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 - Predominant expression of proinflammatory cytokines by carotid atherosclerotic plaque T cells AN - 39624475; 3676812 AU - Nadareishvili, Z G AU - McCarron, R AU - Hamm, T AU - Prat, E AU - Martin, R AU - Degraba, 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/39624475?accountid=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=Predominant+expression+of+proinflammatory+cytokines+by+carotid+atherosclerotic+plaque+T+cells&rft.au=Nadareishvili%2C+Z+G%3BMcCarron%2C+R%3BHamm%2C+T%3BPrat%2C+E%3BMartin%2C+R%3BDegraba%2C+T+J&rft.aulast=Nadareishvili&rft.aufirst=Z&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. P84 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 - Improved candidate DNA vaccines against HIV-1 AN - 39543360; 3673107 AU - Rosati, M AU - Eyler, P AU - Valentin, A AU - Trivedi, H AU - Biragyn, A AU - Kwak, L W AU - Markham, P AU - Woodward, R AU - Von Gegerfelt, A AU - Miller, 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/39543360?accountid=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=Improved+candidate+DNA+vaccines+against+HIV-1&rft.au=Rosati%2C+M%3BEyler%2C+P%3BValentin%2C+A%3BTrivedi%2C+H%3BBiragyn%2C+A%3BKwak%2C+L+W%3BMarkham%2C+P%3BWoodward%2C+R%3BVon+Gegerfelt%2C+A%3BMiller%2C+N&rft.aulast=Rosati&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. 80 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Chemokine regulation by HIV-1 and pro-inflammatory cytokines in human astrocytes and neurons AN - 39542975; 3673036 AU - Lawrence, D M AU - Durham, L C AU - Sanchez, T W AU - Major, E O 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/39542975?accountid=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+regulation+by+HIV-1+and+pro-inflammatory+cytokines+in+human+astrocytes+and+neurons&rft.au=Lawrence%2C+D+M%3BDurham%2C+L+C%3BSanchez%2C+T+W%3BMajor%2C+E+O&rft.aulast=Lawrence&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. 736-W N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Immunologic and hematopoietic effects of recombinant human prolactin after syngeneic bone marrow transplantation in mice AN - 39539471; 3673988 AU - Sun, R AU - Welniak, L AU - Tian, Z AU - Murphy, W 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/39539471?accountid=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=Immunologic+and+hematopoietic+effects+of+recombinant+human+prolactin+after+syngeneic+bone+marrow+transplantation+in+mice&rft.au=Sun%2C+R%3BWelniak%2C+L%3BTian%2C+Z%3BMurphy%2C+W+J&rft.aulast=Sun&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: 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. 65 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 - Long-term persistence and safety of gene-modified syngeneic CD4+ T lymphocytes in HIV-infected patients AN - 39526226; 3672801 AU - Lu, A AU - Tavel, J AU - Herpin, B AU - Natarajan, V AU - Davey, R T AU - Kovacs, J AU - Falloon, J AU - Polis, MA AU - Masur, H AU - Lane, H 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/39526226?accountid=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=Long-term+persistence+and+safety+of+gene-modified+syngeneic+CD4%2B+T+lymphocytes+in+HIV-infected+patients&rft.au=Lu%2C+A%3BTavel%2C+J%3BHerpin%2C+B%3BNatarajan%2C+V%3BDavey%2C+R+T%3BKovacs%2C+J%3BFalloon%2C+J%3BPolis%2C+MA%3BMasur%2C+H%3BLane%2C+H+C&rft.aulast=Lu&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. 525-M N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Positive feedback on CXCR4-tropic HIV infection in the thymus is regulated through interleukin (IL)-7 AN - 39525533; 3672783 AU - Okamoto, Y 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/39525533?accountid=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=Positive+feedback+on+CXCR4-tropic+HIV+infection+in+the+thymus+is+regulated+through+interleukin+%28IL%29-7&rft.au=Okamoto%2C+Y%3BDouek%2C+D%3BKoup%2C+R&rft.aulast=Okamoto&rft.aufirst=Y&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. 509-M N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Lesion probability mapping: Accounting for uncertainty in identifying lesions on MRI of acute stroke in humans AN - 39525413; 3676738 AU - Latour, L L AU - Calabrese, T M AU - Ezzeddine, MA AU - Chalela, JA AU - Luby, M L AU - Warach, 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/39525413?accountid=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=Lesion+probability+mapping%3A+Accounting+for+uncertainty+in+identifying+lesions+on+MRI+of+acute+stroke+in+humans&rft.au=Latour%2C+L+L%3BCalabrese%2C+T+M%3BEzzeddine%2C+MA%3BChalela%2C+JA%3BLuby%2C+M+L%3BWarach%2C+S&rft.aulast=Latour&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: 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. P9 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 - Potentiation of SIV-specific CD4+ and CD8+ T-cell responses by a DNA-SIV and NYVAC-SIV prime-boost regimen AN - 39522698; 3672556 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 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/39522698?accountid=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=Potentiation+of+SIV-specific+CD4%2B+and+CD8%2B+T-cell+responses+by+a+DNA-SIV+and+NYVAC-SIV+prime-boost+regimen&rft.au=Hel%2C+Z%3BTsai%2C+W-P%3BThornton%2C+A%3BNacsa%2C+J%3BGiuliani%2C+L%3BTryniszewska%2C+E%3BPoudyal%2C+M%3BVenzon%2C+D%3BWang%2C+X%3BAltman%2C+J&rft.aulast=Hel&rft.aufirst=Z&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. 303-W 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 - Ischemic tolerance caused by preconditioning with TNF-a and ceramide is accomplished through differential control of NF-kB association with p300 adaptor AN - 39515293; 3676578 AU - Ginis, I O AU - Jaiswal, R AU - Klimanis, D AU - Hallenbeck, J 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/39515293?accountid=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=Ischemic+tolerance+caused+by+preconditioning+with+TNF-a+and+ceramide+is+accomplished+through+differential+control+of+NF-kB+association+with+p300+adaptor&rft.au=Ginis%2C+I+O%3BJaiswal%2C+R%3BKlimanis%2C+D%3BHallenbeck%2C+J+M&rft.aulast=Ginis&rft.aufirst=I&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. 24 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 - Levels of cell-free HIV virions released by latently infected, resting CD4+ T cells: Implications for ongoing viral replication AN - 39509835; 3672765 AU - Chun, T W AU - Justement, J AU - Pandya, P AU - Liu, S AU - McLaughlin, M AU - Ehler, L 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/39509835?accountid=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=Levels+of+cell-free+HIV+virions+released+by+latently+infected%2C+resting+CD4%2B+T+cells%3A+Implications+for+ongoing+viral+replication&rft.au=Chun%2C+T+W%3BJustement%2C+J%3BPandya%2C+P%3BLiu%2C+S%3BMcLaughlin%2C+M%3BEhler%2C+L%3BFauci%2C+A+S&rft.aulast=Chun&rft.aufirst=T&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. 493-M 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 - New real-time RT-PCR assay with an internal virion standard quantifies plasma HIV-1 RNA from 10 super(6) to 1 copy/reaction AN - 39507187; 3672889 AU - Palmer, S AU - Wiegand, A AU - Maldarelli, F AU - Bazmi, H AU - Mican, J AU - Mellors, J AU - Coffin, 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/39507187?accountid=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=New+real-time+RT-PCR+assay+with+an+internal+virion+standard+quantifies+plasma+HIV-1+RNA+from+10+super%286%29+to+1+copy%2Freaction&rft.au=Palmer%2C+S%3BWiegand%2C+A%3BMaldarelli%2C+F%3BBazmi%2C+H%3BMican%2C+J%3BMellors%2C+J%3BCoffin%2C+J&rft.aulast=Palmer&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. 603-T N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Preliminary analysis of the safety and immunologic activity of recombinant IL-2 in children and adolescents with HIV infection AN - 39506289; 3672793 AU - Wood, LV AU - Zuckerman, J AU - Steinberg, S AU - Liewehr, D AU - DeCarlo, E AU - Beals, M AU - Wigginton, 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/39506289?accountid=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=Preliminary+analysis+of+the+safety+and+immunologic+activity+of+recombinant+IL-2+in+children+and+adolescents+with+HIV+infection&rft.au=Wood%2C+LV%3BZuckerman%2C+J%3BSteinberg%2C+S%3BLiewehr%2C+D%3BDeCarlo%2C+E%3BBeals%2C+M%3BWigginton%2C+J&rft.aulast=Wood&rft.aufirst=LV&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. 518-M N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Neural impulse activity in regulating development of myelinating gila in the PNS and CNS AN - 39505648; 3678687 AU - Fields, R D 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/39505648?accountid=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=Neural+impulse+activity+in+regulating+development+of+myelinating+gila+in+the+PNS+and+CNS&rft.au=Fields%2C+R+D&rft.aulast=Fields&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: Elsevier Science Ltd., Pergamon, P.O. Box 800, Kidlington, Oxford OX5 1DX, UK; URL: www.elsevier.nl. Paper No. S2.2 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Novel chimeric Rev, Tat, and Nef antigen as a component of an SIV/HIV vaccine AN - 39505646; 3672553 AU - Hel, Z AU - Johnson, J M AU - Tryniszewska, E AU - Tsai, W-P AU - Harrod, R AU - Fullen, J 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/39505646?accountid=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+chimeric+Rev%2C+Tat%2C+and+Nef+antigen+as+a+component+of+an+SIV%2FHIV+vaccine&rft.au=Hel%2C+Z%3BJohnson%2C+J+M%3BTryniszewska%2C+E%3BTsai%2C+W-P%3BHarrod%2C+R%3BFullen%2C+J%3BTartaglia%2C+J%3BFranchini%2C+G&rft.aulast=Hel&rft.aufirst=Z&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. 300-W 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 - Fine structure analysis of HIV sequence variation in vivo: Longitudinal study of drug naieve patients and dynamics of response to initiating HAART AN - 39491833; 3672856 AU - Maldarelli, F AU - Kearney, M AU - Palmer, S AU - Rock, D AU - Falloon, J AU - Mican, J AU - Liu, S AU - Pau, A AU - VanHoutte, M AU - Michels, 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/39491833?accountid=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=Fine+structure+analysis+of+HIV+sequence+variation+in+vivo%3A+Longitudinal+study+of+drug+naieve+patients+and+dynamics+of+response+to+initiating+HAART&rft.au=Maldarelli%2C+F%3BKearney%2C+M%3BPalmer%2C+S%3BRock%2C+D%3BFalloon%2C+J%3BMican%2C+J%3BLiu%2C+S%3BPau%2C+A%3BVanHoutte%2C+M%3BMichels%2C+L&rft.aulast=Maldarelli&rft.aufirst=F&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. 574-T 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 - Intermittent IL-2 in HIV-infected patients leads to peripheral expansion of a novel subset of naieve CD4+ T cells AN - 39465476; 3672338 AU - Sereti, I AU - Natarajan, V AU - Adelsberger, J W AU - Metcalf, JA AU - Martinez-Wilson, H AU - Anthony, K AU - Kovacs, J AU - Lane, H 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/39465476?accountid=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=Intermittent+IL-2+in+HIV-infected+patients+leads+to+peripheral+expansion+of+a+novel+subset+of+naieve+CD4%2B+T+cells&rft.au=Sereti%2C+I%3BNatarajan%2C+V%3BAdelsberger%2C+J+W%3BMetcalf%2C+JA%3BMartinez-Wilson%2C+H%3BAnthony%2C+K%3BKovacs%2C+J%3BLane%2C+H+C&rft.aulast=Sereti&rft.aufirst=I&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. 104 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 - 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 - Boning up on telomerase AN - 864952215; 13744549 JF - Nature Biotechnology AU - Tuan, Rocky AD - Rocky Tuan is chief of the Cartilage Biology and Orthopaedics Branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-8022 Tuanr[AT]mail.nih.gov. Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 560 EP - 561 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 20 IS - 6 SN - 1087-0156, 1087-0156 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/864952215?accountid=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+Rocky&rft.aulast=Tuan&rft.aufirst=Rocky&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/10.1038%2Fnbt0602-560 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/nbt0602-560 ER - TY - JOUR T1 - Kinematic Strategies for Hyoid Movement in Rapid Sequential Swallowing AN - 85631562; 200509766 AB - Past video-fluoroscopic & 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) & rapid sequential (120 cc) swallowing tasks. Submental ultrasound was conducted with head & 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 & 318 rapid sequential swallows. Repeated-measures analyses of variance were conducted on a number of kinematic variables with corrections for multiple tests & 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 & total durations, & 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. Adapted from the source document JF - Journal of Speech, Language, and Hearing Research AU - Chi-Fishman, Gloria AU - Sonies, Barbara C AD - Clinical Center, National Instit Health, Bethesda, MD gcf@nih.gov Y1 - 2002/06// PY - 2002 DA - June 2002 SP - 457 EP - 468 VL - 45 IS - 3 SN - 1092-4388, 1092-4388 KW - Pharyngeal Structures (64200) KW - Oral Cavity (61200) KW - Articulatory Measurement Techniques (04730) KW - Age Differences (01150) KW - Sex Differences (77850) KW - Motion (55575) KW - article KW - 6210: hearing and speech physiology; hearing and speech physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85631562?accountid=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+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 DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2005-09-01 N1 - Last updated - 2016-09-27 N1 - SubjectsTermNotLitGenreText - Articulatory Measurement Techniques (04730); Pharyngeal Structures (64200); Motion (55575); Oral Cavity (61200); Age Differences (01150); Sex Differences (77850) 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 - 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 - 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 - A Phase I Study of Nonmyeloablative Chemotherapy and Adoptive Transfer of Autologous Tumor Antigen-Specific T Lymphocytes in Patients With Metastatic Melanoma AN - 18413963; 5395105 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 super(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 AU - Dudley, ME AU - Wunderlich, J R AU - Yang, J C AU - Hwu, P AU - Schwartzentruber, D J AU - Topalian, S L AU - Sherry, R M AU - Marincola, F M AU - Leitman, S F AU - Seipp, CA AU - Rogers-Freezer, L AU - Morton, KE AU - Nahvi, A AU - Mavroukakis, SA AD - Surgery Branch, National Cancer Institute, Department of Transfusion Medicine, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2002/06// PY - 2002 DA - Jun 2002 SP - 243 EP - 251 VL - 25 IS - 3 SN - 1067-5582, 1067-5582 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - F 06818:Cancer immunotherapy KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18413963?accountid=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=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+ME%3BWunderlich%2C+J+R%3BYang%2C+J+C%3BHwu%2C+P%3BSchwartzentruber%2C+D+J%3BTopalian%2C+S+L%3BSherry%2C+R+M%3BMarincola%2C+F+M%3BLeitman%2C+S+F%3BSeipp%2C+CA%3BRogers-Freezer%2C+L%3BMorton%2C+KE%3BNahvi%2C+A%3BMavroukakis%2C+SA&rft.aulast=Dudley&rft.aufirst=ME&rft.date=2002-06-01&rft.volume=25&rft.issue=3&rft.spage=243&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 - 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 - 71719362; 11919199 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.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 - The Journal of biological chemistry AU - Kokoska, Robert J AU - Bebenek, Katarzyna AU - Boudsocq, Francois AU - Woodgate, Roger AU - Kunkel, Thomas A AD - Laboratory of Molecular Genetics and Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/05/31/ PY - 2002 DA - 2002 May 31 SP - 19633 EP - 19638 VL - 277 IS - 22 SN - 0021-9258, 0021-9258 KW - Guanine KW - 5Z93L87A1R KW - Cytosine KW - 8J337D1HZY KW - DNA Polymerase beta KW - EC 2.7.7.- KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Cysteine -- chemistry KW - Base Sequence KW - Cytosine -- chemistry KW - Sequence Homology, Nucleic Acid KW - Guanine -- chemistry KW - Kinetics KW - Molecular Sequence Data KW - Mutation KW - Structure-Activity Relationship KW - Gene Deletion KW - Binding Sites KW - DNA Polymerase beta -- genetics KW - DNA Polymerase beta -- chemistry KW - Sulfolobus -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71719362?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Low+fidelity+DNA+synthesis+by+a+y+family+DNA+polymerase+due+to+misalignment+in+the+active+site.&rft.au=Kokoska%2C+Robert+J%3BBebenek%2C+Katarzyna%3BBoudsocq%2C+Francois%3BWoodgate%2C+Roger%3BKunkel%2C+Thomas+A&rft.aulast=Kokoska&rft.aufirst=Robert&rft.date=2002-05-31&rft.volume=277&rft.issue=22&rft.spage=19633&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 - 2002-07-02 N1 - Date created - 2002-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 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 - A Major Human Arsenic Metabolite, Dimethylarsinic Acid, Requires Reduced Glutathione To Induce Apoptosis AN - 18432492; 5410567 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 sub(50) = 35 mu M 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 sub(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, T AU - Qu, W AU - Sakurai, M H AU - Waalkes, M 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 - 2002/05/20/ PY - 2002 DA - 2002 May 20 SP - 629 EP - 637 VL - 15 IS - 5 SN - 0893-228X, 0893-228X KW - cacodylic acid KW - cell lines KW - rats KW - Toxicology Abstracts KW - X 24163:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18432492?accountid=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=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+T%3BQu%2C+W%3BSakurai%2C+M+H%3BWaalkes%2C+M+P&rft.aulast=Sakurai&rft.aufirst=T&rft.date=2002-05-20&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/10.1021%2Ftx0101604 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/tx0101604 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 - 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 - Oxidative DNA and protein damage in metal-induced toxicity and carcinogenesis AN - 18418233; 5403368 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, K S AD - Bldg. 538, Room 205E, NCI 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 - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - N 14100:Reviews KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18418233?accountid=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=Oxidative+DNA+and+protein+damage+in+metal-induced+toxicity+and+carcinogenesis&rft.au=Kasprzak%2C+K+S&rft.aulast=Kasprzak&rft.aufirst=K&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 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 - 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 - Mutations associated with base excision repair deficiency and methylation-induced genotoxic stress AN - 18335439; 5382702 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, USA AU - Sobol, R W AU - Watson, DE AU - Nakamura, J AU - Yakes, F M AU - Hou, E AU - Horton, J K AU - Ladapo, J AU - Van Houten, B AU - Swenberg, JA AU - Tindall, K R AU - Samson, L D AU - Wilson, SH AD - Laboratory of Structural Biology and Environmental Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA, wilson5@niehs.nih.gov Y1 - 2002/05/14/ PY - 2002 DA - 2002 May 14 SP - 6860 EP - 6865 VL - 99 IS - 10 SN - 0027-8424, 0027-8424 KW - mice KW - N-Methyl-N'-nitro-N-nitrosoguanidine KW - N-methyl-N'-nitro-N-nitrosoguanidine KW - alkyladenine-DNA glycosylase KW - base excision repair KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - Methyl methanesulfonate KW - Genotoxicity KW - Mutant frequency KW - DNA repair KW - DNA damage KW - U.V. radiation KW - DNA-directed DNA polymerase KW - Cell lines KW - Mutation KW - X 24200:Nitrosamines & related compounds KW - N 14652:DNA repair UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18335439?accountid=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=Mutations+associated+with+base+excision+repair+deficiency+and+methylation-induced+genotoxic+stress&rft.au=Sobol%2C+R+W%3BWatson%2C+DE%3BNakamura%2C+J%3BYakes%2C+F+M%3BHou%2C+E%3BHorton%2C+J+K%3BLadapo%2C+J%3BVan+Houten%2C+B%3BSwenberg%2C+JA%3BTindall%2C+K+R%3BSamson%2C+L+D%3BWilson%2C+SH&rft.aulast=Sobol&rft.aufirst=R&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%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.092662499 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mutation; Mutant frequency; Cell lines; Methyl methanesulfonate; U.V. radiation; Genotoxicity; DNA repair; DNA damage; DNA-directed DNA polymerase DO - http://dx.doi.org/10.1073/pnas.092662499 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 - Microarray analysis of altered gene expression in the TM4 Sertoli-like cell line exposed to chromium(III) chloride. AN - 71922529; 12128095 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 1mM CrCl(3) x 6H(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 > or = 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 (Elmsford, N.Y.) AU - Cheng, Robert Y S AU - Alvord, W Gregory AU - Powell, Douglas AU - Kasprzak, Kazimierz S AU - Anderson, Lucy M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, National Institutes of Health, Box B, Building 538, Fort Detrick, Frederick, MD 21702, USA. rcheng@ncicrf.gov PY - 2002 SP - 223 EP - 236 VL - 16 IS - 3 SN - 0890-6238, 0890-6238 KW - BACH2 protein, human KW - 0 KW - Bach2 protein, mouse KW - Basic-Leucine Zipper Transcription Factors KW - Carcinogens KW - Chlorides KW - Chromium Compounds KW - RNA, Messenger KW - Transcription Factors KW - chromous chloride KW - CET32HKA21 KW - Index Medicus KW - Gene Expression Profiling KW - Animals KW - RNA, Messenger -- metabolism KW - Transcription Factors -- metabolism KW - Dose-Response Relationship, Drug KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Mice, Inbred BALB C KW - Transcription Factors -- genetics KW - Male KW - Cell Line KW - Sertoli Cells -- drug effects KW - Gene Expression -- drug effects KW - Chlorides -- toxicity KW - Sertoli Cells -- metabolism KW - Oligonucleotide Array Sequence Analysis KW - Carcinogens -- toxicity KW - Chromium Compounds -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71922529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&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+Robert+Y+S%3BAlvord%2C+W+Gregory%3BPowell%2C+Douglas%3BKasprzak%2C+Kazimierz+S%3BAnderson%2C+Lucy+M&rft.aulast=Cheng&rft.aufirst=Robert+Y&rft.date=2002-05-01&rft.volume=16&rft.issue=3&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.issn=08906238&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-11 N1 - Date created - 2002-07-19 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 - 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 - 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 - Health effects from fallout. AN - 71676062; 12003021 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 131I 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 131I 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, Ethel S AU - Land, Charles E AU - Simon, Steven L AD - Division of Cancer Epidemiotogy and Genetics, National Cancer Institute, NIH, 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 - Radioactive Fallout KW - 0 KW - Index Medicus KW - United States KW - Thyroid Neoplasms -- epidemiology KW - Neoplasms, Radiation-Induced -- etiology KW - Risk Factors KW - Neoplasms, Radiation-Induced -- epidemiology KW - Leukemia -- epidemiology KW - Humans KW - Thyroid Neoplasms -- etiology KW - Leukemia -- etiology KW - USSR KW - Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71676062?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&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+Ethel+S%3BLand%2C+Charles+E%3BSimon%2C+Steven+L&rft.aulast=Gilbert&rft.aufirst=Ethel&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 completed - 2002-05-24 N1 - Date created - 2002-05-10 N1 - Date revised - 2017-01-13 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 - 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 - 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 - CONF T1 - Neutrophilic infiltration in alcoholic hepatitis AN - 18478613; 5443826 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 AU - Bautista, A P Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 17 EP - 21 PB - Elsevier Science Inc., Box 882 New York NY 10159 USA VL - 27 IS - 1 KW - infiltration KW - man KW - Toxicology Abstracts KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18478613?accountid=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=Alcohol&rft.atitle=Neutrophilic+infiltration+in+alcoholic+hepatitis&rft.au=Bautista%2C+A+P&rft.aulast=Bautista&rft.aufirst=A&rft.date=2002-05-01&rft.volume=27&rft.issue=1&rft.spage=17&rft.isbn=&rft.btitle=&rft.title=Alcohol&rft.issn=07418329&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 - CONF T1 - Cellular and molecular mechanisms of alcoholic hepatitis: introduction and summary of the symposium AN - 18477656; 5443823 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 AU - Purohit, V AU - Russo, D Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 3 EP - 6 PB - Elsevier Science Inc., Box 882 New York NY 10159 USA VL - 27 IS - 1 KW - man KW - Toxicology Abstracts KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18477656?accountid=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=Alcohol&rft.atitle=Cellular+and+molecular+mechanisms+of+alcoholic+hepatitis%3A+introduction+and+summary+of+the+symposium&rft.au=Purohit%2C+V%3BRusso%2C+D&rft.aulast=Purohit&rft.aufirst=V&rft.date=2002-05-01&rft.volume=27&rft.issue=1&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Alcohol&rft.issn=07418329&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 - CONF T1 - Interaction of alcohol and hepatitis viral proteins: implication in synergistic effect of alcohol drinking and viral hepatitis on liver injury AN - 18473658; 5443834 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 AU - Gao, Bin Y1 - 2002/05// PY - 2002 DA - May 2002 SP - 69 EP - 72 PB - Elsevier Science Inc., Box 882 New York NY 10159 USA VL - 27 IS - 1 KW - HBX protein KW - double prime X protein KW - man KW - Virology & AIDS Abstracts; Toxicology Abstracts KW - V 22122:Symptomatology, pathology & etiology KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18473658?accountid=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=Alcohol&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&rft.issn=07418329&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 - 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 - Role of Yersinia Murine Toxin in Survival of Yersinia pestis in the Midgut of the Flea Vector AN - 18313503; 5364682 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 (Washington) AU - Hinnebusch, B J AU - Rudolph, A E AU - Cherepanov, P AU - Dixon, JE AU - Schwan, T G AU - Forsberg, Aa 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 PB - American Association for the Advancement of Science VL - 296 IS - 5568 SN - 0036-8075, 0036-8075 KW - Oriental rat flea KW - Yersinia murine toxin KW - phospholipase D KW - Entomology Abstracts; Microbiology Abstracts B: Bacteriology KW - Vectors KW - Yersinia pestis KW - Plasmids KW - Toxins KW - Disease transmission KW - Xenopsylla cheopis KW - Plague KW - Midgut KW - Nitrogen KW - J 02855:Human Bacteriology: Others KW - J 02870:Invertebrate bacteriology KW - Z 05206:Medical & veterinary entomology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18313503?accountid=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=Science+%28Washington%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+J%3BRudolph%2C+A+E%3BCherepanov%2C+P%3BDixon%2C+JE%3BSchwan%2C+T+G%3BForsberg%2C+Aa&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+%28Washington%29&rft.issn=00368075&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 - Xenopsylla cheopis; Yersinia pestis; Nitrogen; Plasmids; Midgut; Vectors; Disease transmission; Plague; Toxins 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 - Discovery of a stable dimeric mutant of cyanovirin-N (CV-N) from a T7 phage-displayed CV-N mutant library. AN - 71638950; 11944919 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. JF - Biochemical and biophysical research communications AU - Han, Zhaozhong AU - Xiong, Changyun AU - Mori, Toshiyuki AU - Boyd, Michael R AD - Molecular Targets Drug Discovery Program, NCI-Frederick, Frederick, Maryland 21702-1201, USA. Y1 - 2002/04/12/ PY - 2002 DA - 2002 Apr 12 SP - 1036 EP - 1043 VL - 292 IS - 4 SN - 0006-291X, 0006-291X KW - Anti-HIV Agents KW - 0 KW - Bacterial Proteins KW - Carrier Proteins KW - HIV Envelope Protein gp120 KW - Peptide Library KW - cyanovirin N KW - 184539-38-6 KW - Index Medicus KW - Anti-HIV Agents -- metabolism KW - Electrophoresis, Polyacrylamide Gel KW - Dimerization KW - Escherichia coli -- genetics KW - HIV Envelope Protein gp120 -- metabolism KW - Molecular Weight KW - Structure-Activity Relationship KW - Mutagenesis KW - Chromatography, Gel KW - Anti-HIV Agents -- pharmacology KW - Polymerase Chain Reaction -- methods KW - Protein Folding KW - Molecular Sequence Data KW - Enzyme-Linked Immunosorbent Assay KW - Microbial Sensitivity Tests KW - Amino Acid Substitution KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- genetics KW - Carrier Proteins -- pharmacology KW - Bacteriophage T7 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71638950?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Applied+Social+Psychology&rft.atitle=Perceptions+of+women+condom+proposers+among+Chinese+Americans%2C+Japanese+Americans%2C+and+European+Americans&rft.au=Conley%2C+Terri+D.%3BCollins%2C+Barry+E.%3BGarcia%2C+David&rft.aulast=Conley&rft.aufirst=Terri&rft.date=2000-02-01&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 - 2002-05-13 N1 - Date created - 2002-04-11 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 - 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 - US EPA's acute reference exposure methodology for acute inhalation exposures. AN - 71682891; 12013548 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 concentra tions (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 - The Science of the total environment AU - Strickland, Judy A AU - Foureman, Gary L AD - National Center for Environmental Assessment MD 52, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA. strick12@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 - Air Pollutants KW - 0 KW - Hydrocarbons, Chlorinated KW - Teratogens KW - Xenobiotics KW - hexachlorocyclopentadiene KW - IP6ATU242I KW - Hydrogen Sulfide KW - YY9FVM7NSN KW - Index Medicus KW - United States KW - Reference Values KW - No-Observed-Adverse-Effect Level KW - Hydrocarbons, Chlorinated -- toxicity KW - Humans KW - Teratogens -- toxicity KW - Hydrogen Sulfide -- adverse effects KW - Air Pollutants -- adverse effects KW - Risk Assessment KW - United States Environmental Protection Agency KW - Inhalation Exposure KW - Xenobiotics -- adverse effects KW - Neoplasms -- etiology KW - Models, Theoretical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71682891?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Science+of+the+total+environment&rft.atitle=US+EPA%27s+acute+reference+exposure+methodology+for+acute+inhalation+exposures.&rft.au=Strickland%2C+Judy+A%3BFoureman%2C+Gary+L&rft.aulast=Strickland&rft.aufirst=Judy&rft.date=2002-04-08&rft.volume=288&rft.issue=1-2&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=The+Science+of+the+total+environment&rft.issn=00489697&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-23 N1 - Date created - 2002-05-15 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 - Preferential misincorporation of purine nucleotides by human DNA polymerase eta opposite benzo[a]pyrene 7,8-diol 9,10-epoxide deoxyguanosine adducts. AN - 71572839; 11821420 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(2) of dG, were placed at the fourth nucleotide from the 5'-end in two 16-mer sequence contexts, 5' approximately CG*A approximately and 5' approximately GG*T. poleta 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(max)/K(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 --> T is the most common type of mutation that (+)-BaP DE-2 induces in mammalian cells. JF - The Journal of biological chemistry AU - Chiapperino, Dominic AU - Kroth, Heiko AU - Kramarczuk, Irene H AU - Sayer, Jane M AU - Masutani, Chikahide AU - Hanaoka, Fumio AU - Jerina, Donald M AU - Cheh, Albert M AD - Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/04/05/ PY - 2002 DA - 2002 Apr 05 SP - 11765 EP - 11771 VL - 277 IS - 14 SN - 0021-9258, 0021-9258 KW - DNA Adducts KW - 0 KW - Purines KW - benzo(a)pyrene 7,8-diol-9,10-epoxide-N2-deoxyguanosine KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Rad30 protein KW - Deoxyguanosine KW - G9481N71RO KW - purine KW - W60KTZ3IZY KW - Index Medicus KW - Stereoisomerism KW - Dose-Response Relationship, Drug KW - Kinetics KW - Humans KW - Models, Chemical KW - Magnetic Resonance Spectroscopy KW - Binding Sites KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- metabolism KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- analogs & derivatives KW - Deoxyguanosine -- metabolism KW - Purines -- chemistry KW - Deoxyguanosine -- analogs & derivatives 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/71572839?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=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+Dominic%3BKroth%2C+Heiko%3BKramarczuk%2C+Irene+H%3BSayer%2C+Jane+M%3BMasutani%2C+Chikahide%3BHanaoka%2C+Fumio%3BJerina%2C+Donald+M%3BCheh%2C+Albert+M&rft.aulast=Chiapperino&rft.aufirst=Dominic&rft.date=2002-04-05&rft.volume=277&rft.issue=14&rft.spage=11765&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 - 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 - 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 community epidemiology work group approach. AN - 71890442; 12117070 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 and assessing changes in patterns and trends, detecting emerging "drugs of abuse", characterizing vulnerable populations and determining health and 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, and other interested and qualified members of the community. Timely, accurate, and cost-effective data can be generated through systematic collection and 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, and international levels, and 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. JF - Substance use & misuse AU - Kozel, Nicholas J AU - Robertson, Elizabeth B AU - Falkowski, Carol L AD - National Institutes of Health, National Institute on Drug Abuse, Division of Epidemiology, Services and Prevention Research, Rockville, Maryland, USA. nkozel@ngmsmtp.nida.nih.gov PY - 2002 SP - 783 EP - 803 VL - 37 IS - 5-7 SN - 1082-6084, 1082-6084 KW - Index Medicus KW - International Cooperation KW - Humans KW - Public Health Informatics KW - Population Surveillance KW - Community Networks KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71890442?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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 - 2003-01-22 N1 - Date created - 2002-07-15 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 - Plasma pharmacokinetics of a liver-selective nitric oxide-donating diazeniumdiolate in the male C57BL/6 mouse. AN - 71717615; 12028666 AB - 1. The single-dose plasma pharmacokinetics of O(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. 2. Plasma V-PYRRO/NO concentrations declined rapidly in a bi-exponential manner after i.v. administration of 5 mg kg(-1) body weight to mouse. The terminal half-life was 9.4 min and the mean residence time was 3.4 min. 3. 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. 4. The results provide additional evidence for a liver-selective metabolism of this nitric oxide-donating prodrug. JF - Xenobiotica; the fate of foreign compounds in biological systems AU - Stinson, S F AU - House, T AU - Bramhall, C AU - Saavedra, J E 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. stinson@dtpax2.ncifcrf.gov Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 339 EP - 347 VL - 32 IS - 4 SN - 0049-8254, 0049-8254 KW - Azo Compounds KW - 0 KW - O(2)-vinyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate KW - Pyrrolidines KW - diazeniumdiolate KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Pyrrolidines -- administration & dosage KW - Animals KW - Injections, Intravenous KW - Infusions, Intravenous KW - Mice, Inbred C57BL KW - Mice KW - Male KW - Liver -- blood supply KW - Nitric Oxide -- metabolism KW - Azo Compounds -- blood KW - Liver -- chemistry KW - Azo Compounds -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71717615?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Xenobiotica%3B+the+fate+of+foreign+compounds+in+biological+systems&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+J+E%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%3B+the+fate+of+foreign+compounds+in+biological+systems&rft.issn=00498254&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-08 N1 - Date created - 2002-05-24 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 - 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 - The association between biomarker-based exposure estimates for phthalates and demographic factors in a human reference population. AN - 71581454; 11940459 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, Frederick AU - Kohn, Michael C AU - Masten, Scott A AU - Brock, John W AU - Needham, Larry L AU - Portier, Christopher J AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 405 EP - 410 VL - 110 IS - 4 SN - 0091-6765, 0091-6765 KW - Biomarkers KW - 0 KW - Phthalic Acids KW - phthalic acid KW - 6O7F7IX66E KW - Index Medicus KW - Regression Analysis KW - Educational Status KW - Reference Values KW - Rural Population KW - Reproducibility of Results KW - Humans KW - Income KW - Risk Assessment KW - Demography KW - Adult KW - Middle Aged KW - Sample Size KW - Urban Population KW - Female KW - Male KW - Biomarkers -- analysis KW - Environmental Exposure KW - Phthalic Acids -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71581454?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+between+biomarker-based+exposure+estimates+for+phthalates+and+demographic+factors+in+a+human+reference+population.&rft.au=Koo%2C+Jung-Wan%3BParham%2C+Frederick%3BKohn%2C+Michael+C%3BMasten%2C+Scott+A%3BBrock%2C+John+W%3BNeedham%2C+Larry+L%3BPortier%2C+Christopher+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 completed - 2002-05-14 N1 - Date created - 2002-04-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Toxicol Appl Pharmacol. 1980 Jul;54(3):392-8 [7394794] Nature. 1980 Jan 24;283(5745):397-8 [6766207] Drug Chem Toxicol. 1981;4(3):251-62 [7338205] Arch Toxicol. 1982 May;50(1):1-10 [7115078] Environ Health Perspect. 1982 Nov;45:11-7 [7140682] Environ Health Perspect. 1982 Nov;45:129-33 [7140685] Environ Health Perspect. 1982 Nov;45:3-9 [6754362] Toxicol Lett. 1982 Nov;14(1-2):79-84 [7157420] J Pathol. 1983 Mar;139(3):309-21 [6834175] Bull Environ Contam Toxicol. 1983 Feb;30(2):152-7 [6839039] Drug Metab Dispos. 1983 Jan-Feb;11(1):59-61 [6132798] Toxicol Appl Pharmacol. 1983 Aug;70(1):43-8 [6612737] Food Chem Toxicol. 1984 Feb;22(2):123-31 [6538161] J Toxicol Environ Health. 1986;17(4):445-56 [3959124] Toxicol Appl Pharmacol. 1992 Jul;115(1):116-23 [1321518] Toxicology. 1993 Mar 30;79(1):11-9 [8475496] Environ Health Perspect. 1995 Apr;103 Suppl 3:45-8 [7635111] Food Addit Contam. 1995 Sep-Oct;12(5):637-44 [8522028] Toxicol Lett. 1996 Jul;86(1):19-25 [8685916] Environ Health Perspect. 1997 Aug;105(8):802-11 [9347895] Toxicol Ind Health. 1999 Jan-Mar;15(1-2):94-118 [10188194] Food Chem Toxicol. 1999 Aug;37(8):905-17 [10506015] Biometrics. 2000 Mar;56(1):81-8 [10783780] Risk Anal. 2000 Apr;20(2):261-71 [10859785] Environ Health Perspect. 2000 Oct;108(10):979-82 [11049818] Environ Health Perspect. 2000 Oct;108(10):A440-2 [11097556] Environ Health Perspect. 1973 Jun;4:3-26 [4578674] Toxicology. 1974 Mar;2(1):51-65 [4823738] J Chromatogr. 1974 Jul 17;94(0):209-18 [4844611] Bull Environ Contam Toxicol. 1974 Apr;11(4):371-8 [4433824] Drug Metab Dispos. 1975 May-Jun;3(3):211-9 [238820] Toxicology. 1975 May;4(2):253-64 [1154425] J Agric Food Chem. 1975 Sep-Oct;23(5):854-8 [1159183] Drug Metab Dispos. 1976 May-Jun;4(3):288-95 [6235] Lipids. 1978 Jan;13(1):66-74 [628318] Toxicology. 1978 Feb;9(1-2):109-23 [653732] Toxicol Appl Pharmacol. 1978 Aug;45(2):497-504 [705785] Arch Int Pharmacodyn Ther. 1978 Oct;235(2):187-95 [736698] Clin Chem. 1979 Dec;25(12):2011-4 [509699] Environ Res. 1980 Jun;22(1):245-53 [7418682] 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 - Disposition of inhaled mercury vapor in pregnant rats: maternal toxicity and effects on developmental outcome. AN - 71522010; 11896293 AB - The disposition and toxicity of inhaled elemental mercury (Hg0) 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 Hg0/m(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(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(3) Hg0 gained about 7% less than controls, and rats exposed to 8 mg/m(3) Hg0 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(3) concentration groups, and urinalysis revealed increased levels of protein and alkaline phosphatase activity in urine of all Hg0-exposed rats. Dams exposed to 8 mg/m(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(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(3) Hg0. 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 Hg0 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 : an official journal of the Society of Toxicology 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 AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. morgand@niehs.nih.gov Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 261 EP - 273 VL - 66 IS - 2 SN - 1096-6080, 1096-6080 KW - Metallothionein KW - 9038-94-2 KW - Mercury KW - FXS1BY2PGL KW - Index Medicus KW - Animals KW - Litter Size -- drug effects KW - Rats, Long-Evans KW - Dose-Response Relationship, Drug KW - Volatilization KW - Tissue Distribution KW - Pregnancy KW - Rats KW - Body Weight -- drug effects KW - Metallothionein -- drug effects KW - Urinalysis KW - Administration, Inhalation KW - Female KW - Organ Size -- drug effects KW - Prenatal Exposure Delayed Effects KW - Mercury -- blood KW - Mercury -- pharmacokinetics KW - Mercury -- toxicity KW - Embryonic and Fetal Development -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71522010?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=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&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+%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 - 2002-06-21 N1 - Date created - 2002-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Feasibility of assessing the carcinogenicity of neutrons among neutron therapy patients. AN - 71511706; 11893253 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, Alice J AU - Stovall, Marilyn AU - Kleinerman, Ruth A AU - Maor, Moshe H AU - Taylor, Marie E AU - Boice, John D AU - Ron, Elaine AD - Radiation Epidemiology Branch, National Cancer Institute, 6120 Executive Boulevard, Bethesda, Maryland 20892-7238, USA. sigurdsa@mail.nih.gov Y1 - 2002/04// PY - 2002 DA - April 2002 SP - 483 EP - 489 VL - 157 IS - 4 SN - 0033-7587, 0033-7587 KW - Index Medicus KW - Space life sciences KW - United States KW - Feasibility Studies KW - Dose Fractionation KW - Humans KW - Health Surveys KW - Treatment Outcome KW - Neutrons -- therapeutic use KW - Neutrons -- adverse effects KW - Neoplasms -- radiotherapy KW - Carcinogenicity Tests -- methods KW - Neoplasms -- etiology KW - Radiotherapy -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71511706?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+research&rft.atitle=Feasibility+of+assessing+the+carcinogenicity+of+neutrons+among+neutron+therapy+patients.&rft.au=Sigurdson%2C+Alice+J%3BStovall%2C+Marilyn%3BKleinerman%2C+Ruth+A%3BMaor%2C+Moshe+H%3BTaylor%2C+Marie+E%3BBoice%2C+John+D%3BRon%2C+Elaine&rft.aulast=Sigurdson&rft.aufirst=Alice&rft.date=2002-04-01&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 completed - 2002-04-19 N1 - Date created - 2002-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serotonin releasing agents. Neurochemical, therapeutic and adverse effects. AN - 71505289; 11888573 AB - This review summarizes the neurochemical, therapeutic and adverse effects of serotonin (5-HT) releasing agents. The 5-HT releaser (plus minus)-fenfluramine is composed of two stereoisomers, (+)-fenfluramine and (minus sign)-fenfluramine, which are N-de-ethylated to yield the metabolites, (+)-norfenfluramine and (minus sign)-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(2B) and 5-HT(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, Richard B AU - Baumann, Michael 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 - April 2002 SP - 825 EP - 836 VL - 71 IS - 4 SN - 0091-3057, 0091-3057 KW - Appetite Depressants KW - 0 KW - Serotonin Agents KW - Fenfluramine KW - 2DS058H2CF KW - Serotonin KW - 333DO1RDJY KW - Index Medicus KW - Fenfluramine -- adverse effects KW - Animals KW - Appetite Depressants -- adverse effects KW - Humans KW - Fenfluramine -- therapeutic use KW - Fenfluramine -- pharmacology KW - Appetite Depressants -- therapeutic use KW - Appetite Depressants -- pharmacology KW - Serotonin Agents -- pharmacology KW - Brain Chemistry -- drug effects KW - Serotonin Agents -- therapeutic use KW - Serotonin -- metabolism KW - Serotonin Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71505289?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacology%2C+biochemistry%2C+and+behavior&rft.atitle=Serotonin+releasing+agents.+Neurochemical%2C+therapeutic+and+adverse+effects.&rft.au=Rothman%2C+Richard+B%3BBaumann%2C+Michael+H&rft.aulast=Rothman&rft.aufirst=Richard&rft.date=2002-04-01&rft.volume=71&rft.issue=4&rft.spage=825&rft.isbn=&rft.btitle=&rft.title=Pharmacology%2C+biochemistry%2C+and+behavior&rft.issn=00913057&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-11 N1 - Date created - 2002-03-12 N1 - Date revised - 2017-01-13 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 - 61508785; 200205963 AB - A new theory of substance use disorders is proposed -- the SPFit theory -- that is based on evolutionary biology & adaptive systems. Self-perceived survival ability & reproductive fitness (SPFit) is proposed as a human psychobiological construct that prioritizes & organizes (ie, 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 & expectations about drugs as the individual learns that abused drugs will easily & reliably inflate SPFit. The cortico-mesolimbic dopamine system & its modulating interconnections are viewed as the biological substrate of SPFit; it is proposed to be a survival & 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. 3 Tables, 2 Figures, 93 References. Adapted from the source document. JF - Addiction AU - Newlin, David B AD - National Instit Drug Abuse -- Intramural, Baltimore, MD 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 - Sociobiology KW - Alcoholism KW - Evolutionary Theories KW - Darwinism KW - Drug Abuse KW - article KW - 6129: addiction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61508785?accountid=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=Addiction&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&rft.issn=09652140&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Last updated - 2016-09-28 N1 - CODEN - ADICE5 N1 - SubjectsTermNotLitGenreText - Alcoholism; Drug Abuse; Evolutionary Theories; Darwinism; Sociobiology 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 - 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 - Rb localization and phosphorylation kinetics correlate with the cellular phenotype of cultured breast adenocarcinoma cells AN - 18478235; 5439485 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, J AU - Barhoumi, R AU - Burghardt, R AU - Kochevar, D T AD - Departments of Veterinary Physiology and Pharmacology, 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 - Society for In Vitro Biology VL - 38 IS - 4 SN - 1071-2690, 1071-2690 KW - double prime Rb protein KW - adenocarcinoma KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33220:Cell culture UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18478235?accountid=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+J%3BBarhoumi%2C+R%3BBurghardt%2C+R%3BKochevar%2C+D+T&rft.aulast=Botos&rft.aufirst=J&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%29038%280235%3ARLAPKC%292.0.CO%3B2 L2 - http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=1071-2690&volume=38&page=235 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1290/1071-2690(2002)038(0235:RLAPKC)2.0.CO;2 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 - 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 -