external causes was conducted using data from the 1988 National Health Interview Survey linked with the National Death Index for 1988 through 1995. During the 7.5-year follow-up interval, there were 155 deaths from external causes among the 42,910 adults 18 years of age and over included in the sample. Proportional hazards models were used to adjust for censoring due to competing causes of death and for the effects of potentially confounding background variables including age, gender, marital status, education, smoking and poor health at baseline. Results: Relative to lifetime abstainers and infrequent drinkers, the risk of death from external causes increased directly with volume of intake, exhibiting a logarithmic-shaped risk curve. There was no evidence of reduced risk among light or moderate drinkers. When usual quantity and frequency were examined, the only drinkers at significantly increased risk were those who drank less than once a month but usually drank 5+ drinks (or, to a lesser extent, 3+ drinks) and those who drank at least twice a week and usually drank 2+ drinks. Former drinkers also were at increased risk. Age strongly affected the drinking pattern parameters. Conclusions: Quantity and frequency of drinking are proxies for in-the-event risks associated with alcohol intake and their cumulative effect on mortality risk. The results are discussed with particular attention to the role of factors that may affect the association between usual quantity of drinks consumed and the in-the-event risk of mortality from external causes. JF - Journal of Studies on Alcohol AU - Dawson, DA AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Willco Building, Suite 514, 6000 Executive Boulevard (MSC 7003), Bethesda, Maryland 20892-7003, USA, ddawson@willco.niaaa.nih.gov Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 790 EP - 797 VL - 62 IS - 6 SN - 0096-882X, 0096-882X KW - marital status KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Alcohol KW - Mortality KW - Age KW - Morbidity KW - Education KW - Alcoholism KW - Gender KW - R2 23060:Medical and environmental health KW - X 24180:Social poisons & drug abuse KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18294587?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Studies+on+Alcohol&rft.atitle=Alcohol+and+Mortality+from+External+Causes&rft.au=Dawson%2C+DA&rft.aulast=Dawson&rft.aufirst=DA&rft.date=2001-11-01&rft.volume=62&rft.issue=6&rft.spage=790&rft.isbn=&rft.btitle=&rft.title=Journal+of+Studies+on+Alcohol&rft.issn=0096882X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mortality; Risk assessment; Alcohol; Age; Gender; Education; Alcoholism; Morbidity ER - TY - JOUR T1 - Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4): an archaeal DinB-like DNA polymerase with lesion-bypass properties akin to eukaryotic pol eta AN - 18259825; 5322206 AB - Phylogenetic analysis of Y-family DNA polymerases suggests that it can be subdivided into several discrete branches consisting of UmuC/DinB/Rev1/Rad30/Rad30A and Rad30B. The most diverse is the DinB family that is found in all three kingdoms of life. Searches of the complete genome of the crenarchaeon Sulfolobus solfataricus P2 reveal that it possesses a DinB homolog that has been termed DNA polymerase IV (Dpo4). We have overproduced and purified native Dpo4 protein and report here its enzymatic characterization. Dpo4 is thermostable, but can also synthesize DNA at 37 degree C. Under these conditions, the enzyme exhibits misinsertion fidelities in the range of 8 x 10 super(-3) to 3 x 10 super(-4). Dpo4 is distributive but at high enzyme to template ratios can synthesize long stretches of DNA and can substitute for Taq polymerase in PCR. On damaged DNA templates, Dpo4 can facilitate translesion replication of an abasic site, a cis-syn thymine-thymine dimer, as well as acetyl aminofluorene adducted- and cisplatinated-guanine residues. Thus, although phylogenetically related to DinB polymerases, our studies suggest that the archaeal Dpo4 enzyme exhibits lesion-bypass properties that are, in fact, more akin to those of eukaryotic pol eta . JF - Nucleic Acids Research AU - Boudsocq, F AU - Iwai, Shigenori AU - Hanaoka, Fumio AU - Woodgate, R AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, MD 20892-2725, USA, woodgate@helix.nih.gov Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 4607 EP - 4616 VL - 29 IS - 22 SN - 0305-1048, 0305-1048 KW - crenarchaeaota KW - thermophilic archaea KW - archaeal enzymes KW - abasic sites KW - Dpo4 protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Phylogeny KW - DNA damage KW - Sulfolobus solfataricus KW - Replication KW - DNA-directed DNA polymerase KW - J 02725:DNA KW - N 14722:DNA polymerases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18259825?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=Sulfolobus+solfataricus+P2+DNA+polymerase+IV+%28Dpo4%29%3A+an+archaeal+DinB-like+DNA+polymerase+with+lesion-bypass+properties+akin+to+eukaryotic+pol+eta&rft.au=Boudsocq%2C+F%3BIwai%2C+Shigenori%3BHanaoka%2C+Fumio%3BWoodgate%2C+R&rft.aulast=Boudsocq&rft.aufirst=F&rft.date=2001-11-01&rft.volume=29&rft.issue=22&rft.spage=4607&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Sulfolobus solfataricus; DNA damage; Phylogeny; Replication; DNA-directed DNA polymerase ER - TY - JOUR T1 - Obstructive Pulmonary Function Defects Among Taiwanese Firebrick Workers in a 2-Year Follow-Up Study AN - 18225804; 5292834 AB - The purpose of the study was to follow up an earlier observation of pulmonary function among workers employed in firebrick-manufacturing factories. A 2-year follow-up study of pulmonary function among 442 workers in 30 firebrick-manufacturing factories was designed. Excluding 79 workers with a history of other occupational dust exposure, changes in pulmonary function of 291 firebrick workers were compared with pulmonary function in 72 control subjects over a period of 2 years. Baseline pulmonary function values (ie, forced expiratory volume in 1 second [FEV sub(1)]/forced vital capacity [FVC] and forced expiratory flow after 50% of vital capacity has been expelled [FEF sub(50%)] in smoking firebrick workers, and FEV sub(1)/FVC and FEF sub(75%) in nonsmoking firebrick workers) were significantly lower than those in the comparison group. The statistical method for repeated measurements was used for comparison of the difference between follow-up and baseline lung function. There was no significant difference in FVC and FEV sub(1) changes between firebrick workers and those in the comparison group during the 2-year follow-up period. The decreases in FEV sub(1)/FVC, peak expiratory flow rate, maximal midexpiratory flow, and FEF sub(50%) in the firebrick workers were significantly greater than in the comparison group, after adjustment for smoking status. The FEV sub(1), maximal midexpiratory flow, FEF sub(50%), and FEF sub(75%) also showed a dose-response relationship with job titles. The decrement of pulmonary function in the 2-year follow-up period was the worst in burning work, followed by crushing and molding. The results show that workers in firebrick-manufacturing factories with exposure to silica-containing dusts may contract obstructive pulmonary function defects. JF - Journal of Occupational and Environmental Medicine AU - Chen, Yeong-Hwang AU - Wu, Trong-Neng AU - Liou, Saou-Hsing AD - No. 325, Section 2, Chen-Kung Road, Department of Family Medicine, Tri-Service General Hospital, Nei-Hu, Taipei, Taiwan, 114, Republic of China, shliou@ndmctsgh.edu.tw Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 969 EP - 975 VL - 43 IS - 11 SN - 1076-2752, 1076-2752 KW - silicon dioxide KW - man KW - firebrick KW - Toxicology Abstracts; Health & Safety Science Abstracts; Pollution Abstracts KW - Manufacturing industry KW - Taiwan KW - Dust KW - Respiratory function KW - Industrial pollution KW - Occupational exposure KW - Silica KW - H 1000:Occupational Safety and Health KW - P 6000:TOXICOLOGY AND HEALTH KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18225804?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Occupational+and+Environmental+Medicine&rft.atitle=Obstructive+Pulmonary+Function+Defects+Among+Taiwanese+Firebrick+Workers+in+a+2-Year+Follow-Up+Study&rft.au=Chen%2C+Yeong-Hwang%3BWu%2C+Trong-Neng%3BLiou%2C+Saou-Hsing&rft.aulast=Chen&rft.aufirst=Yeong-Hwang&rft.date=2001-11-01&rft.volume=43&rft.issue=11&rft.spage=969&rft.isbn=&rft.btitle=&rft.title=Journal+of+Occupational+and+Environmental+Medicine&rft.issn=10762752&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Taiwan; Dust; Occupational exposure; Manufacturing industry; Respiratory function; Silica; Industrial pollution ER - TY - JOUR T1 - Hypothyroidism incidence after multimodality treatment for Stage III, and IV squamous cell carcinomas of the head and neck AN - 18221556; 5292304 AB - Purpose: Treatment of head-and-neck cancer patients with surgery, radiotherapy (RT), and chemotherapy has been associated with post-therapy hypothyroidism (HT). We evaluated the rate of post-therapy HT in patients with locally advanced squamous cell carcinoma of the head and neck, treated with multimodality therapy to determine which factors might predict this condition and at what interval the condition developed. Methods: We reviewed the prospectively collected thyroid function data of patients treated with sequential chemotherapy, RT, and neck dissection. The incidence of post-therapy HT was estimated. The patient, tumor, and treatment factors possibly associated with HT were evaluated. Results: Of 203 patients, 118 had data adequate for evaluation. HT developed in 45% at a median of 24.4 months after therapy. HT occurred in 14% and 27% of patients at 6 months and 1 year after treatment, respectively. Univariate and multivariate analyses of sex, age, RT dose, RT fractionation, T and N stage, tumor site, and neck dissection failed to identify a clinically relevant risk factor. Conclusions: A high number of patients undergoing aggressive organ-sparing multimodality therapy for advanced squamous cell carcinoma of the head and neck are at risk for subsequent HT. We recommend that all patients definitively irradiated to the head and neck re i n undergo frequent serum thyroid-stimulating hormone screening for HT, beginning 6 months after RT. JF - International Journal of Radiation Oncology, Biology, & Physics AU - Colevas, AD AU - Read, R AU - Thornhill, J AU - Adak, S AU - Tishler, R AU - Busse, P AU - Li, Y AU - Posner, M AD - Investigational Drug Branch, Cancer Therapy Evaluation Program, DCTD, National Cancer Institute, Executive Plaza North, Room 7131, 6130 Executive Blvd., Rockville, MD 20852-7426, USA, colevasd@ctep.nih.gov Y1 - 2001/11/01/ PY - 2001 DA - 2001 Nov 01 SP - 599 EP - 604 PB - Elsevier Science Inc. VL - 51 IS - 3 SN - 0360-3016, 0360-3016 KW - man KW - head and neck carcinoma KW - Toxicology Abstracts KW - Chemotherapy KW - Surgery KW - Squamous cells KW - Radiotherapy KW - Hypothyroidism KW - Thyroid-stimulating hormone KW - Side effects KW - X 24210:Radiation & radioactive materials KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18221556?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.atitle=Hypothyroidism+incidence+after+multimodality+treatment+for+Stage+III%2C+and+IV+squamous+cell+carcinomas+of+the+head+and+neck&rft.au=Colevas%2C+AD%3BRead%2C+R%3BThornhill%2C+J%3BAdak%2C+S%3BTishler%2C+R%3BBusse%2C+P%3BLi%2C+Y%3BPosner%2C+M&rft.aulast=Colevas&rft.aufirst=AD&rft.date=2001-11-01&rft.volume=51&rft.issue=3&rft.spage=599&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.issn=03603016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Hypothyroidism; Squamous cells; Radiotherapy; Surgery; Chemotherapy; Thyroid-stimulating hormone; Side effects ER - TY - JOUR T1 - Sphingolipids as biomarkers of fumonisin exposure and risk of esophageal squamous cell carcinoma in China AN - 18217869; 5292467 AB - Ecologic studies of esophageal squamous cell carcinoma (ESCC) have reported an association with consumption of maize contaminated with Fusarium verticillioides, which produce fungal toxins referred to as fumonisins. Fumonisins disrupt sphingolipid metabolism and serum sphingolipids have been proposed as biomarkers of fumonisin exposure. We conducted a prospective nested case-control study to examine the relationship between serum sphingolipids and ESCC incidence. Cases and controls were selected from a large prospective trial conducted in Linxian, People's Republic of China. Ninety-eight ESCC cases were randomly selected from the 639 incident ESCC ascertained during the initial 5.25 years of follow-up; 185 controls were also randomly selected based on the distribution of cases among six age and sex strata. Concentrations of sphinganine and sphingosine were determined by high-performance liquid chromatography in serum collected at the study baseline. No significant associations were found between serum sphingosine, sphinganine, or the sphinganine/sphingosine ratio and ESCC incidence in conditional and unconditional logistic regression models with adjustment for age, sex, tobacco use, and alcohol use. Our study is the first prospective study to assess the relationship between sphingolipid levels, as biomarkers of fumonisin exposure, and cancer incidence. We found no significant association between sphingolipid levels and risk of ESCC. JF - Cancer Causes & Control AU - Abnet, C C AU - Borkowf, C B AU - Qiao, You-Lin AU - Albert, P S AU - Wang, E AU - Merrill, AH Jr AU - Mark, S D AU - Dong, Zhi-Wei AU - Taylor, PR AU - Dawsey, S M AD - National Cancer Institute, Center for Cancer Research, Cancer Prevention Studies Branch, 6006 Executive Blvd, Room 321, Bethesda, MD 20892-7058, USA, abnetc@mail.nih.gov Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 821 EP - 828 VL - 12 IS - 9 SN - 0957-5243, 0957-5243 KW - biomarkers KW - man KW - sphingolipids KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Toxicology Abstracts KW - Esophagus KW - Fusarium KW - Fumonisins KW - Squamous cells KW - esophageal carcinoma KW - Cancer KW - Carcinoma KW - Mycotoxins KW - Sphingolipids KW - China, People's Rep. KW - Fusarium verticillioides KW - K 03082:Mycotoxins KW - X 24171:Microbial UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18217869?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Sphingolipids+as+biomarkers+of+fumonisin+exposure+and+risk+of+esophageal+squamous+cell+carcinoma+in+China&rft.au=Abnet%2C+C+C%3BBorkowf%2C+C+B%3BQiao%2C+You-Lin%3BAlbert%2C+P+S%3BWang%2C+E%3BMerrill%2C+AH+Jr%3BMark%2C+S+D%3BDong%2C+Zhi-Wei%3BTaylor%2C+PR%3BDawsey%2C+S+M&rft.aulast=Abnet&rft.aufirst=C&rft.date=2001-11-01&rft.volume=12&rft.issue=9&rft.spage=821&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Fusarium; Fusarium verticillioides; China, People's Rep.; Mycotoxins; Sphingolipids; Fumonisins; Carcinoma; Cancer; Esophagus; esophageal carcinoma; Squamous cells ER - TY - JOUR T1 - Dual-Function Vaccine for Pseudomonas aeruginosa: Characterization of Chimeric Exotoxin A-Pilin Protein AN - 18217162; 5288497 AB - Pseudomonas aeruginosa is the major infectious agent of concern for cystic fibrosis patients. Strategies to prevent colonization by this bacterium and/or neutralize its virulence factors are clearly needed. Here we characterize a dual-function vaccine designed to generate antibodies to reduce bacterial adherence and to neutralize the cytotoxic activity of exotoxin A. To construct the vaccine, key sequences from type IV pilin were inserted into a vector encoding a nontoxic (active-site deletion) version of exotoxin A. The chimeric protein, termed PE64 delta 553pil, was expressed in Escherichia coli, refolded to a near-native conformation, and then characterized by various biochemical and immunological assays. PE64 delta 553pil bound specifically to asialo-GM1, and, when injected into rabbits, produced antibodies that reduced bacterial adherence and neutralized the cell-killing activity of exotoxin A. Results support further evaluation of this chimeric protein as a vaccine to prevent Pseudomonas colonization in susceptible individuals. JF - Infection and Immunity AU - Hertle, R AU - Mrsny, R AU - Fitzgerald, D J AD - Biotherapy Section, Laboratory of Molecular Biology, CCR, National Cancer Institute, Bldg. 37, 4B03, 37 Convent Dr., MSC 4255, Bethesda, MD 20892-4255., djpf@helix.nih.gov Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 6962 EP - 6969 VL - 69 IS - 11 SN - 0019-9567, 0019-9567 KW - man KW - rabbits KW - exotoxin A KW - pilin KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Antibodies KW - Escherichia coli KW - Vaccines KW - Immune response (humoral) KW - Pseudomonas aeruginosa KW - Cystic fibrosis KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization KW - J 02833:Immune response and immune mechanisms KW - A 01099:Bacteria and fungi UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18217162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Dual-Function+Vaccine+for+Pseudomonas+aeruginosa%3A+Characterization+of+Chimeric+Exotoxin+A-Pilin+Protein&rft.au=Hertle%2C+R%3BMrsny%2C+R%3BFitzgerald%2C+D+J&rft.aulast=Hertle&rft.aufirst=R&rft.date=2001-11-01&rft.volume=69&rft.issue=11&rft.spage=6962&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.69.11.6962-6969.2001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Pseudomonas aeruginosa; Escherichia coli; Vaccines; Cystic fibrosis; Immune response (humoral); Antibodies DO - http://dx.doi.org/10.1128/IAI.69.11.6962-6969.2001 ER - TY - JOUR T1 - Determining the probability of pesticide exposures among migrant farmworkers: Results from a feasibility study AN - 18215597; 5288416 AB - Background: Migrant and seasonal farmworkers are exposed to pesticides through their work with crops and livestock. Because workers are usually unaware of the pesticides applied, specific pesticide exposures cannot be determined by interviews. We conducted a study to determine the feasibility of identifying probable pesticide exposures based on work histories. Methods: The study included 162 farm workers in seven states. Interviewers obtained a lifetime work history including the crops, tasks, months, and locations worked. We investigated the availability of survey data on pesticide use for crops and livestock in the seven pilot states. Probabilities of use for pesticide types (herbicides, insecticides, fungicides, etc.) and specific chemicals were calculated from the available data for two farm workers. The work histories were chosen to illustrate how the quality of the pesticide use information varied across crops, states, and years. Results: For most vegetable and fruit crops there were regional pesticide use data in the late 1970s, no data in the 1980s, and state-specific data every other year in the 1990s. Annual use surveys for cotton and potatoes began in the late 1980s. For a few crops, including asparagus, broccoli, lettuce, strawberries, plums, and Christmas trees, there were no federal data or data from the seven states before the 1990s. Conclusions: We conclude that identifying probable pesticide exposures is feasible in some locations. However, the lack of pesticide use data before the 1990s for many crops will limit the quality of historic exposure assessment for most workers. JF - American Journal of Industrial Medicine AU - Ward, M H AU - Prince, J R AU - Stewart, P A AU - Zahm, SH AD - Occupational Epidemiology Branch, National Cancer Institute, 6120 Executive Blvd., EPN-8104, Bethesda, MD 20892-7240, USA, wardm@mail.nih.gov Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 538 EP - 553 PB - John Wiley & Sons, Inc. VL - 40 IS - 5 SN - 0271-3586, 0271-3586 KW - man KW - Toxicology Abstracts; Health & Safety Science Abstracts; Pollution Abstracts KW - Agriculture KW - Farms KW - Migrant workers KW - Surveys KW - Agricultural practices KW - Pesticides KW - Occupational exposure KW - H 5000:Pesticides KW - X 24133:Metabolism KW - P 6000:TOXICOLOGY AND HEALTH KW - X 24136:Environmental impact UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18215597?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Industrial+Medicine&rft.atitle=Determining+the+probability+of+pesticide+exposures+among+migrant+farmworkers%3A+Results+from+a+feasibility+study&rft.au=Ward%2C+M+H%3BPrince%2C+J+R%3BStewart%2C+P+A%3BZahm%2C+SH&rft.aulast=Ward&rft.aufirst=M&rft.date=2001-11-01&rft.volume=40&rft.issue=5&rft.spage=538&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/10.1002%2Fajim.1121 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Agriculture; Pesticides; Occupational exposure; Migrant workers; Farms; Surveys; Agricultural practices DO - http://dx.doi.org/10.1002/ajim.1121 ER - TY - JOUR T1 - Neurotoxicant-Induced Elevation of Adrenomedullin Expression in Hippocampus and Glia Cultures AN - 18208290; 5281021 AB - Adrenomedullin (AM), a vasoactive peptide first isolated from pheochromocytoma, has been reported to be present in neurons in the central nervous system and in tumors of neural and glial origin. In this study, we investigated AM expression both in the hippocampus and in glial cell cultures using a chemical-induced model of injury. An acute intraperitoneal injection of the organo-metal trimethyltin (TMT) results in neurodegeneration of the hippocampal CA3-4 pyramidal cell layer. Within 4 days of injection, sparse, punctate staining for AM and lectin was evident in the CA3-4 region; by 10 days, a minimal level of CA3-4 neuronal degeneration was evident, with an increase in glial fibrillary acidic protein (GFAP)-positive astrocytes throughout the hippocampus. Degeneration progressed in severity until 30 days post-TMT, with distinct positive immunoreactivity for AM in the CA4 region. mRNA levels for tumor necrosis factor (TNF)- alpha , interleukin (IL)-1 alpha , GFAP, and AM in the hippocampus were increased over control levels within 4 days following TMT. In cultured glial cells, a 6 hr exposure to TMT (10 mu M) produced a morphological response of the cells and increased immunoreactivity for vimentin, GFAP, and AM. mRNA levels for TNF alpha , IL-1 alpha , GFAP, vimentin, and AM were elevated within 3-6 hr of exposure. In culture, neutralizing antibodies to IL-1 alpha and TNF alpha were effective in inhibiting the TMT-induced elevation of AM mRNA. These data suggest an interaction between the proinflammatory cytokines and glia response in the regulation of AM in response to injury. JF - Journal of Neuroscience Research AU - Jahnke, G D AU - Brunssen, S AU - Maier, W E AU - Harry, G J AD - Laboratory of Toxicology, MD EC-32, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA, jahnke@niehs.nih.gov Y1 - 2001/11/01/ PY - 2001 DA - 2001 Nov 01 SP - 464 EP - 474 VL - 66 IS - 3 SN - 0360-4012, 0360-4012 KW - tissue culture KW - neurotoxicants KW - adrenomedullin KW - trimethyltin KW - Toxicology Abstracts KW - Hippocampus KW - Heavy metals KW - Glial cells KW - Neurotoxicity KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18208290?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Neuroscience+Research&rft.atitle=Neurotoxicant-Induced+Elevation+of+Adrenomedullin+Expression+in+Hippocampus+and+Glia+Cultures&rft.au=Jahnke%2C+G+D%3BBrunssen%2C+S%3BMaier%2C+W+E%3BHarry%2C+G+J&rft.aulast=Jahnke&rft.aufirst=G&rft.date=2001-11-01&rft.volume=66&rft.issue=3&rft.spage=464&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neuroscience+Research&rft.issn=03604012&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Neurotoxicity; Heavy metals; Glial cells; Hippocampus ER - TY - JOUR T1 - Can Females Gain Extra Paternal Investment by Mating with Multiple Males? A Game Theoretic Approach AN - 18193725; 5237575 AB - Although females may require only one mating to become inseminated, many female animals engage in costly mating with multiple males. One potential benefit of polyandrous mating is gaining parental investment from multiple males. We developed two game theoretic models to explore this possibility. Our first model showed that male care of multiple females' offspring evolves when male help substantially increases offspring fitness, future mating opportunity is limited, and group size is small. In our second model, we assumed that males invest in the offspring of former mates and evaluated the fitness consequences of female monogamous and polyandrous mating strategies. Females benefit only from limited polyandry, that is, mating with several males. Polyandry is discouraged because females must share male investment with other polyandrous females, and paternal care is likely to experience diminishing returns. Females may enhance their access to male investment by competing with rival females and monopolizing investment, however. The results support the argument that females can gain paternal investment by mating with several males in small social groups (e.g., dunnocks Prunella modularis). The results do not support the argument that females can gain paternal investment from pronounced multiple mating in large social groups, however, as observed in many primate species. JF - American Naturalist AU - Soltis, J AU - McElreath, R AD - National Institutes of Health, National Institutes of Health Animal Center, Laboratory of Comparative Ethology, Box 529, Poolesville, Maryland 20837, USA, soltisj@mail.nih.gov Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 519 EP - 529 VL - 158 IS - 5 SN - 0003-0147, 0003-0147 KW - Animal Behavior Abstracts; Ecology Abstracts KW - Fitness KW - Mating behavior KW - Paternal behavior KW - Game theory KW - Reproductive strategy KW - Models KW - Y 25841:General KW - D 04650:Animals - general KW - D 04003:Modeling, mathematics, computer applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18193725?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Naturalist&rft.atitle=Can+Females+Gain+Extra+Paternal+Investment+by+Mating+with+Multiple+Males%3F+A+Game+Theoretic+Approach&rft.au=Soltis%2C+J%3BMcElreath%2C+R&rft.aulast=Soltis&rft.aufirst=J&rft.date=2001-11-01&rft.volume=158&rft.issue=5&rft.spage=519&rft.isbn=&rft.btitle=&rft.title=American+Naturalist&rft.issn=00030147&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Models; Game theory; Mating behavior; Reproductive strategy; Paternal behavior; Fitness ER - TY - JOUR T1 - Proportionate mortality among US migrant and seasonal farmworkers in twenty-four states AN - 18139994; 5288423 AB - Background: US migrant and seasonal farmworkers may be exposed to potentially carcinogenic pesticides and other agents. Little epidemiologic research has been conducted on this population. We examined the proportionate mortality of 26,148 subjects (14,631 white men (WM), 7,299 nonwhite men (NM), 1,081 white women (WW), and 3,137 nonwhite women (NW)) who were identified as farmworkers on death certificates from 24 US states during 1984-1993. Results: Farmworkers had significantly elevated proportionate mortality from injuries, tuberculosis, mental disorders, cerebrovascular disease, respiratory diseases, ulcers, hypertension (NW), and cirrhosis (NW). There was significantly reduced mortality from infectious diseases (other than tuberculosis), endocrine disorders, nervous system diseases, pneumoconioses, arteriosclerotic heart disease (WM), and all cancers combined. Proportionate cancer mortality analyses found excess cancers of the buccal cavity, larynx, esophagus, stomach, skin (NW), and cervix, and deficits for cancers of the colon, breast, kidney, pancreas (NW), and lymphohematopoietic system. Conclusions: The excess deaths from injuries, respiratory disease, and stomach cancer, and the deficits of colon cancer and arteriosclerotic heart disease among farmworkers, are consistent with typical mortality patterns previously observed among farm owner/operators. The excess buccal, laryngeal, esophageal, and cervical cancers, and the deficits of breast cancer and lymphohematopoietic cancers have not generally been observed in studies of farm owner/operators. JF - American Journal of Industrial Medicine AU - Colt, J S AU - Stallones, L AU - Cameron, L L AU - Dosemeci, M AU - Zahm, SH AD - Occupational Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, EPS 8112, Rockville, MD 20892-7240, USA, coltj@mail.nih.gov Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 604 EP - 611 PB - John Wiley & Sons, Inc. VL - 40 IS - 5 SN - 0271-3586, 0271-3586 KW - hypertension KW - respiratory tract diseases KW - tuberculosis KW - Risk Abstracts; Health & Safety Science Abstracts KW - Injuries KW - Migrant workers KW - Occupational exposure KW - Mortality KW - Agrochemicals KW - USA KW - Pesticides KW - Cardiovascular diseases KW - R2 23080:Industrial and labor KW - H 5000:Pesticides UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18139994?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Industrial+Medicine&rft.atitle=Proportionate+mortality+among+US+migrant+and+seasonal+farmworkers+in+twenty-four+states&rft.au=Colt%2C+J+S%3BStallones%2C+L%3BCameron%2C+L+L%3BDosemeci%2C+M%3BZahm%2C+SH&rft.aulast=Colt&rft.aufirst=J&rft.date=2001-11-01&rft.volume=40&rft.issue=5&rft.spage=604&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/10.1002%2Fajim.1126 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - USA; Agrochemicals; Pesticides; Occupational exposure; Mortality; Migrant workers; Injuries; Cardiovascular diseases DO - http://dx.doi.org/10.1002/ajim.1126 ER - TY - JOUR T1 - A Chimeric Human-Bovine Parainfluenza Virus Type 3 Expressing Measles Virus Hemagglutinin Is Attenuated for Replication but Is Still Immunogenic in Rhesus Monkeys AN - 18111880; 5198820 AB - The chimeric recombinant virus rHPIV3-N sub(B), a version of human parainfluenza virus type 3 (HPIV3) that is attenuated due to the presence of the bovine PIV3 nucleocapsid (N) protein open reading frame (ORF) in place of the HPIV3 ORF, was modified to encode the measles virus hemagglutinin (HA) inserted as an additional, supernumerary gene between the HPIV3 P and M genes. This recombinant, designated rHPIV3-N sub(B)HA, replicated like its attenuated rHPIV3-N sub(B) parent virus in vitro and in the upper and lower respiratory tracts of rhesus monkeys, indicating that the insertion of the measles virus HA did not further attenuate rHPIV3-N sub(B) in vitro or in vivo. Monkeys immunized with rHPIV3-N sub(B)HA developed a vigorous immune response to both measles virus and HPIV3, with serum antibody titers to both measles virus (neutralizing antibody) and HPIV3 (hemagglutination inhibiting antibody) of over 1:500. An attenuated HPIV3 expressing a major protective antigen of measles virus provides a method for immunization against measles by the intranasal route, a route that has been shown with HPIV3 and respiratory syncytial virus vaccines to be relatively refractory to the neutralizing and immunosuppressive effects of maternally derived virus-specific serum antibodies. It should now be possible to induce a protective immune response against measles virus in 6-month-old infants, an age group that in developing areas of the world is not responsive to the current measles virus vaccine. JF - Journal of Virology AU - Skiadopoulos, M H AU - Surman AU - Riggs, J M AU - Collins, P L AU - Murphy, B R AD - Room 100, Building 7, NIH, 7 Center Dr. MSC 0720, Bethesda, MD 20892-0720., mskiadopoulos@niaid.nih.gov Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 10498 EP - 10504 VL - 75 IS - 21 SN - 0022-538X, 0022-538X KW - man KW - primates KW - Rhesus monkey KW - M gene KW - P gene KW - double prime M gene KW - double prime P gene KW - nucleocapsid protein KW - Biochemistry Abstracts 2: Nucleic Acids; Immunology Abstracts; Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - ^AP gene KW - ^AM gene KW - Hemagglutinins KW - Bovine parainfluenza virus 3 KW - Measles virus KW - Parainfluenza virus KW - Nucleocapsids KW - Macaca mulatta KW - Human parainfluenza virus 3 KW - DNA biosynthesis KW - Replication KW - Antibody response KW - Chimeras KW - Lung KW - Immunogenicity KW - Immune response KW - Vaccines KW - Capsid protein KW - N 14651:Virus & phage infections KW - V 22099:Immune response & immune mechanisms KW - F 06807:Active immunization KW - A 01097:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18111880?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=A+Chimeric+Human-Bovine+Parainfluenza+Virus+Type+3+Expressing+Measles+Virus+Hemagglutinin+Is+Attenuated+for+Replication+but+Is+Still+Immunogenic+in+Rhesus+Monkeys&rft.au=Skiadopoulos%2C+M+H%3BSurman%3BRiggs%2C+J+M%3BCollins%2C+P+L%3BMurphy%2C+B+R&rft.aulast=Skiadopoulos&rft.aufirst=M&rft.date=2001-11-01&rft.volume=75&rft.issue=21&rft.spage=10498&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/10.1128%2FJVI.75.21.10498-10504.2001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human parainfluenza virus 3; Bovine parainfluenza virus 3; Macaca mulatta; Measles virus; Parainfluenza virus; Vaccines; Immunogenicity; Hemagglutinins; Chimeras; DNA biosynthesis; Immune response; Lung; Replication; Capsid protein; Nucleocapsids; Antibody response DO - http://dx.doi.org/10.1128/JVI.75.21.10498-10504.2001 ER - TY - JOUR T1 - Yaba-Like Disease Virus: an Alternative Replicating Poxvirus Vector for Cancer Gene Therapy AN - 18107235; 5198815 AB - Vaccinia virus is being investigated as a replicating vector for tumor-directed gene therapy. However, the majority of cancer patients have preformed immunologic reactivity against vaccinia virus, as a result of smallpox vaccination, which may limit its use as a vector. The Yaba-like disease (YLD) virus was investigated here as an alternative, replicating poxvirus for cancer gene therapy. We have demonstrated that the YLD virus does not cross-react with vaccinia virus antibodies, and it replicates efficiently in human tumor cells. YLD virus can be expanded and purified to high titer in CV-1 cells under conditions utilized for vaccinia virus. The YLD virus RNA polymerase was able to express genes regulated by a synthetic promoter designed for use in orthopoxviruses. We sequenced the YLD virus TK gene and created a shuttle plasmid, which allowed the recombination of the green fluorescent protein (GFP) gene into the YLD virus. In a murine model of ovarian cancer, up to 38% of cells in the tumor expressed the GFP transgene 12 days after intraperitoneal virus delivery. YLD virus has favorable characteristics as a vector for cancer gene therapy, and this potential should be explored further. JF - Journal of Virology AU - Hu, Y AU - Lee, J AU - McCart, JA AU - Xu, H AU - Moss, B AU - Alexander, H R AU - Bartlett, D L AD - Surgery Branch, NCI, NIH, Building 10, Rm. 2B16, 9000 Rockville Pike, Bethesda, MD 20892., dbart@nih.gov Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 10300 EP - 10308 VL - 75 IS - 21 SN - 0022-538X, 0022-538X KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Virology & AIDS Abstracts KW - Nucleotide sequence KW - Animal models KW - Green fluorescent protein KW - Thymidine kinase KW - Tumor cells KW - Recombination KW - DNA-directed RNA polymerase KW - Ovarian cancer KW - Gene therapy KW - Replication KW - Poxvirus KW - Yaba-like disease virus KW - N 14682:Cloning vectors KW - V 22044:Viral nucleic acid synthesis & synthesis of virus-coded proteins KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18107235?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=Yaba-Like+Disease+Virus%3A+an+Alternative+Replicating+Poxvirus+Vector+for+Cancer+Gene+Therapy&rft.au=Hu%2C+Y%3BLee%2C+J%3BMcCart%2C+JA%3BXu%2C+H%3BMoss%2C+B%3BAlexander%2C+H+R%3BBartlett%2C+D+L&rft.aulast=Hu&rft.aufirst=Y&rft.date=2001-11-01&rft.volume=75&rft.issue=21&rft.spage=10300&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/10.1128%2FJVI.75.21.10300-10308.2001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Poxvirus; Yaba-like disease virus; Thymidine kinase; DNA-directed RNA polymerase; Recombination; Green fluorescent protein; Nucleotide sequence; Replication; Tumor cells; Animal models; Gene therapy; Ovarian cancer DO - http://dx.doi.org/10.1128/JVI.75.21.10300-10308.2001 ER - TY - JOUR T1 - Induction of Gene Expression as a Monitor of Exposure to Ionizing Radiation AN - 17863217; 5973856 AB - The complex molecular responses to genotoxic stress are mediated by a variety of regulatory pathways. The transcription factor TP53 plays a central role in the cellular response to DNA-damaging agents such as ionizing radiation, but other pathways also play important roles. In addition, differences in radiation quality, such as the exposure to high-LET radiation that occurs during space travel, may influence the pattern of responses. The premise is developed that stress gene responses can be employed as molecular markers for radiation exposure using a combination of informatics and functional genomics approaches. Published studies from our laboratory have already demonstrated such transcriptional responses with doses of gamma rays as low as 2 cGy, and in peripheral blood lymphocytes (PBLs) irradiated ex vivo with doses as low as 20 cGy. We have also found several genes elevated in vivo 24 h after whole-body irradiation of mice with 20 cGy. Such studies should provide insight into the molecular responses to physiologically relevant doses, which cannot necessarily be extrapolated from high-dose studies. In addition, ongoing experiments are identifying large numbers of potential biomarkers using microarray hybridization and various irradiation protocols including expression at different times after exposure to low- and high-LET radiation. Computation-intensive informatics analysis methods are also being developed for management of the complex gene expression profiles resulting from these experiments. With further development of these approaches, it may be feasible to monitor changes in gene expression after low-dose radiation exposure and other physiological stresses that may be encountered during manned space flight, such as the planned mission to Mars. JF - Radiation Research AU - Amundson, SA AU - Bittner, M AU - Meltzer, P AU - Trent, J AU - Fornace, A J AD - National Institutes of Health, National Cancer Institute, Division of Basic Science Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 657 EP - 661 PB - Radiation Research Society VL - 156 IS - 5 SN - 0033-7587, 0033-7587 KW - Toxicology Abstracts KW - Travel KW - alpha Radiation KW - Space flight KW - Genotoxicity KW - Stress KW - Peripheral blood KW - Lymphocytes KW - biomarkers KW - DNA microarrays KW - p53 protein KW - Gene expression KW - Radiation KW - Transcription factors KW - Ionizing radiation KW - genomics KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17863217?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+Research&rft.atitle=Induction+of+Gene+Expression+as+a+Monitor+of+Exposure+to+Ionizing+Radiation&rft.au=Amundson%2C+SA%3BBittner%2C+M%3BMeltzer%2C+P%3BTrent%2C+J%3BFornace%2C+A+J&rft.aulast=Amundson&rft.aufirst=SA&rft.date=2001-11-01&rft.volume=156&rft.issue=5&rft.spage=657&rft.isbn=&rft.btitle=&rft.title=Radiation+Research&rft.issn=00337587&rft_id=info:doi/10.1043%2F0033-7587%282001%291562.0.CO%3B2 L2 - http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0033-7587&volume=156&page=657 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Travel; alpha Radiation; Space flight; Genotoxicity; Stress; Peripheral blood; Lymphocytes; DNA microarrays; biomarkers; p53 protein; Gene expression; Radiation; Ionizing radiation; Transcription factors; genomics DO - http://dx.doi.org/10.1043/0033-7587(2001)156<0657:IOGEAA>2.0.CO;2 ER - TY - JOUR T1 - Additive activation of hepatic NF- Kappa B by ethanol and hepatitis B protein X (HBX) or HCV core protein: involvement of TNF- alpha receptor 1-independent and -dependent mechanisms AN - 17089705; 6724741 AB - The present study demonstrates that ethanol activates NF- Kappa B via its metabolite acetaldehyde, which targets a pertussis toxin-sensitive G-protein whereas hepatitis B protein X (HBX) or HCV core protein induces NF- Kappa B by a tumor necrosis factor alpha receptor 1 (TNFR1)-dependent mechanism in hepatic cells. In view of the essential role of TNFR1 in alcoholic liver injury, targeting TNFR1 by hepatitis viral proteins could contribute to cooperative effects of alcohol consumption and viral hepatitis on liver disease. JF - FASEB Journal AU - Kim, Won-Ho AU - Hong, Feng AU - Jaruga, Barbara AU - Hu, Zongyi AU - Fan, Saijun AU - Liang, TJake AU - Gao, Bin AD - LB, NIAAA/NIH, Park Bldg., Rm. 120, 12420 Parklawn Dr., Bethesda, MD 20892, USA, bgao@mail.nih.gov Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 2551 EP - 2553 PB - Federation of American Societies for Experimental Biology VL - 15 IS - 13 SN - 0892-6638, 0892-6638 KW - Toxicology Abstracts; Virology & AIDS Abstracts; Immunology Abstracts KW - Pertussis KW - Liver diseases KW - Injuries KW - Acetaldehyde KW - Guanine nucleotide-binding protein KW - Metabolites KW - Tumor necrosis factor receptors KW - Alcoholics KW - NF- Kappa B protein KW - Hepatitis C virus KW - protein X KW - Hepatitis B KW - Tumor necrosis factor- alpha KW - Core protein KW - Ethanol KW - V 22099:Immune response & immune mechanisms KW - X 24180:Social poisons & drug abuse KW - F 06104:Virus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17089705?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+Journal&rft.atitle=Additive+activation+of+hepatic+NF-+Kappa+B+by+ethanol+and+hepatitis+B+protein+X+%28HBX%29+or+HCV+core+protein%3A+involvement+of+TNF-+alpha+receptor+1-independent+and+-dependent+mechanisms&rft.au=Kim%2C+Won-Ho%3BHong%2C+Feng%3BJaruga%2C+Barbara%3BHu%2C+Zongyi%3BFan%2C+Saijun%3BLiang%2C+TJake%3BGao%2C+Bin&rft.aulast=Kim&rft.aufirst=Won-Ho&rft.date=2001-11-01&rft.volume=15&rft.issue=13&rft.spage=2551&rft.isbn=&rft.btitle=&rft.title=FASEB+Journal&rft.issn=08926638&rft_id=info:doi/10.1096%2Ffj.01-0217 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-10-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Pertussis; Liver diseases; Injuries; Acetaldehyde; Guanine nucleotide-binding protein; Metabolites; Alcoholics; Tumor necrosis factor receptors; NF- Kappa B protein; Hepatitis B; protein X; Tumor necrosis factor- alpha; Ethanol; Core protein; Hepatitis C virus DO - http://dx.doi.org/10.1096/fj.01-0217 ER - TY - JOUR T1 - Stem cells as therapeutics for neurodegenerative disorders? AN - 1008844430; 16482534 AB - Aging is associated with a progressive increase in the risk of several prominent neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, stroke and amyotrophic lateral sclerosis. In each of these disorders specific populations of neurons become dysfunctional, then die and are not replaced. The adult brain and spinal cord contain populations of so-called neural stem cells (self-renewing and multipotent) and neural precursor cells (specified to a certain fate, but still mitotic) that may provide a continuing source of new neurons and glial cells during successful aging and after injury to the nervous system. Recent studies have shown that stem cells from embryos and adults can be transplanted into the nervous system, differentiate into neurons and glia and restore lost function in experimental models of neurodegenerative diseases. Embryonic stem cells may be a particularly effective donor cell type for transplantation-based therapies. Efficacy of stem cell therapies remains to be established in clinical trials in humans. Another approach is to mobilize endogenous neural stem cells. Animals studies have shown that dietary and behavioral modifications can indeed stimulate neurogenesis. Molecular and cellular mechanisms that regulate the proliferation, differentiation and survival of neural stem cells and neural precursor cells are being elucidated and are revealing novel targets for the development of pharmaceuticals that promote neurogenesis. JF - Expert Review of Neurotherapeutics AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging GRC 4F01, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2001/11// PY - 2001 DA - Nov 2001 SP - 267 EP - 273 PB - Future Science Group (FSG), Unitec House, 2 Albert Place London N3 1QB United Kingdom VL - 1 IS - 2 SN - 1473-7175, 1473-7175 KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts KW - Aging KW - Alzheimer's disease KW - Amyotrophic lateral sclerosis KW - Cell proliferation KW - Cell survival KW - Clinical trials KW - Differentiation KW - Embryo cells KW - Movement disorders KW - Nervous system KW - Neural stem cells KW - Neurodegenerative diseases KW - Neurogenesis KW - Pharmaceuticals KW - Recovery of function KW - Reviews KW - Spinal cord injury KW - Stem cells KW - Stroke KW - W 30965:Miscellaneous, Reviews KW - N3 11027:Neurology & neuropathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1008844430?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+Review+of+Neurotherapeutics&rft.atitle=Stem+cells+as+therapeutics+for+neurodegenerative+disorders%3F&rft.au=Mattson%2C+Mark+P&rft.aulast=Mattson&rft.aufirst=Mark&rft.date=2001-11-01&rft.volume=1&rft.issue=2&rft.spage=267&rft.isbn=&rft.btitle=&rft.title=Expert+Review+of+Neurotherapeutics&rft.issn=14737175&rft_id=info:doi/10.1586%2F14737175.1.2.267 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-04-01 N1 - Last updated - 2013-04-19 N1 - SubjectsTermNotLitGenreText - Cell survival; Alzheimer's disease; Aging; Stroke; Spinal cord injury; Recovery of function; Clinical trials; Differentiation; Neurodegenerative diseases; Neurogenesis; Stem cells; Nervous system; Amyotrophic lateral sclerosis; Movement disorders; Embryo cells; Reviews; Pharmaceuticals; Cell proliferation; Neural stem cells DO - http://dx.doi.org/10.1586/14737175.1.2.267 ER - TY - JOUR T1 - Human breast cancer MDA-MB-231 cells fail to express the neurofibromin protein, lack its type I mRNA isoform and show accumulation of P-MAPK and activated Ras. AN - 71187655; 11566491 AB - Neurofibromin is a tumor suppressor protein, which is similar in function to the GTPase activating protein (GAP), p120GAP, in that it accelerates inactivation of Ras. Mutations in the NF1 gene cause neurofibromatosis type 1, NF1, an autosomal dominant disease with a diverse spectrum of clinical manifestations, including neurofibromas. Ras activation (GTP binding) is induced by the GTP exchange factor Sos and its inactivation is regulated through the GAPs (p120GAP and neurofibromin). Strikingly, neurofibromin was nearly absent in MB-231 human breast cancer cells and present in the remaining four cell lines studied, with higher levels in BT-474 and MB-453 than in MCF-7 and BT-20 cells, as tested with polyclonal antibodies to both the N-terminal as well as the C-terminal peptides. Coordinated with the near absence of neurofibromin, these cells also presented with much greater levels of P-MAPK and activated Ras. Further, RT-PCR analysis demonstrated the absence of expression of NF1 mRNA type I isoform only in the MB-231 cell lines. This result documents for the first time an altered NF1 expression at the protein and mRNA levels in MDA-MB-231 breast cancer cells. JF - Cancer letters AU - Ogata, H AU - Sato, H AU - Takatsuka, J AU - De Luca, L M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 2001/10/30/ PY - 2001 DA - 2001 Oct 30 SP - 159 EP - 164 VL - 172 IS - 2 SN - 0304-3835, 0304-3835 KW - Nerve Tissue Proteins KW - 0 KW - Neurofibromin 1 KW - RNA, Messenger KW - Guanosine Triphosphate KW - 86-01-1 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - ras Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Phosphorylation KW - Humans KW - Rabbits KW - Mice KW - Female KW - Guanosine Triphosphate -- metabolism KW - Nerve Tissue Proteins -- analysis KW - ras Proteins -- analysis KW - Breast Neoplasms -- pathology KW - Mitogen-Activated Protein Kinases -- metabolism KW - RNA, Messenger -- analysis KW - Breast Neoplasms -- metabolism KW - Nerve Tissue Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71187655?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Human+breast+cancer+MDA-MB-231+cells+fail+to+express+the+neurofibromin+protein%2C+lack+its+type+I+mRNA+isoform+and+show+accumulation+of+P-MAPK+and+activated+Ras.&rft.au=Ogata%2C+H%3BSato%2C+H%3BTakatsuka%2C+J%3BDe+Luca%2C+L+M&rft.aulast=Ogata&rft.aufirst=H&rft.date=2001-10-30&rft.volume=172&rft.issue=2&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-11-01 N1 - Date created - 2001-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Altered splicing of cancer associated genes during cancer progression AN - 39511948; 3629471 AU - Baker, C C AU - DiPasquale, J AU - Quintero, J AU - Muniz-Medina, V AU - Fu, B Y1 - 2001/10/29/ PY - 2001 DA - 2001 Oct 29 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39511948?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Altered+splicing+of+cancer+associated+genes+during+cancer+progression&rft.au=Baker%2C+C+C%3BDiPasquale%2C+J%3BQuintero%2C+J%3BMuniz-Medina%2C+V%3BFu%2C+B&rft.aulast=Baker&rft.aufirst=C&rft.date=2001-10-29&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: The RNA Society, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-530-7120; email: rna@faseb.org; URL: www.rnasociety.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Genome-wide search identifies 17 novel small RNAs in E. coli AN - 39416221; 3629989 AU - Wassarman, K M AU - Repoila, F AU - Rosenow, C AU - Gottesman, S AU - Storz, G Y1 - 2001/10/29/ PY - 2001 DA - 2001 Oct 29 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39416221?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Genome-wide+search+identifies+17+novel+small+RNAs+in+E.+coli&rft.au=Wassarman%2C+K+M%3BRepoila%2C+F%3BRosenow%2C+C%3BGottesman%2C+S%3BStorz%2C+G&rft.aulast=Wassarman&rft.aufirst=K&rft.date=2001-10-29&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: The RNA Society, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-530-7120; email: rna@faseb.org; URL: www.rnasociety.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Discriminating between ITS2 folding models using a functional assay in S. cerevisiae AN - 39399946; 3629534 AU - Cote, CA AU - Peculis, BA Y1 - 2001/10/29/ PY - 2001 DA - 2001 Oct 29 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39399946?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Discriminating+between+ITS2+folding+models+using+a+functional+assay+in+S.+cerevisiae&rft.au=Cote%2C+CA%3BPeculis%2C+BA&rft.aulast=Cote&rft.aufirst=CA&rft.date=2001-10-29&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: The RNA Society, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-530-7120; email: rna@faseb.org; URL: www.rnasociety.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - ASF/SF2 is not essential in vivo in splicing of bovine papillomavirus type 1 late pre-mRNAs AN - 39398669; 3630017 AU - Zheng, Z M AU - Liu, X F Y1 - 2001/10/29/ PY - 2001 DA - 2001 Oct 29 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39398669?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=ASF%2FSF2+is+not+essential+in+vivo+in+splicing+of+bovine+papillomavirus+type+1+late+pre-mRNAs&rft.au=Zheng%2C+Z+M%3BLiu%2C+X+F&rft.aulast=Zheng&rft.aufirst=Z&rft.date=2001-10-29&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: The RNA Society, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-530-7120; email: rna@faseb.org; URL: www.rnasociety.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Evolutionary conservation of C/D box snoRNA maturation and mechanisms directing 2'O-ribose rRNA methylation AN - 39379951; 3629842 AU - Peculis, BA AU - Peterson, B AU - Baserga, S Y1 - 2001/10/29/ PY - 2001 DA - 2001 Oct 29 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39379951?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Evolutionary+conservation+of+C%2FD+box+snoRNA+maturation+and+mechanisms+directing+2%27O-ribose+rRNA+methylation&rft.au=Peculis%2C+BA%3BPeterson%2C+B%3BBaserga%2C+S&rft.aulast=Peculis&rft.aufirst=BA&rft.date=2001-10-29&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: The RNA Society, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-530-7120; email: rna@faseb.org; URL: www.rnasociety.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Identification and characterization of U8 snoRNA-specific binding proteins AN - 39371200; 3629843 AU - Peculis, BA AU - Tomasevic, N AU - Peterson, B Y1 - 2001/10/29/ PY - 2001 DA - 2001 Oct 29 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39371200?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Identification+and+characterization+of+U8+snoRNA-specific+binding+proteins&rft.au=Peculis%2C+BA%3BTomasevic%2C+N%3BPeterson%2C+B&rft.aulast=Peculis&rft.aufirst=BA&rft.date=2001-10-29&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: The RNA Society, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-530-7120; email: rna@faseb.org; URL: www.rnasociety.org N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - Interleukin-6 regulation of the human DNA methyltransferase (HDNMT) gene in human erythroleukemia cells. AN - 72215210; 11551897 AB - Methylation of mammalian DNA by the DNA methyltransferase enzyme (dnmt-1) at CpG dinucleotide sequences has been recognized as an important epigenetic control mechanism in regulating the expression of cellular genes (Yen, R. W., Vertino, P. M., Nelkin, B. D., Yu, J. J., el-Deiry, W., Cumaraswamy, A., Lennon, G. G., Trask, B. J., Celano, P., and Baylin, S. B. (1992) Nucleic Acids Res. 20, 2287-2291; Ramchandani, S., Bigey, P., and Szyf, M. (1998) Biol. Chem. 379, 535-5401). Here we show that interleukin (IL)-6 regulates the methyltransferase promoter and resulting enzyme activity, which requires transcriptional activation by the Fli-1 transcription factor (Spyropoulos, D. D., Pharr, P. N., Lavenburg, K. R., Jackers, P., Papas, T. S., Ogawa, M., and Watson, D. K. (1998) Mol. Cell. Biol. 15, 5643-5652). The data suggest that inflammatory cytokines such as IL-6 may exert many epigenetic changes in cells via the regulation of the methyltransferase gene. Furthermore, IL-6 regulation of transcription factors like Fli-1, which can help to direct cells along opposing differentiation pathways, may in fact be reflected in part by their ability to regulate the methylation of cellular genes. JF - The Journal of biological chemistry AU - Hodge, D R AU - Xiao, W AU - Clausen, P A AU - Heidecker, G AU - Szyf, M AU - Farrar, W L AD - Intramural Research Support Program, SAIC Frederick, NCI-Frederick Cancer Research and Development Center, National Institutes of Health, Frederick, MD 21702, USA. hodge@mail.ncifcrf.gov Y1 - 2001/10/26/ PY - 2001 DA - 2001 Oct 26 SP - 39508 EP - 39511 VL - 276 IS - 43 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Interleukin-6 KW - Proto-Oncogene Protein c-fli-1 KW - Proto-Oncogene Proteins KW - Trans-Activators KW - DNA (Cytosine-5-)-Methyltransferase KW - EC 2.1.1.37 KW - DNA (cytosine-5-)-methyltransferase 1 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Trans-Activators -- metabolism KW - Promoter Regions, Genetic KW - DNA Methylation KW - Humans KW - Transcriptional Activation -- drug effects KW - Cell Differentiation KW - K562 Cells KW - Megakaryocytes -- cytology KW - DNA-Binding Proteins -- metabolism KW - DNA (Cytosine-5-)-Methyltransferase -- genetics KW - Leukemia, Erythroblastic, Acute -- enzymology KW - Interleukin-6 -- pharmacology KW - Gene Expression Regulation, Neoplastic -- drug effects KW - DNA (Cytosine-5-)-Methyltransferase -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72215210?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Interleukin-6+regulation+of+the+human+DNA+methyltransferase+%28HDNMT%29+gene+in+human+erythroleukemia+cells.&rft.au=Hodge%2C+D+R%3BXiao%2C+W%3BClausen%2C+P+A%3BHeidecker%2C+G%3BSzyf%2C+M%3BFarrar%2C+W+L&rft.aulast=Hodge&rft.aufirst=D&rft.date=2001-10-26&rft.volume=276&rft.issue=43&rft.spage=39508&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-07 N1 - Date created - 2001-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alpha-lipoic acid protects rat cortical neurons against cell death induced by amyloid and hydrogen peroxide through the Akt signalling pathway. AN - 72203787; 11602326 AB - Substantial evidence suggests that the accumulation of beta-amyloid (Abeta)-derived peptides contributes to the aetiology of Alzheimer's disease (AD) by stimulating formation of free radicals. Thus, the antioxidant alpha-lipoate, which is able to cross the blood-brain barrier, would seem an ideal substance in the treatment of AD. We have investigated the potential effectiveness of alpha-lipoic acid (LA) against cytotoxicity induced by Abeta peptide (31-35) (30 microM) and hydrogen peroxide (H(2)O(2)) (100 microM) with the cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction and fluorescence dye propidium iodide assays in primary neurons of rat cerebral cortex. We found that treatment with LA protected cortical neurons against cytotoxicity induced by Abeta or H(2)O(2). In addition, LA-induced increase in the level of Akt in the neurons was observed by Western blot. The LA-induced neuroprotection and Akt increase were attenuated by pre-treatment with the phosphatidylinositol 3-kinase inhibitor, LY294002 (50 microM). Our data suggest that the neuroprotective effects of the antioxidant LA are partly mediated through activation of the PKB/Akt signaling pathway. JF - Neuroscience letters AU - Zhang, L AU - Xing, G Q AU - Barker, J L AU - Chang, Y AU - Maric, D AU - Ma, W AU - Li, B S AU - Rubinow, D R AD - Behavioral Endocrinology Branch, NIMH, NIH, Building 10, Room 3N238, Bethesda, MD 20892, USA. zhangl@codon.nih.gov Y1 - 2001/10/26/ PY - 2001 DA - 2001 Oct 26 SP - 125 EP - 128 VL - 312 IS - 3 SN - 0304-3940, 0304-3940 KW - Amyloid beta-Peptides KW - 0 KW - Antioxidants KW - Coloring Agents KW - Neuroprotective Agents KW - Peptide Fragments KW - Proto-Oncogene Proteins KW - Tetrazolium Salts KW - Thiazoles KW - amyloid beta-protein (31-35) KW - Thioctic Acid KW - 73Y7P0K73Y KW - Hydrogen Peroxide KW - BBX060AN9V KW - Akt1 protein, rat KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - thiazolyl blue KW - EUY85H477I KW - Index Medicus KW - Animals KW - Fetus KW - Cerebral Cortex -- drug effects KW - Cerebral Cortex -- metabolism KW - Biological Assay KW - Cells, Cultured -- drug effects KW - Cerebral Cortex -- physiopathology KW - Rats KW - Cell Survival -- drug effects KW - Amyloid beta-Peptides -- metabolism KW - Peptide Fragments -- metabolism KW - Dose-Response Relationship, Drug KW - Hydrogen Peroxide -- metabolism KW - Hydrogen Peroxide -- antagonists & inhibitors KW - Cells, Cultured -- pathology KW - Drug Interactions -- physiology KW - Peptide Fragments -- antagonists & inhibitors KW - Signal Transduction -- physiology KW - Cells, Cultured -- metabolism KW - Signal Transduction -- drug effects KW - Cell Survival -- physiology KW - Amyloid beta-Peptides -- antagonists & inhibitors KW - Cell Death -- physiology KW - Neurons -- metabolism KW - Alzheimer Disease -- drug therapy KW - Alzheimer Disease -- physiopathology KW - Neurons -- drug effects KW - Proto-Oncogene Proteins -- metabolism KW - Cell Death -- drug effects KW - Neurons -- pathology KW - Neuroprotective Agents -- pharmacology KW - Antioxidants -- pharmacology KW - Proto-Oncogene Proteins -- drug effects KW - Thioctic Acid -- pharmacology KW - Alzheimer Disease -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72203787?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience+letters&rft.atitle=Alpha-lipoic+acid+protects+rat+cortical+neurons+against+cell+death+induced+by+amyloid+and+hydrogen+peroxide+through+the+Akt+signalling+pathway.&rft.au=Zhang%2C+L%3BXing%2C+G+Q%3BBarker%2C+J+L%3BChang%2C+Y%3BMaric%2C+D%3BMa%2C+W%3BLi%2C+B+S%3BRubinow%2C+D+R&rft.aulast=Zhang&rft.aufirst=L&rft.date=2001-10-26&rft.volume=312&rft.issue=3&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Neuroscience+letters&rft.issn=03043940&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-18 N1 - Date created - 2001-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Unusual Conformational Changes in 6-Hydroxymethyl-7,8-dihydropterin Pyrophosphokinase as Revealed by X-ray Crystallography and NMR AN - 18111144; 5204846 AB - The crystal structure of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) in complex with MgADP has been determined at 1.5-Aa resolution with a crystallographic R factor of 0.191. The solution structure of HPPK in complex with Mg super(2+) and beta , gamma -methyleneadenosine 5'-triphosphate (MgAMPPCP) has been determined using a simulated annealing protocol with 3,523 experimental NMR restraints. The root mean square deviation of the ensemble of 20 refined conformers that represent the solution structure from the mean coordinate set derived from them is 0.74 plus or minus 0.26 Aa for all backbone atoms and 0.49 plus or minus 0.22 Aa when residues Pro super(14), Pro super(44)-Gln super(50), and Arg super(84)-Pro super(91) are excluded. Binding of MgADP causes significant changes in the conformation and dynamical property of three loops of HPPK that are involved in catalysis. A dramatic, unusual conformational change is that loop 3 moves away from the active center significantly with some residues moving by >17 Aa. The binding of MgADP also stabilizes loop 1 and loop 3 but makes loop 2 more mobile. Very similar conformational and dynamical changes are observed in the NMR solution structure of HPPK super(.)MgAMPPCP. The conformational and dynamical changes may play important roles in both substrate binding and product release in the catalytic cycle. JF - Journal of Biological Chemistry AU - Xiao, B AU - Shi, G AU - Gao, J AU - Blaszczyk, J AU - Liu, Q AU - Ji, X AU - Yan, H AD - Macromolecular Crystallography Laboratory, NCI, National Institutes of Health, Frederick, Maryland 21702, USA, jix@ncifcrf.gov. Y1 - 2001/10/26/ PY - 2001 DA - 2001 Oct 26 SP - 40274 EP - 40281 VL - 276 IS - 43 SN - 0021-9258, 0021-9258 KW - 6-hydroxymethyl-7,8-dihydropterin KW - Microbiology Abstracts B: Bacteriology KW - X-ray crystallography KW - Crystal structure KW - Escherichia coli KW - N.M.R. KW - Conformational analysis KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18111144?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Unusual+Conformational+Changes+in+6-Hydroxymethyl-7%2C8-dihydropterin+Pyrophosphokinase+as+Revealed+by+X-ray+Crystallography+and+NMR&rft.au=Xiao%2C+B%3BShi%2C+G%3BGao%2C+J%3BBlaszczyk%2C+J%3BLiu%2C+Q%3BJi%2C+X%3BYan%2C+H&rft.aulast=Xiao&rft.aufirst=B&rft.date=2001-10-26&rft.volume=276&rft.issue=43&rft.spage=40274&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; X-ray crystallography; N.M.R.; Conformational analysis; Crystal structure ER - TY - JOUR T1 - MDP-1 is a new and distinct member of the haloacid dehalogenase family of aspartate-dependent phosphohydrolases. AN - 72203795; 11601995 AB - MDP-1 is a eukaryotic magnesium-dependent acid phosphatase with little sequence homology to previously characterized phosphatases. The presence of a conserved motif (Asp-X-Asp-X-Thr) in the N terminus of MDP-1 suggested a relationship to the haloacid dehalogenase (HAD) superfamily, which contains a number of magnesium-dependent acid phosphatases. These phosphatases utilize an aspartate nucleophile and contain a number of conserved active-site residues and hydrophobic patches, which can be plausibly aligned with conserved residues in MDP-1. Seven site-specific point mutants of MDP-1 were produced by modifying the catalytic aspartate, serine, and lysine residues to asparagine or glutamate, alanine, and arginine, respectively. The activity of these mutants confirms the assignment of MDP-1 as a member of the HAD superfamily. Detailed comparison of the sequence of the 15 MDP-1 sequences from various organisms with other HAD superfamily sequences suggests that MDP-1 is not closely related to any particular member of the superfamily. The crystal structures of several HAD family enzymes identify a domain proximal to the active site responsible for important interactions with low molecular weight substrates. The absence of this domain or any other that might perform the same function in MDP-1 suggests an "open" active site capable of interactions with large substrates such as proteins. This suggestion was experimentally confirmed by demonstration that MDP-1 is competent to catalyze the dephosphorylation of tyrosine-phosphorylated proteins. JF - Biochemistry AU - Selengut, J D AD - Laboratory of Biochemistry, National Heart, Lung and Blood Institute, Building 50-2347, National Institutes of Health, 50 South Drive, Bethesda, Maryland 20892-8012, USA. selengut@nih.gov Y1 - 2001/10/23/ PY - 2001 DA - 2001 Oct 23 SP - 12704 EP - 12711 VL - 40 IS - 42 SN - 0006-2960, 0006-2960 KW - Aspartic Acid KW - 30KYC7MIAI KW - Hydrolases KW - EC 3.- KW - MDP-1 protein, human KW - EC 3.1.3.-. KW - MDP-1 protein, mouse KW - EC 3.1.3.16 KW - Phosphoprotein Phosphatases KW - Protein Phosphatase 2C KW - Protein Tyrosine Phosphatases KW - EC 3.1.3.48 KW - 2-haloacid dehalogenase KW - EC 3.8.1.2 KW - Index Medicus KW - Animals KW - Protein Tyrosine Phosphatases -- metabolism KW - Amino Acid Motifs -- genetics KW - Humans KW - Multigene Family KW - Hydrolases -- genetics KW - Amino Acid Sequence KW - Mice KW - Saccharomyces cerevisiae -- enzymology KW - Saccharomyces cerevisiae -- genetics KW - Rats KW - Mutagenesis, Site-Directed KW - Protein Structure, Tertiary -- genetics KW - Sequence Alignment KW - Hydrolases -- chemistry KW - Catalytic Domain -- genetics KW - Molecular Sequence Data KW - Protein Tyrosine Phosphatases -- chemistry KW - Phosphoprotein Phosphatases -- metabolism KW - Phosphoprotein Phosphatases -- genetics KW - Phosphoprotein Phosphatases -- chemistry KW - Sequence Homology, Amino Acid KW - Aspartic Acid -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72203795?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=MDP-1+is+a+new+and+distinct+member+of+the+haloacid+dehalogenase+family+of+aspartate-dependent+phosphohydrolases.&rft.au=Selengut%2C+J+D&rft.aulast=Selengut&rft.aufirst=J&rft.date=2001-10-23&rft.volume=40&rft.issue=42&rft.spage=12704&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-05 N1 - Date created - 2001-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The fidelity of human DNA polymerase gamma with and without exonucleolytic proofreading and the p55 accessory subunit. AN - 72198152; 11504725 AB - Mutations in human mitochondrial DNA influence aging, induce severe neuromuscular pathologies, cause maternally inherited metabolic diseases, and suppress apoptosis. Since the genetic stability of mitochondrial DNA depends on the accuracy of DNA polymerase gamma (pol gamma), we investigated the fidelity of DNA synthesis by human pol gamma. Comparison of the wild-type 140-kDa catalytic subunit to its exonuclease-deficient derivative indicates pol gamma has high base substitution fidelity that results from high nucleotide selectivity and exonucleolytic proofreading. pol gamma is also relatively accurate for single-base additions and deletions in non-iterated and short repetitive sequences. However, when copying homopolymeric sequences longer than four nucleotides, pol gamma has low frameshift fidelity and also generates base substitutions inferred to result from a primer dislocation mechanism. The ability of pol gamma both to make and to proofread dislocation intermediates is the first such evidence for a family A polymerase. Including the p55 accessory subunit, which confers processivity to the pol gamma catalytic subunit, decreases frameshift and base substitution fidelity. Kinetic analyses indicate that p55 promotes extension of mismatched termini to lower the fidelity. These data suggest that homopolymeric runs in mitochondrial DNA may be particularly prone to frameshift mutation in vivo due to replication errors by pol gamma. JF - The Journal of biological chemistry AU - Longley, M J AU - Nguyen, D AU - Kunkel, T A AU - Copeland, W C AD - Laboratory of Molecular Genetics and the Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/10/19/ PY - 2001 DA - 2001 Oct 19 SP - 38555 EP - 38562 VL - 276 IS - 42 SN - 0021-9258, 0021-9258 KW - DNA, Mitochondrial KW - 0 KW - Recombinant Proteins KW - DNA polymerase gamma KW - EC 2.7.7.- KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Phenotype KW - Frameshift Mutation KW - DNA Repair KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Humans KW - Base Pair Mismatch KW - DNA, Mitochondrial -- metabolism KW - Repetitive Sequences, Nucleic Acid KW - Mutation KW - Mutagenesis KW - Gene Deletion KW - Catalysis KW - DNA-Directed DNA Polymerase -- biosynthesis KW - DNA-Directed DNA Polymerase -- metabolism KW - DNA-Directed DNA Polymerase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72198152?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+fidelity+of+human+DNA+polymerase+gamma+with+and+without+exonucleolytic+proofreading+and+the+p55+accessory+subunit.&rft.au=Longley%2C+M+J%3BNguyen%2C+D%3BKunkel%2C+T+A%3BCopeland%2C+W+C&rft.aulast=Longley&rft.aufirst=M&rft.date=2001-10-19&rft.volume=276&rft.issue=42&rft.spage=38555&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Peroxisome proliferator-activated receptor-alpha regulates lipid homeostasis, but is not associated with obesity: studies with congenic mouse lines. AN - 72197779; 11495927 AB - Considerable controversy exists in determining the role of peroxisome proliferator-activated receptor-alpha (PPARalpha) in obesity. Two purebred congenic strains of PPARalpha-null mice were developed to study the role of this receptor in modulating lipid transport and storage. Weight gain and average body weight in wild-type and PPARalpha-null mice on either an Sv/129 or a C57BL/6N background were not markedly different between genotypes from 3 to 9 months of age. However, gonadal adipose stores were significantly greater in both strains of male and female PPARalpha-null mice. Hepatic accumulation of lipids was greater in both strains and sexes of PPARalpha-null mice compared with wild-type controls. Administration of the peroxisome proliferator WY-14643 caused hepatomegaly, alterations in mRNAs encoding proteins that regulate lipid metabolism, and reduced serum triglycerides in a PPARalpha-dependent mechanism. Constitutive differences in serum cholesterol and triglycerides in PPARalpha-null mice were found between genetic backgrounds. Results from this work establish that PPARalpha is a critical modulator of lipid homeostasis in two congenic mouse lines. This study demonstrates that disruption of the murine gene encoding PPARalpha results in significant alterations in constitutive serum, hepatic, and adipose tissue lipid metabolism. However, an overt, obese phenotype in either of the two congenic strains was not observed. In contrast to earlier published work, this study establishes that PPARalpha is not associated with obesity in mice. JF - The Journal of biological chemistry AU - Akiyama, T E AU - Nicol, C J AU - Fievet, C AU - Staels, B AU - Ward, J M AU - Auwerx, J AU - Lee, S S AU - Gonzalez, F J AU - Peters, J M AD - Laboratory of Metabolism, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/10/19/ PY - 2001 DA - 2001 Oct 19 SP - 39088 EP - 39093 VL - 276 IS - 42 SN - 0021-9258, 0021-9258 KW - Pyrimidines KW - 0 KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - pirinixic acid KW - 86C4MRT55A KW - Cholesterol KW - 97C5T2UQ7J KW - Index Medicus KW - Animals KW - Pyrimidines -- pharmacology KW - Liver -- metabolism KW - Mice KW - Mice, Transgenic KW - Organ Size KW - Body Weight KW - Phenotype KW - Cholesterol -- blood KW - Mice, Congenic KW - Mice, Inbred C57BL KW - Time Factors KW - Female KW - Male KW - Obesity -- metabolism KW - Transcription Factors -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- genetics KW - Transcription Factors -- genetics KW - Lipid Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72197779?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Peroxisome+proliferator-activated+receptor-alpha+regulates+lipid+homeostasis%2C+but+is+not+associated+with+obesity%3A+studies+with+congenic+mouse+lines.&rft.au=Akiyama%2C+T+E%3BNicol%2C+C+J%3BFievet%2C+C%3BStaels%2C+B%3BWard%2C+J+M%3BAuwerx%2C+J%3BLee%2C+S+S%3BGonzalez%2C+F+J%3BPeters%2C+J+M&rft.aulast=Akiyama&rft.aufirst=T&rft.date=2001-10-19&rft.volume=276&rft.issue=42&rft.spage=39088&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estrogen receptor-alpha knockout mice exhibit resistance to the developmental effects of neonatal diethylstilbestrol exposure on the female reproductive tract. AN - 72391109; 11784006 AB - Data indicate that estrogen-dependent and -independent pathways are involved in the teratogenic/carcinogenic syndrome that follows developmental exposure to 17beta-estradiol or diethylstilbestrol (DES), a synthetic estrogen. However, the exact role and extent to which each pathway contributes to the resulting pathology remain unknown. We employed the alphaERKO mouse, which lacks estrogen receptor-alpha (ERalpha), to discern the role of ERalpha and estrogen signaling in mediating the effects of neonatal DES exposure. The alphaERKO provides the potential to expose DES actions mediated by the second known ER, ERbeta, and those that are ER-independent. Wild-type and alphaERKO females were treated with vehicle or DES (2 microg/pup/day for Days 1-5) and terminated after 5 days and 2, 4, 8, 12, and 20 months for biochemical and histomorphological analyses. Assays for uterine expression of the genes Hoxa10, Hoxa11, and Wnt7a shortly after treatment indicated significant decreases in DES-treated wild-type but no effect in the alphaERKO. In contrast, the DES effect on uterine expression of Wnt4 and Wnt5a was preserved in both genotypes, suggesting a developmental role for ERbeta. Adult alphaERKO mice exhibited complete resistance to the chronic effects of neonatal DES exposure exhibited in treated wild-type animals, including atrophy, decreased weight, smooth muscle disorganization, and epithelial squamous metaplasia in the uterus; proliferative lesions of the oviduct; and persistent vaginal cornification. Therefore, the lack of DES effects on gene expression and tissue differentiation in the alphaERKO provides unequivocal evidence of an obligatory role for ERalpha in mediating the detrimental actions of neonatal DES exposure in the murine reproductive tract. Copyright 2001 Academic Press. JF - Developmental biology AU - Couse, J F AU - Dixon, D AU - Yates, M AU - Moore, A B AU - Ma, L AU - Maas, R AU - Korach, K S AD - Receptor Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. korach@niehs.nih.gov Y1 - 2001/10/15/ PY - 2001 DA - 2001 Oct 15 SP - 224 EP - 238 VL - 238 IS - 2 SN - 0012-1606, 0012-1606 KW - DNA, Complementary KW - 0 KW - DNA-Binding Proteins KW - Estrogen Receptor alpha KW - HOXA11 protein, human KW - Homeodomain Proteins KW - Hoxa11 protein, mouse KW - Proto-Oncogene Proteins KW - Receptors, Estrogen KW - WNT4 protein, human KW - WNT5A protein, human KW - Wnt Proteins KW - Wnt-5a Protein KW - Wnt4 Protein KW - Wnt4 protein, mouse KW - Wnt7a protein, mouse KW - Hoxa10 protein, mouse KW - 164384-16-1 KW - Estradiol KW - 4TI98Z838E KW - RNA KW - 63231-63-0 KW - Diethylstilbestrol KW - 731DCA35BT KW - Ribonucleases KW - EC 3.1.- KW - Index Medicus KW - Animals KW - Homeodomain Proteins -- biosynthesis KW - DNA-Binding Proteins -- biosynthesis KW - Ribonucleases -- metabolism KW - Radioimmunoassay KW - Mice, Knockout KW - Phenotype KW - Maternal-Fetal Exchange KW - Proto-Oncogene Proteins -- biosynthesis KW - In Situ Hybridization KW - Estradiol -- blood KW - RNA -- metabolism KW - Heterozygote KW - Proto-Oncogene Proteins -- genetics KW - Time Factors KW - Organ Size -- drug effects KW - Vagina -- drug effects KW - Uterine Neoplasms -- chemically induced KW - Cell Differentiation KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Cloning, Molecular KW - Pregnancy KW - Genotype KW - Oviducts -- drug effects KW - DNA, Complementary -- metabolism KW - Immunohistochemistry KW - Muscle, Smooth -- drug effects KW - Female KW - Prenatal Exposure Delayed Effects KW - Receptors, Estrogen -- genetics KW - Genitalia, Female -- drug effects KW - Diethylstilbestrol -- adverse effects KW - Abnormalities, Drug-Induced -- embryology KW - Abnormalities, Drug-Induced -- etiology KW - Embryonic and Fetal Development -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72391109?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+biology&rft.atitle=Estrogen+receptor-alpha+knockout+mice+exhibit+resistance+to+the+developmental+effects+of+neonatal+diethylstilbestrol+exposure+on+the+female+reproductive+tract.&rft.au=Couse%2C+J+F%3BDixon%2C+D%3BYates%2C+M%3BMoore%2C+A+B%3BMa%2C+L%3BMaas%2C+R%3BKorach%2C+K+S&rft.aulast=Couse&rft.aufirst=J&rft.date=2001-10-15&rft.volume=238&rft.issue=2&rft.spage=224&rft.isbn=&rft.btitle=&rft.title=Developmental+biology&rft.issn=00121606&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-23 N1 - Date created - 2002-01-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - International trends and patterns of primary liver cancer. AN - 72220668; 11668511 AB - Primary liver cancer (PLC) is common in many areas of the developing world, but uncommon in most of the developed world. Some evidence suggests, however, that the global pattern of PLC may be changing. To clarify this issue, we examined incidence rates for PLC over the 15-year time period, 1978-92, in selected cancer registries around the world. With some exceptions, developed countries have experienced PLC increases in incidence whereas developing countries have experienced declines. Although the reasons for the trends are not entirely clear, the increased seroprevalence of HCV in the developed world and the elimination of HBV-cofactors in the developing world are likely to have contributed to the patterns. Further progress against PLC may be seen in the developing world once the HBV-vaccinated segment of the population reaches adulthood. Published 2001 Wiley-Liss, Inc. JF - International journal of cancer AU - McGlynn, K A AU - Tsao, L AU - Hsing, A W AU - Devesa, S S AU - Fraumeni, J F AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. mcglynnkmail.nih.gov Y1 - 2001/10/15/ PY - 2001 DA - 2001 Oct 15 SP - 290 EP - 296 VL - 94 IS - 2 SN - 0020-7136, 0020-7136 KW - Aflatoxin B1 KW - 9N2N2Y55MH KW - Index Medicus KW - Registries KW - Aflatoxin B1 -- adverse effects KW - Humans KW - Hepatitis C, Chronic -- complications KW - Incidence KW - Time Factors KW - Male KW - Female KW - Cholangiocarcinoma -- epidemiology KW - Liver Neoplasms -- epidemiology KW - Carcinoma, Hepatocellular -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72220668?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=International+trends+and+patterns+of+primary+liver+cancer.&rft.au=McGlynn%2C+K+A%3BTsao%2C+L%3BHsing%2C+A+W%3BDevesa%2C+S+S%3BFraumeni%2C+J+F&rft.aulast=McGlynn&rft.aufirst=K&rft.date=2001-10-15&rft.volume=94&rft.issue=2&rft.spage=290&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-11-01 N1 - Date created - 2001-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 2-difluoromethylornithine and dehydroepiandrosterone inhibit mammary tumor progression but not mammary or prostate tumor initiation in C3(1)/SV40 T/t-antigen transgenic mice. AN - 72208669; 11606379 AB - Female transgenic mice that express SV40 T/t antigens under the regulatory control of the rat C3(1) gene spontaneously develop multifocal mammary lesions that predictably evolve into invasive, hormone-independent carcinomas, whereas male mice are prone to develop prostate cancer. Chemopreventive agents were administered to female C3(1)/SV40 large T-antigen mice from 7 to 19 weeks of age, during which time the mammary lesions developed and progressed to invasive carcinomas. No significant differences in the numbers of preinvasive mammary intraepithelial neoplasia lesions (histologically similar to human ductal carcinoma in situ) were observed after 2 or 8 weeks of treatment between mice receiving either vehicle alone, dehydroepiandrosterone (DHEA), or 2-difluoromethylornithine (DFMO). However, a dose-response reduction in invasive carcinoma growth was observed for both DFMO, an inhibitor of ornithine decarboxylase, and DHEA, the primary steroid precursor to both androgens and estrogens in primates. Despite unaltered expression of the transgene, tumor incidence was reduced approximately 20% by DFMO (8000 mg/kg) and 30% by DHEA (4000 mg/kg; P < 0.05). Tumor multiplicity was reduced by approximately 50% by both DFMO and DHEA (P < 0.05). DFMO had a dose-dependent effect on total tumor burden, which was reduced by 25% at low doses (4000 mg/kg) and 70% at high doses (8000 mg/kg). DHEA reduced tumor burden by 50% and 66% at low (2000 mg/kg) and high (4000 mg/kg) doses, respectively. Interestingly, despite its inhibitory effects on tumor development, DHEA caused a dose-dependent increase of serum estradiol levels that we have previously shown to increase mammary tumor formation in this model. No effect on the development of the prostate cancer precursor lesions (prostate intraepithelial neoplasia) was observed when mice were treated with DHEA, DFMO, tocopherol acetate, selenomethionine, or 9-cis-retinoic acid, although the effects on late-stage prostate cancer development were not determined. These results demonstrate that despite the expression of the highly transforming C3(1)/SV40 large T-antigen transgene, this transgenic model can be used to study the effects of chemopreventive agents on mammary cancer progression. The tumor-inhibitory effects of DHEA and DFMO on mammary cancer growth appear to occur after the development of preinvasive lesions, suggesting that these agents inhibit tumor progression but not initiation. JF - Cancer research AU - Green, J E AU - Shibata, M A AU - Shibata, E AU - Moon, R C AU - Anver, M R AU - Kelloff, G AU - Lubet, R AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. jegreen@nih.gov Y1 - 2001/10/15/ PY - 2001 DA - 2001 Oct 15 SP - 7449 EP - 7455 VL - 61 IS - 20 SN - 0008-5472, 0008-5472 KW - Anticarcinogenic Agents KW - 0 KW - Antigens, Polyomavirus Transforming KW - Dehydroepiandrosterone KW - 459AG36T1B KW - Estradiol KW - 4TI98Z838E KW - Eflornithine KW - ZQN1G5V6SR KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Cell Division -- drug effects KW - Disease Progression KW - Precancerous Conditions -- drug therapy KW - Disease Models, Animal KW - Mice KW - Antigens, Polyomavirus Transforming -- genetics KW - Rats KW - Estradiol -- blood KW - Transgenes -- drug effects KW - Antigens, Polyomavirus Transforming -- biosynthesis KW - Precancerous Conditions -- prevention & control KW - Apoptosis -- drug effects KW - Female KW - Male KW - Eflornithine -- toxicity KW - Anticarcinogenic Agents -- toxicity KW - Prostatic Neoplasms -- pathology KW - Anticarcinogenic Agents -- pharmacology KW - Dehydroepiandrosterone -- toxicity KW - Mammary Neoplasms, Experimental -- drug therapy KW - Prostatic Neoplasms -- prevention & control KW - Prostatic Neoplasms -- drug therapy KW - Eflornithine -- pharmacology KW - Mammary Neoplasms, Experimental -- prevention & control KW - Dehydroepiandrosterone -- pharmacology KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72208669?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=2-difluoromethylornithine+and+dehydroepiandrosterone+inhibit+mammary+tumor+progression+but+not+mammary+or+prostate+tumor+initiation+in+C3%281%29%2FSV40+T%2Ft-antigen+transgenic+mice.&rft.au=Green%2C+J+E%3BShibata%2C+M+A%3BShibata%2C+E%3BMoon%2C+R+C%3BAnver%2C+M+R%3BKelloff%2C+G%3BLubet%2C+R&rft.aulast=Green&rft.aufirst=J&rft.date=2001-10-15&rft.volume=61&rft.issue=20&rft.spage=7449&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-10-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional significance of XPD polymorphic variants: attenuated apoptosis in human lymphoblastoid cells with the XPD 312 Asp/Asp genotype. AN - 72205682; 11606376 AB - Recent molecular epidemiological studies have identified polymorphisms in the XPD gene that are associated with increased risk of brain gliomas and head, neck, lung, and skin cancers. However, the functional significance of these polymorphic variants in altering cell processes such as cell cycle checkpoints, DNA repair, and apoptosis is uncertain. We have cloned the XPD variants Lys751Gln, Asp312Asn, and Lys751Gln-Asp312Asn into a pcDNA-3.1-expression vector. Using these constructs, we did not find any detectable difference in either in vitro binding with wild-type p53 or in DNA repair proficiency as measured by host cell reactivation assay. We then genotyped 34 different lymphoblastoid cell lines from six Centre d'Etude du Polymorphisme Humaine (CEPH)/Utah pedigree families and a CEPH/French pedigree family for polymorphisms at codons 751 and 312 and assessed their apoptotic response after either UV or ionized radiation exposure. The lymphoblastoid cell lines with homozygous or heterozygous Asp at codon 312 have similar apoptotic rates, whereas cell lines with homozygous Asn at codon 312 showed a 2.5-fold increased response to UV (P = 0.005; Student's t test). This is the first report known to us of a functional polymorphism in a gene involved in DNA damage-induced apoptosis. However, the presence of Lys or Gln at codon 751 did not influence the apoptotic response to UV. The diminished apoptotic response of cells containing the 312 Asp allele could both allow the survival and selective clonal expansion of carcinogen-damaged cells and be a mechanistic explanation for the increased risk of cancer at diverse tissue sites. JF - Cancer research AU - Seker, H AU - Butkiewicz, D AU - Bowman, E D AU - Rusin, M AU - Hedayati, M AU - Grossman, L AU - Harris, C C AD - Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 2001/10/15/ PY - 2001 DA - 2001 Oct 15 SP - 7430 EP - 7434 VL - 61 IS - 20 SN - 0008-5472, 0008-5472 KW - Codon KW - 0 KW - DNA-Binding Proteins KW - Proteins KW - Transcription Factors KW - Tumor Suppressor Protein p53 KW - DNA Helicases KW - EC 3.6.4.- KW - Xeroderma Pigmentosum Group D Protein KW - EC 3.6.4.12 KW - ERCC2 protein, human KW - EC 5.99.- KW - Index Medicus KW - Lymphocytes -- pathology KW - Ataxia Telangiectasia -- genetics KW - Amino Acid Substitution -- physiology KW - DNA Repair KW - Codon -- genetics KW - Humans KW - Lymphocytes -- physiology KW - Ataxia Telangiectasia -- pathology KW - Tumor Suppressor Protein p53 -- metabolism KW - Protein Binding KW - Cell Line KW - Apoptosis -- genetics KW - Polymorphism, Genetic KW - Apoptosis -- radiation effects KW - Proteins -- metabolism KW - Proteins -- genetics KW - Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72205682?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Functional+significance+of+XPD+polymorphic+variants%3A+attenuated+apoptosis+in+human+lymphoblastoid+cells+with+the+XPD+312+Asp%2FAsp+genotype.&rft.au=Seker%2C+H%3BButkiewicz%2C+D%3BBowman%2C+E+D%3BRusin%2C+M%3BHedayati%2C+M%3BGrossman%2C+L%3BHarris%2C+C+C&rft.aulast=Seker&rft.aufirst=H&rft.date=2001-10-15&rft.volume=61&rft.issue=20&rft.spage=7430&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-10-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Indomethacin-induced radiosensitization and inhibition of ionizing radiation-induced NF-kappaB activation in HeLa cells occur via a mechanism involving p38 MAP kinase. AN - 72205293; 11606413 AB - Although ionizing radiation (IR) activates multiple cellular factors that vary depending on dose and tissue specificity, the activation of NF-kappaB appears to be a well-conserved response in tumor cells exposed to IR. Recently, it also has been demonstrated that nonsteroidal anti-inflammatory agents inhibit tumor necrosis factor and interleukin-1-induced NF-kappaB activation and act as radiosensitizing agents. These observations reinforce the growing notion that NF-kappaB may be a protective cellular factor responding to the cytotoxicity of IR and other damaging stimuli. As such, we addressed the idea and mechanism that NF-kappaB is a downstream target of the nonsteroidal anti-inflammatory agent indomethacin and is involved in the process of radiosensitization. In this study, we report that indomethacin inhibited IR-induced activation of NF-kappaB and sensitized HeLa cells to IR-induced cytotoxicity at similar concentrations. Pretreatment of HeLa cells with SB 203580, a pyridinyl imidazole compound that specifically inhibits p38 mitogen-activated protein kinase (MAPK), abrogated the ability of indomethacin to inhibit IR-induced activation of NF-kappaB and diminished the indomethacin radiosensitizing effect. In addition, the transient genetic activation of p38(MAPK) inhibited IR induction of NF-kappaB gene expression in the absence of indomethacin. Finally, permanently transfected cell lines genetically unable to activate NF-kappaB, because of expression of a dominant negative I-kappaBalpha gene, demonstrated increased sensitivity to IR-induced cytotoxicity. Taken together, these results suggest that p38 MAPK is a target involved in indomethacin-induced radiosensitization and that NF-kappaB may be one downstream target in this process. JF - Cancer research AU - Bradbury, C M AU - Markovina, S AU - Wei, S J AU - Rene, L M AU - Zoberi, I AU - Horikoshi, N AU - Gius, D AD - Radiation Oncology Branch, Radiation Oncology Sciences Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 2001/10/15/ PY - 2001 DA - 2001 Oct 15 SP - 7689 EP - 7696 VL - 61 IS - 20 SN - 0008-5472, 0008-5472 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Enzyme Inhibitors KW - I-kappa B Proteins KW - Imidazoles KW - NF-kappa B KW - Pyridines KW - Sulindac KW - 184SNS8VUH KW - DNA KW - 9007-49-2 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - SB 203580 KW - OU13V1EYWQ KW - Sodium Salicylate KW - WIQ1H85SYP KW - Indomethacin KW - XXE1CET956 KW - Index Medicus KW - Drug Interactions KW - Imidazoles -- pharmacology KW - Cell Nucleus -- metabolism KW - HeLa Cells KW - I-kappa B Proteins -- metabolism KW - DNA -- metabolism KW - Humans KW - Sodium Salicylate -- pharmacology KW - Gene Expression Regulation, Neoplastic KW - Transfection KW - Enzyme Activation -- radiation effects KW - Sulindac -- pharmacology KW - Enzyme Activation -- drug effects KW - Enzyme Inhibitors -- pharmacology KW - Cell Survival -- radiation effects KW - I-kappa B Proteins -- genetics KW - I-kappa B Proteins -- biosynthesis KW - Pyridines -- pharmacology KW - Mitogen-Activated Protein Kinases -- antagonists & inhibitors KW - Radiation Tolerance -- drug effects KW - Mitogen-Activated Protein Kinases -- physiology KW - NF-kappa B -- genetics KW - NF-kappa B -- metabolism KW - NF-kappa B -- antagonists & inhibitors KW - Indomethacin -- pharmacology KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72205293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Indomethacin-induced+radiosensitization+and+inhibition+of+ionizing+radiation-induced+NF-kappaB+activation+in+HeLa+cells+occur+via+a+mechanism+involving+p38+MAP+kinase.&rft.au=Bradbury%2C+C+M%3BMarkovina%2C+S%3BWei%2C+S+J%3BRene%2C+L+M%3BZoberi%2C+I%3BHorikoshi%2C+N%3BGius%2C+D&rft.aulast=Bradbury&rft.aufirst=C&rft.date=2001-10-15&rft.volume=61&rft.issue=20&rft.spage=7689&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-10-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Case-cohort analysis of agricultural pesticide applications near maternal residence and selected causes of fetal death. AN - 72179731; 11590082 AB - The potential association between fetal death and residential proximity to agricultural pesticide applications was examined in 10 California counties for 1984. A case-cohort analysis utilized 319 cases of selected causes of fetal death other than congenital anomalies and 611 non-cases. A statewide database of all applications of restricted pesticides was linked to maternal address; residential proximity within 1 mile (1.6 km) provided a surrogate for daily exposure. Pesticides were grouped by chemical class and mechanism of acetylcholinesterase inhibition. Multivariate proportional hazards models using time-dependent exposure variables were fit for each pesticide grouping. Overall, pesticides showed no strong association with fetal death. Slightly elevated risks were observed for women who resided near applications of halogenated hydrocarbons, carbamates, estrogenic pesticides, and carbamate acetylcholinesterase inhibitors during the second trimester, with hazard ratios of 1.3 (95% confidence interval (CI): 1.0, 1.8), 1.3 (95% CI: 1.0, 1.8), 1.4 (95% CI: 0.8, 2.5), and 1.3 (95% CI: 1.0, 1.8), respectively. In a month-by-month analysis, elevated risks were observed when exposure occurred during gestational months 3 and 4 for carbamates and carbamate inhibitors and during months 4 and 5 for halogenated hydrocarbons. Since previous studies have relied on personal recall of exposure, major strengths of this study were the objective source for environmental pesticide exposure assessment and the use of data on the timing of exposure. JF - American journal of epidemiology AU - Bell, E M AU - Hertz-Picciotto, I AU - Beaumont, J J AD - Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, USA. belle@mail.nih.gov Y1 - 2001/10/15/ PY - 2001 DA - 2001 Oct 15 SP - 702 EP - 710 VL - 154 IS - 8 SN - 0002-9262, 0002-9262 KW - Carbamates KW - 0 KW - Cholinesterase Inhibitors KW - Estradiol Congeners KW - Hydrocarbons, Halogenated KW - Insecticides KW - Pesticides KW - Index Medicus KW - Pregnancy Trimester, Second KW - Insecticides -- poisoning KW - Cholinesterase Inhibitors -- poisoning KW - Humans KW - Hydrocarbons, Halogenated -- poisoning KW - Environmental Exposure KW - Estradiol Congeners -- poisoning KW - California -- epidemiology KW - Female KW - Pregnancy KW - Pesticides -- poisoning KW - Fetal Death -- epidemiology KW - Residence Characteristics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72179731?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+epidemiology&rft.atitle=Case-cohort+analysis+of+agricultural+pesticide+applications+near+maternal+residence+and+selected+causes+of+fetal+death.&rft.au=Bell%2C+E+M%3BHertz-Picciotto%2C+I%3BBeaumont%2C+J+J&rft.aulast=Bell&rft.aufirst=E&rft.date=2001-10-15&rft.volume=154&rft.issue=8&rft.spage=702&rft.isbn=&rft.btitle=&rft.title=American+journal+of+epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-10-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Epidemiol. 2002 Apr 15;155(8):779-80; author reply 780 [11943699] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Physiologically Based Pharmacokinetic Model for Inhalation and Intravenous Administration of Naphthalene in Rats and Mice AN - 18125360; 5218398 AB - A diffusion limited physiologically based pharmacokinetic model for rats and mice was developed to characterize the absorption, distribution, metabolism, and elimination of naphthalene after inhalation exposure. This model includes compartments for arterial and venous blood, lung, liver, kidney, fat, and other organs. Primary sites for naphthalene metabolism to naphthalene oxide are the lung and the liver. The data used to create this model were generated from National Toxicology Program inhalation and iv studies on naphthalene and consisted of blood time-course data of the parent compound in both rats and mice. To examine the basis for possible interspecies differences in response to naphthalene, the model was extended to describe the distribution and metabolism of naphthalene oxide and the depletion and resynthesis of glutathione. After testing several alternative models, the one presented in this paper shows the best fit to the data with the fewest assumptions possible. The model indicates that tissue dosimetry of the parent compound alone does not explain why this chemical was carcinogenic to the female mouse lung but not to the rat lung. The species difference may be due to a combination of higher levels of naphthalene oxide in the mouse lung and a greater susceptibility of the mouse lung to epoxide-induced carcinogenesis. However, conclusions regarding which metabolite(s) may be responsible for the lung toxicity could not be reached. JF - Toxicology and Applied Pharmacology AU - Willems, BA AU - Melnick, R L AU - Kohn, M C AU - Portier, C J AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709 Y1 - 2001/10/15/ PY - 2001 DA - 2001 Oct 15 SP - 81 EP - 91 PB - Academic Press VL - 176 IS - 2 SN - 0041-008X, 0041-008X KW - intravenous administration KW - mice KW - rats KW - pharmacokinetics KW - naphthalene oxide KW - Toxicology Abstracts KW - Inhalation KW - Mathematical models KW - Lung KW - Liver KW - Naphthalene KW - X 24153:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18125360?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=A+Physiologically+Based+Pharmacokinetic+Model+for+Inhalation+and+Intravenous+Administration+of+Naphthalene+in+Rats+and+Mice&rft.au=Willems%2C+BA%3BMelnick%2C+R+L%3BKohn%2C+M+C%3BPortier%2C+C+J&rft.aulast=Willems&rft.aufirst=BA&rft.date=2001-10-15&rft.volume=176&rft.issue=2&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1006%2Ftaap.2001.9269 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Lung; Liver; Mathematical models; Inhalation; Naphthalene DO - http://dx.doi.org/10.1006/taap.2001.9269 ER - TY - JOUR T1 - How carcinogens (or telomere dysfunction) induce genetic instability: associated-selection model. AN - 72205880; 11602239 AB - Carcinogens induce carcinogen-specific genetic instability (defects in DNA repair). According to the 'direct-selection' model, defects in DNA repair per se provide an immediate growth advantage. According to the 'associated-selection' model, carcinogens merely select for cells with adaptive mutations. Like any mutations, adaptive mutations occur predominantly in genetically unstable cells. The 'associated-selection' model predicts that carcinogen-driven selection minimizes cytotoxic but maximizes mutagenic effects of carcinogens. A purely mutagenic (neither cytotoxic, nor cytostatic) environment will favor effective DNA repair, whereas any growth-limiting conditions (telomerase deficiency, anticancer drugs) will select for genetically unstable cells. Genetic instability is a postmark of selective pressure rather than a hallmark of cancer per se. Once selected, genetic instability facilitates the development of resistance to any other growth-limiting conditions. As an example, a putative link between prior exposure to carcinogens and the ability to develop a telomerase-independent growth is discussed. JF - FEBS letters AU - Blagosklonny, M V AD - Medicine Branch, National Cancer Institute, NIH, Bldg. 10, R 12 N 226, Bethesda, MD 20892, USA. mikhailb@box-m.nih.gov Y1 - 2001/10/12/ PY - 2001 DA - 2001 Oct 12 SP - 169 EP - 172 VL - 506 IS - 3 SN - 0014-5793, 0014-5793 KW - Carcinogens KW - 0 KW - Index Medicus KW - DNA Repair KW - Carcinogens -- pharmacology KW - Telomere KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72205880?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEBS+letters&rft.atitle=How+carcinogens+%28or+telomere+dysfunction%29+induce+genetic+instability%3A+associated-selection+model.&rft.au=Blagosklonny%2C+M+V&rft.aulast=Blagosklonny&rft.aufirst=M&rft.date=2001-10-12&rft.volume=506&rft.issue=3&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=FEBS+letters&rft.issn=00145793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Agonist-induced signaling, desensitization, and internalization of a phosphorylation-deficient AT1A angiotensin receptor. AN - 72177448; 11495923 AB - An analysis of the functional role of a diacidic motif (Asp236-Asp237) in the third intracellular loop of the AT1A angiotensin II (Ang II) receptor (AT1-R) revealed that substitution of both amino acids with alanine (DD-AA) or asparagine (DD-NN) residues diminished Ang II-induced receptor phosphorylation in COS-7 cells. However, Ang II-stimulated inositol phosphate production, mitogen-activated protein kinase, and AT1 receptor desensitization and internalization were not significantly impaired. Overexpression of dominant negative G protein-coupled receptor kinase 2 (GRK2)K220M decreased agonist-induced receptor phosphorylation by approximately 40%, but did not further reduce the impaired phosphorylation of DD-AA and DD-NN receptors. Inhibition of protein kinase C by bisindolylmaleimide reduced the phosphorylation of both the wild-type and the DD mutant receptors by approximately 30%. The inhibitory effects of GRK2K220M expression and protein kinase C inhibition by bisindolylmaleimide on agonist-induced phosphorylation were additive for the wild-type AT1-R, but not for the DD mutant receptor. Agonist-induced internalization of the wild-type and DD mutant receptors was similar and was unaltered by coexpression of GRK2K220M. These findings demonstrate that an acidic motif at position 236/237 in the third intracellular loop of the AT1-R is required for optimal Ang II-induced phosphorylation of its carboxyl-terminal tail by GRKs. Furthermore, the properties of the DD mutant receptor suggest that not only Ang II-induced signaling, but also receptor desensitization and internalization, are independent of agonist-induced GRK-mediated phosphorylation of the AT1 receptor. JF - The Journal of biological chemistry AU - Olivares-Reyes, J A AU - Smith, R D AU - Hunyady, L AU - Shah, B H AU - Catt, K J AD - Endocrinology and Reproduction Research Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/10/12/ PY - 2001 DA - 2001 Oct 12 SP - 37761 EP - 37768 VL - 276 IS - 41 SN - 0021-9258, 0021-9258 KW - Indoles KW - 0 KW - Inositol Phosphates KW - Maleimides KW - Receptors, Angiotensin KW - Angiotensin I KW - 9041-90-1 KW - bisindolylmaleimide KW - MBK3OO5K8T KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - Phosphorylation KW - COS Cells KW - Amino Acid Motifs KW - Inositol Phosphates -- metabolism KW - Humans KW - Indoles -- pharmacology KW - Amino Acid Sequence KW - Cell Line KW - Maleimides -- pharmacology KW - Endocytosis KW - Receptors, Angiotensin -- chemistry KW - Receptors, Angiotensin -- agonists KW - Receptors, Angiotensin -- metabolism KW - Signal Transduction KW - Receptors, Angiotensin -- genetics KW - Angiotensin I -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72177448?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Agonist-induced+signaling%2C+desensitization%2C+and+internalization+of+a+phosphorylation-deficient+AT1A+angiotensin+receptor.&rft.au=Olivares-Reyes%2C+J+A%3BSmith%2C+R+D%3BHunyady%2C+L%3BShah%2C+B+H%3BCatt%2C+K+J&rft.aulast=Olivares-Reyes&rft.aufirst=J&rft.date=2001-10-12&rft.volume=276&rft.issue=41&rft.spage=37761&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anatomy of Escherichia coli Ribosome Binding Sites AN - 18123789; 5218263 AB - During translational initiation in prokaryotes, the 3' end of the 16S rRNA binds to a region just upstream of the initiation codon. The relationship between this Shine-Dalgarno (SD) region and the binding of ribosomes to translation start-points has been well studied, but a unified mathematical connection between the SD, the initiation codon and the spacing between them has been lacking. Using information theory, we constructed a model that treats these three components uniformly by assigning to the SD and the initiation region (IR) conservations in bits of information, and by assigning to the spacing an uncertainty, also in bits. To build the model, we first aligned the SD region by maximizing the information content there. The ease of this process confirmed the existence of the SD pattern within a set of 4122 reviewed and revised Escherichia coli gene starts. This large data set allowed us to show graphically, by sequence logos, that the spacing between the SD and the initiation region affects both the SD site conservation and its pattern. We used the aligned SD, the spacing, and the initiation region to model ribosome binding and to identify gene starts that do not conform to the ribosome binding site model. A total of 569 experimentally proven starts are more conserved (have higher information content) than the full set of revised starts, which probably reflects an experimental bias against the detection of gene products that have inefficient ribosome binding sites. Models were refined cyclically by removing non-conforming weak sites. After this procedure, models derived from either the original or the revised gene start annotation were similar. Therefore, this information theory-based technique provides a method for easily constructing biologically sensible ribosome binding site models. Such models should be useful for refining gene-start predictions of any sequenced bacterial genome. Copyright 2001 Academic Press JF - Journal of Molecular Biology AU - Shultzaberger, R K AU - Bucheimer, R E AU - Rudd, KE AU - Schneider, T D AD - National Cancer Institute at Frederick, Laboratory of Experimental and Computational Biology, Frederick, MD, 21702-1201, USA Y1 - 2001/10/12/ PY - 2001 DA - 2001 Oct 12 SP - 215 EP - 228 PB - Academic Press VL - 313 IS - 1 SN - 0022-2836, 0022-2836 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Genomes KW - Mathematical models KW - Escherichia coli KW - Transcription KW - Ribosomes KW - rRNA 16S KW - Models KW - Transcription initiation KW - N 14640:Structure & sequence KW - J 02726:RNA and ribosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18123789?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Anatomy+of+Escherichia+coli+Ribosome+Binding+Sites&rft.au=Shultzaberger%2C+R+K%3BBucheimer%2C+R+E%3BRudd%2C+KE%3BSchneider%2C+T+D&rft.aulast=Shultzaberger&rft.aufirst=R&rft.date=2001-10-12&rft.volume=313&rft.issue=1&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1006%2Fjmbi.2001.5040 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Genomes; Mathematical models; rRNA 16S; Ribosomes; Transcription initiation; Models; Transcription DO - http://dx.doi.org/10.1006/jmbi.2001.5040 ER - TY - JOUR T1 - Serotonin, testosterone and alcohol in the etiology of domestic violence. AN - 72203339; 11600187 AB - In a previous study we administered the panicogenic agent sodium lactate to a select group of perpetrators of domestic violence and comparison groups. Results of that study showed that perpetrators exhibited exaggerated lactate-induced fear, panic and rage. In this current study, we compared the cerebral spinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and testosterone obtained from perpetrators of domestic violence and a group of healthy comparison subjects. All subjects were assessed for DSM-III-R diagnoses. Perpetrators with alcohol dependence (DV-ALC) (n=13), perpetrators without alcohol dependence (DV-NALC) (n=10) and healthy comparison subjects (HCS) (n=20) were clinically assessed using the Spielberger Trait Anxiety, Brown-Goodwin Aggression Scale, Buss Durkee Hostility Inventory and Straus Conflict Tactics. Following an overnight fast and bed rest, subjects received a lumbar puncture to obtain CSF concentrations of 5-HIAA and testosterone. Perpetrators scored significantly higher on measures of aggression than HCS. DV-NALC had significantly lower concentrations of CSF 5-HIAA and higher Straus Conflict Tactics (CT) physical violence scores than DV-ALC and HCS. DV-ALC had significantly higher concentrations of CSF testosterone than DV-NALC. DV-ALC also had significantly higher Straus CT physical violence scores than HCS. DV-NALC and DV-ALC differed on 5-HIAA concentrations, testosterone concentrations, Straus CT physical violence scores and alcohol dependence. These results suggest that DV-NALC and DV-ALC groups could have different biological mechanisms mediating domestic violence. JF - Psychiatry research AU - George, D T AU - Umhau, J C AU - Phillips, M J AU - Emmela, D AU - Ragan, P W AU - Shoaf, S E AU - Rawlings, R R AD - Laboratory of Clinical Studies, DICBR, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA. tedg@niaaa.nih.gov Y1 - 2001/10/10/ PY - 2001 DA - 2001 Oct 10 SP - 27 EP - 37 VL - 104 IS - 1 SN - 0165-1781, 0165-1781 KW - Serotonin KW - 333DO1RDJY KW - Testosterone KW - 3XMK78S47O KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Index Medicus KW - Rage -- physiology KW - Conditioning, Classical -- physiology KW - Aggression -- psychology KW - Risk Factors KW - Humans KW - Adult KW - Middle Aged KW - Fear -- physiology KW - Male KW - Aggression -- physiology KW - Serotonin -- physiology KW - Alcoholism -- cerebrospinal fluid KW - Testosterone -- cerebrospinal fluid KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid KW - Spouse Abuse -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72203339?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychiatry+research&rft.atitle=Serotonin%2C+testosterone+and+alcohol+in+the+etiology+of+domestic+violence.&rft.au=George%2C+D+T%3BUmhau%2C+J+C%3BPhillips%2C+M+J%3BEmmela%2C+D%3BRagan%2C+P+W%3BShoaf%2C+S+E%3BRawlings%2C+R+R&rft.aulast=George&rft.aufirst=D&rft.date=2001-10-10&rft.volume=104&rft.issue=1&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Psychiatry+research&rft.issn=01651781&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-22 N1 - Date created - 2001-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dynamic copy choice: steady state between murine leukemia virus polymerase and polymerase-dependent RNase H activity determines frequency of in vivo template switching. AN - 72184215; 11593039 AB - We recently proposed a dynamic copy-choice model for retroviral recombination in which a steady state between the rates of polymerization and RNA degradation determines the frequency of reverse transcriptase (RT) template switching. The relative contributions of polymerase-dependent and polymerase-independent RNase H activities during reverse transcription and template switching in vivo have not been determined. We developed an in vivo trans-complementation assay in which direct repeat deletion through template switching reconstitutes a functional green fluorescent protein gene in a retroviral vector. Complementation in trans between murine leukemia virus Gag-Pol proteins lacking polymerase and RNase H activities restored viral replication. Because only polymerase-independent RNase H activity is present in this cell line, the relative roles of polymerase-dependent and -independent RNase H activities in template switching could be determined. We also analyzed double mutants possessing polymerase and RNase H mutations that increased and decreased template switching, respectively. The double mutants exhibited low template switching frequency, indicating that the RNase H mutations were dominant. Trans-complementation of the double mutants with polymerase-independent RNase H did not restore the high template switching frequency, indicating that polymerase-dependent RNase H activity was essential for the increased frequency of template switching. Additionally, trans-complementation of RNase H mutants in the presence and absence of hydroxyurea, which slows the rate of reverse transcription, showed that hydroxyurea increased template switching only when polymerase-dependent RNase H activity was present. This is, to our knowledge, the first demonstration of polymerase-dependent RNase H activity in vivo. These results provide strong evidence for a dynamic association between the rates of DNA polymerization and polymerase-dependent RNase H activity, which determines the frequency of in vivo template switching. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Hwang, C K AU - Svarovskaia, E S AU - Pathak, V K AD - HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 2001/10/09/ PY - 2001 DA - 2001 Oct 09 SP - 12209 EP - 12214 VL - 98 IS - 21 SN - 0027-8424, 0027-8424 KW - RNA-Directed DNA Polymerase KW - EC 2.7.7.49 KW - Ribonuclease H KW - EC 3.1.26.4 KW - Hydroxyurea KW - X6Q56QN5QC KW - Index Medicus KW - Animals KW - Mice KW - Hydroxyurea -- pharmacology KW - Templates, Genetic KW - Mutagenesis KW - Leukemia Virus, Murine -- genetics KW - Leukemia Virus, Murine -- drug effects KW - Ribonuclease H -- genetics KW - RNA-Directed DNA Polymerase -- metabolism KW - Ribonuclease H -- metabolism KW - RNA-Directed DNA Polymerase -- genetics KW - Leukemia Virus, Murine -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72184215?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Dynamic+copy+choice%3A+steady+state+between+murine+leukemia+virus+polymerase+and+polymerase-dependent+RNase+H+activity+determines+frequency+of+in+vivo+template+switching.&rft.au=Hwang%2C+C+K%3BSvarovskaia%2C+E+S%3BPathak%2C+V+K&rft.aulast=Hwang&rft.aufirst=C&rft.date=2001-10-09&rft.volume=98&rft.issue=21&rft.spage=12209&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-28 N1 - Date created - 2001-10-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochemistry. 1993 Jun 1;32(21):5508-17 [7684924] Science. 1993 Jan 8;259(5092):234-8 [8421784] Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):6900-3 [7688465] EMBO J. 1993 Nov;12(11):4433-8 [7693456] J Virol. 1995 Dec;69(12):7991-8000 [7494312] J Biol Chem. 1996 Jan 26;271(4):2063-70 [8567660] Nucleic Acids Res. 1996 May 1;24(9):1719-26 [8649991] J Virol. 1997 Aug;71(8):6028-36 [9223494] J Virol. 1998 Feb;72(2):1195-202 [9445018] J Virol. 1998 Jun;72(6):5198-206 [9573292] J Gen Virol. 1998 Jun;79 ( Pt 6):1337-45 [9634073] J Virol. 1998 Oct;72(10):7941-9 [9733832] J Virol. 1999 Jul;73(7):5912-7 [10364343] J Virol. 1999 Oct;73(10):7923-32 [10482539] J Virol. 1999 Oct;73(10):8441-7 [10482596] J Biol Chem. 2000 Dec 1;275(48):37664-71 [10956669] Virology. 1971 Dec;46(3):947-52 [4332983] J Biol Chem. 1999 Dec 3;274(49):34547-55 [10574917] J Biol Chem. 2000 Apr 28;275(17):13061-70 [10777611] J Virol. 2000 Aug;74(15):7171-8 [10888659] J Virol. 2000 Oct;74(20):9629-36 [11000235] J Virol. 2000 Nov;74(22):10349-58 [11044079] Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):11978-83 [11035788] J Gen Virol. 1979 Jan;42(1):1-26 [215703] Gene. 1983 Nov;25(2-3):179-88 [6319235] Proc Natl Acad Sci U S A. 1987 Dec;84(23):8553-7 [2825195] Nucleic Acids Res. 1988 Jan 11;16(1):265-77 [2448747] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1777-81 [2450347] Cell. 1988 Jul 1;54(1):57-63 [2838179] J Virol. 1988 Aug;62(8):2636-43 [2839690] J Virol. 1988 Nov;62(11):4376-80 [2459414] J Virol. 1989 Mar;63(3):1455-9 [2915387] J Biol Chem. 1989 Nov 5;264(31):18808-17 [2478553] Proc Natl Acad Sci U S A. 1990 Feb;87(4):1556-60 [2304918] AIDS. 1989 Dec;3(12):777-84 [2483618] Virology. 1990 Apr;175(2):575-80 [1691564] Proc Natl Acad Sci U S A. 1990 Aug;87(16):6024-8 [2166940] J Virol. 1991 Jan;65(1):162-9 [1845882] J Biol Chem. 1991 Jan 5;266(1):406-12 [1702425] Annu Rev Genet. 1990;24:409-45 [1708222] J Biol Chem. 1991 Apr 25;266(12):7423-31 [1708386] Trends Genet. 1991 Mar;7(3):71-4 [2031285] J Mol Biol. 1991 Aug 5;220(3):801-18 [1714505] Nature. 1991 Dec 12;354(6353):453-9 [1721107] J Biol Chem. 1991 Dec 25;266(36):24295-301 [1722202] Science. 1992 Jun 26;256(5065):1783-90 [1377403] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10763-7 [1279694] Science. 1992 Nov 13;258(5085):1112-8 [1279806] J Biol Chem. 1992 Dec 25;267(36):25988-97 [1281479] Biochemistry. 1993 Jul 13;32(27):6908-15 [7687463] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Secreted MD-2 is a large polymeric protein that efficiently confers lipopolysaccharide sensitivity to Toll-like receptor 4 AN - 18183934; 5185562 AB - Toll-like receptor 4 (TLR4), the principal signaling receptor for lipopolysaccharide (LPS) in mammals, requires the binding of MD-2 to its extracellular domain for maximal responsiveness. MD-2 contains a leader sequence but lacks a transmembrane domain, and we asked whether it is secreted into the medium as an active protein. As a source of secreted MD-2 (sMD-2), we used culture supernatants from cells stably transduced with epitope-tagged human MD-2. We show that sMD-2 exists as a heterogeneous collection of large disulfide-linked oligomers formed from stable dimeric subunits and that concentrations of sMD-2 as low as 50 pM enhance the responsiveness of TLR4 reporter cells to LPS. An MD-2-like activity is also released by monocyte-derived dendritic cells from normal donors. When coexpressed, TLR4 indiscriminately associates in the endoplasmic reticulum/cis Golgi with different-sized oligomers of MD-2, and excess MD-2 is secreted into the medium. We conclude that normal and transfected cells secrete a soluble form of MD-2 that binds with high affinity to TLR4 and that could play a role in regulating responses to LPS and other pathogen-derived substances in vivo. JF - Proceedings of the National Academy of Sciences, USA AU - Visintin, A AU - Mazzoni, A AU - Spitzer, JA AU - Segal, D M AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1360, USA, dave_segal@nih.gov Y1 - 2001/10/09/ PY - 2001 DA - 2001 Oct 09 SP - 12156 EP - 12161 VL - 98 IS - 21 SN - 0027-8424, 0027-8424 KW - man KW - MD-2 protein KW - TLR4 protein KW - Toll-like receptors KW - lipopolysaccharides KW - Immunology Abstracts; Toxicology Abstracts KW - Endotoxins KW - Dendritic cells KW - Receptors KW - Lipopolysaccharides KW - Cell culture KW - Monocytes KW - Supernatants KW - X 24171:Microbial KW - F 06767:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18183934?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Secreted+MD-2+is+a+large+polymeric+protein+that+efficiently+confers+lipopolysaccharide+sensitivity+to+Toll-like+receptor+4&rft.au=Visintin%2C+A%3BMazzoni%2C+A%3BSpitzer%2C+JA%3BSegal%2C+D+M&rft.aulast=Visintin&rft.aufirst=A&rft.date=2001-10-09&rft.volume=98&rft.issue=21&rft.spage=12156&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.211445098 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Dendritic cells; Monocytes; Supernatants; Cell culture; Endotoxins; Lipopolysaccharides; Receptors DO - http://dx.doi.org/10.1073/pnas.211445098 ER - TY - JOUR T1 - Multidimensional epistasis and the disadvantage of sex AN - 18106630; 5185550 AB - Sex is thought to facilitate accumulation of initially rare beneficial mutations by allowing simultaneous allele replacements at many loci. However, this advantage of sex depends on a restrictive assumption that the fitness of a genotype is determined by fitness potential, a single intermediate variable to which all loci contribute additively, so that new alleles can accumulate in any order. Individual-based simulations of sexual and asexual populations reveal that under generic selection, sex often retards adaptive evolution. When new alleles are beneficial only if they accumulate in a prescribed order, a sexual population may evolve two or more times slower than an asexual population because only asexual reproduction allows some overlap of successive allele replacements. Many other fitness surfaces lead to an even greater disadvantage of sex. Thus, either sex exists in spite of its impact on the rate of adaptive allele replacements, or natural fitness surfaces have rather specific properties, at least at the scale of intrapopulation genetic variability. JF - Proceedings of the National Academy of Sciences, USA AU - Kondrashov, F A AU - Kondrashov, A S AD - National Center for Biotechnology Information, National Institutes of Health, Building 38A, Bethesda, MD 20892, USA, fkondras@ncbi.nlm.nih.gov Y1 - 2001/10/09/ PY - 2001 DA - 2001 Oct 09 SP - 12089 EP - 12092 VL - 98 IS - 21 SN - 0027-8424, 0027-8424 KW - Ecology Abstracts; Genetics Abstracts KW - Fitness KW - Genetic diversity KW - Genotypes KW - Asexual reproduction KW - Alleles KW - Epistasis KW - Mutation KW - Selection KW - G 07270:Ecological genetics KW - D 04615:Ecology studies - general UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18106630?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Multidimensional+epistasis+and+the+disadvantage+of+sex&rft.au=Kondrashov%2C+F+A%3BKondrashov%2C+A+S&rft.aulast=Kondrashov&rft.aufirst=F&rft.date=2001-10-09&rft.volume=98&rft.issue=21&rft.spage=12089&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.211214298 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Alleles; Asexual reproduction; Genetic diversity; Mutation; Selection; Epistasis; Genotypes; Fitness DO - http://dx.doi.org/10.1073/pnas.211214298 ER - TY - JOUR T1 - Crystal Structure of a Y-Family DNA Polymerase in Action: A Mechanism for Error-Prone and Lesion-Bypass Replication AN - 18130623; 5223174 AB - Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) is a DinB homolog that belongs to the recently described Y-family of DNA polymerases, which are best characterized by their low-fidelity synthesis on undamaged DNA templates and propensity to traverse normally replication-blocking lesions. Crystal structures of Dpo4 in ternary complexes with DNA and an incoming nucleotide, either correct or incorrect, have been solved at 1.7 Angstrom and 2.1 Angstrom resolution, respectively. Despite a conserved active site and a hand-like configuration similar to all known polymerases, Dpo4 makes limited and nonspecific contacts with the replicating base pair, thus relaxing base selection. Dpo4 is also captured in the crystal translocating two template bases to the active site at once, suggesting a possible mechanism for bypassing thymine dimers. JF - Cell AU - Ling, H AU - Boudsocq, F AU - Woodgate, R AU - Yang, W AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Section on DNA Replication, Repair, and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA, wei.yang@nih.gov Y1 - 2001/10/05/ PY - 2001 DA - 2001 Oct 05 SP - 91 EP - 102 VL - 107 IS - 1 SN - 0092-8674, 0092-8674 KW - Dpo4 protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Sulfolobus solfataricus KW - Replication KW - DNA-directed DNA polymerase KW - Crystal structure KW - Active sites KW - J 02725:DNA KW - N 14722:DNA polymerases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18130623?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell&rft.atitle=Crystal+Structure+of+a+Y-Family+DNA+Polymerase+in+Action%3A+A+Mechanism+for+Error-Prone+and+Lesion-Bypass+Replication&rft.au=Ling%2C+H%3BBoudsocq%2C+F%3BWoodgate%2C+R%3BYang%2C+W&rft.aulast=Ling&rft.aufirst=H&rft.date=2001-10-05&rft.volume=107&rft.issue=1&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Cell&rft.issn=00928674&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Sulfolobus solfataricus; Replication; Crystal structure; Active sites; DNA-directed DNA polymerase ER - TY - JOUR T1 - Metabolism of Sucrose and Its Five Linkage-isomeric alpha -D-Glucosyl-D-fructoses by Klebsiella pneumoniae: Participation and Properties of Sucrose-6-Phosphate Hydrolase and Phospho- alpha -glucosidase AN - 18113629; 5183119 AB - Klebsiella pneumoniae is presently unique among bacterial species in its ability to metabolize not only sucrose but also its five linkage-isomeric alpha -D-glucosyl-D-fructoses: trehalulose, turanose, maltulose, leucrose, and palatinose. Growth on the isomeric compounds induced a protein of molecular mass ~ 50 kDa that was not present in sucrose-grown cells and which we have identified as an NAD super(+) and metal ion-dependent 6-phospho- alpha -glucosidase (AglB). The aglB gene has been cloned and sequenced, and AglB (M sub(r) = 49,256) has been purified from a high expression system using the chromogenic p- nitrophenyl alpha -glucopyranoside 6-phosphate as substrate. Phospho- alpha -glucosidase catalyzed the hydrolysis of a wide variety of 6-phospho- alpha -glucosides including maltose-6'-phosphate, maltitol-6-phosphate, isomaltose-6'-phosphate, and all five 6'-phosphorylated isomers of sucrose (K sub(m) similar to 1-5 mM) yet did not hydrolyze sucrose-6-phosphate. By contrast, purified sucrose-6- phosphate hydrolase (M sub(r) similar to 53,000) hydrolyzed only sucrose-6- phosphate (K sub(im) similar to 80 mu M). Differences in molecular shape and lipophilicity potential between sucrose and its isomers may be important determinants for substrate discrimination by the two phosphoglucosyl hydrolases. Phospho- alpha -glucosidase and sucrose-6-phosphate hydrolase exhibit no significant homology, and by sequence-based alignment, the two enzymes are assigned to Families 4 and 32, respectively, of the glycosyl hydrolase superfamily. The phospho- alpha -glucosidase gene (aglB) lies adjacent to a second gene (aglA), which encodes an EII(CB) component of the phosphoenolpyruvate-dependent sugar:phosphotransferase system. We suggest that the products of the two genes facilitate the phosphorylative translocation and subsequent hydrolysis of the five alpha -D-glucosyl-D-fructoses by K. pneumoniae. JF - Journal of Biological Chemistry AU - Thompson, J AU - Robrish, SA AU - Immel, S AU - Lichtenthaler, F W AU - Hall, B G AU - Pikis, A AD - Microbial Biochemistry and Genetics Unit, Oral Infection and Immunity Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA, jthompson@dir.nidcr.nih.gov Y1 - 2001/10/05/ PY - 2001 DA - 2001 Oct 05 SP - 37415 EP - 37425 VL - 276 IS - 40 SN - 0021-9258, 0021-9258 KW - 6-phospho-a-glucosidase KW - cDNA KW - amino acid sequence prediction KW - 6-phospho- alpha -glucosidase KW - AglB gene KW - aglA gene KW - sucrose KW - sucrose-6-phosphate hydrolase KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - 6-phospho-^a-glucosidase KW - Nucleotide sequence KW - Maltose-6'-phosphate glucosidase KW - Klebsiella pneumoniae KW - J 02728:Enzymes KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18113629?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Metabolism+of+Sucrose+and+Its+Five+Linkage-isomeric+alpha+-D-Glucosyl-D-fructoses+by+Klebsiella+pneumoniae%3A+Participation+and+Properties+of+Sucrose-6-Phosphate+Hydrolase+and+Phospho-+alpha+-glucosidase&rft.au=Thompson%2C+J%3BRobrish%2C+SA%3BImmel%2C+S%3BLichtenthaler%2C+F+W%3BHall%2C+B+G%3BPikis%2C+A&rft.aulast=Thompson&rft.aufirst=J&rft.date=2001-10-05&rft.volume=276&rft.issue=40&rft.spage=37415&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Klebsiella pneumoniae; Maltose-6'-phosphate glucosidase; Nucleotide sequence ER - TY - JOUR T1 - The Neural Organization of Discourse: An H215O-PET Study of Narrative Production in English and American Sign Language AN - 85514613; 200200294 AB - In order to identify brain regions that play an essential role in the production of discourse, H215O-PET scans were acquired during spontaneous generation of autobiographical narratives in English & in American Sign Language in hearing subjects who were native users of both. We compared languages that differ maximally in their mode of expression yet share the same core linguistic properties in order to differentiate the stages of discourse production: differences between the languages should reflect later, modality-dependent stages of phonological encoding & articulation; congruencies are more likely to reveal the anatomy of earlier modality-independent stages of conceptualization & lexical access. Common activations were detected in a widespread array of regions; left hemisphere language areas classically related to speech were also robustly activated during sign production, but the common neural architecture extended beyond the classical language areas & included extrasylvian regions in both right & left hemispheres. Furthermore, posterior perisylvian & basal temporal regions appear to play an integral role in spontaneous self-generated formulation & production of language, even in the absence of exteroceptive stimuli. Results additionally indicate that anterior & posterior areas may play distinct roles in early & late stages of language production, & suggest a novel model for lateralization of cerebral activity during the generation of discourse: progression from the early stages of lexical access to later stages of articulatory-motor encoding may constitute a progression from bilateral to left-lateralized activation. This pattern is not predicted by the standard Wernicke-Geschwind model & may become apparent when language is produced in an ecologically valid context. 3 Tables, 3 Figures, 1 Appendix, 80 References. Adapted from the source document JF - Brain AU - Braun, A R AU - Guillemin, A AU - Hosey, L AU - Varga, M AD - Language Section, Voice/Speech/Language Branch, National Instit Deafness & Other Communication Disorders, National Instits Health, Bethesda, MD brauna@nidcd.nih.gov Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 2028 EP - 2044 VL - 124 IS - 10 SN - 0006-8950, 0006-8950 KW - Articulation (04600) KW - Cerebral Dominance (11500) KW - English (21900) KW - Lexical Access (46630) KW - Speech Production (82780) KW - American Sign Language (02350) KW - Language Processing (43550) KW - article KW - 4018: psycholinguistics; neurolinguistics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85514613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain&rft.atitle=The+Neural+Organization+of+Discourse%3A+An+H215O-PET+Study+of+Narrative+Production+in+English+and+American+Sign+Language&rft.au=Braun%2C+A+R%3BGuillemin%2C+A%3BHosey%2C+L%3BVarga%2C+M&rft.aulast=Braun&rft.aufirst=A&rft.date=2001-10-01&rft.volume=124&rft.issue=10&rft.spage=2028&rft.isbn=&rft.btitle=&rft.title=Brain&rft.issn=00068950&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2003-10-01 N1 - Last updated - 2016-09-27 N1 - CODEN - BRAIAK N1 - SubjectsTermNotLitGenreText - Speech Production (82780); Cerebral Dominance (11500); Language Processing (43550); English (21900); American Sign Language (02350); Lexical Access (46630); Articulation (04600) ER - TY - JOUR T1 - Phase I trial of lobradimil (RMP-7) and carboplatin in children with brain tumors. AN - 85294340; pmid-11710627 AB - PURPOSE: To determine the maximum tolerated dose (MTD), the incidence and severity of toxicities, and the pharmacokinetics of lobradimil administered intravenously over 10 min in combination with carboplatin in children with refractory brain tumors. METHODS: A group of 25 children with primary brain tumors received carboplatin and lobradimil on two consecutive days every 28 days. The 10-min lobradimil infusion began 5 min before the end of the carboplatin infusion. Four lobradimil dose levels (100, 300, 450 and 600 ng/kg ideal body weight, IBW) were studied in cohorts of 4 to 13 patients. Carboplatin was adaptively dosed based on the glomerular filtration rate to achieve a target plasma area under the concentration-time curve (AUC) of 7.0 mg min/ml per course (5.0 mg min/ml for patients who had previously received craniospinal radiation or myeloablative chemotherapy). RESULTS: Lobradimil toxicity was immediate, tolerable and rapidly reversible. The most frequent toxicities were hypotension, flushing, headache and gastrointestinal complaints. One patient on the 600 ng/kg dose level had a seizure during the lobradimil infusion. The incidence and severity of lobradimil toxicities were not dose-related and the lobradimil dose was not escalated beyond the 600 ng/kg IBW dose level. Two patients had partial responses and ten patients had stable disease. Myelosuppression (thrombocytopenia more prominent than neutropenia) was the primary toxicity attributed to carboplatin. Lobradimil pharmacokinetics were characterized by rapid clearance from the plasma compartment and substantial interpatient variability. CONCLUSIONS: The combination of carboplatin and lobradimil is safe and tolerable. An MTD for lobradimil was not defined because toxicity was not dose-related. The recommended pediatric phase II dose of lobradimil is 600 ng/kg IBW. JF - Cancer Chemotherapy and Pharmacology AU - Warren, K E AU - Patel, M C AU - Aikin, A A AU - Widemann, B AU - Libucha, M AU - Adamson, P C AU - Neuwirth, R AU - Benziger, D AU - O'Toole, T AU - Ford, K AU - Patronas, N AU - Packer, R J AU - Balis, F M AD - Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD 20892-1928, USA. PY - 2001 SP - 275 EP - 282 VL - 48 IS - 4 SN - 0344-5704, 0344-5704 KW - Hypotension KW - Infusions, Intravenous KW - Area Under Curve KW - Bradykinin KW - Dose-Response Relationship, Drug KW - Human KW - Seizures KW - Child KW - Carboplatin KW - Child, Preschool KW - Drug Therapy, Combination KW - Brain Neoplasms KW - Neutropenia KW - Thrombocytopenia KW - Adult KW - Headache KW - Flushing KW - Adolescent KW - Female KW - Male KW - Blood-Brain Barrier UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85294340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Chemotherapy+and+Pharmacology&rft.atitle=Phase+I+trial+of+lobradimil+%28RMP-7%29+and+carboplatin+in+children+with+brain+tumors.&rft.au=Warren%2C+K+E%3BPatel%2C+M+C%3BAikin%2C+A+A%3BWidemann%2C+B%3BLibucha%2C+M%3BAdamson%2C+P+C%3BNeuwirth%2C+R%3BBenziger%2C+D%3BO%27Toole%2C+T%3BFord%2C+K%3BPatronas%2C+N%3BPacker%2C+R+J%3BBalis%2C+F+M&rft.aulast=Warren&rft.aufirst=K&rft.date=2001-10-01&rft.volume=48&rft.issue=4&rft.spage=275&rft.isbn=&rft.btitle=&rft.title=Cancer+Chemotherapy+and+Pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Altered performance on an ocular fixation task in attention-deficit/hyperactivity disorder. AN - 85249130; pmid-11690600 AB - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder without validated objective markers. Eye movement studies may be useful in providing objective criteria for characterizing the disorder. METHODS: We compared 53 children (29 girls) with ADHD to 44 healthy control children (18 girls) on a 21-sec fixation task. Large saccades (> 4 degrees ) away from the fixation point were analyzed. RESULTS: Children with ADHD made more large saccades that interrupted fixation than did control children (p =.001). Mean scores of the ADHD group did not change significantly with subsequent retesting on placebo (p =.11); however, there was poor intrasubject correlation (r =.16). CONCLUSIONS: Both boys and girls with ADHD made significantly more intrusive saccades during fixation than did control subjects, possibly reflecting intrinsic neurologic dysfunction; however, a probable "floor effect" obviates conclusions about the reliability of this measure. JF - Biological Psychiatry AU - Gould, T D AU - Bastain, T M AU - Israel, M E AU - Hommer, D W AU - Castellanos, F X AD - Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland, USA. PY - 2001 SP - 633 EP - 635 VL - 50 IS - 8 SN - 0006-3223, 0006-3223 KW - Attention Deficit Disorder with Hyperactivity KW - Human KW - Child KW - Predictive Value of Tests KW - Saccades KW - Female KW - Male KW - Fixation, Ocular UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85249130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+Psychiatry&rft.atitle=Altered+performance+on+an+ocular+fixation+task+in+attention-deficit%2Fhyperactivity+disorder.&rft.au=Gould%2C+T+D%3BBastain%2C+T+M%3BIsrael%2C+M+E%3BHommer%2C+D+W%3BCastellanos%2C+F+X&rft.aulast=Gould&rft.aufirst=T&rft.date=2001-10-01&rft.volume=50&rft.issue=8&rft.spage=633&rft.isbn=&rft.btitle=&rft.title=Biological+Psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Effects of high-energy electrons and gamma rays directly on protein molecules. AN - 72364059; 11745722 AB - High-energy electrons and gamma rays ionize molecules at random along their trajectories. In each event, chemical bonds are ruptured, releasing radiolytic products that diffuse away. A solution of macromolecules is mostly water whose principal radiation products are H(+) and OH(-). These can diffuse to and react with macromolecules; this indirect action of radiation is responsible for 99.9% of the damage to proteins. In frozen samples, the ionizations still occur randomly and water is still the principle molecular target, but diffusion of radiation products is limited to only a very small distance. At very low temperatures, essentially all the radiation damage to macromolecules is due to primary ionizations occurring directly in those molecules. Therefore, proteins in frozen solutions are only 10(-3) to 10(-4) as sensitive to radiation as in the liquid state. Every molecule that suffered a direct ionization is destroyed; the only surviving molecules are those that escaped ionization. The survival of frozen proteins after irradiation is a direct measure of the mass of the active structures and independent of the presence of other proteins. Copyright 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1637-1646, 2001 JF - Journal of pharmaceutical sciences AU - Kempner, E S AD - Laboratory of Physical Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 1637 EP - 1646 VL - 90 IS - 10 SN - 0022-3549, 0022-3549 KW - Enzymes KW - 0 KW - Proteins KW - Index Medicus KW - Humans KW - Enzymes -- radiation effects KW - Freezing KW - Radiation Tolerance KW - Poisson Distribution KW - Dose-Response Relationship, Radiation KW - Structure-Activity Relationship KW - Radiation, Ionizing KW - Mathematics KW - Proteins -- chemistry KW - Electrons KW - Gamma Rays KW - Proteins -- radiation effects KW - Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72364059?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+pharmaceutical+sciences&rft.atitle=Effects+of+high-energy+electrons+and+gamma+rays+directly+on+protein+molecules.&rft.au=Kempner%2C+E+S&rft.aulast=Kempner&rft.aufirst=E&rft.date=2001-10-01&rft.volume=90&rft.issue=10&rft.spage=1637&rft.isbn=&rft.btitle=&rft.title=Journal+of+pharmaceutical+sciences&rft.issn=00223549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-14 N1 - Date created - 2001-12-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Pharm Sci 2002 Jan;91(1):301 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of repeated rifabutin administration on the pharmacokinetics of intravenous and oral ciprofloxacin in mice. AN - 72337059; 11760222 AB - The combination of rifabutin and ciprofloxacin is potentially useful for the treatment of disseminated Mycobacterium avium-intracellulare (MAC) diseases in HIV-infected patients. Rifabutin is a metabolic enzyme inducer structurally similar to its predecessor, rifampin. Using a mouse model, the effects of repeated exposure of rifabutin on the pharmacokinetics of ciprofloxacin after intravenous (i.v.) and oral (p.o.) dosing were investigated in the present study. Results showed that repeated exposure of rifabutin, relative to control, caused a 16% increase in the plasma clearance (CL) of ciprofloxacin after i.v. dosing (4.19 vs. 4.87 L/h/kg). Estimates of elimination half-life (T1/2) were not affected by rifabutin (control: 0.81 vs. rifabutin pretreated: 1.18 h). The data obtained after oral dosing showed that repeated rifabutin dosing caused a significant reduction in the maximal plasma concentration (Cmax: 1.34 vs. 0.91 microg/mL) and a longer time to Cmax (Tmax: 0.17 vs. 0.33 h). These changes might be in part attributable to the increase in oral clearance (CL/F) by 18%. With or without rifabutin pretreatment, the T1/2 estimates of ciprofloxacin for p.o. dosing were similar (2.37-2.58 h) and were approximately twice as long as those obtained after i.v. dosing. Since the changes in systemic exposure as a result of rifabutin pretreatment were similar after i.v. and p.o. dosing, the oral bioavailability (F) of ciprofloxacin remained unaffected by rifabutin at approximately 38%. The effects of rifabutin on the pharmacokinetics of ciprofloxacin appear to be moderate in the mouse model which might be attributable to the absorption and distribution behavior of the quinolone antibiotic. The therapeutic implications of this interaction, if any, remain to be defined. JF - Journal of chemotherapy (Florence, Italy) AU - Liu, X G AU - Li, R C AD - NIDDK, National Institute of Health, Bethesda, Maryland, USA. Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 563 EP - 568 VL - 13 IS - 5 SN - 1120-009X, 1120-009X KW - Anti-Infective Agents KW - 0 KW - Antibiotics, Antitubercular KW - Rifabutin KW - 1W306TDA6S KW - Ciprofloxacin KW - 5E8K9I0O4U KW - Index Medicus KW - Administration, Oral KW - Animals KW - Mice, Inbred ICR KW - Drug Interactions KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Half-Life KW - HIV Infections -- complications KW - Absorption KW - Disease Models, Animal KW - Mice KW - Male KW - Ciprofloxacin -- administration & dosage KW - Anti-Infective Agents -- pharmacokinetics KW - Mycobacterium avium-intracellulare Infection -- drug therapy KW - Ciprofloxacin -- pharmacokinetics KW - Antibiotics, Antitubercular -- pharmacology KW - Antibiotics, Antitubercular -- administration & dosage KW - Rifabutin -- administration & dosage KW - Anti-Infective Agents -- administration & dosage KW - Rifabutin -- pharmacokinetics KW - Mycobacterium avium-intracellulare Infection -- etiology KW - Antibiotics, Antitubercular -- pharmacokinetics KW - Rifabutin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72337059?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+chemotherapy+%28Florence%2C+Italy%29&rft.atitle=Effects+of+repeated+rifabutin+administration+on+the+pharmacokinetics+of+intravenous+and+oral+ciprofloxacin+in+mice.&rft.au=Liu%2C+X+G%3BLi%2C+R+C&rft.aulast=Liu&rft.aufirst=X&rft.date=2001-10-01&rft.volume=13&rft.issue=5&rft.spage=563&rft.isbn=&rft.btitle=&rft.title=Journal+of+chemotherapy+%28Florence%2C+Italy%29&rft.issn=1120009X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-04 N1 - Date created - 2001-12-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intracellular distribution of the antimutagenic enzyme MTH1 in the liver, kidney and testis of F344 rats and its modulation by cadmium. AN - 72323016; 11817101 AB - Cellular distribution of the antimutagenic MTH1protein in the liver, kidney, and testis of Fischer rat was evaluated using the immunohistochemical staining with anti-MTH1 polyclonal antibody. The present investigation revealed a non-uniform distribution of MTH1 among cells and among the cytoplasmic, nuclear, and membranal structures of cells within a given tissue. A particularly strong expression of MTH1 was observed for the first time in the perinuclear acrosomic bodies of spermatocytes and in the acrosomic vesicles of sperm heads. Treatment of rats with a single sc dose of 20 micromol Cd(II)/kg body wt. produced histopathologic changes in these organs accompanied by redistribution of the cellular MTH1 protein between the cytoplasm and nuclei. The acute phase of Cd(II) toxicity, that in the liver and especially in the testes (but not in kidneys) led to cell necrosis, was accompanied by a characteristic decrease in the abundance of MTH1-expressing nuclei. Chronic toxicity without necrosis, persisting in the kidney over the entire 14-day study, as well as the survival and proliferation of cells, observed in the liver and testis after the necrotizing phase, were signified by increased number of nuclei expressing MTH1. Thus, unlike previous biochemical studies, immunohistochemistry managed to reveal alterations in the patterns of inter- and intracellular distribution of MTH1, associated apparently with the conditional changes in the dynamics of synthesis of nucleic acids, assisted by this protein. JF - Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie AU - Kasprzak, K S AU - Nakabeppu, Y AU - Kakuma, T AU - Sakai, Y AU - Tsuruya, K AU - Sekiguchi, M AU - Ward, J M AU - Diwan, B A AU - Nagashima, K AU - Kasprzak, B H AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, MD 21702-1201, USA. kasprzak@mail.ncifcrf.gov Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 325 EP - 335 VL - 53 IS - 5 SN - 0940-2993, 0940-2993 KW - Antimutagenic Agents KW - 0 KW - Cadmium KW - 00BH33GNGH KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - 8-oxodGTPase KW - EC 3.6.1.55 KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Cell Nucleus -- enzymology KW - Blotting, Western KW - Organ Specificity KW - Microscopy, Electron KW - Cytoplasm -- enzymology KW - Cytoplasm -- drug effects KW - Immunohistochemistry KW - Male KW - Antimutagenic Agents -- metabolism KW - Liver -- enzymology KW - Testis -- drug effects KW - Liver -- drug effects KW - Kidney -- enzymology KW - Kidney -- drug effects KW - Cadmium -- toxicity KW - Testis -- enzymology KW - Phosphoric Monoester Hydrolases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72323016?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+and+toxicologic+pathology+%3A+official+journal+of+the+Gesellschaft+fur+Toxikologische+Pathologie&rft.atitle=Intracellular+distribution+of+the+antimutagenic+enzyme+MTH1+in+the+liver%2C+kidney+and+testis+of+F344+rats+and+its+modulation+by+cadmium.&rft.au=Kasprzak%2C+K+S%3BNakabeppu%2C+Y%3BKakuma%2C+T%3BSakai%2C+Y%3BTsuruya%2C+K%3BSekiguchi%2C+M%3BWard%2C+J+M%3BDiwan%2C+B+A%3BNagashima%2C+K%3BKasprzak%2C+B+H&rft.aulast=Kasprzak&rft.aufirst=K&rft.date=2001-10-01&rft.volume=53&rft.issue=5&rft.spage=325&rft.isbn=&rft.btitle=&rft.title=Experimental+and+toxicologic+pathology+%3A+official+journal+of+the+Gesellschaft+fur+Toxikologische+Pathologie&rft.issn=09402993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-28 N1 - Date created - 2001-12-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polyglutamine expansion neurodegenerative disease. AN - 72292404; 11719245 AB - Kennedy's disease was the first of eight neurodegenerative disorders found to be caused by expanded polyglutamine repeats. Each of these disorders is likely caused by a toxic gain of function in the disease gene product, often associated with inclusions of mutant protein in susceptible neurons. The mechanism of toxicity may involve sequestration and depletion of a polyglutamine-containing protein that is important to neuronal survival, such as CREB-binding protein. Recent insights into the biochemistry and cellular pathology of the polyglutamine expansion neurodegenerative diseases provide the opportunity for systematic drug screens and a rational approach to effective therapy. JF - Brain research bulletin AU - Fischbeck, K H AD - National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1250, USA. kf@codon.nih.gov PY - 2001 SP - 161 EP - 163 VL - 56 IS - 3-4 SN - 0361-9230, 0361-9230 KW - Peptides KW - 0 KW - polyglutamine KW - 26700-71-0 KW - Index Medicus KW - Humans KW - Muscular Atrophy, Spinal -- genetics KW - Peptides -- genetics KW - Trinucleotide Repeat Expansion KW - Huntington Disease -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72292404?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research+bulletin&rft.atitle=Polyglutamine+expansion+neurodegenerative+disease.&rft.au=Fischbeck%2C+K+H&rft.aulast=Fischbeck&rft.aufirst=K&rft.date=2001-10-01&rft.volume=56&rft.issue=3-4&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Brain+research+bulletin&rft.issn=03619230&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-07 N1 - Date created - 2001-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin-6 and glucocorticoids synergistically induce human immunodeficiency virus type-1 expression in chronically infected U1 cells by a long terminal repeat independent post-transcriptional mechanism. AN - 72279902; 11713366 AB - Glucocorticoids (GC) such as dexamethasone (Dex) can directly upregulate human immunodeficiency virus type-1 (HIV-1) replication in acutely infected cells and potentiate HIV expression from chronically infected promonocytic U1 cells stimulated with tumor necrosis factor-alpha (TNF-alpha). We have here investigated the potential effect of Dex in U1 cells stimulated with interleukin-6 (IL-6), a cytokine inducing virus expression by acting mostly at a post-transcriptional level on the virus life cycle. Virus production in culture supernatants was evaluated by reverse transcriptase (RT) activity. GC receptor expression was tested by both binding of [3H]-Dexamethasone 21-mesylate and Northern blotting. Cell-associated HIV protein expression was analyzed by Western blotting, whereas both HIV and monocyte chemoattractant protein-1 (MCP-1) RNA accumulation were evaluated by Northern blotting. HIV transcription was tested by long terminal repeat (LTR) chloramphenicol acetyl transferase (CAT) assay after transient transfection of U1 or U937 cells. Formation of activating protein-1 (AP-1) DNA binding complex in nuclear cell extracts was visualized by electrophoretic mobility shift assay (EMSA), whereas ERK1/2 mitogen-activated protein kinase (MAPK) phosphorylation was studied by Western blotting. IL-6 and Dex synergistically induced HIV expression in U1 cells, and this effect was blocked by RU 486. No substantial HIV RNA accumulation was demonstrated in U1 cells co-stimulated with IL-6 and Dex, whereas IL-6 upregulated the expression of MCP-1 RNA, and this effect was inhibited by Dex. In contrast, Dex potentiated IL-6 induced activation of AP-1 and ERK1/2 MAPK phosphorylation, as revealed by EMSA. HIV-1 LTR driven transcription was observed in U1 cells stimulated with TNF-alpha and this effect was potentiated by Dex. In sharp contrast, no induction of LTR-directed CAT activity was observed in transfected U1 cells (or in their parental uninfected U937 cells) stimulated with IL-6 and Dex either alone or in combination. High levels of virion production can be induced in latently infected cells by stimulation with IL-6 and Dex in the absence of activation of the HIV LTR or viral transcription in spite of activation of both ERK1/2 MAPK and AP-1. These findings suggest the existence of LTR-independent pathways influenced by cytokine and GC through which HIV can maintain substantial levels of protein expression and virion production. JF - Molecular medicine (Cambridge, Mass.) AU - Kinter, A L AU - Biswas, P AU - Alfano, M AU - Justement, J S AU - Mantelli, B AU - Rizzi, C AU - Gatti, A R AU - Vicenzi, E AU - Bressler, P AU - Poli, G AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 668 EP - 678 VL - 7 IS - 10 SN - 1076-1551, 1076-1551 KW - Autoantigens KW - 0 KW - CCL2 protein, human KW - Chemokine CCL2 KW - Glucocorticoids KW - Interleukin-6 KW - RNA, Viral KW - Receptors, Glucocorticoid KW - Transcription Factor AP-1 KW - Dexamethasone KW - 7S5I7G3JQL KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Mitogen-Activated Protein Kinase Kinases KW - EC 2.7.12.2 KW - dexamethasone 21-methanesulfonate KW - O9S11FMA79 KW - Index Medicus KW - Blotting, Northern KW - Transcription Factor AP-1 -- metabolism KW - Humans KW - RNA, Viral -- biosynthesis KW - Electrophoretic Mobility Shift Assay KW - Autoantigens -- genetics KW - HIV Long Terminal Repeat -- drug effects KW - HIV Long Terminal Repeat -- physiology KW - Chloramphenicol O-Acetyltransferase -- metabolism KW - Receptors, Glucocorticoid -- metabolism KW - Blotting, Western KW - Virus Activation -- drug effects KW - Virus Replication -- drug effects KW - Mitogen-Activated Protein Kinase Kinases -- physiology KW - Autoantigens -- metabolism KW - Drug Synergism KW - Signal Transduction KW - Dexamethasone -- analogs & derivatives KW - Dexamethasone -- pharmacology KW - Monocytes -- drug effects KW - Interleukin-6 -- pharmacology KW - Monocytes -- virology KW - HIV-1 -- physiology KW - Glucocorticoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72279902?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+medicine+%28Cambridge%2C+Mass.%29&rft.atitle=Interleukin-6+and+glucocorticoids+synergistically+induce+human+immunodeficiency+virus+type-1+expression+in+chronically+infected+U1+cells+by+a+long+terminal+repeat+independent+post-transcriptional+mechanism.&rft.au=Kinter%2C+A+L%3BBiswas%2C+P%3BAlfano%2C+M%3BJustement%2C+J+S%3BMantelli%2C+B%3BRizzi%2C+C%3BGatti%2C+A+R%3BVicenzi%2C+E%3BBressler%2C+P%3BPoli%2C+G&rft.aulast=Kinter&rft.aufirst=A&rft.date=2001-10-01&rft.volume=7&rft.issue=10&rft.spage=668&rft.isbn=&rft.btitle=&rft.title=Molecular+medicine+%28Cambridge%2C+Mass.%29&rft.issn=10761551&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-31 N1 - Date created - 2001-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity and carcinogenicity study in F344 rats following 2 years of whole-body exposure to naphthalene vapors. AN - 72257496; 11696867 AB - The toxicologic and carcinogenic potential of naphthalene was studied by exposing groups of 49 male and 49 female F344 rats to atmospheres containing 0, 10, 30, or 60 ppm of the chemical for 6 h daily, 5 days/wk for 2 yr. Mean body weights of exposed groups of male rats were less than for the control group throughout most of the study. Mean body weights of exposed female rats were generally similar to those of controls. Survival of exposed and control rats was similar. Under the conditions of this 2-yr inhalation study, naphthalene was carcinogenic to male and female F344/N rats, causing increased incidences of respiratory epithelial adenoma (males: control, 0%; low dose, 12%, mid dose, 17%; high dose, 31%; females: 0%; 0%; 8%; 4%) and olfactory epithelial neuroblastoma (males: control, 0%; low dose, 0%; mid dose, 8%; high dose, 6%; females: 0; 4%; 6%; 24%) of the nose. In both sexes of rats, exposure to naphthalene also caused significant increases in the incidences of nasal lesions including hyperplasia, atrophy, chronic inflammation, and hyaline degeneration of the olfactory epithelium and hyperplasia; squamous metaplasia, hyaline degeneration, and goblet-cell hyperplasia of the respiratory epithelium; and glandular hyperplasia and squamous metaplasia. JF - Inhalation toxicology AU - Abdo, K M AU - Grumbein, S AU - Chou, B J AU - Herbert, R AD - National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, Research Triangle Park, NC 27709, USA. abdok@niehs.nih.gov Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 931 EP - 950 VL - 13 IS - 10 SN - 0895-8378, 0895-8378 KW - Naphthalenes KW - 0 KW - decalin KW - 88451Q4XYF KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Nose -- pathology KW - Cytochrome P-450 Enzyme System -- physiology KW - Lung -- drug effects KW - Volatilization KW - Lung -- pathology KW - Nose -- drug effects KW - Administration, Inhalation KW - Species Specificity KW - Male KW - Female KW - Naphthalenes -- metabolism KW - Naphthalenes -- administration & dosage KW - Nose Neoplasms -- pathology KW - Nose Neoplasms -- chemically induced KW - Naphthalenes -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72257496?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Inhalation+toxicology&rft.atitle=Toxicity+and+carcinogenicity+study+in+F344+rats+following+2+years+of+whole-body+exposure+to+naphthalene+vapors.&rft.au=Abdo%2C+K+M%3BGrumbein%2C+S%3BChou%2C+B+J%3BHerbert%2C+R&rft.aulast=Abdo&rft.aufirst=K&rft.date=2001-10-01&rft.volume=13&rft.issue=10&rft.spage=931&rft.isbn=&rft.btitle=&rft.title=Inhalation+toxicology&rft.issn=08958378&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-03 N1 - Date created - 2001-11-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Airway inflammation and responsiveness in prostaglandin H synthase-deficient mice exposed to bacterial lipopolysaccharide. AN - 72254118; 11694451 AB - Bacterial lipopolysaccharide (LPS) is a risk factor for exacerbation of asthma and causes airway inflammation. The aim of this study was to examine the effects of disruption of prostaglandin (PG) H synthase (PGHS)-1 and PGHS-2 genes on pulmonary responses to inhaled LPS. PGHS-1(-/-), PGHS-2(-/-), and wild-type (WT) mice were exposed to 4 to 6 microg/m(3) LPS via aerosol. Enhanced pause (PenH), a measure of bronchoconstriction, was assessed using a whole-body plethysmograph before and immediately after a 4-h LPS exposure. Bronchoalveolar lavage (BAL) was performed after LPS exposure to assess inflammatory cells, cytokines/chemokines (tumor necrosis factor-alpha, interleukin-6, and macrophage inflammatory protein-2), and PGE(2). The degree of lung inflammation was scored on hematoxylin-and-eosin-stained sections. PGHS-1 and PGHS-2 protein levels were determined by immunoblotting. All mice exhibited increased PenH and methacholine responsiveness after LPS exposure; however, these changes were much more pronounced in PGHS-1(-/-) and PGHS-2(-/-) mice relative to WT mice (P < 0.05). There were no significant differences in inflammation as assessed by BAL fluid (BALF) cells or lung histology between the genotypes despite reduced BALF cytokines/chemokines and PGE(2) in PGHS-1(-/-) and PGHS-2(-/-) mice relative to WT mice (P < 0.05). PGHS-2 was upregulated more in PGHS-1(-/-) mice compared with WT mice after LPS exposure. We conclude that: (1) airway inflammation and hyperresponsiveness are dissociated in PGHS-1(-/-) and PGHS-2(-/-) mice exposed to LPS; (2) the balance of PGHS-1 and PGHS-2 is important in regulating the functional respiratory responses to inhaled LPS; and (3) neither PGHS-1 nor PGHS-2 is important in regulating basal lung function or the inflammatory responses of the lung to inhaled LPS. JF - American journal of respiratory cell and molecular biology AU - Zeldin, D C AU - Wohlford-Lenane, C AU - Chulada, P AU - Bradbury, J A AU - Scarborough, P E AU - Roggli, V AU - Langenbach, R AU - Schwartz, D A AD - National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Bldg. 101, Rm. D-236, Research Triangle Park, NC 27709, USA. zeldin@niehs.nih.gov Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 457 EP - 465 VL - 25 IS - 4 SN - 1044-1549, 1044-1549 KW - Chemokines KW - 0 KW - Cytokines KW - Isoenzymes KW - Lipopolysaccharides KW - Membrane Proteins KW - Proteins KW - Leukotriene B4 KW - 1HGW4DR56D KW - Cyclooxygenase 1 KW - EC 1.14.99.1 KW - Cyclooxygenase 2 KW - Prostaglandin-Endoperoxide Synthases KW - Ptgs1 protein, mouse KW - Dinoprostone KW - K7Q1JQR04M KW - Index Medicus KW - Animals KW - Dinoprostone -- biosynthesis KW - Disease Models, Animal KW - Mice KW - Cytokines -- metabolism KW - Lung -- pathology KW - Proteins -- metabolism KW - Mice, Inbred Strains KW - Mice, Mutant Strains KW - Chemokines -- metabolism KW - Leukotriene B4 -- biosynthesis KW - Bronchoalveolar Lavage Fluid KW - Up-Regulation KW - Administration, Inhalation KW - Male KW - Female KW - Pneumonia -- chemically induced KW - Lipopolysaccharides -- administration & dosage KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Lipopolysaccharides -- pharmacology KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Prostaglandin-Endoperoxide Synthases -- drug effects KW - Isoenzymes -- drug effects KW - Pneumonia -- physiopathology KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72254118?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+respiratory+cell+and+molecular+biology&rft.atitle=Airway+inflammation+and+responsiveness+in+prostaglandin+H+synthase-deficient+mice+exposed+to+bacterial+lipopolysaccharide.&rft.au=Zeldin%2C+D+C%3BWohlford-Lenane%2C+C%3BChulada%2C+P%3BBradbury%2C+J+A%3BScarborough%2C+P+E%3BRoggli%2C+V%3BLangenbach%2C+R%3BSchwartz%2C+D+A&rft.aulast=Zeldin&rft.aufirst=D&rft.date=2001-10-01&rft.volume=25&rft.issue=4&rft.spage=457&rft.isbn=&rft.btitle=&rft.title=American+journal+of+respiratory+cell+and+molecular+biology&rft.issn=10441549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-31 N1 - Date created - 2001-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical relevance of genetic polymorphisms in the human CYP2C subfamily. AN - 72233799; 11678778 AB - The human CYP2Cs are an important subfamily of P450 enzymes that metabolize approximately 20% of clinically used drugs. There are four members of the subfamily, CYP2C8, CYP2C9, CYP2C19, and CYP2C18. Of these CYP2C8, CYP2C9, and CYP2C19 are of clinical importance. The CYP2Cs also metabolize some endogenous compounds such as arachidonic acid. Each member of this subfamily has been found to be genetically polymorphic. The most well-known of these polymorphisms is in CYP2C19. Poor metabolizers (PMs) of CYP2C19 represent approximately 3-5% of Caucasians, a similar percentage of African-Americans and 12-100% of Asian groups. The polymorphism affects metabolism of the anticonvulsant agent mephenytoin, proton pump inhibitors such as omeprazole, the anxiolytic agent diazepam, certain antidepressants, and the antimalarial drug proguanil. Toxic effects can occur in PMs exposed to diazepam, and the efficacy of some proton pump inhibitors may be greater in PMs than EMs at low doses of these drugs. A number of mutant alleles exist that can be detected by genetic testing. CYP2C9 metabolizes a wide variety of drugs including the anticoagulant warfarin, antidiabetic agents such as tolbutamide, anticonvulsants such as phenytoin, and nonsteroidal anti-inflammatory drugs. The incidence of functional polymorphisms is much lower, estimated to be 1/250 in Caucasians and lower in Asians. However, the clinical consequences of these rarer polymorphisms can be severe. Severe and life-threatening bleeding episodes have been reported in CYP2C9 PMs exposed to warfarin. Phenytoin has been reported to cause severe toxicity in PMs. New polymorphisms have been discovered in CYP2C8, which metabolizes taxol (paclitaxel). Genetic testing is available for all of the known CYP2C variant alleles. JF - British journal of clinical pharmacology AU - Goldstein, J A AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Goldstel@niehs.nih.gov Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 349 EP - 355 VL - 52 IS - 4 SN - 0306-5251, 0306-5251 KW - Anti-Ulcer Agents KW - 0 KW - Anticonvulsants KW - Pharmaceutical Preparations KW - cytochrome P-450 CYP2C subfamily KW - Phenytoin KW - 6158TKW0C5 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Omeprazole KW - KG60484QX9 KW - Mephenytoin KW - R420KW629U KW - Index Medicus KW - Phenytoin -- metabolism KW - Omeprazole -- metabolism KW - Alleles KW - Polymorphism, Genetic KW - Anti-Ulcer Agents -- metabolism KW - Humans KW - Anticonvulsants -- metabolism KW - Mephenytoin -- metabolism KW - Pharmaceutical Preparations -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- physiology KW - Cytochrome P-450 Enzyme System -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72233799?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+clinical+pharmacology&rft.atitle=Clinical+relevance+of+genetic+polymorphisms+in+the+human+CYP2C+subfamily.&rft.au=Goldstein%2C+J+A&rft.aulast=Goldstein&rft.aufirst=J&rft.date=2001-10-01&rft.volume=52&rft.issue=4&rft.spage=349&rft.isbn=&rft.btitle=&rft.title=British+journal+of+clinical+pharmacology&rft.issn=03065251&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-18 N1 - Date created - 2001-10-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Br J Clin Pharmacol. 1996 Dec;42(6):771-3 [8971434] Int Clin Psychopharmacol. 1986 Apr;1(2):102-12 [3571939] J Pharmacol Exp Ther. 1997 Feb;280(2):730-8 [9023285] Pharmacogenetics. 1999 Oct;9(5):581-90 [10591538] Clin Pharmacol Ther. 1999 Dec;66(6):642-6 [10613621] Pharmacogenetics. 2000 Mar;10(2):95-104 [10761997] Ther Drug Monit. 2000 Apr;22(2):230-2 [10774639] Pharmacogenetics. 2000 Apr;10(3):267-70 [10803683] Diabetes. 1979 Jan;28(1):41-51 [569611] J Biol Chem. 1985 Apr 25;260(8):5026-32 [2985574] Clin Pharmacol Ther. 1985 Oct;38(4):414-8 [4042524] Nucleic Acids Res. 1987 Dec 10;15(23):10053-4 [3697070] Clin Pharmacol Ther. 1989 Jan;45(1):72-9 [2910639] Pharmacol Ther. 1989;43(1):53-76 [2675129] Scand J Gastroenterol Suppl. 1989;166:3-11 [2557669] Clin Pharmacol Ther. 1991 Jan;49(1):18-23 [1988236] Br J Clin Pharmacol. 1991 Jun;31(6):689-92 [1867963] Chem Res Toxicol. 1992 Jan-Feb;5(1):54-9 [1581537] Clin Pharmacol Ther. 1992 May;51(5):507-12 [1587064] Ther Drug Monit. 1993 Feb;15(1):11-7 [8451774] Pharmacogenetics. 1992 Feb;2(1):25-31 [1302040] Br J Clin Pharmacol. 1993 Aug;36(2):105-8 [8398577] Clin Pharmacol Ther. 1994 May;55(5):518-27 [8181196] J Biol Chem. 1994 Jun 3;269(22):15419-22 [8195181] Pharmacogenetics. 1994 Feb;4(1):27-38 [8004130] Pharmacogenetics. 1994 Feb;4(1):39-42 [8004131] Br J Clin Pharmacol. 1994 May;37(5):413-20 [8054246] Cancer Res. 1994 Nov 1;54(21):5543-6 [7923194] Mol Pharmacol. 1994 Oct;46(4):594-8 [7969038] Pharmacogenetics. 1994 Dec;4(6):285-99 [7704034] Clin Pharmacol Ther. 1995 Jun;57(6):662-9 [7781266] Clin Pharmacol Ther. 1995 Aug;58(2):143-54 [7648764] Clin Pharmacokinet. 1995 Sep;29(3):192-209 [8521680] FEBS Lett. 1996 Apr 22;384(3):281-4 [8617372] Clin Pharmacol Ther. 1996 Mar;59(3):304-11 [8653993] Pharmacogenetics. 1996 Feb;6(1):117-9 [8845859] Antimicrob Agents Chemother. 1996 Jun;40(6):1531-3 [8726032] Pharmacogenetics. 1995 Dec;5(6):389-92 [8747411] Pharmacogenetics. 1996 Aug;6(4):341-9 [8873220] Br J Clin Pharmacol. 1996 Oct;42(4):471-4 [8904619] J Pharmacol Exp Ther. 1997 Apr;281(1):604-9 [9103550] Clin Pharmacol Ther. 1997 May;61(5):574-82 [9164419] Pharmacogenetics. 1997 Jun;7(3):203-10 [9241660] Clin Pharmacol Ther. 1997 Sep;62(3):287-92 [9333104] Pharmacogenetics. 1997 Oct;7(5):361-7 [9352571] Clin Pharmacol Ther. 1997 Dec;62(6):619-28 [9433390] J Pharmacol Exp Ther. 1998 Jan;284(1):356-61 [9435198] Eur J Clin Pharmacol. 1997;53(3-4):261-4 [9476042] Drug Metab Dispos. 1998 Jul;26(7):609-16 [9660842] J Pharmacol Exp Ther. 1998 Sep;286(3):1490-5 [9732415] Ann Intern Med. 1998 Dec 15;129(12):1027-30 [9867757] Biochem Biophys Res Commun. 1999 Jan 27;254(3):628-31 [9920790] Pharmacogenetics. 1998 Apr;8(2):129-35 [10022751] Lancet. 1999 Feb 27;353(9154):717-9 [10073515] Zhongguo Yao Li Xue Bao. 1997 May;18(3):216-8 [10072936] Clin Pharmacol Ther. 1999 Mar;65(3):348-52 [10096267] Pharmacogenetics. 1999 Feb;9(1):71-80 [10208645] Clin Pharmacol Ther. 1999 May;65(5):552-61 [10340921] J Pharmacol Exp Ther. 1999 Aug;290(2):635-40 [10411572] Br J Clin Pharmacol. 1999 Aug;48(2):158-67 [10417492] Aliment Pharmacol Ther. 1999 Aug;13 Suppl 3:27-36 [10491726] Comment In: Br J Clin Pharmacol. 2002 Apr;53(4):408-9 [11966680] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Iodoacetate protects hippocampal neurons against excitotoxic and oxidative injury: involvement of heat-shock proteins and Bcl-2. AN - 72231989; 11677264 AB - Mild metabolic stress may increase resistance of neurons in the brain to subsequent, more severe insults, as demonstrated by the ability of ischemic pre-conditioning and dietary restriction to protect neurons in experimental models of stroke- and age-related neurodegenerative disorders. In the present study we employed iodoacetic acid (IAA), an inhibitor of glyceraldehyde-3-phosphate dehydrogenase, to test the hypothesis that inhibition of glycolysis can protect neurons. Pre-treatment of cultured hippocampal neurons with IAA can protect them against cell death induced by glutamate, iron and trophic factor withdrawal. Surprisingly, protection occurred with concentrations of IAA (2-200 nM) much lower than those required to inhibit glycolysis. Pre-treatment with IAA results in suppression of oxyradical production and stabilization of mitochondrial function in neurons after exposure to oxidative insults. Levels of the stress heat-shock proteins HSP70 and HSP90, and of the anti-apoptotic protein Bcl-2, were increased in neurons exposed to IAA. Our data demonstrate that IAA can stimulate cytoprotective mechanisms within neurons, and suggest the possible use of IAA and related compounds in the prevention and/or treatment of neurodegenerative conditions. JF - Journal of neurochemistry AU - Guo, Z AU - Lee, J AU - Lane, M AU - Mattson, M AD - Laboratory of Neurosciences, National Institute on Aging-Gerontology Research Center, Baltimore, Maryland 21224, USA. Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 361 EP - 370 VL - 79 IS - 2 SN - 0022-3042, 0022-3042 KW - HSP70 Heat-Shock Proteins KW - 0 KW - HSP90 Heat-Shock Proteins KW - Iodoacetates KW - Neuroprotective Agents KW - Neurotoxins KW - Proto-Oncogene Proteins c-bcl-2 KW - Glutamic Acid KW - 3KX376GY7L KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Iron KW - E1UOL152H7 KW - Iodoacetic Acid KW - WF5188V710 KW - Index Medicus KW - Osmolar Concentration KW - Animals KW - Iron -- pharmacology KW - HSP70 Heat-Shock Proteins -- physiology KW - Proto-Oncogene Proteins c-bcl-2 -- physiology KW - HSP90 Heat-Shock Proteins -- physiology KW - Cell Death -- drug effects KW - Glutamic Acid -- pharmacology KW - Iodoacetic Acid -- pharmacology KW - Neuroprotective Agents -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - Adenosine Triphosphate -- metabolism KW - Membrane Potentials -- drug effects KW - Oxidative Stress -- physiology KW - Iodoacetates -- pharmacology KW - Neurons -- metabolism KW - Hippocampus -- physiology KW - Neurons -- drug effects KW - Hippocampus -- metabolism KW - Hippocampus -- cytology KW - Neurons -- physiology KW - Neurotoxins -- pharmacology KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72231989?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Iodoacetate+protects+hippocampal+neurons+against+excitotoxic+and+oxidative+injury%3A+involvement+of+heat-shock+proteins+and+Bcl-2.&rft.au=Guo%2C+Z%3BLee%2C+J%3BLane%2C+M%3BMattson%2C+M&rft.aulast=Guo&rft.aufirst=Z&rft.date=2001-10-01&rft.volume=79&rft.issue=2&rft.spage=361&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-10-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional and spatiotemporal regulation of prolactin receptor mRNA and cooperativity with progesterone receptor function during ductal branch growth in the mammary gland. AN - 72221646; 11668597 AB - Ductal branching within the mammary gland is stimulated by prolactin (PRL) and progesterone (P) acting through their receptors (PRLR and PR). Analysis of mammary gland PRLR expression revealed increasing expression of the long form (L-PRLR) and two of the three short forms (S1- and S3-PRLR) during puberty that became maximal late in pubescence and early gestation, then declined during gestation. By contrast, S2-PRLR mRNA levels remained constant. Examination of stromal PRLR revealed the consistent expression of L-PRLR mRNA. By contrast, S1-PRLR was present only in the mammary fat pad of neonates, whereas high neonatal expression of S2-PRLR became undetectable during puberty. Stromal expression of S3-PRLR decreased to low levels during puberty and was undetectable during lactation and involution. Exogenous PRL stimulated DNA synthesis in both epithelial and adjacent stromal cells in vivo. Distribution of PRLR mRNA in mammary epithelium was homogeneous before puberty and heterogeneous during puberty, gestation, and early lactation. A mutual role for PRLR and PR was suggested wherein PR mRNA increased beyond 6 weeks to maximal levels during puberty and gestation then became undetectable during lactation. In situ hybridization revealed that PR mRNA distribution is homogeneous in the ductal epithelium before 6 weeks and heterogenous during puberty and gestation and that PRLR and PR are similarly distributed in the ductal epithelium. Neither hormone stimulated DNA synthesis in mammary glands of ovariectomized females while their effects interacted markedly. These results demonstrate differential PRLR transcription by epithelial and stromal cells and a similar distribution of PRLR and PR that may facilitate the interaction between P and PRL during ductal branching in the mammary gland. Copyright 2001 Wiley-Liss, Inc. JF - Developmental dynamics : an official publication of the American Association of Anatomists AU - Hovey, R C AU - Trott, J F AU - Ginsburg, E AU - Goldhar, A AU - Sasaki, M M AU - Fountain, S J AU - Sundararajan, K AU - Vonderhaar, B K AD - Molecular and Cellular Endocrinology Section, Center for Cancer Research, NCI, NIH, 10 Center Drive, Bethesda, MD 20892-1402, USA. rh149d@nih.gov Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 192 EP - 205 VL - 222 IS - 2 SN - 1058-8388, 1058-8388 KW - Estrogens KW - 0 KW - RNA, Messenger KW - Receptors, Progesterone KW - Receptors, Prolactin KW - Progesterone KW - 4G7DS2Q64Y KW - Prolactin KW - 9002-62-4 KW - Index Medicus KW - Animals KW - Progesterone -- pharmacology KW - RNA, Messenger -- analysis KW - Cell Division -- drug effects KW - Cell Division -- physiology KW - Adipose Tissue -- physiology KW - Mice KW - Mice, Inbred BALB C KW - Epithelial Cells -- metabolism KW - Epithelial Cells -- cytology KW - Estrogens -- pharmacology KW - Ovariectomy KW - Stromal Cells -- metabolism KW - Prolactin -- pharmacology KW - Drug Synergism KW - Stromal Cells -- cytology KW - Female KW - Gene Expression Regulation, Developmental KW - Receptors, Progesterone -- genetics KW - Receptors, Prolactin -- metabolism KW - Receptors, Progesterone -- metabolism KW - Mammary Glands, Animal -- cytology KW - Mammary Glands, Animal -- physiology KW - Mammary Glands, Animal -- growth & development KW - Receptors, Prolactin -- genetics KW - Transcription, Genetic -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72221646?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+dynamics+%3A+an+official+publication+of+the+American+Association+of+Anatomists&rft.atitle=Transcriptional+and+spatiotemporal+regulation+of+prolactin+receptor+mRNA+and+cooperativity+with+progesterone+receptor+function+during+ductal+branch+growth+in+the+mammary+gland.&rft.au=Hovey%2C+R+C%3BTrott%2C+J+F%3BGinsburg%2C+E%3BGoldhar%2C+A%3BSasaki%2C+M+M%3BFountain%2C+S+J%3BSundararajan%2C+K%3BVonderhaar%2C+B+K&rft.aulast=Hovey&rft.aufirst=R&rft.date=2001-10-01&rft.volume=222&rft.issue=2&rft.spage=192&rft.isbn=&rft.btitle=&rft.title=Developmental+dynamics+%3A+an+official+publication+of+the+American+Association+of+Anatomists&rft.issn=10588388&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-31 N1 - Date created - 2001-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Msx2 is a repressor of chondrogenic differentiation in migratory cranial neural crest cells. AN - 72218971; 11668602 AB - During early mouse embryogenesis, cranial neural crest cells (CNCC) emigrate from the posterior midbrain and rhombomeres 1 and 2 of the anterior hindbrain into the first branchial arch-derived maxillary and mandibular processes and there provide cell lineages for several phenotypes, including cartilage, bone, and tooth. Here, we report that Sox9 and Msx2 were coexpressed in a subpopulation of CNCC during their migration. Because Sox9 is a transactivator of chondrogenesis, and Msx genes can act as transcriptional repressors, we hypothesized that Sox9 expression indicates the determination of CNCC-derived chondrogenic cell lineage and that Msx2 represses chondrogenic differentiation until CNCC migration is completed within the mandibular processes. To test whether Msx2 represses chondrogenesis, we designed experiments to inhibit Msx2 function in migratory CNCC in primary cultures through the expression of loss-of-function Msx2 mutants. We showed that infection of migratory CNCC with adenovirus Msx2 mutants accelerated the rate and extent of chondrogenesis, as indicated by the expression level of type II collagen and aggrecan, and the amount of alcian blue staining. Adenovirus infections did not apparently interfere with CNCC proliferation or migration. These findings suggest that an important early event in craniofacial morphogenesis is a transient expression of both Sox9 and Msx2 during emigration into the forming mandibular processes followed by restricted expression of Sox9 within CNCC- derived chondroprogenitor cells. We conclude that Msx2 serves as a repressor of chondrogenic differentiation during CNCC migration. Copyright 2001 Wiley-Liss, Inc. JF - Developmental dynamics : an official publication of the American Association of Anatomists AU - Takahashi, K AU - Nuckolls, G H AU - Takahashi, I AU - Nonaka, K AU - Nagata, M AU - Ikura, T AU - Slavkin, H C AU - Shum, L AD - Craniofacial Development Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 6 Center Drive, Bethesda, MD 20892-2745, USA. Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 252 EP - 262 VL - 222 IS - 2 SN - 1058-8388, 1058-8388 KW - Agc1 protein, mouse KW - 0 KW - Aggrecans KW - Collagen Type II KW - Coloring Agents KW - DNA-Binding Proteins KW - Extracellular Matrix Proteins KW - High Mobility Group Proteins KW - Homeodomain Proteins KW - Lectins, C-Type KW - MSX2 protein KW - Proteoglycans KW - SOX9 Transcription Factor KW - SOX9 protein, human KW - Sox9 protein, mouse KW - Transcription Factors KW - Alcian Blue KW - P4448TJR7J KW - Index Medicus KW - Animals KW - Gene Transfer Techniques KW - Humans KW - Mandibulofacial Dysostosis -- genetics KW - Proteoglycans -- genetics KW - High Mobility Group Proteins -- genetics KW - Cartilage -- cytology KW - Kidney -- cytology KW - Collagen Type II -- genetics KW - Mutagenesis -- physiology KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Transcription Factors -- genetics KW - Cartilage -- embryology KW - Adenoviridae -- genetics KW - Cell Differentiation -- physiology KW - Cells, Cultured KW - Cell Movement -- physiology KW - Staining and Labeling KW - Chondrocytes -- cytology KW - Neural Crest -- embryology KW - DNA-Binding Proteins -- genetics KW - Neural Crest -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72218971?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+dynamics+%3A+an+official+publication+of+the+American+Association+of+Anatomists&rft.atitle=Msx2+is+a+repressor+of+chondrogenic+differentiation+in+migratory+cranial+neural+crest+cells.&rft.au=Takahashi%2C+K%3BNuckolls%2C+G+H%3BTakahashi%2C+I%3BNonaka%2C+K%3BNagata%2C+M%3BIkura%2C+T%3BSlavkin%2C+H+C%3BShum%2C+L&rft.aulast=Takahashi&rft.aufirst=K&rft.date=2001-10-01&rft.volume=222&rft.issue=2&rft.spage=252&rft.isbn=&rft.btitle=&rft.title=Developmental+dynamics+%3A+an+official+publication+of+the+American+Association+of+Anatomists&rft.issn=10588388&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-31 N1 - Date created - 2001-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dextran sulphate sodium-induced colitis is ameliorated in interleukin 4 deficient mice. AN - 72212174; 11607786 AB - The importance of IL-4 and its effects in inflammatory bowel disease (IBD) was studied using the dextran sulphate sodium-induced model of experimental colitis. The model resembles ulcerative colitis in humans. IL-4 deficient mice and IL-4+/+ littermates were used to induce colitis. Activity of disease, extent of tissue damage, immunoglobulin isotypes, IFNgamma and IL-10 production was assessed. Both disease activity index (DAI) and histological scores were consistently lower in the IL-4 deficient mice than in the IL-4+/+ littermates. Furthermore, the lower histological scores reflected the milder inflammatory lesions and decreased ulceration found in the IL-4 deficient mice. Analysis of immunoglobulin subtypes showed that IgG1 was almost absent in the sera of IL-4 deficient mice. IFNgamma contents was much higher in colonic tissues from IL-4 deficient mice. Dextran sulphate sodium-induced colitis is ameliorated in IL-4 deficient mice. IL-4 either directly or through its effects on T and B cells influences its severity. It is unclear if the higher immunoglobulin-producing cells in the colonic tissues of IL-4 deficient mice before colitis was induced could have influenced the outcome of the disease. The high IFNgamma contents in colonic tissues of IL-4 deficient mice argue against the role of this cytokine as a crucial mediator of tissue damage during the acute phase of colitis. JF - Genes and immunity AU - Stevceva, L AU - Pavli, P AU - Husband, A AU - Ramsay, A AU - Doe, W F AD - Division of Molecular Medicine, John Curtin School of Medical Research, ANU, Canberra, ACT, 2601, Australia. stevcevl@mail.nih.gov Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 309 EP - 316 VL - 2 IS - 6 SN - 1466-4879, 1466-4879 KW - Immunoglobulins KW - 0 KW - RNA, Messenger KW - Interleukin-10 KW - 130068-27-8 KW - Interleukin-4 KW - 207137-56-2 KW - Interferon-gamma KW - 82115-62-6 KW - Dextran Sulfate KW - 9042-14-2 KW - Index Medicus KW - Animals KW - Colon -- pathology KW - Gene Expression KW - Interferon-gamma -- immunology KW - Mice KW - RNA, Messenger -- genetics KW - Colon -- immunology KW - Mice, Knockout KW - Microscopy, Fluorescence KW - In Situ Hybridization KW - RNA, Messenger -- metabolism KW - Enzyme-Linked Immunosorbent Assay KW - Immunoglobulins -- blood KW - Interleukin-10 -- genetics KW - Time Factors KW - Interferon-gamma -- analysis KW - Interleukin-4 -- genetics KW - Colitis -- immunology KW - Interleukin-4 -- immunology KW - Interleukin-4 -- deficiency KW - Dextran Sulfate -- pharmacology KW - Colitis -- pathology KW - Colitis -- chemically induced KW - Colitis -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72212174?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+and+immunity&rft.atitle=Dextran+sulphate+sodium-induced+colitis+is+ameliorated+in+interleukin+4+deficient+mice.&rft.au=Stevceva%2C+L%3BPavli%2C+P%3BHusband%2C+A%3BRamsay%2C+A%3BDoe%2C+W+F&rft.aulast=Stevceva&rft.aufirst=L&rft.date=2001-10-01&rft.volume=2&rft.issue=6&rft.spage=309&rft.isbn=&rft.btitle=&rft.title=Genes+and+immunity&rft.issn=14664879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-15 N1 - Date created - 2001-10-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toward gene therapy for disorders of globin synthesis. AN - 72207208; 11605174 AB - Inherited disorders of hemoglobin remain desirable targets for genetically based therapies. That stem cell replacement reverses the phenotype of both thalassemia and sickle cell anemia has been well established through allogeneic bone marrow transplantation studies, yet significant toxicities and finite donor availability limit this approach to a minority of affected individuals. Genetically based strategies that have as their goal addition of a normal copy of the human beta-globin gene along with key regulatory sequences to autologous hematopoietic stem cells represent a viable alternative to allogeneic transplantation, but this approach has been impeded by formidable obstacles over the last decade. Large animal models have become the standard for the development of clinically relevant gene addition strategies, and significant progress in the techniques used to deliver potentially therapeutic genes has been achieved. The clinical application of such strategies may be close at hand, at least for disorders in which modest level, constitutive expression is sufficient to correct the phenotype. For the thalassemias and hemoglobinopathies, complex, regulated, lineage specific expression of the beta-globin gene at relatively high levels will be required. The discovery of the beta-globin locus control region renewed interest in the thalassemias and sickle cell anemia as targets for gene transfer, but difficulties in attaining high-titer vectors along with a tendency toward rearrangement when segments of the locus control region (LCR) were incorporated into retroviral vectors stalled further progress. Recent advances in vector construction have circumvented this problem and others limiting both gene transfer efficiency and regulation of transgene expression, offering new hope for clinical application. JF - Seminars in hematology AU - Tisdale, J AU - Sadelain, M AD - Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Disorders, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 382 EP - 392 VL - 38 IS - 4 SN - 0037-1963, 0037-1963 KW - Index Medicus KW - Animals KW - Humans KW - Transduction, Genetic KW - Hematopoietic Stem Cell Transplantation KW - Hematopoietic Stem Cells -- metabolism KW - Genetic Therapy -- methods KW - Hemoglobinopathies -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72207208?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+hematology&rft.atitle=Toward+gene+therapy+for+disorders+of+globin+synthesis.&rft.au=Tisdale%2C+J%3BSadelain%2C+M&rft.aulast=Tisdale&rft.aufirst=J&rft.date=2001-10-01&rft.volume=38&rft.issue=4&rft.spage=382&rft.isbn=&rft.btitle=&rft.title=Seminars+in+hematology&rft.issn=00371963&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-08 N1 - Date created - 2001-10-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A pilot study to rate determinants of exposure from videotaped work activities of farmers' use of pesticides. AN - 72193342; 11599547 AB - Industrial hygienists often observe workers to determine who should be measured based on a predicted exposure level. Such evaluations are usually based on real-time observation, yet surprisingly little research has been conducted on what determinants of exposure industrial hygienists use to rank workers and whether the ranking is accurate. Accuracy of the ranking may also be affected by the observation process, which is limited when conditions in the workers' immediate environment are rapidly changing. An alternative to real-time observation is videotaping workers and evaluating the tapes at a later date. A pilot study was conducted using previously collected data to determine if workers could be ranked by exposure level utilizing a scoring system to rate videotaped work practices. Six farmers had been videotaped and their dermal exposures measured as they applied insecticide to hogs. In this study, scores were developed to rate the farmers' working conditions by exposure level. Two types of determinants were used to describe exposure: touching and work practices. Touching included the number of times parts of the body had contact with surfaces possibly contaminated with insecticide. Work practices included the types of clothing and protective equipment worn as well as specific practices used by the farmer (e.g., application method). Two raters conducted independent assessments of the videotape using the same criteria. One rater reviewed the tape twice. Agreement between the raters for the "touching" score was weak (intra-class coefficient (ICC) = 0.28), but there was excellent agreement between the two raters (ICC = 0.92) for overall quality of work practices. As expected, a greater number of touches was moderately correlated with an increase in total exposure (rs = 0.60) and there was a weak inverse relationship between protective work practices and the exposure under the clothing (rs = -0.26). All other relationships with exposure level were contrary to what was expected. Since videotapes provide the industrial hygienist with a record of work events and can capture details that might otherwise be missed or not considered they may play a useful role in exposure assessment, especially if carefully developed procedures are followed to overcome the limitations found by this pilot study. JF - Applied occupational and environmental hygiene AU - Prince, J R AU - Stewart, P A AU - Nam, J M AU - Blair, A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 973 EP - 978 VL - 16 IS - 10 SN - 1047-322X, 1047-322X KW - Pesticides KW - 0 KW - Index Medicus KW - Swine KW - Animals KW - Humans KW - Animal Husbandry KW - Pilot Projects KW - Pesticides -- analysis KW - Agriculture KW - Videotape Recording KW - Work KW - Occupational Exposure -- analysis KW - Environmental Monitoring -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72193342?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+occupational+and+environmental+hygiene&rft.atitle=A+pilot+study+to+rate+determinants+of+exposure+from+videotaped+work+activities+of+farmers%27+use+of+pesticides.&rft.au=Prince%2C+J+R%3BStewart%2C+P+A%3BNam%2C+J+M%3BBlair%2C+A&rft.aulast=Prince&rft.aufirst=J&rft.date=2001-10-01&rft.volume=16&rft.issue=10&rft.spage=973&rft.isbn=&rft.btitle=&rft.title=Applied+occupational+and+environmental+hygiene&rft.issn=1047322X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-25 N1 - Date created - 2001-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A historical cohort mortality study among shipyard workers in Genoa, Italy. AN - 72191427; 11598985 AB - A historical cohort mortality study was conducted among 3984 shipyard workers assigned to ship repair, refitting, and construction in the harbor of Genoa, Italy, between 1960 and 1981. These workers were exposed to asbestos fibers, welding fumes and gases, silica dust, polycyclic aromatic hydrocarbons, and solvents. Workers were classified in 20 different job-titles depending upon the type of activity. Standardized mortality ratios (SMRs) were computed using male residents of the Province of Genoa as the referent population. For the whole cohort significantly increased SMRs were detected for all causes, all cancers, liver, larynx, lung, pleural and bladder cancers, respiratory tract diseases, and cirrhosis of the liver. The analysis by job-title showed increased SMRs not only for pleural cancer, but also for lung, laryngeal cancers and respiratory tract diseases in occupations entailing heavy asbestos exposure. Bladder and liver cancers and liver cirrhosis mortality also appeared to be related to occupational exposure. Copyright 2001 Wiley-Liss, Inc. JF - American journal of industrial medicine AU - Puntoni, R AU - Merlo, F AU - Borsa, L AU - Reggiardo, G AU - Garrone, E AU - Ceppi, M AD - Environmental Epidemiology and Biostatistics, National Cancer Institute, Largo Rosanna Benzi 19, 16132 Genoa, Italy. puntonir@hp380.ist.unige.it Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 363 EP - 370 VL - 40 IS - 4 SN - 0271-3586, 0271-3586 KW - Polycyclic Compounds KW - 0 KW - Silicon Dioxide KW - 7631-86-9 KW - Index Medicus KW - Ships KW - Humans KW - Liver Neoplasms -- mortality KW - Aged KW - Polycyclic Compounds -- adverse effects KW - Asbestosis -- etiology KW - Silicon Dioxide -- adverse effects KW - Respiratory Tract Neoplasms -- mortality KW - Asbestosis -- mortality KW - Adult KW - Cohort Studies KW - Urinary Bladder Neoplasms -- mortality KW - Follow-Up Studies KW - Middle Aged KW - Italy -- epidemiology KW - Male KW - Industry KW - Occupational Exposure -- statistics & numerical data KW - Occupational Diseases -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72191427?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=A+historical+cohort+mortality+study+among+shipyard+workers+in+Genoa%2C+Italy.&rft.au=Puntoni%2C+R%3BMerlo%2C+F%3BBorsa%2C+L%3BReggiardo%2C+G%3BGarrone%2C+E%3BCeppi%2C+M&rft.aulast=Puntoni&rft.aufirst=R&rft.date=2001-10-01&rft.volume=40&rft.issue=4&rft.spage=363&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics and toxicity of intravitreal chemotherapy for primary intraocular lymphoma. AN - 72190660; 11594954 AB - To investigate the pharmacokinetics and toxicity of intravitreal chemotherapeutic agents in the rabbit eye for the potential treatment of primary intraocular lymphoma and other intraocular malignancies. The ocular pharmacokinetics of intravitreal methotrexate sodium (400 microg) was studied in 10 New Zealand white rabbits, and a single-compartment, first-order elimination model was used to calculate the drug half-life. With the use of these data, a treatment schedule using serial injections of intravitreal methotrexate and single injections of fluorouracil and dexamethasone sodium phosphate was developed. This schedule was studied in 4 New Zealand white rabbits to explore the combined toxicity of these agents. Methotrexate vitreous levels, following a 400-microg intravitreal injection, remained therapeutic (>0.5 microM) in the rabbit eye for 48 to 72 hours. Intravitreal methotrexate, combined with fluorouracil and dexamethasone, showed no evidence of drug toxicity as determined by electroretinography and histopathologic examination. A treatment schedule for primary intraocular lymphoma consisting of methotrexate intravitreal injections every 48 to 72 hours provides therapeutic drug concentrations in the vitreous and, in combination with fluorouracil and dexamethasone, appears to be safe in the rabbit eye. Although responsive to conventional chemotherapy or radiotherapy, recurrence of ocular involvement with primary central nervous system lymphoma occurs in more than 50% of treated cases. Anecdotal reports of the use of intravitreal chemotherapy for primary intraocular lymphoma have been encouraging. However, animal data on the pharmacokinetics and toxicity of combined intravitreal agents for the treatment of this disease are lacking. JF - Archives of ophthalmology (Chicago, Ill. : 1960) AU - Velez, G AU - Yuan, P AU - Sung, C AU - Tansey, G AU - Reed, G F AU - Chan, C C AU - Nussenblatt, R B AU - Robinson, M R AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA. brusie-velez@erols.com Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 1518 EP - 1524 VL - 119 IS - 10 SN - 0003-9950, 0003-9950 KW - Dexamethasone KW - 7S5I7G3JQL KW - Fluorouracil KW - U3P01618RT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Abridged Index Medicus KW - Index Medicus KW - Fluorouracil -- administration & dosage KW - Animals KW - Half-Life KW - Retina -- drug effects KW - Dexamethasone -- administration & dosage KW - Rabbits KW - Retina -- pathology KW - Methotrexate -- administration & dosage KW - Electroretinography -- drug effects KW - Male KW - Female KW - Chromatography, High Pressure Liquid KW - Biological Availability KW - Vitreous Body -- metabolism KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacokinetics KW - Eye Neoplasms -- drug therapy KW - Lymphoma -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72190660?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+ophthalmology+%28Chicago%2C+Ill.+%3A+1960%29&rft.atitle=Pharmacokinetics+and+toxicity+of+intravitreal+chemotherapy+for+primary+intraocular+lymphoma.&rft.au=Velez%2C+G%3BYuan%2C+P%3BSung%2C+C%3BTansey%2C+G%3BReed%2C+G+F%3BChan%2C+C+C%3BNussenblatt%2C+R+B%3BRobinson%2C+M+R&rft.aulast=Velez&rft.aufirst=G&rft.date=2001-10-01&rft.volume=119&rft.issue=10&rft.spage=1518&rft.isbn=&rft.btitle=&rft.title=Archives+of+ophthalmology+%28Chicago%2C+Ill.+%3A+1960%29&rft.issn=00039950&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-25 N1 - Date created - 2001-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I trial and pharmacokinetic study of 9-cis-retinoic acid (ALRT1057) in pediatric patients with refractory cancer: a joint Pediatric Oncology Branch, National Cancer Institute, and Children's Cancer Group study. AN - 72189066; 11595692 AB - To determine the maximum tolerated dose and describe the toxicities of 9-cis-retinoic acid (9cRA, ALRT1057) administered p.o. tid in pediatric patients with refractory cancer and to study the pharmacokinetics of 9cRA and determine whether systemic drug exposure changes with chronic dosing. Children with refractory cancer (stratified by age, 12 years) were treated with p.o. 9cRA for 28 consecutive days. The starting dose was 50 mg/m(2)/day divided into 3 doses with planned escalations to 65, 85, and 110 mg/m(2)/day. Pharmacokinetic sampling was performed on days 1 and 29 of the first cycle. Of the 37 patients entered, 18 patients 12 years of age were evaluable for toxicity. In patients >12 years of age, dose-limiting headache occurred in 2/2 patients at the 110 mg/m(2)/day dose level; 1/8 patients at 85 mg/m(2)/day developed dose-limiting pseudotumor cerebri. In patients < or =12 years of age, 3/5 patients at the starting dose level of 50 mg/m(2)/day developed dose-limiting pseudotumor cerebri; and 0/6 patients experienced dose-limiting toxicity at 35 mg/m(2)/day. Reversible non-dose-limiting hepatotoxicity was observed in 15 patients across all of the dose levels. There was considerable interpatient variability in 9cRA plasma concentrations. Peak plasma concentrations of 9cRA occurred at a median of 1.5 h after a p.o. dose, and the harmonic-mean terminal half-life was 43 min. By day 29 of 9cRA administration, the plasma 9cRA area under the curve declined by an average of 65% from day 1 values. The dose-limiting toxicity of 9cRA in pediatric patients was neurotoxicity, primarily pseudotumor cerebri. Younger children tolerate significantly lower doses of 9cRA than older children. Similar to all-trans-retinoic acid, the pharmacokinetics of 9cRA demonstrated a wide degree of interpatient variability and decreased over time when administered on a daily basis. The recommended Phase II dose of 9cRA in patients 12 years of age is 35 and 85 mg/m(2)/day, respectively. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Adamson, P C AU - Widemann, B C AU - Reaman, G H AU - Seibel, N L AU - Murphy, R F AU - Gillespie, A F AU - Balis, F M AD - Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA. adamson@email.chop.edu Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 3034 EP - 3039 VL - 7 IS - 10 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - Triglycerides KW - alitretinoin KW - 1UA8E65KDZ KW - Tretinoin KW - 5688UTC01R KW - Transaminases KW - EC 2.6.1.- KW - Index Medicus KW - Triglycerides -- blood KW - Age Factors KW - Liver -- enzymology KW - Area Under Curve KW - Dose-Response Relationship, Drug KW - Humans KW - Vomiting -- chemically induced KW - Child KW - Skin Diseases -- chemically induced KW - Child, Preschool KW - Nausea -- chemically induced KW - Headache -- chemically induced KW - Transaminases -- metabolism KW - Adult KW - Treatment Outcome KW - Transaminases -- drug effects KW - Adolescent KW - Female KW - Male KW - Neoplasms -- drug therapy KW - Antineoplastic Agents -- pharmacokinetics KW - Antineoplastic Agents -- therapeutic use KW - Tretinoin -- pharmacokinetics KW - Tretinoin -- therapeutic use KW - Tretinoin -- adverse effects KW - Neoplasms -- metabolism KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72189066?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=A+phase+I+trial+and+pharmacokinetic+study+of+9-cis-retinoic+acid+%28ALRT1057%29+in+pediatric+patients+with+refractory+cancer%3A+a+joint+Pediatric+Oncology+Branch%2C+National+Cancer+Institute%2C+and+Children%27s+Cancer+Group+study.&rft.au=Adamson%2C+P+C%3BWidemann%2C+B+C%3BReaman%2C+G+H%3BSeibel%2C+N+L%3BMurphy%2C+R+F%3BGillespie%2C+A+F%3BBalis%2C+F+M&rft.aulast=Adamson&rft.aufirst=P&rft.date=2001-10-01&rft.volume=7&rft.issue=10&rft.spage=3034&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-05 N1 - Date created - 2001-10-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Clin Cancer Res. 2001 Oct;7(10):2955-7 [11595682] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional effect of adeno-associated virus mediated gene transfer of aromatic L-amino acid decarboxylase into the striatum of 6-OHDA-lesioned rats. AN - 72185248; 11592835 AB - In animal models of Parkinson's disease, gene transfer of aromatic L-amino acid decarboxylase (AADC) leads to an increase in the capacity of the striatum to decarboxylate exogenous L-DOPA. However, the functional effects of enhanced L-DOPA to dopamine conversion have not been explored. Here, we show that following adeno-associated virus (AAV)-AADC transduction, the transgenic AADC is able to decarboxylate exogenous L-DOPA more efficiently so that a dose of L-DOPA ineffective before gene transfer elicits a motor asymmetry (rotational behavior) following gene transfer. Furthermore, rotation scores showed a strong correlation with AADC activity in the lesioned striatum, thus allowing for behavioral screening of successful gene transfer in the brain. In animals receiving AAV2-AADC, dopamine production was restored to 50% of normal levels 12 weeks after the infusion. Microdialysis experiments demonstrated an in vivo enhanced conversion of L-DOPA to dopamine, but no storage capacity as dopamine was released to the extracellular space in a continuous, nonregulated fashion. In addition to the potential clinical benefit of improving decarboxylation efficiency in Parkinson's disease, our approach may be relevant for the treatment of AADC deficiency, a rare, autosomal recessive disorder causing a severe movement disorder and progressive cognitive impairment. JF - Molecular therapy : the journal of the American Society of Gene Therapy AU - Sánchez-Pernaute, R AU - Harvey-White, J AU - Cunningham, J AU - Bankiewicz, K S AD - Molecular Therapeutics Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland 20892, USA. Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 324 EP - 330 VL - 4 IS - 4 SN - 1525-0016, 1525-0016 KW - Levodopa KW - 46627O600J KW - Oxidopamine KW - 8HW4YBZ748 KW - Aromatic-L-Amino-Acid Decarboxylases KW - EC 4.1.1.28 KW - Apomorphine KW - N21FAR7B4S KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Parkinson Disease, Secondary -- chemically induced KW - Apomorphine -- pharmacology KW - Transduction, Genetic KW - Disease Models, Animal KW - Dopamine -- metabolism KW - Levodopa -- chemistry KW - Oxidopamine -- pharmacology KW - Levodopa -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Genetic Therapy -- methods KW - Genetic Vectors -- genetics KW - Rotation KW - Levodopa -- metabolism KW - Neostriatum -- metabolism KW - Parkinson Disease -- therapy KW - Gene Transfer Techniques KW - Aromatic-L-Amino-Acid Decarboxylases -- therapeutic use KW - Neostriatum -- drug effects KW - Dependovirus -- genetics KW - Aromatic-L-Amino-Acid Decarboxylases -- metabolism KW - Parkinson Disease -- physiopathology KW - Neostriatum -- pathology KW - Neostriatum -- enzymology KW - Aromatic-L-Amino-Acid Decarboxylases -- genetics KW - Parkinson Disease -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72185248?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+therapy+%3A+the+journal+of+the+American+Society+of+Gene+Therapy&rft.atitle=Functional+effect+of+adeno-associated+virus+mediated+gene+transfer+of+aromatic+L-amino+acid+decarboxylase+into+the+striatum+of+6-OHDA-lesioned+rats.&rft.au=S%C3%A1nchez-Pernaute%2C+R%3BHarvey-White%2C+J%3BCunningham%2C+J%3BBankiewicz%2C+K+S&rft.aulast=S%C3%A1nchez-Pernaute&rft.aufirst=R&rft.date=2001-10-01&rft.volume=4&rft.issue=4&rft.spage=324&rft.isbn=&rft.btitle=&rft.title=Molecular+therapy+%3A+the+journal+of+the+American+Society+of+Gene+Therapy&rft.issn=15250016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-12 N1 - Date created - 2001-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A murine dopamine neuron-specific cDNA library and microarray: increased COX1 expression during methamphetamine neurotoxicity. AN - 72184865; 11592851 AB - Due to brain tissue heterogeneity, the molecular genetic profile of any neurotransmitter-specific neuronal subtype is unknown. The purpose of this study was to purify a population of dopamine neurons, construct a cDNA library, and generate an initial gene expression profile and a microarray representative of dopamine neuron transcripts. Ventral mesencephalic dopamine neurons were purified by fluorescent-activated cell sorting from embryonic day 13.5 transgenic mice harboring a 4.5-kb rat tyrosine hydroxylase promoter-lacZ fusion. Nine-hundred sixty dopamine neuron cDNA clones were sequenced and arrayed for use in studies of gene expression changes during methamphetamine neurotoxicity. A neurotoxic dose of methamphetamine produced a greater than twofold up-regulation of the mitochondrial cytochrome c oxidase polypeptide I transcript from adult mouse substantia nigra at 12 h posttreatment. This is the first work to describe a gene expression profile for a neuronal subtype and to identify gene expression changes during methamphetamine neurotoxicity. Copyright 2001 Academic Press. JF - Neurobiology of disease AU - Barrett, T AU - Xie, T AU - Piao, Y AU - Dillon-Carter, O AU - Kargul, G J AU - Lim, M K AU - Chrest, F J AU - Wersto, R AU - Rowley, D L AU - Juhaszova, M AU - Zhou, L AU - Vawter, M P AU - Becker, K G AU - Cheadle, C AU - Wood, W H AU - McCann, U D AU - Freed, W J AU - Ko, M S AU - Ricaurte, G A AU - Donovan, D M AD - Research Resources Branch, Laboratory of Genetics, Intramural Research Program, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, Maryland 21224-6825, USA. Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 822 EP - 833 VL - 8 IS - 5 SN - 0969-9961, 0969-9961 KW - DNA, Complementary KW - 0 KW - Dopamine Uptake Inhibitors KW - Nerve Tissue Proteins KW - 3,4-Dihydroxyphenylacetic Acid KW - 102-32-9 KW - Methamphetamine KW - 44RAL3456C KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Electron Transport Complex IV KW - EC 1.9.3.1 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - DNA, Complementary -- genetics KW - Transcription, Genetic KW - Genes, Synthetic KW - Mice KW - Mesencephalon -- cytology KW - Mice, Transgenic KW - Rats KW - Promoter Regions, Genetic KW - Tyrosine 3-Monooxygenase -- genetics KW - 3,4-Dihydroxyphenylacetic Acid -- analysis KW - Molecular Sequence Data KW - Enzyme Induction KW - Mesencephalon -- embryology KW - Lac Operon KW - Female KW - Male KW - Electron Transport Complex IV -- genetics KW - Gene Expression Profiling KW - Dopamine Uptake Inhibitors -- toxicity KW - Neurons -- metabolism KW - Oligonucleotide Array Sequence Analysis KW - Electron Transport Complex IV -- biosynthesis KW - Dopamine -- analysis KW - Nerve Tissue Proteins -- biosynthesis KW - Nerve Tissue Proteins -- genetics KW - Methamphetamine -- toxicity KW - Gene Library UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72184865?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurobiology+of+disease&rft.atitle=A+murine+dopamine+neuron-specific+cDNA+library+and+microarray%3A+increased+COX1+expression+during+methamphetamine+neurotoxicity.&rft.au=Barrett%2C+T%3BXie%2C+T%3BPiao%2C+Y%3BDillon-Carter%2C+O%3BKargul%2C+G+J%3BLim%2C+M+K%3BChrest%2C+F+J%3BWersto%2C+R%3BRowley%2C+D+L%3BJuhaszova%2C+M%3BZhou%2C+L%3BVawter%2C+M+P%3BBecker%2C+K+G%3BCheadle%2C+C%3BWood%2C+W+H%3BMcCann%2C+U+D%3BFreed%2C+W+J%3BKo%2C+M+S%3BRicaurte%2C+G+A%3BDonovan%2C+D+M&rft.aulast=Barrett&rft.aufirst=T&rft.date=2001-10-01&rft.volume=8&rft.issue=5&rft.spage=822&rft.isbn=&rft.btitle=&rft.title=Neurobiology+of+disease&rft.issn=09699961&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-23 N1 - Date created - 2001-10-10 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - BE825801; GENBANK; BE824549; BE824917; BE824908; BE824471; BE824874; BE824475; BE824515; BE824897; BE824514; BE824580; BE824891; BE824488; BE824509; BE824623; BE824608; BE824847; BE824534; BE824543; BE824737; BE824540 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular neurotoxicological models of Parkinsonism: focus on genetic manipulation of mice. AN - 71310749; 11489672 AB - Parkinson's disease is a neurodegenerative disorder that affects mainly the nigrostriatal dopaminergic system in humans. Several propositions have been put forward to explain the cellular and molecular pathobiology of this syndrome. Initial attempts were made through the use of various agents to manipulate the deleterious effects of toxins that destroy dopaminergic cells both in vitro and in vivo. These studies led to the idea that oxidative stress is an important factor in killing these cells. More recent attempts have made use of genetically modified mice to eliminate or over-express genes of interest. These experiments have suggested that the destruction of dopaminergic cells might be the result of the convergence of dependent and independent molecular pathways and that trigger cellular events might lead to the demise of these dopaminergic cells. JF - Parkinsonism & related disorders AU - Cadet, J L AD - Molecular Neuropsychiatry Section, National Institutes of Health/National Institute on Drug Abuse, Intramural Research Program, 5500 Nathan Shock Drive, 21224, Baltimore, MD 21224, USA. jcadet@intra.nida.nih.gov Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 85 EP - 90 VL - 8 IS - 2 SN - 1353-8020, 1353-8020 KW - Dopamine Agents KW - 0 KW - Neurotoxins KW - Methamphetamine KW - 44RAL3456C KW - Oxidopamine KW - 8HW4YBZ748 KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Index Medicus KW - Animals KW - Humans KW - Mice KW - Parkinsonian Disorders -- physiopathology KW - Parkinsonian Disorders -- chemically induced KW - Mice, Transgenic KW - Mice, Knockout UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71310749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Parkinsonism+%26+related+disorders&rft.atitle=Molecular+neurotoxicological+models+of+Parkinsonism%3A+focus+on+genetic+manipulation+of+mice.&rft.au=Cadet%2C+J+L&rft.aulast=Cadet&rft.aufirst=J&rft.date=2001-10-01&rft.volume=8&rft.issue=2&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Parkinsonism+%26+related+disorders&rft.issn=13538020&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-20 N1 - Date created - 2002-05-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cyclosporine A-induced mammary hyperplasia and hyperprolactinemia in New Zealand White rabbits. AN - 71302496; 11924803 AB - To investigate the potential activity of cyclosporin A (CsA) to induce mammary hyperplasia in New Zealand White (NZW) rabbits. Female NZW rabbits were used throughout experiments. To simulate the conditions of immunosuppression, CsA (10 mg/kg of body weight/d) was administered intravenously on a daily basis for 14 days and methylprednisolone (5 mg/kg/d) was administered on the first two days. The CsA (10 mg/kg/d) also was administered without methylprednisolone for 14 days to another cohort of rabbits. Mammary tissue of each rabbit was palpated and serially measured during this treatment period. The CsA was discontinued, and rabbits were monitored for 14 more days during the washout period. Sequential plasma concentrations of prolactin, 17beta-estradiol, and progesterone in each blood sample were determined by use of radioimmunoassay. All NZW rabbits treated with CsA and methylprednisolone for immunosuppression consistently developed striking mammary tissue hyperplasia. At the end of treatment with CsA and methylprednisolone, mammary glands had extensive changes consistent with actively lactating glands. Similar but less extensive hyperplasia developed in response to CsA alone. Plasma concentration of prolactin increased during treatment and decreased during the washout period. Plasma concentration of 17beta-estradiol increased during treatment and continued to increase during the washout period. Plasma progesterone concentration decreased at the end of treatment. On discontinuation of CsA, mammary hyperplasia regressed. Cyclosporine A, with or without methylprednisolone, induces mammary hyperplasia and hyperprolactinemia in NZW rabbits. This rabbit model may be a reliable in vivo system by which to study immunosuppressant-induced structural and functional changes of mammary glands similar to those observed in humans. JF - Comparative medicine AU - Petraitiene, R AU - Petraitis, V AU - Bacher, J AU - Das, S R AU - Parlow, A F AU - Walsh, T J AD - Immunocompromised Host Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 430 EP - 435 VL - 51 IS - 5 SN - 1532-0820, 1532-0820 KW - Immunosuppressive Agents KW - 0 KW - Progesterone KW - 4G7DS2Q64Y KW - Estradiol KW - 4TI98Z838E KW - Cyclosporine KW - 83HN0GTJ6D KW - Prolactin KW - 9002-62-4 KW - Methylprednisolone KW - X4W7ZR7023 KW - Index Medicus KW - Animals KW - Prolactin -- blood KW - Hyperplasia KW - Estradiol -- blood KW - Methylprednisolone -- toxicity KW - Humans KW - Disease Models, Animal KW - Rabbits KW - Progesterone -- blood KW - Female KW - Mammary Glands, Animal -- drug effects KW - Mammary Glands, Animal -- pathology KW - Immunosuppressive Agents -- toxicity KW - Hyperprolactinemia -- blood KW - Cyclosporine -- toxicity KW - Hyperprolactinemia -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71302496?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Comparative+medicine&rft.atitle=Cyclosporine+A-induced+mammary+hyperplasia+and+hyperprolactinemia+in+New+Zealand+White+rabbits.&rft.au=Petraitiene%2C+R%3BPetraitis%2C+V%3BBacher%2C+J%3BDas%2C+S+R%3BParlow%2C+A+F%3BWalsh%2C+T+J&rft.aulast=Petraitiene&rft.aufirst=R&rft.date=2001-10-01&rft.volume=51&rft.issue=5&rft.spage=430&rft.isbn=&rft.btitle=&rft.title=Comparative+medicine&rft.issn=15320820&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-16 N1 - Date created - 2002-04-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Hsp90 inhibitor geldanamycin selectively sensitizes Bcr-Abl-expressing leukemia cells to cytotoxic chemotherapy. AN - 71225038; 11587211 AB - The Bcr-Abl fusion protein drives leukemogenesis and can render leukemia cells resistant to conventional chemotherapy. Geldanamycin (GA), a drug which destabilizes Hsp90-associated proteins, depletes cells of Bcr-Abl, an Hsp90 client, but not of Abl. Both HL60 cells transfected with Bcr-Abl and naturally Ph1-positive K562 leukemia cells are resistant to most cytotoxic drugs, but were found to be sensitive to GA. Furthermore, GA sensitized Bcr-Abl-expressing cells to doxorubicin (DOX) and paclitaxel (PTX). In contrast, in parental HL60 cells, 90 nM GA inhibited PARP cleavage, nuclear fragmentation, and cell death caused by 500 ng/ml DOX. Like GA, STI 571 (an inhibitor of the Abl kinase) sensitized Bcr-Abl-expressing cells to DOX. Unlike GA, STI 571 did not antagonize the cytotoxic effects of DOX in parental HL60 cells. These results indicate that sensitization of Bcr-Abl-expressing cells, but not desensitization of HL60 cells, depends on inhibition of Bcr-Abl. Thus, GA differentially affects leukemia cells depending on their Bcr-Abl expression and selectively increases apoptosis in Bcr-Abl-expressing cells. JF - Leukemia AU - Blagosklonny, M V AU - Fojo, T AU - Bhalla, K N AU - Kim, J S AU - Trepel, J B AU - Figg, W D AU - Rivera, Y AU - Neckers, L M AD - Department of Developmental Therapeutics, Medicine Branch, National Cancer Institute, NIH, Bethesda and Rockville, MD 20892, USA. Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 1537 EP - 1543 VL - 15 IS - 10 SN - 0887-6924, 0887-6924 KW - Antineoplastic Agents KW - 0 KW - Benzoquinones KW - HSP90 Heat-Shock Proteins KW - Lactams, Macrocyclic KW - Quinones KW - Doxorubicin KW - 80168379AG KW - Fusion Proteins, bcr-abl KW - EC 2.7.10.2 KW - Paclitaxel KW - P88XT4IS4D KW - geldanamycin KW - Z3K3VJ16KU KW - Index Medicus KW - Drug Interactions KW - Doxorubicin -- pharmacology KW - Tumor Cells, Cultured -- drug effects KW - Transfection KW - Humans KW - Apoptosis -- drug effects KW - Drug Resistance KW - Paclitaxel -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - Leukemia -- pathology KW - Leukemia -- metabolism KW - Fusion Proteins, bcr-abl -- drug effects KW - HSP90 Heat-Shock Proteins -- antagonists & inhibitors KW - Quinones -- pharmacology KW - Fusion Proteins, bcr-abl -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71225038?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia&rft.atitle=The+Hsp90+inhibitor+geldanamycin+selectively+sensitizes+Bcr-Abl-expressing+leukemia+cells+to+cytotoxic+chemotherapy.&rft.au=Blagosklonny%2C+M+V%3BFojo%2C+T%3BBhalla%2C+K+N%3BKim%2C+J+S%3BTrepel%2C+J+B%3BFigg%2C+W+D%3BRivera%2C+Y%3BNeckers%2C+L+M&rft.aulast=Blagosklonny&rft.aufirst=M&rft.date=2001-10-01&rft.volume=15&rft.issue=10&rft.spage=1537&rft.isbn=&rft.btitle=&rft.title=Leukemia&rft.issn=08876924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-22 N1 - Date created - 2001-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel genomic imbalances and chromosome translocations involving c-myc gene in Burkitt's lymphoma. AN - 71224863; 11587216 AB - In this study, CA46 and ST486, two Epstein-Barr (EBV) negative cell lines derived from sporadic BL, were analyzed by multicolor spectral karyotyping, G-banding, fluorescence in situ hybridization with single-copy gene probes, and comparative genomic hybridization (CGH). In addition to reciprocal t(8;14)(q24;q32) translocation involving c-myc and IgH loci, we identified a t(7;8;14)(q11.2;q24;q32) translocation in CA 46 cells and t(8;14;18)(q24;q32;q23) in ST486 cells. Both rearrangements were not previously described in BL and resulted in transposition of myc sequences in a new genomic configuration. Several DNA imbalances mapped by CGH at the same sites in both lines, may reflect recurrent genomic changes that are relevant to pathogenesis of BL. We tested the tumorigenicity of these lines by injecting cells intraperitoneally in SCID mice. In two separate experiments, CA46 cells produced tumors 2 weeks after cell inoculation while ST486 cells induced only one tumor after a long latency period. Partial duplication of the long arm of chromosome 1 involving variable bands but always band 1q23 is the second most common alteration in BL and is known to be associated with aggressive tumors and poor prognosis. Duplication of the bands 1q23-24 commonly observed in EBV-negative lines was identified only in highly tumorigenic CA46 cells suggesting that this region harbor gene(s) associated with tumor cell invasiveness. JF - Leukemia AU - Zimonjic, D B AU - Keck-Waggoner, C AU - Popescu, N C AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 1582 EP - 1588 VL - 15 IS - 10 SN - 0887-6924, 0887-6924 KW - Index Medicus KW - Neoplasm Transplantation KW - Chromosomes, Human, Pair 1 KW - Animals KW - Cytogenetic Analysis KW - Tumor Cells, Cultured KW - Humans KW - Mice KW - Chromosomes, Human, Pair 8 KW - Mice, SCID KW - Chromosomes, Human, Pair 14 KW - Chromosomes, Human, Pair 7 KW - Burkitt Lymphoma -- etiology KW - Burkitt Lymphoma -- genetics KW - Trisomy KW - Genes, myc -- genetics KW - Translocation, Genetic KW - Burkitt Lymphoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71224863?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia&rft.atitle=Novel+genomic+imbalances+and+chromosome+translocations+involving+c-myc+gene+in+Burkitt%27s+lymphoma.&rft.au=Zimonjic%2C+D+B%3BKeck-Waggoner%2C+C%3BPopescu%2C+N+C&rft.aulast=Zimonjic&rft.aufirst=D&rft.date=2001-10-01&rft.volume=15&rft.issue=10&rft.spage=1582&rft.isbn=&rft.btitle=&rft.title=Leukemia&rft.issn=08876924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-02-22 N1 - Date created - 2001-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunohistochemical localization and semi-quantitation of hepatic tamoxifen-DNA adducts in rats exposed orally to tamoxifen. AN - 71223316; 11577011 AB - Administration of tamoxifen (TAM) has been shown to induce hepatocellular carcinogenesis and TAM-DNA adduct formation in rat liver. Here we present TAM-DNA adduct localization and semi-quantitation in hepatic tissue of rats by immunohistochemical staining followed by image analysis. We have also used a quantitative immunoassay to provide a validation for the immunohistochemical values. Rats were fed diets containing 0, 5, 50, 150 or 500 p.p.m. TAM for 45 weeks. Serial sections of paraffin-embedded liver were stained for TAM-DNA adducts using a polyclonal TAM-DNA antiserum. Subsequently, visualization of TAM-DNA adducts was performed by peroxidase-conjugated secondary antibody-mediated signal amplification using biotinyl tyramide followed by streptavidin-alkaline phosphatase and fast red. Semi-quantitation of nuclear color intensity was achieved with an Automated Cellular Imaging System (ACIS), with a detection limit of 1 TAM-DNA adduct per 10(7) nt for these experiments. In parenchymal cells of liver sections from TAM-exposed animals a dose-dependent increase in nuclear staining was observed by ACIS and the TAM-DNA adduct levels determined by ACIS were validated in liver DNA by quantitative chemiluminescence immunoassay (CIA). Comparison of semi-quantitative values determined by ACIS with quantitative values determined by CIA showed a strong correlation (r = 0.924) between the two methods. At 45 weeks of TAM exposure the liver cytoplasm contained placental glutathione S-transferase (GST-p)-positive foci, as indicated by new fuchsin staining. Staining of serial sections revealed a relative lack of TAM-DNA adducts within these enzyme-altered foci. In addition, some GST-p foci contained islands of cells that did not stain for GST-p but were positive for TAM-DNA adduct formation. This study validates the use of ACIS for TAM-DNA adduct formation and demonstrates that steady-state TAM-DNA adduct levels observed in livers of rats chronically fed TAM for several months increase in relation to dose. In addition, unlike the normal surrounding liver, preneoplastic GST-p-positive foci have virtually no TAM-DNA adducts. JF - Carcinogenesis AU - Divi, R L AU - Dragan, Y P AU - Pitot, H C AU - Poirier, M C AD - National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 1693 EP - 1699 VL - 22 IS - 10 SN - 0143-3334, 0143-3334 KW - DNA Adducts KW - 0 KW - Estrogen Antagonists KW - Tamoxifen KW - 094ZI81Y45 KW - DNA KW - 9007-49-2 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Rats KW - Administration, Oral KW - Animals KW - Rats, Sprague-Dawley KW - Placenta -- enzymology KW - Immunoassay -- methods KW - Luminescent Measurements KW - Dose-Response Relationship, Drug KW - Glutathione Transferase -- metabolism KW - Image Processing, Computer-Assisted KW - Fluorescent Antibody Technique KW - Female KW - Pregnancy KW - Tamoxifen -- pharmacology KW - Liver -- pathology KW - Estrogen Antagonists -- pharmacology KW - Liver -- drug effects KW - DNA -- metabolism KW - Liver -- metabolism KW - DNA Adducts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71223316?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Immunohistochemical+localization+and+semi-quantitation+of+hepatic+tamoxifen-DNA+adducts+in+rats+exposed+orally+to+tamoxifen.&rft.au=Divi%2C+R+L%3BDragan%2C+Y+P%3BPitot%2C+H+C%3BPoirier%2C+M+C&rft.aulast=Divi&rft.aufirst=R&rft.date=2001-10-01&rft.volume=22&rft.issue=10&rft.spage=1693&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Addiction and the brain: the neurobiology of compulsion and its persistence. AN - 71215842; 11584307 AB - People take addictive drugs to elevate mood, but with repeated use these drugs produce serious unwanted effects, which can include tolerance to some drug effects, sensitization to others, and an adapted state - dependence - which sets the stage for withdrawal symptoms when drug use stops. The most serious consequence of repetitive drug taking, however, is addiction: a persistent state in which compulsive drug use escapes control, even when serious negative consequences ensue. Addiction is characterized by a long-lasting risk of relapse, which is often initiated by exposure to drug-related cues. Substantial progress has been made in understanding the molecular and cellular mechanisms of tolerance, dependence and withdrawal, but as yet we understand little of the neural substrates of compulsive drug use and its remarkable persistence. Here we review evidence for the possibility that compulsion and its persistence are based on a pathological usurpation of molecular mechanisms that are normally involved in memory. JF - Nature reviews. Neuroscience AU - Hyman, S E AU - Malenka, R C AD - National Institute of Mental Health, 6001 Executive Boulevard, Bethesda, Maryland 20892-9669, USA. shyman@nih.gov Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 695 EP - 703 VL - 2 IS - 10 SN - 1471-003X, 1471-003X KW - Glutamic Acid KW - 3KX376GY7L KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Corpus Striatum -- physiopathology KW - Reward KW - Humans KW - Dopamine -- physiology KW - Cues KW - Neurobiology -- methods KW - Models, Neurological KW - Glutamic Acid -- physiology KW - Substance-Related Disorders -- physiopathology KW - Brain -- physiopathology KW - Compulsive Behavior -- psychology KW - Substance-Related Disorders -- psychology KW - Compulsive Behavior -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71215842?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+reviews.+Neuroscience&rft.atitle=Addiction+and+the+brain%3A+the+neurobiology+of+compulsion+and+its+persistence.&rft.au=Hyman%2C+S+E%3BMalenka%2C+R+C&rft.aulast=Hyman&rft.aufirst=S&rft.date=2001-10-01&rft.volume=2&rft.issue=10&rft.spage=695&rft.isbn=&rft.btitle=&rft.title=Nature+reviews.+Neuroscience&rft.issn=1471003X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-05 N1 - Date created - 2001-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Psychopharmacology for young children: clinical needs and research opportunities. AN - 71214626; 11581454 AB - In response to concerns about the increasing use of psychotropic medications in preschoolers, the National Institute of Mental Health and the Food and Drug Administration convened a workshop in October 2000 to examine the current state of knowledge regarding psychopharmacology for young children and discuss a variety of topics relevant to research in this age group, including safety, efficacy, investigational methods, and ethical aspects. The meeting gathered researchers, practitioners, ethicists, industry staff, and family and patient representatives. Efficacy and safety of psychotropics have not been systematically evaluated in preschoolers. The major limitation to this research is the diagnostic uncertainty surrounding most manifestations of psychopathology in early childhood. Research in developmental psychopathology is needed to clarify diagnosis and provide sensitive and specific methods for clinical trials. Possible approaches to expanding the research basis of this area of clinical practice, including a recently started study of methylphenidate in preschoolers, are reported here. JF - Pediatrics AU - Vitiello, B AD - Child and Adolescent Treatment and Preventive Interventions Research Branch, National Institute of Mental Health, Bethesda, Maryland, USA. bvitiell@nih.gov Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 983 EP - 989 VL - 108 IS - 4 KW - Psychotropic Drugs KW - 0 KW - Methylphenidate KW - 207ZZ9QZ49 KW - Abridged Index Medicus KW - Index Medicus KW - Age Factors KW - Humans KW - Methylphenidate -- therapeutic use KW - Research Design -- standards KW - Child KW - Child, Preschool KW - Attention Deficit Disorder with Hyperactivity -- drug therapy KW - Mental Disorders -- drug therapy KW - Psychotropic Drugs -- therapeutic use KW - Psychotropic Drugs -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71214626?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=Psychopharmacology+for+young+children%3A+clinical+needs+and+research+opportunities.&rft.au=Vitiello%2C+B&rft.aulast=Vitiello&rft.aufirst=B&rft.date=2001-10-01&rft.volume=108&rft.issue=4&rft.spage=983&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=1098-4275&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-03 N1 - Date created - 2001-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Environmental exposure and cancer in children. A conceptual framework for the pediatrician. AN - 71213685; 11579670 AB - Ultimately, after gathering and assessing all available evidence, pediatricians and health care policymakers must make informed decisions on whether exposure to a specific agent has the potential to cause cancer in children. In the case of DES, for which the results were clear, there was no question that the drug should be taken off the market; however, most cases of suspected carcinogens lack such clear evidence documenting cause and effect. An example of a murky topic is the suspected relationship between residential electromagnetic fields (EMFs) and childhood cancer. Epidemiologic and biologic researchers have tried for more than 2 decades to determine whether exposure to relatively high levels of EMFs poses health hazards, especially cancer in children. Although the preponderance of evidence favors a judgment that this ubiquitous environmental exposure is harmless, concerns remain in many public circles and some scientific ones. Any proposed intervention to remove a potentially carcinogenic agent must be weighed against the cost and inconvenience to the affected community. Pediatricians are placed in a vulnerable position when faced with questions of a carcinogenic potential because of the frequency of claims in the popular literature stating that exposure to a certain product or food is associated with an increased risk for cancer in adults and possibly children. When such studies are published or, more often, released to the press, the strength of the evidence for a causal association with cancer, coupled with the context of the study, should be considered as a reasonable starting point. Better communication models of disseminating cancer-risk information are needed so that the public understands the difference between a weak study that appeared on the local news with little evidence to support a cause-and-effect relationship versus a well-designed study that was published in a peer-reviewed journal and indicates a likely cause-and-effect association. JF - Pediatric clinics of North America AU - DeBaun, M R AU - Gurney, J G AD - Genetic Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 1215 EP - 1221 VL - 48 IS - 5 SN - 0031-3955, 0031-3955 KW - Carcinogens, Environmental KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Concept Formation KW - Epidemiologic Methods KW - Environmental Health -- statistics & numerical data KW - Humans KW - Child KW - Pediatrics -- statistics & numerical data KW - Carcinogens, Environmental -- adverse effects KW - Environmental Exposure -- statistics & numerical data KW - Neoplasms -- epidemiology KW - Environmental Exposure -- adverse effects KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71213685?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatric+clinics+of+North+America&rft.atitle=Environmental+exposure+and+cancer+in+children.+A+conceptual+framework+for+the+pediatrician.&rft.au=DeBaun%2C+M+R%3BGurney%2C+J+G&rft.aulast=DeBaun&rft.aufirst=M&rft.date=2001-10-01&rft.volume=48&rft.issue=5&rft.spage=1215&rft.isbn=&rft.btitle=&rft.title=Pediatric+clinics+of+North+America&rft.issn=00313955&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-25 N1 - Date created - 2001-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deletion of N-terminal myristoylation site of HIV Nef abrogates both MHC-1 and CD4 down-regulation. AN - 71211213; 11578695 AB - HIV-1 Nef is a desirable vaccine component because it is expressed early and abundantly during HIV infection, and contains many CTL, T-helper cell, and B-cell epitopes. Nef, however, down-regulates MHC-1 and CD4 cell surface expression, contributing to viral escape from host immunity. To prevent Nef from down-regulating both MHC-1 and CD4 while preserving most CTL epitopes, a panel of Nef mutants was constructed and assessed. Some mutants, as expected, modulated either MHC-1 or CD4 expression. Others prevented down-regulation of both proteins but sacrificed numerous immunogenic epitopes. Deletion of 19 N-terminal amino acids including the myristoylation signal from Nef completely abrogated both MHC-1 and CD4 down-regulation while preserving most CTL, T-helper and B-cell epitopes. Our results demonstrate that the myristoylation signal in the Nef protein is critical for Nef-mediated endocytosis of both MHC-1 and CD4. Non-myristoylated Nef containing a full complement of CTL epitopes has greater potential as a vaccine component than wild-type Nef. JF - Immunology letters AU - Peng, B AU - Robert-Guroff, M AD - Basic Research Laboratory, National Cancer Institute, National Institutes of Health, 41 Libary Drive, Building 41 Room d804, Bethesda, MD 20892-5055, USA. guroffm@exchange.nih.gov Y1 - 2001/10/01/ PY - 2001 DA - 2001 Oct 01 SP - 195 EP - 200 VL - 78 IS - 3 SN - 0165-2478, 0165-2478 KW - AIDS Vaccines KW - 0 KW - Antigens, CD4 KW - DNA, Viral KW - Gene Products, nef KW - Histocompatibility Antigens Class I KW - Peptide Fragments KW - nef Gene Products, Human Immunodeficiency Virus KW - Myristic Acid KW - 0I3V7S25AW KW - Index Medicus KW - Binding Sites -- immunology KW - DNA Mutational Analysis -- methods KW - Humans KW - Mutagenesis, Site-Directed -- genetics KW - Amino Acid Sequence KW - Molecular Sequence Data KW - Signal Transduction -- genetics KW - Signal Transduction -- immunology KW - Binding Sites -- genetics KW - DNA, Viral -- genetics KW - Cell Line KW - Peptide Fragments -- metabolism KW - Peptide Fragments -- genetics KW - Down-Regulation -- immunology KW - Histocompatibility Antigens Class I -- genetics KW - HIV-1 -- metabolism KW - Gene Products, nef -- metabolism KW - Sequence Deletion -- immunology KW - Gene Products, nef -- genetics KW - Down-Regulation -- genetics KW - Antigens, CD4 -- genetics KW - Sequence Deletion -- genetics KW - Histocompatibility Antigens Class I -- biosynthesis KW - Antigens, CD4 -- biosynthesis KW - Myristic Acid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71211213?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunology+letters&rft.atitle=Deletion+of+N-terminal+myristoylation+site+of+HIV+Nef+abrogates+both+MHC-1+and+CD4+down-regulation.&rft.au=Peng%2C+B%3BRobert-Guroff%2C+M&rft.aulast=Peng&rft.aufirst=B&rft.date=2001-10-01&rft.volume=78&rft.issue=3&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Immunology+letters&rft.issn=01652478&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-26 N1 - Date created - 2001-10-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure and function of the N-terminal 40 kDa fragment of human PMS2: a monomeric GHL ATPase. AN - 71206627; 11574484 AB - Human MutLalpha, a heterodimer of hMLH1 and hPMS2, is essential for DNA mismatch repair. Inactivation of the hmlh1 or hpms2 genes by mutation or epigenesis causes genomic instability and a predisposition to hereditary non-polyposis cancer. We report here the X-ray crystal structures of the conserved N-terminal 40 kDa fragment of hPMS2, NhPMS2, and its complexes with ATPgammaS and ADP at 1.95, 2.7 and 2.7 A resolution, respectively. The NhPMS2 structures closely resemble the ATPase fragment of Escherichia coli MutL, which coordinates protein-protein interactions in mismatch repair by undergoing structural transformation upon binding of ATP. Unlike the E.coli MutL, whose ATPase activity requires protein dimerization, the monomeric form of NhPMS2 is active both in ATP hydrolysis and DNA binding. NhPMS2 is the first example of a GHL ATPase active as a monomer, suggesting that its activity may be modulated by hMLH1 in MutLalpha, and vice versa. The potential heterodimer interface revealed by crystallography provides a mutagenesis target for functional studies of MutLalpha. JF - The EMBO journal AU - Guarné, A AU - Junop, M S AU - Yang, W AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2001/10/01/ PY - 2001 DA - 2001 Oct 01 SP - 5521 EP - 5531 VL - 20 IS - 19 SN - 0261-4189, 0261-4189 KW - Bacterial Proteins KW - 0 KW - Carrier Proteins KW - DNA-Binding Proteins KW - Escherichia coli Proteins KW - MutL protein, E coli KW - Neoplasm Proteins KW - PMS1 protein, human KW - Peptide Fragments KW - adenosine 5'-O-(3-thiotriphosphate) KW - 35094-46-3 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - PMS2 protein, human KW - Mismatch Repair Endonuclease PMS2 KW - EC 3.6.1.3 KW - MutL Proteins KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Bacterial Proteins -- genetics KW - DNA Repair KW - Models, Molecular KW - Humans KW - Colorectal Neoplasms, Hereditary Nonpolyposis -- genetics KW - Amino Acid Sequence KW - Binding Sites KW - Peptide Fragments -- chemistry KW - Base Pair Mismatch KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Sequence Homology, Amino Acid KW - DNA-Binding Proteins -- chemistry KW - Adenosine Triphosphate -- analogs & derivatives KW - Adenosine Triphosphate -- metabolism KW - Adenosine Triphosphatases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71206627?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=Structure+and+function+of+the+N-terminal+40+kDa+fragment+of+human+PMS2%3A+a+monomeric+GHL+ATPase.&rft.au=Guarn%C3%A9%2C+A%3BJunop%2C+M+S%3BYang%2C+W&rft.aulast=Guarn%C3%A9&rft.aufirst=A&rft.date=2001-10-01&rft.volume=20&rft.issue=19&rft.spage=5521&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-09-27 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1H7S; PDB; 1H7U; 1EA6 N1 - SuppNotes - Cited By: Nature. 2000 Oct 12;407(6805):711-7 [11048711] Cell. 1999 Apr 2;97(1):85-97 [10199405] Mol Cell. 2001 Jan;7(1):1-12 [11172706] Nat Struct Biol. 2001 Apr;8(4):353-60 [11276258] EMBO J. 1990 May;9(5):1665-72 [2184035] J Biol Chem. 1999 Nov 5;274(45):32368-75 [10542278] Nat Genet. 2000 Jan;24(1):27-35 [10615123] Annu Rev Genet. 1999;33:533-64 [10690417] Nat Struct Biol. 2000 Aug;7(8):626-33 [10932244] Mol Cell Biol. 2000 Sep;20(17):6390-8 [10938116] EMBO J. 2000 Aug 15;19(16):4383-92 [10944121] Nature. 2000 Oct 12;407(6805):703-10 [11048710] Nucleic Acids Res. 1991 Apr 11;19(7):1549-55 [2027763] Nature. 1991 Jun 20;351(6328):624-9 [1646964] Science. 1993 Mar 5;259(5100):1415-20 [8451638] Biochem Biophys Res Commun. 1994 Nov 15;204(3):1257-64 [7980603] Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):1950-4 [7892206] Curr Opin Genet Dev. 1995 Jun;5(3):382-95 [7549435] Genomics. 1995 Nov 20;30(2):195-206 [8586419] Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1292-7 [8577757] Mol Cell Biol. 1996 Mar;16(3):1085-93 [8622653] Cancer Res. 1996 Mar 15;56(6):1374-81 [8640828] Genes Dev. 1996 Jun 15;10(12):1433-42 [8666228] Annu Rev Biochem. 1996;65:101-33 [8811176] Cell. 1997 Apr 18;89(2):239-50 [9108479] Proc Natl Acad Sci U S A. 1997 May 27;94(11):5831-6 [9159160] Cell. 1997 Jul 11;90(1):65-75 [9230303] Mol Cell Biol. 1997 Aug;17(8):4465-73 [9234704] Gastroenterology. 1997 Oct;113(4):1146-58 [9322509] Nucleic Acids Res. 1998 Feb 15;26(4):948-53 [9461452] Nat Genet. 1998 Mar;18(3):276-9 [9500552] Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21 [9757107] Cell. 1998 Nov 13;95(4):541-52 [9827806] Cell. 1999 Jan 8;96(1):131-41 [9989504] Acta Crystallogr D Biol Crystallogr. 1999 Apr;55(Pt 4):849-61 [10089316] J Biochem. 1999 Apr;125(4):818-25 [10101297] Cell. 2000 Nov 22;103(5):711-21 [11114328] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Beneficial effects of NTP-2000 diet on growth, survival, and kidney and heart diseases of Fischer 344 rats in chronic studies. AN - 71189487; 11568368 AB - Diet is one of the most important environmental factors influencing growth, survival, and appearance of age-associated diseases in rodents. NIH-07 open formula rodent diet was the selected diet for the National Toxicology Program studies from 1980 to 1994. After a number of experimental diets were evaluated, a new one designated as NTP-2000 was selected for rodents in NTP studies beginning in 1994. This report summarizes the results of dosed feed and inhalation studies for differences in growth, survival, and severity of kidney and heart lesions in Fischer 344 rats fed NTP-2000 or NIH-07 diets. In the dosed feed studies, male rats group housed and fed the NTP-2000 diet grew slightly slower, attained maximum body weight later, and lost less body weight by the end of the 2-year studies compared to the groups fed NIH-07. Female rats group housed and fed the NTP-2000 diet in dosed feed studies had significantly slower growth, with lower maximum body weight compared to the groups fed the NIH-07 diet. In the inhalation studies, male rats individually housed and fed the NTP-2000 diet had slightly higher maximum body weight and significantly higher final body weight, with lower loss of weight when compared to similarly housed groups fed the NIH-07 diet. In inhalation studies, female rats fed the NTP-2000 diet and individually housed had significantly slower growth. The NTP-2000 diet significantly increased the survival of male and female rats, with a dramatic increase in survival of males in inhalation studies. This diet also caused significant decreases in severity of nephropathy and cardiomyopathy, and the decrease was marked in males. These observations indicate that diets balanced for nutrients, such as the NTP-2000, could markedly improve the health and increase survival of the rats used in chronic studies. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Rao, G N AU - Morris, R W AU - Seely, J C AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. rao@niehs.nih.gov Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 245 EP - 255 VL - 63 IS - 2 SN - 1096-6080, 1096-6080 KW - Index Medicus KW - Rats KW - Body Weight KW - Animals KW - Animal Nutritional Physiological Phenomena KW - Rats, Inbred F344 KW - Sex Factors KW - Inhalation Exposure KW - Survival KW - Time Factors KW - Male KW - Female KW - Kidney Diseases -- pathology KW - Animal Feed KW - Weight Loss -- drug effects KW - Heart Diseases -- pathology KW - Growth -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71189487?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Beneficial+effects+of+NTP-2000+diet+on+growth%2C+survival%2C+and+kidney+and+heart+diseases+of+Fischer+344+rats+in+chronic+studies.&rft.au=Rao%2C+G+N%3BMorris%2C+R+W%3BSeely%2C+J+C&rft.aulast=Rao&rft.aufirst=G&rft.date=2001-10-01&rft.volume=63&rft.issue=2&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-12 N1 - Date created - 2001-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of Gab1 lacking the pleckstrin homology domain is associated with neoplastic progression. AN - 71184277; 11564873 AB - An in vitro transformation system of carcinogen-treated Syrian hamster embryo (SHE) cell cultures represents multistep genetic and nongenetic changes that develop during the neoplastic progression of normal cells to tumor cells in vivo. During this neoplastic progression, SHE cells demonstrate an altered response to epidermal growth factor (EGF). In the present report, we examined the role of the adapter protein Gab1 (Grb2-associated binder-1) in the neoplastic progression of SHE cells. We used two asbestos-transformed SHE cell clones in different neoplastic stages: a 10W+8 clone, which is immortal and retains the ability to suppress the tumorigenicity of tumor cells in cell-cell hybrid experiments, and a 10W-1 clone, which has lost this tumor suppressor ability. 10W+8 cells expressed full-length 100-kDa Gab1 and associated 5.2-kb mRNA. Upon repeated cell passaging, 10W-1 cells showed increasing expression of a novel 87-kDa form of Gab1 as well as 4.6-kb mRNA with diminishing expression of the original 100-kDa Gab1. cDNA encoding the 87-kDa Gab1 predicts a form of Gab1 lacking the amino-terminal 103 amino acids (Gab1(Delta1-103)), which corresponds to loss of most of the pleckstrin homology (PH) domain. Gab1(Delta1-103) retains the ability to be phosphorylated in an EGF-dependent manner and to associate with the EGF receptor and SHP-2 upon EGF stimulation. The endogenous expression of Gab1(Delta1-103) in 10W-1 cells appeared closely related to EGF-dependent colony formation in soft agar. Moreover, transfection and expression of Gab1(Delta1-103), but not Gab1, in 10W+8 cells enhanced their EGF-dependent colony formation in soft agar. These results demonstrate that Gab1 is a target of carcinogen-induced transformation of SHE cells and that the expression of a Gab1 variant lacking most of the PH domain plays a specific role in the neoplastic progression of SHE cells. JF - Molecular and cellular biology AU - Kameda, H AU - Risinger, J I AU - Han, B B AU - Baek, S J AU - Barrett, J C AU - Abe, T AU - Takeuchi, T AU - Glasgow, W C AU - Eling, T E AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 6895 EP - 6905 VL - 21 IS - 20 SN - 0270-7306, 0270-7306 KW - Blood Proteins KW - 0 KW - Carcinogens KW - DNA, Complementary KW - Phosphoproteins KW - RNA, Messenger KW - platelet protein P47 KW - Asbestos KW - 1332-21-4 KW - Epidermal Growth Factor KW - 62229-50-9 KW - Agar KW - 9002-18-0 KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Disease Progression KW - Agar -- metabolism KW - Phenotype KW - Phosphorylation KW - Transformation, Genetic KW - Molecular Sequence Data KW - Time Factors KW - Signal Transduction KW - Cell Division KW - Plasmids -- metabolism KW - Fluorescent Antibody Technique, Indirect KW - Amino Acid Sequence KW - Reverse Transcriptase Polymerase Chain Reaction KW - Precipitin Tests KW - Cloning, Molecular KW - Blotting, Western KW - Base Sequence KW - MAP Kinase Signaling System KW - RNA, Messenger -- metabolism KW - Transfection KW - Cells, Cultured KW - DNA, Complementary -- metabolism KW - Mesocricetus KW - Protein Structure, Tertiary KW - Epidermal Growth Factor -- metabolism KW - Cell Line KW - Cricetinae KW - Phosphoproteins -- chemistry KW - Phosphoproteins -- biosynthesis KW - Neoplasms -- chemically induced KW - Blood Proteins -- chemistry KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71184277?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Expression+of+Gab1+lacking+the+pleckstrin+homology+domain+is+associated+with+neoplastic+progression.&rft.au=Kameda%2C+H%3BRisinger%2C+J+I%3BHan%2C+B+B%3BBaek%2C+S+J%3BBarrett%2C+J+C%3BAbe%2C+T%3BTakeuchi%2C+T%3BGlasgow%2C+W+C%3BEling%2C+T+E&rft.aulast=Kameda&rft.aufirst=H&rft.date=2001-10-01&rft.volume=21&rft.issue=20&rft.spage=6895&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-11-01 N1 - Date created - 2001-09-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1999 Oct 29;274(44):31719-26 [10531383] Proc Natl Acad Sci U S A. 1986 Aug;83(16):5992-6 [3461473] Mol Cell Biol. 2000 Feb;20(4):1448-59 [10648629] Mol Cell Biol. 2000 Mar;20(5):1526-36 [10669730] Mol Cell Biol. 2000 May;20(10):3695-704 [10779359] Cell Growth Differ. 2001 Jun;12(6):307-18 [11432805] N Engl J Med. 1976 Dec 2;295(23):1302-8 [980063] Proc Natl Acad Sci U S A. 1978 Aug;75(8):3761-5 [278986] Cancer Res. 1979 May;39(5):1504-10 [427793] Cancer Res. 1980 Jan;40(1):91-4 [7349908] Science. 1981 Jun 19;212(4501):1402-4 [6262919] Nature. 1982 Oct 14;299(5884):633-5 [7121596] Cancer Res. 1984 Nov;44(11):5017-22 [6091868] Proc Natl Acad Sci U S A. 1989 Nov;86(22):8773-7 [2813423] Pharmacol Ther. 1990;46(3):469-86 [2188272] Science. 1991 Nov 22;254(5035):1146-53 [1659742] J Biol Chem. 1992 May 25;267(15):10771-9 [1587852] Mol Carcinog. 1993;7(4):249-56 [8394717] Environ Health Perspect. 1993 Apr;100:9-20 [8354184] Nature. 1996 Feb 8;379(6565):560-4 [8596638] Cell. 1996 May 31;85(5):621-4 [8646770] Cell. 1996 Jun 14;85(6):899-909 [8681384] Cell. 1996 Jun 14;85(6):911-20 [8681385] Nature. 1996 Nov 14;384(6605):173-6 [8906793] Cell. 1997 Jan 24;88(2):197-204 [9008160] Cell. 1997 Jan 24;88(2):205-11 [9008161] Crit Rev Oncog. 1995;6(3-6):251-60 [9012585] Br J Haematol. 1997 May;97(2):348-55 [9163601] Cell. 1997 May 30;89(5):693-702 [9182757] Bioessays. 1997 Jun;19(6):491-500 [9204766] J Biol Chem. 1997 Aug 1;272(31):19269-76 [9235921] J Biol Chem. 1997 Aug 8;272(32):20167-72 [9242692] Oncogene. 1997 Dec 18;15(25):3103-11 [9444958] Mol Cell Biol. 1998 Jul;18(7):4109-17 [9632795] J Biol Chem. 1998 Jul 3;273(27):16643-6 [9642214] Annu Rev Biophys Biomol Struct. 1998;27:503-28 [9646876] EMBO J. 1998 Sep 15;17(18):5374-87 [9736615] Oncogene. 1998 Sep 3;17(9):1097-108 [9764820] Mol Cell. 1998 Dec;2(6):729-40 [9885561] Biochemistry. 1999 Jan 5;38(1):151-9 [9890893] Mol Cell Biol. 1999 Mar;19(3):1784-99 [10022866] Blood. 1999 Mar 15;93(6):1809-16 [10068651] J Biol Chem. 1999 Jul 9;274(28):19649-54 [10391903] Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8528-33 [10411909] Prostaglandins Leukot Essent Fatty Acids. 1999 Aug;61(2):137-43 [10509870] J Biol Chem. 1999 Nov 12;274(46):32835-41 [10551845] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insertion of an N-terminal 6-aminohexanoic acid after the 7 amino acid position of glucagon-like peptide-1 produces a long-acting hypoglycemic agent. AN - 71182004; 11564711 AB - The use of glucagon-like peptide-1 (GLP-1) as a routine treatment for type 2 diabetes mellitus is undermined by its short biological half-life. A cause of degradation is its cleavage at the N-terminal HAE sequence by the enzyme dipeptidyl peptidase IV (DPP IV). To protect from DPP IV, we have studied the biological activity of a GLP-1 analog in which 6-aminohexanoic acid (Aha) is inserted between histidine and alanine at positions 7 and 8. We have compared the biological activity of this new compound, GLP-1 Aha(8), with the previously described GLP-1 8-glycine (GLP-1 Gly(8)) analog. GLP-1 Aha(8) (10 nM) was equipotent with GLP-1 (10 nM) in stimulating insulin secretion in RIN 1046-38 cells. As with GLP-1 Gly(8), the binding affinity of GLP-1 Aha(8) for the GLP-1 receptor in intact Chinese hamster ovary (CHO) cells expressing the human GLP-1 receptor (CHO/GLP-1R cells) was reduced (IC(50): GLP-1, 3.7 +/- 0.2 nM; GLP-1 Gly(8), 41 +/- 9 nM; GLP-1 Aha(8), 22 +/- 7 nM). GLP-1 Aha(8) was also shown to stimulate intracellular cAMP production 4-fold above basal at concentrations as low as 0.5 nM. However, it exhibited a higher ED(50) when compared to GLP-1 and GLP-1 Gly(8) (ED(50): GLP-1, 0.036 +/- 0.002 nM, GLP-1 Gly(8), 0.13 +/- 0.02 nM, GLP-1 Aha(8), 0.58 +/- 0.03 nM). A series of D-amino acid-substituted GLP-1 compounds were also examined to assess the importance of putative peptidase-sensitive cleavage sites present in the GLP-1 molecule. They had poor binding affinity for the GLP-1 receptor, and none of these compounds stimulated the production of intracellular cAMP in CHO/GLP-1R cells or insulin secretion in RIN 1046-38 cells. GLP-1 Aha(8) (24 nmol/kg) administered sc to fasted Zucker (fa/fa) rats (mean blood glucose, 195 +/- 32 mg/dl) lowered blood glucose levels to a nadir of 109 +/- 3 mg/dl, and it remained significantly lower for 8 h. Matrix-assisted linear desorption ionization-time of flight mass spectrometry of GLP-1 Aha(8) incubated with DPP IV (37 C, 2 h) did not exhibit an N-terminal degradation product. Taken together, these results show that insertion of Aha after the 7 position in GLP-1 produces an effective, long-acting GLP-1 analog, which may be useful in the treatment of type 2 diabetes mellitus. JF - Endocrinology AU - Doyle, M E AU - Greig, N H AU - Holloway, H W AU - Betkey, J A AU - Bernier, M AU - Egan, J M AD - Diabetes Section, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 4462 EP - 4468 VL - 142 IS - 10 SN - 0013-7227, 0013-7227 KW - Hypoglycemic Agents KW - 0 KW - Peptide Fragments KW - Protein Precursors KW - Glucagon-Like Peptide 1 KW - 89750-14-1 KW - Glucagon KW - 9007-92-5 KW - Aminocaproic Acid KW - U6F3787206 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Diabetes Mellitus, Type 2 -- drug therapy KW - Animals KW - Humans KW - Molecular Sequence Data KW - Diabetes Mellitus, Type 2 -- metabolism KW - Amino Acid Sequence KW - Mutagenesis, Insertional KW - Cell Line KW - Structure-Activity Relationship KW - Protein Precursors -- pharmacology KW - Glucagon -- genetics KW - Hypoglycemic Agents -- therapeutic use KW - Peptide Fragments -- therapeutic use KW - Glucagon -- therapeutic use KW - Peptide Fragments -- genetics KW - Peptide Fragments -- pharmacology KW - Glucagon -- pharmacology KW - Protein Precursors -- genetics KW - Hypoglycemic Agents -- pharmacology KW - Protein Precursors -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71182004?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology&rft.atitle=Insertion+of+an+N-terminal+6-aminohexanoic+acid+after+the+7+amino+acid+position+of+glucagon-like+peptide-1+produces+a+long-acting+hypoglycemic+agent.&rft.au=Doyle%2C+M+E%3BGreig%2C+N+H%3BHolloway%2C+H+W%3BBetkey%2C+J+A%3BBernier%2C+M%3BEgan%2C+J+M&rft.aulast=Doyle&rft.aufirst=M&rft.date=2001-10-01&rft.volume=142&rft.issue=10&rft.spage=4462&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-11-01 N1 - Date created - 2001-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - IL-10 inhibits granulocyte-macrophage colony-stimulating factor-dependent human monocyte survival at the early stage of the culture and inhibits the generation of macrophages. AN - 71181562; 11564774 AB - We previously demonstrated that IL-10 alone does not stimulate growth and differentiation of human monocytes, but enhances those of monocytes stimulated with M-CSF. We studied here the effect of IL-10 on human monocytes stimulated with GM-CSF. Monocytes stimulated with GM-CSF alone survived and developed into macrophages. Monocytes cultured with GM-CSF plus IL-10, however, died through apoptosis. IL-10 decreased expression of bcl-2, bcl-x(L), and mcl-1- but not bax mRNA in monocytes stimulated with GM-CSF. IL-10 did not change the expression of mRNA of both GM-CSFR alpha-chain and beta-chain, but inhibited tyrosine phosphorylation of STAT5 and extracellular signal-regulated kinases 1 and 2 in the monocytes. The inhibitory effect of IL-10 was restricted to treatment 48 h after stimulation with GM-CSF. Addition of IL-10 after that time induced neither apoptosis nor a decrease in expression of bcl-2, bcl-x(L), and mcl-1 mRNA. IL-10, however, inhibited LPS-induced TNF-alpha production even in these cells, indicating that the cells still possessed responsiveness to IL-10. Monocytes pretreated for >48 h with GM-CSF became resistant to GM-CSF withdrawal, and the cells could survive without GM-CSF. These results indicate that IL-10 selectively inhibits GM-CSF-dependent monocyte survival by inhibiting the signaling events induced by GM-CSF, but the timing of addition of IL-10 is critical, and IL-10 had to be added within 48 h after stimulation with GM-CSF to achieve the inhibitory effect. These results taken together with our previous results indicate that IL-10 plays a pivotal role in monocyte survival and development into macrophages in concert with M-CSF and GM-CSF. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Hashimoto, S I AU - Komuro, I AU - Yamada, M AU - Akagawa, K S AD - Department of Immunology, National Institutes of Health, Tokyo, Japan. Y1 - 2001/10/01/ PY - 2001 DA - 2001 Oct 01 SP - 3619 EP - 3625 VL - 167 IS - 7 SN - 0022-1767, 0022-1767 KW - BCL2L1 protein, human KW - 0 KW - DNA-Binding Proteins KW - Milk Proteins KW - Myeloid Cell Leukemia Sequence 1 Protein KW - Neoplasm Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - RNA, Messenger KW - Receptors, Granulocyte-Macrophage Colony-Stimulating Factor KW - STAT5 Transcription Factor KW - Trans-Activators KW - Tumor Necrosis Factor-alpha KW - bcl-X Protein KW - Interleukin-10 KW - 130068-27-8 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Abridged Index Medicus KW - Index Medicus KW - Proto-Oncogene Proteins c-bcl-2 -- biosynthesis KW - Trans-Activators -- metabolism KW - Neoplasm Proteins -- biosynthesis KW - Apoptosis KW - Mitogen-Activated Protein Kinases -- metabolism KW - Humans KW - Cell Differentiation KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - RNA, Messenger -- biosynthesis KW - Cell Survival KW - Cells, Cultured KW - Kinetics KW - Neoplasm Proteins -- genetics KW - Receptors, Granulocyte-Macrophage Colony-Stimulating Factor -- genetics KW - Receptors, Granulocyte-Macrophage Colony-Stimulating Factor -- biosynthesis KW - Proto-Oncogene Proteins c-bcl-2 -- genetics KW - Drug Antagonism KW - DNA-Binding Proteins -- metabolism KW - Macrophages -- immunology KW - Monocytes -- cytology KW - Monocytes -- immunology KW - Interleukin-10 -- pharmacology KW - Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71181562?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=IL-10+inhibits+granulocyte-macrophage+colony-stimulating+factor-dependent+human+monocyte+survival+at+the+early+stage+of+the+culture+and+inhibits+the+generation+of+macrophages.&rft.au=Remaley%2C+Alan+T%3BBark%2C+Samantha%3BWalts%2C+Avram+D%3BFreeman%2C+Lita%3BShulenin%2C+Sergey%3BAnnilo%2C+Tarmo%3BElgin%2C+Eric%3BRhodes%2C+Hope+E%3BJoyce%2C+Charles%3BDean%2C+Michael%3BSantamarina-Fojo%2C+Silvia%3BBrewer%2C+H+Bryan&rft.aulast=Remaley&rft.aufirst=Alan&rft.date=2002-07-12&rft.volume=295&rft.issue=2&rft.spage=276&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Behavioral evidence for the interaction of oleamide with multiple neurotransmitter systems. AN - 71178675; 11561096 AB - While the endogenous fatty acid amide oleamide has hypnotic properties, neither the breadth of its behavioral actions nor the mechanism(s) by which these behaviors may be mediated has been elucidated. Therefore, the effects of oleamide on the performance of rats in tests of motor function, analgesia, and anxiety were investigated. Oleamide reduced the distance traveled in the open field (ED50 = 14, 10-19 mg/kg, mean, 95% confidence interval), induced analgesia and hypothermia, but did not cause catalepsy. Moreover, a dose of oleamide without effect on motor function was anxiolytic in the social interaction test and elevated plus-maze. These actions of a single dose of oleamide lasted for 30 to 60 min. While rats became tolerant to oleamide following 8 days of repeated administration, oleamide is a poor inducer of physical dependence. Pretreatment with antagonists of the serotonin (5HT)1A, 5HT2C, and vanilloid receptors did not modify oleamide's effects. However, the cannabinoid receptor antagonist SR 141716A inhibited oleamide-induced analgesia in the tail-flick assay, the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline reversed the analgesia and hypothermia, and the dopamine D2 receptor antagonist L 741626 blocked oleamide's locomotor and analgesic actions. Interestingly, oleamide analogs resistant to hydrolysis by fatty acid amide hydrolase (FAAH) maintained but did not show increased behavioral potency or duration of action, whereas two FAAH inhibitors produced analogous behavioral effects. Thus, oleamide induces behaviors reminiscent of the actions of endogenous cannabinoids, but the involvement of GABAergic and dopaminergic systems, either directly or indirectly, in the actions of oleamide cannot be ruled out. JF - The Journal of pharmacology and experimental therapeutics AU - Fedorova, I AU - Hashimoto, A AU - Fecik, R A AU - Hedrick, M P AU - Hanus, L O AU - Boger, D L AU - Rice, K C AU - Basile, A S AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0008, USA. Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 332 EP - 342 VL - 299 IS - 1 SN - 0022-3565, 0022-3565 KW - Enzyme Inhibitors KW - 0 KW - Neurotransmitter Agents KW - Oleic Acids KW - oleylamide KW - 7L25QK8BWO KW - Amidohydrolases KW - EC 3.5.- KW - fatty-acid amide hydrolase KW - EC 3.5.1.- KW - Index Medicus KW - Reaction Time -- drug effects KW - Animals KW - Catalepsy -- chemically induced KW - Anxiety -- psychology KW - Body Temperature -- drug effects KW - Social Behavior KW - Amidohydrolases -- metabolism KW - Rats KW - Drug Tolerance KW - Rats, Sprague-Dawley KW - Enzyme Inhibitors -- pharmacology KW - Pain Measurement -- drug effects KW - Substance Withdrawal Syndrome -- psychology KW - Enzyme Inhibitors -- chemical synthesis KW - Motor Activity -- drug effects KW - Male KW - Oleic Acids -- pharmacology KW - Behavior, Animal -- drug effects KW - Oleic Acids -- adverse effects KW - Neurotransmitter Agents -- physiology KW - Oleic Acids -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71178675?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Effects+of+cerebral+ischemia+in+mice+deficient+in+Persephin.&rft.au=Tomac%2C+Andreas+C%3BAgulnick%2C+Alan+D%3BHaughey%2C+Norman%3BChang%2C+Chen-Fu%3BZhang%2C+Yajun%3BB%C3%A4ckman%2C+Cristina%3BMorales%2C+Marisela%3BMattson%2C+Mark+P%3BWang%2C+Yun%3BWestphal%2C+Heiner%3BHoffer%2C+Barry+J&rft.aulast=Tomac&rft.aufirst=Andreas&rft.date=2002-07-09&rft.volume=99&rft.issue=14&rft.spage=9521&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-18 N1 - Date created - 2001-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Correspondence of the functional epitopes of poxvirus and human interleukin-18-binding proteins. AN - 71175224; 11559827 AB - Molluscum contagiosum virus, a human poxvirus that causes persistent small benign skin tumors, encodes a variety of putative immune defense proteins. Three such proteins, MC51L, MC53L, and MC54L, have 20 to 35% amino acid sequence identities with human interleukin-18 (hIL-18)-binding protein (hIL-18BP), a naturally occurring antagonist of the proinflammatory cytokine IL-18. We previously demonstrated that seven amino acids within the immunoglobulin-like domain of hIL-18BP were important for high-affinity binding to hIL-18. Model building indicated that MC54L, which has been shown to bind hIL-18, contains five of the seven amino acids at corresponding positions in its immunoglobulin-like domain, the exceptions being the conservative substitution of isoleucine for a leucine and the nonconservative substitution of valine for a phenylalanine. We found that individual alanine substitutions for these six identical or highly conserved amino acids of MC54L caused changes in affinity and binding free energy for hIL-18 that were quantitatively similar to those produced by mutagenesis of hIL-18BP. Furthermore, when the nonconserved valine of MC54L was mutated to phenylalanine, making it more like hIL-18BP, its affinity for hIL-18 increased more than 10-fold. In addition, the carboxyl-terminal half of MC54L, which has no similarity with hIL-18BP, was dispensable for hIL-18 binding. Thus, despite their relatively low overall sequence identity, MC54L and hIL-18BP have similar hIL-18 binding sites and functional epitopes. On the other hand, MC51L and MC53L have nonconservative substitutions of three to six of the seven critical amino acids of hIL-18BP and neither protein bound hIL-18, suggesting that they may interact with unidentified ligands. JF - Journal of virology AU - Xiang, Y AU - Moss, B AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0445,USA. Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 9947 EP - 9954 VL - 75 IS - 20 SN - 0022-538X, 0022-538X KW - Epitopes KW - 0 KW - Glycoproteins KW - Intercellular Signaling Peptides and Proteins KW - Recombinant Proteins KW - Viral Proteins KW - interleukin-18 binding protein KW - Valine KW - HG18B9YRS7 KW - Index Medicus KW - Epitopes -- genetics KW - Models, Molecular KW - Humans KW - Amino Acid Sequence KW - Protein Binding KW - Binding Sites KW - Sequence Alignment KW - Kinetics KW - Molecular Sequence Data KW - Epitopes -- chemistry KW - Recombinant Proteins -- chemistry KW - Mutation KW - Valine -- chemistry KW - Amino Acid Substitution KW - Viral Proteins -- genetics KW - Molluscum contagiosum virus -- chemistry KW - Glycoproteins -- chemistry KW - Viral Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71175224?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Correspondence+of+the+functional+epitopes+of+poxvirus+and+human+interleukin-18-binding+proteins.&rft.au=Xiang%2C+Y%3BMoss%2C+B&rft.aulast=Xiang&rft.aufirst=Y&rft.date=2001-10-01&rft.volume=75&rft.issue=20&rft.spage=9947&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-11-01 N1 - Date created - 2001-09-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Am Acad Dermatol. 1986 Oct;15(4 Pt 1):645-9 [2429998] Genes Cells. 1999 Sep;4(9):541-9 [10526240] Am J Dermatopathol. 1989 Jun;11(3):248-54 [2471417] J Cutan Pathol. 1990 Aug;17(4):202-5 [2203834] Virology. 1993 Dec;197(2):511-28 [8249275] Int J Dermatol. 1994 Jul;33(7):453-61 [7928025] Virology. 1995 Nov 10;213(2):655-9 [7491789] Nature. 1996 Feb 15;379(6566):591 [8628393] J Immunol. 1996 Jun 1;156(11):4274-9 [8666798] Science. 1996 Aug 9;273(5276):813-6 [8670425] Virology. 1996 Dec 1;226(1):95-101 [8941326] Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1172-6 [9037025] Nature. 1997 Apr 3;386(6624):517-21 [9087414] J Biol Chem. 1997 Apr 11;272(15):9621-4 [9092488] Virology. 1997 Jun 23;233(1):19-42 [9201214] Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9875-80 [9275219] Science. 1998 Jan 2;279(5347):102-5 [9417017] Proc Natl Acad Sci U S A. 1998 May 26;95(11):6403-7 [9600978] J Exp Med. 2000 Jan 3;191(1):171-80 [10620615] J Biol Chem. 2000 Jan 14;275(2):1169-75 [10625660] Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1190-5 [10655506] J Immunol. 2000 Mar 15;164(6):3246-54 [10706717] J Gen Virol. 2000 May;81(Pt 5):1223-30 [10769064] J Virol. 2000 Jun;74(12):5659-66 [10823874] Trends Microbiol. 2000 Sep;8(9):410-8 [10989308] Trends Microbiol. 2000 Oct;8(10):473-7 [11044683] J Virol. 2000 Dec;74(23):11230-9 [11070021] Virology. 2001 Jan 5;279(1):22-6 [11145885] Virology. 2001 Mar 30;282(1):14-25 [11259186] Virology. 2001 Mar 15;281(2):170-92 [11277691] J Biol Chem. 2001 May 18;276(20):17380-6 [11278524] J Cell Biol. 1998 Jun 1;141(5):1243-53 [9606215] Virology. 1998 Oct 25;250(2):397-407 [9792850] J Allergy Clin Immunol. 1999 Jan;103(1 Pt 1):11-24 [9893178] J Infect Dis. 1999 Mar;179(3):701-4 [9952381] Immunity. 1999 Jan;10(1):127-36 [10023777] Virology. 1999 May 10;257(2):297-302 [10329540] Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11537-42 [10500212] Infect Immun. 1989 Feb;57(2):590-5 [2492265] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acetaminophen induces apoptosis of C6 glioma cells by activating the c-Jun NH(2)-terminal protein kinase-related cell death pathway. AN - 71173813; 11562448 AB - Acetaminophen (AAP), a widely used analgesic drug, can damage various organs when taken in large doses. In this study, we investigate whether AAP causes cell damage by altering the early signaling pathways associated with cell death and survival. AAP caused time- and concentration-dependent apoptosis and DNA fragmentation of C6 glioma cells used as a model. AAP activated c-Jun N-terminal protein kinase (JNK) by 5.3-fold within 15 min. The elevated JNK activity persisted for up to 4 h before it returned to the basal level at 8 h. In contrast, activities of other mitogen-activated protein (MAP) kinases and the level of Akt phosphorylation in the cell survival pathway remained unchanged throughout the treatment. Wortmannin, an inhibitor of phosphatidylinositol-3 kinase, or SB203580, an inhibitor of p38 MAP kinase, did not reduce AAP-induced toxicity, indicating that these enzymes do not play a major role in cell toxicity. AAP-induced apoptosis was preceded by the sequential elevation of the pro-apoptotic Bax protein, cytochrome c release, and caspase-3 activity. Treatment with caspase inhibitor benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethyl ketone (Z-DEVD-FMK) significantly reduced AAP-induced caspase-3 activation and cytotoxicity. Transfection of cDNA for the dominant-negative mutant JNK-KR or stress-activated protein kinase kinase-1 Lys-->Arg mutant (SEK1-KR), an immediate upstream kinase of JNK, significantly reduced AAP-induced JNK activation and cell death rate. The noncytotoxic analog of AAP, 3-hydroxyacetanilide, neither increased JNK activity nor caused apoptosis. Pretreatment with YH439, an inhibitor of CYP2E1 gene transcription, markedly reduced CYP2E1 mRNA, protein content, and activity, as well as the rate of AAP-induced JNK activation and cell death. These data indicate that AAP can cause cell damage by activating the JNK-related cell death pathway, providing a new mechanism for AAP-induced cytotoxicity. JF - Molecular pharmacology AU - Bae, M A AU - Pie, J E AU - Song, B J AD - Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20852, USA. Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 847 EP - 856 VL - 60 IS - 4 SN - 0026-895X, 0026-895X KW - Acetanilides KW - 0 KW - Analgesics KW - Analgesics, Non-Narcotic KW - Androstadienes KW - Bax protein, rat KW - Cytochrome c Group KW - Enzyme Inhibitors KW - Imidazoles KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Pyridines KW - Thiazoles KW - YH 439 KW - bcl-2-Associated X Protein KW - Acetaminophen KW - 362O9ITL9D KW - 3-hydroxyacetanilide KW - 621-42-1 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - Mitogen-Activated Protein Kinase Kinases KW - EC 2.7.12.2 KW - Casp3 protein, rat KW - EC 3.4.22.- KW - Caspase 3 KW - Caspases KW - SB 203580 KW - OU13V1EYWQ KW - wortmannin KW - XVA4O219QW KW - Index Medicus KW - Animals KW - Drug Interactions KW - Imidazoles -- pharmacology KW - Dose-Response Relationship, Drug KW - Proto-Oncogene Proteins -- metabolism KW - Analgesics -- pharmacology KW - Androstadienes -- pharmacology KW - Cytochrome P-450 CYP2E1 -- metabolism KW - Mitogen-Activated Protein Kinase Kinases -- metabolism KW - Caspases -- metabolism KW - Thiazoles -- pharmacology KW - Rats KW - Acetanilides -- pharmacology KW - Tumor Cells, Cultured KW - Enzyme Activation -- drug effects KW - Enzyme Inhibitors -- pharmacology KW - DNA Fragmentation -- drug effects KW - Cytochrome c Group -- metabolism KW - Time Factors KW - Pyridines -- pharmacology KW - Glioma -- pathology KW - Analgesics, Non-Narcotic -- pharmacology KW - Apoptosis KW - Mitogen-Activated Protein Kinases -- metabolism KW - Acetaminophen -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71173813?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Acetaminophen+induces+apoptosis+of+C6+glioma+cells+by+activating+the+c-Jun+NH%282%29-terminal+protein+kinase-related+cell+death+pathway.&rft.au=Bae%2C+M+A%3BPie%2C+J+E%3BSong%2C+B+J&rft.aulast=Bae&rft.aufirst=M&rft.date=2001-10-01&rft.volume=60&rft.issue=4&rft.spage=847&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-04 N1 - Date created - 2001-09-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemical mutagenesis of dengue virus type 4 yields mutant viruses which are temperature sensitive in vero cells or human liver cells and attenuated in mice. AN - 71173263; 11559806 AB - A recombinant live attenuated dengue virus type 4 (DEN4) vaccine candidate, 2ADelta30, was found previously to be generally well tolerated in humans, but a rash and an elevation of liver enzymes in the serum occurred in some vaccinees. 2ADelta30, a non-temperature-sensitive (non-ts) virus, contains a 30-nucleotide deletion (Delta30) in the 3' untranslated region (UTR) of the viral genome. In the present study, chemical mutagenesis of DEN4 was utilized to generate attenuating mutations which may be useful in further attenuation of the 2ADelta30 candidate vaccine. Wild-type DEN4 2A virus was grown in Vero cells in the presence of 5-fluorouracil, and a panel of 1,248 clones were isolated. Twenty ts mutant viruses were identified that were ts in both simian Vero and human liver HuH-7 cells (n = 13) or only in HuH-7 cells (n = 7). Each of the 20 ts mutant viruses possessed an attenuation phenotype, as indicated by restricted replication in the brains of 7-day-old mice. The complete nucleotide sequence of the 20 ts mutant viruses identified nucleotide substitutions in structural and nonstructural genes as well as in the 5' and 3' UTRs, with more than one change occurring, in general, per mutant virus. A ts mutation in the NS3 protein (nucleotide position 4995) was introduced into a recombinant DEN4 virus possessing the Delta30 deletion, thereby creating rDEN4Delta30-4995, a recombinant virus which is ts and more attenuated than rDEN4Delta30 virus in the brains of mice. We are assembling a menu of attenuating mutations that should be useful in generating satisfactorily attenuated recombinant dengue vaccine viruses and in increasing our understanding of the pathogenesis of dengue virus. JF - Journal of virology AU - Blaney, J E AU - Johnson, D H AU - Firestone, C Y AU - Hanson, C T AU - Murphy, B R AU - Whitehead, S S AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. jblaney@niaid.nih.gov Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 9731 EP - 9740 VL - 75 IS - 20 SN - 0022-538X, 0022-538X KW - 3' Untranslated Regions KW - 0 KW - 5' Untranslated Regions KW - Mutagens KW - NS3 protein, flavivirus KW - Vaccines, Attenuated KW - Viral Nonstructural Proteins KW - Viral Vaccines KW - Serine Endopeptidases KW - EC 3.4.21.- KW - RNA Helicases KW - EC 3.6.4.13 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Virus Replication KW - Animals, Suckling KW - 5' Untranslated Regions -- genetics KW - Animals KW - Humans KW - Viral Vaccines -- genetics KW - Temperature KW - Brain -- virology KW - Genome, Viral KW - Mice KW - Cloning, Molecular KW - Viral Nonstructural Proteins -- genetics KW - Recombination, Genetic KW - Cercopithecus aethiops KW - Vaccines, Attenuated -- genetics KW - Molecular Sequence Data KW - Vero Cells KW - Genes, Viral KW - 3' Untranslated Regions -- genetics KW - Cell Line KW - Dengue -- virology KW - Dengue Virus -- drug effects KW - Fluorouracil -- pharmacology KW - Dengue Virus -- genetics KW - Mutagens -- pharmacology KW - Dengue Virus -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71173263?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Chemical+mutagenesis+of+dengue+virus+type+4+yields+mutant+viruses+which+are+temperature+sensitive+in+vero+cells+or+human+liver+cells+and+attenuated+in+mice.&rft.au=Blaney%2C+J+E%3BJohnson%2C+D+H%3BFirestone%2C+C+Y%3BHanson%2C+C+T%3BMurphy%2C+B+R%3BWhitehead%2C+S+S&rft.aulast=Blaney&rft.aufirst=J&rft.date=2001-10-01&rft.volume=75&rft.issue=20&rft.spage=9731&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-11-01 N1 - Date created - 2001-09-17 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF375822; GENBANK N1 - SuppNotes - Cited By: Am J Trop Med Hyg. 1988 Jan;38(1):172-80 [3341519] Am J Trop Med Hyg. 1952 Jan;1(1):30-50 [14903434] Virology. 1989 Aug;171(2):637-9 [2548336] Arch Virol. 1990;110(1-2):91-101 [2178591] Virology. 1992 Apr;187(2):573-90 [1312269] Am J Trop Med Hyg. 1992 Sep;47(3):265-70 [1355950] J Infect Dis. 1994 Mar;169(3):512-8 [7908925] J Infect Dis. 1994 Dec;170(6):1448-55 [7995984] J Gen Virol. 1995 Feb;76 ( Pt 2):409-13 [7844560] J Gen Virol. 1995 Nov;76 ( Pt 11):2749-55 [7595382] J Virol. 1996 Jun;70(6):3930-7 [8648730] Vaccine. 1996 Mar;14(4):329-36 [8744561] J Gen Virol. 1996 Oct;77 ( Pt 10):2547-54 [8887489] J Virol. 1997 Apr;71(4):3244-9 [9060688] Am J Trop Med Hyg. 1997 May;56(5):566-72 [9180609] Virology. 1997 Jun 9;232(2):281-90 [9191841] J Infect Dis. 1997 Aug;176(2):313-21 [9237695] J Gen Virol. 1997 Sep;78 ( Pt 9):2287-91 [9292016] Virology. 1999 Oct 10;263(1):70-7 [10544083] Adv Virus Res. 1999;53:35-70 [10582094] Am J Trop Med Hyg. 1999 Nov;61(5):720-4 [10586901] J Infect Dis. 2000 Jan;181(1):2-9 [10608744] J Med Virol. 2000 Apr;60(4):425-31 [10686026] J Med Virol. 2000 Apr;60(4):432-8 [10686027] J Virol. 2000 Apr;74(7):3011-9 [10708415] J Virol. 2000 Apr;74(7):3020-8 [10708416] J Trop Pediatr. 2000 Feb;46(1):40-3 [10730040] J Virol. 2000 Jun;74(12):5477-85 [10823852] Vaccine. 2000 May 26;18 Suppl 2:44-7 [10821973] Nat Med. 2000 Jul;6(7):816-20 [10888933] Virus Res. 2000 Aug;69(1):31-9 [10989183] Southeast Asian J Trop Med Public Health. 2000 Jun;31(2):259-63 [11127322] Virchows Arch. 2001 Feb;438(2):107-15 [11253111] J Virol. 2001 Apr;75(8):3501-8 [11264339] Vaccine. 2001 Apr 30;19(23-24):3179-88 [11312014] Am J Trop Med Hyg. 2001 Nov;65(5):405-13 [11716091] Am J Trop Med Hyg. 2001 Nov;65(5):414-9 [11716092] Am J Epidemiol. 1969 Jun;89(6):669-80 [5787600] Am J Trop Med Hyg. 1969 Nov;18(6):997-1021 [4390977] J Comp Pathol. 1973 Apr;83(2):243-52 [4586764] J Immunol. 1976 Sep;117(3):953-61 [1085314] J Exp Med. 1977 Jul 1;146(1):218-29 [195000] J Infect Dis. 1977 Aug;136(2):256-62 [894078] Infect Immun. 1980 Jan;27(1):175-80 [6766902] J Infect Dis. 1980 Jan;141(1):1-6 [7365271] Cancer Res. 1982 Sep;42(9):3858-63 [6286115] J Infect Dis. 1984 Jun;149(6):1005-10 [6376649] Am J Trop Med Hyg. 1984 Jul;33(4):684-9 [6476216] Am J Trop Med Hyg. 1987 Mar;36(2):435-42 [3826504] Virology. 1987 Aug;159(2):217-28 [3039728] J Virol. 1998 Jan;72(1):624-32 [9420267] J Virol. 1998 Mar;72(3):1762-8 [9499025] J Virol. 1998 Dec;72(12):9729-37 [9811707] J Virol. 1999 Feb;73(2):871-7 [9882287] J Gen Virol. 1999 May;80 ( Pt 5):1167-77 [10355763] Hum Pathol. 1999 Sep;30(9):1106-10 [10492047] Virology. 1999 Sep 1;261(2):309-18 [10497116] J Infect Dis. 1988 Oct;158(4):876-80 [3171230] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - JC virus multiplication in human hematopoietic progenitor cells requires the NF-1 class D transcription factor. AN - 71171920; 11559801 AB - JCV, a small DNA virus of the polyomavirus family, has been shown to infect glial cells of the central nervous system, hematopoietic progenitor cells, and immune system lymphocytes. A family of DNA binding proteins called nuclear factor-1 (NF-1) has been linked with site-coding specific transcription of cellular and viral genes and replication of some viruses, including JC virus (JCV). It is unclear which NF-1 gene product must be expressed by cells to promote JCV multiplication. Previously, it was shown that elevated levels of NF-1 class D mRNA were expressed by human brain cells that are highly susceptible to JCV infection but not by JCV nonpermissive HeLa cells. Recently, we reported that CD34(+) precursor cells of the KG-1 line, when treated with the phorbol ester phorbol 12-myristate 13-acetate (PMA), differentiated to cells with macrophage-like characteristics and lost susceptibility to JCV infection. These studies have now been extended by asking whether loss of JCV susceptibility by PMA-treated KG-1 cells is linked with alterations in levels of NF-1 class D expression. Using reverse transcription-PCR, we have found that PMA-treated KG-1 cells express mRNA that codes for all four classes of NF-1 proteins, although different levels of RNA expression were observed in the hematopoietic cells differentiated into macrophages. Northern hybridization confirms that the expression of NF-1 class D gene is lower in JCV nonpermissive PMA-treated KG-1 cells compared with non-PMA-treated cells. Further, using gel mobility shift assays, we were able to show the induction of specific NF-1-DNA complexes in KG-1 cells undergoing PMA treatment. The binding increases in direct relation to the duration of PMA treatment. These results suggest that the binding pattern of NF-1 class members may change in hematopoietic precursor cells, such as KG-1, as they undergo differentiation to macrophage-like cells. Transfection of PMA-treated KG-1 cells with an NF-1 class D expression vector restored the susceptibility of these cells to JCV infection, while the transfection of PMA-treated KG-1 cells with NF-1 class A, B, and C vectors was not able to restore JCV susceptibility. These data collectively suggest that selective expression of NF-1 class D has a regulatory role in JCV multiplication. JF - Journal of virology AU - Monaco, M C AU - Sabath, B F AU - Durham, L C AU - Major, E O AD - Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2001/10// PY - 2001 DA - October 2001 SP - 9687 EP - 9695 VL - 75 IS - 20 SN - 0022-538X, 0022-538X KW - CCAAT-Enhancer-Binding Proteins KW - 0 KW - DNA-Binding Proteins KW - NFI Transcription Factors KW - Nuclear Proteins KW - RNA, Messenger KW - Transcription Factors KW - Y-Box-Binding Protein 1 KW - YBX1 protein, human KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Virus Replication KW - Blotting, Northern KW - Humans KW - Macrophages -- virology KW - RNA, Messenger -- analysis KW - Cell Differentiation KW - Reverse Transcriptase Polymerase Chain Reaction KW - Transfection KW - Cell Line KW - Macrophages -- metabolism KW - JC Virus -- pathogenicity KW - Transcription Factors -- metabolism KW - CCAAT-Enhancer-Binding Proteins -- metabolism KW - JC Virus -- physiology KW - Hematopoietic Stem Cells -- virology KW - Hematopoietic Stem Cells -- metabolism KW - CCAAT-Enhancer-Binding Proteins -- genetics KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71171920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=JC+virus+multiplication+in+human+hematopoietic+progenitor+cells+requires+the+NF-1+class+D+transcription+factor.&rft.au=Monaco%2C+M+C%3BSabath%2C+B+F%3BDurham%2C+L+C%3BMajor%2C+E+O&rft.aulast=Monaco&rft.aufirst=M&rft.date=2001-10-01&rft.volume=75&rft.issue=20&rft.spage=9687&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-11-01 N1 - Date created - 2001-09-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1987 Jan 16;48(1):79-89 [3024847] Virology. 1997 Feb 17;228(2):269-77 [9123834] Cell. 1988 Feb 12;52(3):405-14 [2830985] Nucleic Acids Res. 1988 May 25;16(10):4419-35 [3380685] Nature. 1988 Jul 21;334(6179):218-24 [3398920] EMBO J. 1988 Oct;7(10):3115-23 [3053160] Proc Natl Acad Sci U S A. 1988 Dec;85(23):8963-7 [3194401] Biochem Biophys Res Commun. 1988 Dec 15;157(2):419-25 [2849429] J Biol Chem. 1989 Apr 25;264(12):7025-32 [2540170] Nucleic Acids Res. 1989 May 11;17(9):3519-33 [2542901] Nucleic Acids Res. 1989 Jun 12;17(11):4061-75 [2544855] Cell. 1989 Aug 25;58(4):741-53 [2504497] Biochemistry. 1989 Oct 3;28(20):8191-200 [2513876] EMBO J. 1990 Feb;9(2):559-66 [2303041] Nucleic Acids Res. 1990 Jan 11;18(1):57-64 [2308836] Biochem Biophys Res Commun. 1990 Mar 16;167(2):648-53 [1690988] Nucleic Acids Res. 1990 May 11;18(9):2607-16 [2339052] J Virol. 1990 Aug;64(8):3864-71 [2164600] J Neurovirol. 2000 Apr;6(2):127-36 [10822326] Gene. 2000 May 16;249(1-2):31-45 [10831836] Anal Biochem. 1976 May 7;72:248-54 [942051] Cancer Res. 1981 Mar;41(3):919-26 [6936077] Proc Natl Acad Sci U S A. 1982 Nov;79(21):6438-42 [6216480] Proc Natl Acad Sci U S A. 1983 Oct;80(20):6177-81 [6336326] J Virol. 1984 Aug;51(2):458-69 [6086957] Proc Natl Acad Sci U S A. 1985 Feb;82(4):1257-61 [2983332] Nature. 1985 Mar 21-27;314(6008):289-92 [3920528] Mol Cell Biol. 1985 May;5(5):964-71 [4039788] Nucleic Acids Res. 1985 Mar 25;13(6):2045-61 [2987840] EMBO J. 1985 Feb;4(2):421-6 [4018031] Nucleic Acids Res. 1985 Jul 11;13(13):4935-52 [4040630] EMBO J. 1985 Jun;4(6):1515-21 [4040852] EMBO J. 1986 Jun;5(6):1367-71 [3015602] EMBO J. 1986 Aug;5(8):1967-71 [3463507] Nucleic Acids Res. 1986 Nov 25;14(22):9117-32 [3786147] Nucleic Acids Res. 1991 May 11;19(9):2499 [2041787] J Virol. 1991 Nov;65(11):5933-43 [1656080] Nucleic Acids Res. 1991 Dec 11;19(23):6641 [1754401] J Biol Chem. 1992 Jul 15;267(20):14204-11 [1321139] Cell Growth Differ. 1994 Feb;5(2):161-9 [8180129] FEBS Lett. 1994 Jul 4;348(1):46-50 [8026582] Nucleic Acids Res. 1994 Sep 25;22(19):3825-33 [7937100] Eur J Immunol. 1996 Jan;26(1):17-27 [8566062] Cell Growth Differ. 1996 Apr;7(4):501-10 [9052991] J Immunol. 1996 Sep 1;157(5):2129-35 [8757337] J Virol. 1996 Oct;70(10):7004-12 [8794345] J Neurovirol. 1996 Apr;2(2):87-100 [8799200] Dev Dyn. 1997 Mar;208(3):313-25 [9056636] J Virol. 1987 May;61(5):1559-70 [3033283] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - National Institutes of Health Consensus Development Conference Statement: Phenylketonuria: Screening and management, October 16-18, 2000 AN - 228379265; 11581453 AB - Genetic testing for PKU has been in place for almost 40 years and has been very successful in preventing severe mental retardiation in thousands of children and adults. Metabolic control is necessary across the lifespan of individuals with PKU. JF - Pediatrics AU - National Institutes of Health Consensus Development Panel AD - National Institutes of Health Consensus Development Panel Y1 - 2001/10// PY - 2001 DA - Oct 2001 SP - 972 EP - 82 CY - Evanston PB - American Academy of Pediatrics VL - 108 IS - 4 SN - 00314005 KW - Medical Sciences--Pediatrics KW - Medical screening KW - Medical disorders KW - Mental retardation KW - Genetics KW - Genetic Screening KW - Humans KW - Adult KW - Incidence KW - Child KW - Phenylketonurias -- therapy KW - Phenylketonurias -- diagnosis KW - Phenylketonurias -- epidemiology KW - Prevalence UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/228379265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=National+Institutes+of+Health+Consensus+Development+Conference+Statement%3A+Phenylketonuria%3A+Screening+and+management%2C+October+16-18%2C+2000&rft.au=National+Institutes+of+Health+Consensus+Development+Panel&rft.aulast=National+Institutes+of+Health+Consensus+Development+Panel&rft.aufirst=&rft.date=2001-10-01&rft.volume=108&rft.issue=4&rft.spage=972&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=00314005&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Academy of Pediatrics Oct 2001 N1 - Last updated - 2014-05-18 N1 - CODEN - PEDIAU ER - TY - JOUR T1 - A Murine Dopamine Neuron-Specific cDNA Library and Microarray: Increased COXI Expression during Methamphetamine Neurotoxicity AN - 19469036; 8068129 AB - Due to brain tissue heterogeneity, the molecular genetic profile of any neurotransmitter-specific neuronal subtype is unknown. The purpose of this study was to purify a population of dopamine neurons, construct a cDNA library, and generate an initial gene expression profile and a microarray representative of dopamine neuron transcripts. Ventral mesencephalic dopamine neurons were purified by fluorescent-activated cell sorting from embryonic day 13.5 transgenic mice harboring a 4.5-kb rat tyrosine hydroxylase promoter-lacZ fusion. Nine-hundred sixty dopamine neuron cDNA clones were sequenced and arrayed for use in studies of gene expression changes during methamphetamine neurotoxicity. A neurotoxic dose of methamphetamine produced a greater than twofold up-regulation of the mitochondrial cytochrome c oxidase polypeptide I transcript from adult mouse substantia nigra at 12 h posttreatment. This is the first work to describe a gene expression profile for a neuronal subtype and to identify gene expression changes during methamphetamine neurotoxicity. JF - Neurobiology of Disease AU - Barrett, Tanya AU - Xie, Tao AU - Piao, Yulan AU - Dillon-Carter, Ora AU - Kargul, George J AU - Lim, Meng K AU - Chrest, Francis J AU - Wersto, Robert AU - Rowley, Daniel L AU - Juhaszova, Magdalena AU - Zhou, Li AU - Vawter, Marquis P AU - Becker, Kevin G AU - Cheadle, Christopher AU - Wood III, William H AU - McCann, Una D AU - Freed, William J AU - Ko, Minoru S AU - Ricaurte, George A AU - Donovan, David M AD - Research Resources Branch, Intramural Research Program, National Institute on Aging, 5600 Nathan Shock Drive Y1 - 2001/10// PY - 2001 DA - Oct 2001 SP - 822 EP - 833 PB - Elsevier Science, The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 8 IS - 5 SN - 0969-9961, 0969-9961 KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts KW - dopamine KW - cDNA library KW - cDNA microarray KW - methamphetamine KW - development KW - gene expression profile KW - Substantia nigra KW - Brain KW - Mitochondria KW - Cytochrome-c oxidase KW - Transgenic mice KW - DNA microarrays KW - Gene expression KW - Methamphetamine KW - Dopamine KW - Neurons KW - Neurotoxicity KW - Embryos KW - Tyrosine 3-monooxygenase KW - W 30925:Genetic Engineering KW - N3 11027:Neurology & neuropathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19469036?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Dopamine+neurons+derived+from+embryonic+stem+cells+function+in+an+animal+model+of+Parkinson%27s+disease&rft.au=Kim%2C+J+H%3BAuerbach%2C+J+M%3BRodriguez-Gomez%2C+JA%3BVelasco%2C+I%3BGavin%2C+D%3BLumelsky%2C+N%3BLee%2C+S-H%3BNguyen%2C+J%3BSanchez-Pernaute%2C+R%3BBankiewicz%2C+K%3BMcKay%2C+R&rft.aulast=Kim&rft.aufirst=J&rft.date=2002-07-04&rft.volume=418&rft.issue=6893&rft.spage=50&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-04-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Substantia nigra; Brain; Mitochondria; Cytochrome-c oxidase; Transgenic mice; DNA microarrays; Gene expression; Methamphetamine; Dopamine; Neurons; Neurotoxicity; Embryos; Tyrosine 3-monooxygenase DO - http://dx.doi.org/10.1006/nbdi.2001.0423 ER - TY - JOUR T1 - The Ethical Challenge of Infection-Inducing Challenge Experiments AN - 18460252; 5432578 AB - Challenge experiments that induce infections in healthy volunteers are an important method for initial efficacy testing of candidate vaccines and for study of the pathogenesis of infectious diseases. Although these studies can be conducted safely for selected infectious diseases that are either fully treatable or self-limiting, they raise significant ethical issues. An ethical framework is offered for evaluating infection-inducing challenge experiments, which focuses on the scientific and public health rationale for conducting these studies, the risks that they pose and the ways in which these risks can be minimized, the symptoms experienced by healthy volunteers that may cause discomfort or distress, the exclusion of vulnerable research subjects, the informed consent process, the payment of volunteers, and the use of isolation of volunteers to prevent infection of others. JF - Clinical Infectious Diseases AU - Miller, F G AU - Grady, C AD - Department of Clinical Bioethics, National Institutes of Health, Bethesda, MD, USA Y1 - 2001/10/01/ PY - 2001 DA - 2001 Oct 01 SP - 1028 EP - 1033 VL - 33 IS - 7 SN - 1058-4838, 1058-4838 KW - clinical trials KW - infectious diseases KW - vaccines KW - Health & Safety Science Abstracts KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18460252?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Infectious+Diseases&rft.atitle=The+Ethical+Challenge+of+Infection-Inducing+Challenge+Experiments&rft.au=Miller%2C+F+G%3BGrady%2C+C&rft.aulast=Miller&rft.aufirst=F&rft.date=2001-10-01&rft.volume=33&rft.issue=7&rft.spage=1028&rft.isbn=&rft.btitle=&rft.title=Clinical+Infectious+Diseases&rft.issn=10584838&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Mechanisms of Arsenic-Induced Cross-Tolerance to Nickel Cytotoxicity, Genotoxicity, and Apoptosis in Rat Liver Epithelial Cells AN - 18434531; 5412000 AB - The purpose of the present study was to investigate the mechanism of cross-tolerance to nickel in arsenic-transformed cells. Chronic arsenite-exposed (CAsE) cells (TRL 1215 cells, which had been continuously exposed to 0.5 mu M arsenite for 20 or more weeks) and control TRL 1215 cells were both exposed to nickel for 24 h, and cell viability was determined by metabolic integrity. The LC sub(50) for nickel was 608 plus or minus 32 mu M in CAsE cells as compared to 232 plus or minus 16 mu M in control cells, a 2.6-fold increase. CAsE and control cells were treated with 200 mu M nickel for 4 h and cellular-free radical production was measured using ESR spectrometry. Hydroxyl radical generation was decreased in CAsE cells. Thiobarbituric acid reactive substances, indicative of lipid peroxidation, and 8-oxo-2'-deoxyguanosine, indicative of oxidative DNA damage, were reduced in CAsE cells. Flow cytometric analysis using Annexin/FITC revealed that nickel-induced apoptosis was reduced in CAsE cells. CAsE cells showed generalized resistance to oxidant-induced toxicity as evidenced by a marked reduction in sensitivity to hydrogen peroxide. Interestingly, intracellular reduced glutathione (GSH) levels were significantly increased in CAsE cells, and when GSH was depleted, CAsE cells lost their nickel resistance. The mechanism of arsenic-induced cross-tolerance to cytotoxicity, genotoxicity, and apoptosis induced by nickel appears related to a generalized resistance to oxidant-induced injury, probably based, at least in part, in increased cellular GSH levels. JF - Toxicological Sciences AU - Qu, W AU - Kasprzak, K S AU - Kadiiska, M AU - Liu, J AU - Chen, H AU - Maciag, A AU - Mason, R P AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences; Metals Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Maryland, USA Y1 - 2001/10// PY - 2001 DA - Oct 2001 SP - 189 EP - 195 VL - 63 IS - 2 SN - 1096-6080, 1096-6080 KW - rats KW - Toxicology Abstracts KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18434531?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Mechanisms+of+Arsenic-Induced+Cross-Tolerance+to+Nickel+Cytotoxicity%2C+Genotoxicity%2C+and+Apoptosis+in+Rat+Liver+Epithelial+Cells&rft.au=Qu%2C+W%3BKasprzak%2C+K+S%3BKadiiska%2C+M%3BLiu%2C+J%3BChen%2C+H%3BMaciag%2C+A%3BMason%2C+R+P%3BWaalkes%2C+M+P&rft.aulast=Qu&rft.aufirst=W&rft.date=2001-10-01&rft.volume=63&rft.issue=2&rft.spage=189&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=08966273&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Staphylococcus aureus and Staphylococcus epidermidis peptide pheromones produced by the accessory gene regulator agr system AN - 18430100; 5409625 AB - The accessory gene regulator (agr) system of staphylococci regulates the expression of virulence factors in response to cell density. The extracellular signaling molecule encoded by this system is a thiolactone-containing pheromone peptide whose primary sequence varies among staphylococcal strains. A post-translational modification of the peptide is believed to be carried out by an enzyme with a novel function, AgrB. Staphylococcal pheromones show cross-inhibiting properties: Pheromones of self and pheromones of non-self induce and suppress the agr response, respectively, and have therefore been proposed as novel anti-staphylococcal drugs. As inhibition of agr leads to diminished expression of toxins, but to increased expression of colonization factors and biofilm formation, their therapeutic potential remains yet to be evaluated in depth. JF - Peptides AU - Otto, M AD - Rocky Mountain Laboratory, Laboratory of Human Bacterial Pathogenesis, NIAID, NIH, 903 South 4th Street, Hamilton, MT 59840, USA, motto@niaid.nih.gov Y1 - 2001/10// PY - 2001 DA - Oct 2001 SP - 1603 EP - 1608 VL - 22 IS - 10 SN - 0196-9781, 0196-9781 KW - AgrB protein KW - accessory proteins KW - virulence factors KW - Microbiology Abstracts B: Bacteriology KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18430100?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Peptides&rft.atitle=Staphylococcus+aureus+and+Staphylococcus+epidermidis+peptide+pheromones+produced+by+the+accessory+gene+regulator+agr+system&rft.au=Otto%2C+M&rft.aulast=Otto&rft.aufirst=M&rft.date=2001-10-01&rft.volume=22&rft.issue=10&rft.spage=1603&rft.isbn=&rft.btitle=&rft.title=Peptides&rft.issn=01969781&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special Issue: Bacterial and Anti Bacterial Peptides. N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Level of Maternal Antibody Required to Protect Neonates against Early-Onset Disease Caused by Group B Streptococcus Type Ia: A Multicenter, Seroepidemiology Study AN - 18254012; 5311649 AB - Because of the difficulty of conducting efficacy trials of vaccines against group B streptococcus (GBS), the licensure of these vaccines may have to rely on studies that measure vaccine-induced antibody levels that correlate with protection. This study estimates the level of maternal antibody required to protect neonates against early-onset disease (EOD) caused by GBS type Ia. Levels of maternal serum IgG GBS Ia antibodies, measured by ELISAs in 45 case patients (neonates with EOD caused by GBS Ia) and in 319 control subjects (neonates colonized by GBS Ia but without EOD) born at greater than or equal to 34 weeks gestation were compared. The probability of developing EOD declined with increasing maternal levels of IgG GBS Ia antibody (P = .03). Neonates whose mothers had levels of IgG GBS Ia antibody greater than or equal to 5 mu g/mL had an 88% lower risk (95% confidence interval, 7%-98%) of developing type-specific EOD, compared with those whose mothers had levels <0.5 mu g/mL. A vaccine that induces IgG GBS Ia antibody levels greater than or equal to 5 mu g/mL in mothers can be predicted to confer a high degree of type-specific immunity to EOD to their infants. JF - Journal of Infectious Diseases AU - Lin, F-YC AU - Philips, JB III AU - Azimi, PH AU - Weisman, LE AU - Clark, P AU - Rhoads, G G AU - Regan, J AU - Concepcion, N F AU - Frasch, CE AU - Troendle, J AU - Brenner, R A AU - Gray, B M AU - Bhushan, R AU - Fitzgerald, G AD - National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2001/10// PY - 2001 DA - Oct 2001 SP - 1022 EP - 1028 VL - 184 IS - 8 SN - 0022-1899, 0022-1899 KW - streptococci KW - Microbiology Abstracts B: Bacteriology KW - Streptococcus KW - Maternal inheritance KW - Immunity KW - Seroepidemiology KW - Vaccines KW - Infants KW - J 02834:Vaccination and immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18254012?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Level+of+Maternal+Antibody+Required+to+Protect+Neonates+against+Early-Onset+Disease+Caused+by+Group+B+Streptococcus+Type+Ia%3A+A+Multicenter%2C+Seroepidemiology+Study&rft.au=Lin%2C+F-YC%3BPhilips%2C+JB+III%3BAzimi%2C+PH%3BWeisman%2C+LE%3BClark%2C+P%3BRhoads%2C+G+G%3BRegan%2C+J%3BConcepcion%2C+N+F%3BFrasch%2C+CE%3BTroendle%2C+J%3BBrenner%2C+R+A%3BGray%2C+B+M%3BBhushan%2C+R%3BFitzgerald%2C+G&rft.aulast=Lin&rft.aufirst=F-YC&rft.date=2001-10-01&rft.volume=184&rft.issue=8&rft.spage=1022&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus; Infants; Maternal inheritance; Vaccines; Seroepidemiology; Immunity ER - TY - JOUR T1 - Different risks of symptomatic brain necrosis in NPC patients treated with different altered fractionated radiotherapy techniques AN - 18210437; 5282500 AB - Purpose: To report our observation of excessive temporal lobe necrosis in nasopharyngeal carcinoma (NPC) patients treated with 160 cGy b.i.d. radiotherapy technique. During the same period, patients treated with 120 cGy b.i.d. have not shown a similar tendency. Our experience may be useful for designing unconventional radiotherapy regimens for NPC patients. Methods and Materials: During the period from October 1991 to January 1998, 81 M0, previously untreated NPC patients completed altered fractionated radiotherapy. Seventy patients were treated with the hyperfractionated technique, and 11 were treated using the accelerated-hyperfractionated scheme. Hyperfractionated radiotherapy was delivered using 120 cGy b.i.d. separated by 6-h intervals throughout the course. A minimum tumor dose of 8000 cGy was the standard dose over an 8-week period. With the accelerated-hyperfractionated scheme, 160 cGy was given twice daily, also with an interval of 6 h. The minimum tumor dose ranged between 6840 and 7640 cGy, with 7 of the 11 patients receiving 7000 cGy. The arrangement of portals was the same for both regimens. The follow-up period for patients alive was from 32 to 102 months with a median of 61 months for the hyperfractionated patients. For the accelerated-hyperfractionated group, it ranged from 67 to 82 months with a median of 72 months. No patient was lost to follow-up. Results: At the time of analysis, 49 of the 70 patients in the hyperfractionated group were alive. In the accelerated group, 8 of the 11 patients were alive. The estimated radiation dose to the temporal lobe for the hyperfractionated group was 6000-7440 cGy with a median of 7080 cGy. For the accelerated-hyperfractionated group, the dose range was 4480-6700 cGy with a median of 6400 cGy. Of the 70 patients treated with hyperfractionated radiotherapy, none developed symptomatic brain necrosis, despite the higher total dose to the temporal lobe in general. In contrast, 3 of the 11 (27%) patients irradiated using the accelerated-hyperfractionated regimen suffered from temporal lobe necrosis at 16, 19, and 40 months after completion of radiotherapy. Conclusion: An excessive incidence of temporal lobe necrosis was noted when an accelerated-hyperfractionated regimen with 160 cGy b.i.d. was used in NPC patients with a median brain dose of 6400 cGy. There has been no such event in patients treated using a hyperfractionated regimen with 120 cGy and a median brain dose of 7000 cGy. The real causes of this discrepancy are not known. However, a high sensitivity of the human brain to a change in fraction size may play a role. JF - International Journal of Radiation Oncology, Biology, & Physics AU - Jen, Y-M AU - Hsu, W-L AU - Chen, C-Y AU - Hwang, J-M AU - Chang, L-P AU - Lin, Y-S AU - Su, W-F AU - Chen, C-M AU - Liu, D-W AU - Chao, H-L AD - Department of Radiation Oncology, Tri-Service General Hospital, 325, Section 2 Cheng-Kong Road, Nei-Hu, Taipei, Taiwan, ROC, ymjen@seed.net.tw Y1 - 2001/10/01/ PY - 2001 DA - 2001 Oct 01 SP - 344 EP - 348 VL - 51 IS - 2 SN - 0360-3016, 0360-3016 KW - man KW - Toxicology Abstracts KW - Risk assessment KW - Necrosis KW - Nasopharyngeal carcinoma KW - Dosimetry KW - Cancer patients KW - Brain KW - Radiotherapy KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18210437?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.atitle=Different+risks+of+symptomatic+brain+necrosis+in+NPC+patients+treated+with+different+altered+fractionated+radiotherapy+techniques&rft.au=Jen%2C+Y-M%3BHsu%2C+W-L%3BChen%2C+C-Y%3BHwang%2C+J-M%3BChang%2C+L-P%3BLin%2C+Y-S%3BSu%2C+W-F%3BChen%2C+C-M%3BLiu%2C+D-W%3BChao%2C+H-L&rft.aulast=Jen&rft.aufirst=Y-M&rft.date=2001-10-01&rft.volume=51&rft.issue=2&rft.spage=344&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.issn=03603016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Radiotherapy; Nasopharyngeal carcinoma; Risk assessment; Brain; Necrosis; Dosimetry; Cancer patients ER - TY - JOUR T1 - Proteomic profiling of the cancer microenvironment by antibody arrays AN - 18205204; 5278218 AB - Critical changes in protein expression that enable tumors to initiate and progress originate in the local tissue microenvironment, and there are increasing indications that these microenvironmental alterations in protein expression play critical roles in shaping and directing this process. As a model to better understand how patterns of protein expression shape the tissue microenvironment, we analyzed protein expression in tissue derived from squamous cell carcinoma of the oral cavity through an antibody microarray approach for high-throughput proteomic analysis. Utilizing laser capture microdissection to procure total protein from specific microscopic cellular populations, we demonstrate that quantitative, and potentially qualitative, differences in expression patterns of multiple proteins within epithelial cells reproducibly correlate with oral cavity tumor progression. Furthermore, differential expression of multiple proteins was also found in stromal cells surrounding and adjacent to regions of diseased epithelium that directly correlated with tumor progression of the epithelium. Most of the proteins identified in both cell types are involved in signal transduction pathways, thus we hypothesize that extensive molecular communication involving complex cellular signaling between epithelium and stroma play a key role in driving oral cavity cancer progression. JF - Proteomics AU - Knezevic, V AU - Leethanakul, C AU - Bichsel, V E AU - Worth, J M AU - Prabhu, V V AU - Gutkind, J S AU - Liotta, LA AU - Munson, P J AU - Petricoin, EF III AU - Krizman, D B AD - National Cancer Institute, NIH, Advanced Technology Center-134F, 8717 Grovement Circle, Gaithersburg, MD 20877, USA, dkrizman@helix.nih.gov Y1 - 2001/10// PY - 2001 DA - Oct 2001 SP - 1271 EP - 1278 VL - 1 IS - 10 SN - 1615-9853, 1615-9853 KW - microarrays KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Antibodies KW - Protein biosynthesis KW - Microenvironments KW - Oral cavity KW - Cancer KW - Signal transduction KW - W3 33120:Receptor based (antibodies, etc.) KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18205204?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proteomics&rft.atitle=Proteomic+profiling+of+the+cancer+microenvironment+by+antibody+arrays&rft.au=Knezevic%2C+V%3BLeethanakul%2C+C%3BBichsel%2C+V+E%3BWorth%2C+J+M%3BPrabhu%2C+V+V%3BGutkind%2C+J+S%3BLiotta%2C+LA%3BMunson%2C+P+J%3BPetricoin%2C+EF+III%3BKrizman%2C+D+B&rft.aulast=Knezevic&rft.aufirst=V&rft.date=2001-10-01&rft.volume=1&rft.issue=10&rft.spage=1271&rft.isbn=&rft.btitle=&rft.title=Proteomics&rft.issn=16159853&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cancer; Microenvironments; Antibodies; Oral cavity; Signal transduction; Protein biosynthesis ER - TY - JOUR T1 - Beta-helix model for the filamentous haemagglutinin adhesin of Bordetella pertussis and related bacterial secretory proteins AN - 18198288; 5224992 AB - Bordetella pertussis establishes infection by attaching to epithelial cells of the respiratory tract. One of its adhesins is filamentous haemagglutinin (FHA), a 500-Aa-long secreted protein that is rich in beta -structure and contains two regions, R1 and R2, of tandem 19-residue repeats. Two models have been proposed in which the central shaft is (i) a hairpin made up of a pairing of two long antiparallel beta -sheets; or (ii) a beta -helix in which the polypeptide chain is coiled to form three long parallel beta -sheets. We have analysed a truncated variant of FHA by electron microscopy (negative staining, shadowing and scanning transmission electron microscopy of unstained specimens): these observations support the latter model. Further support comes from detailed sequence analysis and molecular modelling studies. We applied a profile search method to the sequences adjacent to and between R1 and R2 and found additional 'covert' copies of the same motifs that may be recognized in overt form in the R1 and R2 sequence repeats. Their total number is sufficient to support the tenet of the beta -helix model that the shaft domain - a 350 Aa rod - should consist of a continuous run of these motifs, apart from loop inserts. The N-terminus, which does not contain such repeats, was found to be weakly homologous to cyclodextrin transferase, a protein of known immunoglobulin-like structure. Drawing on crystal structures of known beta -helical proteins, we developed structural models of the coil motifs putatively formed by the R1 and R2 repeats. Finally, we applied the same profile search method to the sequence database and found several other proteins - all large secreted proteins of bacterial provenance - that have similar repeats and probably also similar structures. JF - Molecular Microbiology AU - Kajava, A V AU - Cheng, N AU - Cleaver, R AU - Kessel, M AU - Simon, M N AU - Willery, E AU - Jacob-Dubuisson, F AU - Locht, C AU - Steven, A C AD - Laboratory of Structural Biology, National Institute of Arthritis, Musculoskeletal and, Skin Diseases, Bldg 6, Room B2-34, MSC 2717, National Institutes of Health, Bethesda, MD 20892-2717, USA., Alasdair_Steven@nih.gov Y1 - 2001/10// PY - 2001 DA - Oct 2001 SP - 279 EP - 292 PB - Blackwell Science Ltd VL - 42 IS - 2 SN - 0950-382X, 0950-382X KW - Microbiology Abstracts B: Bacteriology KW - Repeated sequence KW - Adhesins KW - Bordetella pertussis KW - Hemagglutinins KW - Epithelium KW - Respiratory tract KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18198288?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Beta-helix+model+for+the+filamentous+haemagglutinin+adhesin+of+Bordetella+pertussis+and+related+bacterial+secretory+proteins&rft.au=Kajava%2C+A+V%3BCheng%2C+N%3BCleaver%2C+R%3BKessel%2C+M%3BSimon%2C+M+N%3BWillery%2C+E%3BJacob-Dubuisson%2C+F%3BLocht%2C+C%3BSteven%2C+A+C&rft.aulast=Kajava&rft.aufirst=A&rft.date=2001-10-01&rft.volume=42&rft.issue=2&rft.spage=279&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2001.02598.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bordetella pertussis; Respiratory tract; Hemagglutinins; Epithelium; Adhesins; Repeated sequence DO - http://dx.doi.org/10.1046/j.1365-2958.2001.02598.x ER - TY - JOUR T1 - Protection from experimental endotoxemia by a recombinant adeno-associated virus encoding interleukin 10 AN - 18193309; 5216449 AB - Interleukin 10 (IL-10) is a homodimeric cytokine that shows considerable clinical promise. Adeno-associated virus (AAV) vectors appear increasingly useful for in vivo gene-transfer applications. A recombinant AAV type 2 vector encoding human IL-10 (rAAVhIL10) was constructed by using an adenoviral-free, three-plasmid co-transfection. Cytokine production was measured by using an enzyme-linked immunosorbent assay. Endotoxic shock was induced by lipopolysaccharide (LPS) injection. As media from rAAVhIL10-infected COS cells caused a dose-dependent blockade of IL-12 secretion from spleen cells of IL-10 knockout (KO) mice challenged with Brucella abortus, it was clear that vector-derived hIL-10 was biologically active in vitro. Intravenous or intramuscular administration of relatively modest levels of rAAVhIL10 (10 super(10) genomes) to IL-10 KO mice resulted in hIL-10 secretion into the bloodstream, which, at 8 weeks, gave median serum levels of 0.9 and 0.45 pg/ml, respectively. Acute endotoxic shock led to a 33% mortality rate, and severe morbidity, in control IL-10 KO mice, whereas no mortality and little morbidity were seen in IL-10 KO mice given rAAVhIL10 7 weeks earlier. The findings demonstrate that a modest dose of rAAVhIL10 administered in vivo provides long-term protection against LPS-induced endotoxic shock in a murine model. Thus, this vector may be useful for clinical applications requiring sustained IL-10 expression, for example in the treatment of several autoimmune diseases. JF - Journal of Gene Medicine AU - Yamano, S AU - Scott, DE AU - Huang, Li-Yun AU - Mikolajczyk, M AU - Pillemer AU - Chiorini, JA AU - Golding, B AU - Baum, B J AD - GTTB/NIDCR/NIH, 10 Center Drive, MSC 1190, Building 10, Room 1A01, Bethesda, MD 20892, USA, syamano@dir.nidcr.nih.gov Y1 - 2001/10// PY - 2001 DA - Oct 2001 SP - 450 EP - 457 VL - 3 IS - 5 SN - 1099-498X, 1099-498X KW - knockout mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Adeno-associated virus 2 KW - Enzyme-linked immunosorbent assay KW - Gene therapy KW - Autoimmune diseases KW - Brucella abortus KW - Endotoxemia KW - Endotoxin shock KW - Interleukin 10 KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18193309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Gene+Medicine&rft.atitle=Protection+from+experimental+endotoxemia+by+a+recombinant+adeno-associated+virus+encoding+interleukin+10&rft.au=Yamano%2C+S%3BScott%2C+DE%3BHuang%2C+Li-Yun%3BMikolajczyk%2C+M%3BPillemer%3BChiorini%2C+JA%3BGolding%2C+B%3BBaum%2C+B+J&rft.aulast=Yamano&rft.aufirst=S&rft.date=2001-10-01&rft.volume=3&rft.issue=5&rft.spage=450&rft.isbn=&rft.btitle=&rft.title=Journal+of+Gene+Medicine&rft.issn=1099498X&rft_id=info:doi/10.1002%2Fjgm.213 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adeno-associated virus 2; Brucella abortus; Endotoxemia; Interleukin 10; Autoimmune diseases; Gene therapy; Endotoxin shock; Expression vectors; Enzyme-linked immunosorbent assay DO - http://dx.doi.org/10.1002/jgm.213 ER - TY - JOUR T1 - Genetic Background but Not Metallothionein Phenotype Dictates Sensitivity to Cadmium-Induced Testicular Injury in Mice AN - 18110850; 5201208 AB - Sensitivity to cadmium (Cd)-induced testicular injury varies greatly among mouse strains. For instance, 129/SvJ (129) mice are highly sensitive while C57BL/6J (C57) mice are refractory to Cd-induced testicular injury. Metallothionein (MT), a Cd-binding protein, is thought to be responsible for the strain susceptibility to Cd toxicity. In this study, MT-I/II knockout (MT-null) and wild-type 129 mice were used to determine the role of MT in Cd-induced testicular injury. Two additional strains of mice (C57 and the C57 x 129 F1cross) were also used to help define the role of genetic background in Cd toxicity. Mice were given 5-20 mu mol/kg ip CdCl sub(2) and testicular injury was examined 24 h later by histopathology and testicular hemoglobin concentration. Cd produced dose-dependent testicular injury in all strains of mice, except for C57 mice, in which testicular injury could not be produced. MT-null mice were more sensitive than C57 x 129 mice but were equally sensitive as 129 mice to Cd-induced testicular injury. Fourteen days after 15 mu mol/kg ip Cd administration, testicular atrophy was evident in MT-null, 129, and C57 x 129 mice but was absent in C57 mice. The resistance of C57 mice to Cd-induced testicular injury could not be attributed solely to a decreased uptake of super(109)Cd nor to a greater amount of testicular MT. Microarray analysis revealed a higher expression of glutathione peroxidase in the testes of C57 mice, as well as genes encoding antioxidant components and DNA damage/repair, but their significance to Cd-induced injury is not immediately clear. Thus, this study demonstrates that it is genetic strain, not MT genotype, that is mechanistically important in determining susceptibility to Cd-induced testicular injury. Copyright 2001 Academic Press. JF - Toxicology and Applied Pharmacology AU - Liu, J AU - Corton, C AU - Dix, D J AU - Liu, Y AU - Waalkes, M P AU - Klaassen, C D AD - Department of Pharmacology, Toxicology and Therapeutics, Inorganic Carcinogenesis, NCI at NIEHS, Research Triangle Park, North Carolina, 27709 Y1 - 2001/10/01/ PY - 2001 DA - 2001 Oct 01 SP - 1 EP - 9 PB - Academic Press VL - 176 IS - 1 SN - 0041-008X, 0041-008X KW - mice KW - Toxicology Abstracts KW - Testes KW - Genetics KW - Metallothionein KW - Heavy metals KW - Cadmium KW - X 24161:Acute exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18110850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=Genetic+Background+but+Not+Metallothionein+Phenotype+Dictates+Sensitivity+to+Cadmium-Induced+Testicular+Injury+in+Mice&rft.au=Liu%2C+J%3BCorton%2C+C%3BDix%2C+D+J%3BLiu%2C+Y%3BWaalkes%2C+M+P%3BKlaassen%2C+C+D&rft.aulast=Liu&rft.aufirst=J&rft.date=2001-10-01&rft.volume=176&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1006%2Ftaap.2001.9262 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Testes; Heavy metals; Genetics; Metallothionein; Cadmium DO - http://dx.doi.org/10.1006/taap.2001.9262 ER - TY - JOUR T1 - Genetics and Regulation of Chitobiose Utilization in Borrelia burgdorferi AN - 17911613; 5181563 AB - Borrelia burgdorferi spends a significant proportion of its life cycle within an ixodid tick, which has a cuticle containing chitin, a polymer of N-acetylglucosamine (GlcNAc). The B. burgdorferi celA, celB, and celC genes encode products homologous to transporters for cellobiose and chitobiose (the dimer subunit of chitin) in other bacteria, which could be useful for bacterial nutrient acquisition during growth within ticks. We found that chitobiose efficiently substituted for GlcNAc during bacterial growth in culture medium. We inactivated the celB gene, which encodes the putative membrane-spanning component of the transporter, and compared growth of the mutant in various media to that of its isogenic parent. The mutant was no longer able to utilize chitobiose, while neither the mutant nor the wild type can utilize cellobiose. We propose renaming the three genes chbA, chbB, and chbC, since they probably encode a chitobiose transporter. We also found that the chbC gene was regulated in response to growth temperature and during growth in medium lacking GlcNAc. JF - Journal of Bacteriology AU - Tilly, K AU - Elias, A F AU - Errett, J AU - Fischer, E AU - Iyer, R AU - Schwartz, I AU - Bono, J L AU - Rosa, P AD - 903 S. 4th St., Hamilton, MT 59840., ktilly@nih.gov Y1 - 2001/10// PY - 2001 DA - Oct 2001 SP - 5544 EP - 5553 VL - 183 IS - 19 SN - 0021-9193, 0021-9193 KW - cDNA KW - amino acid sequence prediction KW - N-Acetyl-D-glucosamine KW - N-Acetylglucosamine KW - N-acetylglucosamine KW - celA gene KW - celB gene KW - celC gene KW - chbA gene KW - chbB gene KW - chbC gene KW - chitin KW - chitobiose KW - Biochemistry Abstracts 2: Nucleic Acids; Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Temperature effects KW - Borrelia burgdorferi KW - Nucleotide sequence KW - Chitin KW - N 14640:Structure & sequence KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17911613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Genetics+and+Regulation+of+Chitobiose+Utilization+in+Borrelia+burgdorferi&rft.au=Tilly%2C+K%3BElias%2C+A+F%3BErrett%2C+J%3BFischer%2C+E%3BIyer%2C+R%3BSchwartz%2C+I%3BBono%2C+J+L%3BRosa%2C+P&rft.aulast=Tilly&rft.aufirst=K&rft.date=2001-10-01&rft.volume=183&rft.issue=19&rft.spage=5544&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.183.19.5544-5553.2001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Borrelia burgdorferi; Temperature effects; Chitin; Nucleotide sequence DO - http://dx.doi.org/10.1128/JB.183.19.5544-5553.2001 ER - TY - JOUR T1 - Growth Phase and Growth Rate Regulation of the rapA Gene, Encoding the RNA Polymerase-Associated Protein RapA in Escherichia coli AN - 17909459; 5181620 AB - The Escherichia coli rapA gene encodes the RNA polymerase (RNAP)-associated protein RapA, which is a bacterial member of the SWI/SNF helicase-like protein family. We have studied the rapA promoter and its regulation in vivo and determined the interaction between RNAP and the promoter in vitro. We have found that the expression of rapA is growth phase dependent, peaking at the early log phase. The growth phase control of rapA is determined at least by one particular feature of the promoter: it uses CTP as the transcription-initiating nucleotide instead of a purine, which is used for most E. coli promoters. We also found that the rapA promoter is subject to growth rate regulation in vivo and that it forms intrinsic unstable initiation complexes with RNAP in vitro. Furthermore, we have shown that a GC-rich or discriminator sequence between the -10 and +1 positions of the rapA promoter is responsible for its growth rate control and the instability of its initiation complexes with RNAP. JF - Journal of Bacteriology AU - Cabrera, JE AU - Jin, D J AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Building 37, Room 2B16, 9000 Rockville Pike, Bethesda, MD 20892., djjin@helix.nih.gov Y1 - 2001/10// PY - 2001 DA - Oct 2001 SP - 6126 EP - 6134 VL - 183 IS - 20 SN - 0021-9193, 0021-9193 KW - RapA protein KW - SWI/SNF helicase KW - rapA gene KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - DNA-directed RNA polymerase KW - Gene regulation KW - Escherichia coli KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17909459?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Growth+Phase+and+Growth+Rate+Regulation+of+the+rapA+Gene%2C+Encoding+the+RNA+Polymerase-Associated+Protein+RapA+in+Escherichia+coli&rft.au=Cabrera%2C+JE%3BJin%2C+D+J&rft.aulast=Cabrera&rft.aufirst=JE&rft.date=2001-10-01&rft.volume=183&rft.issue=20&rft.spage=6126&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.183.20.6126-6134.2001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA-directed RNA polymerase; Gene regulation DO - http://dx.doi.org/10.1128/JB.183.20.6126-6134.2001 ER - TY - JOUR T1 - Inhibition of rat PC12 cell calpain activity by glutathione, oxidized glutathione and nitric oxide. AN - 71215435; 11567795 AB - Calpain, a calcium activated neutral protease, is involved in mediating neurotoxicity resulting from conditions of oxidative stress and free radical formation, such as hypoxia and ischemia. Nitric oxide (NO) may also be involved in modulating the cytotoxic effects of oxidative stress. We investigated the roles of reduced glutathione (GSH), oxidized glutathione (GSSG), and NO in modulating calpain activity in PC12 cells. Cell extracts were treated with GSSG, GSH, or the NO-donor S-nitroso-N-acetylpenicillamine. Calpain activity was determined by means of a fluorescent assay. Non-linear regression analysis was used to determine the type of inhibition (competitive, uncompetitive, or non-competitive). GSH displayed uncompetitive inhibition, with K(i)=7.0+/-2.0 mM (Mean+/-SEM) while GSSG exhibited competitive inhibition with K(i)=2.5+/-0.3 mM. NO was an irreversible inhibitor of calpain activity. These results suggest that both GSH and GSSG may be important physiological modulators of calpain activity. JF - Neuroscience letters AU - Rackoff, J AU - Yang, Q AU - DePetrillo, P B AD - Division of Intramural Clinical and Biochemical Research, National Institute on Alcohol Abuse and Alcoholism, NIH 10/ 3C103, 10 Center Drive, MSC 1256, Bethesda, MD 20892-1256, USA. Y1 - 2001/09/28/ PY - 2001 DA - 2001 Sep 28 SP - 129 EP - 132 VL - 311 IS - 2 SN - 0304-3940, 0304-3940 KW - Nitric Oxide Donors KW - 0 KW - Nitric Oxide KW - 31C4KY9ESH KW - S-Nitroso-N-Acetylpenicillamine KW - 79032-48-7 KW - Calpain KW - EC 3.4.22.- KW - Glutathione Disulfide KW - ULW86O013H KW - Index Medicus KW - Rats KW - Nitric Oxide Donors -- pharmacology KW - S-Nitroso-N-Acetylpenicillamine -- pharmacology KW - Animals KW - Oxidative Stress -- drug effects KW - PC12 Cells KW - Glutathione Disulfide -- metabolism KW - Neurons -- cytology KW - Calpain -- antagonists & inhibitors KW - Nitric Oxide -- metabolism KW - Neurons -- enzymology KW - Calpain -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71215435?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience+letters&rft.atitle=Inhibition+of+rat+PC12+cell+calpain+activity+by+glutathione%2C+oxidized+glutathione+and+nitric+oxide.&rft.au=Rackoff%2C+J%3BYang%2C+Q%3BDePetrillo%2C+P+B&rft.aulast=Rackoff&rft.aufirst=J&rft.date=2001-09-28&rft.volume=311&rft.issue=2&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Neuroscience+letters&rft.issn=03043940&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular basis for selectivity of high affinity peptide antagonists for the gastrin-releasing peptide receptor. AN - 71188564; 11463790 AB - Few gastrointestinal hormones/neurotransmitters have high affinity peptide receptor antagonists, and little is known about the molecular basis of their selectivity or affinity. The receptor mediating the action of the mammalian bombesin (Bn) peptide, gastrin-releasing peptide receptor (GRPR), is an exception, because numerous classes of peptide antagonists are described. To investigate the molecular basis for their high affinity for the GRPR, two classes of peptide antagonists, a statine analogue, JMV594 ([d-Phe(6),Stat(13)]Bn(6-14)), and a pseudopeptide analogue, JMV641 (d-Phe-Gln-Trp-Ala-Val-Gly-His-Leupsi(CHOH-CH(2))-(CH(2))(2)-CH(3)), were studied. Each had high affinity for the GRPR and >3,000-fold selectivity for GRPR over the closely related neuromedin B receptor (NMBR). To investigate the basis for this, we used a chimeric receptor approach to make both GRPR loss of affinity and NMBR gain of affinity chimeras and a site-directed mutagenesis approach. Chimeric or mutated receptors were transiently expressed in Balb/c 3T3. Only substitution of the fourth extracellular (EC) domain of the GRPR by the comparable NMBR domain markedly decreased the affinity for both antagonists. Substituting the fourth EC domain of NMBR into the GRPR resulted in a 300-fold gain in affinity for JMV594 and an 11-fold gain for JMV641. Each of the 11 amino acid differences between the GRPR and NMBR in this domain were exchanged. The substitutions of Thr(297) in GRPR by Pro from the comparable position in NMBR, Phe(302) by Met, and Ser(305) by Thr decreased the affinity of each antagonist. Simultaneous replacement of Thr(297), Phe(302), and Ser(305) in GRPR by the three comparable NMBR amino acids caused a 500-fold decrease in affinity for both antagonists. Replacing the comparable three amino acids in NMBR by those from GRPR caused a gain in affinity for each antagonist. Receptor modeling showed that each of these three amino acids faced inward and was within 5 A of the putative binding pocket. These results demonstrate that differences in the fourth EC domain of the mammalian Bn receptors are responsible for the selectivity of these two peptide antagonists. They demonstrate that Thr(297), Phe(302), and Ser(305) of the fourth EC domain of GRPR are the critical residues for determining GRPR selectivity and suggest that both receptor-ligand cation-pi interactions and hydrogen bonding are important for their high affinity interaction. JF - The Journal of biological chemistry AU - Tokita, K AU - Katsuno, T AU - Hocart, S J AU - Coy, D H AU - Llinares, M AU - Martinez, J AU - Jensen, R T AD - Digestive Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1804, USA. Y1 - 2001/09/28/ PY - 2001 DA - 2001 Sep 28 SP - 36652 EP - 36663 VL - 276 IS - 39 SN - 0021-9258, 0021-9258 KW - Amino Acids KW - 0 KW - DNA, Complementary KW - Peptides KW - Receptors, Bombesin KW - Serine KW - 452VLY9402 KW - Phenylalanine KW - 47E5O17Y3R KW - Methionine KW - AE28F7PNPL KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Models, Molecular KW - Amino Acid Sequence KW - Mice KW - Protein Binding KW - Serine -- chemistry KW - Binding Sites KW - Rats KW - Phenylalanine -- chemistry KW - Mutagenesis, Site-Directed KW - Transfection KW - Amino Acids -- chemistry KW - DNA, Complementary -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Inhibitory Concentration 50 KW - Sequence Homology, Amino Acid KW - Protein Structure, Tertiary KW - Methionine -- chemistry KW - Peptides -- chemistry KW - Receptors, Bombesin -- antagonists & inhibitors KW - Receptors, Bombesin -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71188564?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Molecular+basis+for+selectivity+of+high+affinity+peptide+antagonists+for+the+gastrin-releasing+peptide+receptor.&rft.au=Tokita%2C+K%3BKatsuno%2C+T%3BHocart%2C+S+J%3BCoy%2C+D+H%3BLlinares%2C+M%3BMartinez%2C+J%3BJensen%2C+R+T&rft.aulast=Tokita&rft.aufirst=K&rft.date=2001-09-28&rft.volume=276&rft.issue=39&rft.spage=36652&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-11-01 N1 - Date created - 2001-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Unusual Molecular Architecture of the Yersinia pestis Cytotoxin YopM: A Leucine-rich Repeat Protein with the Shortest Repeating Unit AN - 18111640; 5201118 AB - Many Gram-negative bacterial pathogens employ a contact-dependent (type III) secretion system to deliver effector proteins into the cytosol of animal or plant cells. Collectively, these effectors enable the bacteria to evade the immune response of the infected organism by modulating host-cell functions. YopM, a member of the leucine-rich repeat protein superfamily, is an effector produced by the bubonic plague bacterium, Yersinia pestis, that is essential for virulence. Here, we report crystal structures of YopM at 2.4 and 2.1 Aa resolution. Among all leucine-rich repeat family members whose atomic coordinates have been reported, the repeating unit of YopM has the least canonical secondary structure. In both crystals, four YopM monomers form a hollow cylinder with an inner diameter of 35 Aa. The domain that targets YopM for translocation into eukaryotic cells adopts a well-ordered, alpha -helical conformation that packs tightly against the proximal leucine-rich repeat module. A similar alpha -helical domain can be identified in virulence-associated leucine-rich repeat proteins produced by Salmonella typhimurium and Shigella flexneri, and in the conceptual translation products of several open reading frames in Y. pestis. JF - Journal of Molecular Biology AU - Evdokimov, A G AU - Anderson, DE AU - Routzahn, K M AU - Waugh, D S AD - Protein Engineering Section Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, MD, 21702-1201, USA Y1 - 2001/09/28/ PY - 2001 DA - 2001 Sep 28 SP - 807 EP - 821 PB - Academic Press VL - 312 IS - 4 SN - 0022-2836, 0022-2836 KW - molecular architecture KW - YopM protein KW - Microbiology Abstracts B: Bacteriology; Toxicology Abstracts KW - Cytotoxins KW - Secondary structure KW - Yersinia pestis KW - Salmonella typhimurium KW - Helix KW - Protein structure KW - Shigella flexneri KW - Crystal structure KW - Leucine KW - J 02822:Biosynthesis and physicochemical properties KW - X 24171:Microbial UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18111640?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Unusual+Molecular+Architecture+of+the+Yersinia+pestis+Cytotoxin+YopM%3A+A+Leucine-rich+Repeat+Protein+with+the+Shortest+Repeating+Unit&rft.au=Evdokimov%2C+A+G%3BAnderson%2C+DE%3BRoutzahn%2C+K+M%3BWaugh%2C+D+S&rft.aulast=Evdokimov&rft.aufirst=A&rft.date=2001-09-28&rft.volume=312&rft.issue=4&rft.spage=807&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1006%2Fjmbi.2001.4973 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Salmonella typhimurium; Shigella flexneri; Yersinia pestis; Leucine; Crystal structure; Helix; Secondary structure; Protein structure; Cytotoxins DO - http://dx.doi.org/10.1006/jmbi.2001.4973 ER -