TY - JOUR T1 - In vivo fiber tractography using DT-MRI data. AN - 85276134; pmid-11025519 AB - Fiber tract trajectories in coherently organized brain white matter pathways were computed from in vivo diffusion tensor magnetic resonance imaging (DT-MRI) data. First, a continuous diffusion tensor field is constructed from this discrete, noisy, measured DT-MRI data. Then a Frenet equation, describing the evolution of a fiber tract, was solved. This approach was validated using synthesized, noisy DT-MRI data. Corpus callosum and pyramidal tract trajectories were constructed and found to be consistent with known anatomy. The method's reliability, however, degrades where the distribution of fiber tract directions is nonuniform. Moreover, background noise in diffusion-weighted MRIs can cause a computed trajectory to hop from tract to tract. Still, this method can provide quantitative information with which to visualize and study connectivity and continuity of neural pathways in the central and peripheral nervous systems in vivo, and holds promise for elucidating architectural features in other fibrous tissues and ordered media. JF - Magnetic Resonance in Medicine AU - Basser, P J AU - Pajevic, S AU - Pierpaoli, C AU - Duda, J AU - Aldroubi, A AD - Section on Tissue Biophysics and Biomimetics, NICHD, Bethesda, Maryland 20892-5772, USA. PY - 2000 SP - 625 EP - 632 VL - 44 IS - 4 SN - 0740-3194, 0740-3194 KW - Artifacts KW - Human KW - Brain KW - Support, U.S. Gov't, Non-P.H.S. KW - Image Processing, Computer-Assisted KW - Nerve Fibers KW - Magnetic Resonance Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85276134?accountid=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=In+vivo+fiber+tractography+using+DT-MRI+data.&rft.au=Basser%2C+P+J%3BPajevic%2C+S%3BPierpaoli%2C+C%3BDuda%2C+J%3BAldroubi%2C+A&rft.aulast=Basser&rft.aufirst=P&rft.date=2000-10-01&rft.volume=44&rft.issue=4&rft.spage=625&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 - Enhancing the quality of studies using transcranial magnetic and electrical stimulation with a new computer-controlled system. AN - 85271775; pmid-11000414 AB - Transcranial magnetic (TMS) and electrical (TES) stimulation of the human brain have become useful tools in neurophysiological and neuropsychological research. Here we describe an integrated system that allows experimental control, data recording and analysis of neurophysiological and neuropsychological TMS and TES procedures (including motor thresholds, recruitment curves, intracortical inhibition and facilitation with paired pulses). The system uses a multifunction input/output board and a set of virtual instruments (VI) programmed with the Labview graphical programming language. It also includes online curve fitting of recruitment curves using the Boltzmann sigmoid function and monitoring of the preinnervation grade of the target muscle. Modules for neuropsychological stimulus presentation or faster repetitive stimulation can be easily added. This system yields more accurate data recording and analysis in a user friendly and unified environment. JF - Journal of Neuroscience Methods AU - Kaelin-Lang, A AU - Cohen, L G AD - Human Cortical Physiology Section, National Institute of Neurological Disorders and Stroke, NIH, Bldg.10, Room 5N234, 10 Center Drive, MSC 1430, Bethesda, MD 20892, USA. PY - 2000 SP - 81 EP - 89 VL - 102 IS - 1 SN - 0165-0270, 0165-0270 KW - Motor Cortex KW - Software KW - Conditioning, Classical KW - Computers KW - Evoked Potentials, Motor KW - Human KW - Automatic Data Processing KW - Image Processing, Computer-Assisted KW - Software Design KW - Magnetics KW - Electric Stimulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85271775?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Neuroscience+Methods&rft.atitle=Enhancing+the+quality+of+studies+using+transcranial+magnetic+and+electrical+stimulation+with+a+new+computer-controlled+system.&rft.au=Kaelin-Lang%2C+A%3BCohen%2C+L+G&rft.aulast=Kaelin-Lang&rft.aufirst=A&rft.date=2000-10-01&rft.volume=102&rft.issue=1&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neuroscience+Methods&rft.issn=01650270&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Acute effects of polychlorinated biphenyl-containing and -free transformer fluids on rat testicular steroidogenesis. AN - 85257179; pmid-11049815 AB - Polychlorinated biphenyl (PCB)-based transformer fluids belong to a class of environmentally persistent mixtures with known toxic effects. Here, we studied the acute effects of Askarel (which contains Aroclor 1260) and two substitute transformer fluids (the silicone oil-based DC561 and the mineral oil-based ENOL C) on rat testicular steroidogenesis. Single intraperitoneal (ip; 10 mg/kg body weight) or bilateral intratesticular (itt; 25 microg/testis) injections of Askarel markedly decreased serum androgen levels 24 hr after administration. In acute testicular cultures from these animals, chorionic gonadotropin-stimulated progesterone and androgen productions were severely attenuated. When itt was injected or added in vitro, Askarel inhibited 3ss-hydroxysteroid dehydrogenase (3ssHSD), stimulated 17[alpha]-hydroxylase/lyase (P450c17), and did not affect 17ss-hydroxysteroid dehydrogenase in testicular postmitochondrial fractions. The ip-injected Askarel did not affect 3ssHSD, but inhibited P450c17, suggesting that a more intensive metabolism of peripherally injected Askarel reduces the circulating levels of active ingredients below the threshold needed for inhibition of 3ssHSD and generates a derivative that inhibits P450c17. In contrast to Askarel, itt-injection (25 microg/testis) of DC561 and ENOL C did not affect in vivo and in vitro steroidogenesis. These findings show the acute effects of Askarel, but not silicone and mineral oils, on testicular steroidogenesis. JF - Environmental Health Perspectives AU - Andric, S A AU - Kostic, T S AU - Dragisic, S M AU - Andric, N L AU - Stojilkovic, S S AU - Kovacevic, R Z AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, Bethesda, Maryland, USA. PY - 2000 SP - 955 EP - 959 VL - 108 IS - 10 SN - 0091-6765, 0091-6765 KW - Rats KW - Aroclors KW - Testis KW - Polychlorinated Biphenyls KW - Animal KW - Rats, Wistar KW - Testicular Hormones KW - Infusions, Parenteral KW - Tissue Culture KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85257179?accountid=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=Environmental+Health+Perspectives&rft.atitle=Acute+effects+of+polychlorinated+biphenyl-containing+and+-free+transformer+fluids+on+rat+testicular+steroidogenesis.&rft.au=Andric%2C+S+A%3BKostic%2C+T+S%3BDragisic%2C+S+M%3BAndric%2C+N+L%3BStojilkovic%2C+S+S%3BKovacevic%2C+R+Z&rft.aulast=Andric&rft.aufirst=S&rft.date=2000-10-01&rft.volume=108&rft.issue=10&rft.spage=955&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Fluctuation of motor charge in the lateral membrane of the cochlear outer hair cell. AN - 85255885; pmid-11023893 AB - Functioning of the membrane motor of the outer hair cell is tightly associated with transfer of charge across the membrane. To obtain further insights into the motor mechanism, we examined kinetics of charge transfer across the membrane in two different modes. One is to monitor charge transfer induced by changes in the membrane potential as an excess membrane capacitance. The other is to measure spontaneous flip-flops of charges across the membrane under voltage-clamp conditions as current noise. The noise spectrum of current was inverse Lorentzian, and the capacitance was Lorentzian, as theoretically expected. The characteristic frequency of the capacitance was approximately 10 kHz, and that for current noise was approximately 30 kHz. The difference in the characteristic frequencies seems to reflect the difference in the modes of mechanical movement associated with the two physical quantities. JF - Biophysical Journal AU - Dong, X AU - Ehrenstein, D AU - Iwasa, Kuni H AD - Biophysics Section, Laboratory of Cellular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892-0922 USA.; National Institute on Deafness and Other Communication Disorders PY - 2000 SP - 1876 EP - 1882 VL - 79 IS - 4 SN - 0006-3495, 0006-3495 KW - In Vitro KW - Patch-Clamp Techniques KW - Guinea Pigs KW - Hair Cells, Outer KW - Animal KW - Membrane Potentials KW - Models, Biological KW - Biomechanics KW - Biophysics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85255885?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biophysical+Journal&rft.atitle=Fluctuation+of+motor+charge+in+the+lateral+membrane+of+the+cochlear+outer+hair+cell.&rft.au=Dong%2C+X%3BEhrenstein%2C+D%3BIwasa%2C+Kuni+H&rft.aulast=Dong&rft.aufirst=X&rft.date=2000-10-01&rft.volume=79&rft.issue=4&rft.spage=1876&rft.isbn=&rft.btitle=&rft.title=Biophysical+Journal&rft.issn=00063495&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Activation of language cortex with automatic speech tasks. AN - 85168642; pmid-11071493 AB - OBJECTIVE: To identify automatic speech tasks that reliably demonstrate increased regional cerebral blood flow (rCBF) in Broca's and Wernicke's areas of the cortex using PET. BACKGROUND: Localizing language with direct cortical stimulation mapping requires that patients have a stable baseline on tests that engage eloquent cortex. For dysphasic patients or younger children, automatic speech tasks such as counting are often used in lieu of more complex language tests. Evidence from both lesion and neuroimaging studies suggests that these tasks may not adequately engage language cortices. In this study, we examined rCBF during automatic oromotor and speech tasks of varying complexity to identify those eliciting increased CBF in Broca's and Wernicke's areas. METHODS: Eight normal volunteers underwent PET during rest, tongue movements, and three automatic speech tasks: repeating a phoneme sequence, repeating the months of the year, and reciting a memorized prose passage. Images were averaged across subjects and compared across tasks for regional localization and laterality. RESULTS: Whereas all activation tasks produced increased relative CBF in brain regions that correlated with articulation and auditory processing, only the two tasks that used real words (versus phonemes) showed left-lateralized rCBF increases in posterior superior temporal lobe (Wernicke's area), and only the prose repetition task produced left lateralized activity in Broca's area. CONCLUSIONS: Whereas automatic speech typically does not engage language cortex, repeating a memorized prose passage showed unambiguous activation in both Broca's and Wernicke's areas. These results caution against the use of common automatic speech tasks for mapping eloquent cortex and suggest an alternative task for those with poor language abilities or acquired dysphasia who cannot perform standardized language tests reliably. JF - Neurology AU - Bookheimer, S Y AU - Zeffiro, T A AU - Blaxton, T A AU - Gaillard, P W AU - Theodore, W H AD - Epilepsy Research Branch, NINDS, National Institutes of Health, Bethesda, MD, USA. PY - 2000 SP - 1151 EP - 1157 VL - 55 IS - 8 SN - 0028-3878, 0028-3878 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85168642?accountid=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=Neurology&rft.atitle=Activation+of+language+cortex+with+automatic+speech+tasks.&rft.au=Bookheimer%2C+S+Y%3BZeffiro%2C+T+A%3BBlaxton%2C+T+A%3BGaillard%2C+P+W%3BTheodore%2C+W+H&rft.aulast=Bookheimer&rft.aufirst=S&rft.date=2000-10-01&rft.volume=55&rft.issue=8&rft.spage=1151&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Varicella zoster meningitis preceeded by thrombophlebitis in a patient with Hodgkin's disease. AN - 72608568; 11342324 AB - Varicella zoster (V-Z) infections are common among patients with hematological malignancies, particularly Hodgkin's disease (HD). The common denominator in both HD and V-Z infections is immunosuppression. Most of V-Z infections occur in patients with HD during the remission period, who have mixed cellularity sub-type, with stage III disease and who have received combined chemo-radiation therapy. Involvement of the central nervous system usually manifests as post-herpetic neuralgia or encephalitis. Angiitis has also been found in association with V-Z infections. The authors describe a case of HD who developed V-Z meningitis preceeded by superficial thrombophlebitis of upper extremities during the period of active chemotherapy. JF - Leukemia & lymphoma AU - Saif, M W AU - Hamilton, J M AU - Allegra, C J AD - Medicine Branch, National Cancer Institute, National Naval Medical Center, Bethesda, MD 20889, USA. saifw@mail.nih.gov Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 421 EP - 426 VL - 39 IS - 3-4 SN - 1042-8194, 1042-8194 KW - Index Medicus KW - Humans KW - Adult KW - Immunocompromised Host KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Herpes Zoster -- chemically induced KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Male KW - Hodgkin Disease -- drug therapy KW - Hodgkin Disease -- virology KW - Hodgkin Disease -- complications KW - Thrombophlebitis -- virology KW - Meningitis, Viral -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72608568?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Varicella+zoster+meningitis+preceeded+by+thrombophlebitis+in+a+patient+with+Hodgkin%27s+disease.&rft.au=Saif%2C+M+W%3BHamilton%2C+J+M%3BAllegra%2C+C+J&rft.aulast=Saif&rft.aufirst=M&rft.date=2000-10-01&rft.volume=39&rft.issue=3-4&rft.spage=421&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 - 2001-10-04 N1 - Date created - 2001-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pathophysiology and treatment of secondary obsessive-compulsive behaviors and tics. AN - 72593714; 11291021 AB - Advances in neurobiological research suggest that certain frontal-subcortical circuits play important roles in idiopathic obsessive-compulsive disorder and Tourette's syndrome. Tics and obsessive-compulsive behaviors secondary to neurologic insult appear to involve the same neural circuitry. There are few systematic studies of the treatment of obsessive-compulsive behaviors and tics associated with neurologic disorders. However knowledge of the circuitry and associated neurochemistry of these disorders can help to outline a rational approach to these behaviors. Copyright 2000 by W.B. Saunders Company JF - Seminars in clinical neuropsychiatry AU - Bhangoo, R K AD - Pediatric and Developmental Neuropsychiatry Branch, National Institute of Mental Health, 10 Center Drive, Building 10 Room 4N-208, Bethesda, MD 20892, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 250 EP - 258 VL - 5 IS - 4 SN - 1084-3612, 1084-3612 KW - Neurotransmitter Agents KW - 0 KW - Psychotropic Drugs KW - Index Medicus KW - Neural Pathways -- physiopathology KW - Tourette Syndrome -- drug therapy KW - Akathisia, Drug-Induced -- prevention & control KW - Humans KW - Tourette Syndrome -- physiopathology KW - Prefrontal Cortex -- physiopathology KW - Basal Ganglia -- physiopathology KW - Basal Ganglia Diseases -- physiopathology KW - Basal Ganglia Diseases -- complications KW - Obsessive-Compulsive Disorder -- physiopathology KW - Neurotransmitter Agents -- metabolism KW - Psychotropic Drugs -- therapeutic use KW - Obsessive-Compulsive Disorder -- metabolism KW - Obsessive-Compulsive Disorder -- drug therapy KW - Tics -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72593714?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+clinical+neuropsychiatry&rft.atitle=Pathophysiology+and+treatment+of+secondary+obsessive-compulsive+behaviors+and+tics.&rft.au=Bhangoo%2C+R+K&rft.aulast=Bhangoo&rft.aufirst=R&rft.date=2000-10-01&rft.volume=5&rft.issue=4&rft.spage=250&rft.isbn=&rft.btitle=&rft.title=Seminars+in+clinical+neuropsychiatry&rft.issn=10843612&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-31 N1 - Date created - 2001-04-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional interaction of vega2 and goosecoid homeobox genes in zebrafish. AN - 72551688; 11064422 AB - The gastrula organizer forms in the dorsal region of the zebrafish embryo, where the bozozok/dharma homeobox gene downregulates expression of the vega1 transcriptional repressor. Here, we describe a novel Vega family homeobox gene, vega2. Expression of vega2 is initiated at the ventral blastoderm margin during blastula stages, and by gastrulation becomes complementary to but partially overlapping with the dorsal expression domain of the homeobox gene goosecoid (gsc). This dorsal exclusion of vega2 expression is not observed in bozozok mutants in which organizer formation is impaired. Both vega2 and vega1 can physically interact with Gsc. Zebrafish embryos injected with vega2 mRNA failed to express gsc and developed a headless phenotype. Conversely, a putative dominant negative form of vega2, VP16-vega2, elicited the expansion of gsc expression and a dorsalized phenotype. We suggest that vega2, in cooperation with vega1, functions as a negative regulator of organizer genes including gsc, and participates in the refinement of the gastrula organizer domain. JF - Genesis (New York, N.Y. : 2000) AU - Kawahara, A AU - Wilm, T AU - Solnica-Krezel, L AU - Dawid, I B AD - Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 58 EP - 67 VL - 28 IS - 2 SN - 1526-954X, 1526-954X KW - Goosecoid Protein KW - 0 KW - Homeodomain Proteins KW - Repressor Proteins KW - Transcription Factors KW - Zebrafish Proteins KW - gsc protein, zebrafish KW - vent protein, zebrafish KW - Luciferases KW - EC 1.13.12.- KW - Index Medicus KW - Protein Biosynthesis KW - Animals KW - Promoter Regions, Genetic KW - Blotting, Western KW - Embryo, Nonmammalian -- physiology KW - Transfection KW - Molecular Sequence Data KW - Luciferases -- metabolism KW - Embryo, Nonmammalian -- embryology KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Gene Expression Regulation, Developmental KW - Mutagenesis KW - Organizers, Embryonic -- embryology KW - Repressor Proteins -- metabolism KW - Organizers, Embryonic -- physiology KW - Zebrafish Proteins -- metabolism KW - Repressor Proteins -- genetics KW - Homeodomain Proteins -- chemistry KW - Homeodomain Proteins -- genetics KW - Body Patterning -- physiology KW - Homeodomain Proteins -- metabolism KW - Zebrafish Proteins -- genetics KW - Zebrafish -- embryology KW - Zebrafish -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72551688?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genesis+%28New+York%2C+N.Y.+%3A+2000%29&rft.atitle=Functional+interaction+of+vega2+and+goosecoid+homeobox+genes+in+zebrafish.&rft.au=Kawahara%2C+A%3BWilm%2C+T%3BSolnica-Krezel%2C+L%3BDawid%2C+I+B&rft.aulast=Kawahara&rft.aufirst=A&rft.date=2000-10-01&rft.volume=28&rft.issue=2&rft.spage=58&rft.isbn=&rft.btitle=&rft.title=Genesis+%28New+York%2C+N.Y.+%3A+2000%29&rft.issn=1526954X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-04-30 N1 - Date created - 2001-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Consciousness of drug abuse problems and motivational intention for primary community intervention among the community residents]. AN - 72499904; 11144153 AB - An influence of the community factor has a tremendous significance over the policy taken for the social rehabilitation of drug addicts as well as for the prevention of the drug problems. This study focuses, from a sociological viewpoint, on attitudes and consciousness of the community residents on drug abuse problems, particularly addressing their motivational intention of primary intervention in the community settings. A social investigation with a random sampling of the adult male population of a ward community in Osaka was conducted by combining the self-administered schedule method and the individual interview method at the door. 1) More than 90% of the respondents recognized the drug abuse problem in Japan as one of the most severe social problems; 2) as for countermeasures against the drug problems, crack-down by police and severe legal punishments were much more preferred overwhelmingly to the soft measures such as education, therapy and social services; 3) ex-patients of drug abuse and dependence discharged from mental hospitals would be supposed to be faced with harsh, rejective interactions in their community life; 4) 15.4% of the respondents reported their recognition of the illegal drug users in the last three years prior to the survey and those reporting the recognition in their life time were found by 26.5%; 5) the active motivation for primary intervention with drug users on the community basis was widely shared among the community residents. It was implied that this motivational asset excavated in the community should be activated in one way or another by community programs for the primary prevention against drug abuse. JF - Nihon Arukoru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence AU - Shimizu, S AD - Division of Adult Mental Health, National Institute of Mental Health, NCNP, 1-7-3 Kohnodai, Ichikawa-shi, Chiba 272-0827, Japan. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 330 EP - 340 VL - 35 IS - 5 SN - 1341-8963, 1341-8963 KW - Index Medicus KW - Humans KW - Adult KW - Male KW - Japan KW - Motivation KW - Community Participation -- psychology KW - Substance-Related Disorders KW - Awareness KW - Social Problems UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72499904?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nihon+Arukoru+Yakubutsu+Igakkai+zasshi+%3D+Japanese+journal+of+alcohol+studies+%26+drug+dependence&rft.atitle=%5BConsciousness+of+drug+abuse+problems+and+motivational+intention+for+primary+community+intervention+among+the+community+residents%5D.&rft.au=Shimizu%2C+S&rft.aulast=Shimizu&rft.aufirst=S&rft.date=2000-10-01&rft.volume=35&rft.issue=5&rft.spage=330&rft.isbn=&rft.btitle=&rft.title=Nihon+Arukoru+Yakubutsu+Igakkai+zasshi+%3D+Japanese+journal+of+alcohol+studies+%26+drug+dependence&rft.issn=13418963&rft_id=info:doi/ LA - Japanese DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-15 N1 - Date created - 2000-12-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polyomavirus JC genotypes in an urban United States population reflect the history of African origin and genetic admixture in modern African Americans. AN - 72498796; 11126728 AB - The human polyomavirus JC (JC virus), a small, circular, double-stranded DNA virus, has a worldwide distribution and is excreted harmlessly in urine by 20% to 70% of adults. DNA sequence analysis has identified seven distinct genotypes that likely coevolved with modern humans, although the mode of virus transmission is unknown. Type 1 is European in its distribution. Types 2 and 7 are Asian, while Types 3 and 6 are African. Type 4, closely related to Type 1, is of uncertain origin, having been found in population groups in parts of Europe and in the United States, but not in Africa. Here we have studied the JCV partial genomic DNA sequences amplified by polymerase chain reaction techniques from urines of an urban, mainly African American population cohort from Washington, D.C. The predominant genotype identified was Type 4 (32/78 JCV strains, 41%). Type 1 strain was found in 32% of African Americans, while JCV Type 3 strain was found in 18% of African Americans. These African strains have persisted in modern African Americans after 200 to 400 years of minority existence and genetic admixture in the New World. An ancient West African genotype, Type 6, was absent in this African American cohort. However, one Type 6 strain was found in a patient from Sierra Leone (West Africa), domiciled in the United States for 20 years. Type 2A, the most common subtype in Native Americans, was seen in only two African-Americans (3%). A Type 7 strain, previously reported only in Taiwan and South China, was identified in a Vietnamese immigrant. These data support the history of African origin, migration, and genetic admixture of modern African Americans. Analysis of JCV strains in the present American populations provides a novel tool for reconstructing human migrations and genetic admixture in the New World. JF - Human biology AU - Chima, S C AU - Ryschkewitsch, C F AU - Fan, K J AU - Stoner, G L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4126, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 837 EP - 850 VL - 72 IS - 5 SN - 0018-7143, 0018-7143 KW - DNA, Viral KW - 0 KW - Index Medicus KW - Phylogeny KW - Sequence Analysis, DNA -- methods KW - Humans KW - Aged KW - Child KW - Emigration and Immigration -- statistics & numerical data KW - Child, Preschool KW - Genotype KW - Polymerase Chain Reaction KW - District of Columbia KW - Genetic Testing KW - Aged, 80 and over KW - Adult KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - JC Virus -- genetics KW - JC Virus -- classification KW - Urban Population -- statistics & numerical data KW - African Continental Ancestry Group -- genetics KW - Genome, Viral KW - Genetic Variation -- genetics KW - DNA, Viral -- urine KW - DNA, Viral -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72498796?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+biology&rft.atitle=Polyomavirus+JC+genotypes+in+an+urban+United+States+population+reflect+the+history+of+African+origin+and+genetic+admixture+in+modern+African+Americans.&rft.au=Chima%2C+S+C%3BRyschkewitsch%2C+C+F%3BFan%2C+K+J%3BStoner%2C+G+L&rft.aulast=Chima&rft.aufirst=S&rft.date=2000-10-01&rft.volume=72&rft.issue=5&rft.spage=837&rft.isbn=&rft.btitle=&rft.title=Human+biology&rft.issn=00187143&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-01 N1 - Date created - 2000-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Social epidemiology of chronic liver disease and cirrhosis mortality in the United States, 1935-1997: trends and differentials by ethnicity, socioeconomic status, and alcohol consumption. AN - 72496714; 11126726 AB - This study examines trends and ethnic and socioeconomic differentials in chronic liver disease and cirrhosis mortality in the United States. Age-adjusted death rates from the National Vital Statistics System were used to analyze race and sex-specific mortality trends from 1968 through 1997. Age-adjusted liver cirrhosis mortality and per capita alcohol consumption data from 1935 through 1996 were modeled using time-series regression. Moreover, the Cox hazards regression was applied to the National Longitudinal Mortality Study, 1979-1989, to examine socioeconomic differentials at the individual level, whereas multivariate ordinary least squares regression was used to model state-specific cirrhosis mortality from 1990 to 1992 as a function of socioeconomic variables and alcohol consumption at the ecological level. Chronic liver disease and cirrhosis continues to be an important cause of death in the United States, even after three decades of consistently declining mortality rates. For both men and women aged 25 years and older, significant mortality differentials were found by age, race/ethnicity, marital status, family income, and employment status. For men, marked differentials were also found by nativity, rural-urban residence, and education. Unemployment, minority concentration, and alcohol consumption were major predictors of state-specific cirrhosis mortality. Both time-series and cross-sectional data indicate a strong correlation between alcohol consumption and US cirrhosis mortality. Substantial ethnic and socioeconomic differences in cirrhosis mortality suggest the need for social and public health policies and interventions that target such high-risk groups as American Indians, Hispanic Americans, the socially isolated, and the poor. JF - Human biology AU - Singh, G K AU - Hoyert, D L AD - National Institutes of Health, National Cancer Institute, Division of Cancer Control and Population Sciences, Bethesda, MD 20892-7352, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 801 EP - 820 VL - 72 IS - 5 SN - 0018-7143, 0018-7143 KW - Index Medicus KW - Educational Status KW - Humans KW - Aged KW - Unemployment -- statistics & numerical data KW - Longitudinal Studies KW - Population Surveillance KW - Multivariate Analysis KW - Age Distribution KW - Cross-Sectional Studies KW - Adult KW - Least-Squares Analysis KW - Chronic Disease KW - Middle Aged KW - United States -- epidemiology KW - Sex Distribution KW - Female KW - Male KW - Proportional Hazards Models KW - Liver Cirrhosis -- ethnology KW - African Americans -- statistics & numerical data KW - European Continental Ancestry Group -- statistics & numerical data KW - Liver Diseases -- mortality KW - Indians, North American -- statistics & numerical data KW - Poverty -- ethnology KW - Hispanic Americans -- statistics & numerical data KW - Liver Diseases -- ethnology KW - Liver Diseases -- etiology KW - Liver Cirrhosis -- etiology KW - Alcoholism -- complications KW - Liver Cirrhosis -- mortality KW - Poverty -- statistics & numerical data KW - Cause of Death -- trends UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72496714?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+biology&rft.atitle=Social+epidemiology+of+chronic+liver+disease+and+cirrhosis+mortality+in+the+United+States%2C+1935-1997%3A+trends+and+differentials+by+ethnicity%2C+socioeconomic+status%2C+and+alcohol+consumption.&rft.au=Singh%2C+G+K%3BHoyert%2C+D+L&rft.aulast=Singh&rft.aufirst=G&rft.date=2000-10-01&rft.volume=72&rft.issue=5&rft.spage=801&rft.isbn=&rft.btitle=&rft.title=Human+biology&rft.issn=00187143&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-01 N1 - Date created - 2000-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A histone variant, Htz1p, and a Sir1p-like protein, Esc2p, mediate silencing at HMR. AN - 72493956; 11090616 AB - Silencing at HMR requires silencers, and one of the roles of the silencer is to recruit Sir proteins. This work focuses on the function of Sir1p once it is recruited to the silencer. We have generated mutants of Sir1p that are recruited to the silencer but are unable to silence, and we have utilized these mutants to identify four proteins, Sir3p, Sir4p, Esc2p, and Htz1p, that when overexpressed, restored silencing. The isolation of Sir3p and Sir4p validated this screen. Molecular analysis suggested that Esc2p contributed to silencing in a manner similar to Sir1p and probably helped recruit or stabilize the other Sir proteins, while Htz1p present at HMR assembled a specialized chromatin structure necessary for silencing. JF - Molecular cell AU - Dhillon, N AU - Kamakaka, R T AD - Unit on Chromatin and Transcription, NICHD/NIH, Bethesda, Maryland 20892, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 769 EP - 780 VL - 6 IS - 4 SN - 1097-2765, 1097-2765 KW - Chromatin KW - 0 KW - DNA-Binding Proteins KW - Fungal Proteins KW - GAL4 protein, S cerevisiae KW - Histones KW - Peptides KW - SIR1 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - Silent Information Regulator Proteins, Saccharomyces cerevisiae KW - Trans-Activators KW - Transcription Factors KW - Mating Factor KW - 61194-02-3 KW - Index Medicus KW - Alleles KW - Genes, Fungal KW - Suppression, Genetic KW - Chromatin -- physiology KW - Peptides -- genetics KW - Transcription Factors -- genetics KW - Chromatin -- ultrastructure KW - Mutagenesis KW - Saccharomyces cerevisiae -- genetics KW - Trans-Activators -- metabolism KW - Fungal Proteins -- metabolism KW - Saccharomyces cerevisiae -- metabolism KW - Trans-Activators -- genetics KW - Gene Silencing KW - Histones -- metabolism KW - Saccharomyces cerevisiae -- growth & development KW - Fungal Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72493956?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+histone+variant%2C+Htz1p%2C+and+a+Sir1p-like+protein%2C+Esc2p%2C+mediate+silencing+at+HMR.&rft.au=Dhillon%2C+N%3BKamakaka%2C+R+T&rft.aulast=Dhillon&rft.aufirst=N&rft.date=2000-10-01&rft.volume=6&rft.issue=4&rft.spage=769&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 - 2000-12-07 N1 - Date created - 2000-11-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. AN - 72492859; 11090624 AB - The determinant of verapamil-reversible chloroquine resistance (CQR) in a Plasmodium falciparum genetic cross maps to a 36 kb segment of chromosome 7. This segment harbors a 13-exon gene, pfcrt, having point mutations that associate completely with CQR in parasite lines from Asia, Africa, and South America. These data, transfection results, and selection of a CQR line harboring a novel K761 mutation point to a central role for the PfCRT protein in CQR. This transmembrane protein localizes to the parasite digestive vacuole (DV), the site of CQ action, where increased compartment acidification associates with PfCRT point mutations. Mutations in PfCRT may result in altered chloroquine flux or reduced drug binding to hematin through an effect on DV pH. JF - Molecular cell AU - Fidock, D A AU - Nomura, T AU - Talley, A K AU - Cooper, R A AU - Dzekunov, S M AU - Ferdig, M T AU - Ursos, L M AU - Sidhu, A B AU - Naudé, B AU - Deitsch, K W AU - Su, X Z AU - Wootton, J C AU - Roepe, P D AU - Wellems, T E AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 861 EP - 871 VL - 6 IS - 4 SN - 1097-2765, 1097-2765 KW - Membrane Proteins KW - 0 KW - Membrane Transport Proteins KW - PfCRT protein, Plasmodium falciparum KW - Protozoan Proteins KW - Recombinant Proteins KW - Chloroquine KW - 886U3H6UFF KW - Verapamil KW - CJ0O37KU29 KW - Tetrahydrofolate Dehydrogenase KW - EC 1.5.1.3 KW - Index Medicus KW - Animals KW - Exons KW - Humans KW - Digestive System -- metabolism KW - Drug Resistance KW - Amino Acid Sequence KW - Animals, Genetically Modified KW - Verapamil -- pharmacology KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Transfection KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Tetrahydrofolate Dehydrogenase -- genetics KW - Protozoan Proteins -- chemistry KW - Protozoan Proteins -- metabolism KW - Chloroquine -- pharmacology KW - Membrane Proteins -- chemistry KW - Plasmodium falciparum -- genetics KW - Membrane Proteins -- metabolism KW - Protozoan Proteins -- genetics KW - Membrane Proteins -- genetics KW - Vacuoles -- physiology KW - Plasmodium falciparum -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72492859?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutations+in+the+P.+falciparum+digestive+vacuole+transmembrane+protein+PfCRT+and+evidence+for+their+role+in+chloroquine+resistance.&rft.au=Fidock%2C+D+A%3BNomura%2C+T%3BTalley%2C+A+K%3BCooper%2C+R+A%3BDzekunov%2C+S+M%3BFerdig%2C+M+T%3BUrsos%2C+L+M%3BSidhu%2C+A+B%3BNaud%C3%A9%2C+B%3BDeitsch%2C+K+W%3BSu%2C+X+Z%3BWootton%2C+J+C%3BRoepe%2C+P+D%3BWellems%2C+T+E&rft.aulast=Fidock&rft.aufirst=D&rft.date=2000-10-01&rft.volume=6&rft.issue=4&rft.spage=861&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 - 2000-12-07 N1 - Date created - 2000-11-09 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF233068; GENBANK; AF233067; AF233064; AF233066; AF233065; AF030694 N1 - SuppNotes - Cited By: Mol Pharmacol. 1998 Jul;54(1):170-9 [9658203] Novartis Found Symp. 1999;226:265-77; discussion 277-80 [10645551] Mol Med. 1999 Nov;5(11):753-67 [10656877] Nature. 2000 Feb 24;403(6772):906-9 [10706290] Genetics. 2000 Mar;154(3):985-97 [10757748] Mol Biochem Parasitol. 2000 Sep;110(1):1-10 [10989140] Mol Biochem Parasitol. 2000 Sep;110(1):107-24 [10989149] Mol Biochem Parasitol. 2000 Sep;110(1):125-34 [10989150] Science. 1970 Jul 17;169(3942):289-90 [4988896] EMBO J. 1984 Nov;3(11):2695-700 [6391917] J Cell Biol. 1985 Dec;101(6):2302-9 [3905824] Science. 1987 Feb 20;235(4791):899-901 [3544220] Science. 1988 Dec 2;242(4883):1301-3 [3057629] Lancet. 1989 Aug 5;2(8658):334-5 [2569137] Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10931-6 [9380737] Am J Trop Med Hyg. 1996 Dec;55(6):579-83 [9025680] J Gen Physiol. 1996 Oct;108(4):295-313 [8894978] Antimicrob Agents Chemother. 1996 Aug;40(8):1846-54 [8843292] Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1130-4 [8577727] J Biol Chem. 1995 Sep 22;270(38):22393-8 [7673225] Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):973-7 [7862676] Biochemistry. 1994 Jun 14;33(23):7239-49 [7911682] Mol Biochem Parasitol. 1992 Jun;52(2):149-57 [1620155] J Cell Biol. 1991 Jun;113(5):1033-42 [1674943] Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3382-6 [1673031] Mol Biochem Parasitol. 1990 Aug;42(1):83-91 [2233901] Nature. 1990 May 17;345(6272):253-5 [1970614] Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12833-8 [10536008] Am J Trop Med Hyg. 1999 Jan;60(1):109-18 [9988333] Mol Pharmacol. 1998 Dec;54(6):1140-7 [9855645] Biochem Pharmacol. 1998 Nov 15;56(10):1305-13 [9825729] C R Acad Sci III. 1998 Aug;321(8):689-97 [9769862] Lancet. 1998 Sep 19;352(9132):924 [9752813] Biochem Pharmacol. 1998 Aug 1;56(3):313-20 [9744568] Proc Natl Acad Sci U S A. 1990 Apr;87(8):2931-5 [2183218] Exp Parasitol. 1998 Jun;89(2):262-5 [9635451] Biochem Pharmacol. 1998 Mar 15;55(6):727-36 [9586944] Mol Biochem Parasitol. 1997 Dec 1;90(1):131-44 [9497038] J Cell Biol. 1998 Jan 26;140(2):335-45 [9442109] Cell. 1997 Nov 28;91(5):593-603 [9393853] Science. 1999 Nov 12;286(5443):1351-3 [10558988] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endotoxin (lipopolysaccharide)-induced nitric oxide production in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated Fischer rats: detection of nitrosyl hemoproteins by EPR spectroscopy. AN - 72416613; 11080054 AB - Electron paramagnetic resonance (EPR) spectroscopy was used to study the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on endotoxin (lipopolysaccharide)-induced nitric oxide (NO) production in Fischer rats. We found that rats treated with 50 microg/kg TCDD had increased sensitivity to endotoxin, resulting in an approximately 2-fold increase in the level of NO production detected as nitrosylhemoglobin (HbNO) in venous blood. At lower concentrations (< or = 5 microg/kg), TCDD did not affect the endotoxin-induced NO production. The TNF-alpha serum concentration was found to parallel that of NO. TCDD alone did not induce the production of detectable HbNO or TNF-alpha. We found that TCDD induced a dose-dependent increase in the EPR signal intensity of (Fe(3+)) low-spin methemoprotein complexes found in the liver and kidney. These species with EPR resonance at g = 2.43, 2.26, and 1.92 are attributed to low-spin Fe(3+) in cytochromes P450 and P420. Our data confirm previous studies that have shown that TCDD induces a dose-dependent increase in the production of some cytochrome P450 enzymes. However, in rats that were subsequently challenged with endotoxin, a smaller increase in the EPR intensity of these species was observed. The decrease in the low-spin Fe(3+) cytochrome P450 EPR signal in endotoxin-challenged rats could be due to one or more of the following occurring: (1) cytochrome destruction, (2) reduction of the ferric to the ESR-silent ferrous oxidation state of cytochromes by nitric oxide, and/or (3) formation of ferrous nitrosyl cytochrome complexes that contribute, in part, to the characteristic five-coordinate nitrosyl hemoprotein triplet also observed in these tissues. Since low concentrations of endotoxin can leak from the gut lumen into the systemic circulation, this investigation explores the possibility that endotoxin interaction with TCDD may be, in part, responsible for the effects of TCDD observed in these tissues. JF - Chemical research in toxicology AU - Glover, R E AU - Germolec, D R AU - Patterson, R AU - Walker, N J AU - Lucier, G W AU - Mason, R P AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Science, National Institutes of Health, P.O. Box 12233, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 1051 EP - 1055 VL - 13 IS - 10 SN - 0893-228X, 0893-228X KW - Cytochromes KW - 0 KW - Cytokines KW - Endotoxins KW - Hemeproteins KW - Lipopolysaccharides KW - Polychlorinated Dibenzodioxins KW - endotoxin, Escherichia coli KW - 67924-63-4 KW - cytochrome P420 KW - 9035-49-8 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Rats KW - Cytokines -- analysis KW - Animals KW - Rats, Inbred F344 KW - Electron Spin Resonance Spectroscopy KW - Enzyme-Linked Immunosorbent Assay KW - Cytochrome P-450 Enzyme System -- metabolism KW - Kidney -- chemistry KW - Liver -- chemistry KW - Female KW - Cytochromes -- metabolism KW - Hemeproteins -- metabolism KW - Polychlorinated Dibenzodioxins -- toxicity KW - Lipopolysaccharides -- toxicity KW - Hemeproteins -- chemistry KW - Endotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72416613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Endotoxin+%28lipopolysaccharide%29-induced+nitric+oxide+production+in+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin-treated+Fischer+rats%3A+detection+of+nitrosyl+hemoproteins+by+EPR+spectroscopy.&rft.au=Glover%2C+R+E%3BGermolec%2C+D+R%3BPatterson%2C+R%3BWalker%2C+N+J%3BLucier%2C+G+W%3BMason%2C+R+P&rft.aulast=Glover&rft.aufirst=R&rft.date=2000-10-01&rft.volume=13&rft.issue=10&rft.spage=1051&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-26 N1 - Date created - 2001-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced tumorigenesis and reduced transforming growth factor-beta type II receptor in lung tumors from mice with reduced gene dosage of transforming growth factor-beta1. AN - 72403876; 11074608 AB - To elucidate the role of transforming growth factor-beta1 (TGF-beta1) and the TGF-beta type II receptor (TGF-beta RII) as tumor-suppressor genes in lung carcinogenesis, we mated C57BL/6 mice heterozygous (HT) for deletion of the TGF-beta1 gene with A/J mice to produce AJBL6 TGF-beta1 HT progeny and their wild-type (WT) littermates. Immunohistochemical staining, in situ hybridization, and northern blot analyses showed lower staining and hybridization for TGF-beta1 protein and mRNA, respectively, in the lungs of normal HT mice versus WT mice. Competitive reverse transcription-polymerase chain reaction (CRT-PCR) amplification showed the level of TGF-beta1 mRNA in the lungs of HT mice to be fourfold lower than the level in WT lung. When challenged with ethyl carbamate, lung adenomas were detected in 55% of HT mice by 4 mo but only in 25% of WT littermates at this time. Whereas all HT mice had adenomas by 6 mo, it was not until 10 mo before all WT mice had adenomas. After 12 mo, the average number of adenomas was fivefold higher in HT lungs than in WT lungs. Most dramatic was the appearance of lung carcinomas in HT mice 8 mo before they were visible in WT mice. Thus, the AJBL6 TGF-beta1 HT mouse provides an excellent model system to examine carcinogen-induced lung tumorigenesis by increasing progressive lesion incidence and multiplicity relative to their WT littermates. Immunohistochemical staining showed expression of the TGF-beta type I receptor (TGF-beta RI) at moderate to strong levels in lung adenomas and carcinomas in HT and WT mice. In contrast, whereas weak immunostaining for TGF-beta RII was detected in 67% of HT carcinomas at 12 mo, only 22% of WT carcinomas showed weak staining for this protein. Individual lung carcinomas showing reduced TGF-beta RII expression and adjacent normal bronchioles were excised from HT lungs using laser capture microdissection, and CRT-PCR amplification of the extracted RNA showed 12-fold less TGF-beta RII mRNA in these carcinomas compared with bronchioles. Decreasing TGF-beta RII mRNA levels occurred with increasing tumorigenesis in lung hyperplasias, adenomas, and carcinomas, with carcinomas having fourfold and sevenfold lower levels of TGF-beta RII mRNA than adenomas and hyperplasias, respectively. These data show enhanced ethyl carbamate-induced lung tumorigenesis in AJBL6 HT mice compared with WT mice, suggesting that both TGF-beta1 alleles are necessary for tumor-suppressor activity. Reduction of TGF-beta RII mRNA expression in progressive stages of lung tumorigenesis in HT mice suggests that loss of TGF-beta RII may play an important role in the promotion of lung carcinogenesis in mice with reduced TGF-beta1 gene dosage when challenged with carcinogen. JF - Molecular carcinogenesis AU - Kang, Y AU - Mariano, J M AU - Angdisen, J AU - Moody, T W AU - Diwan, B A AU - Wakefield, L M AU - Jakowlew, S B AD - Medicine Branch, National Cancer Institute, Rockville, Maryland 20850, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 112 EP - 126 VL - 29 IS - 2 SN - 0899-1987, 0899-1987 KW - Carcinogens KW - 0 KW - RNA, Messenger KW - Receptors, Transforming Growth Factor beta KW - Tgfb1 protein, mouse KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - Urethane KW - 3IN71E75Z5 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 - Animals KW - Blotting, Northern KW - Genes, Tumor Suppressor KW - Carcinogens -- toxicity KW - Mice KW - Lung -- metabolism KW - Reverse Transcriptase Polymerase Chain Reaction KW - RNA, Messenger -- genetics KW - Gene Amplification KW - Mice, Inbred A KW - In Situ Hybridization KW - RNA, Messenger -- metabolism KW - Mice, Inbred C57BL KW - Crosses, Genetic KW - Urethane -- toxicity KW - Gene Dosage KW - Immunohistochemistry KW - Female KW - Male KW - Transforming Growth Factor beta -- biosynthesis KW - Receptors, Transforming Growth Factor beta -- genetics KW - Lung Neoplasms -- genetics KW - Receptors, Transforming Growth Factor beta -- biosynthesis KW - Transforming Growth Factor beta -- genetics KW - Lung Neoplasms -- pathology KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72403876?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+carcinogenesis&rft.atitle=Enhanced+tumorigenesis+and+reduced+transforming+growth+factor-beta+type+II+receptor+in+lung+tumors+from+mice+with+reduced+gene+dosage+of+transforming+growth+factor-beta1.&rft.au=Kang%2C+Y%3BMariano%2C+J+M%3BAngdisen%2C+J%3BMoody%2C+T+W%3BDiwan%2C+B+A%3BWakefield%2C+L+M%3BJakowlew%2C+S+B&rft.aulast=Kang&rft.aufirst=Y&rft.date=2000-10-01&rft.volume=29&rft.issue=2&rft.spage=112&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-30 N1 - Date created - 2000-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The proportions of mutagens among chemicals in commerce. AN - 72403674; 11067778 AB - It has been estimated that there are approximately 80,000 chemicals in commerce. Thus, it is not possible to test all these substances for mutagenicity and carcinogenicity; it is possible, however, to test or make estimates from selected subsets of these chemicals. For example, in the U.S. National Toxicology Program (NTP), 35% of the chemicals tested for mutagenicity in Salmonella were positive, as were 52% of the chemicals tested for carcinogenicity in rodents. In contrast, in the U.S. EPA Gene-Tox database, the proportions of chemicals that are Salmonella mutagens is 56%. These and other databases may be biased toward positive responses because they generally have been developed to look at specific structural or use classes of chemicals or chemicals suspected of genetic or carcinogenic activity. To address the question of the proportions of mutagens among all chemicals in commerce, a database of 100 chemicals was created from a random selection of chemicals in commerce. These chemicals were tested for mutagenicity in Salmonella and 22% were mutagenic. The mutagenicity of the 46 highest U.S. production organic chemicals was also compiled; 20% were mutagenic. These values provide a more accurate estimate of the proportions of mutagens among chemicals in commerce than can be derived from published mutagenicity databases. Copyright 2000 Academic Press. JF - Regulatory toxicology and pharmacology : RTP AU - Zeiger, E AU - Margolin, B H AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709-2233, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 219 EP - 225 VL - 32 IS - 2 SN - 0273-2300, 0273-2300 KW - Hazardous Substances KW - 0 KW - Mutagens KW - Index Medicus KW - Mutagenicity Tests KW - Humans KW - Government Programs KW - Databases, Factual KW - Salmonella typhimurium -- drug effects KW - Salmonella typhimurium -- genetics KW - Toxicology KW - Commerce -- statistics & numerical data KW - Environmental Exposure -- analysis KW - Mutagens -- toxicity KW - Hazardous Substances -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72403674?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+death+domain+kinase+RIP+is+essential+for+TRAIL+%28Apo2L%29-induced+activation+of+IkappaB+kinase+and+c-Jun+N-terminal+kinase.&rft.au=Lin%2C+Y%3BDevin%2C+A%3BCook%2C+A%3BKeane%2C+M+M%3BKelliher%2C+M%3BLipkowitz%2C+S%3BLiu%2C+Z+G&rft.aulast=Lin&rft.aufirst=Y&rft.date=2000-09-01&rft.volume=20&rft.issue=18&rft.spage=6638&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 - 2000-12-22 N1 - Date created - 2000-12-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Regul Toxicol Pharmacol. 2001 Jun;33(3):399 [11407941] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - De novo synthesis of minus strand RNA by the rotavirus RNA polymerase in a cell-free system involves a novel mechanism of initiation. AN - 72399408; 11073221 AB - The replicase activity of rotavirus open cores has been used to study the synthesis of (-) strand RNA from viral (+) strand RNA in a cell-free replication system. The last 7 nt of the (+) strand RNA, 5'-UGUGACC-3', are highly conserved and are necessary for efficient (-) strand synthesis in vitro. Characterization of the cell-free replication system revealed that the addition of NaCl inhibited (-) strand synthesis. By preincubating open cores with (+) strand RNA and ATP, CTP, and GTP prior to the addition of NaCl and UTP, the salt-sensitive step was overcome. Thus, (-) strand initiation, but not elongation, was a salt-sensitive process in the cell-free system. Further analysis of the requirements for initiation showed that preincubating open cores and the (+) strand RNA with GTP or UTP, but not with ATP or CTP, allowed (-) strand synthesis to occur in the presence of NaCl. Mutagenesis suggested that in the presence of GTP, (-) strand synthesis initiated at the 3'-terminal C residue of the (+) strand template, whereas in the absence of GTP, an aberrant initiation event occurred at the third residue upstream from the 3' end of the (+) strand RNA. During preincubation with GTP, formation of the dinucleotides pGpG and ppGpG was detected; however, no such products were made during preincubation with ATP, CTP, or UTP. Replication assays showed that pGpG, but not GpG, pApG, or ApG, served as a specific primer for (-) strand synthesis and that the synthesis of pGpG may occur by a template-independent process. From these data, we conclude that initiation of rotavirus (-) strand synthesis involves the formation of a ternary complex consisting of the viral RNA-dependent RNA polymerase, viral (+) strand RNA, and possibly a 5'-phosphorylated dinucleotide, that is, pGpG or ppGpG. JF - RNA (New York, N.Y.) AU - Chen, D AU - Patton, J T AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 1455 EP - 1467 VL - 6 IS - 10 SN - 1355-8382, 1355-8382 KW - DNA Primers KW - 0 KW - Nucleotides KW - RNA, Viral KW - Viral Proteins KW - Sodium Chloride KW - 451W47IQ8X KW - bacteriophage T7 RNA polymerase KW - EC 2.7.7.- KW - RNA Replicase KW - EC 2.7.7.48 KW - DNA-Directed RNA Polymerases KW - EC 2.7.7.6 KW - Index Medicus KW - Nucleotides -- metabolism KW - Sodium Chloride -- antagonists & inhibitors KW - Genes, Viral -- genetics KW - Base Sequence KW - Conserved Sequence -- genetics KW - Virus Replication -- drug effects KW - Kinetics KW - Mutation -- genetics KW - Templates, Genetic KW - Nucleotides -- pharmacology KW - Cell-Free System KW - Sodium Chloride -- pharmacology KW - Transcription, Genetic -- drug effects KW - RNA Replicase -- metabolism KW - RNA, Viral -- biosynthesis KW - Rotavirus -- genetics KW - RNA, Viral -- genetics KW - Rotavirus -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72399408?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=RNA+%28New+York%2C+N.Y.%29&rft.atitle=De+novo+synthesis+of+minus+strand+RNA+by+the+rotavirus+RNA+polymerase+in+a+cell-free+system+involves+a+novel+mechanism+of+initiation.&rft.au=Chen%2C+D%3BPatton%2C+J+T&rft.aulast=Chen&rft.aufirst=D&rft.date=2000-10-01&rft.volume=6&rft.issue=10&rft.spage=1455&rft.isbn=&rft.btitle=&rft.title=RNA+%28New+York%2C+N.Y.%29&rft.issn=13558382&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-16 N1 - Date created - 2000-11-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Virology. 1999 Nov 10;264(1):167-80 [10544142] J Virol. 1999 Feb;73(2):1382-91 [9882343] Virology. 1999 Dec 5;265(1):120-30 [10603323] Nature. 1970 Aug 15;227(5259):680-5 [5432063] J Virol. 1977 Jan;21(1):24-34 [833924] Proc Natl Acad Sci U S A. 1980 May;77(5):2601-5 [6930654] Virology. 1983 Apr 15;126(1):204-12 [6302982] J Virol. 1983 Jul;47(1):125-36 [6306269] J Virol. 1985 Mar;53(3):949-54 [2983101] J Virol. 1986 May;58(2):561-8 [2422396] Virology. 1989 Oct;172(2):616-27 [2552662] Virology. 1990 Jul;177(1):324-31 [2162107] J Virol. 1990 Oct;64(10):4988-96 [2168982] J Gen Virol. 1991 Feb;72 ( Pt 2):325-32 [1704411] J Virol. 1991 Jul;65(7):3964-7 [1645806] Virology. 1992 May;188(1):77-84 [1314468] J Virol. 1994 Nov;68(11):7030-9 [7933085] J Gen Virol. 1994 Dec;75 ( Pt 12):3423-30 [7996135] J Virol. 1996 May;70(5):2736-42 [8627747] J Virol. 1996 Jun;70(6):3961-71 [8648733] Nature. 1996 Aug 1;382(6590):471-3 [8684490] J Virol. 1996 Oct;70(10):6826-30 [8794323] J Virol. 1996 Nov;70(11):7833-41 [8892905] J Virol. 1996 Nov;70(11):7940-7 [8892917] Adv Virus Res. 1996;47:159-251 [8895833] J Virol. 1997 Oct;71(10):7353-60 [9311813] J Virol. 1997 Dec;71(12):9618-26 [9371626] J Virol. 1998 Sep;72(9):7387-96 [9696835] J Virol. 1999 Dec;73(12):9934-43 [10559306] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Concepts in design of comparative clinical trials of antifungal therapy in neutropenic patients. AN - 72373286; 11053799 AB - Fundamental to the successful implementation of antifungal compounds in neutropenic patients is the appropriate design of comparative clinical trials investigating their safety and efficacy. The key elements of comparative clinical trial design include issues of enrollment, stratification, randomization, blinding, administration of study drugs, monitoring of drug toxicity, definitions, and key statistical elements of end points, sample size, and tools for data analysis. The initial selection of compounds and the timing of initiation of antifungal therapy in comparative clinical trials are predicated to a large degree on the in vitro and in vivo activities, plasma pharmacokinetics, profiles of safety and toxicity of the study drugs. Phase I and II studies have a critical role in designing comparative clinical trials of antifungal therapy by providing data on safety, tolerance, and plasma pharmacokinetics of the investigational agent. As new antifungal agents are developed in response to the challenge of invasive fungal infections in immunocompromised patients with cancer, thoughtfully designed and carefully implemented clinical trials will be essential in determining the future utility of these promising compounds. JF - International journal of antimicrobial agents AU - Walsh, T J AU - Roden, M AU - Roilides, E AU - Groll, A AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bldg 10, Rm 13N-240, Bethesda, MD 20892, USA. walsht@mail.nih.gov Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 151 EP - 156 VL - 16 IS - 2 SN - 0924-8579, 0924-8579 KW - Antifungal Agents KW - 0 KW - Index Medicus KW - Humans KW - Research Design KW - Mycoses -- prevention & control KW - Neutropenia -- complications KW - Clinical Trials as Topic KW - Mycoses -- drug therapy KW - Antifungal Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72373286?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+antimicrobial+agents&rft.atitle=Concepts+in+design+of+comparative+clinical+trials+of+antifungal+therapy+in+neutropenic+patients.&rft.au=Walsh%2C+T+J%3BRoden%2C+M%3BRoilides%2C+E%3BGroll%2C+A&rft.aulast=Walsh&rft.aufirst=T&rft.date=2000-10-01&rft.volume=16&rft.issue=2&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=International+journal+of+antimicrobial+agents&rft.issn=09248579&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-20 N1 - Date created - 2000-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Redox control of aryl sulfotransferase specificity. AN - 72357682; 11051102 AB - Aryl sulfotransferase IV from rat liver has the very broad substrate range that is characteristic of the enzymes of detoxication. With the conventional assay substrates, 4-nitrophenol and PAPS, sulfation was considered optimal at pH 5.5 whereas the enzyme in the physiological pH range was curiously ineffective. These properties would seem to preclude a physiological function for this cytosolic enzyme. Partial oxidation of the enzyme, however, results not only in a substantial increase in the rate of sulfation of 4-nitrophenol at physiological pH but also in a shift of the pH optimum to this range and radically altered overall substrate specificity. The mechanism for this dependence on redox environment involves oxidation at Cys66, a process previously shown to occur by formation of a mixed disulfide with glutathione or by the formation of an internal disulfide with Cys232. Oxidation at Cys66 acts only as a molecular redox switch and is not directly part of the catalytic mechanism. Underlying the activation process is a change in the nature of the ternary complex formed between enzyme, phenol, and the reaction product, adenosine 3',5'-bisphosphate. The reduced enzyme gives rise to an inhibitory, dead-end ternary complex, the stability of which is dictated by the ionization of the specific phenol substrate. Ternary complex formation impedes the binding of PAPS that is necessary to initiate a further round of the reaction and is manifest as profound, substrate-dependent inhibition. In contrast, the ternary complex formed when the enzyme is in the partially oxidized state allows binding of PAPS and the unhindered completion of the reaction cycle. JF - Archives of biochemistry and biophysics AU - Marshall, A D AU - McPhie, P AU - Jakoby, W B AD - Laboratory of Biochemistry and Metabolism, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/10/01/ PY - 2000 DA - 2000 Oct 01 SP - 95 EP - 104 VL - 382 IS - 1 SN - 0003-9861, 0003-9861 KW - Disulfides KW - 0 KW - Nitrophenols KW - Nucleotides KW - Recombinant Proteins KW - Phenol KW - 339NCG44TV KW - Phosphoadenosine Phosphosulfate KW - 482-67-7 KW - Arylsulfotransferase KW - EC 2.8.2.1 KW - Glutathione KW - GAN16C9B8O KW - Cysteine KW - K848JZ4886 KW - Oxygen KW - S88TT14065 KW - 4-nitrophenol KW - Y92ZL45L4R KW - Index Medicus KW - Nucleotides -- metabolism KW - Animals KW - Phosphoadenosine Phosphosulfate -- pharmacology KW - Dose-Response Relationship, Drug KW - Oxygen -- metabolism KW - Hydrogen-Ion Concentration KW - Nitrophenols -- pharmacology KW - Protein Binding KW - Hydrolysis KW - Rats KW - Mutagenesis, Site-Directed KW - Cysteine -- chemistry KW - Phenol -- metabolism KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Glutathione -- chemistry KW - Spectrophotometry KW - Chromatography, Thin Layer KW - Models, Chemical KW - Substrate Specificity KW - Recombinant Proteins -- chemistry KW - Time Factors KW - Oxidation-Reduction KW - Liver -- enzymology KW - Arylsulfotransferase -- chemistry KW - Arylsulfotransferase -- metabolism KW - Arylsulfotransferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72357682?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Redox+control+of+aryl+sulfotransferase+specificity.&rft.au=Marshall%2C+A+D%3BMcPhie%2C+P%3BJakoby%2C+W+B&rft.aulast=Marshall&rft.aufirst=A&rft.date=2000-10-01&rft.volume=382&rft.issue=1&rft.spage=95&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 - 2000-11-13 N1 - Date created - 2000-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel therapeutic agents for the treatment of myelodysplastic syndromes. AN - 72355888; 11049023 AB - Few chemotherapy agents have demonstrated activity in patients with myelodysplastic syndromes (MDS) and supportive management remains the standard of care. An increasing number of new drugs in development are being directed at specific molecular or biological targets of these diseases. Topotecan, a topoisomerase I inhibitor, has shown single-agent activity and is now being combined with other agents, including cytarabine. The aminothiol amifostine induces responses in about 30% of patients; however, its role is still being clarified. Agents that inhibit histone deacetylase and target DNA hypermethylation, thus permitting derepression of normal genes, include 5-azacytidine, decitabine, phenylbutyrate, and depsipeptide. Arsenic trioxide has demonstrated impressive activity in acute promyelocytic leukemia and preclinical data suggest the potential for activity in MDS. UCN-01 is a novel agent that inhibits protein kinase C and other protein kinases important for progression through the G1 and G2 phases of the cell cycle. Dolastatin-10 has extremely potent in vitro activity against a variety of tumor cell lines. Since its dose-limiting toxicities include myelosuppression, it is being studied in acute myelogenous leukemia (AML) and MDS. Ras may play a role in MDS, and activation of this gene and its signaling pathways may require farnesylation. Several farnesyl transferase inhibitors are now available for study in patients with MDS. An increasing body of data suggests a possible role for angiogenesis in MDS, and several antiangiogenesis agents are in clinical trials, including thalidomide, SU5416, and anti-vascular endothelial growth factor (VEGF) antibodies. Development of new drugs and regimens will be facilitated by recently developed standardized response criteria. Future clinical trials should focus on rational combinations of these agents and others with the goal of curing patients with MDS. JF - Seminars in oncology AU - Cheson, B D AU - Zwiebel, J A AU - Dancey, J AU - Murgo, A AD - Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 560 EP - 577 VL - 27 IS - 5 SN - 0093-7754, 0093-7754 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Humans KW - Myelodysplastic Syndromes -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72355888?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Novel+therapeutic+agents+for+the+treatment+of+myelodysplastic+syndromes.&rft.au=Cheson%2C+B+D%3BZwiebel%2C+J+A%3BDancey%2C+J%3BMurgo%2C+A&rft.aulast=Cheson&rft.aufirst=B&rft.date=2000-10-01&rft.volume=27&rft.issue=5&rft.spage=560&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 - 2000-11-02 N1 - Date created - 2000-10-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Randomized trial of fenretinide in superficial bladder cancer using DNA flow cytometry as an intermediate end point. AN - 72355442; 11045790 AB - Retinoids have shown a potential activity in preventing tumor recurrence in superficial bladder cancer. We assessed the activity of the synthetic retinoid fenretinide in superficial bladder cancer using DNA flow cytometry and conventional cytology as surrogate biomarkers. A total of 99 subjects with resected superficial bladder cancer (pTa, pT1) were randomized to either fenretinide (200 mg day p.o. for 24 months) or no intervention. Cystoscopy and bladder washing for DNA flow cytometry end points (proportion of DNA aneuploid histograms, hyperdiploid fraction, and percentage of apoptotic cells) and proportion of abnormal cytological examinations were repeated every 4 months for up to 36 months. The primary study end point was the proportion of DNA aneuploid histograms after 12 months. This figure was 48.9% in the fenretinide arm and 41.9% in the control arm (odds ratio, 1.16; 95% confidence interval, 0.44-3.07). There was no difference in any other response biomarker between the two groups up to 36 months, nor was any biomarker able to predict recurrence risk. Recurrence-free survival was comparable between the arms (27 events in the fenretinide arm versus 21 in the control arm; P = 0.36). Twelve subjects in the fenretinide arm complained of diminished dark adaptability, and nine subjects in the fenretinide arm versus one control subject had mild dermatological alterations. We conclude that fenretinide showed a lack of effect on the DNA content distribution and the morphology of urothelial cells obtained in serial bladder washings. Recurrence-free survival was comparable between groups. Because our data are hampered by the lack of predictivity of the selected biomarkers, additional studies are necessary to assess the activity of fenretinide in preventing bladder cancer. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Decensi, A AU - Torrisi, R AU - Bruno, S AU - Costantini, M AU - Curotto, A AU - Nicolò, G AU - Malcangi, B AU - Baglietto, L AU - Bruttini, G P AU - Gatteschi, B AU - Rondanina, G AU - Varaldo, M AU - Perloff, M AU - Malone, W F AU - Bruzzi, P AD - Division of Medical Oncology II, National Cancer Institute, Genoa, Italy. andrea.decensi@ieo.it Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 1071 EP - 1078 VL - 9 IS - 10 SN - 1055-9965, 1055-9965 KW - Antineoplastic Agents KW - 0 KW - Biomarkers, Tumor KW - DNA, Neoplasm KW - Fenretinide KW - 187EJ7QEXL KW - Index Medicus KW - Urinary Bladder -- pathology KW - Disease-Free Survival KW - Humans KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Flow Cytometry KW - Neoplasm Recurrence, Local KW - Male KW - Female KW - Fenretinide -- adverse effects KW - Fenretinide -- therapeutic use KW - Urinary Bladder Neoplasms -- genetics KW - Urinary Bladder Neoplasms -- drug therapy KW - Biomarkers, Tumor -- analysis KW - DNA, Neoplasm -- genetics KW - DNA, Neoplasm -- analysis KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72355442?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Randomized+trial+of+fenretinide+in+superficial+bladder+cancer+using+DNA+flow+cytometry+as+an+intermediate+end+point.&rft.au=Decensi%2C+A%3BTorrisi%2C+R%3BBruno%2C+S%3BCostantini%2C+M%3BCurotto%2C+A%3BNicol%C3%B2%2C+G%3BMalcangi%2C+B%3BBaglietto%2C+L%3BBruttini%2C+G+P%3BGatteschi%2C+B%3BRondanina%2C+G%3BVaraldo%2C+M%3BPerloff%2C+M%3BMalone%2C+W+F%3BBruzzi%2C+P&rft.aulast=Decensi&rft.aufirst=A&rft.date=2000-10-01&rft.volume=9&rft.issue=10&rft.spage=1071&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/10.1038%2F79649 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-08 N1 - Date created - 2001-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of hydrocodone in human urine following controlled codeine administration. AN - 72355320; 11043655 AB - Allegations of illicit hydrocodone use have been made against individuals who were taking physician-prescribed oral codeine but denied hydrocodone use. Drug detection was based on positive urine opiate immunoassay results with subsequent confirmation of hydrocodone by gas chromatography-mass spectrometry (GC-MS). In these cases, low concentrations of hydrocodone (approximately 100 ng/mL) were detected in urine specimens containing high concentrations of codeine (> 5000 ng/mL). Although hydrocodone has been reported to be a minor metabolite of codeine in humans, there has been little study of this unusual metabolic pathway. We investigated the occurrence of hydrocodone excretion in urine specimens of subjects who were administered codeine. In a controlled study, two African-American and three Caucasian male subjects were orally administered 60 mg/70 kg/day and 120 mg/70 kg/day of codeine sulfate on separate days. Urine specimens were collected prior to and for approximately 30-40 h following drug administration. In a second case study, a postoperative patient self-administered 960 mg/day (240 mg four times per day) of physician-prescribed oral codeine phosphate, and urine specimens were collected on the third day of the dosing regimen. Samples from both studies were extracted on copolymeric solid-phase columns and analyzed by GC-MS. In the controlled study, codeine was detected in the first post-drug-administration specimen from all subjects. Peak concentrations appeared at 2-5 h and ranged from 1475 to 61,695 ng/mL. Codeine was detected at concentrations above the 10-ng/mL limit of quantitation for the assay throughout the 40-h collection period. Hydrocodone was initially detected at 6-11 h following codeine administration and peaked at 10-18 h (32-135 ng/mL). Detection times for hydrocodone following oral codeine administration ranged from 6 h to the end of the collection period. Confirmation of hydrocodone in a urine specimen was always accompanied by codeine detection. Codeine and hydrocodone were detected in all specimens collected from the postoperative patient, and concentrations ranged from 2099 to 4020 and 47 to 129 ng/mL, respectively. Analyses of the codeine formulations administered to subjects revealed no hydrocodone present at the limit of detection of the assay (10 ng/mL). These data confirm that hydrocodone can be produced as a minor metabolite of codeine in humans and may be excreted in urine at concentrations as high as 11% of parent drug concentration. Consequently, the detection of minor amounts of hydrocodone in urine containing high concentrations of codeine should not be interpreted as evidence of hydrocodone abuse. JF - Journal of analytical toxicology AU - Oyler, J M AU - Cone, E J AU - Joseph, R E AU - Huestis, M A AD - Chemistry and Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 530 EP - 535 VL - 24 IS - 7 SN - 0146-4760, 0146-4760 KW - Analgesics, Opioid KW - 0 KW - Hydrocodone KW - 6YKS4Y3WQ7 KW - Codeine KW - Q830PW7520 KW - Index Medicus KW - Administration, Oral KW - Dose-Response Relationship, Drug KW - Humans KW - Gas Chromatography-Mass Spectrometry KW - Opioid-Related Disorders -- rehabilitation KW - Postoperative Period KW - Male KW - Codeine -- analysis KW - Codeine -- administration & dosage KW - Substance Abuse Detection KW - Hydrocodone -- urine KW - Codeine -- therapeutic use KW - Codeine -- pharmacokinetics KW - Analgesics, Opioid -- therapeutic use KW - Analgesics, Opioid -- pharmacokinetics KW - Analgesics, Opioid -- analysis KW - Analgesics, Opioid -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72355320?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+analytical+toxicology&rft.atitle=Identification+of+hydrocodone+in+human+urine+following+controlled+codeine+administration.&rft.au=Oyler%2C+J+M%3BCone%2C+E+J%3BJoseph%2C+R+E%3BHuestis%2C+M+A&rft.aulast=Oyler&rft.aufirst=J&rft.date=2000-10-01&rft.volume=24&rft.issue=7&rft.spage=530&rft.isbn=&rft.btitle=&rft.title=Journal+of+analytical+toxicology&rft.issn=01464760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-22 N1 - Date created - 2001-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Monitoring opiate use in substance abuse treatment patients with sweat and urine drug testing. AN - 72353290; 11043653 AB - Although urine testing remains the standard for drug use monitoring, sweat testing for drugs of abuse is increasing, especially in criminal justice programs. One reason for this increase is sweat testing may widen the detection window compared to urine testing. Drug metabolites are rapidly excreted in urine limiting the window of detection of a single use to a few days. In contrast, sweat collection devices can be worn for longer periods of time. This study was designed to compare the efficacy of sweat testing versus urine testing for detecting drug use. Paired sweat patches that were applied and removed weekly on Tuesdays were compared to 3-5 consecutive urine specimens collected Mondays, Wednesdays, and Fridays (355 matched sweat and urine specimen sets) from 44 patients in a methadone-maintenance outpatient treatment program. All patches (N = 925) were extracted in 2.5 mL of solvent and analyzed by ELISA immunoassay for opiates (cutoff concentration 10 ng/mL). A subset (N = 389) of patches was analyzed by gas chromatography-mass spectrometry (GC-MS). Urine specimens (N = 1886) were subjected to qualitative analysis by EMIT (cutoff 300 ng/mL). Results were evaluated to (1) determine the identity and relative amounts of opiates in sweat; (2) assess replicability in duplicate patches; (3) compare ELISA and GC-MS results for opiates in sweat; and (4) compare the detection of opiate use by sweat and urine testing. Opiates were detected in 38.5% of the sweat patches with the ELISA screen. GC-MS analysis confirmed 83.4% of the screen-positive sweat patches for heroin, 6-acetylmorphine, morphine, and/or codeine (cutoff concentration 5 ng/mL) and 90.2% of the screen-negative patches. The sensitivity, specificity, and efficiency of ELISA opiate results as compared to GC-MS results in sweat were 96.7%, 72.2%, and 89.5%, respectively. Heroin and/or 6-acetylmorphine were detected in 78.1% of the GC-MS-positive sweat patches. Median concentrations of heroin, 6-acetylmorphine, morphine, and codeine in the positive sweat samples were 10.5, 13.6, 15.9, and 13.0 ng/mL, respectively. Agreement in paired sweat patch test results was 90.6% by ELISA analysis. For the purposes of this comparison of ELISA sweat patch to EMIT urine screening for opiates, the more commonly used urine test was considered to be the reference method. The sensitivity, specificity, and efficiency of sweat patch results to urine results for opiates were 68.6%, 86.1%, and 78.6%, respectively. There were 13.5% false-negative and 7.9% false-positive sweat results as compared to urine tests. Analysis of sweat patches provides an alternate method for objectively monitoring drug use and provides an advantage over urine drug testing by extending drug detection times to one week or longer. In addition, identification of heroin and/or 6-acetylmorphine in sweat patches confirmed the use of heroin in 78.1% of the positive cases and differentiated illicit heroin use from possible ingestion of codeine or opiate-containing foods. However, the percentage of false-negative results, at least in this treatment population, indicates that weekly sweat testing may be less sensitive than thrice weekly urine testing in detecting opiate use. JF - Journal of analytical toxicology AU - Huestis, M A AU - Cone, E J AU - Wong, C J AU - Umbricht, A AU - Preston, K L AD - Chemistry and Drug Metabolism Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland 21224, USA. mhuestis@irp.nida.nih.gov Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 509 EP - 521 VL - 24 IS - 7 SN - 0146-4760, 0146-4760 KW - Narcotics KW - 0 KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Sensitivity and Specificity KW - Methadone -- therapeutic use KW - Reproducibility of Results KW - Enzyme Multiplied Immunoassay Technique KW - Humans KW - Aged KW - Patch Tests KW - Adult KW - Gas Chromatography-Mass Spectrometry KW - Enzyme-Linked Immunosorbent Assay KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Opioid-Related Disorders -- diagnosis KW - Sweat -- chemistry KW - Narcotics -- immunology KW - Narcotics -- urine KW - Narcotics -- therapeutic use KW - Opioid-Related Disorders -- rehabilitation KW - Opioid-Related Disorders -- urine KW - Substance Abuse Detection -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72353290?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+analytical+toxicology&rft.atitle=Monitoring+opiate+use+in+substance+abuse+treatment+patients+with+sweat+and+urine+drug+testing.&rft.au=Huestis%2C+M+A%3BCone%2C+E+J%3BWong%2C+C+J%3BUmbricht%2C+A%3BPreston%2C+K+L&rft.aulast=Huestis&rft.aufirst=M&rft.date=2000-10-01&rft.volume=24&rft.issue=7&rft.spage=509&rft.isbn=&rft.btitle=&rft.title=Journal+of+analytical+toxicology&rft.issn=01464760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-22 N1 - Date created - 2001-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of all-trans and 9-cis retinoic acid on growth and metastasis of xenotransplanted canine osteosarcoma cells in athymic mice. AN - 72346644; 11039554 AB - To determine effects of all-trans and 9-cis retinoic acid (RA) on tumor growth and metastatic ability of canine osteosarcoma cells transplanted into athymic (nude) mice. Forty-five 5-week-old female BALB/c nude mice. 1 X 10(7) POS osteosarcoma cells were transplanted subcutaneously into the intrascapular region of mice. All-trans RA (3 or 30 microg/kg of body weight in 0.1 ml of sesame oil), 9-cis RA (3 or 30 mg/kg in 0.1 ml of sesame oil), or sesame oil (0.1 ml; control treatment) were administered intragastrically 5 d/wk for 4 weeks beginning 3 days after transplantation (n = 4 mice/group) or after formation of a palpable tumor (5 mice/group). Tumor weight was estimated weekly by measuring tumor length and width, and retinoid toxic effects were evaluated daily. Two weeks after the final treatment, mice were euthanatized, and number of mice with pulmonary metastases was determined. Adverse treatment effects were not detected. Tumor weight was less in mice treated with either dose of 9-cis RA than in control mice, although this difference was not significant. Treatment with 30 mg of 9-cis RA/kg initiated after tumor formation significantly reduced the incidence of pulmonary metastasis, compared with the control group. 9-cis RA decreased the incidence of pulmonary metastasis in nude mice transplanted with canine osteosarcoma cells and may be a potential adjunct therapy for treatment of osteosarcoma in dogs. JF - American journal of veterinary research AU - Hong, S H AU - Kadosawa, T AU - Mochizuki, M AU - Matsunaga, S AU - Nishimura, R AU - Sasaki, N AD - Pediatrics Oncology Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 1241 EP - 1244 VL - 61 IS - 10 SN - 0002-9645, 0002-9645 KW - Antineoplastic Agents KW - 0 KW - alitretinoin KW - 1UA8E65KDZ KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - Neoplasm Transplantation KW - Animals KW - Tumor Cells, Cultured KW - Dogs KW - Transplantation, Heterologous KW - Mice, Nude KW - Mice KW - Neoplasm Metastasis -- prevention & control KW - Mice, Inbred BALB C KW - Female KW - Bone Neoplasms -- veterinary KW - Osteosarcoma -- drug therapy KW - Lung Neoplasms -- secondary KW - Osteosarcoma -- veterinary KW - Osteosarcoma -- pathology KW - Bone Neoplasms -- drug therapy KW - Dog Diseases -- pathology KW - Dog Diseases -- drug therapy KW - Bone Neoplasms -- pathology KW - Antineoplastic Agents -- therapeutic use KW - Tretinoin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72346644?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+veterinary+research&rft.atitle=Effect+of+all-trans+and+9-cis+retinoic+acid+on+growth+and+metastasis+of+xenotransplanted+canine+osteosarcoma+cells+in+athymic+mice.&rft.au=Hong%2C+S+H%3BKadosawa%2C+T%3BMochizuki%2C+M%3BMatsunaga%2C+S%3BNishimura%2C+R%3BSasaki%2C+N&rft.aulast=Hong&rft.aufirst=S&rft.date=2000-10-01&rft.volume=61&rft.issue=10&rft.spage=1241&rft.isbn=&rft.btitle=&rft.title=American+journal+of+veterinary+research&rft.issn=00029645&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-15 N1 - Date created - 2001-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ovarian tumors in rats induced by chronic 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment. AN - 72334424; 11034082 AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a multispecies reproductive toxicant, and it has been recently classified by IARC as a known human carcinogen. Here, we report that TCDD promotes the development of ovarian tumors in an initiation-promotion model in female Sprague Dawley rats. Rats were initiated with diethylnitrosamine (DEN) or vehicle at 70 days of age. Starting 2 or 18 weeks after initiation, rats were exposed biweekly to TCDD at a daily average dose of 125 ng/kg/day for 14, 30, or 60 weeks continuously or for 30 weeks plus withdrawal periods of 16 or 30 weeks. Fifteen of 76 (20%) rats initiated with DEN and promoted with TCDD for various lengths of time developed ovarian sex cord-stromal tumors of Sertoli cell type, whereas no ovarian tumors developed in 86 rats used as vehicle controls or that received DEN alone or TCDD alone. The highest tumor incidence occurred in 6 of 14 rats (43%) after 60 weeks of continuous TCDD after DEN initiation. One of six rats developed a tumor by 30 weeks of exposure. Because most effects of TCDD can be attributed to its activation of the aryl hydrocarbon receptor (AhR), the presence and localization of AhR was determined in the rat ovary and in the ovarian tumors by reverse transcription-PCR, immunohistochemistry, and in situ hybridization. AhR was localized to oocytes, granulosa and thecal cells of growing follicles, surface epithelial cells, and epithelial cells lining single tubules in ovaries from adult control Sprague Dawley rats. Neoplastic cells in the ovarian tumors were also positive for both AhR message and protein. These results indicate that the ability of TCDD to cause ovarian tumors is dependent on initiation, length of promotion, and age of the animal when exposed and evaluated. The tumor type induced by TCDD in this experimental system is the same histological subtype as that reported from an early study of youngsters exposed during an industrial accident in Seveso, Italy. JF - Cancer research AU - Davis, B J AU - Mccurdy, E A AU - Miller, B D AU - Lucier, G W AU - Tritscher, A M AD - Laboratory of Women's, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Davis1@NIEHS.NIH.GOV Y1 - 2000/10/01/ PY - 2000 DA - 2000 Oct 01 SP - 5414 EP - 5419 VL - 60 IS - 19 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - Carcinogens, Environmental KW - Environmental Pollutants KW - Polychlorinated Dibenzodioxins KW - Receptors, Aryl Hydrocarbon KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Progesterone KW - 4G7DS2Q64Y KW - Estradiol KW - 4TI98Z838E KW - Index Medicus KW - Animals KW - Drug Administration Schedule KW - Environmental Pollutants -- toxicity KW - Sertoli Cell Tumor -- chemically induced KW - Ovary -- drug effects KW - Rats KW - Rats, Sprague-Dawley KW - Estradiol -- blood KW - Receptors, Aryl Hydrocarbon -- physiology KW - Drug Synergism KW - Progesterone -- blood KW - Female KW - Sertoli Cell Tumor -- pathology KW - Ovarian Neoplasms -- pathology KW - Polychlorinated Dibenzodioxins -- toxicity KW - Ovarian Neoplasms -- chemically induced KW - Carcinogens, Environmental -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72334424?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Ovarian+tumors+in+rats+induced+by+chronic+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin+treatment.&rft.au=Davis%2C+B+J%3BMccurdy%2C+E+A%3BMiller%2C+B+D%3BLucier%2C+G+W%3BTritscher%2C+A+M&rft.aulast=Davis&rft.aufirst=B&rft.date=2000-10-01&rft.volume=60&rft.issue=19&rft.spage=5414&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 - 2000-10-27 N1 - Date created - 2000-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NK cell inhibitory receptors prevent tyrosine phosphorylation of the activation receptor 2B4 (CD244). AN - 72332094; 11034353 AB - 2B4 is an NK cell activation receptor that can provide a co-stimulatory signal to other activation receptors and whose mode of signal transduction is still unknown. We show that cross-linking of 2B4 on NK cells results in its rapid tyrosine phosphorylation, implying that this initial step in 2B4 signaling does not require coligation of other receptors. Ligation of 2B4 in the context of an NK cell-target cell interaction leads to 2B4 tyrosine phosphorylation, target cell lysis, and IFN-gamma release. Coligation of 2B4 with the inhibitory receptors killer cell Ig-like receptor (KIR)2DL1 or CD94/NKG2 completely blocks NK cell activation. The rapid tyrosine phosphorylation of 2B4 observed upon contact of NK cells with sensitive target cells is abrogated when KIR2DL1 or CD94/NKG2 are engaged by their cognate MHC class I ligand on resistant target cells. These results demonstrate that NK inhibitory receptors can interfere with a step as proximal as phosphorylation of an activation receptor. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Watzl, C AU - Stebbins, C C AU - Long, E O AD - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA. Y1 - 2000/10/01/ PY - 2000 DA - 2000 Oct 01 SP - 3545 EP - 3548 VL - 165 IS - 7 SN - 0022-1767, 0022-1767 KW - Antigens, CD KW - 0 KW - CD244 protein, human KW - KLRC1 protein, human KW - KLRD1 protein, human KW - Lectins, C-Type KW - Membrane Glycoproteins KW - NK Cell Lectin-Like Receptor Subfamily C KW - NK Cell Lectin-Like Receptor Subfamily D KW - Receptors, Immunologic KW - Receptors, KIR KW - Receptors, KIR2DL1 KW - Receptors, Natural Killer Cell KW - Signaling Lymphocytic Activation Molecule Family KW - Tyrosine KW - 42HK56048U KW - Abridged Index Medicus KW - Index Medicus KW - Antigens, CD -- physiology KW - Phosphorylation KW - Humans KW - Cytotoxicity Tests, Immunologic KW - Cell Communication -- immunology KW - Cytotoxicity, Immunologic KW - Membrane Glycoproteins -- physiology KW - Lymphocyte Activation -- immunology KW - Receptors, Immunologic -- physiology KW - Membrane Glycoproteins -- antagonists & inhibitors KW - Tyrosine -- metabolism KW - Killer Cells, Natural -- metabolism KW - Killer Cells, Natural -- immunology KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72332094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=NK+cell+inhibitory+receptors+prevent+tyrosine+phosphorylation+of+the+activation+receptor+2B4+%28CD244%29.&rft.au=Watzl%2C+C%3BStebbins%2C+C+C%3BLong%2C+E+O&rft.aulast=Watzl&rft.aufirst=C&rft.date=2000-10-01&rft.volume=165&rft.issue=7&rft.spage=3545&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 - 2000-11-03 N1 - Date created - 2000-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coiled-coil trigger motifs in the 1B and 2B rod domain segments are required for the stability of keratin intermediate filaments. AN - 72330076; 11029054 AB - Many alpha-helical proteins that form two-chain coiled coils possess a 13-residue trigger motif that seems to be required for the stability of the coiled coil. However, as currently defined, the motif is absent from intermediate filament (IF) protein chains, which nevertheless form segmented two-chain coiled coils. In the present work, we have searched for and identified two regions in IF chains that are essential for the stability necessary for the formation of coiled-coil molecules and thus may function as trigger motifs. We made a series of point substitutions with the keratin 5/keratin 14 IF system. Combinations of the wild-type and mutant chains were assembled in vitro and in vivo, and the stabilities of two-chain (one-molecule) and two-molecule assemblies were examined with use of a urea disassembly assay. Our new data document that there is a region located between residues 100 and 113 of the 2B rod domain segment that is absolutely required for molecular stability and IF assembly. This potential trigger motif differs slightly from the consensus in having an Asp residue at position 4 (instead of a Glu) and a Thr residue at position 9 (instead of a charged residue), but there is an absolute requirement for a Glu residue at position 6. Because these 13 residues are highly conserved, it seems possible that this motif functions in all IF chains. Likewise, by testing keratin IF with substitutions in both chains, we identified a second potential trigger motif between residues 79 and 91 of the 1B rod domain segment, which may also be conserved in all IF chains. However, we were unable to find a trigger motif in the 1A rod domain segment. In addition, many other point substitutions had little detectable effect on IF assembly, except for the conserved Lys-23 residue of the 2B rod domain segment. Cross-linking and modeling studies revealed that Lys-23 may lie very close to Glu-106 when two molecules are aligned in the A(22) mode. Thus, the Glu-106 residue may have a dual role in IF structure: it may participate in trigger formation to afford special stability to the two-chain coiled-coil molecule, and it may participate in stabilization of the two-molecule hierarchical stage of IF structure. JF - Molecular biology of the cell AU - Wu, K C AU - Bryan, J T AU - Morasso, M I AU - Jang, S I AU - Lee, J H AU - Yang, J M AU - Marekov, L N AU - Parry, D A AU - Steinert, P M AD - Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 3539 EP - 3558 VL - 11 IS - 10 SN - 1059-1524, 1059-1524 KW - DNA Primers KW - 0 KW - Recombinant Fusion Proteins KW - Keratins KW - 68238-35-7 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Recombinant Fusion Proteins -- analysis KW - Animals KW - Protein Structure, Secondary KW - Base Sequence KW - Sequence Alignment KW - Transfection KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Consensus Sequence KW - Sequence Homology, Amino Acid KW - Cell Line KW - Amino Acid Substitution KW - Recombinant Fusion Proteins -- chemistry KW - Keratins -- genetics KW - Keratins -- chemistry KW - Intermediate Filaments -- ultrastructure KW - Keratins -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72330076?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Coiled-coil+trigger+motifs+in+the+1B+and+2B+rod+domain+segments+are+required+for+the+stability+of+keratin+intermediate+filaments.&rft.au=Wu%2C+K+C%3BBryan%2C+J+T%3BMorasso%2C+M+I%3BJang%2C+S+I%3BLee%2C+J+H%3BYang%2C+J+M%3BMarekov%2C+L+N%3BParry%2C+D+A%3BSteinert%2C+P+M&rft.aulast=Wu&rft.aufirst=K&rft.date=2000-10-01&rft.volume=11&rft.issue=10&rft.spage=3539&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 - 2000-12-07 N1 - Date created - 2000-11-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Biol. 1998 Oct 5;143(1):147-57 [9763427] Curr Opin Struct Biol. 1998 Apr;8(2):177-85 [9631290] Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13419-24 [9811815] J Biol Chem. 1999 Jan 15;274(3):1657-66 [9880545] J Mol Biol. 1999 Mar 12;286(5):1403-20 [10064706] J Invest Dermatol. 1999 Mar;112(3):376-9 [10084317] Br J Dermatol. 1999 May;140(5):815-28 [10354017] Cell Mol Life Sci. 1999 Aug 30;55(11):1416-31 [10518990] Structure. 2000 Mar 15;8(3):223-30 [10745004] J Mol Biol. 2000 May 19;298(5):817-32 [10801351] Q Rev Biophys. 1999 May;32(2):99-187 [10845237] J Mol Biol. 1976 Dec 15;108(3):547-67 [1018318] Methods Enzymol. 1983;91:254-9 [6406786] Proteins. 1990;7(1):1-15 [2184436] Science. 1991 Oct 25;254(5031):539-44 [1948029] Cell. 1992 Feb 21;68(4):699-708 [1739975] J Struct Biol. 1991 Oct;107(2):157-74 [1725489] J Mol Biol. 1993 Mar 20;230(2):436-52 [7681879] Biochemistry. 1993 Sep 28;32(38):10046-56 [7691168] J Biol Chem. 1993 Nov 25;268(33):24916-25 [7693709] J Cell Biol. 1993 Dec;123(6 Pt 1):1517-33 [8253847] Science. 1994 Jan 28;263(5146):488-9 [8290957] EMBO J. 1994 Jun 15;13(12):2849-61 [8026470] Nature. 1994 Sep 1;371(6492):80-3 [8072533] Annu Rev Biochem. 1994;63:345-82 [7979242] Proc Natl Acad Sci U S A. 1995 Jan 3;92(1):92-6 [7816855] Proteins. 1994 Oct;20(2):174-84 [7531336] Protein Eng. 1994 Nov;7(11):1365-72 [7700868] Science. 1995 Apr 21;268(5209):436-9 [7716550] J Mol Biol. 1996 Jan 26;255(3):367-72 [8568882] J Biol Chem. 1997 Dec 19;272(51):32557-65 [9405470] Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2067-72 [9482839] EMBO J. 1998 Apr 1;17(7):1883-91 [9524112] J Mol Biol. 1998 Nov 13;283(5):993-1012 [9799639] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The absence of ribonuclease H1 or H2 alters the sensitivity of Saccharomyces cerevisiae to hydroxyurea, caffeine and ethyl methanesulphonate: implications for roles of RNases H in DNA replication and repair. AN - 72328295; 11029655 AB - RNA of RNA-DNA hybrids can be degraded by ribonucleases H present in all organisms including the eukaryote Saccharomyces cerevisiae. Determination of the number and roles of the RNases H in eukaryotes is quite feasible in S. cerevisiae. Two S. cerevisiae RNases H, related to Escherichia coli RNase HI and HII, are not required for growth under normal conditions, yet, compared with wild-type cells, a double-deletion strain has an increased sensitivity to hydroxyurea (HU) and is hypersensitive to caffeine and ethyl methanesulphonate (EMS). In the absence of RNase H1, RNase H2 activity increases, and cells are sensitive to EMS but not HU and are more tolerant of caffeine; the latter requires RNase H2 activity. Cells missing only RNase H2 exhibit increased sensitive to HU and EMS but not caffeine Mutant phenotypes infer that some RNA-DNA hybrids are recognized by both RNases H1 and H2, while other hybrids appear to be recognized only by RNase H2. Undegraded RNA-DNA hybrids have an effect when DNA synthesis is impaired, DNA damage occurs or the cell cycle is perturbed by exposure to caffeine suggesting a role in DNA replication/repair that can be either beneficial or detrimental to cell viability. JF - Genes to cells : devoted to molecular & cellular mechanisms AU - Arudchandran, A AU - Cerritelli, S AU - Narimatsu, S AU - Itaya, M AU - Shin, D Y AU - Shimada, Y AU - Crouch, R J AD - Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2790, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 789 EP - 802 VL - 5 IS - 10 SN - 1356-9597, 1356-9597 KW - DNA, Fungal KW - 0 KW - Nucleic Acid Synthesis Inhibitors KW - Recombinant Fusion Proteins KW - Caffeine KW - 3G6A5W338E KW - Ethyl Methanesulfonate KW - 9H154DI0UP KW - ribonuclease HII KW - EC 3.1.26.- KW - Ribonuclease H KW - EC 3.1.26.4 KW - ribonuclease HI KW - Hydroxyurea KW - X6Q56QN5QC KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Phenotype KW - Nucleic Acid Synthesis Inhibitors -- pharmacology KW - Cell Nucleus -- enzymology KW - DNA Repair KW - Genes, Fungal KW - DNA, Fungal -- metabolism KW - Cell Cycle KW - DNA Replication KW - Gene Deletion KW - DNA, Fungal -- biosynthesis KW - Saccharomyces cerevisiae -- genetics KW - Ethyl Methanesulfonate -- pharmacology KW - Caffeine -- pharmacology KW - Hydroxyurea -- pharmacology KW - Saccharomyces cerevisiae -- enzymology KW - Ribonuclease H -- metabolism KW - Saccharomyces cerevisiae -- drug effects KW - Saccharomyces cerevisiae -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72328295?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+to+cells+%3A+devoted+to+molecular+%26+cellular+mechanisms&rft.atitle=The+absence+of+ribonuclease+H1+or+H2+alters+the+sensitivity+of+Saccharomyces+cerevisiae+to+hydroxyurea%2C+caffeine+and+ethyl+methanesulphonate%3A+implications+for+roles+of+RNases+H+in+DNA+replication+and+repair.&rft.au=Arudchandran%2C+A%3BCerritelli%2C+S%3BNarimatsu%2C+S%3BItaya%2C+M%3BShin%2C+D+Y%3BShimada%2C+Y%3BCrouch%2C+R+J&rft.aulast=Arudchandran&rft.aufirst=A&rft.date=2000-10-01&rft.volume=5&rft.issue=10&rft.spage=789&rft.isbn=&rft.btitle=&rft.title=Genes+to+cells+%3A+devoted+to+molecular+%26+cellular+mechanisms&rft.issn=13569597&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-01 N1 - Date created - 2000-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A new xeroderma pigmentosum group C poly(AT) insertion/deletion polymorphism. AN - 72323203; 11023539 AB - We found a common biallelic polymorphism (PAT) in the xeroderma pigmentosum complementation group C (XPC) DNA repair gene consisting of an insertion of 83 bases of A and T [poly(AT)] and a 5 base deletion within intron 9. We developed a PCR assay to resolve the XPC PAT+ and PAT- alleles and found that the PAT+ allele frequency was 0.44 in 156 cancer-free donors from the Johns Hopkins School of Public Health, 0.41 in 263 cancer-free donors from the Baltimore Longitudinal Study of Aging and 0.36 in samples from 216 unselected donors from NIH. We also found a single nucleotide polymorphism in exon 15 of the XPC gene (A2920C, Lys939-->Gln) that creates a new enzyme restriction site. This XPC exon 15 single nucleotide polymorphism occurred at a frequency of 0.38 in 98 NIH donors and is in linkage disequilibrium with the PAT locus. We developed an allele-specific complementation assay utilizing post-UV host cell reactivation to assess DNA repair capacity of polymorphic alleles. We found similar DNA repair with XPC 2920A and XPC 2920C. These common polymorphisms in the XPC DNA repair gene may be useful for molecular epidemiological studies of cancer susceptibility. JF - Carcinogenesis AU - Khan, S G AU - Metter, E J AU - Tarone, R E AU - Bohr, V A AU - Grossman, L AU - Hedayati, M AU - Bale, S J AU - Emmert, S AU - Kraemer, K H AD - National Cancer Institute, National Institute of Aging and National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 1821 EP - 1825 VL - 21 IS - 10 SN - 0143-3334, 0143-3334 KW - Poly A KW - 24937-83-5 KW - Poly T KW - 25086-81-1 KW - poly A-T KW - 27156-07-6 KW - Index Medicus KW - Humans KW - Aged KW - Child KW - Linkage Disequilibrium KW - Introns -- genetics KW - Child, Preschool KW - Skin Neoplasms -- genetics KW - Infant KW - DNA Repair -- genetics KW - Exons -- genetics KW - Genotype KW - Alleles KW - Adult KW - Genetic Complementation Test KW - Middle Aged KW - Genetic Predisposition to Disease KW - Adolescent KW - Male KW - Female KW - Poly T -- genetics KW - Poly A -- genetics KW - Xeroderma Pigmentosum -- genetics KW - Polymorphism, Single Nucleotide -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72323203?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+new+xeroderma+pigmentosum+group+C+poly%28AT%29+insertion%2Fdeletion+polymorphism.&rft.au=Khan%2C+S+G%3BMetter%2C+E+J%3BTarone%2C+R+E%3BBohr%2C+V+A%3BGrossman%2C+L%3BHedayati%2C+M%3BBale%2C+S+J%3BEmmert%2C+S%3BKraemer%2C+K+H&rft.aulast=Khan&rft.aufirst=S&rft.date=2000-10-01&rft.volume=21&rft.issue=10&rft.spage=1821&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-03 N1 - Date created - 2000-11-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hemoglobin-based blood substitutes and the hazards of blood radicals. AN - 72316108; 11022843 AB - Cell-free hemoglobins, chemically altered or genetically expressed in microbial host systems, have been developed as oxygen-carrying therapeutics. Site-directed modifications are introduced and serve to stabilize the protein molecules in a tetrameric and/or a polymeric functional form. Animal studies, as well as recent clinical studies, have suggested these proteins probably deliver oxygen to tissues. However, concerns still persist regarding the interference of hemoglobin and its oxidation products with the vascular redox balance, potentially impeding its clinical usefulness. This article reviews our current understanding of heme-mediated toxicities and some of the emerging protective strategies used to overcome hemoglobin side reactions. JF - Free radical research AU - Alayash, A I AD - Laboratory of Plasma Derivatives, Center for Biologics Evaluation and Research, Food and Drug Administration, National Institutes of Health Campus, Bethesda, Maryland 20892, USA. alayash@cber.fda.gov Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 341 EP - 348 VL - 33 IS - 4 SN - 1071-5762, 1071-5762 KW - Blood Substitutes KW - 0 KW - Free Radicals KW - Hemoglobins KW - Recombinant Proteins KW - Solutions KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Oxidation-Reduction KW - Animals KW - Humans KW - Recombinant Proteins -- adverse effects KW - Nitric Oxide -- metabolism KW - Hemoglobins -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72316108?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+research&rft.atitle=Hemoglobin-based+blood+substitutes+and+the+hazards+of+blood+radicals.&rft.au=Alayash%2C+A+I&rft.aulast=Alayash&rft.aufirst=A&rft.date=2000-10-01&rft.volume=33&rft.issue=4&rft.spage=341&rft.isbn=&rft.btitle=&rft.title=Free+radical+research&rft.issn=10715762&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-01 N1 - Date created - 2001-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oligonucleotide microarray based detection of repetitive sequence changes. AN - 72307517; 11013446 AB - Prior studies of oligonucleotide microarray-based mutational analysis have demonstrated excellent sensitivity and specificity except in circumstances where a frameshift mutation occurs in the context of a short repeated sequence. To further evaluate this circumstance, a series of nucleic acid samples having heterozygous mutations within repetitive BRCA1 sequence tracts was prepared and evaluated. These mutations included single nucleotide insertions and deletions in homopolymer runs, insertions and deletions of trinucleotide repeats, and duplications. Two-color comparative hybridization experiments were used wherein wild type reference and test targets are co-hybridized to microarrays designed to screen the entire BRCA1 coding sequence for all possible sequence changes. Mutations in simulated heterozygote samples were detected by observing relative losses of test target hybridization signal to select perfect match oligonucleotide probes. While heterozygous mutations could be readily distinguished above background noise in 9/19 cases, it was not possible to detect alterations in a poly dA/dT tract, small triplet repeat expansions, and a 10 bp direct repeat. Unexpectedly, samples containing (GAT)(3) triplet repeat expansions showed significantly higher affinity toward specific perfect match probes relative to their wild type counterparts. Therefore, markedly increased as well as decreased test sample hybridization to perfect match probes should be used to raise a suspicion of repetitive sequence changes. Copyright 2000 Wiley-Liss, Inc. JF - Human mutation AU - Hacia, J G AU - Edgemon, K AU - Fang, N AU - Mayer, R A AU - Sudano, D AU - Hunt, N AU - Collins, F S AD - National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 354 EP - 363 VL - 16 IS - 4 KW - DNA, Complementary KW - 0 KW - Index Medicus KW - Sensitivity and Specificity KW - Exons -- genetics KW - Trinucleotide Repeat Expansion -- genetics KW - Heterozygote Detection KW - Genes, BRCA1 -- genetics KW - Humans KW - DNA Mutational Analysis KW - Algorithms KW - Nucleic Acid Hybridization KW - Loss of Heterozygosity -- genetics KW - Mutagenesis, Insertional KW - Sequence Analysis, DNA -- methods KW - Oligonucleotide Array Sequence Analysis -- methods KW - Repetitive Sequences, Nucleic Acid -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72307517?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+mutation&rft.atitle=Oligonucleotide+microarray+based+detection+of+repetitive+sequence+changes.&rft.au=Hacia%2C+J+G%3BEdgemon%2C+K%3BFang%2C+N%3BMayer%2C+R+A%3BSudano%2C+D%3BHunt%2C+N%3BCollins%2C+F+S&rft.aulast=Hacia&rft.aufirst=J&rft.date=2000-10-01&rft.volume=16&rft.issue=4&rft.spage=354&rft.isbn=&rft.btitle=&rft.title=Human+mutation&rft.issn=1098-1004&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-27 N1 - Date created - 2000-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A role for cytosolic hsp70 in yeast [PSI(+)] prion propagation and [PSI(+)] as a cellular stress. AN - 72304297; 11014806 AB - [PSI(+)] is a prion (infectious protein) of Sup35p, a subunit of the Saccharomyces cerevisiae translation termination factor. We isolated a dominant allele, SSA1-21, of a gene encoding an Hsp70 chaperone that impairs [PSI(+)] mitotic stability and weakens allosuppression caused by [PSI(+)]. While [PSI(+)] stability is normal in strains lacking SSA1, SSA2, or both, SSA1-21 strains with a deletion of SSA2 cannot propagate [PSI(+)]. SSA1-21 [PSI(+)] strains are hypersensitive to curing of [PSI(+)] by guanidine-hydrochloride and partially cured of [PSI(+)] by rapid induction of the heat-shock response but not by growth at 37 degrees. The number of inheritable [PSI(+)] particles is significantly reduced in SSA1-21 cells. SSA1-21 effects on [PSI(+)] appear to be independent of Hsp104, another stress-inducible protein chaperone known to be involved in [PSI(+)] propagation. We propose that cytosolic Hsp70 is important for the formation of Sup35p polymers characteristic of [PSI(+)] from preexisting material and that Ssa1-21p both lacks and interferes with this activity. We further demonstrate that the negative effect of heat stress on [PSI(+)] phenotype directly correlates with solubility of Sup35p and find that in wild-type strains the presence of [PSI(+)] causes a stress that elevates basal expression of Hsp104 and SSA1. JF - Genetics AU - Jung, G AU - Jones, G AU - Wegrzyn, R D AU - Masison, D C AD - Laboratory of Biochemistry and Genetics, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0851, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 559 EP - 570 VL - 156 IS - 2 SN - 0016-6731, 0016-6731 KW - Fungal Proteins KW - 0 KW - HSP70 Heat-Shock Proteins KW - Peptide Termination Factors KW - Prions KW - Protein Subunits KW - SUP35 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - SSA1 protein, S cerevisiae KW - EC 3.6.1.3 KW - Index Medicus KW - Peptide Chain Termination, Translational KW - Genotype KW - Hot Temperature KW - Homozygote KW - Mitosis KW - Mutagenesis KW - Diploidy KW - Saccharomyces cerevisiae -- genetics KW - Prions -- genetics KW - HSP70 Heat-Shock Proteins -- metabolism KW - HSP70 Heat-Shock Proteins -- genetics KW - Saccharomyces cerevisiae -- physiology KW - Fungal Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72304297?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=A+role+for+cytosolic+hsp70+in+yeast+%5BPSI%28%2B%29%5D+prion+propagation+and+%5BPSI%28%2B%29%5D+as+a+cellular+stress.&rft.au=Jung%2C+G%3BJones%2C+G%3BWegrzyn%2C+R+D%3BMasison%2C+D+C&rft.aulast=Jung&rft.aufirst=G&rft.date=2000-10-01&rft.volume=156&rft.issue=2&rft.spage=559&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-30 N1 - Date created - 2000-10-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1987 Jul;7(7):2568-77 [3302682] EMBO J. 1999 Apr 1;18(7):1974-81 [10202160] Yeast. 1988 Sep;4(3):159-78 [3059716] J Bacteriol. 1989 May;171(5):2680-8 [2651414] Genetics. 1989 May;122(1):19-27 [2659436] Mol Microbiol. 1989 Feb;3(2):215-20 [2548059] Genome. 1989;31(2):684-9 [2698838] J Biol Chem. 1990 Nov 5;265(31):18912-21 [2121731] Methods Enzymol. 1991;194:273-81 [2005792] Methods Enzymol. 1991;194:3-21 [2005794] Trends Biochem Sci. 1991 Apr;16(4):135-40 [1877088] Yeast. 1991 Oct;7(7):699-716 [1776361] J Mol Evol. 1994 Jan;38(1):1-17 [8151709] Science. 1994 Apr 22;264(5158):566-9 [7909170] Nature. 1994 Dec 1;372(6505):475-8 [7984243] Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2944-8 [7708753] Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):240-4 [10618402] J Mol Biol. 1975 Jun 5;94(4):595-610 [171412] Proc Natl Acad Sci U S A. 1976 Oct;73(10):3651-5 [790391] Mol Gen Genet. 1977 Feb 15;150(3):265-70 [321935] Genetics. 1981 Aug;98(4):691-711 [7037537] Mol Cell Biol. 1982 Nov;2(11):1388-98 [6761581] Methods Enzymol. 1983;101:181-91 [6310321] Science. 1995 May 12;268(5212):880-4 [7754373] J Mol Biol. 1995 Aug 18;251(3):334-45 [7650736] EMBO J. 1996 Jun 17;15(12):3127-34 [8670813] Science. 1996 Aug 2;273(5275):622-6 [8662547] Genetics. 1996 Dec;144(4):1375-86 [8978027] Cell. 1997 May 30;89(5):811-9 [9182769] Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6618-22 [9192614] Science. 1997 Jul 18;277(5324):381-3 [9219697] Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12503-8 [9356479] Cell. 1998 Jun 26;93(7):1241-52 [9657156] J Biol Chem. 1998 Nov 6;273(45):29727-37 [9792686] Mol Cell Biol. 1999 Feb;19(2):1325-33 [9891066] Gene. 1987;60(2-3):237-43 [3327750] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intermediate dose recombinant interferon-alpha as second-line treatment for patients with recurrent cutaneous melanoma who were pretreated with low dose interferon. AN - 72302417; 11013362 AB - Interferon (IFN) is widely considered the most effective agent in the adjuvant therapy of patients with cutaneous melanoma (CM). However, little is known about the effect of IFN on pretreated CM patients who experience disease recurrence. The authors conducted a Phase II study to determine whether intermediate doses of IFN could be beneficial for these patients. A series of 24 consecutive CM patients who had undergone surgery for local, in-transit, or lymph node disease recurrence during adjuvant therapy with low dose IFN (IFNalpha-2b, 3 million units [MU] per day, three times per week) were enrolled for second-line therapy with intermediate dose IFN (IFNalpha-2b, 10 MU per day) for one year. IFN was discontinued in 7 patients (29.2%) because of toxicity. Several patients complained of impairment in their daily activities. Progression of disease was registered in 17 patients (70. 8%), with a median disease free survival of 5.5 months (95% confidence interval, 3.4-14.2). The median follow-up for the 7 patients who did not experience disease recurrence was 15 months (range, 13-22 months). An increased dose of IFN as second-line adjuvant treatment was poorly tolerated and produced negative clinical outcomes in patients with CM. However, these patients probably were unresponsive to IFN regardless of the dosage level. In fact, the first adjuvant IFN treatment was ineffective in all patients. Thus, the key factor in the treatment of CM seems to be patient responsiveness to IFN rather than the total dosage achieved. Copyright 2000 American Cancer Society. JF - Cancer AU - Ascierto, P A AU - Daponte, A AU - Parasole, R AU - Perrone, F AU - Caracò, C AU - Melucci, M AU - Palmieri, G AU - Napolitano, M AU - Mozzillo, N AU - Castello, G AD - Department of Clinical Immunology, National Cancer Institute, Naples, Italy. pasciert@tin.it Y1 - 2000/10/01/ PY - 2000 DA - 2000 Oct 01 SP - 1490 EP - 1494 VL - 89 IS - 7 SN - 0008-543X, 0008-543X KW - Antineoplastic Agents KW - 0 KW - Interferon-alpha KW - Abridged Index Medicus KW - Index Medicus KW - Drug Administration Schedule KW - Disease-Free Survival KW - Neoplasm Recurrence, Local -- drug therapy KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Treatment Outcome KW - Disease Progression KW - Aged KW - Middle Aged KW - Male KW - Female KW - Skin Neoplasms -- drug therapy KW - Skin Neoplasms -- surgery KW - Interferon-alpha -- therapeutic use KW - Melanoma -- pathology KW - Melanoma -- surgery KW - Interferon-alpha -- administration & dosage KW - Antineoplastic Agents -- administration & dosage KW - Melanoma -- drug therapy KW - Skin Neoplasms -- pathology KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72302417?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Intermediate+dose+recombinant+interferon-alpha+as+second-line+treatment+for+patients+with+recurrent+cutaneous+melanoma+who+were+pretreated+with+low+dose+interferon.&rft.au=Ascierto%2C+P+A%3BDaponte%2C+A%3BParasole%2C+R%3BPerrone%2C+F%3BCarac%C3%B2%2C+C%3BMelucci%2C+M%3BPalmieri%2C+G%3BNapolitano%2C+M%3BMozzillo%2C+N%3BCastello%2C+G&rft.aulast=Ascierto&rft.aufirst=P&rft.date=2000-10-01&rft.volume=89&rft.issue=7&rft.spage=1490&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-17 N1 - Date created - 2000-10-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nuclear import of the retrotransposon Tf1 is governed by a nuclear localization signal that possesses a unique requirement for the FXFG nuclear pore factor Nup124p. AN - 72291262; 11003674 AB - Retroviruses, such as human immunodeficiency virus, that infect nondividing cells generate integration precursors that must cross the nuclear envelope to reach the host genome. As a model for retroviruses, we investigated the nuclear entry of Tf1, a long-terminal-repeat-containing retrotransposon of the fission yeast Schizosaccharomyces pombe. Because the nuclear envelope of yeasts remains intact throughout the cell cycle, components of Tf1 must be transported through the envelope before integration can occur. The nuclear localization of the Gag protein of Tf1 is different from that of other proteins tested in that it has a specific requirement for the FXFG nuclear pore factor, Nup124p. Using extensive mutagenesis, we found that Gag contained three nuclear localization signals (NLSs) which, when included individually in a heterologous protein, were sufficient to direct nuclear import. In the context of the intact transposon, mutations in the NLS that mapped to the first 10 amino acid residues of Gag significantly impaired Tf1 retrotransposition and abolished nuclear localization of Gag. Interestingly, this NLS activity in the heterologous protein was specifically dependent upon the presence of Nup124p. Deletion analysis of heterologous proteins revealed the surprising result that the residues in Gag with the NLS activity were independent from the residues that conveyed the requirement for Nup124p. In fact, a fragment of Gag that lacked NLS activity, residues 10 to 30, when fused to a heterologous protein, was sufficient to cause the classical NLS of simian virus 40 to require Nup124p for nuclear import. Within the context of the current understanding of nuclear import, these results represent the novel case of a short amino acid sequence that specifies the need for a particular nuclear pore complex protein. JF - Molecular and cellular biology AU - Dang, V D AU - Levin, H L AD - Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 7798 EP - 7812 VL - 20 IS - 20 SN - 0270-7306, 0270-7306 KW - Gene Products, gag KW - 0 KW - Nuclear Localization Signals KW - Nuclear Pore Complex Proteins KW - Nuclear Proteins KW - Recombinant Fusion Proteins KW - Retroelements KW - Schizosaccharomyces pombe Proteins KW - nup124 protein, S pombe KW - Index Medicus KW - Virus Assembly KW - Retroviridae -- metabolism KW - Active Transport, Cell Nucleus KW - Gene Products, gag -- genetics KW - Simian virus 40 -- genetics KW - Amino Acid Sequence KW - Gene Products, gag -- chemistry KW - Gene Products, gag -- metabolism KW - Models, Biological KW - Mutagenesis KW - Recombinant Fusion Proteins -- metabolism KW - Terminal Repeat Sequences -- genetics KW - Nuclear Pore -- metabolism KW - Recombinant Fusion Proteins -- genetics KW - Genes, Reporter KW - Molecular Sequence Data KW - Simian virus 40 -- metabolism KW - Retroviridae -- genetics KW - Protein Structure, Tertiary KW - Fluorescent Antibody Technique KW - Sequence Deletion KW - Schizosaccharomyces -- genetics KW - Retroelements -- genetics KW - Nuclear Proteins -- genetics KW - Nuclear Localization Signals -- physiology KW - Cell Nucleus -- metabolism KW - Schizosaccharomyces -- metabolism KW - Nuclear Proteins -- metabolism KW - Nuclear Localization Signals -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72291262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nuclear+import+of+the+retrotransposon+Tf1+is+governed+by+a+nuclear+localization+signal+that+possesses+a+unique+requirement+for+the+FXFG+nuclear+pore+factor+Nup124p.&rft.au=Dang%2C+V+D%3BLevin%2C+H+L&rft.aulast=Dang&rft.aufirst=V&rft.date=2000-10-01&rft.volume=20&rft.issue=20&rft.spage=7798&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 - 2000-10-30 N1 - Date created - 2000-10-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1993 Jan;67(1):119-30 [8380067] EMBO J. 1992 Aug;11(8):3053-8 [1322294] Nature. 1993 Oct 14;365(6447):666-9 [8105392] EMBO J. 1993 Dec;12(12):4885-95 [8223497] J Virol. 1994 Aug;68(8):4946-54 [8035493] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6992-6 [8041734] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7311-5 [8041786] Cell. 1995 Feb 10;80(3):379-88 [7859280] J Virol. 1995 Jun;69(6):3949-54 [7745752] Mol Cell Biol. 1995 Jun;15(6):3310-7 [7760826] Cell. 1995 Nov 17;83(4):569-76 [7585960] Mol Cell Biol. 1996 Jan;16(1):338-46 [8524313] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):96-100 [8552683] J Virol. 1996 Feb;70(2):1027-32 [8551560] Science. 1996 Mar 15;271(5255):1513-8 [8599106] Annu Rev Cell Dev Biol. 1995;11:155-88 [8689555] Mol Cell Biol. 1996 Oct;16(10):5645-54 [8816477] J Virol. 1996 Dec;70(12):8255-62 [8970944] Cell. 1997 Jan 24;88(2):171-3; discussion 173-4 [9008157] Genes Dev. 1997 Jan 15;11(2):270-85 [9009208] Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9825-30 [9275210] EMBO J. 1997 Oct 1;16(19):5998-6007 [9312057] Genes Dev. 1998 Jan 15;12(2):175-85 [9436978] J Virol. 1998 Feb;72(2):1324-33 [9445033] EMBO J. 1998 Feb 16;17(4):909-17 [9463369] J Virol. 1998 Jul;72(7):6004-13 [9621063] Mol Cell. 1998 Jan;1(2):223-34 [9659919] J Cell Biol. 1998 Nov 16;143(4):875-85 [9817747] Gene. 1998 Nov 26;223(1-2):157-63 [9858717] J Cell Biol. 1998 Dec 28;143(7):1813-30 [9864357] Annu Rev Microbiol. 1998;52:627-86 [9891810] Mol Cell Biol. 1999 Mar;19(3):2351-65 [10022921] Curr Opin Cell Biol. 1999 Jun;11(3):391-401 [10395558] Mol Cell Biol. 1999 Aug;19(8):5768-84 [10409764] Mol Biol Cell. 1999 Dec;10(12):4043-57 [10588642] EMBO J. 1997 Aug 1;16(15):4531-9 [9303297] Annu Rev Cell Dev Biol. 1999;15:607-60 [10611974] J Cell Biol. 2000 Feb 21;148(4):635-51 [10684247] Int Rev Cytol. 1975;43:167-227 [816751] Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 [388439] J Bacteriol. 1984 May;158(2):636-43 [6233260] Nature. 1986 Jul 10-16;322(6075):130-6 [2425264] Methods Enzymol. 1987;154:164-75 [3323810] J Gen Virol. 1989 Jul;70 ( Pt 7):1617-39 [2544657] J Cell Biol. 1990 Apr;110(4):883-94 [2324201] Mol Cell Biol. 1990 Dec;10(12):6791-8 [2174117] Methods Enzymol. 1991;194:795-823 [2005825] J Exp Med. 1991 Dec 1;174(6):1477-82 [1720811] EMBO J. 1992 Mar;11(3):1145-53 [1312461] Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6580-4 [1631159] EMBO J. 1993 May;12(5):2099-108 [8491198] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemical-induced hippocampal neurodegeneration and elevations in TNFalpha, TNFbeta, IL-1alpha, IP-10, and MCP-1 mRNA in osteopetrotic (op/op) mice. AN - 72288787; 11002296 AB - The osteopetrotic (op/op) mouse, deficient in biologically active colony stimulating factor 1 (CSF-1), was used to examine the role of microglia in chemical-induced trauma. Op/op mice and normal phenotype littermates (non-op/op) received an acute i.p. injection of the hippocampal toxicant, trimethyltin hydroxide (TMT; 1.5 or 2.0 mg/kg). At 2.0 mg/kg, both mice displayed severe degeneration of dentate granule neurons. At 1.5 mg/kg, non-op/op mice showed a limited punctate pattern of neuronal death while op/op mice showed prominent neuronal death. TMT-induced astrocyte reactivity was similar in both groups. RNase protection assays were conducted on hippocampal tissue at 24 hr post-TMT. Elevations were seen in mRNA levels for the host response genes: intercellular cell adhesion molecule (ICAM-1; non-op/op 80%, op/op 85%), the protease inhibitor EB22 (non-op/op 60%, op/op 300%), and glial fibrillary acidic protein (GFAP; non-op/op 300%, op/op 480%) within 24 hr. Macrophage-1 antigen (Mac-1) mRNA levels were lower in all op/op mice and were not induced by TMT exposure. Macrophage inflammatory protein (MIP)-1alpha and MIP-1beta mRNA levels were elevated in non-op/op mice while mRNA levels for interferon inducible protein (IP-10) and monocyte chemoattractant protein (MCP-1) were elevated in op/op mice. Tumor necrosis factor alpha (TNFalpha) mRNA levels were significantly elevated in both non-op/op (100%) and op/op (600%) mice. TNFbeta mRNA levels in op/op mice were elevated 200% and interleukin 1alpha (IL-1alpha) 150%. Reverse transcriptase polymerase chain reaction (RT-PCR) showed a TMT-induced elevation in INFalpha and INFbeta mRNA levels and no elevation of INFgamma. mRNA levels of the CSF-1 receptor, c-fms, were unaltered. JF - Journal of neuroscience research AU - Bruccoleri, A AU - Harry, G J AD - Neurotoxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000/10/01/ PY - 2000 DA - 2000 Oct 01 SP - 146 EP - 155 VL - 62 IS - 1 SN - 0360-4012, 0360-4012 KW - Chemokine CCL2 KW - 0 KW - Chemokine CXCL10 KW - Chemokines, CXC KW - Cytokines KW - Glial Fibrillary Acidic Protein KW - Interleukin-1 KW - Lymphotoxin-alpha KW - RNA, Messenger KW - Trimethyltin Compounds KW - Tumor Necrosis Factor-alpha KW - Intercellular Adhesion Molecule-1 KW - 126547-89-5 KW - trimethyltin hydroxide KW - 56-24-6 KW - Receptor, Macrophage Colony-Stimulating Factor KW - EC 2.7.10.1 KW - Ribonucleases KW - EC 3.1.- KW - Index Medicus KW - Lymphotoxin-alpha -- metabolism KW - Animals KW - Lymphotoxin-alpha -- genetics KW - Astrocytes -- drug effects KW - Neurons -- drug effects KW - Glial Fibrillary Acidic Protein -- metabolism KW - Intercellular Adhesion Molecule-1 -- genetics KW - Tumor Necrosis Factor-alpha -- genetics KW - Ribonucleases -- metabolism KW - Receptor, Macrophage Colony-Stimulating Factor -- metabolism KW - Neurons -- pathology KW - Cell Survival -- drug effects KW - Interleukin-1 -- genetics KW - Astrocytes -- pathology KW - Male KW - Intercellular Adhesion Molecule-1 -- metabolism KW - Chemokines, CXC -- metabolism KW - Chemokine CCL2 -- genetics KW - Dose-Response Relationship, Drug KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Chemokine CCL2 -- metabolism KW - Receptor, Macrophage Colony-Stimulating Factor -- genetics KW - Mice, Mutant Strains KW - Interleukin-1 -- metabolism KW - Tumor Necrosis Factor-alpha -- metabolism KW - Chemokines, CXC -- genetics KW - Female KW - Astrocytes -- metabolism KW - Osteopetrosis -- complications KW - Neurodegenerative Diseases -- chemically induced KW - RNA, Messenger -- metabolism KW - Neurodegenerative Diseases -- metabolism KW - Hippocampus -- metabolism KW - Osteopetrosis -- genetics KW - Neurodegenerative Diseases -- pathology KW - Cytokines -- chemistry KW - Neurodegenerative Diseases -- complications KW - Hippocampus -- pathology KW - Osteopetrosis -- metabolism KW - Microglia -- metabolism KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72288787?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chemical-induced+hippocampal+neurodegeneration+and+elevations+in+TNFalpha%2C+TNFbeta%2C+IL-1alpha%2C+IP-10%2C+and+MCP-1+mRNA+in+osteopetrotic+%28op%2Fop%29+mice.&rft.au=Bruccoleri%2C+A%3BHarry%2C+G+J&rft.aulast=Bruccoleri&rft.aufirst=A&rft.date=2000-10-01&rft.volume=62&rft.issue=1&rft.spage=146&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 - 2000-11-30 N1 - Date created - 2000-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term therapy of chronic hepatitis B with lamivudine. AN - 72288213; 11003630 AB - Lamivudine therapy induces improvements in chronic hepatitis B in a high proportion of patients, but prolonged therapy is limited by the development of viral resistance. We analyzed clinical responses and virologic resistance in 27 patients treated continuously with lamivudine for 2 to 4 years. Serum transaminases, hepatitis B virus (HBV) DNA by both branched DNA (bDNA) signal amplification and quantitative polymerase chain reaction were monitored at 4- to 8-week intervals. Virologic resistance to lamivudine was confirmed by the presence of mutations in the YMDD motif of the polymerase gene by restriction fragment-length polymorphism analysis. Serum HBV-DNA levels decreased rapidly in all treated patients, falling by 4 to 5 logs within 1 year. Transaminase levels also decreased and were normal in 70% of patients at 1 year, at which point liver histology had improved in 81% of patients. Viral resistance began to emerge after 8 months of therapy, eventually developing in 14 patients, including 76% of hepatitis B e antigen (HBeAg)-positive patients but only 10% of HBeAg-negative patients. Lamivudine withdrawal led to reappearance of wild-type HBV species, but retreatment led to more rapid reappearance of the mutant virus. Clinical, serum biochemical, and histologic improvements were maintained in the 13 patients who did not develop resistance. Thus, long-term therapy with lamivudine resulted in maintained improvements in virologic, biochemical, and histologic features of disease in most patients with HBeAg-negative chronic hepatitis B and in the subgroup of HBeAg-positive patients with high serum transaminase levels. A high rate of resistance limited efficacy, particularly in patients who remained HBeAg positive on therapy. JF - Hepatology (Baltimore, Md.) AU - Lau, D T AU - Khokhar, M F AU - Doo, E AU - Ghany, M G AU - Herion, D AU - Park, Y AU - Kleiner, D E AU - Schmid, P AU - Condreay, L D AU - Gauthier, J AU - Kuhns, M C AU - Liang, T J AU - Hoofnagle, J H AD - Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 828 EP - 834 VL - 32 IS - 4 Pt 1 SN - 0270-9139, 0270-9139 KW - DNA, Viral KW - 0 KW - Hepatitis B Surface Antigens KW - Hepatitis B e Antigens KW - Reverse Transcriptase Inhibitors KW - Lamivudine KW - 2T8Q726O95 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Index Medicus KW - AIDS/HIV KW - Liver -- pathology KW - Alanine Transaminase -- blood KW - Hepatitis B Surface Antigens -- analysis KW - DNA, Viral -- analysis KW - Humans KW - Adult KW - Drug Resistance KW - Aged KW - Middle Aged KW - Hepatitis B e Antigens -- analysis KW - Male KW - Female KW - Lamivudine -- adverse effects KW - Hepatitis B, Chronic -- virology KW - Hepatitis B, Chronic -- pathology KW - Lamivudine -- therapeutic use KW - Reverse Transcriptase Inhibitors -- therapeutic use KW - Hepatitis B, Chronic -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72288213?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Long-term+therapy+of+chronic+hepatitis+B+with+lamivudine.&rft.au=Lau%2C+D+T%3BKhokhar%2C+M+F%3BDoo%2C+E%3BGhany%2C+M+G%3BHerion%2C+D%3BPark%2C+Y%3BKleiner%2C+D+E%3BSchmid%2C+P%3BCondreay%2C+L+D%3BGauthier%2C+J%3BKuhns%2C+M+C%3BLiang%2C+T+J%3BHoofnagle%2C+J+H&rft.aulast=Lau&rft.aufirst=D&rft.date=2000-10-01&rft.volume=32&rft.issue=4+Pt+1&rft.spage=828&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 - 2000-10-19 N1 - Date created - 2000-10-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Hepatology. 2000 Oct;32(4 Pt 1):866-7 [11003636] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sustained long-term hematologic recovery despite a marked quantitative defect in the stem cell compartment of patients with aplastic anemia after immunosuppressive therapy. AN - 72278186; 10996829 AB - Previously, we reported that patients with aplastic anemia (AA) have profoundly decreased numbers of hematopoietic progenitor and stem cells as measured in the long-term culture initiating cell (LTC-IC) assay (Blood 1996;88:1983-1991). We now present results of a long-term prospective study of LTC-IC numbers in peripheral blood (PB) and bone marrow (BM) of patients treated with antithymocyte globulin and cyclosporin A. Numbers of secondary colony forming cells (secondary CFC) in long-term bone marrow culture (LTBMC) were used to quantitate LTC-IC. BM (N = 35) and PB (N = 41) secondary CFC from both untreated severe AA patients and responders to immunosuppressive therapy who were sampled up to 6 years after initial treatment were compared. Normal controls showed 148 +/- 38 (N = 17) and 16 +/- 3 (N= 14) secondary CFC per 10(6) in BM and PB, respectively. In cross-sectional analysis, prior to therapy, AA patients showed 2.6 +/- 1 (mean +/- SD) secondary CFC/10(6) BM MNC; within the first year after initial treatment (N = 14), secondary CFC number rose modestly to 8.2 +/- 2.2/10(6) MNC, and further increased to 15.8 +/- 7 (N = 17) at 2 years and 16.2 +/- 7/10(6) MNC (N = 25) 3 years after treatment. There was no further improvement in the secondary CFC numbers at 4, 5, and > or =6 years (N = 37). Thus, while BM secondary CFC increased about 6-fold at 3 years post-therapy compared to presentation, they remained about only 10% of normal despite hematologic recovery. Similar data were obtained for PB, with approximately 4-fold increase in secondary CFC numbers within 2 years of therapy, to about 15% of normal values. We confirmed these observations in patients studied serially over a period of 4 years: initial secondary CFC were 2.35 +/- 1/10(6) BM MNC and 0.11 +/- 0.1/10(6) PB MNC improving to an average of 6 +/- 1. 2 (BM; N = 12) and 2.4 +/- 1/10(6) MNC (PB; N = 14). In many cases of partial recovery, PB counts improve but do not normalize. When we studied secondary CFC numbers only in patients who achieved complete normalization of PB counts (ANC >1,500/mm(3); platelets >10(5)/mm(3) and absolute reticulocytes >5 x 10(4)/mm(3)), BM secondary CFC were significantly higher than in patients with partial recovery; the PB secondary CFC number was modestly increased but remained below the normal values. Within the group of patients with complete recovery, there was no correlation between the secondary CFC and time after initial treatment. In addition, there also was no correlation between the secondary CFC number at presentation and the quality of hematopoietic recovery. Despite a limited expansion potential of a severely reduced stem cell pool, their numbers are sufficient to provide a long-term supply of mature blood cells. Am. J. Hematol. 65:123-131, 2000. Published 2000 Wiley-Liss, Inc. JF - American journal of hematology AU - Maciejewski, J P AU - Kim, S AU - Sloand, E AU - Selleri, C AU - Young, N S AD - Hematology Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892, USA. Renosaurus@aol.com Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 123 EP - 131 VL - 65 IS - 2 SN - 0361-8609, 0361-8609 KW - Immunosuppressive Agents KW - 0 KW - Index Medicus KW - Stem Cells -- drug effects KW - Karyotyping KW - Hemoglobinuria, Paroxysmal -- pathology KW - Clone Cells -- pathology KW - Disease-Free Survival KW - Stem Cells -- cytology KW - Prospective Studies KW - Hemoglobinuria, Paroxysmal -- chemically induced KW - Humans KW - Bone Marrow Cells -- cytology KW - Time Factors KW - Blood Cell Count KW - Hematopoiesis -- drug effects KW - Anemia, Aplastic -- complications KW - Anemia, Aplastic -- blood KW - Immunosuppressive Agents -- therapeutic use KW - Anemia, Aplastic -- therapy KW - Immunosuppressive Agents -- pharmacology KW - Immunosuppressive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72278186?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+hematology&rft.atitle=Sustained+long-term+hematologic+recovery+despite+a+marked+quantitative+defect+in+the+stem+cell+compartment+of+patients+with+aplastic+anemia+after+immunosuppressive+therapy.&rft.au=Maciejewski%2C+J+P%3BKim%2C+S%3BSloand%2C+E%3BSelleri%2C+C%3BYoung%2C+N+S&rft.aulast=Maciejewski&rft.aufirst=J&rft.date=2000-10-01&rft.volume=65&rft.issue=2&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=American+journal+of+hematology&rft.issn=03618609&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-31 N1 - Date created - 2000-10-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of lysosomal and Golgi localization signals in GAP and ARF domains of ARF domain protein 1. AN - 72254217; 10982851 AB - ADP ribosylation factors (ARFs) are approximately 20-kDa guanine nucleotide-binding proteins that activate cholera toxin and phospholipase D and are critical components of vesicular trafficking pathways. ARF domain protein 1 (ARD1), a member of the ARF superfamily, contains a 46-kDa amino-terminal extension, which acts as a GTPase-activating protein (GAP) with activity towards its ARF domain. When overexpressed, ARD1 was associated with lysosomes and the Golgi apparatus. In agreement with this finding, lysosomal and Golgi membranes isolated from human liver by immunoaffinity contained native ARD1. ARD1, expressed as a green fluorescent fusion protein, was initially associated with the Golgi network and subsequently appeared on lysosomes, suggesting that ARD1 might undergo vectorial transport between the two organelles. Here we show by microscopic colocalization that GAP and ARF domains determine lysosomal and Golgi localization, respectively, consistent with the presence of more than one signal motif. Using truncated ARD1 molecules, expressed as green fluorescent fusion proteins, it was found that the signal for lysosomal localization was present in residues 301 to 402 of the GAP domain. Site-specific mutagenesis demonstrated that the sequence (369)KXXXQ(373) in the GAP domain was responsible for lysosomal localization. Association of ARD1 with the Golgi apparatus required tyrosine-based motifs. A green fluorescent fusion protein containing the QKQQQQF motif was partially associated with lysosomes, suggesting that this motif contains the information sufficient for lysosomal targeting. These results suggest that ARD1 is a multidomain protein with ARF and GAP regions, which contain Golgi and lysosomal localization signals, respectively, that could function in vesicular trafficking. JF - Molecular and cellular biology AU - Vitale, N AU - Ferrans, V J AU - Moss, J AU - Vaughan, M AD - Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 7342 EP - 7352 VL - 20 IS - 19 SN - 0270-7306, 0270-7306 KW - Peptide Fragments KW - 0 KW - Protein Sorting Signals KW - Recombinant Fusion Proteins KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - GTP Phosphohydrolases KW - EC 3.6.1.- KW - Index Medicus KW - Peptide Fragments -- metabolism KW - 3T3 Cells KW - Animals KW - Peptide Fragments -- genetics KW - Models, Molecular KW - Enzyme Activation KW - Humans KW - Amino Acid Sequence KW - Mice KW - Adenosine Diphosphate Ribose -- metabolism KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Microscopy, Fluorescence KW - Amino Acid Motifs KW - GTP Phosphohydrolases -- metabolism KW - Point Mutation KW - Molecular Sequence Data KW - Protein Structure, Tertiary KW - Amino Acid Substitution KW - Protein Conformation KW - Catalysis KW - Protein Sorting Signals -- chemistry KW - Lysosomes -- metabolism KW - Golgi Apparatus -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72254217?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+lysosomal+and+Golgi+localization+signals+in+GAP+and+ARF+domains+of+ARF+domain+protein+1.&rft.au=Vitale%2C+N%3BFerrans%2C+V+J%3BMoss%2C+J%3BVaughan%2C+M&rft.aulast=Vitale&rft.aufirst=N&rft.date=2000-10-01&rft.volume=20&rft.issue=19&rft.spage=7342&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 - 2000-10-19 N1 - Date created - 2000-10-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 2000 Aug;20(16):5998-6007 [10913182] Annu Rev Biochem. 1998;67:509-44 [9759496] J Biol Chem. 1986 May 25;261(15):6853-9 [3700419] Cell. 1986 Jul 4;46(1):5-9 [2872968] J Biol Chem. 1988 May 15;263(14):6797-805 [3360807] J Cell Biol. 1989 Mar;108(3):855-64 [2921284] Biochem J. 1990 Aug 15;270(1):97-102 [2204342] J Biol Chem. 1991 Feb 15;266(5):2772-7 [1993656] DNA Cell Biol. 1991 Jun;10(5):319-28 [1713771] Biochem J. 1992 Apr 15;283 ( Pt 2):313-6 [1575675] J Biol Chem. 1992 May 5;267(13):9202-9 [1577755] J Biol Chem. 1993 Apr 25;268(12):8801-7 [8473324] EMBO J. 1993 May;12(5):2219-28 [8491209] J Biol Chem. 1993 Jul 15;268(20):14715-23 [7686903] Annu Rev Cell Biol. 1993;9:129-61 [8280459] EMBO J. 1994 Jan 1;13(1):18-33 [7508380] Science. 1995 Feb 24;267(5201):1175-8 [7855600] Mol Cell Biochem. 1994 Sep;138(1-2):157-66 [7898460] J Biol Chem. 1995 May 26;270(21):12327-30 [7759471] Science. 1995 Sep 29;269(5232):1872-5 [7569928] EMBO J. 1995 Oct 16;14(20):4961-75 [7588625] Science. 1995 Dec 22;270(5244):1999-2002 [8533093] J Cell Biol. 1996 Feb;132(4):565-76 [8647888] J Cell Biol. 1996 Jun;133(6):1217-36 [8682860] Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1941-4 [8700863] Eur J Neurosci. 1996 Jun;8(6):1275-85 [8752599] J Biol Chem. 1996 Sep 27;271(39):24005-9 [8798635] Cold Spring Harb Symp Quant Biol. 1995;60:229-34 [8824395] Proc Assoc Am Physicians. 1996 Jul;108(4):285-95 [8863342] EMBO J. 1996 Nov 15;15(22):6096-110 [8947032] Annu Rev Cell Dev Biol. 1996;12:575-625 [8970738] J Biol Chem. 1997 Jan 31;272(5):2788-93 [9006918] J Biol Chem. 1997 Feb 14;272(7):3897-904 [9020091] J Biol Chem. 1997 Mar 21;272(12):7688-92 [9065426] J Cell Biol. 1997 May 19;137(4):825-34 [9151685] J Cell Biol. 1997 Oct 6;139(1):49-61 [9314528] J Biol Chem. 1998 Jan 9;273(2):981-8 [9422759] J Biol Chem. 1998 Jan 16;273(3):1373-9 [9430671] J Biol Chem. 1998 Jan 30;273(5):2553-60 [9446556] J Biol Chem. 1998 Feb 13;273(7):4006-11 [9461590] EMBO J. 1998 Apr 15;17(8):2148-55 [9545228] J Cell Sci. 1998 Aug;111 ( Pt 15):2257-67 [9664047] Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8613-8 [9671726] J Biol Chem. 1998 Aug 21;273(34):21431-4 [9705267] J Biol Chem. 1998 Sep 18;273(38):24786-91 [9733781] J Cell Biol. 1981 Oct;91(1):184-94 [7028761] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role for mitochondrial oxidants as regulators of cellular metabolism. AN - 72250344; 10982848 AB - Leakage of mitochondrial oxidants contributes to a variety of harmful conditions ranging from neurodegenerative diseases to cellular senescence. We describe here, however, a physiological and heretofore unrecognized role for mitochondrial oxidant release. Mitochondrial metabolism of pyruvate is demonstrated to activate the c-Jun N-terminal kinase (JNK). This metabolite-induced rise in cytosolic JNK1 activity is shown to be triggered by increased release of mitochondrial H(2)O(2). We further demonstrate that in turn, the redox-dependent activation of JNK1 feeds back and inhibits the activity of the metabolic enzymes glycogen synthase kinase 3beta and glycogen synthase. As such, these results demonstrate a novel metabolic regulatory pathway activated by mitochondrial oxidants. In addition, they suggest that although chronic oxidant production may have deleterious effects, mitochondrial oxidants can also function acutely as signaling molecules to provide communication between the mitochondria and the cytosol. JF - Molecular and cellular biology AU - Nemoto, S AU - Takeda, K AU - Yu, Z X AU - Ferrans, V J AU - Finkel, T AD - Laboratory of Molecular Biology, National Heart Lung and Blood Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 7311 EP - 7318 VL - 20 IS - 19 SN - 0270-7306, 0270-7306 KW - Neoplasm Proteins KW - 0 KW - Oxidants KW - Reactive Oxygen Species KW - antimycin KW - 11118-72-2 KW - Antimycin A KW - 642-15-9 KW - Pyruvic Acid KW - 8558G7RUTR KW - Hydrogen Peroxide KW - BBX060AN9V KW - Glycogen Synthase KW - EC 2.4.1.11 KW - Glycogen Synthase Kinases KW - EC 2.7.11.- KW - Ribosomal Protein S6 Kinases KW - EC 2.7.11.1 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - Glycogen Synthase Kinase 3 KW - EC 2.7.11.26 KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Pyruvic Acid -- pharmacology KW - Cytosol -- enzymology KW - Humans KW - Kidney -- embryology KW - Oxidation-Reduction KW - Antimycin A -- pharmacology KW - Glycogen Synthase -- metabolism KW - Enzyme Activation -- drug effects KW - Feedback KW - Neoplasm Proteins -- metabolism KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - MAP Kinase Signaling System -- drug effects KW - Endothelium, Vascular -- metabolism KW - Endothelium, Vascular -- cytology KW - HeLa Cells KW - Hydrogen Peroxide -- metabolism KW - Mice KW - Ribosomal Protein S6 Kinases -- physiology KW - Muscle, Skeletal -- embryology KW - Cells, Cultured -- metabolism KW - Antimycin A -- analogs & derivatives KW - Umbilical Veins KW - 3T3 Cells -- metabolism KW - Pyruvic Acid -- metabolism KW - Mitochondria -- physiology KW - Mitogen-Activated Protein Kinases -- metabolism KW - Energy Metabolism -- physiology KW - Oxidants -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72250344?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+for+mitochondrial+oxidants+as+regulators+of+cellular+metabolism.&rft.au=Nemoto%2C+S%3BTakeda%2C+K%3BYu%2C+Z+X%3BFerrans%2C+V+J%3BFinkel%2C+T&rft.aulast=Nemoto&rft.aufirst=S&rft.date=2000-10-01&rft.volume=20&rft.issue=19&rft.spage=7311&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 - 2000-10-19 N1 - Date created - 2000-10-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1999 Nov 12;274(46):32596-602 [10551813] Proc Soc Exp Biol Med. 2000 Feb;223(2):136-48 [10654616] Science. 2000 Jan 7;287(5450):138-42 [10615049] J Sports Sci. 2000 Mar;18(3):213-25 [10737272] Nature. 2000 Apr 13;404(6779):787-90 [10783895] Biochem J. 1973 Jul;134(3):707-16 [4749271] Eur J Biochem. 1978 Jan 16;82(2):563-7 [203456] FEBS Lett. 1979 Oct 15;106(2):284-8 [115716] Circ Res. 1994 Jun;74(6):1141-8 [8187280] Herz. 1995 Feb;20(1):5-15 [7713477] Mol Cell Biol. 1995 Aug;15(8):4353-63 [7623830] Science. 1995 Oct 13;270(5234):296-9 [7569979] Science. 1996 Jul 5;273(5271):59-63 [8658196] Biochem J. 1996 Sep 1;318 ( Pt 2):379-82 [8809022] J Biol Chem. 1996 Nov 29;271(48):30765-73 [8940056] Mol Cell Biol. 1996 Dec;16(12):7115-21 [8943367] J Biol Chem. 1997 Jan 3;272(1):217-21 [8995250] FASEB J. 1997 Feb;11(2):118-24 [9039953] Science. 1997 Mar 14;275(5306):1649-52 [9054359] Biochem Biophys Res Commun. 1997 Jun 27;235(3):739-42 [9207231] Exp Cell Res. 1997 Nov 25;237(1):176-85 [9417880] Arch Biochem Biophys. 1998 Feb 1;350(1):118-26 [9466828] Mol Biol Cell. 1998 Mar;9(3):561-73 [9487126] Cell. 1998 Mar 20;92(6):773-84 [9529253] Physiol Rev. 1998 Apr;78(2):547-81 [9562038] Curr Opin Cell Biol. 1998 Apr;10(2):248-53 [9561849] J Biol Chem. 1998 May 8;273(19):11401-4 [9565547] Science. 1998 May 8;280(5365):898-902 [9572733] Mol Cell Biochem. 1998 May;182(1-2):31-48 [9609112] Nat Genet. 1998 Jun;19(2):105-6 [9620757] J Biol Chem. 1998 Jun 19;273(25):15366-72 [9624118] J Biol Chem. 1998 Jul 17;273(29):17991-4 [9660749] J Clin Invest. 1998 Sep 1;102(5):929-37 [9727061] Trends Pharmacol Sci. 1998 Aug;19(8):328-34 [9745361] J Biol Chem. 1998 Nov 6;273(45):29986-94 [9792719] EMBO J. 1999 Mar 1;18(5):1321-34 [10064598] J Biol Chem. 1999 Mar 19;274(12):7936-40 [10075689] Endocrinology. 1999 May;140(5):2145-51 [10218965] Exp Mol Med. 1999 Jun 30;31(2):53-9 [10410302] J Biol Chem. 1999 Aug 6;274(32):22699-704 [10428852] Nature. 1999 Sep 2;401(6748):79-82 [10485709] J Biol Chem. 1999 Nov 26;274(48):33881-7 [10567349] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - RAS transformation causes sustained activation of epidermal growth factor receptor and elevation of mitogen-activated protein kinase in human mammary epithelial cells. AN - 72213421; 10962438 AB - Activation of the ras oncogene is an important step in carcinogenesis. Human MCF-10A mammary epithelial cells were transformed with a point-mutated form of the Ha-ras oncogene. Epidermal growth factor receptor (EGFR) phosphorylation levels were chronically elevated after EGF induction and the EGFR ligand-driven internalization rate was slower in Ha-ras transformed MCF-10A cells. Additionally, basal levels of p42/44 mitogen-activated protein kinase (MAPK) expression and enzyme activity were significantly higher in Ha-ras transformed cells, localized predominantly in the nucleus. The anti-EGFR monoclonal antibody (MAb) 225 and the EGFR tyrosine kinase inhibitor PD153035 blocked anchorage-independent growth of Ha-ras transformed cells in soft agar and were more effective when used in combination. The MEK inhibitor PD98059 and anti-erbB-2 MAb L26 also suppressed colony formation of Ha-ras transformed cells in soft agar. Therefore, Ha-ras transformation leads to an augmentation in signaling through the EGFR as a result of an increase in ligand-dependent phosphorylation, a decrease in its internalization and an up-regulation in basal p44/42 MAPK levels. These effects may contribute to uncontrolled growth of Ha-ras-transformed human mammary epithelial cells. Copyright 2000 Wiley-Liss, Inc. JF - International journal of cancer AU - Martínez-Lacaci, I AU - Kannan, S AU - De Santis, M AU - Bianco, C AU - Kim, N AU - Wallace-Jones, B AU - Ebert, A D AU - Wechselberger, C AU - Salomon, D S AD - Tumor Growth Factor Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/10/01/ PY - 2000 DA - 2000 Oct 01 SP - 44 EP - 52 VL - 88 IS - 1 SN - 0020-7136, 0020-7136 KW - Antibodies, Monoclonal KW - 0 KW - Enzyme Inhibitors KW - Growth Inhibitors KW - Epidermal Growth Factor KW - 62229-50-9 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - Mitogen-Activated Protein Kinases KW - HRAS protein, human KW - EC 3.6.5.2 KW - Proto-Oncogene Proteins p21(ras) KW - Index Medicus KW - Proto-Oncogene Proteins p21(ras) -- metabolism KW - MAP Kinase Signaling System -- physiology KW - Humans KW - Antibodies, Monoclonal -- pharmacology KW - Mitogen-Activated Protein Kinase 1 -- biosynthesis KW - Antibodies, Monoclonal -- immunology KW - Antibody Specificity KW - Phosphorylation KW - Point Mutation KW - Gene Expression Regulation KW - Cell Line, Transformed KW - Subcellular Fractions -- enzymology KW - Proto-Oncogene Proteins p21(ras) -- genetics KW - Enzyme Activation KW - Proto-Oncogene Proteins c-raf -- metabolism KW - Epidermal Growth Factor -- pharmacokinetics KW - Transfection KW - Cells, Cultured KW - Mitogen-Activated Protein Kinase 1 -- metabolism KW - Growth Inhibitors -- pharmacology KW - Proto-Oncogene Proteins c-raf -- genetics KW - Enzyme Inhibitors -- pharmacology KW - Substrate Specificity KW - Epidermal Growth Factor -- metabolism KW - Female KW - Mitogen-Activated Protein Kinase 1 -- antagonists & inhibitors KW - Receptor, Epidermal Growth Factor -- metabolism KW - Genes, ras -- genetics KW - Receptor, Epidermal Growth Factor -- genetics KW - Mitogen-Activated Protein Kinases -- metabolism KW - Genes, ras -- physiology KW - Cell Transformation, Neoplastic -- metabolism KW - Breast -- enzymology KW - Mitogen-Activated Protein Kinases -- antagonists & inhibitors KW - Breast -- pathology KW - Receptor, Epidermal Growth Factor -- physiology KW - Mitogen-Activated Protein Kinases -- biosynthesis KW - Cell Transformation, Neoplastic -- genetics KW - Breast -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72213421?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=RAS+transformation+causes+sustained+activation+of+epidermal+growth+factor+receptor+and+elevation+of+mitogen-activated+protein+kinase+in+human+mammary+epithelial+cells.&rft.au=Mart%C3%ADnez-Lacaci%2C+I%3BKannan%2C+S%3BDe+Santis%2C+M%3BBianco%2C+C%3BKim%2C+N%3BWallace-Jones%2C+B%3BEbert%2C+A+D%3BWechselberger%2C+C%3BSalomon%2C+D+S&rft.aulast=Mart%C3%ADnez-Lacaci&rft.aufirst=I&rft.date=2000-10-01&rft.volume=88&rft.issue=1&rft.spage=44&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 - 2000-09-26 N1 - Date created - 2000-09-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhancing effects of Thai edible plants on 2-amino-3, 8-dimethylimidazo(4,5-f)quinoxaline-hepatocarcinogenesis in a rat medium-term bioassay. AN - 72208905; 10960770 AB - Boesenbergia pandurata (Zingiberaceae), Languas galanga (Zingiberaceae) and Citrus hystrix (Rutaceae) are edible plants that are commonly used as flavors or condiments in various Thai food dishes. They are known to exert strong anti-promoting activity in a test of tumor promoter-induced Epstein-Barr virus (EBV) activation. In the present study their effects on hepatocarcinogenesis were investigated in a medium-term bioassay using F344 male rats. C. hystrix significantly enhanced 2-amino-3,8-dimethylimidazo(4, 5-f)quinoxaline-associated preneoplastic liver cell focus development while B. pandurata and L. galanga had borderline effects. The results suggest that C. hystrix as well as B. pandurata and L. galanga may contain agents augmenting the hepatocarcinogenicity of 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline. JF - Cancer letters AU - Tiwawech, D AU - Hirose, M AU - Futakuchi, M AU - Lin, C AU - Thamavit, W AU - Ito, N AU - Shirai, T AD - Research Division, National Cancer Institute, Bangkok, Thailand. tdanai@hotmail.com Y1 - 2000/10/01/ PY - 2000 DA - 2000 Oct 01 SP - 195 EP - 201 VL - 158 IS - 2 SN - 0304-3835, 0304-3835 KW - Carcinogens KW - 0 KW - Isoenzymes KW - Quinoxalines KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline KW - 77500-04-0 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Animals KW - Liver -- enzymology KW - Liver -- pathology KW - Thailand KW - Glutathione Transferase -- metabolism KW - Isoenzymes -- drug effects KW - Isoenzymes -- metabolism KW - Rats KW - Diethylnitrosamine -- toxicity KW - Rats, Inbred F344 KW - Liver -- drug effects KW - Carcinogenicity Tests -- methods KW - Glutathione Transferase -- drug effects KW - Diet KW - Drug Synergism KW - Male KW - Organ Size -- drug effects KW - Plants, Medicinal -- toxicity KW - Liver Neoplasms, Experimental -- pathology KW - Quinoxalines -- toxicity KW - Carcinogens -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72208905?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Enhancing+effects+of+Thai+edible+plants+on+2-amino-3%2C+8-dimethylimidazo%284%2C5-f%29quinoxaline-hepatocarcinogenesis+in+a+rat+medium-term+bioassay.&rft.au=Tiwawech%2C+D%3BHirose%2C+M%3BFutakuchi%2C+M%3BLin%2C+C%3BThamavit%2C+W%3BIto%2C+N%3BShirai%2C+T&rft.aulast=Tiwawech&rft.aufirst=D&rft.date=2000-10-01&rft.volume=158&rft.issue=2&rft.spage=195&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 - 2000-10-31 N1 - Date created - 2000-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cocaine medications, cocaine consumption and societal costs. AN - 70547131; 15344308 AB - To estimate the benefits of reduced cocaine consumption in terms of reduced societal costs resulting from the introduction of a medication for cocaine dependence with a small incremental treatment effect. Cost-benefit analysis is applied to study the implications of reduced cocaine consumption. A modelling approach extrapolates the magnitude of treatment effects. Epidemiological data on cocaine use and consumption as well as economic methods of cost-benefit analysis are utilised. Estimates of societal costs associated with heavy users of cocaine, who are most likely addicted and in need of immediate treatment, are developed using 1995 data. In the first analysis, a postulated 1% reduction in consumption of cocaine among heavy users is examined to approximate a small treatment effect, resulting in a minimal consumption benefit. It is estimated that such a reduction would be valued at $US259 million. The cost-benefit analysis indicated that a cocaine medication with a small treatment effect (10 percentage point increase in abstinence rates) would result in a benefit to cost ratio in the range of 1.58 to 5.79, depending on prescribing behaviour and type of patient. Such estimates of the benefits of these small treatment effects are conservative, and they may be biased downwards since the willingness to pay for such a cocaine medication could far exceed the benefit to cost estimation used in this paper. Nevertheless, the substantial benefits found in this paper indicate how important investment in cocaine medication is for public health policy; costs may be reduced with efficient prescribing behaviour. Market and governmental barriers to the utilisation of a cocaine medication could reduce the benefits and increase costs. Clinical trials, cost-effectiveness studies, and cost-benefit studies must be conducted to establish the actual pattern of benefits and costs that could be obtained for an efficacious and effective cocaine medication. JF - PharmacoEconomics AU - Cartwright, W S AD - National Institute on Drug Abuse, Bethesda, Maryland 20892, USA. wc34b@nih.gov Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 405 EP - 413 VL - 18 IS - 4 SN - 1170-7690, 1170-7690 KW - Cocaine KW - I5Y540LHVR KW - Health technology assessment KW - Humans KW - Cocaine-Related Disorders -- economics KW - Cocaine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70547131?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=PharmacoEconomics&rft.atitle=Cocaine+medications%2C+cocaine+consumption+and+societal+costs.&rft.au=Cartwright%2C+W+S&rft.aulast=Cartwright&rft.aufirst=W&rft.date=2000-10-01&rft.volume=18&rft.issue=4&rft.spage=405&rft.isbn=&rft.btitle=&rft.title=PharmacoEconomics&rft.issn=11707690&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-16 N1 - Date created - 2004-09-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Social and Environmental Predictors of Maternal Depression in Current and Recent Welfare Recipients AN - 61502855; 200102680 AB - Depression is highly prevalent in welfare recipients, & is associated with failure to move from welfare to work. This paper examines the relationship between social & environmental factors in a large, community-based sample of mothers who currently or recently received welfare benefits. Specific & modifiable risk factors related to poverty, gender, & race were found to predict major depression beyond traditional risk factors. Research & practice implications are discussed. 3 Tables, 147 References. Adapted from the source document. JF - American Journal of Orthopsychiatry AU - Siefert, Kristine AU - Bowman, Phillip J AU - Heflin, Colleen M AU - Danziger, Sheldon AU - Williams, David R AD - NIMH Research Center Poverty/Risk/Mental Health, School Social Work, U Michigan, Ann Arbor Y1 - 2000/10// PY - 2000 DA - October 2000 SP - 510 EP - 522 VL - 70 IS - 4 SN - 0002-9432, 0002-9432 KW - Socioeconomic Factors KW - Depression (Psychology) KW - Mothers KW - Welfare Recipients KW - Michigan KW - Environmental Factors KW - article KW - 6142: mental & emotional health problems KW - 6141: poverty & homelessness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61502855?accountid=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=American+Journal+of+Orthopsychiatry&rft.atitle=Social+and+Environmental+Predictors+of+Maternal+Depression+in+Current+and+Recent+Welfare+Recipients&rft.au=Siefert%2C+Kristine%3BBowman%2C+Phillip+J%3BHeflin%2C+Colleen+M%3BDanziger%2C+Sheldon%3BWilliams%2C+David+R&rft.aulast=Siefert&rft.aufirst=Kristine&rft.date=2000-10-01&rft.volume=70&rft.issue=4&rft.spage=510&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Orthopsychiatry&rft.issn=00029432&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Last updated - 2016-09-28 N1 - CODEN - AJORAG N1 - SubjectsTermNotLitGenreText - Mothers; Depression (Psychology); Welfare Recipients; Socioeconomic Factors; Environmental Factors; Michigan ER - TY - JOUR T1 - COMPARATIVE IN VITRO CYTOTOXICITY OF ETHYL ACRYLATE AND TRIPROPYLENE GLYCOL DIACRYLATE TO NORMAL HUMAN SKIN AND LUNG CELLS AN - 19335075; 8696060 AB - The potential for occupational exposure to the esters of acrylic acid (acrylates) is considerable, and, thus, requires a greater understanding of the their toxicity. Confluent (70-90%) cultures of normal human epidermal keratinocytes (NHEK), dermal fibroblasts (NHDF), or bronchial epithelium (NHBE) were exposed to the monofunctional ethyl acrylate (EA), the multifunctional tripropylene glycol diacrylate (TPGDA), or TPGDA monomer in a radiation curable lacquer (Lacquer A) at equimolar dosages in order to determine human in vitro cytotoxicity. Viability of the cells after 2-24-h exposure to the representative monofunctional or multifunctional acrylate or solvent control was used to calculate an index of acute cytotoxicity (50% inhibitory dose; ID50) and to determine the shape of the dose-response curves. TPGDA, Lacquer A, and EA were equally cytotoxic (ID50 approximately 0.1 mu mol/cm2) to NHEK at equimolar doses. TPGDA or Lacquer A were more cytotoxic ( approximately 100) to NHDF or NHBE than EA. Sequential exposure of UVA and TPGDA to NHEK indicate the potential for a synergistic cytotoxic response. These findings are consistent with observed decreases in free sulfhydryl groups (e.g., glutathione or cysteine) that parallel the dose-response-related decreases in viability. Together, these data suggest possible differences in toxicity between the monofunctional EA and multifunctional TPGDA to NHEK, NHDF, or NHBE, possibly due to the difference in the number of functional acrylate groups and/or physicochemical differences (e.g., vapor pressure) between the acrylates investigated. JF - In Vitro Cellular & Developmental Biology - Animal AU - Nylander-French, Leena A AU - French, John E AD - Department of Environmental Sciences and Engineering (L. A. N.-F.), School of Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 and Laboratory of Environmental Carcinogenesis and Mutagenesis (L. A. N.-F., J. E. F.), National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, leena_french@unc.edu Y1 - 2000/10// PY - 2000 DA - Oct 2000 SP - 611 EP - 616 PB - Allen Press, Inc., 810 East Tenth St. VL - 36 IS - 9 SN - 1071-2690, 1071-2690 KW - Health & Safety Science Abstracts; Biotechnology and Bioengineering Abstracts KW - human keratinocytes KW - bronchiolar cells KW - acrylates KW - cytotoxicity KW - fibroblasts KW - Glutathione KW - Acrylic acid KW - Cell culture KW - Fibroblasts KW - vapor pressure KW - Vapors KW - Dose-response effects KW - Epithelium KW - Keratinocytes KW - Pressure KW - Occupational exposure KW - alpha Radiation KW - Skin KW - Data processing KW - Physicochemical properties KW - Solvents KW - Toxicity KW - Sulfhydryl groups KW - Esters KW - Monomers KW - Cytotoxicity KW - Cysteine KW - Lung KW - W 30925:Genetic Engineering KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19335075?accountid=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=The+Journal+of+biological+chemistry&rft.atitle=Minor+groove+interactions+at+the+DNA+polymerase+beta+active+site+modulate+single-base+deletion+error+rates.&rft.au=Osheroff%2C+W+P%3BBeard%2C+W+A%3BYin%2C+S%3BWilson%2C+S+H%3BKunkel%2C+T+A&rft.aulast=Osheroff&rft.aufirst=W&rft.date=2000-09-08&rft.volume=275&rft.issue=36&rft.spage=28033&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 revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - alpha Radiation; Data processing; Skin; Glutathione; Acrylic acid; Solvents; Cell culture; Sulfhydryl groups; Toxicity; Esters; Fibroblasts; Monomers; Vapors; Cytotoxicity; Lung; Cysteine; Epithelium; Keratinocytes; Pressure; Occupational exposure; vapor pressure; Dose-response effects; Physicochemical properties DO - http://dx.doi.org/10.1290/1071-2690(2000)036<0611:CIVCOE>2.0.CO;2 ER - TY - JOUR T1 - Geographic information systems. A new tool in environmental epidemiology. AN - 1859344586; 11018420 AB - PURPOSE: Geographic Information Systems (GIS) are useful tools for identifying populations with potential exposure to environmental contaminants. Using a GIS, features of the local environment around an individual's home, work, or school can be described. We present two examples illustrating methods and issues in identifying populations potentially exposed to agricultural pesticides and to toxic releases from the Toxic Release Inventory (TRI).METHODS: We used USDA Farm Service Agency records as ground reference data to classify a late summer 1984 satellite image into crop species in 3 counties in Nebraska. We located residences from a case-control study of non-Hodgkin's lymphoma (NHL) on the crop maps and calculated the distance to crop fields. Residences from a 4-center study of NHL were mapped and the distance to TRI sites was determined.RESULTS: Twenty-two percent of residences had crop fields within 500 meters of the home, an intermediate distance for the range of drift effects from pesticide applications. After accounting for the extent of primary drift from ground applications of pesticides, we estimated that 30 percent of residences were potentially exposed to crop pesticides. In the 4-center study, residence locations determined by address-matching methods and by a global positioning system were compared; the population 1 mile from specific TRI sites is described.CONCLUSIONS: These examples demonstrate the utility of a GIS in environmental epidemiology studies. A GIS can be a useful addition to questionnaire and other methods of exposure assessment in health studies. JF - Annals of epidemiology AU - Ward AU - Nuckols AU - Weigel AU - Maxwell AU - Cantor AU - Miller AD - Division of Cancer Epidemiology and Genetics, NCI, Bethesda, MD, USA Y1 - 2000/10/01/ PY - 2000 DA - 2000 Oct 01 SP - 477 VL - 10 IS - 7 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859344586?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+epidemiology&rft.atitle=Geographic+information+systems.+A+new+tool+in+environmental+epidemiology.&rft.au=Ward%3BNuckols%3BWeigel%3BMaxwell%3BCantor%3BMiller&rft.aulast=Ward&rft.aufirst=&rft.date=2000-10-01&rft.volume=10&rft.issue=7&rft.spage=477&rft.isbn=&rft.btitle=&rft.title=Annals+of+epidemiology&rft.issn=1873-2585&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2000-10-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Privileged Access Model of 1,3-Butadiene Disposition AN - 17885674; 5118692 AB - In previous attempts to model disposition of 1,3-butadiene in mice and rats, parameter values for 1,2-epoxybut-3-ene metabolism were optimized to reproduce elimination of this gas from closed chambers. However, each of these models predicted much higher concentrations of circulating epoxybutene than were subsequently measured in animals exposed to butadiene. To account for this discrepancy, a previous physiologically based pharmacokinetic model of butadiene disposition was modified to describe a transient complex between cytochrome P450 and epoxide hydrolase on the endoplasmic reticulum membrane. In this model the epoxide products are directly transferred from the P450 to the epoxide hydrolase in competition with release of products into the cytosol. The model includes flow-restricted delivery of butadiene and epoxides to gastrointestinal tract, liver, lung, kidney, fat, other rapidly perfused tissues, and other slowly perfused tissues. Blood was distributed among compartments for arterial, venous, and capillary spaces. Oxidation of butadiene and epoxybutene and hydrolysis and glutathione conjugation of epoxides were included in liver, lung, and kidney. The model reproduces observed uptake of butadiene and epoxybutene from closed chambers by mice and rats and steady-state concentrations of butadiene, epoxybutene, and 1,2; 3,4-diepoxybutane concentrations in blood of mice and rats exposed by nose only. Successful replication of these observations indicates that the proposed privileged access of epoxides formed in situ to epoxide hydrolase is a plausible mechanistic representation for the metabolic clearance of epoxide-forming chemicals. JF - Environmental Health Perspectives AU - Kohn, M C AU - Melnick, R L AD - Laboratory of Computational Biology and Risk Analysis, NIEHS, PO Box 12233, Mail Drop A3-06, Research Triangle Park, NC 27709-2233, USA, kohn@valiant.niehs.nih.gov Y1 - 2000/10// PY - 2000 DA - Oct 2000 SP - 911 EP - 917 VL - 108 SN - 0091-6765, 0091-6765 KW - disposition KW - mice KW - rats KW - Toxicology Abstracts KW - Mathematical models KW - 1,3-Butadiene KW - Cytochrome P450 KW - Epoxide hydrolase KW - X 24153:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17885674?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=The+Privileged+Access+Model+of+1%2C3-Butadiene+Disposition&rft.au=Kohn%2C+M+C%3BMelnick%2C+R+L&rft.aulast=Kohn&rft.aufirst=M&rft.date=2000-10-01&rft.volume=108&rft.issue=&rft.spage=911&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cytochrome P450; 1,3-Butadiene; Mathematical models; Epoxide hydrolase ER - TY - JOUR T1 - Current Directions in Physiological Modeling for Environmental Health Sciences: An Overview AN - 17881443; 5118687 AB - Characterization of the risks to human health associated with exposure to environmental pollutants has historically followed the model of toxicology, namely, observing the incidence of pathology in experimental animals consequent to exposure at several doses. The incidence of the response was then (usually linearly) extrapolated from the experimental doses to exposures typical in the environment and occupational settings. Regulatory agencies estimate doses in humans that would produce the extrapolated response by scaling the extrapolated dose for animals by the two-thirds power of body weight. Owing to lack of knowledge and in order to protect human health, humans are assumed to be as sensitive to the toxicant as is the most sensitive animal species. Physiological models typically use mean values for their physiological and biochemical parameters. The observed values include both uncertainties in measurement and variation due to genetic differences among individuals. Human populations may exhibit large interindividual variability, and a subpopulation may be significantly more sensitive than the average individual. JF - Environmental Health Perspectives AU - Kohn, M C AD - Laboratory of Computational Biology and Risk Analysis, NIEHS, PO Box 12233, MD A3-06, Research Triangle Park, NC 27709, USA, kohn@valiant.niehs.nih.gov Y1 - 2000/10// PY - 2000 DA - Oct 2000 SP - 857 EP - 859 VL - 108 SN - 0091-6765, 0091-6765 KW - physiological models KW - Toxicology Abstracts KW - Reviews KW - Pollution effects KW - Environmental factors KW - Models KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17881443?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Current+Directions+in+Physiological+Modeling+for+Environmental+Health+Sciences%3A+An+Overview&rft.au=Kohn%2C+M+C&rft.aulast=Kohn&rft.aufirst=M&rft.date=2000-10-01&rft.volume=108&rft.issue=&rft.spage=857&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Environmental factors; Pollution effects; Reviews; Models ER - TY - JOUR T1 - Seropidemiology of Helicobacter pylori infection in a population of Egyptian children AN - 17846941; 4872714 AB - Background: To describe the seroepidemiology of Helicobacter pylori infection in a population of Egyptian children under 3 years. Methods: A cohort of children under 36 months, residing in Abu Homos, Egypt, were visited at home twice weekly. Information regarding the child's breastfeeding status was obtained, and periodic anthropometric and household hygiene surveys were performed. In June 1997, a serosurvey was conducted on 187 study participants over 6 months old. The serosurvey was repeated in October 1997. All sera were tested for IgG antibodies to H. pylori. Results: The June prevalence of H. pylori infection was 10%, and the incidence from June to October was 15%. Between June and October, 8 (42%) of 19 children that were positive for H. pylori infection seroreverted to negative. All seroreversions occurred in children 6-17 months. Other than age, no sociodemographic or environmental factor was significantly associated with incident H. pylori infection. There was no significant differences in the weight-for-age, weight-for-height, and height-for-age z-scores between children with and without prevalent H. pylori infection. Conclusions: Infection with H. pylori is common in Egyptian children under 3 years old and is not associated with malnutrition. No predictors for H. pylori infection were found. Our preliminary evidence for transient H. pylori infections in young children needs to be confirmed in a prospective cohort study, and predictors for persistent infection should be sought, since only these may be relevant to the known sequellae of infection. JF - International Journal of Epidemiology AU - Naficy, AB AU - Frenck, R W AU - Abu-Elyazeed, R AU - Kim, Y AU - Rao, M R AU - Savarino, S J AU - Wierzba, T F AU - Hall, E AU - Clemens, J D AD - Epidemiology Branch, National Institute of Child Health and Human Development, Room 7B03, 6100 Executive Boulevard, Rockville, MD 20852, USA Y1 - 2000/10// PY - 2000 DA - Oct 2000 SP - 928 EP - 932 VL - 29 IS - 5 SN - 0300-5771, 0300-5771 KW - Egypt KW - Microbiology Abstracts B: Bacteriology KW - Serological surveys KW - Helicobacter pylori KW - Malnutrition KW - Children KW - J 02846:Gastrointestinal tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17846941?accountid=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=Seropidemiology+of+Helicobacter+pylori+infection+in+a+population+of+Egyptian+children&rft.au=Naficy%2C+AB%3BFrenck%2C+R+W%3BAbu-Elyazeed%2C+R%3BKim%2C+Y%3BRao%2C+M+R%3BSavarino%2C+S+J%3BWierzba%2C+T+F%3BHall%2C+E%3BClemens%2C+J+D&rft.aulast=Naficy&rft.aufirst=AB&rft.date=2000-10-01&rft.volume=29&rft.issue=5&rft.spage=928&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 N1 - SubjectsTermNotLitGenreText - Helicobacter pylori; Serological surveys; Malnutrition; Children ER - TY - JOUR T1 - A pot-pourri of plasmid paradoxes: effects of a second copy AN - 17834230; 4866007 AB - Bacterial plasmids are exemplary subjects for study, being conveniently isolated, dissected, reassembled, and introduced into various hosts. Their versatility and power make them eminently worthy of our attention. In what follows I consider some consequences of simply doubling the dosage of particular plasmid genes or of forming a plasmid dimer. These consequences can be perverse, paradoxical, or informative. They bear on questions of cell viability, copy number limitation, clonal homogeneity, check-point control, and the recovery of mutants. They have relevance to biotechnology, evolution and medicine. In reviewing these effects, my motivation is largely to share my enthusiasm for certain kinds of biological narratives, the nature of which is best left for the reader to discern. JF - Molecular Microbiology AU - Yarmolinsky, B M AD - Laboratory of Biochemistry, National Cancer Institute, N. I. H. , 37 Convent Drive, Bethesda, MD 20892-4255, USA. Y1 - 2000/10// PY - 2000 DA - Oct 2000 SP - 1 EP - 7 PB - Blackwell Science Ltd VL - 38 IS - 1 SN - 0950-382X, 0950-382X KW - genes KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Bacteria KW - Reviews KW - Viability KW - Plasmids KW - J 02760:Plasmids KW - G 07203:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17834230?accountid=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=A+pot-pourri+of+plasmid+paradoxes%3A+effects+of+a+second+copy&rft.au=Yarmolinsky%2C+B+M&rft.aulast=Yarmolinsky&rft.aufirst=B&rft.date=2000-10-01&rft.volume=38&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2000.02127.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bacteria; Plasmids; Reviews; Viability DO - http://dx.doi.org/10.1046/j.1365-2958.2000.02127.x ER - TY - JOUR T1 - Improved template preparation for PCR-based assays for detection of food-borne bacterial pathogens AN - 17739526; 4794982 AB - Shigella flexneri, Salmonella enterica serotype Typhimurium, and Listeria monocytogenes were applied to FTA filters, and the filters were used directly as templates to demonstrate their sensitivity and applicability in PCR-based detection assays. With pure cultures, the sensitivities of detection by FTA filter-based PCR were 30 to 50 and 200 CFU for the gram-negative enterics and Listeria, respectively. Different numbers of S. flexneri cells were used in controlled contamination experiments with several different foods (produce, beef, and apple cider). Aliquots from concentrated food washes subsequently spotted onto FTA filters and assayed by PCR gave consistently positive results and detection limits similar to those observed with pure-culture dilutions. This universal method for PCR template preparation from bacterial cells is rapid and highly sensitive and reduces interference from food-associated inhibitors of PCR. In addition, its broad applicability eliminates the need for multiple methods for analysis of food matrices. JF - Applied and Environmental Microbiology AU - Lampel, KA AU - Orlandi, P A AU - Kornegay, L AD - Food and Drug Administration, HFS-237, 200 C St., SW, Washington, DC 20204, USA, kal@codon.nih.gov Y1 - 2000/10// PY - 2000 DA - Oct 2000 SP - 4539 EP - 4542 VL - 66 IS - 10 SN - 0099-2240, 0099-2240 KW - Microbiology Abstracts A: Industrial & Applied Microbiology KW - Listeria monocytogenes KW - Bioassays KW - Salmonella enterica KW - Shigella flexneri KW - Detection KW - Polymerase chain reaction KW - Pathogens KW - Food-borne diseases KW - A 01116:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17739526?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+and+Environmental+Microbiology&rft.atitle=Improved+template+preparation+for+PCR-based+assays+for+detection+of+food-borne+bacterial+pathogens&rft.au=Lampel%2C+KA%3BOrlandi%2C+P+A%3BKornegay%2C+L&rft.aulast=Lampel&rft.aufirst=KA&rft.date=2000-10-01&rft.volume=66&rft.issue=10&rft.spage=4539&rft.isbn=&rft.btitle=&rft.title=Applied+and+Environmental+Microbiology&rft.issn=00992240&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 - Shigella flexneri; Listeria monocytogenes; Salmonella enterica; Bioassays; Polymerase chain reaction; Food-borne diseases; Detection; Pathogens ER - TY - JOUR T1 - Production of HIV-1 gp120 in Packed-Bed Bioreactor Using the Vaccinia Virus/T7 Expression System AN - 17725307; 4789089 AB - The HeLa cell-vaccinia virus system is an attractive method for producing recombinant mammalian proteins with proper post-translation modifications. This approach is especially important for the production of HIV-1 envelope glycoprotein, gp120, since more than half of its total mass is due to carbohydrates. A recombinant vaccinia virus/T7 RNA polymerase expression system was developed to express and produce large amounts of gp120 tagged with six histidine residues. In this system, the expressed T7 RNA polymerase from one virus drives the transcription of the gp120 encoded in the second virus. During the process development phase, the following parameters were studied: infection time, infection duration, multiplicity of infection, ratio of the two viruses, medium composition, and medium replacement strategy during the infection phase. The chosen production method was based on using the packed-bed bioreactor. The HeLa cells were immobilized on fibrous disks (Fibra-Cel) packed in an internal basket positioned in a vertically mixed bioreactor (Celligen Plus), and 25 g of carriers were packed in a 1.6-L (working volume) reactor. The process included a growth stage followed by a production stage. In the growth stage, the bed was perfused with a serum-containing medium, allowing the cells to grow to saturation, and in the production stage, done using serum-free medium, the cells were infected with the two recombinant viruses. The expressed protein was secreted, collected from the culture fluid, and purified. The specific production was found to be between 2 and 3 mu g of protein/10 super(6) cells, and the volumetric production was around 10 mg/50 g carriers. JF - Biotechnology Progress AU - Hu, Y-C AU - Kaufman, J AU - Cho, M W AU - Golding, H AU - Shiloach, J AD - Biotechnology Unit, Bldg. 6, Rm. B1-33, NIH, Bethesda, MD 20892, USA, yossi@nih.gov Y1 - 2000/10// PY - 2000 DA - Oct 2000 SP - 744 EP - 750 VL - 16 IS - 5 SN - 8756-7938, 8756-7938 KW - HIV-1 KW - glycoprotein gp120 KW - human immunodeficiency virus 1 KW - phage T7 KW - vaccinia virus KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Phage T7 KW - Immobilized cells KW - Gene expression KW - HeLa cells KW - DNA-directed RNA polymerase KW - Envelopes KW - Vaccinia virus KW - Bioreactors KW - Envelope protein KW - Human immunodeficiency virus 1 KW - V 22002:AIDS: Molecular and in vitro aspects KW - W3 33580:Process engineering KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17725307?accountid=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+Progress&rft.atitle=Production+of+HIV-1+gp120+in+Packed-Bed+Bioreactor+Using+the+Vaccinia+Virus%2FT7+Expression+System&rft.au=Hu%2C+Y-C%3BKaufman%2C+J%3BCho%2C+M+W%3BGolding%2C+H%3BShiloach%2C+J&rft.aulast=Hu&rft.aufirst=Y-C&rft.date=2000-10-01&rft.volume=16&rft.issue=5&rft.spage=744&rft.isbn=&rft.btitle=&rft.title=Biotechnology+Progress&rft.issn=87567938&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Phage T7; Human immunodeficiency virus 1; Vaccinia virus; Bioreactors; Envelopes; DNA-directed RNA polymerase; Immobilized cells; HeLa cells; Gene expression; Envelope protein ER - TY - JOUR T1 - X-linked severe combined immunodeficiency: from molecular cause to gene therapy within seven years AN - 17723897; 4793891 AB - X-linked severe combined immunodeficiency (XSCID) is the most common form of SCID. The discovery of the genetic defect in this disease, namely mutations in the gene encoding the common cytokine receptor gamma chain, gamma sub(c), was reported just over seven years ago. In the subsequent period, a tremendous amount of knowledge about the biology and function of this protein has been generated. Moreover, gamma sub(c)-knockout mice have been generated and their immune systems successfully reconstituted by gene therapy. Furthermore, initial attempts at using gene therapy to treat patients with XSCID have been successful for more than ten months, making this disease perhaps the most promising to date for treatment with such a strategy. JF - Molecular Medicine Today AU - Leonard, W J AD - Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1674, USA, wjl@helix.nih.gov Y1 - 2000/10// PY - 2000 DA - Oct 2000 SP - 403 EP - 407 VL - 6 IS - 10 SN - 1357-4310, 1357-4310 KW - knockout mice KW - ^g-chain KW - immunology KW - man KW - X-linked severe combined immunodeficiency KW - gamma -chain KW - cytokine receptors KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - Gene therapy KW - Gene transfer KW - Reviews KW - Severe combined immunodeficiency KW - F 06857:Combined KW - W3 33056:Animal models of human disease KW - G 07444:Animal models KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17723897?accountid=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=Molecular+Medicine+Today&rft.atitle=X-linked+severe+combined+immunodeficiency%3A+from+molecular+cause+to+gene+therapy+within+seven+years&rft.au=Leonard%2C+W+J&rft.aulast=Leonard&rft.aufirst=W&rft.date=2000-10-01&rft.volume=6&rft.issue=10&rft.spage=403&rft.isbn=&rft.btitle=&rft.title=Molecular+Medicine+Today&rft.issn=13574310&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 - Gene therapy; Gene transfer; Reviews; Severe combined immunodeficiency ER - TY - JOUR T1 - Encephalitogenic potential of the myelin basic protein peptide (amino acids 83-99) in multiple sclerosis: Results of a phase II clinical trial with an altered peptide ligand AN - 17710551; 4782603 AB - Myelin-specific T lymphocytes are considered essential in the pathogenesis of multiple sclerosis. The myelin basic protein peptide (a.a. 83-99) represents one candidate antigen; therefore, it was chosen to design an altered peptide ligand, CGP77116, for specific immunotherapy of multiple sclerosis. A magnetic resonance imaging-controlled phase II clinical trial with this altered peptide ligand documented that it was poorly tolerated at the dose tested, and the trial had therefore to be halted. Improvement or worsening of clinical or magnetic resonance imaging parameters could not be demonstrated in this small group of individuals because of the short treatment duration. Three patients developed exacerbations of multiple sclerosis, and in two this could be linked to altered peptide ligand treatment by immunological studies demonstrating the encephalitogenic potential of the myelin basic protein peptide (a.a. 83-99) in a subgroup of patients. These data raise important considerations for the use of specific immunotherapies in general. JF - Nature Medicine AU - Bielekova, B AU - Goodwin, B AU - Richert, N AU - Cortese, I AU - Kondo, Takayuki AU - Afshar, G AU - Gran, B AU - Eaton, J AU - Antel, J AU - Frank, JA AU - McFarland, H F AU - Martin, R AD - Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Clinical Center, National Institutes of Health, Bethesda, MD 20892-1400, USA Y1 - 2000/10// PY - 2000 DA - Oct 2000 SP - 1167 EP - 1175 VL - 6 IS - 10 SN - 1078-8956, 1078-8956 KW - man KW - ligands KW - clinical trials KW - immunology KW - myelin basic protein KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Multiple sclerosis KW - Immunotherapy KW - Magnetic resonance imaging KW - Neuroimmunology KW - Pathogenesis KW - Clinical trials KW - Lymphocytes T KW - Ligands KW - Myelin basic protein KW - F 068765:Multiple sclerosis KW - W3 33190:Therapy: Other KW - F 06840:Immunotherapy of immune diseases KW - N3 11110:Neuroimmunology KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17710551?accountid=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+Medicine&rft.atitle=Encephalitogenic+potential+of+the+myelin+basic+protein+peptide+%28amino+acids+83-99%29+in+multiple+sclerosis%3A+Results+of+a+phase+II+clinical+trial+with+an+altered+peptide+ligand&rft.au=Bielekova%2C+B%3BGoodwin%2C+B%3BRichert%2C+N%3BCortese%2C+I%3BKondo%2C+Takayuki%3BAfshar%2C+G%3BGran%2C+B%3BEaton%2C+J%3BAntel%2C+J%3BFrank%2C+JA%3BMcFarland%2C+H+F%3BMartin%2C+R&rft.aulast=Bielekova&rft.aufirst=B&rft.date=2000-10-01&rft.volume=6&rft.issue=10&rft.spage=1167&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Multiple sclerosis; Lymphocytes T; Magnetic resonance imaging; Immunotherapy; Pathogenesis; Neuroimmunology; Myelin basic protein; Ligands; Clinical trials ER - TY - JOUR T1 - Comparison of Six Commercial DNA Extraction Kits for Recovery of Cytomegalovirus DNA from Spiked Human Specimens AN - 17697563; 4776906 AB - We evaluated six commercially available DNA extraction kits for their ability to recover DNA from various dilutions of cytomegalovirus (CMV) added to four different specimens: bronchoalveolar lavage, cerebral spinal fluid, plasma, and whole blood. The kits evaluated included the Puregene DNA isolation kit (PG), Generation Capture Column kit, MasterPure DNA purification kit, IsoQuick nucleic acid extraction kit, QIAamp blood kit, and NucliSens isolation kit (NS). All six kits evaluated effectively removed PCR inhibitors from each of the four specimen types and produced consistently positive results down to a spiked concentration of 200 PFU of whole CMV per ml. However, the NS and PG resulted in the most consistently positive results at the lowest concentrations of spiked CMV (4 and 0.4 PFU/ml) and, in this evaluation, offered the most sensitive methods for extracting CMV DNA from the four different spiked specimens. Processing time and cost were also evaluated. JF - Journal of Clinical Microbiology AU - Fahle, G A AU - Fischer, SH AD - National Institutes of Health, Microbiology Service, Building 10, Room 2C-385, Bethesda, MD 20892-1508, USA, gfahle@nih.gov Y1 - 2000/10// PY - 2000 DA - Oct 2000 SP - 3860 EP - 3863 VL - 38 IS - 10 SN - 0095-1137, 0095-1137 KW - DNA extraction KW - bronchoalveolar lavage KW - Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Blood KW - Human cytomegalovirus KW - Cerebrospinal fluid KW - Plasma KW - Extraction KW - V 22021:Virus purification & preparation KW - A 01114:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17697563?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Microbiology&rft.atitle=Comparison+of+Six+Commercial+DNA+Extraction+Kits+for+Recovery+of+Cytomegalovirus+DNA+from+Spiked+Human+Specimens&rft.au=Fahle%2C+G+A%3BFischer%2C+SH&rft.aulast=Fahle&rft.aufirst=G&rft.date=2000-10-01&rft.volume=38&rft.issue=10&rft.spage=3860&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human cytomegalovirus; Cerebrospinal fluid; Blood; Plasma; Extraction ER - TY - JOUR T1 - Analyzing DNA Strand Compositional Asymmetry to Identify Candidate Replication Origins of Borrelia burgdorferi Linear and Circular Plasmids AN - 17647477; 4792448 AB - The Lyme disease agent Borrelia burgdorferi has a genome composed of a linear chromosome and a series of linear and circular plasmids. We previously mapped the oriC of the linear chromosome to the center of the molecule, where a pronounced switch in CG skew occurs. In this study, we analyzed B. burgdorferi plasmid sequences for AT and CG skew in an effort to similarly identify plasmid replication origins. Cumulative skew diagrams of the plasmids suggested that they, like the linear chromosome, replicate bidirectionally from an internal origin. The B. burgdorferi linear chromosome contains homologs to partitioning protein genes soj and spoOJ, which are closely linked to oriC at the minimum cumulative skew point of the 1-Mb molecule. A soj/parA homolog also maps to cumulative skew minima of the B. burgdorferi linear and circular plasmids, further suggesting that these regions contain the replication origin. The heterogeneity in these genes and in the nucleotide sequences of the putative origin regions could account for the mutual compatibility of the multiple DNA elements in B. burgdorferi. JF - Genome Research AU - Picardeau, M AU - Lobry, J R AU - Hinnebusch, B J AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Laboratory of Human Bacterial Pathogenesis, Hamilton, Montana 59840, USA, jhinnebusch@niaid.nih.gov Y1 - 2000/10// PY - 2000 DA - Oct 2000 SP - 1594 EP - 1604 VL - 10 IS - 10 SN - 1054-9803, 1054-9803 KW - parA gene KW - replication origins KW - soj gene KW - spoOJ gene KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids; Genetics Abstracts KW - Borrelia burgdorferi KW - Plasmids KW - Chromosomes KW - Lyme disease KW - N 14640:Structure & sequence KW - J 02760:Plasmids KW - G 07320:Bacterial genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17647477?accountid=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=Genome+Research&rft.atitle=Analyzing+DNA+Strand+Compositional+Asymmetry+to+Identify+Candidate+Replication+Origins+of+Borrelia+burgdorferi+Linear+and+Circular+Plasmids&rft.au=Picardeau%2C+M%3BLobry%2C+J+R%3BHinnebusch%2C+B+J&rft.aulast=Picardeau&rft.aufirst=M&rft.date=2000-10-01&rft.volume=10&rft.issue=10&rft.spage=1594&rft.isbn=&rft.btitle=&rft.title=Genome+Research&rft.issn=10549803&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 - Borrelia burgdorferi; Lyme disease; Plasmids; Chromosomes ER - TY - JOUR T1 - DNA Exchange and Insertional Inactivation in Spirochetes AN - 17644452; 4793591 AB - Spirochetes have complex life cycles and are associated with a number of diseases in humans and animals. Despite their significance as pathogens, spirochete genetics are in their early stages. However, gene inactivation has been achieved in Borrelia burgdorferi, Brachyspira hyodysenteriae, and Treponema denticola. Here, we review methods that have been used in spirochetes for gene inactivation and DNA exchange, with a primary focus on B. burgdorferi. We also describe factors influencing electrotransformation in B. burgdorferi. In summary, optimal transformation frequencies are obtained with log phase bacteria, large amounts of DNA (up to 50 mu g per transformation), and high field strength (12.5-37.5 kV/cm). Infectious B. burgdorferi isolates transform with frequencies 100-fold lower than those found for high passage, non-infectious strains. Surface characteristics of the bacteria, which often correlate with infectivity, are among the obstacles to effective transformation by electroporation. JF - Journal of Molecular Microbiology and Biotechnology AU - Tilly, K AU - Elias, A F AU - Bono, J L AU - Stewart, P AU - Rosa, P AD - Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, 903 S. 4th Street, Hamilton, Montana USA, prosa@nih.gov Y1 - 2000/10// PY - 2000 DA - Oct 2000 SP - 433 EP - 442 VL - 2 IS - 4 SN - 1464-1801, 1464-1801 KW - gene inactivation KW - DNA exchange KW - electroporation KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Transformation KW - Borrelia burgdorferi KW - Reviews KW - Brachyspira hyodysenteriae KW - Treponema denticola KW - J 02725:DNA KW - N 14100:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17644452?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Microbiology+and+Biotechnology&rft.atitle=DNA+Exchange+and+Insertional+Inactivation+in+Spirochetes&rft.au=Tilly%2C+K%3BElias%2C+A+F%3BBono%2C+J+L%3BStewart%2C+P%3BRosa%2C+P&rft.aulast=Tilly&rft.aufirst=K&rft.date=2000-10-01&rft.volume=2&rft.issue=4&rft.spage=433&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Microbiology+and+Biotechnology&rft.issn=14641801&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 - Borrelia burgdorferi; Brachyspira hyodysenteriae; Treponema denticola; Reviews; Transformation ER - TY - JOUR T1 - Bacterial Homologs of the Small Subunit of Eukaryotic DNA Primase AN - 17641399; 4793602 AB - Primases are RNA polymerases that synthesize the primer RNA that provides the 3' OH for strand elongation by DNA polymerases. Currently, three independent classes of primases are recognized. The best characterized of these are the DnaG-like proteins, which function as replicative primases in bacteria and some bacteriophages, and also have highly conserved homologs, whose function remains unknown, in all archaeal genomes sequenced to date. In bacteriophages, the DnaG-type primase domain is fused to the DnaB-like helicases, and this helicase-primase apparently has been acquired by eukaryotes via horizontal gene transfer. The catalytic domain of the DnaG-family proteins, the Toprim domain, is shared with topoisomerases (excluding topo IB from eukaryotes), OLD family nucleases and recR/M proteins. Almost complementary to the DnaG-like primases, in terms of phyletic distribution, are the eukaryote-type primases (EPs) that are comprised of two subunits. The small subunit is a divalent cation-dependent enzyme that shows no detectable relationship with the Toprim domain. Nevertheless, it contains a highly conserved DxD dyad that resembles the equivalent dyad of the Toprim domain. The large, non-catalytic subunit of these primases is poorly conserved and appears to be required for DNA-binding and association of the newly synthesized primer with DNA polymerase alpha . Both EP subunits are conserved in all archaea and in baculoviruses. A distinct third type of primase is encoded by herpesviruses; these appear to be unrelated to the DnaG and EP families, but also possess a conserved DXD dyad associated with the active site. Thus bacteria and eukaryotes use unrelated primases for genome replication, whereas archaea are peculiar in possessing both bacterial and eukaryote-type primases in an otherwise typically "eukaryotic" replication system. Here we report the detection of previously unrecognized homologs of the catalytic subunit of EP in several groups of bacteria. JF - Journal of Molecular Microbiology and Biotechnology AU - Koonin, E V AU - Wolf, YI AU - Kondrashov, A S AU - Aravind, L AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bldg. 38A, 8600 Rockville Pike, Bethesda MD 20894, USA, koonin@ncbi.nlm.nih.gov Y1 - 2000/10// PY - 2000 DA - Oct 2000 SP - 509 EP - 512 VL - 2 IS - 4 SN - 1464-1801, 1464-1801 KW - Toprim domain KW - DNA primase KW - DnaG protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Bacteria KW - DNA-directed RNA polymerase KW - Replication KW - Reviews KW - J 02725:DNA KW - N 14100:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17641399?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Microbiology+and+Biotechnology&rft.atitle=Bacterial+Homologs+of+the+Small+Subunit+of+Eukaryotic+DNA+Primase&rft.au=Koonin%2C+E+V%3BWolf%2C+YI%3BKondrashov%2C+A+S%3BAravind%2C+L&rft.aulast=Koonin&rft.aufirst=E&rft.date=2000-10-01&rft.volume=2&rft.issue=4&rft.spage=509&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Microbiology+and+Biotechnology&rft.issn=14641801&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 - Bacteria; Replication; Reviews; DNA-directed RNA polymerase ER - TY - JOUR T1 - Serodiagnosis of Louse-Borne Relapsing Fever with Glycerophosphodiester Phosphodiesterase (GlpQ) from Borrelia recurrentis AN - 17638592; 4776854 AB - Human louse-borne relapsing fever occurs in sporadic outbreaks in central and eastern Africa that are characterized by significant morbidity and mortality. Isolates of the causative agent, Borrelia recurrentis, were obtained from the blood of four patients during a recent epidemic of the disease in southern Sudan. The glpQ gene, encoding glycerophosphodiester phosphodiesterase, from these isolates was sequenced and compared with the glpQ sequences obtained from other relapsing-fever spirochetes. Previously we showed that GlpQ of Borrelia hermsii is an immunogenic protein with utility as a serological test antigen for discriminating tick-borne relapsing fever from Lyme disease. In the present work, we cloned and expressed the glpQ gene from B. recurrentis and used recombinant GlpQ in serological tests. Acute- and convalescent-phase serum samples obtained from 42 patients with louse-borne relapsing fever were tested with an indirect immunofluorescence assay (IFA) and an enzyme-linked immunosorbent assay (ELISA) that used whole cells of B. recurrentis and with immunoblotting to whole-cell lysates of the spirochete and Escherichia coli producing recombinant GlpQ. The geometric mean titers of the acute- and convalescent-phase serum samples measured by IFA were 1:83 and 1:575, respectively. The immunoblot analysis identified a high level of reactivity and seroconversion to GlpQ, and the assay was more sensitive than the whole-cell IFA and ELISA using purified, recombinant histidine-tagged GlpQ. Serum antibodies to GlpQ and other antigens persisted for 27 years in one patient. We conclude that assessment of anti-GlpQ antibodies will allow serological confirmation of louse-borne relapsing fever and determination of disease prevalence. JF - Journal of Clinical Microbiology AU - Porcella, S F AU - Raffel, S J AU - Schrumpf, ME AU - Schriefer, ME AU - Dennis, D T AU - Schwan, T G AD - Rocky Mountain Laboratories, 903 S. Fourth St., Hamilton, MT 59840, USA, tom_schwan@nih.gov Y1 - 2000/10// PY - 2000 DA - Oct 2000 SP - 3561 EP - 3571 VL - 38 IS - 10 SN - 0095-1137, 0095-1137 KW - man KW - louse-borne relapsing fever KW - serodiagnosis KW - Africa KW - GlpQ protein KW - glpQ gene KW - Microbiology Abstracts B: Bacteriology KW - Borrelia recurrentis KW - Relapsing fever KW - Borreliosis KW - Glycerophosphodiester phosphodiesterase KW - Sudan KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17638592?accountid=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=Serodiagnosis+of+Louse-Borne+Relapsing+Fever+with+Glycerophosphodiester+Phosphodiesterase+%28GlpQ%29+from+Borrelia+recurrentis&rft.au=Porcella%2C+S+F%3BRaffel%2C+S+J%3BSchrumpf%2C+ME%3BSchriefer%2C+ME%3BDennis%2C+D+T%3BSchwan%2C+T+G&rft.aulast=Porcella&rft.aufirst=S&rft.date=2000-10-01&rft.volume=38&rft.issue=10&rft.spage=3561&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&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 - Borrelia recurrentis; Sudan; Relapsing fever; Borreliosis; Glycerophosphodiester phosphodiesterase ER - TY - JOUR T1 - Cocaine and Metabolite Elimination Patterns in Chronic Cocaine Users During Cessation: Plasma and Saliva Analysis AN - 17634322; 4780636 AB - Several reports suggest a prolonged elimination of cocaine and metabolites after chronic use compared with single or occasional use. This study was designed to measure the half-lives of cocaine in plasma and saliva of individuals who consumed cocaine on a frequent basis. The disposition and elimination patterns of cocaine and metabolites in the body fluids of chronic high-dose cocaine users during acute cessation of use were investigated. Plasma and saliva specimens were collected over a 12-h period during cessation and analyzed by gas chromatography-mass spectrometry. Pharmacokinetic parameters were derived by noncompartmental analysis of plasma and saliva data. Results indicated a cocaine terminal T1U2 of 3.8 h in plasma and 7.9 h in saliva. The terminal T1U2 of benzoylecgonine was 6.6 h in plasma and 9.2 h in saliva. Compared with prior studies of acute low-dose cocaine administration, these findings suggest that cocaine's half-life is longer in active street users than in occasional users though the half-life of its main metabolite benzoylecgonine remains similar (as do cocaine saliva-to-plasma ratios). Thus, regular use of cocaine appears to alter the disposition and elimination of cocaine when compared to single or occasional use. JF - Journal of Analytical Toxicology AU - Moolchan, E T AU - Cone, E J AU - Wstadik, A AU - Huestis, MA AU - Preston, K L AD - Pharmacology and Therapeutics Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA Y1 - 2000/10// PY - 2000 DA - Oct 2000 SP - 458 EP - 466 PB - Preston Publications, Inc. VL - 24 IS - 7 SN - 0146-4760, 0146-4760 KW - plasma levels KW - man KW - chronic exposure KW - pharmacokinetics KW - Toxicology Abstracts KW - Gas chromatography KW - Saliva KW - Cocaine KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17634322?accountid=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+Analytical+Toxicology&rft.atitle=Cocaine+and+Metabolite+Elimination+Patterns+in+Chronic+Cocaine+Users+During+Cessation%3A+Plasma+and+Saliva+Analysis&rft.au=Moolchan%2C+E+T%3BCone%2C+E+J%3BWstadik%2C+A%3BHuestis%2C+MA%3BPreston%2C+K+L&rft.aulast=Moolchan&rft.aufirst=E&rft.date=2000-10-01&rft.volume=24&rft.issue=7&rft.spage=458&rft.isbn=&rft.btitle=&rft.title=Journal+of+Analytical+Toxicology&rft.issn=01464760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special issue: Society of Forensic Toxicologists, Inc. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cocaine; Saliva; Gas chromatography ER - TY - JOUR T1 - On the kinetics of voltage formation in purple membranes of Halobacterium salinarium AN - 17633842; 4779173 AB - The kinetics of the bacteriorhodopsin photocycle, measured by voltage changes in a closed membrane system using the direct electrometrical method (DEM) of Drachev, L.A., Jasaitus, A.A., Kaulen, A.D., Kondrashin, A.A., Liberman, E.A., Nemecek, I.B., Ostroumov, S.A., Semenov, Yu, A. & Skulachev, V.P. (1974) Nature249, 321-324 are sixfold slower than the kinetics obtained in optical studies with suspensions of purple membrane patches. In this study, we have investigated the reasons for this discrepancy. In the presence of the uncouplers carbonyl cyanide m-chlorophenylhydrazone or valinomycin, the rates in the DEM system are similar to the rates in suspensions of purple membrane. Two alternative explanations for the effects of uncouplers were evaluated: (a) the 'back-pressure' of the Delta mu similar to sub(H+) slows the kinetic steps leading to its formation, and (b) the apparent difference between the two systems is due to slow major electrogenic events that produce little or no change in optical absorbance. In the latter case, the uncouplers would decrease the RC time constant for membrane capacitance leading to a quicker discharge of voltage and concomitant decrease in photocycle turnover time. The experimental results show that the primary cause for the slower kinetics of voltage changes in the DEM system is thermodynamic back-pressure as described by Westerhoff, H.V. & Dancshazy, Z. (1984) Trends Biochem. Sci.9, 112-117. JF - European Journal of Biochemistry AU - Hendler, R W AU - Drachev, LA AU - Bose, S AU - Joshi, M K AD - Laboratory of Cell Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 2000/10// PY - 2000 DA - Oct 2000 SP - 5879 EP - 5890 VL - 267 IS - 19 SN - 0014-2956, 0014-2956 KW - kinetics KW - bacteriorhodopsin KW - Microbiology Abstracts B: Bacteriology KW - Membranes KW - Photocycles KW - Thermodynamics KW - Voltage KW - Purple membranes KW - Halobacterium salinarium KW - J 02723:Photosynthesis, electron transport and related phenomena UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17633842?accountid=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=European+Journal+of+Biochemistry&rft.atitle=On+the+kinetics+of+voltage+formation+in+purple+membranes+of+Halobacterium+salinarium&rft.au=Hendler%2C+R+W%3BDrachev%2C+LA%3BBose%2C+S%3BJoshi%2C+M+K&rft.aulast=Hendler&rft.aufirst=R&rft.date=2000-10-01&rft.volume=267&rft.issue=19&rft.spage=5879&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Biochemistry&rft.issn=00142956&rft_id=info:doi/10.1046%2Fj.1432-1327.2000.01620.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Halobacterium salinarium; Photocycles; Thermodynamics; Purple membranes; Membranes; Voltage DO - http://dx.doi.org/10.1046/j.1432-1327.2000.01620.x ER - TY - JOUR T1 - Mortality among workers exposed to cutting oil mist: Update of previous reports AN - 17626857; 4773310 AB - Earlier reports of the mortality experience of this cohort of automotive workers followed from 1938 to 1967 who were exposed to cutting oil mist noted an excess of gastrointestinal cancer. The present report describes the mortality experience of these workers followed for mortality through 1980. Cause-specific standardized mortality ratios were calculated by comparing the observed number of deaths to the expected numbers based on rates for the U.S. male population. The SMRs for liver and biliary tract, and testicular cancers were significantly elevated. Among the subset of workers with heavy oil mist exposure, SMRs were significantly elevated for cancers of the lung and testis, and for Hodgkin's disease. The risk of death due to lung cancer was greatest among workers with heavy exposure to oil mist employed for 15 or more years. Mortality due to stomach cancer was in excess among workers with heavy exposure to oil mist who were employed for 5 or more years. There were significant excesses of deaths due to asthma and emphysema. Further studies with information on the presence of contaminants and additives in oil mists will help elucidate the relationship between oil mist exposure and cancer. JF - American Journal of Industrial Medicine AU - Kazerouni, N AU - Thomas, T L AU - Petralia, SA AU - Hayes, R B AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., Executive Plaza South 7013, Rockville, MD 20892, USA, kazeroun@mail.nih.gov Y1 - 2000/10// PY - 2000 DA - Oct 2000 SP - 410 EP - 416 VL - 38 IS - 4 SN - 0271-3586, 0271-3586 KW - cutting oil mist KW - man KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - Emphysema KW - Mortality KW - Mists KW - Automotive industry KW - Lung diseases KW - Oils KW - Asthma KW - Toxicity KW - Cancer KW - Hazardous materials KW - Carcinogenesis KW - Gastrointestinal tract KW - Occupational exposure KW - H 1000:Occupational Safety and Health KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17626857?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Industrial+Medicine&rft.atitle=Mortality+among+workers+exposed+to+cutting+oil+mist%3A+Update+of+previous+reports&rft.au=Kazerouni%2C+N%3BThomas%2C+T+L%3BPetralia%2C+SA%3BHayes%2C+R+B&rft.aulast=Kazerouni&rft.aufirst=N&rft.date=2000-10-01&rft.volume=38&rft.issue=4&rft.spage=410&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/10.1002%2F1097-0274%28200010%2938%3A43.3.CO%3B2-X LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Hazardous materials; Toxicity; Cancer; Mists; Automotive industry; Occupational exposure; Oils; Mortality; Gastrointestinal tract; Carcinogenesis; Lung diseases; Asthma; Emphysema DO - http://dx.doi.org/10.1002/1097-0274(200010)38:4<410::AID-AJIM6>3.3.CO;2-X ER - TY - JOUR T1 - Recombinant Respiratory Syncytial Virus That Does Not Express the NS1 or M2-2 Protein Is Highly Attenuated and Immunogenic in Chimpanzees AN - 17618762; 4759128 AB - Mutant recombinant respiratory syncytial viruses (RSV) which cannot express the NS1 and M2-2 proteins, designated rA2 Delta NS1 and rA2 Delta M2-2 respectively, were evaluated as live-attenuated RSV vaccines. The rA2 Delta NS1 virus contains a large deletion that should have the advantageous property of genetic stability during replication in vitro and in vivo. In vitro, rA2 Delta NS1 replicated approximately 10-fold less well than wild-type recombinant RSV (rA2), while rA2 Delta M2-2 had delayed growth kinetics but reached a final titer similar to that of rA2. Each virus was administered to the respiratory tracts of RSV-seronegative chimpanzees to assess replication, immunogenicity, and protective efficacy. The rA2 Delta NS1 and rA2 Delta M2-2 viruses were 2,200- to 55,000-fold restricted in replication in the upper and lower respiratory tracts but induced a level of RSV- neutralizing antibody in serum that was only slightly reduced compared to the level induced by wild-type RSV. The replication of wild-type RSV in immunized chimpanzees after challenge was reduced more than 10,000-fold at each site. Importantly, rA2 Delta NS1 and rA2 Delta M2-2 were 10-fold more restricted in replication in the upper respiratory tract than was the cpts248/404 virus, a vaccine candidate that retained mild reactogenicity in the upper respiratory tracts of 1-month-old infants. Thus, either rA2 Delta NS1 or rA2 Delta M2-2 might be appropriately attenuated for this age group, which is the major target population for an RSV vaccine. In addition, these results show that neither NS1 nor M2-2 is essential for RSV replication in vivo, although each is important for efficient replication. JF - Journal of Virology AU - Teng, M N AU - Whitehead, S S AU - Bermingham, A AU - Claire AU - Elkins, W R AU - Murphy, B R AU - Collins, P L AD - LID, NIAID, 7 Center Dr., MSC 0720, Bethesda, MD 20892-0720, pcollins@niaid.nih.gov Y1 - 2000/10// PY - 2000 DA - Oct 2000 SP - 9317 EP - 9321 VL - 74 IS - 19 SN - 0022-538X, 0022-538X KW - chimpanzees KW - recombinants KW - M2-2 protein KW - NS1 protein KW - Respiratory syncytial virus KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Immunogenicity KW - Attenuation KW - Vaccines KW - Infants KW - Respiratory tract KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - V 22150:Animal models & experimentally-induced viral infections KW - V 22097:Immunization: Vaccines & vaccination: Human KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17618762?accountid=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=Recombinant+Respiratory+Syncytial+Virus+That+Does+Not+Express+the+NS1+or+M2-2+Protein+Is+Highly+Attenuated+and+Immunogenic+in+Chimpanzees&rft.au=Teng%2C+M+N%3BWhitehead%2C+S+S%3BBermingham%2C+A%3BClaire%3BElkins%2C+W+R%3BMurphy%2C+B+R%3BCollins%2C+P+L&rft.aulast=Teng&rft.aufirst=M&rft.date=2000-10-01&rft.volume=74&rft.issue=19&rft.spage=9317&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/10.1128%2FJVI.74.19.9317-9321.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Respiratory syncytial virus; Respiratory tract; Vaccines; Infants; Immunogenicity; Attenuation DO - http://dx.doi.org/10.1128/JVI.74.19.9317-9321.2000 ER - TY - JOUR T1 - Identification and characterization of JunD missense mutants that lack menin binding. AN - 72331086; 11032020 AB - Menin, the product of the MEN1 tumor suppressor gene, binds to the AP1 transcription factor JunD and represses JunD transcriptional activity. The effects of human or mouse JunD missense mutations upon menin interaction were studied by random and alanine scanning mutagenesis of the menin binding region of JunD (amino acids 1-70). JunD mutant proteins were tested for menin binding in a reverse yeast two-hybrid assay, and for transcriptional regulation by menin in AP1-reporter assays. Random mutagenesis identified two different mutations that disrupted menin interaction at mouse JunD amino acid 42 (G42E and G42R). Mutation G42A generated by alanine scanning did not affect menin binding, likely reflecting the conserved nature of this amino acid substitution. Furthermore, by size exclusion chromatography menin co-migrated with wild type JunD but not with the JunD mutant tested (G42E). Alanine scanning mutagenesis of residues 30-55 revealed two different amino acids, P41 and P44, of mouse JunD that were critical for interaction with menin. Mouse JunD missense mutants P41A, G42R, G42E and P44A failed to bind menin and also escaped menin's control over their transcriptional activity. At lower amounts of transfected menin, the transcriptional effect of menin on the mutants P41A, G42R and G42E was changed from repression to activation, similar to that with c-jun. In conclusion, a small N-terminal region of JunD mediates a key difference between JunD and c-jun, and a component of this difference is dependent on JunD binding to menin. JF - Oncogene AU - Knapp, J I AU - Heppner, C AU - Hickman, A B AU - Burns, A L AU - Chandrasekharappa, S C AU - Collins, F S AU - Marx, S J AU - Spiegel, A M AU - Agarwal, S K AD - Metabolic Diseases Branch, NIDDK, NIH, Bethesda, Maryland 20892, USA. Y1 - 2000/09/28/ PY - 2000 DA - 2000 Sep 28 SP - 4706 EP - 4712 VL - 19 IS - 41 SN - 0950-9232, 0950-9232 KW - MEN1 protein, human KW - 0 KW - Neoplasm Proteins KW - Protein Isoforms KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-jun KW - Index Medicus KW - Animals KW - Humans KW - Two-Hybrid System Techniques KW - Amino Acid Sequence KW - Mice KW - Protein Binding KW - Transcriptional Activation KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Rats KW - Sequence Alignment KW - Chromatography, Gel KW - Transfection KW - Kidney KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Protein Structure, Tertiary KW - Cell Line KW - Protein Isoforms -- metabolism KW - Proto-Oncogene Proteins c-jun -- genetics KW - Proto-Oncogene Proteins c-jun -- metabolism KW - Protein Isoforms -- genetics KW - Neoplasm Proteins -- metabolism KW - Mutation, Missense KW - Amino Acid Substitution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72331086?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+and+characterization+of+JunD+missense+mutants+that+lack+menin+binding.&rft.au=Knapp%2C+J+I%3BHeppner%2C+C%3BHickman%2C+A+B%3BBurns%2C+A+L%3BChandrasekharappa%2C+S+C%3BCollins%2C+F+S%3BMarx%2C+S+J%3BSpiegel%2C+A+M%3BAgarwal%2C+S+K&rft.aulast=Knapp&rft.aufirst=J&rft.date=2000-09-28&rft.volume=19&rft.issue=41&rft.spage=4706&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-13 N1 - Date created - 2000-11-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Flavonoid Baicalin Inhibits HIV-1 Infection at the Level of Viral Entry AN - 17624598; 4771475 AB - Baicalin (BA) is a flavonoid compound purified from medicinal plant Scutellaria baicalensis Georgi and has been shown to possess anti-inflammatory and anti-HIV-1 activities. In an effort to elucidate the mechanism of the anti-inflammatory effect of BA, we recently found that this flavonoid compound was able to form complexes with selected chemokines and attenuated their capacity to bind and activate receptors on the cell surface. These observations prompted us to investigate whether BA could inhibit HIV-1 infection by interfering with viral entry, a process known to involve interaction between HIV-1 envelope proteins and the cellular CD4 and chemokine receptors. We found that BA at the noncytotoxic concentrations, inhibited both T cell tropic (X4) and monocyte tropic (R5) HIV-1 Env protein mediated fusion with cells expressing CD4/CXCR4 or CD4/CCR5. Furthermore, presence of BA at the initial stage of HIV-1 viral adsorption blocked the replication of HIV-1 early strong stop DNA in cells. Since BA did not inhibit binding of HIV-1 gp120 to CD4, we propose that BA may interfere with the interaction of HIV-1 Env with chemokine coreceptors and block HIV-1 entry of target cells. Therefore, BA can be used as a basis for developing novel anti-HIV-1 agents. JF - Biochemical and Biophysical Research Communications AU - Li, B Q AU - Fu, T AU - Dongyan, Y AU - Mikovits, JA AU - Ruscetti, F W AU - Wang, J M AD - Laboratory of Antiviral Drug Mechanism, National Cancer Institute-Frederick Cancer Development Center, 21702, Maryland, bqli@mail.ncifcrf.gov Y1 - 2000/09/24/ PY - 2000 DA - 2000 Sep 24 SP - 534 EP - 538 PB - Academic Press VL - 276 IS - 2 SN - 0006-291X, 0006-291X KW - HIV-1 KW - Baicalin KW - CCR5 protein KW - CXCR4 protein KW - flavonoids KW - Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Medicinal plants KW - Chemokine receptors KW - Antiviral agents KW - Envelope protein KW - Human immunodeficiency virus 1 KW - Plant extracts KW - Antiinflammatory agents KW - Scutellaria baicalensis KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01068:Antiviral & viricidal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17624598?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+Biophysical+Research+Communications&rft.atitle=Flavonoid+Baicalin+Inhibits+HIV-1+Infection+at+the+Level+of+Viral+Entry&rft.au=Li%2C+B+Q%3BFu%2C+T%3BDongyan%2C+Y%3BMikovits%2C+JA%3BRuscetti%2C+F+W%3BWang%2C+J+M&rft.aulast=Li&rft.aufirst=B&rft.date=2000-09-24&rft.volume=276&rft.issue=2&rft.spage=534&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+Biophysical+Research+Communications&rft.issn=0006291X&rft_id=info:doi/10.1006%2Fbbrc.2000.3485 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Scutellaria baicalensis; Human immunodeficiency virus 1; Antiinflammatory agents; Plant extracts; Envelope protein; Medicinal plants; Antiviral agents; Chemokine receptors DO - http://dx.doi.org/10.1006/bbrc.2000.3485 ER - TY - JOUR T1 - Genetic dissection of a rat model for rheumatoid arthritis: significant gender influences on autosomal modifier loci. AN - 72282573; 11001927 AB - Rheumatoid arthritis (RA) is a common, chronic, autoimmune, inflammatory disease that is influenced by genetic factors including gender. Many studies suggest that the genetic risk for RA is determined by the MHC, in particular class II alleles with a 'shared epitope' (SE), and multiple non-MHC loci. Other studies indicate that RA and other autoimmune diseases, in particular insulin-dependent diabetes mellitus (IDDM) and autoimmune thyroid disease (ATD), share genetic risk factors. Rat collagen-induced arthritis (CIA) is an experimental model with many features that resemble RA. The spontaneous diabetes-resistant bio-breeding rat, BB(DR), is of interest because it is susceptible to experimentally induced CIA, IDDM and ATD, and it has an SE in its MHC class II allele. To explore the genetics of CIA, including potential gender influences and the genetic relationships between CIA and other autoimmune diseases, we conducted a genome-wide scan for CIA regulatory loci in the F(2) progeny of BB(DR) and CIA-resistant BN rats. We identified 10 quantitative trait loci (QTLs), including 5 new ones (Cia15, Cia16*, Cia17, Cia18* and Cia19 on chromosomes 9, 10, 18 and two on the X chromosome, respectively), that regulated CIA severity. We also identified four QTLs, including two new ones (Ciaa4* and Ciaa5* on chromosomes 4 and 5, respectively), that regulated autoantibody titer to rat type II collagen. Many of these loci appeared to be gender influenced, and most co-localized with several other autoimmune trait loci. Our data support the view that multiple autoimmune diseases may share genetic risk factors, and suggest that many of these loci are gender influenced. JF - Human molecular genetics AU - Furuya, T AU - Salstrom, J L AU - McCall-Vining, S AU - Cannon, G W AU - Joe, B AU - Remmers, E F AU - Griffiths, M M AU - Wilder, R L AD - Inflammatory Joint Diseases Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-1820, USA. Y1 - 2000/09/22/ PY - 2000 DA - 2000 Sep 22 SP - 2241 EP - 2250 VL - 9 IS - 15 SN - 0964-6906, 0964-6906 KW - Autoantibodies KW - 0 KW - Collagen KW - 9007-34-5 KW - Index Medicus KW - Rats KW - Genetic Linkage KW - Animals KW - Major Histocompatibility Complex -- genetics KW - Collagen -- immunology KW - Sex Factors KW - Collagen -- metabolism KW - Autoantibodies -- blood KW - Disease Models, Animal KW - Crosses, Genetic KW - Male KW - Female KW - Quantitative Trait, Heritable KW - Arthritis, Rheumatoid -- genetics KW - Arthritis, Rheumatoid -- chemically induced KW - Arthritis, Rheumatoid -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72282573?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+molecular+genetics&rft.atitle=Genetic+dissection+of+a+rat+model+for+rheumatoid+arthritis%3A+significant+gender+influences+on+autosomal+modifier+loci.&rft.au=Furuya%2C+T%3BSalstrom%2C+J+L%3BMcCall-Vining%2C+S%3BCannon%2C+G+W%3BJoe%2C+B%3BRemmers%2C+E+F%3BGriffiths%2C+M+M%3BWilder%2C+R+L&rft.aulast=Furuya&rft.aufirst=T&rft.date=2000-09-22&rft.volume=9&rft.issue=15&rft.spage=2241&rft.isbn=&rft.btitle=&rft.title=Human+molecular+genetics&rft.issn=09646906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-08 N1 - Date created - 2000-10-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. AN - 72324530; 11030617 AB - Mice lacking the nuclear bile acid receptor FXR/BAR developed normally and were outwardly identical to wild-type littermates. FXR/BAR null mice were distinguished from wild-type mice by elevated serum bile acid, cholesterol, and triglycerides, increased hepatic cholesterol and triglycerides, and a proatherogenic serum lipoprotein profile. FXR/BAR null mice also had reduced bile acid pools and reduced fecal bile acid excretion due to decreased expression of the major hepatic canalicular bile acid transport protein. Bile acid repression and induction of cholesterol 7alpha-hydroxylase and the ileal bile acid binding protein, respectively, did not occur in FXR/BAR null mice, establishing the regulatory role of FXR/BAR for the expression of these genes in vivo. These data demonstrate that FXR/BAR is critical for bile acid and lipid homeostasis by virtue of its role as an intracellular bile acid sensor. JF - Cell AU - Sinal, C J AU - Tohkin, M AU - Miyata, M AU - Ward, J M AU - Lambert, G AU - Gonzalez, F J AD - Laboratory of Metabolism, Division of Basic Sciences, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/09/15/ PY - 2000 DA - 2000 Sep 15 SP - 731 EP - 744 VL - 102 IS - 6 SN - 0092-8674, 0092-8674 KW - Bile Acids and Salts KW - 0 KW - Cholesterol, Dietary KW - DNA-Binding Proteins KW - RNA, Messenger KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - Triglycerides KW - farnesoid X-activated receptor KW - Cholesterol 7-alpha-Hydroxylase KW - EC 1.14.14.23 KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Cholesterol 7-alpha-Hydroxylase -- metabolism KW - RNA, Messenger -- analysis KW - Liver -- metabolism KW - Mice KW - Receptors, Cytoplasmic and Nuclear -- genetics KW - Mice, Knockout KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Biological Transport -- physiology KW - Gene Expression -- physiology KW - Female KW - Male KW - Triglycerides -- blood KW - Bile Acids and Salts -- blood KW - Transcription Factors -- metabolism KW - DNA-Binding Proteins -- genetics KW - Homeostasis -- physiology KW - Cholesterol, Dietary -- blood KW - Bile Acids and Salts -- toxicity KW - Transcription Factors -- genetics KW - Homeostasis -- drug effects KW - Bile Acids and Salts -- biosynthesis KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72324530?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell&rft.atitle=Targeted+disruption+of+the+nuclear+receptor+FXR%2FBAR+impairs+bile+acid+and+lipid+homeostasis.&rft.au=Sinal%2C+C+J%3BTohkin%2C+M%3BMiyata%2C+M%3BWard%2C+J+M%3BLambert%2C+G%3BGonzalez%2C+F+J&rft.aulast=Sinal&rft.aufirst=C&rft.date=2000-09-15&rft.volume=102&rft.issue=6&rft.spage=731&rft.isbn=&rft.btitle=&rft.title=Cell&rft.issn=00928674&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-30 N1 - Date created - 2000-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Progress in antiangiogenic gene therapy of cancer. AN - 72288468; 11002212 AB - Because tumors require angiogenesis for growth, inhibiting angiogenesis is a promising strategy for treating cancer patients. Although numerous endogenous angiogenesis inhibitors have been discovered, the clinical evaluation of these agents has been hindered by high dose requirements, manufacturing constraints, and relative instability of the corresponding recombinant proteins. Therefore the delivery of these proteins using gene therapy has become increasingly attractive. Based on their own antiangiogenic gene therapy research, the authors evaluated the published experience with antiangiogenic gene therapy models using the National Library of Medicine's PubMed search service and the reference lists of the publications cited. Greater than 40 endogenous inhibitors of angiogenesis have been characterized. Thirteen have been employed in gene therapy models, all of which showed antitumor activity in experimental animals. Other approaches have inhibited the expression or activity of proangiogenic cytokines such as vascular endothelial growth factor. The ideal gene delivery vector would target tumor tissue preferentially to minimize systemic toxicity of the transgene product. However, the low toxicity profile of endogenous inhibitors of angiogenesis has allowed the success of systemic antiangiogenic gene therapy in a number of preclinical models, in which normal host tissues act as a "factory" to produce high circulating concentrations of antiangiogenic proteins. Difficulties with the large-scale use of antiangiogenic agents have hindered their investigation in clinical trials. Antiangiogenic gene therapy offers the potential for cancer patients to manufacture their own antiangiogenic proteins. This strategy has been increasingly successful in preclinical models and represents an exciting new approach to cancer therapy. Copyright 2000 American Cancer Society. JF - Cancer AU - Feldman, A L AU - Libutti, S K AD - Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2000/09/15/ PY - 2000 DA - 2000 Sep 15 SP - 1181 EP - 1194 VL - 89 IS - 6 SN - 0008-543X, 0008-543X KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Humans KW - Neoplasms -- blood supply KW - Genetic Therapy -- methods KW - Neoplasms -- therapy KW - Neovascularization, Pathologic -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72288468?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Progress+in+antiangiogenic+gene+therapy+of+cancer.&rft.au=Feldman%2C+A+L%3BLibutti%2C+S+K&rft.aulast=Feldman&rft.aufirst=A&rft.date=2000-09-15&rft.volume=89&rft.issue=6&rft.spage=1181&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-03 N1 - Date created - 2000-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcription termination by RNA polymerase III in fission yeast. A genetic and biochemically tractable model system. AN - 72249888; 10843998 AB - In order for RNA polymerase (pol) III to produce a sufficient quantity of RNAs of appropriate structure, initiation, termination, and reinitiation must be accurate and efficient. Termination-associated factors have been shown to facilitate reinitiation and regulate transcription in some species. Suppressor tRNA genes that differ in the dT(n) termination signal were examined for function in Schizosaccharomyces pombe. We also developed an S. pombe extract that is active for tRNA transcription that is described here for the first time. The ability of this tRNA gene to be transcribed in extracts from different species allowed us to compare termination in three model systems. Although human pol III terminates efficiently at 4 dTs and S. pombe at 5 dTs, Saccharomyces cerevisiae pol III requires 6 dTs to direct comparable but lower termination efficiency and also appears qualitatively distinct. Interestingly, this pattern of sensitivity to a minimal dT(n) termination signal was found to correlate with the sensitivity to alpha-amanitin, as S. pombe was intermediate between human and S. cerevisiae pols III. The results establish that the pols III of S. cerevisiae, S. pombe, and human exhibit distinctive properties and that termination occurs in S. pombe in a manner that is functionally more similar to human than is S. cerevisiae. JF - The Journal of biological chemistry AU - Hamada, M AU - Sakulich, A L AU - Koduru, S B AU - Maraia, R J AD - Laboratory of Molecular Growth Regulation, NICHHD, National Institutes of Health, Bethesda, Maryland 20892-2753, USA. Y1 - 2000/09/15/ PY - 2000 DA - 2000 Sep 15 SP - 29076 EP - 29081 VL - 275 IS - 37 SN - 0021-9258, 0021-9258 KW - Amanitins KW - 0 KW - RNA, Transfer KW - 9014-25-9 KW - RNA Polymerase III KW - EC 2.7.7.6 KW - Index Medicus KW - Saccharomyces cerevisiae -- genetics KW - RNA, Transfer -- metabolism KW - RNA, Transfer -- genetics KW - Amanitins -- pharmacology KW - Species Specificity KW - Schizosaccharomyces -- genetics KW - RNA Polymerase III -- physiology KW - Transcription, Genetic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72249888?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transcription+termination+by+RNA+polymerase+III+in+fission+yeast.+A+genetic+and+biochemically+tractable+model+system.&rft.au=Hamada%2C+M%3BSakulich%2C+A+L%3BKoduru%2C+S+B%3BMaraia%2C+R+J&rft.aulast=Hamada&rft.aufirst=M&rft.date=2000-09-15&rft.volume=275&rft.issue=37&rft.spage=29076&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 - 2000-10-13 N1 - Date created - 2000-10-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A transgenic mouse expressing human CYP1A2 in the pancreas. AN - 71747265; 10930541 AB - A transgenic mouse line expressing the human cytochrome P450 CYP1A2 in the pancreas under the control of the mouse elastase promoter was established. The expression of CYP1A2 was specific to the transgenic pancreas and was not found in the control wild-type mouse pancreas. The level of CYP1A2 expressed in pancreatic microsomes from transgenic mice was comparable to that of the endogenously expressed CYP1A2 protein in the liver, as judged by western blotting analyses. Estrone metabolism was used to determine the activity of CYP1A2 expressed in the pancreas of the transgenic mouse. The transgenic pancreas exhibited almost one-third to one-half of the activity of wild-type or CYP1A2 transgenic mouse liver, whereas the wild-type pancreas demonstrated no activity. The addition of NADPH-cytochrome P450 oxidoreductase to the reaction mixture containing pancreatic microsomes from the transgenic mice did not increase the estrone metabolism activity significantly. This transgenic mouse line provides another useful tool to study human CYP1A2 and its relation to chemical toxicity and carcinogenesis. JF - Biochemical pharmacology AU - Ueno, T AU - Tamura, S AU - Frels, W I AU - Shou, M AU - Gonzalez, F J AU - Kimura, S AD - Laboratory of Metabolism, National Cancer Institute, Bethesda, MD 20850, USA. Y1 - 2000/09/15/ PY - 2000 DA - 2000 Sep 15 SP - 857 EP - 863 VL - 60 IS - 6 SN - 0006-2952, 0006-2952 KW - Recombinant Proteins KW - 0 KW - Estrone KW - 2DI9HA706A KW - Cytochrome P-450 CYP1A2 KW - EC 1.14.14.1 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Recombinant Proteins -- metabolism KW - Microsomes, Liver -- metabolism KW - Humans KW - Microsomes, Liver -- enzymology KW - Mice, Inbred C57BL KW - Gene Expression KW - Mice KW - Recombinant Proteins -- genetics KW - Mice, Transgenic KW - Estrone -- metabolism KW - Female KW - Cytochrome P-450 CYP1A2 -- genetics KW - Pancreas -- metabolism KW - Pancreas -- enzymology KW - Cytochrome P-450 CYP1A2 -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71747265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=A+transgenic+mouse+expressing+human+CYP1A2+in+the+pancreas.&rft.au=Ueno%2C+T%3BTamura%2C+S%3BFrels%2C+W+I%3BShou%2C+M%3BGonzalez%2C+F+J%3BKimura%2C+S&rft.aulast=Ueno&rft.aufirst=T&rft.date=2000-09-15&rft.volume=60&rft.issue=6&rft.spage=857&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-29 N1 - Date created - 2000-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Autoradiographic evidence that prolonged withdrawal from intermittent cocaine reduces mu-opioid receptor expression in limbic regions of the rat brain. AN - 71232450; 10891866 AB - Numerous reports support evidence that dopaminergic mesolimbic pathways interact with opioid systems to influence the reinforcing properties of cocaine. Withdrawal from chronic administration of cocaine in rats causes an upregulation of mesocorticolimbic mu-opioid receptors during early stages, but information about prolonged cocaine abstinence is lacking. We addressed this issue by treating rats with cocaine or saline (control) intermittently (1 mg/kg, i.v., every 12 min for 2 h daily) for 10 days followed by a 10- or 20-day withdrawal period. The animals were then decapitated and the brains removed for quantitative in vitro autoradiographic analysis of 14 brain regions with (125)I-DAMGO. A separate group of animals received two consecutive cycles of the 10-day cocaine/10-day withdrawal regimen. Only the group that participated in the two consecutive cycles showed a significant effect of treatment: downregulation of mu-opiate receptors in limbic cortical layer 3 (17% lower than saline-treated controls, P = 0.03), the core of the nucleus accumbens (16% decrease, P = 0.05), and the nucleus of the diagonal band (18% decrease, P = 0.05). The mu-receptor may manifest, as do other neural markers (e.g., dopamine transporter, dopamine efflux), a biphasic temporal pattern with upregulation during early phases of cocaine withdrawal but a downregulation at later times. JF - Synapse (New York, N.Y.) AU - Sharpe, L G AU - Pilotte, N S AU - Shippenberg, T S AU - Goodman, C B AU - London, E D AD - Behavioral Neuroscience Branch, National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD 21224, USA. lsharpe@irp.nida.nih.gov Y1 - 2000/09/15/ PY - 2000 DA - 2000 Sep 15 SP - 292 EP - 297 VL - 37 IS - 4 SN - 0887-4476, 0887-4476 KW - Analgesics, Opioid KW - 0 KW - Dopamine Uptake Inhibitors KW - Iodine Radioisotopes KW - Receptors, Opioid, mu KW - Enkephalin, Ala(2)-MePhe(4)-Gly(5)- KW - 100929-53-1 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Animals KW - Rats, Inbred Lew KW - Septal Nuclei -- metabolism KW - Nucleus Accumbens -- drug effects KW - Analgesics, Opioid -- metabolism KW - Enkephalin, Ala(2)-MePhe(4)-Gly(5)- -- metabolism KW - Autoradiography KW - Nucleus Accumbens -- physiopathology KW - Rats KW - Septal Nuclei -- physiopathology KW - Enkephalin, Ala(2)-MePhe(4)-Gly(5)- -- pharmacology KW - Analgesics, Opioid -- pharmacology KW - Nucleus Accumbens -- metabolism KW - Septal Nuclei -- drug effects KW - Down-Regulation -- drug effects KW - Cocaine-Related Disorders -- metabolism KW - Male KW - Substance Withdrawal Syndrome -- metabolism KW - Limbic System -- drug effects KW - Limbic System -- metabolism KW - Receptors, Opioid, mu -- metabolism KW - Cocaine -- pharmacology KW - Dopamine Uptake Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71232450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Autoradiographic+evidence+that+prolonged+withdrawal+from+intermittent+cocaine+reduces+mu-opioid+receptor+expression+in+limbic+regions+of+the+rat+brain.&rft.au=Sharpe%2C+L+G%3BPilotte%2C+N+S%3BShippenberg%2C+T+S%3BGoodman%2C+C+B%3BLondon%2C+E+D&rft.aulast=Sharpe&rft.aufirst=L&rft.date=2000-09-15&rft.volume=37&rft.issue=4&rft.spage=292&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 - 2000-09-14 N1 - Date created - 2000-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Requirement for Phe36 for DNA binding and mismatch repair by Escherichia coli MutS protein AN - 17623608; 4767133 AB - The MutS family of DNA repair proteins recognizes base pair mismatches and insertion/deletion mismatches and targets them for repair in a strand-specific manner. Photocrosslinking and mutational studies previously identified a highly conserved Phe residue at the N-terminus of Thermus aquaticus MutS protein that is critical for mismatch recognition in vitro. Here, a mutant Escherichia coli MutS protein harboring a substitution of Ala for the corresponding Phe36 residue is assessed for proficiency in mismatch repair in vivo and DNA binding and ATP hydrolysis in vitro. The F36A protein is unable to restore mismatch repair proficiency to a mutS strain as judged by mutation to rifampicin or reversion of a specific point mutation in lacZ. The F36A protein is also severely deficient for binding to heteroduplexes containing an unpaired thymidine or a G:T mismatch although its intrinsic ATPase activity and subunit oligomerization are very similar to that of the wild-type MutS protein. Thus, the F36A mutation appears to confer a defect specific for recognition of insertion/deletion and base pair mismatches. JF - Nucleic Acids Research AU - Yamamoto, Akira AU - Schofield, MJ AU - Biswas, I AU - Hsieh, P AD - Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1810, USA, hsieh@ncifcrf.gov Y1 - 2000/09/15/ PY - 2000 DA - 2000 Sep 15 SP - 3564 EP - 3569 VL - 28 IS - 18 SN - 0305-1048, 0305-1048 KW - MutS protein KW - mismatch repair KW - rifampicin KW - rifampin KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Adenosinetriphosphatase KW - Escherichia coli KW - DNA repair KW - Mutagenesis KW - J 02725:DNA KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17623608?accountid=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=Requirement+for+Phe36+for+DNA+binding+and+mismatch+repair+by+Escherichia+coli+MutS+protein&rft.au=Yamamoto%2C+Akira%3BSchofield%2C+MJ%3BBiswas%2C+I%3BHsieh%2C+P&rft.aulast=Yamamoto&rft.aufirst=Akira&rft.date=2000-09-15&rft.volume=28&rft.issue=18&rft.spage=3564&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 - Escherichia coli; Mutagenesis; Adenosinetriphosphatase; DNA repair ER - TY - JOUR T1 - Holliday junction resolvases and related nucleases: identification of new families, phyletic distribution and evolutionary trajectories AN - 17620602; 4767115 AB - Holliday junction resolvases (HJRs) are key enzymes of DNA recombination. A detailed computer analysis of the structural and evolutionary relationships of HJRs and related nucleases suggests that the HJR function has evolved independently from at least four distinct structural folds, namely RNase H, endonuclease, endonuclease VII-colicin E and RusA. The endonuclease fold, whose structural prototypes are the phage lambda exonuclease, the very short patch repair nuclease (Vsr) and type II restriction enzymes, is shown to encompass by far a greater diversity of nucleases than previously suspected. This fold unifies archaeal HJRs, repair nucleases such as RecB and Vsr, restriction enzymes and a variety of predicted nucleases whose specific activities remain to be determined. Within the RNase H fold a new family of predicted HJRs, which is nearly ubiquitous in bacteria, was discovered, in addition to the previously characterized RuvC family. The proteins of this family, typified by Escherichia coli YqgF, are likely to function as an alternative to RuvC in most bacteria, but could be the principal HJRs in low-GC Gram-positive bacteria and Aquifex. Endonuclease VII of phage T4 is shown to serve as a structural template for many nucleases, including McrA and other type II restriction enzymes. Together with colicin E7, endonuclease VII defines a distinct metal-dependent nuclease fold. As a result of this analysis, the principal HJRs are now known or confidently predicted for all bacteria and archaea whose genomes have been completely sequenced, with many species encoding multiple potential HJRs. Horizontal gene transfer, lineage-specific gene loss and gene family expansion, and non-orthologous gene displacement seem to have been major forces in the evolution of HJRs and related nucleases. A remarkable case of displacement is seen in the Lyme disease spirochete Borrelia burgdorferi, which does not possess any of the typical HJRs, but instead encodes, in its chromosome and each of the linear plasmids, members of the lambda exonuclease family predicted to function as HJRs. The diversity of HJRs and related nucleases in bacteria and archaea contrasts with their near absence in eukaryotes. The few detected eukaryotic representatives of the endonuclease fold and the RNase H fold have probably been acquired from bacteria via horizontal gene transfer. The identity of the principal HJR(s) involved in recombination in eukaryotes remains uncertain; this function could be performed by topoisomerase IB or by a novel, so far undetected, class of enzymes. Likely HJRs and related nucleases were identified in the genomes of numerous bacterial and eukaryotic DNA viruses. Gene flow between viral and cellular genomes has probably played a major role in the evolution of this class of enzymes. This analysis resulted in the prediction of numerous previously unnoticed nucleases, some of which are likely to be new restriction enzymes. JF - Nucleic Acids Research AU - Aravind, L AU - Makarova, K S AU - Koonin, E V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA, aravind@ncbi.nlm.nih.gov Y1 - 2000/09/15/ PY - 2000 DA - 2000 Sep 15 SP - 3417 EP - 3432 VL - 28 IS - 18 SN - 0305-1048, 0305-1048 KW - Holliday junctions KW - nuclease KW - recombination KW - resolvase KW - ribonuclease H KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids; Genetics Abstracts KW - Nucleotide sequence KW - Phage ^l KW - Phage T4 KW - Phage l KW - DNA viruses KW - Gene flow KW - Escherichia coli KW - Aquifex KW - Evolution KW - J 02725:DNA KW - N 14710:General KW - G 07260:Taxonomy, systematics and evolutionary genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17620602?accountid=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=Holliday+junction+resolvases+and+related+nucleases%3A+identification+of+new+families%2C+phyletic+distribution+and+evolutionary+trajectories&rft.au=Aravind%2C+L%3BMakarova%2C+K+S%3BKoonin%2C+E+V&rft.aulast=Aravind&rft.aufirst=L&rft.date=2000-09-15&rft.volume=28&rft.issue=18&rft.spage=3417&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 - Escherichia coli; Aquifex; Phage T4; Phage ^l; Phage l; Evolution; Gene flow; Nucleotide sequence; DNA viruses ER - TY - JOUR T1 - Identification of oxidant-sensitive proteins: TNF-alpha induces protein glutathiolation. AN - 72285017; 10998251 AB - Reactive oxygen species are thought to play a role in a variety of physiologic and pathophysiological processes. One possible mediator of oxidant effects at the molecular level is a subset of proteins containing reactive cysteine thiols that can be readily oxidized. The transient incorporation of glutathione into cellular proteins is an established response to oxidant stress and could provide a mechanism for reversible covalent modification in response to reactive oxygen species. To better understand the function of protein S-glutathiolation in vivo, a biotinylated membrane-permeant analogue of glutathione, biotinylated glutathione ethyl ester, was developed and used to detect proteins into which glutathione is incorporated under oxidant stress. Oxidant stress from exogenous hydrogen peroxide or generated in response to TNF-alpha was found to increase incorporation of biotinylated glutathione ethyl ester into several HeLa cell proteins. The identity of two of these proteins was determined by peptide sequencing and mass spectrometric peptide mapping. A 23 kDa S-glutathiolated protein was identified as thioredoxin peroxidase II, a member of the peroxiredoxin family of peroxidases known to play a role in redox-dependent growth factor and cytokine signal transduction. A second, 36 kDa, protein was identified as annexin II. Further investigation revealed a single reactive cysteine in the annexin II tail domain. Deletion of the identified cysteine was found to abolish S-glutathiolation of annexin II. These findings demonstrate a specific posttranslational modification associated with an endogenously generated oxidant stress and suggest a mechanism by which TNF-alpha might selectively regulate protein function in a redox-dependent fashion. JF - Biochemistry AU - Sullivan, D M AU - Wehr, N B AU - Fergusson, M M AU - Levine, R L AU - Finkel, T AD - Laboratories of Molecular Biology and Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/09/12/ PY - 2000 DA - 2000 Sep 12 SP - 11121 EP - 11128 VL - 39 IS - 36 SN - 0006-2960, 0006-2960 KW - Annexin A2 KW - 0 KW - Neoplasm Proteins KW - Oxidants KW - Proteins KW - Reactive Oxygen Species KW - Succinimides KW - Tumor Necrosis Factor-alpha KW - sulfo-N-hydroxysuccinimide-biotin KW - Biotin KW - 6SO6U10H04 KW - S-ethyl glutathione KW - 7W95D60F4J KW - Hydrogen Peroxide KW - BBX060AN9V KW - Peroxidases KW - EC 1.11.1.- KW - PRDX3 protein, human KW - EC 1.11.1.15 KW - Peroxiredoxin III KW - Peroxiredoxins KW - Glyceraldehyde-3-Phosphate Dehydrogenases KW - EC 1.2.1.- KW - Glutathione KW - GAN16C9B8O KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Cysteine -- metabolism KW - Solubility KW - Glyceraldehyde-3-Phosphate Dehydrogenases -- metabolism KW - Dose-Response Relationship, Drug KW - HeLa Cells KW - Humans KW - Hydrogen Peroxide -- pharmacology KW - Cattle KW - Succinimides -- metabolism KW - Annexin A2 -- metabolism KW - Peroxidases -- metabolism KW - Oxidants -- pharmacology KW - Biotin -- analogs & derivatives KW - Glutathione -- metabolism KW - Tumor Necrosis Factor-alpha -- physiology KW - Tumor Necrosis Factor-alpha -- metabolism KW - Proteins -- metabolism KW - Glutathione -- analogs & derivatives KW - Biotin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72285017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Identification+of+oxidant-sensitive+proteins%3A+TNF-alpha+induces+protein+glutathiolation.&rft.au=Sullivan%2C+D+M%3BWehr%2C+N+B%3BFergusson%2C+M+M%3BLevine%2C+R+L%3BFinkel%2C+T&rft.aulast=Sullivan&rft.aufirst=D&rft.date=2000-09-12&rft.volume=39&rft.issue=36&rft.spage=11121&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-13 N1 - Date created - 2000-10-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolic and anthropometric consequences of interruption of highly active antiretroviral therapy. AN - 72274189; 10997397 AB - HAART has been associated with metabolic abnormalities (hyperlipidemia, insulin resistance, alterations in cortisol metabolism) and fat redistribution. A prospective study of 26 Caucasian men (median age 43.5 years) with HIV-1 viral loads < 500 copies/ml for 12 months while on highly active antiretroviral therapy (HAART) who interrupted treatment for a median of 7.0 weeks (range 4.9-10.3 weeks). Seventeen (65.4%) patients reported at least one fat redistribution symptom at baseline. Serum lipids, glucose and insulin levels during an oral glucose tolerance test, 24-h urinary free cortisol and 17-hydroxycorticosteroids, and anthropometric parameters were measured before HAART cessation and prior to its reinstitution. When baseline values were compared with those obtained after HAART interruption (means +/- SD), there was a significant decrease in total cholesterol (194+/-47.3 versus 159+/-29.3 mg/dl; P < 0.0001), low density lipoprotein (LDL) cholesterol (114+/-32.6 versus 96+/-24.7 mg/dl; P = 0.0013), triglycerides (261+/-244.3 versus 185+/-165.4 mg/dl; P = 0.008), and 24-hour urinary 17-hydroxycorticosteroids (15+/-7.9 versus 5+/-2.5 mg/24 h, P < 0.0001) and a significant increase in 24-hour urinary free cortisol (45+/-34.1 versus 62+/-32.2 microg/24 h; P = 0.016). There were no significant changes in glucose or insulin levels or in anthropometric measurements. A relatively brief interruption of HAART resulted in significant improvements in total cholesterol, LDL cholesterol, and triglyceride levels. No changes were observed in insulin resistance profiles or anthropometric measurements, perhaps because of the brief duration of HAART interruption. These results suggest that hyperlipidemia and alterations in corticosteroid metabolism in the setting of HAART are a direct drug effect that reverses with drug withdrawal. However, glucose metabolism and fat redistribution do not change over the short term. JF - AIDS (London, England) AU - Hatano, H AU - Miller, K D AU - Yoder, C P AU - Yanovski, J A AU - Sebring, N G AU - Jones, E C AU - Davey, R T AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Maryland 20892-1880, USA. Y1 - 2000/09/08/ PY - 2000 DA - 2000 Sep 08 SP - 1935 EP - 1942 VL - 14 IS - 13 SN - 0269-9370, 0269-9370 KW - HIV Protease Inhibitors KW - 0 KW - Lipids KW - Reverse Transcriptase Inhibitors KW - Triglycerides KW - Cholesterol KW - 97C5T2UQ7J KW - Hydrocortisone KW - WI4X0X7BPJ KW - Index Medicus KW - AIDS/HIV KW - Triglycerides -- blood KW - Reverse Transcriptase Inhibitors -- administration & dosage KW - Skinfold Thickness KW - Humans KW - HIV Protease Inhibitors -- therapeutic use KW - Reverse Transcriptase Inhibitors -- adverse effects KW - Cholesterol -- blood KW - Prospective Studies KW - Hyperlipidemias -- chemically induced KW - Adult KW - Lipodystrophy -- chemically induced KW - Hydrocortisone -- urine KW - Hypercholesterolemia -- chemically induced KW - Middle Aged KW - Reverse Transcriptase Inhibitors -- therapeutic use KW - HIV Protease Inhibitors -- adverse effects KW - HIV Protease Inhibitors -- administration & dosage KW - Male KW - Lipids -- blood KW - Antiretroviral Therapy, Highly Active -- adverse effects KW - HIV Infections -- virology KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy KW - HIV Infections -- metabolism KW - Body Composition KW - Insulin Resistance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72274189?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+%28London%2C+England%29&rft.atitle=Metabolic+and+anthropometric+consequences+of+interruption+of+highly+active+antiretroviral+therapy.&rft.au=Hatano%2C+H%3BMiller%2C+K+D%3BYoder%2C+C+P%3BYanovski%2C+J+A%3BSebring%2C+N+G%3BJones%2C+E+C%3BDavey%2C+R+T&rft.aulast=Hatano&rft.aufirst=H&rft.date=2000-09-08&rft.volume=14&rft.issue=13&rft.spage=1935&rft.isbn=&rft.btitle=&rft.title=AIDS+%28London%2C+England%29&rft.issn=02699370&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-08 N1 - Date created - 2000-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Minor groove interactions at the DNA polymerase beta active site modulate single-base deletion error rates. AN - 72237590; 10851238 AB - The structures of open and closed conformations of DNA polymerase beta (pol beta) suggests that the rate of single-nucleotide deletions during synthesis may be modulated by interactions in the DNA minor groove that align the templating base with the incoming dNTP. To test this hypothesis, we measured the single-base deletion error rates of wild-type pol beta and lysine and alanine mutants of Arg(283), whose side chain interacts with the minor groove edge of the templating nucleotide at the active site. The error rates of both mutant enzymes are increased >100-fold relative to wild-type pol beta. Template engineering experiments performed to distinguish among three possible models for deletion formation suggest that most deletions in repetitive sequences by pol beta initiate by strand slippage. However, pol beta also generates deletions by a different mechanism that is strongly enhanced by the substitutions at Arg(283). Analysis of error specificity suggests that this mechanism involves nucleotide misinsertion followed by primer relocation, creating a misaligned intermediate. The structure of pol beta bound to non-gapped DNA also indicates that the templating nucleotide and its downstream neighbor are out of register in the open conformation and this could facilitate misalignment (dNTP or primer terminus) with the next template base. JF - The Journal of biological chemistry AU - Osheroff, W P AU - Beard, W A AU - Yin, S AU - Wilson, S H AU - Kunkel, T A AD - Laboratory of Molecular Genetics and Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000/09/08/ PY - 2000 DA - 2000 Sep 08 SP - 28033 EP - 28038 VL - 275 IS - 36 SN - 0021-9258, 0021-9258 KW - Deoxyribonucleotides KW - 0 KW - Recombinant Proteins KW - DNA Polymerase beta KW - EC 2.7.7.- KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Lysine KW - K3Z4F929H6 KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - AIDS/HIV KW - Protein Structure, Secondary KW - Models, Molecular KW - HIV Reverse Transcriptase -- chemistry KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Deoxyribonucleotides -- metabolism KW - HIV Reverse Transcriptase -- metabolism KW - Templates, Genetic KW - Recombinant Proteins -- chemistry KW - Amino Acid Substitution KW - Sequence Deletion KW - Protein Conformation KW - DNA Polymerase beta -- chemistry KW - DNA Polymerase beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72237590?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Minor+groove+interactions+at+the+DNA+polymerase+beta+active+site+modulate+single-base+deletion+error+rates.&rft.au=Osheroff%2C+W+P%3BBeard%2C+W+A%3BYin%2C+S%3BWilson%2C+S+H%3BKunkel%2C+T+A&rft.aulast=Osheroff&rft.aufirst=W&rft.date=2000-09-08&rft.volume=275&rft.issue=36&rft.spage=28033&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 - 2000-10-13 N1 - Date created - 2000-10-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New and highly efficient synthesis of cis- and trans-opened Benzo[a]pyrene 7,8-diol 9,10-epoxide adducts at the exocyclic N(2)-amino group of deoxyguanosine. AN - 72234948; 10970294 AB - We describe a new and facile method for the synthesis of both cis- and trans-opened N(2)-deoxyguanosine (dG) adducts of (+/-)-7alpha, 8beta-dihydoxy-9beta,10beta-epoxy-7,8,9,10-tetra hydrobenzo[a]pyrene and (+/-)-7alpha,8beta-dihydoxy-9alpha,10alpha -epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene at C-10. The key step in our approach is the direct coupling of O(6)-allyl-3', 5'-di-O-(tert-butyldimethylsilyl)-2'-deoxyguanosine with these epoxides followed by the separation of the mixtures of cis- and trans-diastereomers produced. Overall coupling yields ranged from 45 to 65%. Stereochemistry of addition of the N(2)-exocyclic amino group of dG (cis-trans, approximately 1:1) was assigned by NMR, and the absolute configuration of the dG adducts was unequivocally assigned by CD spectroscopy after separation of each individual diastereomer and cleavage of the allyl protecting group. A strong CD band at 279 nm in the O(6)-protected adduct was found to be diagnostic for configuration at C-10, with a negative band correlating with 10R configuration. The synthetic methodology described allows easy access to cis- and trans-opened N(2)-dG adducts which are valuable building blocks for the synthesis of adduct-containing oligonucleotides for physical and biochemical studies. JF - The Journal of organic chemistry AU - Kroth, H AU - Yagi, H AU - Seidel, A AU - Jerina, D M AD - Laboratory of Bioorganic Chemistry, National Institutes of Diabetes and Digestive and Kidney Diseases, The National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/09/08/ PY - 2000 DA - 2000 Sep 08 SP - 5558 EP - 5564 VL - 65 IS - 18 SN - 0022-3263, 0022-3263 KW - DNA Adducts KW - 0 KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Spectrum Analysis KW - DNA Adducts -- chemistry KW - Deoxyguanosine -- chemistry KW - DNA Adducts -- chemical synthesis KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72234948?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+organic+chemistry&rft.atitle=New+and+highly+efficient+synthesis+of+cis-+and+trans-opened+Benzo%5Ba%5Dpyrene+7%2C8-diol+9%2C10-epoxide+adducts+at+the+exocyclic+N%282%29-amino+group+of+deoxyguanosine.&rft.au=Kroth%2C+H%3BYagi%2C+H%3BSeidel%2C+A%3BJerina%2C+D+M&rft.aulast=Kroth&rft.aufirst=H&rft.date=2000-09-08&rft.volume=65&rft.issue=18&rft.spage=5558&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+organic+chemistry&rft.issn=00223263&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-18 N1 - Date created - 2000-10-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of transforming growth factor-beta signaling in cancer. AN - 72250030; 10974075 AB - Signaling from transforming growth factor-beta (TGF-beta) through its unique transmembrane receptor serine-threonine kinases plays a complex role in carcinogenesis, having both tumor suppressor and oncogenic activities. Tumor cells often escape from the antiproliferative effects of TGF-beta by mutational inactivation or dysregulated expression of components in its signaling pathway. Decreased receptor function and altered ratios of the TGF-beta type I and type II receptors found in many tumor cells compromise the tumor suppressor activities of TGF-beta and enable its oncogenic functions. Recent identification of a family of intracellular mediators, the Smads, has provided new paradigms for understanding mechanisms of subversion of TGF-beta signaling by tumor cells. In addition, several proteins recently have been identified that can modulate the Smad-signaling pathway and may also be targets for mutation in cancer. Other pathways such as various mitogen-activated protein kinase cascades also contribute substantially to TGF-beta signaling. Understanding the interplay between these signaling cascades as well as the complex patterns of cross-talk with other signaling pathways is an important area of investigation that will ultimately contribute to understanding of the bifunctional tumor suppressor/oncogene role of TGF-beta in carcinogenesis. JF - Journal of the National Cancer Institute AU - de Caestecker, M P AU - Piek, E AU - Roberts, A B AD - Laboratory of Cell Regulation and Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-5055, USA. Y1 - 2000/09/06/ PY - 2000 DA - 2000 Sep 06 SP - 1388 EP - 1402 VL - 92 IS - 17 SN - 0027-8874, 0027-8874 KW - DNA-Binding Proteins KW - 0 KW - Receptors, Transforming Growth Factor beta KW - SMAD2 protein, human KW - SMAD3 protein, human KW - SMAD4 protein, human KW - Smad2 Protein KW - Smad3 Protein KW - Smad4 Protein KW - Trans-Activators KW - Transforming Growth Factor beta KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Trans-Activators -- metabolism KW - Animals KW - Genes, Tumor Suppressor -- genetics KW - Humans KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Signal Transduction KW - DNA-Binding Proteins -- metabolism KW - Transforming Growth Factor beta -- genetics KW - Transforming Growth Factor beta -- metabolism KW - Mutation KW - Neoplasms -- genetics KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72250030?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Role+of+transforming+growth+factor-beta+signaling+in+cancer.&rft.au=de+Caestecker%2C+M+P%3BPiek%2C+E%3BRoberts%2C+A+B&rft.aulast=de+Caestecker&rft.aufirst=M&rft.date=2000-09-06&rft.volume=92&rft.issue=17&rft.spage=1388&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-22 N1 - Date created - 2000-12-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 2001 Apr 4;93(7):555-7 [11287452] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Health costs due to outdoor air pollution by traffic. AN - 72316487; 11022919 JF - Lancet (London, England) AU - London, S J AU - Romieu, I AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000/09/02/ PY - 2000 DA - 2000 Sep 02 SP - 782 EP - 783 VL - 356 IS - 9232 SN - 0140-6736, 0140-6736 KW - Vehicle Emissions KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Europe KW - Public Policy KW - Health Care Costs -- statistics & numerical data KW - Air Pollution -- adverse effects KW - Air Pollution -- economics KW - Vehicle Emissions -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72316487?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet+%28London%2C+England%29&rft.atitle=Redox+control+of+aryl+sulfotransferase+specificity.&rft.au=Marshall%2C+A+D%3BMcPhie%2C+P%3BJakoby%2C+W+B&rft.aulast=Marshall&rft.aufirst=A&rft.date=2000-10-01&rft.volume=382&rft.issue=1&rft.spage=95&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 - 2000-10-19 N1 - Date created - 2000-10-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Lancet. 2001 Jan 6;357(9249):69-70; author reply 71 [11197384] Comment On: Lancet. 2000 Sep 2;356(9232):795-801 [11022926] Erratum In: Lancet 2000 Sep 9;356(9233):946 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional activation analysis using bioluminescent reporter assays AN - 954577679; 13859807 AB - Analysis of promoter and enhancer DNA sequences provides the researcher with valuable information regarding the expression patterns of genes. Insertion of small DNA fragments containing the regulatory sequence of interest into vectors carrying reporter genes allows for the accurate quantitative analysis of the gene's expression patterns and responses to various stimuli. The use of bioluminescent reporter genes provides a simple, rapid, and inexpensive system that generates virtually no toxic or radioactive waste products. In addition, bioluminescent reporter vectors are more sensitive than previous methods such as the chloramphenicol acetyl transferase (CAT) systems, that require the use of hazardous chemicals and isotopically labeled reagents. JF - Molecular Biotechnology AU - Hodge, David R AU - Clausen, Peter A AD - Laboratory for Molecular Immunoregulation, Cytokine Molecular Mechanisms Section, NCI-FCRDC-NIH, Frederick, MD, hodge@ncifcrf.gov Y1 - 2000/09// PY - 2000 DA - Sep 2000 SP - 67 EP - 76 PB - Humana Press Inc., 999 Riverview Dr., Ste. 208 Totowa NJ 07512 USA VL - 16 IS - 1 SN - 1073-6085, 1073-6085 KW - Biotechnology and Bioengineering Abstracts KW - Gene expression KW - Expression vectors KW - Enhancers KW - Promoters KW - Chloramphenicol KW - Activation analysis KW - Nucleotide sequence KW - Regulatory sequences KW - Radioactive wastes KW - Transcription activation KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/954577679?accountid=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=Molecular+Biotechnology&rft.atitle=Transcriptional+activation+analysis+using+bioluminescent+reporter+assays&rft.au=Hodge%2C+David+R%3BClausen%2C+Peter+A&rft.aulast=Hodge&rft.aufirst=David&rft.date=2000-09-01&rft.volume=16&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Molecular+Biotechnology&rft.issn=10736085&rft_id=info:doi/10.1385%2FMB%3A16%3A1%3A67 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-03-01 N1 - Last updated - 2012-03-30 N1 - SubjectsTermNotLitGenreText - Expression vectors; Gene expression; Promoters; Enhancers; Chloramphenicol; Activation analysis; Regulatory sequences; Nucleotide sequence; Radioactive wastes; Transcription activation DO - http://dx.doi.org/10.1385/MB:16:1:67 ER - TY - JOUR T1 - Levovist-enhanced Doppler sonography versus spiral computed tomography to evaluate response to percutaneous ethanol injection in hepatocellular carcinoma. AN - 85355105; pmid-10993437 AB - The aim of the current study was to compare Levovist-enhanced power Doppler (PD) imaging with contrast-enhanced spiral computed tomography (CT) in the evaluation of intratumoral vascularity of hepatocellular carcinomas at diagnosis and after percutaneous ethanol injection (PEI). Nineteen patients with hepatocellular carcinoma (HCC) underwent PD with and without Levovist and spiral CT at diagnosis and 1 month after PEI treatment. Compared to spiral CT at baseline evaluation, the PD showed intratumoral vascularity in 36.8% of the cases; this percentage reached 78.9% after Levovist enhancement. One month after PEI, only 5 out of 19 treated HCCs appeared as hypodense areas at CT and showed no contrast enhancement. Only 3 of the 14 patients with a positive spiral CT scan were positive at the PD performed without the Levovist administration (sensitivity, 21.4%). The use of contrast-enhanced ultrasonography led to detection of residual signal in six other HCCs treated by ethanol injection (sensitivity, 64.2%). We confirm that spiral CT is the most sensitive and accurate technique in evaluating the effect of ethanol injection in HCC. It correctly identifies most cases of treatment failure as enhanced areas within the lesion. The lower rate of detection of tumoral vascularity by Doppler sonography was significantly increased by Levovist. The evidence of residual vascularity within HCC at Levovist Doppler sonography allows the targeting of additional ethanol injections. JF - Journal of clinical gastroenterology AU - Fiore, F AU - Vallone, P AU - Ricchi, P AU - Tambaro, R AU - Daniele, B AU - Sandomenico, F AU - De Vivo, R AU - Civiletti, C AU - Izzo, F AU - Pignata, S AU - Ziviello, M AD - National Cancer Institute, Naples, Italy. Y1 - 2000/09// PY - 2000 DA - Sep 2000 SP - 164 EP - 168 VL - 31 IS - 2 SN - 0192-0790, 0192-0790 KW - Index Medicus KW - National Library of Medicine KW - Sensitivity and Specificity KW - Carcinoma, Hepatocellular -- blood supply KW - Humans KW - Aged KW - Liver Neoplasms -- diagnosis KW - Carcinoma, Hepatocellular -- diagnosis KW - Liver Neoplasms -- blood supply KW - Carcinoma, Hepatocellular -- drug therapy KW - Liver Neoplasms -- drug therapy KW - Injections, Subcutaneous KW - Image Enhancement KW - Middle Aged KW - Male KW - Female KW - Tomography, X-Ray Computed -- methods KW - Ultrasonography, Doppler -- methods KW - Ethanol -- administration & dosage KW - Contrast Media KW - Polysaccharides -- diagnostic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85355105?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+gastroenterology&rft.atitle=Levovist-enhanced+Doppler+sonography+versus+spiral+computed+tomography+to+evaluate+response+to+percutaneous+ethanol+injection+in+hepatocellular+carcinoma.&rft.au=Fiore%2C+F%3BVallone%2C+P%3BRicchi%2C+P%3BTambaro%2C+R%3BDaniele%2C+B%3BSandomenico%2C+F%3BDe+Vivo%2C+R%3BCiviletti%2C+C%3BIzzo%2C+F%3BPignata%2C+S%3BZiviello%2C+M&rft.aulast=Fiore&rft.aufirst=F&rft.date=2000-09-01&rft.volume=31&rft.issue=2&rft.spage=164&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+gastroenterology&rft.issn=01920790&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - Differential distribution of glutamate receptors in the cochlear nuclei. AN - 85350435; pmid-10962173 AB - Glutamate receptors are the major excitatory neurotransmitter receptors of the mammalian central nervous system, and include AMPA, kainate, delta, NMDA, and metabotropic types. In the cochlear nucleus (CN), the AMPA receptor subunits GluR2-4 are found in major kinds of neurons, while GluR1 subunit distribution is more restricted. GluR2 is low in the anteroventral CN, suggesting that many AMPA receptors here are calcium-permeable. Delta receptors are most prevalent in cartwheel cells in the dorsal CN. Of the NMDA receptors, NR1 is widespread while the NR2 subunits show more restricted distributions. Of the metabotropic glutamate receptors, mGluR1alpha is most prevalent in the dorsal CN, and mGluR2 is concentrated in Golgi cells and unipolar brush cells. AMPA receptors in endbulb synapses in the anteroventral CN are mainly GluR3+4 complexes: probably an adaptation for rapid auditory neurotransmission. Glutamate receptors are differentially distributed in synapses of fusiform cells of the dorsal CN; GluR4 and mGluR1alpha are present only at basal dendrite synapses (auditory nerve), while other glutamate receptors occupy both apical and basal synapses. Analysis of cytoplasmic distribution suggests that a selective targeting mechanism may restrict movement of GluR4 and mGluR1alpha to basal dendrites, although other targeting mechanisms may be present. JF - Hearing research AU - Petralia, R S AU - Rubio, M E AU - Wang, Y X AU - Wenthold, R J AD - NIDCD/NIH, 36/5D08, 36 CONVENT DR MSC 4162, Bethesda, MD 20892-4162, USA. Y1 - 2000/09// PY - 2000 DA - Sep 2000 SP - 59 EP - 69 VL - 147 IS - 1-2 SN - 0378-5955, 0378-5955 KW - Index Medicus KW - National Library of Medicine KW - Animals KW - Dendrites -- metabolism KW - Cochlear Nucleus -- anatomy & histology KW - Receptors, Kainic Acid -- metabolism KW - Receptors, Metabotropic Glutamate -- metabolism KW - Mice KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Tissue Distribution KW - Receptors, AMPA -- metabolism KW - Rats KW - Receptors, Opioid, delta -- metabolism KW - Cochlear Nucleus -- metabolism KW - Synapses -- metabolism KW - Receptors, Glutamate -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85350435?accountid=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=Hearing+research&rft.atitle=Differential+distribution+of+glutamate+receptors+in+the+cochlear+nuclei.&rft.au=Petralia%2C+R+S%3BRubio%2C+M+E%3BWang%2C+Y+X%3BWenthold%2C+R+J&rft.aulast=Petralia&rft.aufirst=R&rft.date=2000-09-01&rft.volume=147&rft.issue=1-2&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Hearing+research&rft.issn=03785955&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - Effects of neuroleptic medications on speech disorganization in schizophrenia: biasing associative networks towards meaning. AN - 85264928; pmid-12027048 AB - BACKGROUND: While some cognitive accounts of disorganized speech, or thought disorder, in schizophrenia have emphasized failures in working memory/discourse planning or selective attention, we have suggested that thought disorder resides in the semantic system. In this study we assessed the effect of neuroleptic medication on thought disorder and semantic processing. METHODS: Seventeen patients with schizophrenia were assessed while receiving neuroleptic medications and in crossover fashion, placebo. A number of measures were obtained: clinically rated thought disorder (using the Thought, Language and Communication Scale); working memory letter number span); lexical integrity (naming and receptive vocabulary); and, semantic priming of intracategorical word pairs. RESULTS: Semantic priming measures improved with neuroleptic medication, as did clinically rated thought disorder. No other measure changed significantly. Priming selectively covaried with changes in thought disorder. CONCLUSION: Changes in spreading semantic activation, measured in a semantic priming paradigm and presumably brought about by neuroleptics' influence on dopaminergic neuromodulatory systems, might reflect changes in the biases of pre-existing associative networks that favour or increase the accessibility of representations related by shared features. This study also has implications for the architecture of normal language in that a dissociation between the lexical and semantic levels was observed, due to the selective compromise of tasks demanding semantic processing. JF - Psychological Medicine AU - Goldberg, T E AU - Dodge, M AU - Aloia, M AU - Egan, M F AU - Weinberger, D R AD - Clinical Brain Disorders Branch, IRP, NIMH, Bethesda, MD 20892, USA. PY - 2000 SP - 1123 EP - 1130 VL - 30 IS - 5 SN - 0033-2917, 0033-2917 KW - Schizophrenia, Disorganized KW - Verbal Behavior KW - Thinking KW - Double-Blind Method KW - Human KW - Antipsychotic Agents KW - Paired-Associate Learning KW - Schizophrenia, Paranoid KW - Adult KW - Treatment Outcome KW - Cross-Over Studies KW - Middle Age KW - Male KW - Female KW - Schizophrenic Language KW - Semantics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85264928?accountid=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=Psychological+Medicine&rft.atitle=Effects+of+neuroleptic+medications+on+speech+disorganization+in+schizophrenia%3A+biasing+associative+networks+towards+meaning.&rft.au=Goldberg%2C+T+E%3BDodge%2C+M%3BAloia%2C+M%3BEgan%2C+M+F%3BWeinberger%2C+D+R&rft.aulast=Goldberg&rft.aufirst=T&rft.date=2000-09-01&rft.volume=30&rft.issue=5&rft.spage=1123&rft.isbn=&rft.btitle=&rft.title=Psychological+Medicine&rft.issn=00332917&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Cognitive impairments in patients with schizophrenia displaying preserved and compromised intellect. AN - 85260851; pmid-10986554 AB - BACKGROUND: Although intellectual and neurocognitive deficits accompany schizophrenia, there are inconsistencies in the literature concerning issues of intellectual decline, premorbid deficits, a modal deficit pattern, and preserved abilities. METHODS: A battery of neuropsychological tests was administered once to 117 consecutively admitted patients with chronic schizophrenia and a group of 27 healthy control subjects to examine patterns of premorbid and current intellect (measured by means of reading scores and IQ, respectively) and the attendant cognitive profiles in schizophrenia using classification methods based on clinically derived (IQ levels) and atheoretical (cluster) techniques. RESULTS: Sixty patients (51%) with schizophrenia who displayed a general intellectual decline of 10 points or greater from estimated premorbid levels also exhibited deficits of executive function, memory, and attention. Twenty-eight patients (23%) with consistently low estimated premorbid intellect and current intellectual levels who displayed no evidence of IQ decline exhibited language and visual processing deficits in addition to deficits present in the intellectually declining group. The remaining 29 patients (25%) who displayed average estimated premorbid intellectual levels did not show IQ decline and exhibited a cognitive profile similar to normal, with the exception of executive function and attention impairment. Atheoretical analyses support the findings from clinically derived subgroups. CONCLUSIONS: These results suggest that IQ decline, although modal in schizophrenia, is not universally characteristic and that executive function and attention deficits may be core features of schizophrenia, independent of IQ variations. JF - Archives of General Psychiatry AU - Weickert, T W AU - Goldberg, T E AU - Gold, J M AU - Bigelow, L B AU - Egan, M F AU - Weinberger, D R AD - Clinical Brain Disorders Branch, NIMH/NIH, MSC 1379, 10 Center Dr, Bethesda, MD 20892-1379, USA. PY - 2000 SP - 907 EP - 913 VL - 57 IS - 9 SN - 0003-990X, 0003-990X KW - Schizophrenia KW - Intelligence KW - Hospitalization KW - Human KW - Adult KW - Chronic Disease KW - Neuropsychological Tests KW - Cluster Analysis KW - Male KW - Female KW - Cognition Disorders KW - Intelligence Tests KW - Schizophrenic Psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85260851?accountid=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=Archives+of+General+Psychiatry&rft.atitle=Cognitive+impairments+in+patients+with+schizophrenia+displaying+preserved+and+compromised+intellect.&rft.au=Weickert%2C+T+W%3BGoldberg%2C+T+E%3BGold%2C+J+M%3BBigelow%2C+L+B%3BEgan%2C+M+F%3BWeinberger%2C+D+R&rft.aulast=Weickert&rft.aufirst=T&rft.date=2000-09-01&rft.volume=57&rft.issue=9&rft.spage=907&rft.isbn=&rft.btitle=&rft.title=Archives+of+General+Psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Toremifene as a substitute for adjuvant tamoxifen in breast cancer patients. AN - 72597471; 11268435 AB - Toremifene is a new antiestrogen, which in nonclinical studies appears less carcinogenic than tamoxifen. Clinical trials of adjuvant toremifene vs. tamoxifen in breast cancer patients are ongoing. This study aimed to evaluate the short-term effects of changing from adjuvant tamoxifen to toremifene. Twenty postmenopausal breast cancer patients receiving adjuvant tamoxifen, 20 mg/day, were switched to toremifene 60 mg/day. The effects on the uterus were evaluated prospectively by transvaginal ultrasound; tolerability was assessed clinically. In 14 patients who had uterine abnormalities (endometrial thickening or polyps) under tamoxifen, no significant changes occurred during a median of 18 months (range 7-24) of toremifene treatment. Out of six patients who had entered the study due to intolerance to tamoxifen, however, 3 tolerated toremifene well. Toremifene does not modify previous uterine changes induced by tamoxifen. For some patients who do not tolerate tamoxifen, however, switching to toremifene may allow the continuation of adjuvant antiestrogenic therapy. JF - Anticancer research AU - Bertelli, G AU - Queirolo, P AU - Vecchio, S AU - Angiolini, C AU - Bergaglio, M AU - Del Mastro, L AU - Signorini, A AU - Valenzano, M AU - Venturini, M AD - Medical Oncology Division and University, National Cancer Institute, Genova, Italy. bertelli@hp380.ist.unige.it PY - 2000 SP - 3659 EP - 3661 VL - 20 IS - 5C SN - 0250-7005, 0250-7005 KW - Antineoplastic Agents, Hormonal KW - 0 KW - Receptors, Estrogen KW - Receptors, Progesterone KW - Tamoxifen KW - 094ZI81Y45 KW - Toremifene KW - 7NFE54O27T KW - Index Medicus KW - Prospective Studies KW - Postmenopause KW - Humans KW - Aged KW - Receptors, Estrogen -- analysis KW - Middle Aged KW - Ultrasonography KW - Uterus -- drug effects KW - Female KW - Chemotherapy, Adjuvant KW - Uterus -- diagnostic imaging KW - Receptors, Progesterone -- analysis KW - Toremifene -- adverse effects KW - Breast Neoplasms -- drug therapy KW - Toremifene -- therapeutic use KW - Tamoxifen -- therapeutic use KW - Tamoxifen -- adverse effects KW - Breast Neoplasms -- surgery KW - Antineoplastic Agents, Hormonal -- therapeutic use KW - Antineoplastic Agents, Hormonal -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72597471?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Toremifene+as+a+substitute+for+adjuvant+tamoxifen+in+breast+cancer+patients.&rft.au=Bertelli%2C+G%3BQueirolo%2C+P%3BVecchio%2C+S%3BAngiolini%2C+C%3BBergaglio%2C+M%3BDel+Mastro%2C+L%3BSignorini%2C+A%3BValenzano%2C+M%3BVenturini%2C+M&rft.aulast=Bertelli&rft.aufirst=G&rft.date=2000-09-01&rft.volume=20&rft.issue=5C&rft.spage=3659&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-12 N1 - Date created - 2001-03-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunotoxins. AN - 72577075; 11249483 AB - Immunotoxins are molecules which contain a protein toxin connected to a targeting antibody. The goal of therapy is for the molecule to bind selectively to cancer cells, or to cells mediating autoimmune disease, internalise and then for the toxin to kill the cell. Several immunotoxins meeting this definition are in preclinical and clinical development, but none are approved yet for use in general practice. One close relative of immunotoxins is the growth factor fusion toxin, wherein the targeting antibody is replaced with a growth factor that selectively binds and this ligand is fused in a recombinant fashion to a protein toxin. One such molecule, containing human interleukin-2 (IL-2) fused to truncated diphtheria toxin (DT), has recently been approved under the name Ontak, and others are under development. A newer class of immunotoxins, termed recombinant immunotoxins, contain the variable or antigen binding domains of an antibody fused in recombinant fashion to a toxin. Recombinant immunotoxins, like growth factor fusion toxins, can be produced efficiently from bacteria and have a defined structure with respect to the linkage between the toxin and the ligand. However, they can, like conventional immunotoxins, be directed to antigens other than growth factor receptors, including receptor subunits. Several recombinant immunotoxins are under clinical testing and major responses have been reported, particularly in haematological malignancies. Some of these molecules may enter clinical practice in the future as targeted therapy, which is a modality distinct from those of chemotherapy, surgery and radiation therapy. JF - Expert opinion on pharmacotherapy AU - Kreitman, R J AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, 37/4B27, 37 Convent Drive Msc 4255 Bethesda, MD 20892, USA. kreitmar@mail.nih.gov Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 1117 EP - 1129 VL - 1 IS - 6 SN - 1465-6566, 1465-6566 KW - Antineoplastic Agents KW - 0 KW - Immunotoxins KW - Index Medicus KW - Animals KW - Humans KW - Immunotoxins -- chemistry KW - Neoplasms -- drug therapy KW - Antineoplastic Agents -- immunology KW - Immunotoxins -- immunology KW - Immunotoxins -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- chemistry KW - Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72577075?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+opinion+on+pharmacotherapy&rft.atitle=Immunotoxins.&rft.au=Kreitman%2C+R+J&rft.aulast=Kreitman&rft.aufirst=R&rft.date=2000-09-01&rft.volume=1&rft.issue=6&rft.spage=1117&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+pharmacotherapy&rft.issn=14656566&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-05 N1 - Date created - 2001-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development of DNA-based radiopharmaceuticals carrying Auger-electron emitters for anti-gene radiotherapy. AN - 72454840; 11105589 AB - Targeting of radiation damage to specific DNA sequences is the essence of antigene radiotherapy. This technique also provides a tool to study molecular mechanisms of DNA repair on a defined, single radiodamaged site. We achieved such sequence-specific radiodamage by combining the highly localized DNA damage produced by the decay of Auger-electron-emitters such as 125I with the sequence-specific action of triplex-forming oligonucleotides (TFO). TFO complementary to polypurine-polypyrimidine regions of human genes were synthesized and labeled with 125I-dCTP by the primer extension method. 125I-TFO were delivered into cells with several delivery systems. In addition, human enzymes capable of supporting DNA single-strand-break repair were isolated and assessed for their role in the repair of this lesion. Also, the mutagenicity and repairability of 125I-TFO-induced double strand breaks (DSB) were assessed by repair of a plasmid possessing a site-specific DSB lesion. Using plasmids containing target polypurine-polypyrimidine tracts, we obtained the fine structure of sequence-specific DNA breaks produced by decay of 125I with single-nucleotide resolution. We showed that the designed 125I-TFO in nanomolar concentrations could bind to and introduce double-strand breaks into the target sequences in situ, i.e., within isolated nuclei and intact digitonin-permeabilized cells. We also showed 125I-TFO-induced DSB to be highly mutagenic lesions resulting in a mutation frequency of nearly 80%, with deletions comprising the majority of mutations. The results obtained demonstrate the ability of 125I-TFO to target specific sequences in their natural environment--within eucaryotic nucleus. Repair of 125I-TFO-induced DNA damage should typically result in mutagenic gene inactivation. JF - The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) AU - Panyutin, I G AU - Winters, T A AU - Feinendegen, L E AU - Neumann, R D AD - Department of Nuclear Medicine, National Institutes of Health, Bethesda, MD 20892-1180, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 256 EP - 267 VL - 44 IS - 3 SN - 1125-0135, 1125-0135 KW - Iodine Radioisotopes KW - 0 KW - Oligonucleotides KW - Radiopharmaceuticals KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Iodine Radioisotopes -- therapeutic use KW - Animals KW - DNA Repair KW - Neoplasms -- radiotherapy KW - Neoplasms -- diagnostic imaging KW - Humans KW - Iodine Radioisotopes -- pharmacology KW - DNA Damage -- radiation effects KW - Nucleic Acid Conformation KW - Neoplasms -- genetics KW - Radionuclide Imaging KW - Radiopharmaceuticals -- therapeutic use KW - Radiopharmaceuticals -- pharmacology KW - Oligonucleotides -- therapeutic use KW - Oligonucleotides -- pharmacology KW - DNA -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72454840?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+quarterly+journal+of+nuclear+medicine+%3A+official+publication+of+the+Italian+Association+of+Nuclear+Medicine+%28AIMN%29+%5Band%5D+the+International+Association+of+Radiopharmacology+%28IAR%29&rft.atitle=Development+of+DNA-based+radiopharmaceuticals+carrying+Auger-electron+emitters+for+anti-gene+radiotherapy.&rft.au=Panyutin%2C+I+G%3BWinters%2C+T+A%3BFeinendegen%2C+L+E%3BNeumann%2C+R+D&rft.aulast=Panyutin&rft.aufirst=I&rft.date=2000-09-01&rft.volume=44&rft.issue=3&rft.spage=256&rft.isbn=&rft.btitle=&rft.title=The+quarterly+journal+of+nuclear+medicine+%3A+official+publication+of+the+Italian+Association+of+Nuclear+Medicine+%28AIMN%29+%5Band%5D+the+International+Association+of+Radiopharmacology+%28IAR%29&rft.issn=11250135&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-22 N1 - Date created - 2000-12-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dysregulation of the hypothalamic-pituitary-adrenal axis in short children with and without growth hormone deficiency. AN - 72418145; 11085187 AB - The effects of L-dopamine (LD) administration and insulin-induced hypoglycemia in adrenocorticotropin (ACTH) and cortisol secretion were studied in 14 short boys. LD caused moderate changes in both hormones. The four boys with isolated, idiopathic growth hormone (GH) deficiency (IGD) demonstrated a greater cortisol increase in response to hypoglycemia than the 10 boys with normal GH secretion. In at least some short children with IGD, abnormal regulation of the hypothalamic-pituitary-adrenal axis may be present. JF - Journal of pediatric endocrinology & metabolism : JPEM AU - Stratakis, C A AU - Rusovici, D E AU - Kulin, H E AU - Finkelstein, J W AD - Unit of Genetics & Endocrinology, DEB, NICHD, NIH, Bethesda, MD 20892-1862, USA. stratakc@cc1.nichd.nih.gov PY - 2000 SP - 1095 EP - 1100 VL - 13 IS - 8 SN - 0334-018X, 0334-018X KW - Hypoglycemic Agents KW - 0 KW - Insulin KW - Human Growth Hormone KW - 12629-01-5 KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Dopamine KW - VTD58H1Z2X KW - Hydrocortisone KW - WI4X0X7BPJ KW - Index Medicus KW - Human Growth Hormone -- deficiency KW - Dopamine -- pharmacology KW - Humans KW - Hypoglycemia -- blood KW - Child KW - Hypoglycemia -- chemically induced KW - Adolescent KW - Male KW - Hydrocortisone -- blood KW - Adrenocorticotropic Hormone -- blood KW - Body Height KW - Hypothalamo-Hypophyseal System -- physiopathology KW - Pituitary-Adrenal System -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72418145?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pediatric+endocrinology+%26+metabolism+%3A+JPEM&rft.atitle=Dysregulation+of+the+hypothalamic-pituitary-adrenal+axis+in+short+children+with+and+without+growth+hormone+deficiency.&rft.au=Stratakis%2C+C+A%3BRusovici%2C+D+E%3BKulin%2C+H+E%3BFinkelstein%2C+J+W&rft.aulast=Stratakis&rft.aufirst=C&rft.date=2000-09-01&rft.volume=13&rft.issue=8&rft.spage=1095&rft.isbn=&rft.btitle=&rft.title=Journal+of+pediatric+endocrinology+%26+metabolism+%3A+JPEM&rft.issn=0334018X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-01 N1 - Date created - 2001-02-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potential use of lipoxygenase inhibitors for cancer chemoprevention. AN - 72390808; 11060797 AB - Increasing evidence suggests that lipoxygenase (LO)-catalysed metabolites have a profound influence on the development and progression of human cancers. Compared with normal tissues, significantly elevated levels of LO products have been found in breast tumours, colon cancers, lung, skin and prostate cancers, as well as in cells from patients with both acute and chronic leukaemias. LO-mediated products elicit diverse biological activities needed for neoplastic cell growth, influencing growth factor and transcription factor activation, oncogene induction, stimulation of tumour cell adhesion and regulation of apoptotic cell death. Agents that block LO catalytic activity may be effective in preventing cancer by interfering with signalling events needed for tumour growth. In the past ten years, pharmaceuticals agents that specifically inhibit the 5-LO metabolic pathway have been developed to treat inflammatory diseases such as asthma, arthritis and psoriasis. Some of these compounds possess anti-oxidant properties and may be effective in preventing cancer by blocking free radical-induced genetic damage or by preventing the metabolic activation of carcinogens. Other compounds may work by negatively modulating DNA synthesis. Pharmacological profiles of potential chemopreventive agents are compiled from enzyme assays, in vitro testing (e.g., cell proliferation inhibition in human cancer cells) and in vivo animal carcinogenesis models (e.g., N-methyl-N-nitrosourea-induced rat mammary cancer, benzo(a)pyrene-induced lung tumours in strain A/J mice and hormone-induced prostate tumours in rats). In this way, compounds are identified for chemoprevention trials in human subjects. Based on currently available data, it is expected that the prevention of lung and prostate cancer will be initially studied in human trials of LO inhibitors. JF - Expert opinion on investigational drugs AU - Steele, V E AU - Holmes, C A AU - Hawk, E T AU - Kopelovich, L AU - Lubet, R A AU - Crowell, J A AU - Sigman, C C AU - Kelloff, G J AD - Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland 20892, USA. vs1y@nih.gov Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 2121 EP - 2138 VL - 9 IS - 9 SN - 1354-3784, 1354-3784 KW - Lipoxygenase Inhibitors KW - 0 KW - Arachidonic Acid KW - 27YG812J1I KW - Lipoxygenase KW - EC 1.13.11.12 KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Chemoprevention -- methods KW - Mice KW - Drug Screening Assays, Antitumor -- methods KW - Arachidonic Acid -- metabolism KW - Lipoxygenase Inhibitors -- chemistry KW - Lipoxygenase -- metabolism KW - Neoplasms -- enzymology KW - Lipoxygenase -- drug effects KW - Lipoxygenase Inhibitors -- pharmacology KW - Lipoxygenase Inhibitors -- therapeutic use KW - Neoplasms -- prevention & control KW - Lipoxygenase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72390808?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+opinion+on+investigational+drugs&rft.atitle=Potential+use+of+lipoxygenase+inhibitors+for+cancer+chemoprevention.&rft.au=Steele%2C+V+E%3BHolmes%2C+C+A%3BHawk%2C+E+T%3BKopelovich%2C+L%3BLubet%2C+R+A%3BCrowell%2C+J+A%3BSigman%2C+C+C%3BKelloff%2C+G+J&rft.aulast=Steele&rft.aufirst=V&rft.date=2000-09-01&rft.volume=9&rft.issue=9&rft.spage=2121&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+investigational+drugs&rft.issn=13543784&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-11 N1 - Date created - 2000-12-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A case-control study of nitrate in drinking water and non-Hodgkin's lymphoma in Minnesota. AN - 72384652; 11063407 AB - Nitrate in drinking water has been implicated as a possible risk factor for non-Hodgkin's lymphoma. The authors examined the association between non-Hodgkin's lymphoma and waterborne nitrate through a population-based case-control study of white men in Minnesota. The authors, by linking residential histories with community water records, estimated average long-term exposure to nitrate in drinking water from 1947 to 1975 for 73 cases diagnosed between 1980 and 1982 and for 147 controls who used community water supplies. No association was found between nitrate levels in community water supplies and non-Hodgkin's lymphoma within the range of study exposures (median of highest exposure category = 2.4 mg nitrate/l [range = 0.1-7.2 mg/l]). The findings provide some safety assurance for those who use water systems that have nitrate levels that are less than 2.4 mg/l. JF - Archives of environmental health AU - Freedman, D M AU - Cantor, K P AU - Ward, M H AU - Helzlsouer, K J AD - Radiation Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. PY - 2000 SP - 326 EP - 329 VL - 55 IS - 5 SN - 0003-9896, 0003-9896 KW - Nitrates KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Drinking KW - Reference Values KW - Odds Ratio KW - Humans KW - Aged KW - Population Surveillance KW - Age Distribution KW - Logistic Models KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Confidence Intervals KW - Incidence KW - Middle Aged KW - Sex Distribution KW - Minnesota -- epidemiology KW - Female KW - Male KW - Lymphoma, Non-Hodgkin -- epidemiology KW - Water Supply -- analysis KW - Lymphoma, Non-Hodgkin -- etiology KW - Water Pollution, Chemical -- adverse effects KW - Nitrates -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72384652?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+case-control+study+of+nitrate+in+drinking+water+and+non-Hodgkin%27s+lymphoma+in+Minnesota.&rft.au=Freedman%2C+D+M%3BCantor%2C+K+P%3BWard%2C+M+H%3BHelzlsouer%2C+K+J&rft.aulast=Freedman&rft.aufirst=D&rft.date=2000-09-01&rft.volume=55&rft.issue=5&rft.spage=326&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 - 2000-11-21 N1 - Date created - 2000-11-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Update on adjuvant chemotherapy for early breast cancer. AN - 72339733; 11033824 AB - Adjuvant chemotherapy represents a significant advance in the management of early-stage breast cancer and, as such, has saved many lives. Worldwide, adjuvant chemotherapy has benefitted all groups tested, including pre- and postmenopausal women, those with node-negative and node-positive disease, and those with estrogen-receptor (ER)-positive and ER-negative disease. However, the significant number of women who relapse despite adjuvant therapy provides the impetus to develop more efficacious regimens. Results from large randomized clinical trials, which will mature over the next few years, will clarify the potential benefits of the taxanes in the adjuvant setting, provide answers as to the efficacy of a dose-dense approach, and define a role, if any, for high-dose chemotherapy. A shift toward targeted therapies has also begun, with the incorporation of trastuzumab (Herceptin) into the adjuvant setting. Minimizing the long-term toxicity of adjuvant therapy for the large number of women who survive their disease is paramount. This article highlights the need to develop predictive factors to help tailor individual therapy. JF - Oncology (Williston Park, N.Y.) AU - McCarthy, N J AU - Swain, S M AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 1267 EP - 80; discussion 1280-4, 1287-8 VL - 14 IS - 9 SN - 0890-9091, 0890-9091 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Humans KW - Clinical Trials as Topic KW - Female KW - Chemotherapy, Adjuvant KW - Breast Neoplasms -- drug therapy KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72339733?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Update+on+adjuvant+chemotherapy+for+early+breast+cancer.&rft.au=McCarthy%2C+N+J%3BSwain%2C+S+M&rft.aulast=McCarthy&rft.aufirst=N&rft.date=2000-09-01&rft.volume=14&rft.issue=9&rft.spage=1267&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 - 2001-01-11 N1 - Date created - 2001-01-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Oncology (Huntingt) 2000 Dec;14(12):1697 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preventing dangerous drug interactions. AN - 72334800; 11029865 AB - Although most drug interactions are clinically insignificant, some pose a significant risk. A basic knowledge of the mechanisms of drug interactions can help pharmacists to identify and avert potentially risky combinations. Review all medications, including dietary supplements and nonprescription drugs, when taking a medication history. Pay special attention to patients who take several medications, use herbal products, or use prescription medications associated with serious adverse events or toxicities. JF - Journal of the American Pharmaceutical Association (Washington,D.C. : 1996) AU - Piscitelli, S AD - Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, Md., USA. PY - 2000 SP - S44 EP - S45 VL - 40 IS - 5 Suppl 1 SN - 1086-5802, 1086-5802 KW - Index Medicus KW - Humans KW - Herb-Drug Interactions KW - Plants, Medicinal -- adverse effects KW - Pharmacists KW - Drug Interactions KW - Drug-Related Side Effects and Adverse Reactions UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72334800?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Pharmaceutical+Association+%28Washington%2CD.C.+%3A+1996%29&rft.atitle=Preventing+dangerous+drug+interactions.&rft.au=Piscitelli%2C+S&rft.aulast=Piscitelli&rft.aufirst=S&rft.date=2000-09-01&rft.volume=40&rft.issue=5+Suppl+1&rft.spage=S44&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Pharmaceutical+Association+%28Washington%2CD.C.+%3A+1996%29&rft.issn=10865802&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-30 N1 - Date created - 2000-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Spectroscopic imaging of radiation-induced effects in the white matter of glioma patients. AN - 72332828; 11027879 AB - External radiation therapy of brain tumors may cause adverse effects on normal brain tissue, resulting in severe neuropsychological and cognitive impairment. We investigated the late delayed radiation effects in the white matter (WM) using (1)H magnetic resonance spectroscopic imaging ((1)HMRSI). Nine glioma patients with local radiation-induced signal abnormalities in the T(2)-weighted MR images were studied with nine age- and sex-matched controls. The metabolite ratios in the radiation-induced hyper intensity area (RIHA) and in the normal appearing white matter (NAWM) of the patients were compared with respective WM areas of the controls. In RIHA, choline/creatine (Cho/Cr) was 17% decreased (1.22 +/- 0.13 vs 1.47 +/- 0.16, p = 0.0027, significant (s), unpaired Student's t test with Bonferroni correction) in the patients compared to the controls, while there was no difference in N-acetyl aspartate/Cr (NAA/Cr) (2.49 +/- 0.57 vs 2.98 +/- 0.32, p = 0.039) or NAA/Cho (2. 03 +/- 0.40 vs 2.04 +/- 0.17, p = 0.95). In NAWM, Cho/Cr was 24% decreased (1.21 +/- 0.15 vs 1.59 +/- 0.13, p < 0.0001, s) and NAA/Cho was 20% increased (2.49 +/- 0.49 vs 1.98 +/- 0.15, p = 0. 0082, s) in the patients compared to the controls, while there was no difference in NAA/Cr (2.99 +/- 0.46 vs 3.16 +/- 0.32, p = 0.38). NAA(RIHA)/NAA(NAWM) was 25% decreased (0.75 +/- 0.20 vs 1.00 +/- 0. 12, p = 0.0043, s) and Cr(RIHA)/Cr(NAWM) was 16% decreased (0.89 +/- 0.15 vs 1.06 +/- 0.10, p = 0.013, s) in the patients compared to the controls, while there was no difference in Cho(RIHA)/Cho(NAWM) (0.92 +/- 0.23 vs 0.98 +/- 0.10, p = 0.47). (1)HMRSI reveals widespread chemical changes in the WM after radiation therapy. In RIHA, there is loss of NAA, Cho, and Cr implying axonal and membrane damage and in NAWM, there is loss of Cho, reflecting membrane damage. JF - Magnetic resonance imaging AU - Virta, A AU - Patronas, N AU - Raman, R AU - Dwyer, A AU - Barnett, A AU - Bonavita, S AU - Tedeschi, G AU - Lundbom, N AD - Neuroimaging Branch, NINDS, Clinical Center, National Institutes of Health, Bethesda, MD, USA. anevir@earthlink.net Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 851 EP - 857 VL - 18 IS - 7 SN - 0730-725X, 0730-725X KW - Index Medicus KW - Sensitivity and Specificity KW - Radiation Dosage KW - Probability KW - Reference Values KW - Myelin Sheath -- pathology KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - Cranial Irradiation -- methods KW - Male KW - Female KW - Magnetic Resonance Spectroscopy -- methods KW - Glioma -- diagnosis KW - Brain -- radiation effects KW - Brain -- pathology KW - Brain Neoplasms -- radiotherapy KW - Brain Neoplasms -- diagnosis KW - Glioma -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72332828?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+resonance+imaging&rft.atitle=Spectroscopic+imaging+of+radiation-induced+effects+in+the+white+matter+of+glioma+patients.&rft.au=Virta%2C+A%3BPatronas%2C+N%3BRaman%2C+R%3BDwyer%2C+A%3BBarnett%2C+A%3BBonavita%2C+S%3BTedeschi%2C+G%3BLundbom%2C+N&rft.aulast=Virta&rft.aufirst=A&rft.date=2000-09-01&rft.volume=18&rft.issue=7&rft.spage=851&rft.isbn=&rft.btitle=&rft.title=Magnetic+resonance+imaging&rft.issn=0730725X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-15 N1 - Date created - 2000-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Homogenous expression of killer cell immunoglobulin-like receptors (KIR) on polyclonal natural killer cells detected by a monoclonal antibody to KIR2D. AN - 72332687; 11034560 AB - The activity of human natural killer (NK) cells is in part regulated by the expression of killer cell immunoglobulin (Ig)-like receptors (KIR) that recognize major histocompatibility complex (MHC) class I and can inhibit NK cell cytotoxicity. A monoclonal anti-KIR antibody was established and designated Lig1. Lig1 was shown to be specific for KIR in cell-surface staining and to react with all KIR2D, except KIR2DL4 which lacks a D1 domain, but not with KIR3D molecules in an enzyme-linked immunoadsorbent assay (ELISA) and Western blotting. Unlike other anti-KIR antibodies, Lig1 did not inhibit binding of KIR-Ig-fusion proteins to MHC-class I expressing cells nor did it interfere with KIR-mediated inhibition of NK cell cytotoxicity in a functional assay. Lig1 reacted with all NK cells in polyclonal NK populations from different donors, demonstrating that all NK cells express at least one KIR2D receptor. JF - Tissue antigens AU - Watzl, C AU - Peterson, M AU - Long, E O AD - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 240 EP - 247 VL - 56 IS - 3 SN - 0001-2815, 0001-2815 KW - Antibodies, Monoclonal KW - 0 KW - Histocompatibility Antigens Class I KW - Immunoglobulins KW - KIR2DL4 protein, human KW - Peptides KW - Protein Isoforms KW - Receptors, Immunologic KW - Receptors, KIR KW - Receptors, KIR2DL4 KW - Recombinant Fusion Proteins KW - Index Medicus KW - Animals KW - Immunoglobulins -- genetics KW - Recombinant Fusion Proteins -- immunology KW - Humans KW - Peptides -- immunology KW - Amino Acid Sequence KW - Mice KW - Mice, Inbred BALB C KW - Protein Isoforms -- immunology KW - Blotting, Western KW - Sequence Alignment KW - Protein Isoforms -- chemistry KW - Cells, Cultured KW - Cytotoxicity Tests, Immunologic KW - Flow Cytometry KW - Protein Structure, Tertiary KW - Cell Line KW - Female KW - Receptors, Immunologic -- genetics KW - Receptors, Immunologic -- immunology KW - Histocompatibility Antigens Class I -- immunology KW - Receptors, Immunologic -- chemistry KW - Killer Cells, Natural -- immunology KW - Antibodies, Monoclonal -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72332687?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tissue+antigens&rft.atitle=Homogenous+expression+of+killer+cell+immunoglobulin-like+receptors+%28KIR%29+on+polyclonal+natural+killer+cells+detected+by+a+monoclonal+antibody+to+KIR2D.&rft.au=Watzl%2C+C%3BPeterson%2C+M%3BLong%2C+E+O&rft.aulast=Watzl&rft.aufirst=C&rft.date=2000-09-01&rft.volume=56&rft.issue=3&rft.spage=240&rft.isbn=&rft.btitle=&rft.title=Tissue+antigens&rft.issn=00012815&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-22 N1 - Date created - 2001-01-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Progesterone prevents estradiol-induced dendritic spine formation in cultured hippocampal neurons. AN - 72318742; 11025407 AB - Estradiol has been shown to cause an increase in dendritic spine density in cultured hippocampal neurons, an effect mediated by downregulation of brain-derived neurotrophic factor (BDNF) and glutamic acid decarboxylase (GAD), and the subsequent phosphorylation of cAMP response element binding protein (CREB) in response to enhanced activity levels. Interestingly, progesterone was shown to counteract the effects of estradiol on dendritic spine density in vivo and in vitro. The present study examined how progesterone may act to block the effects of estradiol in the molecular cascade of cellular events leading to formation of dendritic spines. Progesterone did not affect the estradiol-induced downregulation of BDNF or GAD, but it did block the effect of estradiol on CREB phosphorylation. The latter effects of progesterone on the pCREB response and spine formation were reversed by indomethacin, which prevents the conversion of progesterone to the neurosteroid tetrahydroprogesterone (THP). We therefore examined if the progesterone effects were caused by its active metabolite THP. Progesterone treatment caused a 60-fold increase in THP in the culture medium. THP itself enhanced spontaneous GABAergic activity in patch-clamped cultured neurons. Finally, THP blocked the estradiol-induced increase in spine density. These results suggest that progesterone, through conversion to THP, blocks the effects of estradiol on dendritic spines not via a direct nuclear receptor interaction but by counteracting the enhanced excitability produced by estradiol in the cultured network. Copyright 2000 S. Karger AG, Basel. JF - Neuroendocrinology AU - Murphy, D D AU - Segal, M AD - NINDS, NIH, Bethesda, MD, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 133 EP - 143 VL - 72 IS - 3 SN - 0028-3835, 0028-3835 KW - Brain-Derived Neurotrophic Factor KW - 0 KW - Cyclic AMP Response Element-Binding Protein KW - Mifepristone KW - 320T6RNW1F KW - Progesterone KW - 4G7DS2Q64Y KW - Estradiol KW - 4TI98Z838E KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Pregnanolone KW - BXO86P3XXW KW - Glutamate Decarboxylase KW - EC 4.1.1.15 KW - Indomethacin KW - XXE1CET956 KW - Index Medicus KW - Animals KW - Fetus KW - Cell Size -- physiology KW - Pregnanolone -- pharmacology KW - Pregnanolone -- metabolism KW - Cells, Cultured -- cytology KW - Cells, Cultured -- drug effects KW - Pregnanolone -- analogs & derivatives KW - Mifepristone -- pharmacology KW - Drug Interactions -- physiology KW - Cell Size -- drug effects KW - Glutamate Decarboxylase -- metabolism KW - Indomethacin -- pharmacology KW - Rats KW - Signal Transduction -- physiology KW - Rats, Sprague-Dawley KW - Brain-Derived Neurotrophic Factor -- metabolism KW - Cyclic AMP Response Element-Binding Protein -- metabolism KW - Patch-Clamp Techniques KW - Cells, Cultured -- metabolism KW - Signal Transduction -- drug effects KW - Microscopy, Electron KW - gamma-Aminobutyric Acid -- metabolism KW - Progesterone -- analogs & derivatives KW - Dendrites -- metabolism KW - Progesterone -- metabolism KW - Hippocampus -- ultrastructure KW - Progesterone -- pharmacology KW - Hippocampus -- metabolism KW - Estradiol -- pharmacology KW - Dendrites -- ultrastructure KW - Neuronal Plasticity -- physiology KW - Neuronal Plasticity -- drug effects KW - Dendrites -- drug effects KW - Hippocampus -- drug effects KW - Estradiol -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72318742?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroendocrinology&rft.atitle=Progesterone+prevents+estradiol-induced+dendritic+spine+formation+in+cultured+hippocampal+neurons.&rft.au=Murphy%2C+D+D%3BSegal%2C+M&rft.aulast=Murphy&rft.aufirst=D&rft.date=2000-09-01&rft.volume=72&rft.issue=3&rft.spage=133&rft.isbn=&rft.btitle=&rft.title=Neuroendocrinology&rft.issn=00283835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-21 N1 - Date created - 2000-10-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dynorphin A (2-17) attenuates the unconditioned but not the conditioned effects of opiate withdrawal in the rat. AN - 72315183; 11026742 AB - An unbiased place preference conditioning procedure was used to examine the influence of the non-opioid peptide, dynorphin A 2-17 (DYN 2-17), upon the conditioned and unconditioned effects of opiate withdrawal in the rat. Rats were implanted SC with two pellets containing 75 mg morphine or placebo. Single-trial place conditioning sessions with saline and the opioid receptor antagonist naloxone (0.1-1.0 mg/kg; SC) commenced 4 days later. Ten minutes before SC injections, animals received an IV infusion of saline or DYN 2-17 (0.1-5.0 mg/kg). Additional groups of placebo- and morphine-pelleted animals were conditioned with saline and DYN 2-17. During each 30-min conditioning session, somatic signs of withdrawal were quantified. Tests of place conditioning were conducted in pelleted animals 24 h later. Naloxone produced wet-dog shakes, body weight loss, ptosis and diarrhea in morphine-pelleted animals. Morphine-pelleted animals also exhibited significant aversions for an environment previously associated with the administration of naloxone. These effects were not observed in placebo-pelleted animals. DYN 2-17 pretreatment resulted in a dose-related attenuation of somatic withdrawal signs. However, conditioned place aversions were still observed in morphine-pelleted animals that had received DYN 2-17 in combination with naloxone. Furthermore, the magnitude of this effect did not differ from control animals. These data demonstrate that the administration of DYN 2-17 attenuates the somatic, but not the conditioned aversive effects of antagonist-precipitated withdrawal from morphine in the rat. Differential effects of this peptide in modulating the conditioned and unconditioned effects of opiate withdrawal are suggested. JF - Psychopharmacology AU - Shippenberg, T S AU - Funada, M AU - Schutz, C G AD - Integrative Neuroscience Unit, Behavioral Pharmacology Branch, National Institute of Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. TShippen@intra.nida.nih.gov Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 351 EP - 358 VL - 151 IS - 4 SN - 0033-3158, 0033-3158 KW - Peptide Fragments KW - 0 KW - Receptors, N-Methyl-D-Aspartate KW - Naloxone KW - 36B82AMQ7N KW - Dynorphins KW - 74913-18-1 KW - dynorphin (2-17) KW - 83608-80-4 KW - Index Medicus KW - Rats KW - Naloxone -- pharmacology KW - Animals KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Rats, Sprague-Dawley KW - Male KW - Peptide Fragments -- pharmacology KW - Substance Withdrawal Syndrome -- drug therapy KW - Peptide Fragments -- pharmacokinetics KW - Opioid-Related Disorders -- drug therapy KW - Dynorphins -- pharmacokinetics KW - Dynorphins -- pharmacology KW - Conditioning (Psychology) -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72315183?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Dynorphin+A+%282-17%29+attenuates+the+unconditioned+but+not+the+conditioned+effects+of+opiate+withdrawal+in+the+rat.&rft.au=Shippenberg%2C+T+S%3BFunada%2C+M%3BSchutz%2C+C+G&rft.aulast=Shippenberg&rft.aufirst=T&rft.date=2000-09-01&rft.volume=5&rft.issue=10&rft.spage=789&rft.isbn=&rft.btitle=&rft.title=Genes+to+cells+%3A+devoted+to+molecular+%26+cellular+mechanisms&rft.issn=13569597&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-18 N1 - Date created - 2001-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Applying biomarker research. AN - 72314870; 11017898 JF - Environmental health perspectives AU - Bennett, D A AU - Waters, M D Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 907 EP - 910 VL - 108 IS - 9 KW - Biomarkers KW - 0 KW - Environmental Pollutants KW - Index Medicus KW - Public Health KW - Epidemiologic Studies KW - Humans KW - Research Design KW - Biomarkers -- analysis KW - Risk Assessment -- methods KW - Environmental Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72314870?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Environmental+health+perspectives&rft.atitle=Applying+biomarker+research.&rft.au=Bennett%2C+D+A%3BWaters%2C+M+D&rft.aulast=Bennett&rft.aufirst=D&rft.date=2000-09-01&rft.volume=108&rft.issue=9&rft.spage=907&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 - 2000-12-22 N1 - Date created - 2000-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Complementation of an hMSH2 defect in human colorectal carcinoma cells by human chromosome 2 transfer. AN - 72311466; 11020245 AB - The human colorectal tumor cell line LoVo has a homozygous deletion in the hMSH2 gene from exon 3 to exon 8, is deficient in mismatch repair (MMR) activity, and exhibits microsatellite instability. To determine whether the introduction of a wild type hMSH2 into LoVo restores MMR activity and stabilizes microsatellite loci, we transferred a chromosome 2 fragment containing hMSH2 into a homologous recombination-proficient chicken DT40/human hybrid (DT40 2C) and a human chromosome 2 in a mouse A9 hybrid to LoVo. Transfers of these chromosomes into LoVo resulted in LoVo both with and without a wild-type hMSH2. Complete correlation was found between the presence of the wild-type hMSH2 and hMSH2 expression, an increased stability in microsatellite loci, and competency in MMR. The hMSH2-positive LoVo hybrids also showed an increased sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine. This enhanced toxicity is associated with G(2) cell-cycle arrest followed by premature mitosis and cell death. These results suggest that hMSH2 may be responsible for complementing mutator and drug-resistant phenotypes in chromosome 2-transferred LoVo cells. To test whether the hMSH2 in DT40 2C cells can be modified by homologous recombination, we transfected DT40 2C with a targeting vector containing an hMSH2 exon 4 disrupted by the zeocin-resistant gene. The results showed that the hMSH2 locus in DT40 2C was efficiently targeted by an exogeneously transfected homologous sequence, suggesting that transfer of a modified hMSH2 from DT40 2C to LoVo via chromosome transfer could be used to determine the function of hMSH2. JF - Molecular carcinogenesis AU - Watanabe, Y AU - Haugen-Strano, A AU - Umar, A AU - Yamada, K AU - Hemmi, H AU - Kikuchi, Y AU - Takano, S AU - Shibata, Y AU - Barrett, J C AU - Kunkel, T A AU - Koi, M AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 37 EP - 49 VL - 29 IS - 1 SN - 0899-1987, 0899-1987 KW - DNA Primers KW - 0 KW - DNA-Binding Proteins KW - Proto-Oncogene Proteins KW - Methylnitronitrosoguanidine KW - 12H3O2UGSF KW - MSH2 protein, human KW - EC 3.6.1.3 KW - Msh2 protein, mouse KW - MutS Homolog 2 Protein KW - Index Medicus KW - Animals KW - Microsatellite Repeats -- genetics KW - G2 Phase -- drug effects KW - Base Sequence KW - Humans KW - Methylnitronitrosoguanidine -- pharmacology KW - Mice KW - Gene Targeting KW - Cell Death -- drug effects KW - Chromosomes, Human, Pair 2 KW - Colorectal Neoplasms -- pathology KW - Genetic Complementation Test KW - Colorectal Neoplasms -- genetics KW - Proto-Oncogene Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72311466?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+carcinogenesis&rft.atitle=Complementation+of+an+hMSH2+defect+in+human+colorectal+carcinoma+cells+by+human+chromosome+2+transfer.&rft.au=Watanabe%2C+Y%3BHaugen-Strano%2C+A%3BUmar%2C+A%3BYamada%2C+K%3BHemmi%2C+H%3BKikuchi%2C+Y%3BTakano%2C+S%3BShibata%2C+Y%3BBarrett%2C+J+C%3BKunkel%2C+T+A%3BKoi%2C+M&rft.aulast=Watanabe&rft.aufirst=Y&rft.date=2000-09-01&rft.volume=29&rft.issue=1&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-26 N1 - Date created - 2000-10-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disparate effects of phorbol esters, CD3 and the costimulatory receptors CD2 and CD28 on RANTES secretion by human T lymphocytes. AN - 72307656; 11012750 AB - This study has examined the stimuli required for secretion of regulated upon activation, normal T-cell expressed, presumed secreted (RANTES) from T lymphocytes and found that stimuli such as phorbol 12-myristate 13-acetate (PMA), which are unable to support T-cell proliferation and interleukin-2 (IL-2) production, are nevertheless able to elicit strong secretion of RANTES. Conversely, stimuli such as CD2 and CD28 ligation, which are able to support T-cell proliferation, are unable to elicit RANTES secretion. Coligation of CD3 and CD28 drives T-cell proliferation to a similar degree as CD2 and CD28 coligation, yet also supports modest RANTES secretion. Furthermore, CD28 ligation enhances the secretion of RANTES stimulated by PMA and this costimulatory effect is abrogated by the phosphoinositide 3-kinase inhibitor wortmannin. Our data also indicate that the observed effects of PMA on RANTES secretion are probably due to activation of protein kinase C (PKC) isoenzymes, since RANTES secretion was unaffected by the non-PKC activating 4alpha-phorbol ester, whilst the general PKC inhibitor Ro-32-0432 inhibits PMA-stimulated RANTES secretion. Moreover, the effect of PMA appears to be chemokine-specific because PMA was unable to increase secretion of the related CC chemokine MIP-1alpha. Under stimulation conditions where increases in [Ca2+]i occur (e.g. PMA plus ionomycin or CD3 plus CD28 ligation) RANTES secretion can be severely reduced compared with the levels observed in response to the phorbol ester PMA. Hence, whilst PKC-dependent pathways are sufficient for strong RANTES secretion, a calcium-dependent factor is activated which negatively regulates RANTES secretion. This correlates well with the observation that ligation of cytolytic T lymphocyte-associated antigen-4 (CTLA-4) (expression of which has been reported to be dependent on a sustained calcium signal), inhibits RANTES secretion induced by CD3/CD28, but has no effect on PMA-stimulated RANTES secretion. JF - Immunology AU - Sotsios, Y AU - Blair, P J AU - Westwick, J AU - Ward, S G AD - Department of Pharmacy and Pharmacology, Bath University, Bath, UK and T Cell Function Section, NIDDK-Navy Transplantation and Autoimmunity Branch, Naval Medical Research Center, Bethesda MD, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 30 EP - 37 VL - 101 IS - 1 SN - 0019-2805, 0019-2805 KW - Androstadienes KW - 0 KW - Antigens, CD KW - Antigens, CD2 KW - Antigens, CD28 KW - Antigens, CD3 KW - Antigens, Differentiation KW - CTLA-4 Antigen KW - CTLA4 protein, human KW - Chemokine CCL5 KW - Immunoconjugates KW - Phosphodiesterase Inhibitors KW - Abatacept KW - 7D0YB67S97 KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - wortmannin KW - XVA4O219QW KW - Index Medicus KW - Phosphodiesterase Inhibitors -- pharmacology KW - Humans KW - Antigens, Differentiation -- immunology KW - Androstadienes -- pharmacology KW - Cell Culture Techniques KW - Down-Regulation -- immunology KW - Antigens, CD3 -- immunology KW - Calcium -- metabolism KW - Cell Division -- immunology KW - Antigens, CD2 -- immunology KW - Phosphatidylinositol 3-Kinases -- antagonists & inhibitors KW - Antigens, CD28 -- immunology KW - Tetradecanoylphorbol Acetate -- immunology KW - Chemokine CCL5 -- metabolism KW - Tetradecanoylphorbol Acetate -- antagonists & inhibitors KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72307656?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunology&rft.atitle=Disparate+effects+of+phorbol+esters%2C+CD3+and+the+costimulatory+receptors+CD2+and+CD28+on+RANTES+secretion+by+human+T+lymphocytes.&rft.au=Sotsios%2C+Y%3BBlair%2C+P+J%3BWestwick%2C+J%3BWard%2C+S+G&rft.aulast=Sotsios&rft.aufirst=Y&rft.date=2000-09-01&rft.volume=101&rft.issue=1&rft.spage=30&rft.isbn=&rft.btitle=&rft.title=Immunology&rft.issn=00192805&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-16 N1 - Date created - 2000-10-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Eur J Immunol. 1989 Jan;19(1):17-23 [2563972] J Immunol. 1988 Sep 15;141(6):1904-11 [2459194] J Immunol. 1990 Feb 1;144(3):1010-4 [1688586] Immunol Rev. 1989 Oct;111:111-44 [2576417] J Immunol. 1991 Jan 15;146(2):560-4 [1670946] J Immunol. 1991 Jun 1;146(11):3709-12 [1674518] Eur J Immunol. 1991 Sep;21(9):2203-9 [1679714] Eur J Immunol. 1992 Jan;22(1):45-9 [1346114] J Immunol. 1992 Jul 15;149(2):373-9 [1352526] J Immunol. 1992 Dec 15;149(12):3795-801 [1281186] J Immunol. 1997 Apr 1;158(7):3483-91 [9120310] J Immunol. 1997 Jun 1;158(11):5545-53 [9164979] Eur J Immunol. 1997 Oct;27(10):2495-501 [9368602] J Exp Med. 1993 Mar 1;177(3):845-50 [7679711] Eur J Immunol. 1993 Mar;23(3):608-13 [8095456] Nature. 1993 Nov 4;366(6450):76-9 [7694153] J Immunol. 1994 Sep 15;153(6):2515-23 [8077662] Immunol Today. 1994 Jul;15(7):321-31 [7522010] Science. 1995 Nov 10;270(5238):985-8 [7481803] Immunity. 1995 Nov;3(5):541-7 [7584144] Int Immunol. 1995 Jun;7(6):957-66 [7577804] Mol Cell Biol. 1996 Jan;16(1):202-10 [8524297] Immunity. 1996 Jun;4(6):535-43 [8673700] Science. 1996 Jun 28;272(5270):1939-43 [8658167] Annu Rev Immunol. 1996;14:233-58 [8717514] Biochem J. 1996 Sep 1;318 ( Pt 2):361-77 [8809021] J Immunol. 1996 Oct 15;157(8):3290-7 [8871623] J Immunol. 1997 Mar 1;158(5):2025-34 [9036945] Immunity. 1998 Jul;9(1):1-11 [9697831] J Immunol. 1998 Oct 15;161(8):3919-24 [9780158] J Immunol. 1998 Nov 1;161(9):4506-12 [9794375] J Biol Chem. 1999 May 28;274(22):15454-65 [10336436] Curr Biol. 1999 Jun 3;9(11):601-4 [10359702] J Immunol. 1999 Aug 15;163(4):1809-16 [10438913] Nature. 1999 Sep 2;401(6748):82-5 [10485710] Nature. 1999 Sep 2;401(6748):86-90 [10485711] J Immunol. 1998 Jan 1;160(1):12-5 [9551948] Cell. 1984 Apr;36(4):897-906 [6231105] Proc Natl Acad Sci U S A. 1984 Nov;81(21):6836-40 [6093124] Eur J Immunol. 1986 Sep;16(9):1063-8 [2428622] Eur J Immunol. 1987 Jan;17(1):55-60 [2434339] Annu Rev Immunol. 1987;5:223-52 [3109455] Mol Cell Biol. 1987 Dec;7(12):4472-81 [2830495] EMBO J. 1988 Jul;7(7):1973-7 [2901344] Eur J Immunol. 1989 Dec;19(12):2183-9 [2481585] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Seizure threshold estimation by formula method: a prospective study in unilateral ECT. AN - 72298042; 11005047 AB - Formula methods of estimating seizure threshold in bilateral electroconvulsive therapy (ECT) have been successful in 75% (at the first ECT) and 80% (at the sixth ECT) of treatments (Gangadhar et al., 1998). This study showed the same results for unilateral (UL) ECT patients. Its aim was to compare formula and titration methods for threshold determination. The seizure threshold (dependent variable) was determined by the titration method used at the first ECT in consecutive consenting patients (n = 80) prescribed UL ECT under general anesthesia. The independent variables were age, gender, diagnosis, illness severity, concurrent drugs, head circumference, and inion-nasion distance. Forward, step-wise, linear regression analysis showed age as the only significant predictor of seizure threshold (15% of variance). A formula based on regression analysis was prospectively applied in an independent sample (n = 30) of patients receiving UL ECT using the titration method for threshold determination. The results calculated a higher threshold than the actual threshold used in 14 patients, a threshold level in 8 patients, and below threshold in 8 patients. Formula-based estimates would have been successful in 22 (73%) patients, but the majority of them would have received higher than the recommended stimulus dose. Titration is the method preferred for clinical use. However, if a patient's doctor wishes to use the formula-based method, he or she should do so with specific considerations. JF - The journal of ECT AU - Girish, K AU - Mayur, P M AU - Saravanan, E S AU - Janakiramaiah, N AU - Gangadhar, B N AU - Subbakrishna, D K AU - Rao, G S AD - Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, India. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 258 EP - 262 VL - 16 IS - 3 SN - 1095-0680, 1095-0680 KW - Index Medicus KW - Regression Analysis KW - Prospective Studies KW - Humans KW - Electroencephalography KW - Adult KW - Algorithms KW - Dose-Response Relationship, Radiation KW - Male KW - Female KW - Seizures -- physiopathology KW - Electroconvulsive Therapy -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72298042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+ECT&rft.atitle=Seizure+threshold+estimation+by+formula+method%3A+a+prospective+study+in+unilateral+ECT.&rft.au=Girish%2C+K%3BMayur%2C+P+M%3BSaravanan%2C+E+S%3BJanakiramaiah%2C+N%3BGangadhar%2C+B+N%3BSubbakrishna%2C+D+K%3BRao%2C+G+S&rft.aulast=Girish&rft.aufirst=K&rft.date=2000-09-01&rft.volume=16&rft.issue=3&rft.spage=258&rft.isbn=&rft.btitle=&rft.title=The+journal+of+ECT&rft.issn=10950680&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-02 N1 - Date created - 2001-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CYP1A1 I462V genetic polymorphism and lung cancer risk in a cohort of men in Shanghai, China. AN - 72291762; 11008920 AB - Cytochrome P450 (CYP) CYP1A1 activates tobacco-related carcinogens. A point mutation at codon 462 in exon 7 of CYP1A1 results in a substitution of isoleucine by valine near the heme binding site. This mutation is rare in Caucasians but common in Japanese populations, in which association with increased risk of lung cancer has been reported. There are few data in other Asian populations. We investigated this I462V polymorphism using DNA from 214 incident cases of lung cancer and 669 controls in a prospective cohort study of 18,244 middle-aged and older men in Shanghai, China. The valine allele frequency was 0.138 among the control population. The I462V genotype was not appreciably associated with lung cancer risk overall. There was some suggestion that having at least one valine allele might be related to increased risk of lung cancer among smokers of <20 cigarettes/day (odds ratio, 1.72; 95% confidence interval, 0.82-3.62), particularly among those with homozygous deletion of GSTM1 (odds ratio, 2.80; 95% confidence interval, 1.07-7.33), which is involved in the detoxification of activated tobacco carcinogens. In this Chinese cohort, with CYP1A1 valine allele frequency intermediate between Japanese and Caucasian populations, the I462V polymorphism is not related to lung cancer overall, but it might play a role at lower levels of cigarette smoking among subjects with impaired carcinogen detoxification as assessed by the GSTM1-null genotype. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - London, S J AU - Yuan, J M AU - Coetzee, G A AU - Gao, Y T AU - Ross, R K AU - Yu, M C AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 987 EP - 991 VL - 9 IS - 9 SN - 1055-9965, 1055-9965 KW - Carcinogens KW - 0 KW - Benzo(a)pyrene KW - 3417WMA06D KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - glutathione S-transferase M1 KW - Index Medicus KW - Polymorphism, Single Nucleotide KW - Odds Ratio KW - Humans KW - Glutathione Transferase -- genetics KW - Smoking -- genetics KW - Prospective Studies KW - Carcinogens -- metabolism KW - Inactivation, Metabolic KW - Logistic Models KW - Polymorphism, Restriction Fragment Length KW - Risk Factors KW - China -- epidemiology KW - Cohort Studies KW - Smoking -- metabolism KW - Middle Aged KW - Male KW - Benzo(a)pyrene -- metabolism KW - Lung Neoplasms -- enzymology KW - Lung Neoplasms -- epidemiology KW - Cytochrome P-450 Enzyme System -- genetics KW - Lung Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72291762?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=CYP1A1+I462V+genetic+polymorphism+and+lung+cancer+risk+in+a+cohort+of+men+in+Shanghai%2C+China.&rft.au=London%2C+S+J%3BYuan%2C+J+M%3BCoetzee%2C+G+A%3BGao%2C+Y+T%3BRoss%2C+R+K%3BYu%2C+M+C&rft.aulast=London&rft.aufirst=S&rft.date=2000-09-01&rft.volume=9&rft.issue=9&rft.spage=987&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-11 N1 - Date created - 2001-01-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic dissection of collagen-induced arthritis in Chromosome 10 quantitative trait locus speed congenic rats: evidence for more than one regulatory locus and sex influences. AN - 72287742; 11003387 AB - Rat Chromosome 10 (RNO10) harbors Cia5, a non-MHC quantitative trait locus (QTL) that regulates the severity of type II collagen-induced arthritis (CIA) in DAxF344 and DAxBN F2 rats. CIA is an animal model with many features that resemble rheumatoid arthritis. To facilitate analysis of Cia5 independently of the other CIA regulatory loci on other chromosomes, DA recombinant QTL speed congenic rats, DA.F344(Cia5), were generated. These QTL congenic rats have a large chromosomal segment containing Cia5 (interval size < or =80.1 cM) from CIA-resistant F344 rats introgressed into their genome. Phenotypic analyses of these rats for susceptibility and severity of CIA confirmed that Cia5 is an important disease-modifying locus. CIA severity was significantly lower in the Cia5 congenic rats than in DA controls. We also generated DA Cia5 speed sub-congenic rats, DA.F344(Cia5a), which had a smaller segment of the F344 genome, Cia5a, comprising only the distal q-telomeric end (interval size < or = 22.5 cM) of Cia5, introgressed into their genome. DA.F344(Cia5a) sub-congenic rats also exhibited reduced CIA disease severity compared with the parental DA rats. The regulatory effects in both congenic strains were sex influenced. The disease-ameliorating effect of the larger fragment, Cia5, was greater in males than in females, but the effect of the smaller fragment, Cia5a, was greater in females. We also present an improved genetic linkage map covering the Cia5/Cia5a region, which we have integrated with two rat radiation hybrid maps. Comparative homology analysis of this genomic region with mouse and human chromosomes was also undertaken. Regulatory loci for multiple autoimmune/inflammatory diseases in rats (RNO10), mice (MMU11), and humans (HSA17 and HSA5q23-q31) map to chromosomal segments homologous to Cia5 and Cia5a. JF - Immunogenetics AU - Joe, B AU - Remmers, E F AU - Dobbins, D E AU - Salstrom, J L AU - Furuya, T AU - Dracheva, S AU - Gulko, P S AU - Cannon, G W AU - Griffiths, M M AU - Wilder, R L AD - Inflammatory Joint Diseases Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 930 EP - 944 VL - 51 IS - 11 SN - 0093-7711, 0093-7711 KW - Collagen KW - 9007-34-5 KW - Index Medicus KW - Genetic Linkage KW - Animals KW - Sex Factors KW - Humans KW - Mice KW - Chromosome Mapping KW - Rats KW - Regulatory Sequences, Nucleic Acid KW - Rats, Inbred F344 KW - Collagen -- immunology KW - Animals, Congenic KW - Time Factors KW - Female KW - Male KW - Cricetinae KW - Quantitative Trait, Heritable KW - Arthritis, Rheumatoid -- genetics KW - Arthritis, Rheumatoid -- chemically induced KW - Arthritis, Rheumatoid -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72287742?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunogenetics&rft.atitle=Genetic+dissection+of+collagen-induced+arthritis+in+Chromosome+10+quantitative+trait+locus+speed+congenic+rats%3A+evidence+for+more+than+one+regulatory+locus+and+sex+influences.&rft.au=Joe%2C+B%3BRemmers%2C+E+F%3BDobbins%2C+D+E%3BSalstrom%2C+J+L%3BFuruya%2C+T%3BDracheva%2C+S%3BGulko%2C+P+S%3BCannon%2C+G+W%3BGriffiths%2C+M+M%3BWilder%2C+R+L&rft.aulast=Joe&rft.aufirst=B&rft.date=2000-09-01&rft.volume=51&rft.issue=11&rft.spage=930&rft.isbn=&rft.btitle=&rft.title=Immunogenetics&rft.issn=00937711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-20 N1 - Date created - 2000-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Topical delivery of 13-cis-retinoic acid by inhalation up-regulates expression of rodent lung but not liver retinoic acid receptors. AN - 72276760; 10999756 AB - Chemopreventive retinoids may be more effective if delivered to the lung epithelium by inhalation. 13-cis-Retinoic acid (13-cis-RA) was comparable to all-trans-retinoic acid (RA) in inducing transglutaminase II (TGase II) in cultured human cells. Inhaled 13-cis-RA had a significant stimulatory activity on TGase II in rat lung (P < 0.001) but not in liver tissue (P < 0.544). Furthermore, inhaled 13-cis-RA at daily deposited doses of 1.9 mg/kg/day up-regulated the expression of lung retinoic acid receptors (RARs) alpha, beta, and gamma at day 1 (RARalpha by 3.4-fold, RARbeta by 7.2-fold, and RARgamma by 9.7-fold) and at day 17 (RARalpha by 4.2-fold, RARbeta by 10.0-fold, and RARgamma by 12.9-fold). At a lower aerosol concentration, daily deposited doses of 0.6 mg/kg/day were also effective at 28 days. Lung RARalpha was induced by 4.7-fold, RARbeta by 8.0-fold, and RARgamma by 8.1-fold. Adjustment of dose by exposure duration was also effective; thus, inhalation of an aerosol concentration of 62.2 microg/liter, for durations from 5 to 240 min daily for 14 days, induced all RARs from 30.6- to 74-fold at the shortest exposure time. None of the animals exposed to 13-cis-RA aerosols showed RAR induction in livers. By contrast, a diet containing pharmacological RA (30 microg/g of diet) failed to induce RARs in SENCAR mouse lung, although it induced liver RARs (RARalpha, 21.8-fold; RARbeta, 13.5-fold; RARgamma, 12.5-fold); it also failed to induce lung TGase II. A striking increase of RARalpha expression was evident in the nuclei of hepatocytes. Pharmacological dietary RA stimulated RARalpha, RARbeta, and RARgamma as early as day 1 by 2-, 4-, and 2.1-fold, respectively, without effect on lung RARs. Therefore, 13-cis-RA delivered to lung tissue of rats is a potent stimulant of lung but not liver RARs. Conversely, dietary RA stimulates liver but not lung RARs. These data support the concept that epithelial delivery of chemopreventive retinoids to lung tissue is a more efficacious way to attain up-regulation of TGase II and the retinoid receptors and possibly to achieve chemoprevention. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Wang, D L AU - Marko, M AU - Dahl, A R AU - Engelke, K S AU - Placke, M E AU - Imondi, A R AU - Mulshine, J L AU - De Luca, L M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 3636 EP - 3645 VL - 6 IS - 9 SN - 1078-0432, 1078-0432 KW - Anticarcinogenic Agents KW - 0 KW - Receptors, Retinoic Acid KW - transglutaminase 2 KW - EC 2.3.2.- KW - Transglutaminases KW - EC 2.3.2.13 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Isotretinoin KW - EH28UP18IF KW - Index Medicus KW - Animals KW - GTP-Binding Proteins -- biosynthesis KW - Transglutaminases -- genetics KW - Humans KW - Transglutaminases -- biosynthesis KW - Mice KW - GTP-Binding Proteins -- genetics KW - Stimulation, Chemical KW - Rats KW - Rats, Sprague-Dawley KW - Transglutaminases -- metabolism KW - Tumor Cells, Cultured KW - Enzyme Induction -- drug effects KW - GTP-Binding Proteins -- metabolism KW - Up-Regulation -- drug effects KW - Diet KW - Mice, Inbred SENCAR KW - Administration, Inhalation KW - Breast Neoplasms -- enzymology KW - Male KW - Receptors, Retinoic Acid -- genetics KW - Isotretinoin -- administration & dosage KW - Receptors, Retinoic Acid -- biosynthesis KW - Liver -- enzymology KW - Liver -- drug effects KW - Lung -- drug effects KW - Liver -- metabolism KW - Lung -- metabolism KW - Anticarcinogenic Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72276760?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Topical+delivery+of+13-cis-retinoic+acid+by+inhalation+up-regulates+expression+of+rodent+lung+but+not+liver+retinoic+acid+receptors.&rft.au=Wang%2C+D+L%3BMarko%2C+M%3BDahl%2C+A+R%3BEngelke%2C+K+S%3BPlacke%2C+M+E%3BImondi%2C+A+R%3BMulshine%2C+J+L%3BDe+Luca%2C+L+M&rft.aulast=Wang&rft.aufirst=D&rft.date=2000-09-01&rft.volume=6&rft.issue=9&rft.spage=3636&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-01 N1 - Date created - 2000-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Marked differences in base selectivity between DNA and the free nucleotides upon adduct formation from Bay- and Fjord-region diol epoxides. AN - 72275019; 10995261 AB - Distributions of adducts formed from each of the four optically active isomers of 3,4-dihydroxy-1,2-epoxy-1,2,3, 4-tetrahydrobenzo[c]phenanthrene and of 7,8-dihydroxy-9,10-epoxy-7,8, 9,10- tetrahydrobenzo[a]pyrene (BcPh and BaP diol epoxides) on reaction with an equimolar mixture of deoxyadenosine and deoxyguanosine 5'-monophosphates were compared with the known adduct distributions from these diol epoxides (DEs) upon reaction with calf thymus DNA in vitro. In the presence of an equimolar (100 mM total) mixture of dAMP and dGMP, the efficiency of formation of all types of adducts relative to tetraols is comparable for both the BaP ( approximately 40-60%) and BcPh ( approximately 30-40%) diol epoxides. This is in contrast to the partitioning between tetraols and adducts observed with DNA, where the BcPh DEs form adducts much more efficiently than the BaP DEs. Preference for trans versus cis ring opening by the exocyclic amino groups of the free nucleotides in the dAMP/dGMP mixture is greater for the DE diastereomer in which the benzylic hydroxyl group and the epoxide oxygen are trans (DE-2). This is qualitatively similar to the preferences for trans versus cis adduct formation on reaction of these isomers with DNA, as well as trans versus cis tetraol formation on their acid hydrolysis. For the BcPh DE isomers, competitive reaction between dGMP and dAMP gives 40-62% of the total exocyclic amino group adducts as dA adducts. A similar distribution of dG versus dA adducts had previously been observed on reaction of the BcPh DEs with DNA, except in the case of (+)-3(R),4(S)-dihydroxy-1(R),2(S)-epoxy-1,2,3, 4-tetrahydrobenzo[c]phenanthrene, which gives approximately 85% dA adducts on reaction with DNA. With the BaP DEs, 60-77% of the exocyclic amino group adducts formed upon competitive reaction with the free nucleotides are derived from dGMP. The observed dG selectivity of these BaP DEs is much smaller with the nucleotide mixture than it is with DNA, leading to the conclusion that DNA structure has a much larger modifying effect on the base selectivity of the BaP relative to the BcPh DEs. JF - Chemical research in toxicology AU - Vepachedu, S R AU - Ya, N AU - Yagi, H AU - Sayer, J M AU - Jerina, D M AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, The National Institutes of Health, Bethesda, Maryland 20892-0820, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 883 EP - 890 VL - 13 IS - 9 SN - 0893-228X, 0893-228X KW - DNA Adducts KW - 0 KW - Deoxyadenine Nucleotides KW - Deoxyguanine Nucleotides KW - Epoxy Compounds KW - Phenanthrenes KW - Benzo(a)pyrene KW - 3417WMA06D KW - DNA KW - 9007-49-2 KW - benzo(c)phenanthrene KW - H22XVR3V8A KW - Index Medicus KW - Animals KW - Cattle KW - Benzo(a)pyrene -- chemistry KW - Phenanthrenes -- chemistry KW - Deoxyguanine Nucleotides -- chemistry KW - Deoxyadenine Nucleotides -- chemistry KW - DNA Adducts -- chemistry KW - Epoxy Compounds -- chemistry KW - DNA -- chemistry KW - Bay-Region, Polycyclic Aromatic Hydrocarbon UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72275019?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Marked+differences+in+base+selectivity+between+DNA+and+the+free+nucleotides+upon+adduct+formation+from+Bay-+and+Fjord-region+diol+epoxides.&rft.au=Vepachedu%2C+S+R%3BYa%2C+N%3BYagi%2C+H%3BSayer%2C+J+M%3BJerina%2C+D+M&rft.aulast=Vepachedu&rft.aufirst=S&rft.date=2000-09-01&rft.volume=13&rft.issue=9&rft.spage=883&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-06 N1 - Date created - 2000-10-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Chem Res Toxicol 2001 Jan;14(1):148 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Decreased bone mineral density during low dose glucocorticoid administration in a randomized, placebo controlled trial. AN - 72263518; 10990237 AB - While osteoporosis and bone fractures are clearly recognized side effects of high dose glucocorticoids, the effect of low dose glucocorticoids remains controversial. We investigated the effect of 3 months of low dose hydrocortisone on bone mineral density (BMD). Subjects, 18 to 55 years old with chronic fatigue syndrome and no medical or psychiatric illness requiring medication, were randomized in a double blind, placebo controlled trial to receive oral hydrocortisone, 13 mg/m2 body surface area every morning and 3 mg/m2 every afternoon (25 to 35 mg/day, equivalent to about 7.5 mg prednisone/day) or placebo for 12 weeks. Before and after treatment BMD of the lumbar spine was measured by dual energy x-ray absorptiometry. We studied 23 subjects (19 women, 4 men). For the 11 hydrocortisone recipients there was a mean decrease in BMD: mean change from baseline of the lateral spine was -2.0% (95% CI -3.5 to -0.6. p = 0.03) and mean change of the anteroposterior spine was -0.8% (95% CI -1.5 to -0.1, p = 0.06). Corresponding changes for the 12 placebo recipients were +1.0% (95% CI -1.0 to 3.0, p = 0.34) and +0.2% (95% CI -1.4 to 1.5, p = 0.76). A 12 week course of low dose glucocorticoids given to ambulatory subjects with chronic fatigue syndrome was associated with a decrease in BMD of the lumbar spine. This decrease was statistically significant in lateral spine measurements and nearly so in anteroposterior spine measurements. JF - The Journal of rheumatology AU - McKenzie, R AU - Reynolds, J C AU - O'Fallon, A AU - Dale, J AU - Deloria, M AU - Blackwelder, W AU - Straus, S E AD - Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Maryland , USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 2222 EP - 2226 VL - 27 IS - 9 SN - 0315-162X, 0315-162X KW - Glucocorticoids KW - 0 KW - Index Medicus KW - Spine -- diagnostic imaging KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Fatigue Syndrome, Chronic -- drug therapy KW - Adult KW - Spine -- drug effects KW - Radiography KW - Spine -- pathology KW - Male KW - Female KW - Bone Density -- drug effects KW - Glucocorticoids -- administration & dosage KW - Glucocorticoids -- adverse effects KW - Osteoporosis -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72263518?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+rheumatology&rft.atitle=Decreased+bone+mineral+density+during+low+dose+glucocorticoid+administration+in+a+randomized%2C+placebo+controlled+trial.&rft.au=McKenzie%2C+R%3BReynolds%2C+J+C%3BO%27Fallon%2C+A%3BDale%2C+J%3BDeloria%2C+M%3BBlackwelder%2C+W%3BStraus%2C+S+E&rft.aulast=McKenzie&rft.aufirst=R&rft.date=2000-09-01&rft.volume=27&rft.issue=9&rft.spage=2222&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+rheumatology&rft.issn=0315162X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-25 N1 - Date created - 2000-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Limited value of sonohysterography for endometrial screening in asymptomatic, postmenopausal patients treated with tamoxifen. AN - 72260003; 10985880 AB - Sonohysterography (SHG) has been proposed as a useful tool for the surveillance of the endometrium in patients receiving tamoxifen. This study aimed to assess the value of SHG in asymptomatic patients who would have been biopsy candidates because of abnormal transvaginal ultrasound (TVUS) results. The study population included postmenopausal breast cancer patients receiving adjuvant tamoxifen who had asymptomatic abnormalities at TVUS (endometrial thickness >/=8 mm or endometrial echo not adequately visualized). SHG was performed with an Aloka SSD 680 system using a 5-MHz vaginal probe, with sterile saline solution as contrast medium. Forty-one patients entered the study. A regular endometrial echo was identified by SHG in 9 patients (21.9%). Histology was obtained in the remaining 32 patients with positive (n = 27, 65.8%) or unsuccessful (n = 5, 12.2%) SHG. Benign polyps (n = 15, 36.6%) and endometrial atrophy (n = 14, 34.1%) were the most common findings; 3 patients (7.3%) had simple hyperplasia. Breast cancer patients with asymptomatic, tamoxifen-associated TVUS abnormalities have little additional benefit from SHG. More than 23 remain candidates for biopsy, which usually yields benign or insignificant findings. Copyright 2000 Academic Press. JF - Gynecologic oncology AU - Bertelli, G AU - Valenzano, M AU - Costantini, S AU - Rissone, R AU - Angiolini, C AU - Signorini, A AU - Gustavino, C AD - Department of Medical Oncology, National Cancer Institute, Genoa, 16132, Italy. bertelli@hp380.ist.unige.it Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 275 EP - 277 VL - 78 IS - 3 Pt 1 SN - 0090-8258, 0090-8258 KW - Antineoplastic Agents, Hormonal KW - 0 KW - Tamoxifen KW - 094ZI81Y45 KW - Index Medicus KW - Breast Neoplasms -- drug therapy KW - Reproducibility of Results KW - Humans KW - Endometrial Neoplasms -- pathology KW - Aged KW - Ultrasonography KW - Breast Neoplasms -- complications KW - Atrophy -- chemically induced KW - Polyps -- diagnostic imaging KW - Aged, 80 and over KW - Risk Factors KW - Middle Aged KW - Polyps -- pathology KW - Chemotherapy, Adjuvant KW - Female KW - Hysterosalpingography -- methods KW - Endometrial Neoplasms -- diagnostic imaging KW - Endometrium -- diagnostic imaging KW - Endometrium -- drug effects KW - Tamoxifen -- therapeutic use KW - Tamoxifen -- adverse effects KW - Endometrium -- pathology KW - Postmenopause -- physiology KW - Antineoplastic Agents, Hormonal -- therapeutic use KW - Antineoplastic Agents, Hormonal -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72260003?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gynecologic+oncology&rft.atitle=Limited+value+of+sonohysterography+for+endometrial+screening+in+asymptomatic%2C+postmenopausal+patients+treated+with+tamoxifen.&rft.au=Bertelli%2C+G%3BValenzano%2C+M%3BCostantini%2C+S%3BRissone%2C+R%3BAngiolini%2C+C%3BSignorini%2C+A%3BGustavino%2C+C&rft.aulast=Bertelli&rft.aufirst=G&rft.date=2000-09-01&rft.volume=78&rft.issue=3+Pt+1&rft.spage=275&rft.isbn=&rft.btitle=&rft.title=Gynecologic+oncology&rft.issn=00908258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-25 N1 - Date created - 2000-09-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Gynecol Oncol. 2001 Aug;82(2):406-7 [11531305] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic disruption of Ptgs-1, as well as Ptgs-2, reduces intestinal tumorigenesis in Min mice. AN - 72257635; 10987272 AB - Two isoforms of cyclooxygenase (COX) are known, and to date most studies have implicated COX-2, rather than COX-1, as the isoform involved in colon carcinogenesis. In the present study, we show that homologous disruption of either Ptgs-1 or Ptgs-2 (genes coding for COX-1 or COX-2, respectively) reduced polyp formation in Min/+ mice by approximately 80%. Only COX-1 protein was immunohistochemically detected in normal intestinal tissue, whereas both COX-1 and variable levels of COX-2 protein were detected in polyps. Prostaglandin E2 was increased in polyps compared with normal tissue, and both COX-1 and COX-2 contributed to the PGE2 produced. The results indicate that COX-1, as well as COX-2, plays a key role in intestinal tumorigenesis and that COX-1 may also be a chemotherapeutic target for nonsteroidal anti-inflammatory drugs. JF - Cancer research AU - Chulada, P C AU - Thompson, M B AU - Mahler, J F AU - Doyle, C M AU - Gaul, B W AU - Lee, C AU - Tiano, H F AU - Morham, S G AU - Smithies, O AU - Langenbach, R AD - Laboratory of Experimental Carcinogenesis and Mutagenesis, NIH, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. chulada@niehs.nih.gov Y1 - 2000/09/01/ PY - 2000 DA - 2000 Sep 01 SP - 4705 EP - 4708 VL - 60 IS - 17 SN - 0008-5472, 0008-5472 KW - Isoenzymes KW - 0 KW - Membrane Proteins KW - Cyclooxygenase 1 KW - EC 1.14.99.1 KW - Cyclooxygenase 2 KW - Prostaglandin-Endoperoxide Synthases KW - Ptgs1 protein, mouse KW - Dinoprostone KW - K7Q1JQR04M KW - Index Medicus KW - Animals KW - Reference Values KW - Dinoprostone -- biosynthesis KW - Mice KW - Mice, Knockout KW - Intestines -- enzymology KW - Mice, Inbred C57BL KW - Crosses, Genetic KW - Female KW - Male KW - Prostaglandin-Endoperoxide Synthases -- deficiency KW - Intestinal Polyps -- enzymology KW - Isoenzymes -- deficiency KW - Intestinal Polyps -- prevention & control KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Intestinal Neoplasms -- genetics KW - Intestinal Neoplasms -- enzymology KW - Intestinal Polyps -- genetics KW - Isoenzymes -- genetics KW - Intestinal Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72257635?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetic+disruption+of+Ptgs-1%2C+as+well+as+Ptgs-2%2C+reduces+intestinal+tumorigenesis+in+Min+mice.&rft.au=Chulada%2C+P+C%3BThompson%2C+M+B%3BMahler%2C+J+F%3BDoyle%2C+C+M%3BGaul%2C+B+W%3BLee%2C+C%3BTiano%2C+H+F%3BMorham%2C+S+G%3BSmithies%2C+O%3BLangenbach%2C+R&rft.aulast=Chulada&rft.aufirst=P&rft.date=2000-09-01&rft.volume=60&rft.issue=17&rft.spage=4705&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 - 2000-09-28 N1 - Date created - 2000-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Persistent activation of GABA(A) receptor/Cl(-) channels by astrocyte-derived GABA in cultured embryonic rat hippocampal neurons. AN - 72243493; 10980012 AB - Whole cell patch-clamp recordings using Cl(-)-filled pipettes revealed more negative levels of baseline current and associated current variance in embryonic rat hippocampal neurons co-cultured on a monolayer of astrocytes than those cultured on poly-D-lysine. These effects were mimicked by culturing neurons on poly-D-lysine in astrocyte-conditioned medium (ACM). The baseline current and variance decreased immediately in all cells after either local perfusion with saline or exposure to bicuculline, an antagonist of GABA at GABA(A) receptor/Cl(-) channels. Baseline current and variance in all cells reached a nadir at approximately 0 mV, the calculated equilibrium potential for Cl(-). Perfusion of ACM rapidly induced a sustained current in neurons, which also reversed polarity at approximately 0 mV. Bicuculline attenuated or eliminated the ACM-induced current at a concentration that completely blocked micromolar GABA-induced current. Quantitative analyses of spontaneously occurring fluctuations superimposed on the ACM-induced current revealed estimated unitary properties of the underlying channel activity similar to those calculated for GABA's activation of GABA(A) receptor/Cl(-) channels. Bicuculline-sensitive synaptic-like transients, which reversed at approximately 0 mV, were also detected in neurons cultured in ACM, and these were immediately eliminated along with the negative baseline current and superimposed current fluctuations by perfusion. Furthermore bicuculline-sensitive synaptic-like transients were rapidly and reversibly triggered when ACM was acutely applied. ACM induced an increase in cytoplasmic Ca(2+) in cultured embryonic hippocampal neurons that was completely blocked by bicuculline and strychnine. We conclude that astrocytes release diffusible substances, most likely GABA, that persistently activate GABA(A) receptor/Cl(-) channels in co-cultured neurons. JF - Journal of neurophysiology AU - Liu, Q Y AU - Schaffner, A E AU - Chang, Y H AU - Maric, D AU - Barker, J L AD - Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4066, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 1392 EP - 1403 VL - 84 IS - 3 SN - 0022-3077, 0022-3077 KW - Chloride Channels KW - 0 KW - Chlorides KW - Culture Media, Conditioned KW - GABA Antagonists KW - GABA-A Receptor Antagonists KW - Glycine Agents KW - Receptors, GABA-A KW - 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester KW - 139890-68-9 KW - Egtazic Acid KW - 526U7A2651 KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - 3-Mercaptopropionic Acid KW - B03TJ3QU9M KW - Strychnine KW - H9Y79VD43J KW - Calcium KW - SY7Q814VUP KW - Bicuculline KW - Y37615DVKC KW - Index Medicus KW - Bicuculline -- pharmacology KW - Culture Media, Conditioned -- pharmacology KW - 3-Mercaptopropionic Acid -- pharmacology KW - Animals KW - Coculture Techniques KW - Membrane Potentials -- physiology KW - Chlorides -- metabolism KW - GABA Antagonists -- pharmacology KW - Rats KW - Calcium -- metabolism KW - Animals, Newborn KW - Patch-Clamp Techniques KW - Cells, Cultured KW - Culture Media, Conditioned -- chemistry KW - Strychnine -- pharmacology KW - Glycine Agents -- pharmacology KW - Cell Differentiation -- drug effects KW - Egtazic Acid -- analogs & derivatives KW - Neurons -- metabolism KW - Neurons -- cytology KW - Hippocampus -- metabolism KW - Hippocampus -- cytology KW - Receptors, GABA-A -- metabolism KW - Chloride Channels -- metabolism KW - gamma-Aminobutyric Acid -- metabolism KW - Chloride Channels -- antagonists & inhibitors KW - Hippocampus -- embryology KW - Astrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72243493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurophysiology&rft.atitle=Persistent+activation+of+GABA%28A%29+receptor%2FCl%28-%29+channels+by+astrocyte-derived+GABA+in+cultured+embryonic+rat+hippocampal+neurons.&rft.au=Liu%2C+Q+Y%3BSchaffner%2C+A+E%3BChang%2C+Y+H%3BMaric%2C+D%3BBarker%2C+J+L&rft.aulast=Liu&rft.aufirst=Q&rft.date=2000-09-01&rft.volume=84&rft.issue=3&rft.spage=1392&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-03 N1 - Date created - 2000-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Testosterone inhibits estrogen-induced mammary epithelial proliferation and suppresses estrogen receptor expression. AN - 72239613; 10973921 AB - This study investigated the effect of sex steroids and tamoxifen on primate mammary epithelial proliferation and steroid receptor gene expression. Ovariectomized rhesus monkeys were treated with placebo, 17beta estradiol (E2) alone or in combination with progesterone (E2/P) or testosterone (E2/T), or tamoxifen for 3 days. E2 alone increased mammary epithelial proliferation by approximately sixfold (P:<0.0001) and increased mammary epithelial estrogen receptor (ERalpha) mRNA expression by approximately 50% (P:<0.0001; ERbeta mRNA was not detected in the primate mammary gland). Progesterone did not alter E2's proliferative effects, but testosterone reduced E2-induced proliferation by approximately 40% (P:<0.002) and entirely abolished E2-induced augmentation of ERalpha expression. Tamoxifen had a significant agonist effect in the ovariectomized monkey, producing a approximately threefold increase in mammary epithelial proliferation (P:<0.01), but tamoxifen also reduced ERalpha expression below placebo level. Androgen receptor (AR) mRNA was detected in mammary epithelium by in situ hybridization. AR mRNA levels were not altered by E2 alone but were significantly reduced by E2/T and tamoxifen treatment. Because combined E2/T and tamoxifen had similar effects on mammary epithelium, we investigated the regulation of known sex steroid-responsive mRNAs in the primate mammary epithelium. E2 alone had no effect on apolipoprotein D (ApoD) or IGF binding protein 5 (IGFBP5) expression, but E2/T and tamoxifen treatment groups both demonstrated identical alterations in these mRNAs (ApoD was decreased and IGFBP5 was increased). These observations showing androgen-induced down-regulation of mammary epithelial proliferation and ER expression suggest that combined estrogen/androgen hormone replacement therapy might reduce the risk of breast cancer associated with estrogen replacement. In addition, these novel findings on tamoxifen's androgen-like effects on primate mammary epithelial sex steroid receptor expression suggest that tamoxifen's protective action on mammary gland may involve androgenic effects. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Zhou, J AU - Ng, S AU - Adesanya-Famuiya, O AU - Anderson, K AU - Bondy, C A AD - Developmental Endocrinology Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 1725 EP - 1730 VL - 14 IS - 12 SN - 0892-6638, 0892-6638 KW - Estrogen Antagonists KW - 0 KW - Estrogens KW - Receptors, Androgen KW - Receptors, Estrogen KW - Tamoxifen KW - 094ZI81Y45 KW - Testosterone KW - 3XMK78S47O KW - Progesterone KW - 4G7DS2Q64Y KW - Estradiol KW - 4TI98Z838E KW - Index Medicus KW - Tamoxifen -- pharmacology KW - Animals KW - Drug Interactions KW - Progesterone -- pharmacology KW - Estradiol -- pharmacology KW - Cell Division -- drug effects KW - Epithelial Cells -- metabolism KW - Epithelial Cells -- cytology KW - Epithelial Cells -- drug effects KW - Estrogen Antagonists -- pharmacology KW - Receptors, Androgen -- metabolism KW - Macaca mulatta KW - Female KW - Gene Expression -- drug effects KW - Testosterone -- pharmacology KW - Receptors, Estrogen -- genetics KW - Receptors, Estrogen -- biosynthesis KW - Estrogens -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72239613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Testosterone+inhibits+estrogen-induced+mammary+epithelial+proliferation+and+suppresses+estrogen+receptor+expression.&rft.au=Zhou%2C+J%3BNg%2C+S%3BAdesanya-Famuiya%2C+O%3BAnderson%2C+K%3BBondy%2C+C+A&rft.aulast=Zhou&rft.aufirst=J&rft.date=2000-09-01&rft.volume=14&rft.issue=12&rft.spage=1725&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=08926638&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-26 N1 - Date created - 2000-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amplitude-dependent spike-broadening and enhanced Ca(2+) signaling in GnRH-secreting neurons. AN - 72235846; 10968994 AB - In GnRH-secreting (GT1) neurons, activation of Ca(2+)-mobilizing receptors induces a sustained membrane depolarization that shifts the profile of the action potential (AP) waveform from sharp, high-amplitude to broad, low-amplitude spikes. Here we characterize this shift in the firing pattern and its impact on Ca(2+) influx experimentally by using prerecorded sharp and broad APs as the voltage-clamp command pulse. As a quantitative test of the experimental data, a mathematical model based on the membrane and ionic current properties of GT1 neurons was also used. Both experimental and modeling results indicated that inactivation of the tetrodotoxin-sensitive Na(+) channels by sustained depolarization accounted for a reduction in the amplitude of the spike upstroke. The ensuing decrease in tetraethylammonium-sensitive K(+) current activation slowed membrane repolarization, leading to AP broadening. This change in firing pattern increased the total L-type Ca(2+) current and facilitated AP-driven Ca(2+) entry. The leftward shift in the current-voltage relation of the L-type Ca(2+) channels expressed in GT1 cells allowed the depolarization-induced AP broadening to facilitate Ca(2+) entry despite a decrease in spike amplitude. Thus the gating properties of the L-type Ca(2+) channels expressed in GT1 neurons are suitable for promoting AP-driven Ca(2+) influx in receptor- and non-receptor-depolarized cells. JF - Biophysical journal AU - Van Goor, F AU - LeBeau, A P AU - Krsmanovic, L Z AU - Sherman, A AU - Catt, K J AU - Stojilkovic, S S AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 USA. fredrick@box-f.nih.gov Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 1310 EP - 1323 VL - 79 IS - 3 SN - 0006-3495, 0006-3495 KW - Calcium Channel Blockers KW - 0 KW - Calcium Channels, L-Type KW - Potassium Channels KW - Sodium Channels KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Tetrodotoxin KW - 4368-28-9 KW - Tetraethylammonium KW - 66-40-0 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Tetraethylammonium -- pharmacology KW - Membrane Potentials -- physiology KW - Sodium Channels -- physiology KW - Potassium Channels -- physiology KW - Potassium Channels -- drug effects KW - Calcium -- metabolism KW - Patch-Clamp Techniques KW - Calcium Channel Blockers -- pharmacology KW - Kinetics KW - Membrane Potentials -- drug effects KW - Tetrodotoxin -- pharmacology KW - Sodium Channels -- drug effects KW - Cell Line KW - Calcium Signaling -- physiology KW - Calcium Channels, L-Type -- physiology KW - Neurons -- physiology KW - Gonadotropin-Releasing Hormone -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72235846?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biophysical+journal&rft.atitle=Amplitude-dependent+spike-broadening+and+enhanced+Ca%282%2B%29+signaling+in+GnRH-secreting+neurons.&rft.au=Van+Goor%2C+F%3BLeBeau%2C+A+P%3BKrsmanovic%2C+L+Z%3BSherman%2C+A%3BCatt%2C+K+J%3BStojilkovic%2C+S+S&rft.aulast=Van+Goor&rft.aufirst=F&rft.date=2000-09-01&rft.volume=79&rft.issue=3&rft.spage=1310&rft.isbn=&rft.btitle=&rft.title=Biophysical+journal&rft.issn=00063495&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-18 N1 - Date created - 2000-10-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Gen Physiol. 1977 Nov;70(5):549-66 [591911] Nature. 1997 Apr 24;386(6627):855-8 [9126747] J Biol Chem. 1999 Mar 12;274(11):7508-15 [10066818] Cell Calcium. 1998 Nov-Dec;24(5-6):307-23 [10091001] J Neurosci. 1997 Jun 15;17(12):4517-26 [9169512] J Neurosci. 1997 Sep 1;17(17):6512-21 [9254663] J Neurosci. 1997 Sep 1;17(17):6639-46 [9254676] J Physiol. 1997 Jul 15;502 ( Pt 2):265-79 [9263909] Science. 1998 Jan 9;279(5348):227-30 [9422695] Annu Rev Physiol. 1998;60:327-46 [9558467] J Neurosci. 1998 Sep 1;18(17):6757-66 [9712647] J Neurophysiol. 1998 Dec;80(6):3047-61 [9862905] Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4101-6 [10097170] Mol Endocrinol. 1999 Apr;13(4):587-603 [10194765] J Neurosci. 1999 Jul 1;19(13):5205-12 [10377332] J Neurosci. 1999 Jul 1;19(13):5301-10 [10377341] Curr Opin Neurobiol. 1999 Jun;9(3):288-92 [10395568] J Neurophysiol. 1999 Jul;82(1):429-35 [10400969] J Physiol. 1952 Aug;117(4):500-44 [12991237] J Neurosci. 1999 Mar 1;19(5):1663-74 [10024353] Am J Physiol. 1986 Feb;250(2 Pt 2):H325-9 [3946631] Nature. 1989 Aug 24;340(6235):636-8 [2475781] Neuron. 1990 Jul;5(1):1-10 [2196069] Neuron. 1989 Dec;3(6):695-704 [2561976] Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):380-4 [1988937] Neuron. 1991 Jul;7(1):119-27 [1648936] J Physiol. 1990 Dec;431:343-64 [1983120] J Neurosci Methods. 1991 Mar;37(1):15-26 [2072734] Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11481-5 [1333612] Physiol Rev. 1993 Jan;73(1):197-227 [8380502] J Membr Biol. 1993 Oct;136(1):85-96 [7505828] Neuroendocrinology. 1994 Mar;59(3):297-308 [8159279] Neuron. 1994 Apr;12(4):819-29 [8161454] J Neurosci Methods. 1994 Jan;51(1):107-16 [8189746] Methods Cell Biol. 1994;40:155-81 [8201975] J Neurophysiol. 1995 Jan;73(1):56-64 [7714589] Science. 1995 Apr 14;268(5208):297-300 [7716524] Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3918-22 [7537379] J Physiol. 1995 May 15;485 ( Pt 1):43-57 [7658382] Prog Brain Res. 1995;105:65-78 [7568898] J Neurosci. 1996 Mar 1;16(5):1668-78 [8774435] Neuron. 1996 Sep;17(3):501-12 [8816713] Neuroendocrinology. 1996 Feb;63(2):101-11 [9053774] J Neurophysiol. 1995 Oct;74(4):1395-403 [8989380] Nature. 1983 Dec 1-7;306(5942):436-41 [6316158] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - IF-LCM: laser capture microdissection of immunofluorescently defined cells for mRNA analysis rapid communication. AN - 72235158; 10972700 AB - The next phase of the molecular revolution will bring functional genomics down to the level of individual cells in a tissue. Laser capture microdissection (LCM) coupled with reverse transcription-polymerase chain reaction (RT-PCR) can measure gene expression in normal, cancerous, injured, or fibrotic tissue. Nevertheless, targeting of specific cells may be difficult using routine morphologic stains. Immunohistochemistry can identify cells with specific antigens; however, exposure to aqueous solutions destroys 99% of the mRNA. Consequently, there is an overwhelming need to identify specific tissue cells for LCM without mRNA loss. We report on a rapid immunofluorescent LCM (IF-LCM) procedure that allows targeted analysis of gene expression. A LCM microscope was outfitted for epifluorescence and light level video microscopy. Heat filters were added to shield the image intensifier from the laser. Frozen sections were fluorescently labeled by a rapid one minute incubation with anti-Tamm-Horsfall antibody and an ALEXA-linked secondary antibody. Fluorescently labeled thick ascending limb (TAL) cells were detected by low light level video microscopy, captured by LCM, and mRNA was analyzed by RT-PCR for basic amino acid transporter, Tamm-Horsfall protein, and aquaporin-2. The immunofluorescently identified TAL could be cleanly microdissected without contamination from surrounding tubules. The recovery of RNA following rapid immunofluorescence staining was similar to that obtained following hematoxylin and eosin staining, as assessed by RT-PCR for malate dehydrogenase. We conclude that the new apparatus and method for the immunofluorescent labeling of tissue cells targeted for LCM can isolate pure populations of targeted cells from a sea of surrounding cells with highly acceptable preservation of mRNA. Since the TAL is minimally injured following ischemia, identification of the different responses between TAL and surrounding tissue in damaged kidneys may provide new therapeutic targets or agents for the treatment of acute renal failure. JF - Kidney international AU - Murakami, H AU - Liotta, L AU - Star, R A AD - Renal Diagnostics and Therapeutics Unit, and Laboratory of Pathology, National Institutes of Health, Bethesda, Maryland 20892-1268, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 1346 EP - 1353 VL - 58 IS - 3 SN - 0085-2538, 0085-2538 KW - Coloring Agents KW - 0 KW - Oligonucleotide Probes KW - RNA, Messenger KW - Acridine Orange KW - F30N4O6XVV KW - Eosine Yellowish-(YS) KW - TDQ283MPCW KW - Hematoxylin KW - YKM8PY2Z55 KW - Index Medicus KW - Animals KW - Optics and Photonics KW - Gene Expression KW - Mice KW - Image Cytometry -- methods KW - Reverse Transcriptase Polymerase Chain Reaction KW - Mice, Inbred BALB C KW - Image Cytometry -- instrumentation KW - Fluorescent Antibody Technique KW - Female KW - Loop of Henle -- cytology KW - Dissection -- instrumentation KW - Loop of Henle -- physiology KW - RNA, Messenger -- analysis KW - Microscopy, Video -- methods KW - Lasers KW - Microscopy, Video -- instrumentation KW - Dissection -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72235158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Kidney+international&rft.atitle=IF-LCM%3A+laser+capture+microdissection+of+immunofluorescently+defined+cells+for+mRNA+analysis+rapid+communication.&rft.au=Murakami%2C+H%3BLiotta%2C+L%3BStar%2C+R+A&rft.aulast=Murakami&rft.aufirst=H&rft.date=2000-09-01&rft.volume=58&rft.issue=3&rft.spage=1346&rft.isbn=&rft.btitle=&rft.title=Kidney+international&rft.issn=00852538&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-12 N1 - Date created - 2000-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glomerulosclerosis and viral gene expression in HIV-transgenic mice: role of nef. AN - 72234979; 10972678 AB - Human immunodeficiency virus (HIV)-associated nephropathy is characterized by focal segmental glomerulosclerosis and microcystic tubular dilation. We have previously described a mouse transgenic for a Deltagag-pol HIV-1 genome, which develops glomerulosclerosis, cutaneous papillomas, and cataracts. We developed mice transgenic for a Deltagag-pol-nef HIV genome in order to investigate the role of the nef gene in these phenotypes. One transgenic line, X5, expressed HIV mRNA in kidney and consistently manifested focal segmental glomerulosclerosis and tubular dilation by six weeks of age. Northern analysis indicated that renal transgene expression was higher in the Deltagag-pol-nef mice compared with the Deltagag-pol mice. In situ hybridization and immunostaining demonstrated HIV RNA and protein expression within the glomerular epithelial cells and tubular epithelial cells. These cell types showed histologic evidence of toxicity, including vacuolation and detachment from basement membrane, and exhibited increased rates of apoptosis. These data suggest that the renal disease seen in the Deltagag-pol-nef transgenic mouse may be caused by the expression of HIV genes within renal epithelial cells, that this expression may induce cellular toxicity, including apoptosis, and that nef is not required for the induction of renal disease. We have previously described mice bearing the nef gene, which do not manifest renal disease. In further experiments, Deltagag-pol-nef mice were bred with nef mice; these dual-transgenic mice developed renal disease that generally resembled that seen in Deltagag-pol-nef mice, but with somewhat more severe glomerulosclerosis and less severe tubulointerstitial injury. The results of these transgenic studies suggest that the role of nef is complex and may act both to reduce transgene expression and to potentiate glomerular injury induced by other HIV-1 gene products. JF - Kidney international AU - Kajiyama, W AU - Kopp, J B AU - Marinos, N J AU - Klotman, P E AU - Dickie, P AD - Kidney Disease Section, Metabolic Diseases Branch, NIDDK, and Imaging Facility, NIDR, NIH, Bethesda, Maryland, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 1148 EP - 1159 VL - 58 IS - 3 SN - 0085-2538, 0085-2538 KW - Gene Products, gag KW - 0 KW - Gene Products, nef KW - Gene Products, pol KW - HIV Envelope Protein gp120 KW - RNA, Messenger KW - RNA, Viral KW - nef Gene Products, Human Immunodeficiency Virus KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Gene Products, gag -- genetics KW - Blotting, Northern KW - RNA, Messenger -- analysis KW - HIV Envelope Protein gp120 -- genetics KW - Mice KW - Transgenes -- genetics KW - Gene Products, pol -- genetics KW - Mice, Transgenic KW - Renal Insufficiency -- physiopathology KW - Mice, Inbred Strains KW - Apoptosis -- genetics KW - In Situ Hybridization KW - Renal Insufficiency -- virology KW - Female KW - Male KW - RNA, Viral -- analysis KW - HIV-1 -- genetics KW - Glomerulosclerosis, Focal Segmental -- pathology KW - Glomerulosclerosis, Focal Segmental -- physiopathology KW - Gene Products, nef -- genetics KW - Gene Expression Regulation, Viral KW - AIDS-Associated Nephropathy -- pathology KW - AIDS-Associated Nephropathy -- genetics KW - Glomerulosclerosis, Focal Segmental -- virology KW - AIDS-Associated Nephropathy -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72234979?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Kidney+international&rft.atitle=Glomerulosclerosis+and+viral+gene+expression+in+HIV-transgenic+mice%3A+role+of+nef.&rft.au=Kajiyama%2C+W%3BKopp%2C+J+B%3BMarinos%2C+N+J%3BKlotman%2C+P+E%3BDickie%2C+P&rft.aulast=Kajiyama&rft.aufirst=W&rft.date=2000-09-01&rft.volume=58&rft.issue=3&rft.spage=1148&rft.isbn=&rft.btitle=&rft.title=Kidney+international&rft.issn=00852538&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-12 N1 - Date created - 2000-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Applications of genetically manipulated mice in pharmacogenetics and pharmacogenomics. AN - 72234855; 10971200 AB - Gene knockout mice have proven to be very useful in understanding the role of xenobiotic-metabolizing enzymes in chemical toxicity and carcinogenesis. The combination of gene knockout technology with transgenic mouse technology should provide more versatile and suitable animal models to study the risks of chemical exposures in humans in terms of toxicity and carcinogenesis, as well as development and design of new therapeutic drugs. Recent studies using genetically manipulated mice are summarized. Copyright 2000 S. Karger AG, Basel JF - Pharmacology AU - Kimura, S AU - Gonzalez, F J AD - Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. shioko@helix.nih.gov Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 147 EP - 153 VL - 61 IS - 3 SN - 0031-7012, 0031-7012 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Animals KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- metabolism KW - Mice KW - Pharmacogenetics -- methods KW - Mice, Transgenic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72234855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Applications+of+genetically+manipulated+mice+in+pharmacogenetics+and+pharmacogenomics.&rft.au=Kimura%2C+S%3BGonzalez%2C+F+J&rft.aulast=Kimura&rft.aufirst=S&rft.date=2000-09-01&rft.volume=61&rft.issue=3&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Pharmacology&rft.issn=00317012&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-07 N1 - Date created - 2000-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Defective nuclear localization of p53 protein in a Chinese hamster cell line is associated with the formation of stable cytoplasmic protein multimers in cells with gene amplification. AN - 72215552; 10964093 AB - Many p53 functions require p53 transport into the nucleus. Mutant p53 also generally accumulates in the nucleus of transformed or neoplastic cells. However, examples of cytoplasmic accumulation of wild-type or mutant p53 have also been reported. Various explanations have been provided for defective nuclear localization. Here we propose a novel example of cytoplasmic p53 localization which occurs in cells showing gene amplification and appears to be due to the formation of stable p53 multimers. We studied a methotrexate-resistant Chinese hamster cell line (MTX M) carrying amplified dihydrofolate reductase genes and derived from a cell line with p53 nuclear accumulation. MTX M showed cytoplasmic p53 localization and, on immunoblots, several extra bands in the high molecular weight region, besides the expected 53 kDa band. p53 localization and the appearance of high molecular weight bands appeared to be correlated with the degree of DNA amplification. However, amplification of dihydrofolate reductase itself was not involved. Changing the p53 phosphorylation status quantitatively influenced the formation of high molecular weight bands. Cell fusion experiments demonstrated that p53 cytoplasmic localization in MTX M is a dominant phenotype. This result suggests that the defect causing lack of nuclear localization in this cell line does not reside in the nucleus. In the cytoplasm of MTX M and of wild-type/MTX M heterodikaryons p53 gives rise to protein complexes that are unable to re-enter the nucleus. The formation of such protein complexes is dependent on the amplification of an unknown gene product. JF - Carcinogenesis AU - Ottaggio, L AU - Bozzo, S AU - Moro, F AU - Sparks, A AU - Campomenosi, P AU - Miele, M AU - Bonatti, S AU - Fronza, G AU - Lane, D P AU - Abbondandolo, A AD - Mutagenesis Laboratory, National Cancer Institute (IST), Largo Rosanna Benzi 10, 16132 Genova, Italy. ottaggio@hp380.ist.unige.it Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 1631 EP - 1638 VL - 21 IS - 9 SN - 0143-3334, 0143-3334 KW - Antimetabolites, Antineoplastic KW - 0 KW - Tumor Suppressor Protein p53 KW - Sodium Dodecyl Sulfate KW - 368GB5141J KW - DNA KW - 9007-49-2 KW - Tetrahydrofolate Dehydrogenase KW - EC 1.5.1.3 KW - Dithiothreitol KW - T8ID5YZU6Y KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Immunoblotting KW - Animals KW - Methotrexate -- pharmacology KW - Cricetulus KW - Humans KW - DNA -- metabolism KW - Burkitt Lymphoma -- genetics KW - Mice KW - Drug Resistance, Neoplasm KW - Precipitin Tests KW - Antimetabolites, Antineoplastic -- pharmacology KW - Phenotype KW - Tumor Cells, Cultured KW - Phosphorylation KW - Cytoplasm -- metabolism KW - Burkitt Lymphoma -- enzymology KW - DNA -- genetics KW - 3T3 Cells -- metabolism KW - Cell Line, Transformed KW - Burkitt Lymphoma -- metabolism KW - Cricetinae KW - Gene Amplification -- physiology KW - Cell Nucleus -- metabolism KW - Tumor Suppressor Protein p53 -- genetics KW - Tumor Suppressor Protein p53 -- metabolism KW - Tetrahydrofolate Dehydrogenase -- metabolism KW - Tetrahydrofolate Dehydrogenase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72215552?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Defective+nuclear+localization+of+p53+protein+in+a+Chinese+hamster+cell+line+is+associated+with+the+formation+of+stable+cytoplasmic+protein+multimers+in+cells+with+gene+amplification.&rft.au=Ottaggio%2C+L%3BBozzo%2C+S%3BMoro%2C+F%3BSparks%2C+A%3BCampomenosi%2C+P%3BMiele%2C+M%3BBonatti%2C+S%3BFronza%2C+G%3BLane%2C+D+P%3BAbbondandolo%2C+A&rft.aulast=Ottaggio&rft.aufirst=L&rft.date=2000-09-01&rft.volume=21&rft.issue=9&rft.spage=1631&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-02 N1 - Date created - 2000-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Directions for biomedical research in alcohol and HIV: where are we now and where can we go? AN - 72213528; 10957717 JF - AIDS research and human retroviruses AU - Isaki, L AU - Kresina, T F AD - Division of Basic Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/09/01/ PY - 2000 DA - 2000 Sep 01 SP - 1197 EP - 1207 VL - 16 IS - 13 SN - 0889-2229, 0889-2229 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Humans KW - Acquired Immunodeficiency Syndrome -- complications KW - HIV Infections -- complications KW - Research -- trends KW - Alcoholism -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72213528?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+research+and+human+retroviruses&rft.atitle=Directions+for+biomedical+research+in+alcohol+and+HIV%3A+where+are+we+now+and+where+can+we+go%3F&rft.au=Isaki%2C+L%3BKresina%2C+T+F&rft.aulast=Isaki&rft.aufirst=L&rft.date=2000-09-01&rft.volume=16&rft.issue=13&rft.spage=1197&rft.isbn=&rft.btitle=&rft.title=AIDS+research+and+human+retroviruses&rft.issn=08892229&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-27 N1 - Date created - 2000-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CREB-binding protein sequestration by expanded polyglutamine. AN - 72213305; 10958659 AB - Spinal and bulbar muscular atrophy (SBMA) is one of eight inherited neurodegenerative diseases known to be caused by CAG repeat expansion. The expansion results in an expanded polyglutamine tract, which likely confers a novel, toxic function to the affected protein. Cell culture and transgenic mouse studies have implicated the nucleus as a site for pathogenesis, suggesting that a critical nuclear factor or process is disrupted by the polyglutamine expansion. In this report we present evidence that CREB-binding protein (CBP), a transcriptional co-activator that orchestrates nuclear response to a variety of cell signaling cascades, is incorporated into nuclear inclusions formed by polyglutamine-containing proteins in cultured cells, transgenic mice and tissue from patients with SBMA. We also show CBP incorporation into nuclear inclusions formed in a cell culture model of another polyglutamine disease, spinocerebellar ataxia type 3. We present evidence that soluble levels of CBP are reduced in cells expressing expanded polyglutamine despite increased levels of CBP mRNA. Finally, we demonstrate that over-expression of CBP rescues cells from polyglutamine-mediated toxicity in neuronal cell culture. These data support a CBP-sequestration model of polyglutamine expansion disease. JF - Human molecular genetics AU - McCampbell, A AU - Taylor, J P AU - Taye, A A AU - Robitschek, J AU - Li, M AU - Walcott, J AU - Merry, D AU - Chai, Y AU - Paulson, H AU - Sobue, G AU - Fischbeck, K H AD - Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, Building 10, Room 3B11, Bethesda, MD 20892-1250, USA. mccampba@ninds.nih.gov Y1 - 2000/09/01/ PY - 2000 DA - 2000 Sep 01 SP - 2197 EP - 2202 VL - 9 IS - 14 SN - 0964-6906, 0964-6906 KW - DNA-Binding Proteins KW - 0 KW - Fungal Proteins KW - GAL4 protein, S cerevisiae KW - Luminescent Proteins KW - Nerve Tissue Proteins KW - Nuclear Proteins KW - Peptides KW - RNA, Messenger KW - Repressor Proteins KW - Saccharomyces cerevisiae Proteins KW - Tetrazolium Salts KW - Thiazoles KW - Trans-Activators KW - Transcription Factors KW - Green Fluorescent Proteins KW - 147336-22-9 KW - polyglutamine KW - 26700-71-0 KW - Luciferases KW - EC 1.13.12.- KW - CREB-Binding Protein KW - EC 2.3.1.48 KW - CREBBP protein, human KW - Crebbp protein, mouse KW - ATXN3 protein, human KW - EC 3.4.19.12 KW - Ataxin-3 KW - Atxn3 protein, mouse KW - thiazolyl blue KW - EUY85H477I KW - Index Medicus KW - Animals KW - Muscular Atrophy, Spinal -- genetics KW - Transcription Factors -- metabolism KW - Cell Nucleus -- metabolism KW - Machado-Joseph Disease -- genetics KW - Machado-Joseph Disease -- metabolism KW - Humans KW - Transcription, Genetic KW - Mice, Transgenic KW - Tetrazolium Salts -- pharmacology KW - Muscular Atrophy, Spinal -- metabolism KW - Scrotum -- metabolism KW - Time Factors KW - Male KW - HeLa Cells KW - Luciferases -- metabolism KW - Luminescent Proteins -- metabolism KW - Mice KW - Cell Death -- drug effects KW - Thiazoles -- pharmacology KW - Fungal Proteins -- metabolism KW - RNA, Messenger -- metabolism KW - Cells, Cultured KW - Nerve Tissue Proteins -- metabolism KW - Cell Line KW - Trans-Activators -- metabolism KW - Peptides -- metabolism KW - Peptides -- pharmacology KW - Nuclear Proteins -- metabolism KW - Trinucleotide Repeat Expansion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72213305?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+molecular+genetics&rft.atitle=CREB-binding+protein+sequestration+by+expanded+polyglutamine.&rft.au=McCampbell%2C+A%3BTaylor%2C+J+P%3BTaye%2C+A+A%3BRobitschek%2C+J%3BLi%2C+M%3BWalcott%2C+J%3BMerry%2C+D%3BChai%2C+Y%3BPaulson%2C+H%3BSobue%2C+G%3BFischbeck%2C+K+H&rft.aulast=McCampbell&rft.aufirst=A&rft.date=2000-09-01&rft.volume=9&rft.issue=14&rft.spage=2197&rft.isbn=&rft.btitle=&rft.title=Human+molecular+genetics&rft.issn=09646906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-21 N1 - Date created - 2000-09-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deficiency of PTEN in Jurkat T cells causes constitutive localization of Itk to the plasma membrane and hyperresponsiveness to CD3 stimulation. AN - 72212979; 10958690 AB - Pleckstrin homology (PH) domain binding to D3-phosphorylated phosphatidylinositides (PI) provides a reversible means of recruiting proteins to the plasma membrane, with the resultant change in subcellular localization playing a key role in the activation of multiple intracellular signaling pathways. Previously we found that the T-cell-specific PH domain-containing kinase Itk is constitutively membrane associated in Jurkat T cells. This distribution was unexpected given that the closely related B-cell kinase, Btk, is almost exclusively cytosolic. In addition to constitutive membrane association of Itk, unstimulated JTAg T cells also exhibited constitutive phosphorylation of Akt on Ser-473, an indication of elevated basal levels of the phosphatidylinositol 3-kinase (PI3K) products PI-3,4-P(2) and PI-3,4,5-P(3) in the plasma membrane. Here we describe a defect in expression of the D3 phosphoinositide phosphatase, PTEN, in Jurkat and JTAg T cells that leads to unregulated PH domain interactions with the plasma membrane. Inhibition of D3 phosphorylation by PI3K inhibitors, or by expression of PTEN, blocked constitutive phosphorylation of Akt on Ser-473 and caused Itk to redistribute to the cytosol. The PTEN-deficient cells were also hyperresponsive to T-cell receptor (TCR) stimulation, as measured by Itk kinase activity, tyrosine phosphorylation of phospholipase C-gamma1, and activation of Erk compared to those in PTEN-replete cells. These data support the idea that PH domain-mediated association with the plasma membrane is required for Itk activation, provide evidence for a negative regulatory role of PTEN in TCR stimulation, and suggest that signaling models based on results from Jurkat T-cell lines may underestimate the role of PI3K in TCR signaling. JF - Molecular and cellular biology AU - Shan, X AU - Czar, M J AU - Bunnell, S C AU - Liu, P AU - Liu, Y AU - Schwartzberg, P L AU - Wange, R L AD - Laboratory of Biological Chemistry, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224-6825, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 6945 EP - 6957 VL - 20 IS - 18 SN - 0270-7306, 0270-7306 KW - Antigens, CD3 KW - 0 KW - Antigens, Polyomavirus Transforming KW - Blood Proteins KW - Isoenzymes KW - Phosphatidylinositol Phosphates KW - Phosphoproteins KW - Proto-Oncogene Proteins KW - Tumor Suppressor Proteins KW - phosphatidylinositol 3,4,5-triphosphate KW - phosphatidylinositol 3,4-diphosphate KW - platelet protein P47 KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - emt protein-tyrosine kinase KW - EC 2.7.10.2 KW - AKT1 protein, human KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - B59 protein, human KW - EC 3.1.3.- KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - Protein Tyrosine Phosphatases KW - EC 3.1.3.48 KW - PTEN Phosphohydrolase KW - EC 3.1.3.67 KW - PTEN protein, human KW - Type C Phospholipases KW - EC 3.1.4.- KW - Phospholipase C gamma KW - EC 3.1.4.3 KW - Index Medicus KW - Animals KW - Protein-Serine-Threonine Kinases -- metabolism KW - Protein Tyrosine Phosphatases -- metabolism KW - Humans KW - Jurkat Cells KW - Biological Transport KW - Proto-Oncogene Proteins -- metabolism KW - Transcription, Genetic KW - Isoenzymes -- metabolism KW - Type C Phospholipases -- metabolism KW - Mutagenesis KW - Tumor Cells, Cultured KW - Phosphorylation KW - Molecular Sequence Data KW - Phosphoproteins -- metabolism KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Exons KW - Enzyme Activation KW - Phosphatidylinositol Phosphates -- metabolism KW - Rabbits KW - Antigens, Polyomavirus Transforming -- genetics KW - Binding Sites KW - Base Sequence KW - Cytosol KW - Cell Membrane -- metabolism KW - Blood Proteins -- metabolism KW - T-Lymphocytes -- metabolism KW - Antigens, CD3 -- metabolism KW - Antigens, CD3 -- pharmacology KW - Phosphoric Monoester Hydrolases -- genetics KW - Phosphoric Monoester Hydrolases -- biosynthesis KW - T-Lymphocytes -- drug effects KW - Protein-Tyrosine Kinases -- metabolism KW - Phosphoric Monoester Hydrolases -- physiology KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72212979?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Deficiency+of+PTEN+in+Jurkat+T+cells+causes+constitutive+localization+of+Itk+to+the+plasma+membrane+and+hyperresponsiveness+to+CD3+stimulation.&rft.au=Shan%2C+X%3BCzar%2C+M+J%3BBunnell%2C+S+C%3BLiu%2C+P%3BLiu%2C+Y%3BSchwartzberg%2C+P+L%3BWange%2C+R+L&rft.aulast=Shan&rft.aufirst=X&rft.date=2000-09-01&rft.volume=20&rft.issue=18&rft.spage=6945&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 - 2000-09-22 N1 - 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Last updated - 2017-01-18 ER - TY - JOUR T1 - Hypermethylation of the p16 (Ink4a) promoter in B6C3F1 mouse primary lung adenocarcinomas and mouse lung cell lines. AN - 72212791; 10964101 AB - Primary lung tumors from B6C3F1 mice and mouse lung cell lines were examined to investigate the role of transcriptional silencing of the p16 (Ink4a) tumor suppressor gene by DNA hypermethylation during mouse lung carcinogenesis. Hypermethylation (>/=50% methylation at two or more of the CpG sites examined) of the p16 (Ink4a) promoter region was detected in DNA from 12 of 17 (70%) of the B6C3F1 primary mouse lung adenocarcinomas examined, whereas hypermethylation was not detected in normal B6C3F1, C57BL/6 and C3H/He mouse lung tissues. Immunohistochemistry performed on the B6C3F1 lung adenocarcinomas revealed heterogeneous expression of the p16 protein within and among the tumors. Laser capture microdissection was employed to collect cells from immunostained sections of four tumors displaying areas of relatively high and low p16 expression. The methylation status of the microdissected samples was assessed by sodium bisulfite genomic sequencing. The pattern of p16 expression correlated inversely with the DNA methylation pattern at promoter CpG sites in nine of 11 (82%) of the microdissected areas displaying variable p16 expression. To provide further evidence that hypermethylation is involved in the loss of p16 (Ink4a) gene expression, three mouse lung tumor cell lines (C10, sp6c and CMT64) displaying complete methylation at seven promoter CpG sites and no p16 (Ink4a) expression were treated with the demethylating agent, 5-aza-2'-deoxycytidine. Re-expression of p16 (Ink4a) and partial demethylation of the p16 (Ink4a) promoter were observed in two cell lines (C10 and sp6c) following treatment. These are the first reported studies to provide strong evidence that DNA methylation is a mechanism for p16 inactivation in mouse lung tumors. JF - Carcinogenesis AU - Patel, A C AU - Anna, C H AU - Foley, J F AU - Stockton, P S AU - Tyson, F L AU - Barrett, J C AU - Devereux, T R AD - Laboratory of Molecular Carcinogenesis, Chemical Exposures and Molecular Biology Branch, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 1691 EP - 1700 VL - 21 IS - 9 SN - 0143-3334, 0143-3334 KW - Antimetabolites, Antineoplastic KW - 0 KW - Carrier Proteins KW - Cyclin-Dependent Kinase Inhibitor p16 KW - DNA, Neoplasm KW - decitabine KW - 776B62CQ27 KW - DNA Modification Methylases KW - EC 2.1.1.- KW - Azacitidine KW - M801H13NRU KW - 6-azacytidine KW - YD42UEH51C KW - Index Medicus KW - Animals KW - Genes, Tumor Suppressor KW - DNA Modification Methylases -- antagonists & inhibitors KW - DNA Mutational Analysis KW - Cell Division -- drug effects KW - Gene Expression KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Antimetabolites, Antineoplastic -- pharmacology KW - Mice, Inbred A KW - Loss of Heterozygosity KW - Tumor Cells, Cultured KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - CpG Islands -- physiology KW - Immunohistochemistry KW - Female KW - Promoter Regions, Genetic -- physiology KW - Adenocarcinoma -- metabolism KW - Azacitidine -- pharmacology KW - Carrier Proteins -- genetics KW - Azacitidine -- analogs & derivatives KW - DNA Methylation -- drug effects KW - Lung Neoplasms -- genetics KW - DNA, Neoplasm -- genetics KW - Adenocarcinoma -- genetics KW - DNA, Neoplasm -- metabolism KW - Carrier Proteins -- biosynthesis KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72212791?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hypermethylation+of+the+p16+%28Ink4a%29+promoter+in+B6C3F1+mouse+primary+lung+adenocarcinomas+and+mouse+lung+cell+lines.&rft.au=Patel%2C+A+C%3BAnna%2C+C+H%3BFoley%2C+J+F%3BStockton%2C+P+S%3BTyson%2C+F+L%3BBarrett%2C+J+C%3BDevereux%2C+T+R&rft.aulast=Patel&rft.aufirst=A&rft.date=2000-09-01&rft.volume=74&rft.issue=19&rft.spage=9317&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/10.1128%2FJVI.74.19.9317-9321.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-02 N1 - Date created - 2000-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The death domain kinase RIP is essential for TRAIL (Apo2L)-induced activation of IkappaB kinase and c-Jun N-terminal kinase. AN - 72212726; 10958661 AB - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) (Apo2 ligand [Apo2L]) is a member of the TNF superfamily and has been shown to have selective antitumor activity. Although it is known that TRAIL (Apo2L) induces apoptosis and activates NF-kappaB and Jun N-terminal kinase (JNK) through receptors such as TRAIL-R1 (DR4) and TRAIL-R2 (DR5), the components of its signaling cascade have not been well defined. In this report, we demonstrated that the death domain kinase RIP is essential for TRAIL-induced IkappaB kinase (IKK) and JNK activation. We found that ectopic expression of the dominant negative mutant RIP, RIP(559-671), blocks TRAIL-induced IKK and JNK activation. In the RIP null fibroblasts, TRAIL failed to activate IKK and only partially activated JNK. The endogenous RIP protein was detected by immunoprecipitation in the TRAIL-R1 complex after TRAIL treatment. More importantly, we found that RIP is not involved in TRAIL-induced apoptosis. In addition, we also demonstrated that the TNF receptor-associated factor 2 (TRAF2) plays little role in TRAIL-induced IKK activation although it is required for TRAIL-mediated JNK activation. These results indicated that the death domain kinase RIP, a key factor in TNF signaling, also plays a pivotal role in TRAIL-induced IKK and JNK activation. JF - Molecular and cellular biology AU - Lin, Y AU - Devin, A AU - Cook, A AU - Keane, M M AU - Kelliher, M AU - Lipkowitz, S AU - Liu, Z G AD - Department of Cell and Cancer Biology, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 6638 EP - 6645 VL - 20 IS - 18 SN - 0270-7306, 0270-7306 KW - Apoptosis Regulatory Proteins KW - 0 KW - Ligands KW - Membrane Glycoproteins KW - Proteins KW - Receptors, TNF-Related Apoptosis-Inducing Ligand KW - Receptors, Tumor Necrosis Factor KW - Recombinant Fusion Proteins KW - TNF Receptor-Associated Factor 2 KW - TNF-Related Apoptosis-Inducing Ligand KW - TNFRSF10A protein, human KW - TNFSF10 protein, human KW - Tnfsf10 protein, mouse KW - Tumor Necrosis Factor-alpha KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - RIPK1 protein, human KW - Receptor-Interacting Protein Serine-Threonine Kinases KW - Ripk1 protein, mouse KW - CHUK protein, human KW - EC 2.7.11.10 KW - Chuk protein, mouse KW - I-kappa B Kinase KW - IKBKB protein, human KW - IKBKE protein, human KW - Ikbkb protein, mouse KW - Ikbke protein, mouse KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - Index Medicus KW - Animals KW - Enzyme Activation KW - HeLa Cells KW - Humans KW - Fibroblasts -- cytology KW - Mice KW - Mutagenesis KW - Recombinant Fusion Proteins -- metabolism KW - Recombinant Fusion Proteins -- genetics KW - Receptors, Tumor Necrosis Factor -- metabolism KW - Signal Transduction KW - Cell Line KW - Protein-Serine-Threonine Kinases -- metabolism KW - Apoptosis KW - Mitogen-Activated Protein Kinases -- metabolism KW - Protein-Serine-Threonine Kinases -- genetics KW - Tumor Necrosis Factor-alpha -- metabolism KW - Tumor Necrosis Factor-alpha -- genetics KW - Proteins -- metabolism KW - Proteins -- genetics KW - Proteins -- physiology KW - Membrane Glycoproteins -- metabolism KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72212726?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+death+domain+kinase+RIP+is+essential+for+TRAIL+%28Apo2L%29-induced+activation+of+IkappaB+kinase+and+c-Jun+N-terminal+kinase.&rft.au=Lin%2C+Y%3BDevin%2C+A%3BCook%2C+A%3BKeane%2C+M+M%3BKelliher%2C+M%3BLipkowitz%2C+S%3BLiu%2C+Z+G&rft.aulast=Lin&rft.aufirst=Y&rft.date=2000-09-01&rft.volume=20&rft.issue=18&rft.spage=6638&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 - 2000-09-22 N1 - Date created - 2000-09-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Immunity. 1997 Dec;7(6):821-30 [9430227] Cell. 1996 Nov 1;87(3):565-76 [8898208] Science. 1998 Mar 20;279(5358):1954-8 [9506948] Nature. 1998 Mar 19;392(6673):296-300 [9521326] Immunity. 1998 Mar;8(3):297-303 [9529147] J Biol Chem. 1998 Jun 5;273(23):14363-7 [9603945] Blood. 1998 Jun 15;91(12):4624-31 [9616159] Science. 1998 Aug 28;281(5381):1305-8 [9721089] J Biol Chem. 1998 Dec 4;273(49):33091-8 [9830064] Eur Cytokine Netw. 1998 Dec;9(4):687-8 [9889416] Nat Med. 1999 Feb;5(2):157-63 [9930862] Cancer Res. 1999 Feb 1;59(3):734-41 [9973225] J Clin Invest. 1999 Jul;104(2):155-62 [10411544] EMBO J. 1996 Nov 15;15(22):6189-96 [8947041] Science. 1997 Jan 10;275(5297):200-3 [8985011] Nature. 1997 Feb 6;385(6616):540-4 [9020361] EMBO J. 1997 Mar 3;16(5):1080-92 [9118946] Curr Opin Cell Biol. 1997 Apr;9(2):240-6 [9069263] Science. 1997 Apr 4;276(5309):111-3 [9082980] Cell. 1997 Jul 25;90(2):373-83 [9244310] Science. 1997 Aug 8;277(5327):815-8 [9242610] Science. 1997 Aug 8;277(5327):818-21 [9242611] Nature. 1997 Aug 7;388(6642):548-54 [9252186] EMBO J. 1997 Sep 1;16(17):5386-97 [9311998] Cell. 1997 Oct 17;91(2):243-52 [9346241] Science. 1997 Oct 31;278(5339):860-6 [9346484] Immunity. 1997 Nov;7(5):703-13 [9390693] Immunity. 1997 Nov;7(5):715-25 [9390694] Curr Biol. 1998 Jan 15;8(2):113-6 [9427646] Immunity. 1997 Dec;7(6):813-20 [9430226] Genes Dev. 1999 Oct 1;13(19):2514-26 [10521396] J Biol Chem. 1999 Oct 22;274(43):30603-10 [10521444] Mol Cell. 1999 Oct;4(4):563-71 [10549288] Leukemia. 1999 Nov;13(11):1817-24 [10557057] Nat Struct Biol. 1999 Nov;6(11):1048-53 [10542098] Annu Rev Cell Biol. 1993;9:317-43 [8280464] Cell. 1994 Mar 25;76(6):959-62 [8137429] Science. 1994 Dec 9;266(5191):1719-23 [7992057] Mol Cell Biol. 1995 Mar;15(3):1302-11 [7862124] Science. 1995 Mar 10;267(5203):1449-56 [7533326] Annu Rev Cell Biol. 1994;10:405-55 [7888182] Cell. 1995 May 19;81(4):495-504 [7758105] Immunity. 1995 Dec;3(6):673-82 [8777713] Cell. 1996 Jan 26;84(2):299-308 [8565075] Immunity. 1996 Apr;4(4):387-96 [8612133] J Biol Chem. 1996 May 31;271(22):12687-90 [8663110] Curr Biol. 1996 Jun 1;6(6):750-2 [8793301] Cell. 1996 Oct 4;87(1):13-20 [8858144] Science. 1996 Nov 1;274(5288):782-4 [8864118] Science. 1996 Nov 1;274(5288):784-7 [8864119] Science. 1996 Nov 1;274(5288):787-9 [8864120] Immunity. 1997 Dec;7(6):831-6 [9430228] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rituximab anti-CD20 monoclonal antibody therapy in non-Hodgkin's lymphoma: safety and efficacy of re-treatment. AN - 72211787; 10963642 AB - This phase II trial investigated the safety and efficacy of re-treatment with rituximab, a chimeric anti-CD20 monoclonal antibody, in patients with low-grade or follicular non-Hodgkin's lymphoma who relapsed after a response to rituximab therapy. Fifty-eight patients were enrolled onto this study, and two were re-treated within the study. Patients received an intravenous infusion of 375 mg/m(2) of rituximab weekly for 4 weeks. All patients had at least two prior therapies and had received at least one prior course of rituximab, with a median interval of 14.5 months between rituximab courses. Most adverse experiences (AEs) were transient grade 1 or 2 events occurring during the treatment period. Clinically significant myelosuppression was not observed; hematologic toxicity was generally mild and reversible. No patient developed human antichimeric antibodies after treatment. The type, frequency, and severity of AEs in this study were not apparently different from those reported in the phase III trial of rituximab. The overall response rate in 57 assessable patients was 40% (11% complete response and 30% partial responses). Median time to progression (TTP) in responders and median duration of response (DR) have not been reached, but Kaplan-Meier estimated medians are 17.8 months (range, 5.4+ to 26.6 months) and 16.3 months (range, 3.7+ to 25.1 months), respectively. These estimated medians are longer than the medians achieved in the patients' prior course of rituximab (TTP and DR of 12.4 and 9.8 months, respectively, P: >.1) and in a previously reported phase III trial (TTP in responders and DR of 13.2 and 11.6 months, respectively). Responses are ongoing in seven of 23 responders. In this re-treatment population, safety and efficacy were not apparently different from those after initial rituximab exposure. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Davis, T A AU - Grillo-López, A J AU - White, C A AU - McLaughlin, P AU - Czuczman, M S AU - Link, B K AU - Maloney, D G AU - Weaver, R L AU - Rosenberg, J AU - Levy, R AD - Stanford University, CA, USA. davist@ctep.nci.nih.gov Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 3135 EP - 3143 VL - 18 IS - 17 SN - 0732-183X, 0732-183X KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Murine-Derived KW - Antigens, CD20 KW - Antineoplastic Agents KW - Rituximab KW - 4F4X42SYQ6 KW - Index Medicus KW - Disease-Free Survival KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Humans KW - Neutropenia -- chemically induced KW - Aged KW - Aged, 80 and over KW - Leukopenia -- chemically induced KW - Adult KW - Middle Aged KW - Female KW - Male KW - Lymphoma, B-Cell -- blood KW - Lymphoma, Non-Hodgkin -- blood KW - Antibodies, Monoclonal -- blood KW - Neoplasm Recurrence, Local -- blood KW - Lymphoma, Follicular -- drug therapy KW - Antineoplastic Agents -- blood KW - Antibodies, Monoclonal -- therapeutic use KW - Antineoplastic Agents -- adverse effects KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Lymphoma, B-Cell -- drug therapy KW - Neoplasm Recurrence, Local -- drug therapy KW - Lymphoma, Follicular -- blood KW - Antibodies, Monoclonal -- adverse effects KW - Antineoplastic Agents -- therapeutic use KW - Antigens, CD20 -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72211787?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Rituximab+anti-CD20+monoclonal+antibody+therapy+in+non-Hodgkin%27s+lymphoma%3A+safety+and+efficacy+of+re-treatment.&rft.au=Davis%2C+T+A%3BGrillo-L%C3%B3pez%2C+A+J%3BWhite%2C+C+A%3BMcLaughlin%2C+P%3BCzuczman%2C+M+S%3BLink%2C+B+K%3BMaloney%2C+D+G%3BWeaver%2C+R+L%3BRosenberg%2C+J%3BLevy%2C+R&rft.aulast=Davis&rft.aufirst=T&rft.date=2000-09-01&rft.volume=18&rft.issue=17&rft.spage=3135&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 - 2000-09-19 N1 - Date created - 2000-09-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Study of A(2A) adenosine receptor gene deficient mice reveals that adenosine analogue CGS 21680 possesses no A(2A) receptor-unrelated lymphotoxicity. AN - 72210159; 10960067 AB - Cell surface A(2A) adenosine receptor (A(2A)R) mediated signalling affects a variety of important processes and adenosine analogues possess promising pharmacological properties. Demonstrating the receptor specificity of potentially lymphotoxic adenosine-based drugs facilitates their development for clinical applications. To distinguish between the receptor-dependent and -independent lymphotoxicity and apoptotic activity of adenosine and its analogues we used lymphocytes from A(2A)R-deficient mice. Comparison of A(2A)R-expressing (+/+) and A(2A)R-deficient (-/-) cells in cyclic AMP accumulation assays confirmed that the A(2A)R agonist CGS 21680 is indeed selective for A(2A) receptors in T-lymphocytes. Incubation of A(2A)R-expressing thymocytes with extracellular adenosine or CGS 21680 in vitro results in the death of about 7-15% of thymocytes. In contrast, no death was induced in parallel assays in cells from A(2A)R-deficient mice, providing genetic evidence that CGS 21680 does not display adenosine receptor-independent intracellular cytotoxicity. The A(2A) receptor-specific lymphotoxicity of CGS 21680 is also demonstrated in a long-term (6-day) in vitro model of thymocyte positive selection where addition of A(2A)R antagonist ZM 241,385 did block the effects of CGS 21680, allowing the survival of T cells. The use of cells from adenosine receptor-deficient animals is proposed as a part of the screening process for potential adenosine-based drugs for their receptor-independent cytotoxicity and lymphotoxicity. JF - British journal of pharmacology AU - Apasov, S G AU - Chen, J F AU - Smith, P T AU - Schwarzschild, M A AU - Fink, J S AU - Sitkovsky, M V AD - Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, MD 20892-1892, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 43 EP - 50 VL - 131 IS - 1 SN - 0007-1188, 0007-1188 KW - Phenethylamines KW - 0 KW - Receptors, Antigen, T-Cell KW - Receptors, Purinergic P1 KW - 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine KW - 120225-54-9 KW - Cyclic AMP KW - E0399OZS9N KW - Adenosine KW - K72T3FS567 KW - Index Medicus KW - Animals KW - Cell Survival -- drug effects KW - Apoptosis -- drug effects KW - Cyclic AMP -- metabolism KW - Mice KW - Receptors, Antigen, T-Cell -- physiology KW - Receptors, Purinergic P1 -- deficiency KW - Receptors, Purinergic P1 -- physiology KW - Phenethylamines -- toxicity KW - Adenosine -- toxicity KW - Adenosine -- analogs & derivatives KW - T-Lymphocytes -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72210159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+pharmacology&rft.atitle=Study+of+A%282A%29+adenosine+receptor+gene+deficient+mice+reveals+that+adenosine+analogue+CGS+21680+possesses+no+A%282A%29+receptor-unrelated+lymphotoxicity.&rft.au=Apasov%2C+S+G%3BChen%2C+J+F%3BSmith%2C+P+T%3BSchwarzschild%2C+M+A%3BFink%2C+J+S%3BSitkovsky%2C+M+V&rft.aulast=Apasov&rft.aufirst=S&rft.date=2000-09-01&rft.volume=131&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=British+journal+of+pharmacology&rft.issn=00071188&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-03 N1 - Date created - 2000-11-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Neurosci. 1999 Nov 1;19(21):9192-200 [10531422] Exp Cell Res. 1994 Jul;213(1):242-52 [8020596] J Biol Chem. 1990 Mar 25;265(9):5280-4 [1690738] Trends Pharmacol Sci. 1990 Apr;11(4):150-5 [2159198] Physiol Rev. 1990 Jul;70(3):761-845 [2194223] J Immunol. 1990 Aug 15;145(4):1227-30 [2166110] Cytometry. 1992;13(8):795-808 [1333943] Nature. 1994 Nov 3;372(6501):100-3 [7969401] Biochem J. 1994 Dec 15;304 ( Pt 3):877-85 [7818494] Biochem Biophys Res Commun. 1995 Aug 24;213(3):908-15 [7654253] Clin Immunol Immunopathol. 1995 Sep;76(3 Pt 2):S219-27 [7554472] Biochem J. 1995 Oct 15;311 ( Pt 2):585-8 [7487899] Immunol Rev. 1995 Aug;146:5-19 [7493760] J Exp Med. 1995 Nov 1;182(5):1545-56 [7595224] J Physiol. 1995 Oct 1;488 ( Pt 1):123-38 [8568648] Biochem Biophys Res Commun. 1996 Feb 27;219(3):904-10 [8645277] Naunyn Schmiedebergs Arch Pharmacol. 1996 Feb;353(3):250-60 [8692279] Cell. 1996 Jul 12;86(1):147-57 [8689682] Trends Pharmacol Sci. 1996 Mar;17(3):108-13 [8936347] Immunity. 1997 Mar;6(3):245-55 [9075925] J Immunol. 1997 Jun 1;158(11):5095-105 [9164924] Bioessays. 1997 Jun;19(6):501-7 [9204767] Nature. 1997 Aug 14;388(6643):674-8 [9262401] Blood. 1997 Aug 15;90(4):1600-10 [9269779] J Biol Chem. 1997 Oct 10;272(41):25881-9 [9325320] J Exp Med. 1997 Nov 3;186(9):1615-20 [9348321] Biochem Biophys Res Commun. 1997 Dec 18;241(2):297-304 [9425266] Neurochem Int. 1998 May-Jun;32(5-6):493-504 [9676749] Mol Pharmacol. 1999 Mar;55(3):614-24 [10051547] Int Immunol. 1999 Feb;11(2):179-89 [10069416] Proc Soc Exp Biol Med. 1970 Apr;133(4):1361-5 [4314861] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of a uterine insulin-like growth factor I signaling pathway by clinical and environmental estrogens: requirement of estrogen receptor-alpha. AN - 72208521; 10965916 AB - Recent data indicate that insulin-like growth factor I (IGF-I) may have a function in mediating the mitogenic effects of 17beta-estradiol (E2) in the uterus and in regulating the growth of uterine neoplasms. This study was designed to determine whether synthetic and plant-derived chemicals that interact with estrogen receptor-alpha (ERalpha) and elicit estrogenic responses also mimic E2 by activating the uterine IGF-I signaling pathway. Ovariectomized adult female mice were treated with both environmental and clinically relevant chemicals previously reported to display estrogenic and/or antiestrogenic properties, and their uteri were evaluated for an activated IGF-I signaling pathway. Diethylstilbestrol, 4-hydroxytamoxifen, the raloxifene analog LY353381, 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), bisphenol A, and genistein were shown to mimic E2 in the uterus by increasing the level of IGF-I messenger RNA, inducing IGF-I receptor (IGF-IR) tyrosine phosphorylation, stimulating the formation of IGF-IR signaling complexes, and increasing both proliferating cell nuclear antigen expression and the number of mitotic cells in the epithelium. The dose of chemical necessary to activate IGF-I signaling varied, with the order of potency: E2 = diethylstilbestrol > LY353381 > 4-hydroxytamoxifen > genistein > HPTE > bisphenol A. Administration of the chemicals to ERalpha knockout mice did not activate IGF-IR, indicating that ERalpha is required for activation of uterine IGF-IR by these diverse chemicals. This study demonstrates that several chemicals shown previously to display estrogenic activities also mimic E2 by activating uterine IGF-I signaling. JF - Endocrinology AU - Klotz, D M AU - Hewitt, S C AU - Korach, K S AU - Diaugustine, R P AD - Laboratories of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 3430 EP - 3439 VL - 141 IS - 9 SN - 0013-7227, 0013-7227 KW - Benzhydryl Compounds KW - 0 KW - Estradiol Congeners KW - Estrogen Antagonists KW - Estrogen Receptor alpha KW - Estrogens KW - Estrogens, Non-Steroidal KW - LY 353381 KW - Phenols KW - Piperidines KW - Proliferating Cell Nuclear Antigen KW - RNA, Messenger KW - Receptors, Estrogen KW - Thiophenes KW - Tamoxifen KW - 094ZI81Y45 KW - afimoxifene KW - 17197F0KYM KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Ribonucleases KW - EC 3.1.- KW - 2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane KW - H58165YO91 KW - bisphenol A KW - MLT3645I99 KW - Abridged Index Medicus KW - Index Medicus KW - Tamoxifen -- pharmacology KW - Animals KW - Blotting, Northern KW - Phenols -- pharmacology KW - Mice KW - Precipitin Tests KW - Ribonucleases -- metabolism KW - Tamoxifen -- analogs & derivatives KW - RNA, Messenger -- biosynthesis KW - Mice, Knockout KW - Piperidines -- pharmacology KW - Estrogen Antagonists -- pharmacology KW - Thiophenes -- pharmacology KW - Mitosis -- drug effects KW - Ovariectomy KW - Estrogens, Non-Steroidal -- pharmacology KW - Proliferating Cell Nuclear Antigen -- metabolism KW - Female KW - Uterus -- metabolism KW - Signal Transduction -- physiology KW - Insulin-Like Growth Factor I -- physiology KW - Receptors, Estrogen -- drug effects KW - Estrogens -- pharmacology KW - Insulin-Like Growth Factor I -- metabolism KW - Estradiol Congeners -- pharmacology KW - Receptors, Estrogen -- metabolism KW - Receptors, Estrogen -- agonists UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72208521?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology&rft.atitle=Activation+of+a+uterine+insulin-like+growth+factor+I+signaling+pathway+by+clinical+and+environmental+estrogens%3A+requirement+of+estrogen+receptor-alpha.&rft.au=Klotz%2C+D+M%3BHewitt%2C+S+C%3BKorach%2C+K+S%3BDiaugustine%2C+R+P&rft.aulast=Klotz&rft.aufirst=D&rft.date=2000-09-01&rft.volume=141&rft.issue=9&rft.spage=3430&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-21 N1 - Date created - 2000-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Liver cancers in Mayak workers. AN - 72202827; 10956429 AB - Liver cancer mortality risks were evaluated in 11,000 workers who started working at the "Mayak" Production Association in 1948-1958 and who were exposed to both internally deposited plutonium and external gamma radiation. Comparisons with Russian liver cancer incidence rates indicate excess risk, especially among those with detectable plutonium body burdens and among female workers in the plutonium plant. Comparisons within the Mayak worker cohort which evaluate the role of plutonium body burden with adjustment for cumulative external dose indicate excess risk among workers with burdens estimated to exceed 7.4 kBq (relative risk = 17; 95% CI = 8. 0-36) and among workers in the plutonium plant who did not have routine plutonium monitoring data based on urine measurements (relative risk = 2.8; 95% CI = 1.3-6.2). In addition, analyses treating the estimated plutonium body burden as a continuous variable indicate increasing risk with increasing burden (P < 0.001). Relative risks tended to be higher for females than for males, probably because of the lower baseline risk and the higher levels of plutonium measured in females. Because of limitations in current plutonium dosimetry, no attempt was made to quantify liver cancer risks from plutonium in terms of organ dose, and risk from external dose could not be reliably evaluated. JF - Radiation research AU - Gilbert, E S AU - Koshurnikova, N A AU - Sokolnikov, M AU - Khokhryakov, V F AU - Miller, S AU - Preston, D L AU - Romanov, S A AU - Shilnikova, N S AU - Suslova, K G AU - Vostrotin, V V AD - Radiation Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20852, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 246 EP - 252 VL - 154 IS - 3 SN - 0033-7587, 0033-7587 KW - Plutonium KW - 53023GN24M KW - Index Medicus KW - Space life sciences KW - Risk KW - Sex Factors KW - Radiometry KW - England -- epidemiology KW - Humans KW - Body Burden KW - Cohort Studies KW - Middle Aged KW - United States -- epidemiology KW - Male KW - Liver -- radiation effects KW - Female KW - Russia -- epidemiology KW - Occupational Exposure KW - Gamma Rays -- adverse effects KW - Neoplasms, Radiation-Induced -- etiology KW - Neoplasms, Radiation-Induced -- epidemiology KW - Cholangiocarcinoma -- etiology KW - Liver Neoplasms -- mortality KW - Occupational Diseases -- etiology KW - Neoplasms, Radiation-Induced -- mortality KW - Liver Neoplasms -- epidemiology KW - Carcinoma, Hepatocellular -- epidemiology KW - Occupational Diseases -- mortality KW - Cholangiocarcinoma -- mortality KW - Hemangiosarcoma -- etiology KW - Carcinoma, Hepatocellular -- etiology KW - Hemangiosarcoma -- mortality KW - Plutonium -- adverse effects KW - Plutonium -- urine KW - Cholangiocarcinoma -- epidemiology KW - Occupational Diseases -- epidemiology KW - Liver Neoplasms -- etiology KW - Hemangiosarcoma -- epidemiology KW - Carcinoma, Hepatocellular -- mortality KW - Nuclear Energy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72202827?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Liver+cancers+in+Mayak+workers.&rft.au=Gilbert%2C+E+S%3BKoshurnikova%2C+N+A%3BSokolnikov%2C+M%3BKhokhryakov%2C+V+F%3BMiller%2C+S%3BPreston%2C+D+L%3BRomanov%2C+S+A%3BShilnikova%2C+N+S%3BSuslova%2C+K+G%3BVostrotin%2C+V+V&rft.aulast=Gilbert&rft.aufirst=E&rft.date=2000-09-01&rft.volume=154&rft.issue=3&rft.spage=246&rft.isbn=&rft.btitle=&rft.title=Radiation+research&rft.issn=00337587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-28 N1 - Date created - 2000-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vibrio cholerae O139 conjugate vaccines: synthesis and immunogenicity of V. cholerae O139 capsular polysaccharide conjugates with recombinant diphtheria toxin mutant in mice. AN - 71761424; 10948122 AB - Epidemiologic and experimental data provide evidence that a critical level of serum immunoglobulin G (IgG) antibodies to the surface polysaccharide of Vibrio cholerae O1 (lipopolysaccharide) and of Vibrio cholerae O139 (capsular polysaccharide [CPS]) is associated with immunity to the homologous pathogen. The immunogenicity of polysaccharides, especially in infants, may be enhanced by their covalent attachment to proteins (conjugates). Two synthetic schemes, involving 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) as activating agents, were adapted to prepare four conjugates of V. cholerae O139 CPS with the recombinant diphtheria toxin mutant, CRMH21G. Adipic acid dihydrazide was used as a linker. When injected subcutaneously into young outbred mice by a clinically relevant dose and schedule, these conjugates elicited serum CPS antibodies of the IgG and IgM classes with vibriocidal activity to strains of capsulated V. cholerae O139. Treatment of these sera with 2-mercaptoethanol (2-ME) reduced, but did not eliminate, their vibriocidal activity. These results indicate that the conjugates elicited IgG with vibriocidal activity. Conjugates also elicited high levels of serum diphtheria toxin IgG. Convalescent sera from 20 cholera patients infected with V. cholerae O139 had vibriocidal titers ranging from 100 to 3,200: absorption with the CPS reduced the vibriocidal titer of all sera to < or =50. Treatment with 2-ME reduced the titers of 17 of 20 patients to < or =50. These data show that, like infection with V. cholerae O1, infection with V. cholerae O139 induces vibriocidal antibodies specific to the surface polysaccharide of this bacterium (CPS) that are mostly of IgM class. Based on these data, clinical trials with the V. cholerae O139 CPS conjugates with recombinant diphtheria toxin are planned. JF - Infection and immunity AU - Kossaczka, Z AU - Shiloach, J AU - Johnson, V AU - Taylor, D N AU - Finkelstein, R A AU - Robbins, J B AU - Szu, S C AD - National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2720, USA. kossaczz@mail.nih.gov Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 5037 EP - 5043 VL - 68 IS - 9 SN - 0019-9567, 0019-9567 KW - Antibodies, Bacterial KW - 0 KW - Cholera Vaccines KW - Diphtheria Toxin KW - Immunoglobulin G KW - Polysaccharides, Bacterial KW - Vaccines, Conjugate KW - Vaccines, Synthetic KW - Index Medicus KW - Immunoglobulin G -- blood KW - Vaccines, Conjugate -- immunology KW - Animals KW - Blood Bactericidal Activity KW - Antibodies, Bacterial -- blood KW - Mice KW - Female KW - Diphtheria Toxin -- immunology KW - Cholera Vaccines -- immunology KW - Vaccines, Synthetic -- immunology KW - Polysaccharides, Bacterial -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71761424?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Vibrio+cholerae+O139+conjugate+vaccines%3A+synthesis+and+immunogenicity+of+V.+cholerae+O139+capsular+polysaccharide+conjugates+with+recombinant+diphtheria+toxin+mutant+in+mice.&rft.au=Kossaczka%2C+Z%3BShiloach%2C+J%3BJohnson%2C+V%3BTaylor%2C+D+N%3BFinkelstein%2C+R+A%3BRobbins%2C+J+B%3BSzu%2C+S+C&rft.aulast=Kossaczka&rft.aufirst=Z&rft.date=2000-09-01&rft.volume=68&rft.issue=9&rft.spage=5037&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 - 2000-09-08 N1 - Date created - 2000-09-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11388-92 [7972070] Microb Pathog. 1994 Mar;16(3):235-41 [8090081] J Bacteriol. 1995 Feb;177(3):835-8 [7836323] J Infect Dis. 1995 Apr;171(4):903-8 [7706818] Lancet. 1995 Apr 15;345(8955):949-52 [7715293] J Infect Dis. 1995 Jun;171(6):1387-98 [7769272] J Infect Dis. 1995 Sep;172(3):883-6 [7658089] Eur J Biochem. 1995 Sep 1;232(2):391-6 [7556186] Infect Immun. 1996 Jan;64(1):343-5 [8557361] Am J Epidemiol. 1996 Feb 1;143(3):263-8 [8561160] Infect Immun. 1996 Jul;64(7):2709-15 [8698499] Infect Immun. 1996 Sep;64(9):3778-85 [8751929] Carbohydr Res. 1996 Aug 26;290(1):43-58 [8805781] Vaccine. 1996 Aug;14(12):1137-42 [8911010] Vaccine. 1996 Feb;14(3):190-8 [8920699] Microbiology. 1997 Jan;143 ( Pt 1):23-34 [9025275] Clin Diagn Lab Immunol. 1997 May;4(3):264-9 [9144361] Infect Immun. 1997 Jun;65(6):2088-93 [9169736] Infect Immun. 1998 Jul;66(7):3095-9 [9632571] Arch Microbiol. 1998 Oct;170(5):339-44 [9818353] Vaccine. 1999 Jul 16;17(22):2844-52 [10438055] Biochemistry. 1999 Sep 14;38(37):12062-71 [10508410] FEBS Lett. 1983 Apr 5;154(1):209-10 [19552007] Bull World Health Organ. 1968;38(2):277-85 [5302303] Biochemistry. 1969 Oct;8(10):4074-82 [5388146] J Infect Dis. 1970 May;121(5):505-13 [4986889] J Infect Dis. 1970 May;121:Suppl 121:25+ [4912070] Prog Immunobiol Stand. 1971;5:485-91 [4633975] Anal Biochem. 1976 May 7;72:248-54 [942051] Trans R Soc Trop Med Hyg. 1979;73(1):3-9 [442179] J Exp Med. 1980 Aug 1;152(2):361-76 [6967514] Appl Microbiol Biotechnol. 1991 Oct;36(1):65-9 [1367778] J Biol Chem. 1994 Feb 11;269(6):4349-54 [8308004] J Infect Dis. 1994 Aug;170(2):278-83 [8035010] Infect Immun. 1994 Sep;62(9):3859-63 [8063402] Vaccine. 1994 Aug;12(11):1000-3 [7975839] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevention of beta-amyloid neurotoxicity by blockade of the ubiquitin-proteasome proteolytic pathway. AN - 71760246; 10936209 AB - In many neurodegenerative disorders, such as Alzheimer's disease, inclusions containing ubiquitinated proteins have been found in the brain, suggesting a pathophysiological role for ubiquitin-mediated proteasomal degradation of neuronal proteins. Here we show for the first time that the beta-amyloid fragment 1-40, which in micromolar levels causes the death of cortical neurons, also induces the ubiquitination of several neuronal proteins. Prevention of ubiquitination and inhibition of proteasome activity block the neurotoxic effect of beta-amyloid. These data suggest that beta-amyloid neurotoxicity may cause toxicity through the activation of protein degradation via the ubiquitin-proteasome pathway. These findings suggest possible new pharmacological targets for the prophylaxis and/or treatment of Alzheimer's disease and possibly for other related neurodegenerative disorders. JF - Journal of neurochemistry AU - Favit, A AU - Grimaldi, M AU - Alkon, D L AD - Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20817, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 1258 EP - 1263 VL - 75 IS - 3 SN - 0022-3042, 0022-3042 KW - Amyloid beta-Peptides KW - 0 KW - Cysteine Proteinase Inhibitors KW - Multienzyme Complexes KW - Neurotoxins KW - Peptide Fragments KW - Ubiquitins KW - amyloid beta-protein (1-40) KW - lactacystin KW - 133343-34-7 KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Cysteine Proteinase Inhibitors -- pharmacology KW - Fetus KW - Cerebral Cortex -- cytology KW - Animals KW - Cerebral Cortex -- metabolism KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Multienzyme Complexes -- metabolism KW - Peptide Fragments -- toxicity KW - Ubiquitins -- antagonists & inhibitors KW - Neurons -- metabolism KW - Ubiquitins -- metabolism KW - Acetylcysteine -- analogs & derivatives KW - Neurons -- drug effects KW - Cysteine Endopeptidases -- metabolism KW - Amyloid beta-Peptides -- toxicity KW - Neurons -- cytology KW - Acetylcysteine -- pharmacology KW - Neurotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71760246?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Prevention+of+beta-amyloid+neurotoxicity+by+blockade+of+the+ubiquitin-proteasome+proteolytic+pathway.&rft.au=Favit%2C+A%3BGrimaldi%2C+M%3BAlkon%2C+D+L&rft.aulast=Favit&rft.aufirst=A&rft.date=2000-09-01&rft.volume=75&rft.issue=3&rft.spage=1258&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 - 2000-09-12 N1 - Date created - 2000-09-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - To model a psychiatric disorder in animals: schizophrenia as a reality test. AN - 71755330; 10942847 AB - Animal modeling has been instrumental in dissecting pathophysiological mechanisms and designing more effective therapies in many areas of medicine but not so in psychiatry. The critical obstacle in modeling psychiatric disorders has been limited information about their origin and underlying neural mechanisms. Recently, with rapidly growing knowledge about the neurobiology and genetics of psychiatric disorders, animal models of these diseases are gaining popularity in psychiatric research. New models of schizophrenia mimic biological phenomena associated with the clinical condition, particularly developmental changes in the cortex, abnormalities of glutamate neurotransmission, and genetic characteristics of selected behavioral traits. The biological fidelity of some aspects of these new models suggests that they will be useful in the development of new therapies, in identifying candidate genes, and in providing new insights about pathophysiology and etiology. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Lipska, B K AU - Weinberger, D R AD - Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, NIH, IRP,., Bethesda, MD 20892-1385, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 223 EP - 239 VL - 23 IS - 3 SN - 0893-133X, 0893-133X KW - Index Medicus KW - Animals KW - Humans KW - Mental Disorders -- genetics KW - Mental Disorders -- chemically induced KW - Disease Models, Animal KW - Schizophrenia -- chemically induced KW - Schizophrenia -- genetics KW - Schizophrenia -- physiopathology KW - Mental Disorders -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71755330?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=To+model+a+psychiatric+disorder+in+animals%3A+schizophrenia+as+a+reality+test.&rft.au=Lipska%2C+B+K%3BWeinberger%2C+D+R&rft.aulast=Lipska&rft.aufirst=B&rft.date=2000-09-01&rft.volume=23&rft.issue=3&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-11 N1 - Date created - 2000-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lead effects on protamine-DNA binding. AN - 71751789; 10940971 AB - Lead impairs male fertility and may affect offspring of exposed males, but the mechanisms for this impairment are not completely clear. Protamine P1 and P2 families pack and protect mammalian sperm DNA. Human HP2 is a zinc-protein and may have an important role in fertility. As lead has affinity for zinc-containing proteins, we evaluated its ability in vitro to bind to HP2 and its effects on HP2-DNA binding. Methods and Results UV/VIS spectroscopic data indicated that HP2 binds both Pb(2+) and Zn(2+)(as chloride salts). They also provided evidence that thiol groups mainly participate for Zn(2+)-binding; however, HP2 has additional binding sites for Pb(2+). The mobility shift assay showed that lead interaction with HP2 caused a dose-dependent decrease on HP2 binding to DNA, suggesting that lead may alter chromatin stability. These in vitro results demonstrate that lead can interact with HP2 altering the DNA-protamine binding. This chemical interaction of lead with protamines may result in chromatin alterations, which in turn may lead to male fertility problems and eventually to DNA damage. Copyright 2000 Wiley-Liss, Inc. JF - American journal of industrial medicine AU - Quintanilla-Vega, B AU - Hoover, D AU - Bal, W AU - Silbergeld, E K AU - Waalkes, M P AU - Anderson, L D AD - National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. mquintan@mail.cinvestav.mx Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 324 EP - 329 VL - 38 IS - 3 SN - 0271-3586, 0271-3586 KW - Chromatin KW - 0 KW - Protamines KW - Lead KW - 2P299V784P KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Protein Binding -- drug effects KW - Humans KW - Spermatozoa KW - Chromatin -- drug effects KW - Spectrophotometry KW - Male KW - Fertility -- drug effects KW - Lead -- adverse effects KW - DNA -- metabolism KW - Protamines -- metabolism KW - Protamines -- drug effects KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71751789?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Lead+effects+on+protamine-DNA+binding.&rft.au=Quintanilla-Vega%2C+B%3BHoover%2C+D%3BBal%2C+W%3BSilbergeld%2C+E+K%3BWaalkes%2C+M+P%3BAnderson%2C+L+D&rft.aulast=Quintanilla-Vega&rft.aufirst=B&rft.date=2000-09-01&rft.volume=38&rft.issue=3&rft.spage=324&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-21 N1 - Date created - 2000-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced anticonvulsant activity of ganaxolone after neurosteroid withdrawal in a rat model of catamenial epilepsy. AN - 71748120; 10945840 AB - Perimenstrual catamenial epilepsy, the exacerbation of seizures in association with menstruation, may in part be due to withdrawal of the progesterone metabolite allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), an endogenous anticonvulsant neurosteroid that is a positive allosteric modulator of gamma-aminobutyric acid(A) receptors. Neurosteroid replacement is a potential approach to therapy, but natural neurosteroids have poor bioavailability and may be converted to metabolites with undesired progestational activity. The synthetic neuroactive steroid ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnane-20-one) is an orally active analog of allopregnanolone that is not converted to the hormonally active 3-keto form. To assess the potential of ganaxolone in the treatment of catamenial seizure exacerbations, a state of persistently high serum progesterone (pseudopregnancy) was induced in 26-day-old female rats with gonadotropins, and neurosteroids were withdrawn on postnatal day 39 with finasteride, a 5alpha-reductase inhibitor that blocks the conversion of progesterone to allopregnanolone. Finasteride treatment during pseudopregnancy results in a reduction in the threshold for pentylenetetrazol seizures. During this state of enhanced seizure susceptibility, there was a 3-fold increase in the anticonvulsant potency of ganaxolone (control ED(50) = 3.5 mg/kg; withdrawn = 1.2 mg/kg) without a change in the potency for induction of motor toxicity in the rotarod test. The plasma concentrations of ganaxolone did not differ significantly in control and withdrawn animals; the estimated plasma concentrations of ganaxolone producing 50% seizure protection were approximately 500 and approximately 225 ng/ml in control and withdrawn rats, respectively. Unlike ganaxolone, neurosteroid withdrawal was associated with a decrease in the anticonvulsant potency of diazepam (control ED(50) = 1.9 mg/kg; withdrawn = 4.1 mg/kg) and valproate (control ED(50) = 279 mg/kg; withdrawn = 460 mg/kg). The enhanced anticonvulsant potency of ganaxolone after neurosteroid withdrawal supports the use of ganaxolone as a specific treatment for perimenstrual catamenial epilepsy. JF - The Journal of pharmacology and experimental therapeutics AU - Reddy, D S AU - Rogawski, M A AD - Neuronal Excitability Section, Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1408, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 909 EP - 915 VL - 294 IS - 3 SN - 0022-3565, 0022-3565 KW - Anticonvulsants KW - 0 KW - Convulsants KW - Enzyme Inhibitors KW - Steroids KW - Finasteride KW - 57GNO57U7G KW - Valproic Acid KW - 614OI1Z5WI KW - ganaxolone KW - 98WI44OHIQ KW - Pregnanolone KW - BXO86P3XXW KW - Oxidoreductases KW - EC 1.- KW - 3-oxo-5-alpha-steroid 4-dehydrogenase (NADP(+)) KW - EC 1.3.1.22 KW - Diazepam KW - Q3JTX2Q7TU KW - Pentylenetetrazole KW - WM5Z385K7T KW - Index Medicus KW - Seizures -- chemically induced KW - Animals KW - Pseudopregnancy -- physiopathology KW - Seizures -- physiopathology KW - Diazepam -- pharmacology KW - Disease Models, Animal KW - Seizures -- drug therapy KW - Finasteride -- pharmacology KW - Oxidoreductases -- antagonists & inhibitors KW - Valproic Acid -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Enzyme Inhibitors -- pharmacology KW - Female KW - Anticonvulsants -- pharmacology KW - Epilepsy -- physiopathology KW - Steroids -- antagonists & inhibitors KW - Anticonvulsants -- toxicity KW - Pregnanolone -- pharmacology KW - Menstruation KW - Epilepsy -- drug therapy KW - Pregnanolone -- analogs & derivatives KW - Pregnanolone -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71748120?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Enhanced+anticonvulsant+activity+of+ganaxolone+after+neurosteroid+withdrawal+in+a+rat+model+of+catamenial+epilepsy.&rft.au=Reddy%2C+D+S%3BRogawski%2C+M+A&rft.aulast=Reddy&rft.aufirst=D&rft.date=2000-09-01&rft.volume=294&rft.issue=3&rft.spage=909&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 - 2000-09-12 N1 - Date created - 2000-09-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Properties of various Rho1 mutant alleles of Cryptococcus neoformans. AN - 71744394; 10940044 AB - The RHO1 homologue of Cryptococcus neoformans complemented Saccharomyces cerevisiae rho1 mutations. The results of overexpression and site-specific mutagenesis of CnRHO1 in C. neoformans and S. cerevisiae indicated that although CnRHO1 could functionally substitute for the RHO1 gene of S. cerevisiae, mutants of cnrho1 manifested unique features in certain aspects. JF - Journal of bacteriology AU - Chang, Y C AU - Penoyer, L A AD - Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. yc3z@nih.gov Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 4987 EP - 4991 VL - 182 IS - 17 SN - 0021-9193, 0021-9193 KW - DNA, Fungal KW - 0 KW - Saccharomyces cerevisiae Proteins KW - Glucosyltransferases KW - EC 2.4.1.- KW - glucan synthase KW - RHO1 protein, S cerevisiae KW - EC 3.6.5.2 KW - rho GTP-Binding Proteins KW - Index Medicus KW - Saccharomyces cerevisiae -- genetics KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Temperature KW - Molecular Sequence Data KW - Glucosyltransferases -- metabolism KW - Gene Expression KW - Cloning, Molecular KW - Cryptococcus neoformans -- enzymology KW - Alleles KW - Genes, Fungal KW - rho GTP-Binding Proteins -- genetics KW - rho GTP-Binding Proteins -- physiology KW - Cryptococcus neoformans -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71744394?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Properties+of+various+Rho1+mutant+alleles+of+Cryptococcus+neoformans.&rft.au=Chang%2C+Y+C%3BPenoyer%2C+L+A&rft.aulast=Chang&rft.aufirst=Y&rft.date=2000-09-01&rft.volume=182&rft.issue=17&rft.spage=4987&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 - 2000-09-21 N1 - Date created - 2000-09-21 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF242351; GENBANK N1 - SuppNotes - Cited By: J Exp Med. 2000 Mar 6;191(5):871-82 [10704467] Yeast. 1999 Aug;15(11):1133-9 [10455236] Proc Natl Acad Sci U S A. 1986 Aug;83(16):5808-12 [2942941] Proc Natl Acad Sci U S A. 1987 Feb;84(3):779-83 [3543936] Curr Top Med Mycol. 1985;1:24-56 [3916769] Carbohydr Res. 1990 Apr 2;198(1):23-38 [2191777] Nature. 1991 Jan 10;349(6305):117-27 [1898771] Antimicrob Agents Chemother. 1992 Aug;36(8):1648-57 [1416847] J Cell Biol. 1994 Jun;125(5):1077-93 [8195291] Mol Cell Biol. 1994 Jul;14(7):4912-9 [8007987] J Biol Chem. 1994 Dec 9;269(49):31267-74 [7983071] Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12907-11 [7528927] Annu Rev Microbiol. 1994;48:471-97 [7826015] EMBO J. 1995 Jan 16;14(2):292-302 [7835340] Yeast. 1995 Jan;11(1):25-32 [7762298] Trends Biochem Sci. 1995 Jun;20(6):227-31 [7543224] Eur J Biochem. 1995 Aug 1;231(3):845-54 [7649185] Mol Cell Biol. 1995 Oct;15(10):5671-81 [7565718] Microbiol Rev. 1995 Sep;59(3):345-86 [7565410] EMBO J. 1995 Dec 1;14(23):5931-8 [8846785] Science. 1996 Apr 12;272(5259):277-9 [8602514] Science. 1996 Apr 12;272(5259):279-81 [8602515] J Biol Chem. 1996 Apr 19;271(16):9193-6 [8621575] J Biol Chem. 1996 Jun 14;271(24):14604-9 [8662910] Mol Cell Biol. 1996 Aug;16(8):4396-403 [8754840] Trends Biochem Sci. 1996 May;21(5):178-81 [8871402] EMBO J. 1996 Sep 2;15(17):4584-91 [8887550] EMBO J. 1996 Nov 15;15(22):6060-8 [8947028] Science. 1997 Apr 4;276(5309):118-22 [9082982] J Med Vet Mycol. 1997 Mar-Apr;35(2):79-86 [9147267] Antimicrob Agents Chemother. 1997 Sep;41(9):1957-60 [9303393] J Bacteriol. 1997 Dec;179(24):7734-41 [9401032] Microbiol Mol Biol Rev. 1998 Mar;62(1):130-80 [9529890] J Bacteriol. 1999 Jan;181(2):444-53 [9882657] J Antibiot (Tokyo). 1982 Feb;35(2):203-9 [7042670] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure and dynamic properties of a glucocorticoid receptor-induced chromatin transition. AN - 71735253; 10938123 AB - Activation of the mouse mammary tumor virus (MMTV) promoter by the glucocorticoid receptor (GR) is associated with a chromatin structural transition in the B nucleosome region of the viral long terminal repeat (LTR). Recent evidence indicates that this transition extends upstream of the B nucleosome, encompassing a region larger than a single nucleosome (G. Fragoso, W. D. Pennie, S. John, and G. L. Hager, Mol. Cell. Biol. 18:3633-3644). We have reconstituted MMTV LTR DNA into a polynucleosome array using Drosophila embryo extracts. We show binding of purified GR to specific GR elements within a large, multinucleosome array and describe a GR-induced nucleoprotein transition that is dependent on ATP and a HeLa nuclear extract. Previously uncharacterized GR binding sites in the upstream C nucleosome region are involved in the extended region of chromatin remodeling. We also show that GR-dependent chromatin remodeling is a multistep process; in the absence of ATP, GR binds to multiple sites on the chromatin array and prevents restriction enzyme access to recognition sites. Upon addition of ATP, GR induces remodeling and a large increase in access to enzymes sites within the transition region. These findings suggest a dynamic model in which GR first binds to chromatin after ligand activation, recruits a remodeling activity, and is then lost from the template. This model is consistent with the recent description of a "hit-and-run" mechanism for GR action in living cells (J. G. McNally, W. G. Müller, D. Walker, and G. L. Hager, Science 287:1262-1264, 2000). JF - Molecular and cellular biology AU - Fletcher, T M AU - Ryu, B W AU - Baumann, C T AU - Warren, B S AU - Fragoso, G AU - John, S AU - Hager, G L AD - Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-5055, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 6466 EP - 6475 VL - 20 IS - 17 SN - 0270-7306, 0270-7306 KW - Chromatin KW - 0 KW - Ligands KW - Nucleosomes KW - Receptors, Glucocorticoid KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Deoxyribonuclease I KW - EC 3.1.21.1 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Plasmids -- metabolism KW - Cell Nucleus -- metabolism KW - Dose-Response Relationship, Drug KW - HeLa Cells KW - Humans KW - Nucleosomes -- metabolism KW - Mice KW - Protein Binding KW - Hydrolysis KW - Mammary Tumor Virus, Mouse -- genetics KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Transfection KW - Deoxyribonuclease I -- metabolism KW - Adenosine Triphosphate -- metabolism KW - Electrophoresis, Agar Gel KW - CHO Cells KW - Terminal Repeat Sequences KW - Cricetinae KW - Chromatin -- metabolism KW - Receptors, Glucocorticoid -- metabolism KW - Receptors, Glucocorticoid -- genetics KW - Chromatin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71735253?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Structure+and+dynamic+properties+of+a+glucocorticoid+receptor-induced+chromatin+transition.&rft.au=Fletcher%2C+T+M%3BRyu%2C+B+W%3BBaumann%2C+C+T%3BWarren%2C+B+S%3BFragoso%2C+G%3BJohn%2C+S%3BHager%2C+G+L&rft.aulast=Fletcher&rft.aufirst=T&rft.date=2000-09-01&rft.volume=20&rft.issue=17&rft.spage=6466&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 - 2000-09-21 N1 - Date created - 2000-09-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1991 Nov 29;67(5):977-86 [1683601] Nucleic Acids Res. 1991 Apr 11;19(7):1563-9 [1851294] Mol Cell Biol. 1992 May;12(5):2241-9 [1569951] EMBO J. 1993 Nov;12(11):4279-90 [8223438] Mol Cell Biol. 1994 Jan;14(1):32-41 [8264599] J Steroid Biochem Mol Biol. 1993 Dec;47(1-6):1-10 [8274422] EMBO J. 1994 Jan 15;13(2):373-9 [8313882] Cold Spring Harb Symp Quant Biol. 1993;58:63-71 [7956078] J Biol Chem. 1994 Dec 16;269(50):31983-90 [7989375] Mol Cell Biol. 1995 Apr;15(4):2125-34 [7891707] Biophys J. 1995 Feb;68(2):402-26 [7696496] EMBO J. 1995 Apr 18;14(8):1727-36 [7737124] EMBO J. 1995 Apr 18;14(8):1737-51 [7737125] J Virol. 1995 Jun;69(6):3759-70 [7745724] Genes Dev. 1995 Aug 1;9(15):1933-47 [7649476] J Mol Biol. 1995 Oct 27;253(3):453-72 [7473727] Cell. 1995 Dec 15;83(6):1011-20 [8521501] J Biol Chem. 1996 Jan 5;271(1):153-9 [8550551] Proc Natl Acad Sci U S A. 1996 May 14;93(10):5072-7 [8643531] J Biol Chem. 1996 May 10;271(19):11434-40 [8626700] Genes Dev. 1996 Sep 1;10(17):2131-44 [8804308] Mol Cell Biol. 1997 Feb;17(2):895-905 [9001244] Nature. 1997 Aug 7;388(6642):598-602 [9252192] Mol Cell Biol. 1997 Sep;17(9):5275-87 [9271405] J Biol Chem. 1997 Oct 31;272(44):27493-6 [9346875] Nature. 1998 May 7;393(6680):88-91 [9590696] Mol Cell Biol. 1998 Jun;18(6):3633-44 [9584204] Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):1995-2000 [10051583] Mol Cell. 1999 Jul;4(1):45-54 [10445026] Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9485-90 [10449719] Nucleic Acids Res. 1999 Aug 15;27(16):e11 [10454648] Genes Dev. 1999 Sep 15;13(18):2369-74 [10500094] Nature. 1991 Aug 8;352(6335):497-505 [1865905] Science. 2000 Feb 18;287(5456):1262-5 [10678832] Cell. 1983 Dec;35(2 Pt 1):381-92 [6317184] Cell. 1984 Aug;38(1):29-38 [6088072] Cell. 1987 Jan 30;48(2):261-70 [3026639] EMBO J. 1987 Aug;6(8):2321-8 [2822386] DNA. 1988 Jan-Feb;7(1):47-55 [3349904] EMBO J. 1988 May;7(5):1403-10 [2842149] EMBO J. 1988 Oct;7(10):3073-9 [2846275] Nature. 1988 Dec 1;336(6198):427-8 [3194030] Cell. 1990 Mar 9;60(5):719-31 [2155706] Biotechniques. 1988 May;6(5):454-8 [2908509] Mol Endocrinol. 1990 Jan;4(1):162-70 [2157974] Nucleic Acids Res. 1990 Apr 25;18(8):2017-24 [2159634] J Biol Chem. 1990 Oct 5;265(28):17222-9 [2170368] Mol Cell Biol. 1990 Nov;10(11):5822-9 [1700274] Mol Endocrinol. 1987 Sep;1(9):659-65 [2856414] Mol Cell Biol. 1991 Feb;11(2):688-98 [1846670] Science. 1992 Mar 20;255(5051):1573-6 [1347958] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Economic evaluation of traffic safety measures for transport companies. AN - 71227916; 10908141 AB - This paper addresses the economic feasibility of measures to reduce the material damage of transport companies. Results are presented of a series of interviews among transport companies as well as from a postal questionnaire survey. Next, calculations are presented for three types of companies: a small family company, a large family company and a large formalised company. From the viewpoint of costs and benefits, damage prevention measures appear to be particularly interesting to larger companies. Small companies, being the largest group, tend to have an informal culture in which measures are less effective. Especially those measures for which no large investments are needed, which influence the behaviour of drivers and need not to be contracted out, are perceived as attractive by the transport companies. JF - Accident; analysis and prevention AU - Rienstra, S A AU - Rietveld, P AU - Lindeijer, J E AD - Transport Division, Netherlands Economic Institute, Rotterdam. rienstra@nei.nl Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 679 EP - 687 VL - 32 IS - 5 SN - 0001-4575, 0001-4575 KW - Index Medicus KW - Organizational Policy KW - Humans KW - Cost-Benefit Analysis KW - Surveys and Questionnaires KW - Netherlands KW - Accidents, Occupational -- prevention & control KW - Safety Management -- economics KW - Accidents, Traffic -- prevention & control KW - Accidents, Traffic -- economics KW - Accidents, Occupational -- economics KW - Motor Vehicles -- economics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71227916?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Accident%3B+analysis+and+prevention&rft.atitle=Economic+evaluation+of+traffic+safety+measures+for+transport+companies.&rft.au=Rienstra%2C+S+A%3BRietveld%2C+P%3BLindeijer%2C+J+E&rft.aulast=Rienstra&rft.aufirst=S&rft.date=2000-09-01&rft.volume=32&rft.issue=5&rft.spage=679&rft.isbn=&rft.btitle=&rft.title=Accident%3B+analysis+and+prevention&rft.issn=00014575&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-02 N1 - Date created - 2001-01-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serum withdrawal potentiates the toxic effects of methamphetamine in vitro. AN - 70599096; 11085311 AB - Methamphetamine (METH) has been shown to cause neurotoxic damage both in vitro and in vivo. The mechanisms of action are thought to involve the production of pathophysiologic concentration of free radicals. The present study was undertaken to assess the toxic effects of METH caused dose-dependent increased production of reactive oxygen species (ROS) and cell death. Cell death caused by METH was characterized by cytoplasmic vacuolar formation, shrinkage of cytoplasm and nuclear dissolution. Flow cytometric evaluation also revealed that this toxin causes changes similar to those observed in cells undergoing apoptosis. When taken together these observations suggest the METH can cause these cells to die via apoptosis. Further experiments indicated that growth of these cells in low (1%) serum or in the absence of serum markedly enhanced the apoptotic effects of METH. These data provide further support for the ideas that METH can cause ROS-mediated apoptosis. JF - Annals of the New York Academy of Sciences AU - Cadet, J L AU - Ordonez, S AD - Molecular Neuropsychiatry Section, NIH/NIDA, Intramural Research Program, Baltimore, Maryland 21224, USA. jcadet@intra.nida.nih.gov Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 82 EP - 91 VL - 914 SN - 0077-8923, 0077-8923 KW - Central Nervous System Stimulants KW - 0 KW - Reactive Oxygen Species KW - Methamphetamine KW - 44RAL3456C KW - Index Medicus KW - Rats KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Cell Count KW - Dose-Response Relationship, Drug KW - In Vitro Techniques KW - Apoptosis -- drug effects KW - Mesencephalon -- cytology KW - Time Factors KW - Cell Line KW - In Situ Nick-End Labeling -- methods KW - Flow Cytometry -- methods KW - Serum -- metabolism KW - Central Nervous System Stimulants -- toxicity KW - Neurons -- drug effects KW - Methamphetamine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70599096?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Serum+withdrawal+potentiates+the+toxic+effects+of+methamphetamine+in+vitro.&rft.au=Cadet%2C+J+L%3BOrdonez%2C+S&rft.aulast=Cadet&rft.aufirst=J&rft.date=2000-09-01&rft.volume=914&rft.issue=&rft.spage=82&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 - 2006-01-04 N1 - Date created - 2005-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serotonin transporters, serotonin release, and the mechanism of fenfluramine neurotoxicity. AN - 70597706; 11085319 AB - Administration of d,l-fenfluramine (FEN), or the more active isomer d-fenfluramine (dFEN), causes long-term depletion of forebrain serotonin (5-HT) in animals. The mechanism underlying FEN-induced 5-HT depletion is not known, but appears to involve 5-HT transporters (SERTs) in the brain. Some investigators have postulated that 5-HT release evoked by FEN is responsible for the deleterious effects of the drug. In the present work, we sought to examine the relationship between drug-induced 5-HT release and long-term 5-HT depletion. The acute 5-HT-releasing effects of dFEN and the non-amphetamine 5-HT agonist 1-(m-chlorophenyl)piperazine (mCPP) were evaluated using in vivo microdialysis in rat nucleus accumbens. The ability of dFEN and mCPP to interact with SERTs was assessed using in vitro assays for [3H]-transmitter uptake and release in rat forebrain synaptosomes. Drugs were subsequently tested for potential long-lasting effects on brain tissue 5-HT after repeated dosing (2.7 or 8.1 mg/kg, ip x 4). dFEN and mCPP were essentially equipotent in their ability to stimulate acute 5-HT release in vivo and in vitro. Both drugs produced very selective effects on 5-HT with minimal effects on dopamine. Interestingly, when dFEN or mCPP was administered repeatedly, only dFEN caused long-term 5-HT depletion in the forebrain at 2 weeks later. These data suggest that acute 5-HT release per se does not mediate the long-term 5-HT depletion associated with dFEN. We hypothesize that dFEN and other amphetamine-type releasers gain entrance into 5-HT neurons via interaction with SERTs. Once internalized in nerve terminals, drugs accumulate to high concentrations, causing damage to cells. The relevance of this hypothesis for explaining clinical side effects of FEN and dFEN, such as cardiac valvulopathy and primary pulmonary hypertension, warrants further study. JF - Annals of the New York Academy of Sciences AU - Baumann, M H AU - Ayestas, M A AU - Dersch, C M AU - Partilla, J S AU - Rothman, R B AD - Medications Development Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. mbaumann@intra.nida.nih.gov Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 172 EP - 186 VL - 914 SN - 0077-8923, 0077-8923 KW - Dopamine Uptake Inhibitors KW - 0 KW - Piperazines KW - Serotonin Receptor Agonists KW - Serotonin Uptake Inhibitors KW - Tritium KW - 10028-17-8 KW - Fenfluramine KW - 2DS058H2CF KW - Serotonin KW - 333DO1RDJY KW - vanoxerine KW - 90X28IKH43 KW - 1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine KW - 9J9974WIBA KW - 1-(3-chlorophenyl)piperazine KW - REY0CNO998 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Tritium -- pharmacokinetics KW - Serotonin Receptor Agonists -- administration & dosage KW - Animals KW - Analysis of Variance KW - Dose-Response Relationship, Drug KW - Brain Chemistry -- drug effects KW - Disease Models, Animal KW - Dopamine -- metabolism KW - Piperazines -- pharmacology KW - Piperazines -- administration & dosage KW - Microdialysis -- methods KW - Rats KW - Electrochemistry -- methods KW - Rats, Sprague-Dawley KW - Chromatography, High Pressure Liquid -- methods KW - Models, Neurological KW - Male KW - Dopamine Uptake Inhibitors -- pharmacology KW - Fenfluramine -- administration & dosage KW - Serotonin Uptake Inhibitors -- administration & dosage KW - Brain -- drug effects KW - Brain -- anatomy & histology KW - Brain -- metabolism KW - Neurotoxicity Syndromes -- metabolism KW - Serotonin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70597706?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Serotonin+transporters%2C+serotonin+release%2C+and+the+mechanism+of+fenfluramine+neurotoxicity.&rft.au=Baumann%2C+M+H%3BAyestas%2C+M+A%3BDersch%2C+C+M%3BPartilla%2C+J+S%3BRothman%2C+R+B&rft.aulast=Baumann&rft.aufirst=M&rft.date=2000-09-01&rft.volume=914&rft.issue=&rft.spage=172&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 - 2006-01-04 N1 - Date created - 2005-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methamphetamine dependence: medication development efforts based on the dual deficit model of stimulant addiction. AN - 70597026; 11085310 AB - Converging lines of evidence indicate that withdrawal from prolonged exposure to stimulants and alcohol results in synaptic deficits of both dopamine (DA) and serotonin (5-HT). According to the dual deficit model proposed by the authors, DA dysfunction during cocaine or alcohol withdrawal underlies anhedonia and psychomotor retardation, whereas 5-HT dysfunction gives rise to depressed mood, obsessional thoughts, and lack of impulse control. This model predicts that pharmacotherapies which correct only one of the two neurochemical deficits will not be effective. On the other hand, pharmacotherapies which "correct" both of the proposed DA and 5-HT abnormalities should be effective in treating stimulant and alcohol dependence. This paper reviews two approaches, based on the dual deficit model, taken by our laboratory to develop medications to treat stimulant abuse. JF - Annals of the New York Academy of Sciences AU - Rothman, R B AU - Partilla, J S AU - Dersch, C M AU - Carroll, F I AU - Rice, K C AU - Baumann, M H AD - Clinical Psychopharmacology Section, Intramural Research Program, NIDA, NIH, Baltimore, Maryland 21224, USA. rrothman@intra.nida.nih.gov Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 71 EP - 81 VL - 914 SN - 0077-8923, 0077-8923 KW - Biogenic Amines KW - 0 KW - Neurotransmitter Uptake Inhibitors KW - Tritium KW - 10028-17-8 KW - Methamphetamine KW - 44RAL3456C KW - Index Medicus KW - Tritium -- pharmacokinetics KW - Rats KW - Animals KW - Drug Interactions KW - Synaptosomes -- drug effects KW - Dose-Response Relationship, Drug KW - Neurotransmitter Uptake Inhibitors -- pharmacology KW - Disease Models, Animal KW - Inhibitory Concentration 50 KW - Synaptosomes -- metabolism KW - Behavior, Addictive -- chemically induced KW - Biogenic Amines -- pharmacokinetics KW - Behavior, Addictive -- metabolism KW - Methamphetamine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70597026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Methamphetamine+dependence%3A+medication+development+efforts+based+on+the+dual+deficit+model+of+stimulant+addiction.&rft.au=Rothman%2C+R+B%3BPartilla%2C+J+S%3BDersch%2C+C+M%3BCarroll%2C+F+I%3BRice%2C+K+C%3BBaumann%2C+M+H&rft.aulast=Rothman&rft.aufirst=R&rft.date=2000-09-01&rft.volume=914&rft.issue=&rft.spage=405&rft.isbn=&rft.btitle=&rft.title=PharmacoEconomics&rft.issn=11707690&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-01-04 N1 - Date created - 2005-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - IL-4 receptor-directed cytotoxin for therapy of AIDS-associated KS tumors. AN - 70543893; 12937611 AB - AIDS-associated Kaposi's sarcoma (AIDS-KS) represents one of the most common malignancies associated with human immunodeficiency virus infection. To target effective therapeutic agents, we have discovered that AIDS-KS cells express high-affinity receptors for interleukin-4 (IL-4), a pleiotropic immune regulatory cytokine. Molecular studies have revealed that AIDS-KS cells express type II IL-4 receptors, in which IL-4 forms a productive complex with primary IL-4 binding protein (IL-4R beta, also known as IL-4R alpha) and a shared subunit between IL-4 and IL-13R systems (IL-13R alpha', also known as IL-13R alpha 1). A recombinant fusion protein composed of IL-4 and a mutated form of a powerful bacterial toxin called Pseudomonas exotoxin (PE)--the fusion protein is termed IL4(3837)-PE38KDEL or cpIL4-PE--was found to be highly and specifically cytotoxic to AIDS-KS cells in vitro. Normal human immune cells (e.g., resting T and B cells and monocytes) or endothelial cells, a possible precursor of AIDS-KS, expressed low numbers of IL-4R and showed little or no sensitivity to cpIL4-PE. Administration of cpIL4-PE in nude mice with established subcutaneously growing AIDS-KS tumors produced remarkable antitumor activity in a dose-dependent manner with the highest dose exhibiting complete responses without any visible toxicity. KS tumors produced metabolic changes including cachexia, hypoglycemia and lymphopenia, all of which were prevented by cpIL4-PE treatment. These studies indicate that cpIL4-PE is a promising experimental therapeutic agent for treatment of AIDS-KS. JF - Drug news & perspectives AU - Puri, R K AD - Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 395 EP - 402 VL - 13 IS - 7 SN - 0214-0934, 0214-0934 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70543893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+news+%26+perspectives&rft.atitle=IL-4+receptor-directed+cytotoxin+for+therapy+of+AIDS-associated+KS+tumors.&rft.au=Puri%2C+R+K&rft.aulast=Puri&rft.aufirst=R&rft.date=2000-09-01&rft.volume=13&rft.issue=7&rft.spage=395&rft.isbn=&rft.btitle=&rft.title=Drug+news+%26+perspectives&rft.issn=02140934&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-07 N1 - Date created - 2003-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Concordance between Parent Reports of Children's Mental Health Services and Service Records: The Services Assessment for Children and Adolescents (SACA) AN - 61524399; 200201554 AB - The concordance between parent reports of children's mental health services & medical & administrative service records were assessed in a field test of the Services Assessment for Children & Adolescents (SACA) interview instrument. Service use reports from primary caregivers, usually mothers, for their child's emotional or behavioral problems were compared against inpatient, outpatient, & school records in Saint Louis, one of the pilot sites for the Multi-Site Study of Service Use, Need, Outcomes & Costs in Child & Adolescent Populations (UNOCCAP). A global "any use" service variable, comprised of inpatient, outpatient, & school reports, yielded an overall service use concordance kappa of .76 between parent reports & records. Parent reports of inpatient hospitalization services using the SACA yielded the highest agreement with medical records, with kappa statistics of 1.00 for use of any inpatient hospital care & for medication use. Parent reports of specific inpatient services concurred with medical records more moderately, yielding kappas from .50 to .66. Reports of any outpatient mental health services yielded variable rates of agreement, with kappas ranging from .67 for any use of outpatient care, to .66 for medication use, to negligible kappas for specific treatments. Parent reports of school services were weakly related to records for most services, except for moderate agreement (.48) on placement in special classrooms for emotional or behavioral problems. Family burden or impact discriminated more powerfully than other variables between respondents who concurred with records & those who did not. 5 Tables, 24 References. Adapted from the source document. JF - Journal of Child and Family Studies AU - Hoagwood, Kimberly AU - Horwitz, Sarah AU - Stiffman, Arlene AU - Weisz, John AU - Bean, Donna AU - Rae, Donald AU - Compton, Wilson AU - Cottler, Linda AU - Bickman, Leonard AU - Leaf, Philip AD - National Instit Mental Health, Rockville, MD e-mail:khoagwoo@mail.nih.gov Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 315 EP - 331 VL - 9 IS - 3 SN - 1062-1024, 1062-1024 KW - Reports KW - Mental Health Services KW - Records (Documents) KW - Parents KW - Children KW - Adolescents KW - article KW - 6142: mental & emotional health problems KW - 6143: child & family welfare UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61524399?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Child+and+Family+Studies&rft.atitle=Concordance+between+Parent+Reports+of+Children%27s+Mental+Health+Services+and+Service+Records%3A+The+Services+Assessment+for+Children+and+Adolescents+%28SACA%29&rft.au=Hoagwood%2C+Kimberly%3BHorwitz%2C+Sarah%3BStiffman%2C+Arlene%3BWeisz%2C+John%3BBean%2C+Donna%3BRae%2C+Donald%3BCompton%2C+Wilson%3BCottler%2C+Linda%3BBickman%2C+Leonard%3BLeaf%2C+Philip&rft.aulast=Hoagwood&rft.aufirst=Kimberly&rft.date=2000-09-01&rft.volume=9&rft.issue=3&rft.spage=315&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+and+Family+Studies&rft.issn=10621024&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Last updated - 2016-09-28 N1 - CODEN - JCFSES N1 - SubjectsTermNotLitGenreText - Mental Health Services; Children; Adolescents; Parents; Records (Documents); Reports ER - TY - JOUR T1 - The Link between Family History and Early Onset Alcoholism: Earlier Initiation of Drinking or More Rapid Development of Dependence? AN - 61458573; 200100827 AB - Using cross-sectional, retrospective data from a large, nationally representative sample of US adults, discrete time proportional hazards models were used to assess the effects of family history saturation (% of alcoholic first- & second-degree relatives) on: (1) the risk of initiating drinking among all adults (N = 42,862; 58.4% female); & (2) the risk of progressing from initiation of drinking to onset of dependence among lifetime drinkers (N = 27,616; 50.7% male). Models were estimated for different time periods, to see if the effect of family history saturation varied over time in a manner suggestive of a stronger association with early onset dependence. The positive effect of family history saturation on the risk of initiating drinking was strongest prior to age 15 & declined steadily with increasing age. It was slightly weaker for men than women. After controlling for early initiation of drinking, the direct positive effect of family history saturation on the risk of progressing to dependence increased over time & was slightly reduced among individuals who started drinking before age 18. The indirect effect of family history on the risk of developing dependence, via its effect on early drinking as a risk factor for dependence, was strongest in the interval from 3 to 9 years after initiation of drinking. The association between family history & early onset alcoholism appears to be driven most clearly by family history, predicting earlier initiation of drinking. While supporting the possibility of genetic effects via dopaminergic & serotonergic function, these findings also suggest that environmental factors may play an important part in helping to explain the association between family history & early onset alcoholism. 5 Tables, 55 References. Adapted from the source document. JF - Journal of Studies on Alcohol AU - Dawson, Deborah A AD - Division Biometry & Epidemiology, National Instit Alcohol Abuse & Alcoholism, National Instits Health, Bethesda, MD ddawson@willco.niaa.nih.gov Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 637 EP - 646 VL - 61 IS - 5 SN - 0096-882X, 0096-882X KW - Alcoholism KW - Drinking Behavior KW - United States of America KW - Social Background KW - Adults KW - article KW - 6129: addiction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61458573?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Studies+on+Alcohol&rft.atitle=The+Link+between+Family+History+and+Early+Onset+Alcoholism%3A+Earlier+Initiation+of+Drinking+or+More+Rapid+Development+of+Dependence%3F&rft.au=Dawson%2C+Deborah+A&rft.aulast=Dawson&rft.aufirst=Deborah&rft.date=2000-09-01&rft.volume=61&rft.issue=5&rft.spage=637&rft.isbn=&rft.btitle=&rft.title=Journal+of+Studies+on+Alcohol&rft.issn=0096882X&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Last updated - 2016-09-28 N1 - CODEN - JSALDP N1 - SubjectsTermNotLitGenreText - Alcoholism; Drinking Behavior; Social Background; United States of America; Adults ER - TY - JOUR T1 - Trait Psychology and the Revival of Personality and Culture Studies AN - 60457130; 200307106 AB - Personality & culture studies have largely disappeared since the 1960s, but progress in trait psychology makes their revival feasible. A review of evidence on the consensual validity, longitudinal stability, heritability, & structure of personality traits suggests new approaches to old issues. At the transcultural level, claims of universality are addressed. At the intercultural level, associations are sought between mean levels of personality traits & corresponding culture-level variables; cultural institutions may be either causes or effects of personality. At the intracultural level, culture-specific manifestations of universal traits are documented. The new discipline of personality traits & culture draws on multiple methodologies to understand human nature in social context. 89 References. [Copyright 2000 Sage Publications, Inc.] JF - American Behavioral Scientist AU - Mccrae, Robert R AD - Gerontology Research Center, National Instit Aging, National Instits Health jeffm@lpc.grc.nia.nih.gov Y1 - 2000/09// PY - 2000 DA - September 2000 SP - 10 EP - 31 VL - 44 IS - 1 SN - 0002-7642, 0002-7642 KW - Cultural Relativism KW - Culture KW - Personality Traits KW - Psychological Research KW - Sociology of Culture KW - Cultural Universals KW - Crosscultural Differences KW - article KW - 0312: social psychology; personality & social roles (individual traits, social identity, adjustment, conformism, & deviance) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/60457130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Behavioral+Scientist&rft.atitle=Trait+Psychology+and+the+Revival+of+Personality+and+Culture+Studies&rft.au=Mccrae%2C+Robert+R&rft.aulast=Mccrae&rft.aufirst=Robert&rft.date=2000-09-01&rft.volume=44&rft.issue=1&rft.spage=10&rft.isbn=&rft.btitle=&rft.title=American+Behavioral+Scientist&rft.issn=00027642&rft_id=info:doi/10.1177_0002764200044001003 LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Last updated - 2016-09-28 N1 - SubjectsTermNotLitGenreText - Personality Traits; Culture; Cultural Relativism; Cultural Universals; Psychological Research; Sociology of Culture; Crosscultural Differences DO - http://dx.doi.org/10.1177_0002764200044001003 ER - TY - JOUR T1 - Advances in skin gene therapy AN - 20368579; 9051911 AB - Specific anatomical and biological properties make the skin a very interesting target organ for gene therapy approaches. Different cell types of the epidermis, such as keratinocytes, melanocytes, or dendritic cells, can be genetically modified to treat a broad spectrum of diseases, including genetically inherited skin disorders, tumour diseases, metabolic disorders and infectious diseases. The easy accessibility of skin suggests that different methods for gene delivery can be pursued, depending on the desired application. The approach used to deliver DNA to the skin will influence not only the efficiency of DNA delivery, but also the level and duration of transgene expression. Furthermore, the desired biological effect will also influence the decision of which gene transfer method is the best choice. Among the current challenges of cutaneous gene therapy are: optimising the efficiency of direct in vivo gene delivery; targeting specific epidermal cells, including keratinocyte stem cells; achieving sustained gene expression and regulating gene expression in vivo. This review summarises recent advances in the field of skin gene therapy and evaluates possible strategies to overcome obstacles and achieve successful clinical applications of skin gene therapy. JF - Expert Opinion on Investigational Drugs AU - Pfutzner, W AU - Vogel, J C AD - National Institute of Health, Dermatology Branch, National Cancer Institute, 6130 Executive Blvd, Bethesda, MD 20892-1908, USA Y1 - 2000/09// PY - 2000 DA - Sep 2000 SP - 2069 EP - 2083 PB - Ashley Publications Ltd., Unitec House, 3rd Floor 2 Albert Place, Finchley Central London, N3 1QB UK, [URL:http://ernesto.ashley-pub.com/] VL - 9 IS - 9 SN - 1354-3784, 1354-3784 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - DNA vaccination KW - epidermis KW - genetic skin diseases KW - skin gene therapy KW - Skin KW - Gene therapy KW - Metabolic disorders KW - Therapeutic applications KW - Melanocytes KW - Epidermis KW - Dendritic cells KW - Stem cells KW - Infectious diseases KW - Skin diseases KW - Gene transfer KW - Reviews KW - DNA KW - Keratinocytes KW - W 30905:Medical Applications KW - G 07730:Development & Cell Cycle UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20368579?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+Opinion+on+Investigational+Drugs&rft.atitle=Advances+in+skin+gene+therapy&rft.au=Pfutzner%2C+W%3BVogel%2C+J+C&rft.aulast=Pfutzner&rft.aufirst=W&rft.date=2000-09-01&rft.volume=9&rft.issue=9&rft.spage=2069&rft.isbn=&rft.btitle=&rft.title=Expert+Opinion+on+Investigational+Drugs&rft.issn=13543784&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-03-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Skin; Gene therapy; Metabolic disorders; Therapeutic applications; Melanocytes; Dendritic cells; Epidermis; Stem cells; Skin diseases; Infectious diseases; Gene transfer; Reviews; DNA; Keratinocytes ER - TY - JOUR T1 - High ammonia tolerance in fishes of the family Batrachoididae (Toadfish and Midshipmen). AN - 1859330640; 10958955 AB - Three fish species of the family Batrachoididae, the gulf toadfish (Opsanus beta), the oyster toadfish (Opsanus tau), and the plainfin midshipman (Porichthys notatus) demonstrated exceptionally high tolerances to elevated water ammonia with 96-h LC50 values of 9.75, 19.72 and 6 mM total ammonia, respectively. Using pH values we calculated the corresponding unionized ammonia (NH(3)) values to be 519, 691 and 101 µM, respectively. These values are well above typical values for most teleost fishes, but close to those of ureotelic fish examined to date. Following sublethal high ammonia exposure (HAE) blood and tissue (brain, liver and muscle) sampling confirmed that internal ammonia levels rose substantially in all three species, suggesting that they were not simply avoiding toxicity by impermeance to ammonia. The three species of batrachoidids can be characterized in the following manner with respect to the inabilities to synthesize and excrete urea, based on these studies and prior research: O. beta (fully ureotelic)>O. tau (moderately ureotelic)>P. notatus (ammoniotelic). While some of the high ammonia tolerance for O. beta and O. tau can be explained by their ability to detoxify it to urea, other mechanisms must be at play for P. notatus. Further experiments determined that all three species possess rather high activities of glutamine synthetase (GSase) in brain especially (60-180 U g(-1)), that glutamine accumulates in many tissues, and that LC50 values are correlated positively with brain GSase activity. Taken together, our results suggest that alternative/additional mechanisms for ammonia detoxification via urea synthesis must be considered to explain the exceptionally high ammonia tolerance of this group. JF - Aquatic toxicology (Amsterdam, Netherlands) AU - Wang AU - Walsh AD - Division of Marine Biology and Fisheries, NIEHS Marine and Freshwater Biomedical Sciences Center, Rosenstiel School of Marine and Atmospheric Science, University of Miami, 4600 Rickenbacker Causeway, 33149, Miami, FL, USA Y1 - 2000/09/01/ PY - 2000 DA - 2000 Sep 01 SP - 205 EP - 219 VL - 50 IS - 3 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859330640?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Aquatic+toxicology+%28Amsterdam%2C+Netherlands%29&rft.atitle=High+ammonia+tolerance+in+fishes+of+the+family+Batrachoididae+%28Toadfish+and+Midshipmen%29.&rft.au=Wang%3BWalsh&rft.aulast=Wang&rft.aufirst=&rft.date=2000-09-01&rft.volume=50&rft.issue=3&rft.spage=205&rft.isbn=&rft.btitle=&rft.title=Aquatic+toxicology+%28Amsterdam%2C+Netherlands%29&rft.issn=1879-1514&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2000-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glycosaminoglycan content of human bladders. a method of analysis using cold-cup biopsies. AN - 1859325764; 10973714 AB - A glycocalyx layer composed of glycosaminoglycans (GAGs) and other molecules lines the transitional epithelium of the urinary bladder. This layer forms a barrier between the transitional cells and urinary bladder environment and is believed to help prevent the adherence of bacteria, minerals and carcinogens. Investigators postulate that quantitative and/or qualitative defects in the GAG component may be responsible for a spectrum of acute and chronic disease processes ranging from urinary tract infections to cancer. While the presence of epithelium GAGs has been confirmed biochemically and histochemically, few rigorous characterizations have been performed. This study establishes the methodology and feasibility of using routine cold-cup biopsies from cadaveric human bladders for GAG analysis and establishes baseline contents of the sulfated and non-sulfated GAGs in the urinary bladder glycocalyx. Using detergent extraction, the GAGs from cold-cup biopsies (n = 34) from four cadaveric bladders were isolated. The isolates were subjected to two colorimetric assays to quantify both sulfated and non-sulfated GAGs. The nonsulfated GAG content of the bladder epithelium ranged from 2.15 x 10(-4) to 5.50 x 10(-4) mmol/kg of dry, defatted bladder. The sulfated GAG content ranged from 2.00 x 10(-1) to 7.40 x 10(-1) mmol/kg of dry, defatted bladder. These values are consistent with reports found in the literature using electrophoresis on full-thickness human bladder specimens. The GAG content of human bladder epithelium can be readily and accurately characterized from cold-cup biopsy samples. Our future plans involve using this routinely used technique to analyze samples from live control and disease-state bladders thereby demonstrating any quantitative and/or qualitative differences in GAG constituents. JF - Urologic oncology AU - Poggi AU - Johnstone AU - Conner AD - Radiation Oncology Branch, National Cancer Institute, 20892, Bethesda, MD, USA Y1 - 2000/09/01/ PY - 2000 DA - 2000 Sep 01 SP - 234 EP - 237 VL - 5 IS - 5 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859325764?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=RNA+%28New+York%2C+N.Y.%29&rft.atitle=De+novo+synthesis+of+minus+strand+RNA+by+the+rotavirus+RNA+polymerase+in+a+cell-free+system+involves+a+novel+mechanism+of+initiation.&rft.au=Chen%2C+D%3BPatton%2C+J+T&rft.aulast=Chen&rft.aufirst=D&rft.date=2000-10-01&rft.volume=6&rft.issue=10&rft.spage=1455&rft.isbn=&rft.btitle=&rft.title=RNA+%28New+York%2C+N.Y.%29&rft.issn=13558382&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2000-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of Potential mRNA Biomarkers in Peripheral Blood Lymphocytes for Human Exposure to Ionizing Radiation AN - 17858689; 5973603 AB - Since early in the Atomic Age, biological indicators of radiation exposure have been sought, but currently available methods are not entirely satisfactory. Using cDNA microarray hybridization to discover new potential biomarkers, we have identified genes expressed at increased levels in human peripheral blood lymphocytes after ex vivo irradiation. We recently used this technique to identify a large set of ionizing radiation-responsive genes in a human cell line (Oncogene 18, 3666-3672, 1999). The present set of radiation markers in peripheral blood lymphocytes was identified 24 h after treatment, and while the magnitude of mRNA induction generally decreased over time, many markers were still significantly elevated up to 72 h after irradiation. In all donors, the most highly responsive gene identified was DDB2, which codes for the p48 subunit of XPE, a protein known to play a crucial role in repair of ultraviolet (UV) radiation damage in DNA. Induction of DDB2, CDKN1A (also known as CIP1/WAF1) and XPC showed a linear dose-response relationship between 0.2 and 2 Gy at 24 and 48 h after irradiation, with less linearity at earlier or later times. These results suggest that relative levels of gene expression in peripheral blood cells may provide estimates of environmental radiation exposures. JF - Radiation Research AU - Amundson, SA AU - Do, K T AU - Shahab, S AU - Bittner, M AU - Meltzer, P AU - Trent, J AU - Fornace, AJ Jr AD - National Institutes of Health, National Cancer Institute, Division of Basic Science Y1 - 2000/09// PY - 2000 DA - Sep 2000 SP - 342 EP - 346 PB - Radiation Research Society VL - 154 IS - 3 SN - 0033-7587, 0033-7587 KW - Toxicology Abstracts KW - Peripheral blood KW - Lymphocytes KW - biomarkers KW - DNA microarrays KW - DNA damage KW - Waf1 protein KW - Oncogenes KW - U.V. radiation KW - Radiation KW - cyclin-dependent kinase inhibitor p21 KW - Ionizing radiation KW - DNA KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17858689?accountid=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=Identification+of+Potential+mRNA+Biomarkers+in+Peripheral+Blood+Lymphocytes+for+Human+Exposure+to+Ionizing+Radiation&rft.au=Amundson%2C+SA%3BDo%2C+K+T%3BShahab%2C+S%3BBittner%2C+M%3BMeltzer%2C+P%3BTrent%2C+J%3BFornace%2C+AJ+Jr&rft.aulast=Amundson&rft.aufirst=SA&rft.date=2000-09-01&rft.volume=154&rft.issue=3&rft.spage=342&rft.isbn=&rft.btitle=&rft.title=Radiation+Research&rft.issn=00337587&rft_id=info:doi/10.1043%2F0033-7587%282000%291542.0.CO%3B2 L2 - http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0033-7587&volume=154&page=342 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - DNA damage; Waf1 protein; U.V. radiation; Oncogenes; cyclin-dependent kinase inhibitor p21; Radiation; Ionizing radiation; DNA; Peripheral blood; Lymphocytes; DNA microarrays; biomarkers DO - http://dx.doi.org/10.1043/0033-7587(2000)154<0342:IOPMBI>2.0.CO;2 ER - TY - JOUR T1 - Thermal stability of xylanases produced by Aspergillus awamori AN - 17847781; 4879703 AB - The effect of temperature on the activity and stability of endoxylanase and beta -xylosidase from Aspergillus awamori was investigated. The growth of A. awamori in milled sugar cane bagasse produced predominantly extracellular endoxylanase (30 U/ml) and lower amounts of beta -xylosidase (1.3 U/ml). Grown in sugar cane bagasse as the principal carbon source, the microorganism produced a quite stable beta -xylosidase in a temperature range of 35-55 degree C, but it exhibited a lower thermostable endoxylanase. The thermostability of endoxylanase was enhanced through addition of polyhydric alcohols, mainly 2 M xylitol and sorbitol solutions. Particular stability upon storage (100%) was found for endoxylanase at -4 degree C for 165 days. Yet for beta -xylosidase, an activity decrease of approximately 20% was observed during the first 15 days of storage, maintaining roughly 75% of initial activity until the end of the experiment. JF - Brazilian Journal of Microbiology AU - Lemos, JLS AU - Bon, EPS AU - de Fatima Ebole Santana, M AU - Pereira, N Jr AD - Departamento de Engenharia Bioquimica, Escola de Quimica, Centro de Tecnologia, UFRJ, Ilha do Fundao, CEP: 21949-900, Rio de Janeiro, RJ, Brasil, nei@eq.ufrj.br Y1 - 2000/09// PY - 2000 DA - Sep 2000 SP - 206 EP - 211 VL - 31 IS - 3 SN - 1517-8382, 1517-8382 KW - b-xylosidase KW - beta -xylosidase KW - endoxylanase KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Xylan endo-1,3-b-xylosidase KW - Carbon sources KW - Xylan 1,4-b-xylosidase KW - Storage conditions KW - Xylan 1,4-^b-xylosidase KW - Xylan endo-1,3-^b-xylosidase KW - Thermal stability KW - Aspergillus awamori KW - A 01006:Enzymes & cofactors KW - K 03020:Fungi UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17847781?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brazilian+Journal+of+Microbiology&rft.atitle=Thermal+stability+of+xylanases+produced+by+Aspergillus+awamori&rft.au=Lemos%2C+JLS%3BBon%2C+EPS%3Bde+Fatima+Ebole+Santana%2C+M%3BPereira%2C+N+Jr&rft.aulast=Lemos&rft.aufirst=JLS&rft.date=2000-09-01&rft.volume=31&rft.issue=3&rft.spage=206&rft.isbn=&rft.btitle=&rft.title=Brazilian+Journal+of+Microbiology&rft.issn=15178382&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Aspergillus awamori; Xylan 1,4-b-xylosidase; Xylan endo-1,3-b-xylosidase; Thermal stability; Carbon sources; Storage conditions; Xylan 1,4-^b-xylosidase; Xylan endo-1,3-^b-xylosidase ER - TY - JOUR T1 - The Stringent Response of Mycobacterium tuberculosis Is Required for Long-Term Survival AN - 17822870; 4859482 AB - The stringent response utilizes hyperphosphorylated guanine [(p)ppGpp] as a signaling molecule to control bacterial gene expression involved in long-term survival under starvation conditions. In gram-negative bacteria, (p)ppGpp is produced by the activity of the related RelA and SpoT proteins. Mycobacterium tuberculosis contains a single homolog of these proteins (Rel sub(Mtb)) and responds to nutrient starvation by producing (p)ppGpp. A rel sub(Mtb) knockout strain was constructed in a virulent strain of M. tuberculosis, H37Rv, by allelic replacement. The rel sub(Mtb) mutant displayed a significantly slower aerobic growth rate than the wild type in synthetic liquid media, whether rich or minimal. The growth rate of the wild type was equivalent to that of the mutant when citrate or phospholipid was employed as the sole carbon source. These two organisms also showed identical growth rates within a human macrophage-like cell line. These results suggest that the in vivo carbon source does not represent a stressful condition for the bacilli, since it appears to be utilized in a similar Rel sub(Mtb)-independent manner. In vitro growth in liquid media represents a condition that benefits from Rel sub(Mtb)-mediated adaptation. Long-term survival of the rel sub(Mtb) mutant during in vitro starvation or nutrient run out in normal media was significantly impaired compared to that in the wild type. In addition, the mutant was significantly less able to survive extended anaerobic incubation than the wild-type virulent organism. Thus, the Rel sub(Mtb) protein is required for long-term survival of pathogenic mycobacteria under starvation conditions. JF - Journal of Bacteriology AU - Primm, T P AU - Andersen, S J AU - Mizrahi, V AU - Avarbock, D AU - Rubin, H AU - Barry III, CE AD - Tuberculosis Research Section, LHD/NIAID, National Institutes of Health, Twinbrook II, Room 239, 12441 Parklawn Dr., Rockville, MD 20852, clifton_barry@nih.gov clifton_barry@nih.gov Y1 - 2000/09// PY - 2000 DA - Sep 2000 SP - 4889 EP - 4898 VL - 182 IS - 17 SN - 0021-9193, 0021-9193 KW - (p)ppGpp KW - RelA protein KW - SpoT protein KW - stringent response KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Starvation KW - Virulence KW - Carbon sources KW - Mutants KW - Mycobacterium tuberculosis KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17822870?accountid=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=The+Stringent+Response+of+Mycobacterium+tuberculosis+Is+Required+for+Long-Term+Survival&rft.au=Primm%2C+T+P%3BAndersen%2C+S+J%3BMizrahi%2C+V%3BAvarbock%2C+D%3BRubin%2C+H%3BBarry+III%2C+CE&rft.aulast=Primm&rft.aufirst=T&rft.date=2000-09-01&rft.volume=182&rft.issue=17&rft.spage=4889&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium tuberculosis; Virulence; Carbon sources; Mutants; Starvation ER - TY - JOUR T1 - Biomarkers (sex-hormone binding globulin (SHBG), bioavailable oestradiol, and bioavailable testosterone) and processing of blood samples in epidemiological studies AN - 17790254; 6069950 JF - Biomarkers AU - Fillmore, C M AU - Fears, T R AU - Hoover, R N AU - Falk, R T AU - Vaught, J B AU - Chandler, D W AU - Stanczyk, F Z AU - Galmarini, M AU - Ziegler, R G AD - Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Executive Plaza North, 6120 Executive Blvd, Mailstop 7240, Bethesda, Maryland 20892, USA Y1 - 2000/09// PY - 2000 DA - Sep 2000 SP - 395 EP - 398 PB - Taylor & Francis Ltd., 11 New Fetter Lane London EC4P 4EE UK, [mailto:info@tandf.co.uk], [URL:http://www.tandf.co.uk] VL - 5 IS - 5 SN - 1354-750X, 1354-750X KW - Toxicology Abstracts KW - Blood KW - Testosterone KW - Globulins KW - biomarkers KW - X 24222:Analytical procedures UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17790254?accountid=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=Biomarkers&rft.atitle=Biomarkers+%28sex-hormone+binding+globulin+%28SHBG%29%2C+bioavailable+oestradiol%2C+and+bioavailable+testosterone%29+and+processing+of+blood+samples+in+epidemiological+studies&rft.au=Fillmore%2C+C+M%3BFears%2C+T+R%3BHoover%2C+R+N%3BFalk%2C+R+T%3BVaught%2C+J+B%3BChandler%2C+D+W%3BStanczyk%2C+F+Z%3BGalmarini%2C+M%3BZiegler%2C+R+G&rft.aulast=Fillmore&rft.aufirst=C&rft.date=2000-09-01&rft.volume=5&rft.issue=5&rft.spage=395&rft.isbn=&rft.btitle=&rft.title=Biomarkers&rft.issn=1354750X&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 - biomarkers; Globulins; Blood; Testosterone ER - TY - JOUR T1 - Behavioral prevention is today's AIDS vaccine! AN - 17726675; 4791233 AB - Introduction: Behavioral prevention is currently the only effective way to stem the further spread of HIV. This article reviews the pro-active programmatic model of behavioral research that has led to the development and testing of successful HIV/STD preventive interventions in the last fifteen years. Objective: To present (1) a model of behavioral prevention adapting phases of clinical trials research: Phase I: Discovery; Phase II: Exploratory; Phase III: Efficacy; and Phase IV: Effectiveness; and (2) a theoretical framework for behavioral prevention; and (3) A Lifespan Model of Health Promotion and Disease Prevention which can be used to design HIV/STD prevention programs across the lifespan, at different levels (e.g., individual, couple, family, community, societal) using different intervention modalities. Conclusions: Behavioral prevention is effective with different age groups and at different levels of intervention when the prevention program has a theoretical basis. Behavioral prevention works now and can be mobilized within a community to address all of the factors associated with the rapid development of an epidemic. Behavioral prevention is cost effective and can be delivered in communities that have limited resources. JF - AIDS AU - Pequegnat, W AU - Stover, E AD - Center for Mental Health Research on AIDS, National Institute of Mental Health, National Institutes of Health, 6001 Executive Boulevard, Room 6205, MSC 9619, Bethesda, MD 20892, USA, Wpequegn@nih.gov Y1 - 2000/09// PY - 2000 DA - Sep 2000 SP - S1 EP - S7 VL - 14 SN - 0269-9370, 0269-9370 KW - man KW - epidemiology KW - HIV KW - disease transmission KW - sexual behavior KW - sexually transmitted diseases KW - Risk Abstracts; Health & Safety Science Abstracts; Virology & AIDS Abstracts KW - Age KW - Acquired immune deficiency syndrome KW - Sexually-transmitted diseases KW - Sexual behavior KW - Disease transmission KW - Behavior KW - Human immunodeficiency virus KW - Reviews KW - H 11000:Diseases/Injuries/Trauma KW - V 22005:AIDS: Epidemiological aspects KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17726675?accountid=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=AIDS&rft.atitle=Behavioral+prevention+is+today%27s+AIDS+vaccine%21&rft.au=Pequegnat%2C+W%3BStover%2C+E&rft.aulast=Pequegnat&rft.aufirst=W&rft.date=2000-09-01&rft.volume=14&rft.issue=&rft.spage=S1&rft.isbn=&rft.btitle=&rft.title=AIDS&rft.issn=02699370&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; Acquired immune deficiency syndrome; Behavior; Age; Disease transmission; Reviews; Sexually-transmitted diseases; Sexual behavior ER - TY - JOUR T1 - Antibacterial activity and cytotoxicity of Miliusa velutina AN - 17724674; 4796896 AB - Goniothalamusin and two mixtures, acetogenins-A and acetogenins-B, isolated from a petroleum ether extract of the stem bark of Miliusa velutina exhibited significant antibacterial and cytotoxic activities. JF - Fitoterapia AU - Jumana, S AU - Hasan, C M AU - Rashid, MA AD - SAIC Frederick, NCI-Frederick Cancer Research and Development Center, Bldg. 560, Rm. 32-63B, Post Box B, Frederick, MD 21702, USA, rashid@mail.ncifcrf.gov Y1 - 2000/09// PY - 2000 DA - Sep 2000 SP - 559 EP - 561 VL - 71 IS - 5 SN - 0367-326X, 0367-326X KW - acetogenins KW - goniothalamusin KW - petroleum ether KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology KW - Cytotoxicity KW - Miliusa velutina KW - Bark KW - Antibacterial agents KW - A 01066:Antibacterial & bactericidal KW - J 02812:Antibacterial Agents: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17724674?accountid=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=Fitoterapia&rft.atitle=Antibacterial+activity+and+cytotoxicity+of+Miliusa+velutina&rft.au=Jumana%2C+S%3BHasan%2C+C+M%3BRashid%2C+MA&rft.aulast=Jumana&rft.aufirst=S&rft.date=2000-09-01&rft.volume=71&rft.issue=5&rft.spage=559&rft.isbn=&rft.btitle=&rft.title=Fitoterapia&rft.issn=0367326X&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 - Miliusa velutina; Antibacterial agents; Bark; Cytotoxicity ER - TY - JOUR T1 - Sensitization of Cancer Cells to Interleukin 13-Pseudomonas Exotoxin-Induced Cell Death by Gene Transfer of Interleukin 13 Receptor alpha Chain AN - 17685127; 4765357 AB - We have demonstrated that primary interleukin 13 (IL-13) binding protein IL-13 receptor (IL-13R) alpha chain plays an important role in IL-13 binding and internalization in the IL-13R system. Although IL-13R alpha chain is expressed on many cancer cell lines, some cancer types do not express or express low levels of this receptor chain. Consequently, these cells show no or low sensitivity to the cytotoxic effect of a recombinant chimeric protein composed of IL-13 and a mutated form of a Pseudomonas exotoxin, IL13-PE38QQR. Here we demonstrate that pancreatic cancer, renal cell carcinoma, head and neck cancer, and glioblastoma cell lines that were genetically altered to express high levels of IL-13R alpha chain increase their binding affinity for IL-13, and increase their sensitivity to IL13-PE38QQR by at least 6-fold to 1000-fold compared with mock-transfected control cells. This observation was made by protein synthesis inhibition assay and confirmed by clonogenic assay. Our studies provide a proof of principle for a novel strategy for cancer therapy that combines gene transfer and targeted cytotoxin therapy. JF - Human Gene Therapy AU - Kawakami, Koji AU - Joshi, B H AU - Puri, R K AD - Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research Food and Drug Administration, National Institutes of Health, Building 29B, Room 2NN10, 29 Lincoln Drive MSC 4555, Bethesda, MD 20892, USA, puri@cber.fda.gov Y1 - 2000/09/01/ PY - 2000 DA - 2000 Sep 01 SP - 1829 EP - 1835 VL - 11 IS - 13 SN - 1043-0342, 1043-0342 KW - man KW - Head and neck carcinoma KW - Pseudomonas KW - glioblastoma KW - interleukin 13 receptors KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Cell death KW - Interleukin 13 KW - Gene therapy KW - Gene transfer KW - Pancreas KW - Cytotoxins KW - Exotoxins KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17685127?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Sensitization+of+Cancer+Cells+to+Interleukin+13-Pseudomonas+Exotoxin-Induced+Cell+Death+by+Gene+Transfer+of+Interleukin+13+Receptor+alpha+Chain&rft.au=Kawakami%2C+Koji%3BJoshi%2C+B+H%3BPuri%2C+R+K&rft.aulast=Kawakami&rft.aufirst=Koji&rft.date=2000-09-01&rft.volume=11&rft.issue=13&rft.spage=1829&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene transfer; Interleukin 13; Cell death; Cytotoxins; Exotoxins; Pancreas; Gene therapy ER - TY - JOUR T1 - HIV-inhibitory diterpenoid from Anisomeles indica AN - 17647052; 4796899 AB - The super(1)H- and super(13)C-NMR spectral data of ovatodiolide, a diterpenoid from Anisomeles indica, and its anti-HIV activity are reported. JF - Fitoterapia AU - Alam AU - Quader, MA AU - Rashid, MA AD - SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Bldg. 560, Rm. 32-63B, P.O. Box B, Frederick, MD 21702, USA, rashid@mail.ncifcrf.gov Y1 - 2000/09// PY - 2000 DA - Sep 2000 SP - 574 EP - 576 VL - 71 IS - 5 SN - 0367-326X, 0367-326X KW - HIV KW - diterpenoids KW - ovatodiolide KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - Antiviral agents KW - Human immunodeficiency virus KW - Anisomeles indica KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01068:Antiviral & viricidal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17647052?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fitoterapia&rft.atitle=HIV-inhibitory+diterpenoid+from+Anisomeles+indica&rft.au=Alam%3BQuader%2C+MA%3BRashid%2C+MA&rft.aulast=Alam&rft.aufirst=&rft.date=2000-09-01&rft.volume=71&rft.issue=5&rft.spage=574&rft.isbn=&rft.btitle=&rft.title=Fitoterapia&rft.issn=0367326X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; Anisomeles indica; Antiviral agents ER - TY - JOUR T1 - Permissive factors for HIV-1 infection of macrophages AN - 17635192; 4779219 AB - Immunodeficiency, the consequence of HIV-1 infection, predisposes the host to opportunistic infectious. In turn, opportunistic pathogens influence target cell susceptibility to HIV-1 infection and replication. Although the advent of highly active antiretroviral therapy (HAART) has altered these sequelae, co-infections may prevail in some parts of the world and in failed HAART regimens. Moreover, immune activation as occurs in tonsil and non-infectious mucosal inflammatory lesions may also be associated with proximal sites of viral replication. These connections between enhancement of HIV-1 infection and activation/inflammation warrant further elucidation of the factors promoting permissiveness to HIV-1 infection. Using the opportunistic pathogen Mycobacterium avium as an in vitro model, we demonstrated that co-infection facilitated HIV-1 infection of monocyte-macrophages by multiple pathways. M. avium activated NF- Kappa B, the downstream consequences of which included augmented expression of tumor necrosis factor alpha and CCR5 receptors, both permissive for sustaining HIV-1 infection. Pronounced viral replication in lymph nodes co-infected with M. avium and HIV-1 paralleled these in vitro findings. Furthermore, reduction in viral burden is associated with treatment of infected or inflamed tissues, underscoring the link between immune activation and viral replication. JF - Journal of Leukocyte Biology AU - Wahl, S M AU - Greenwell-Wild, T AU - Hale-Donze, H AU - Moutsopoulos, N AU - Orenstein, J M AD - NIDCR, NIH, 30 Convent Drive, MSC 4352, Building 30, Room 332, Bethesda, MD 20892-4352, USA, smwahl@dir.nidcr.nih.gov Y1 - 2000/09// PY - 2000 DA - Sep 2000 SP - 303 EP - 310 VL - 68 IS - 3 SN - 0741-5400, 0741-5400 KW - permissive factors KW - inflammation KW - co-infection KW - HIV-1 KW - immunology KW - CCR5 protein KW - Human immunodeficiency virus 1 KW - Mycobacterium avium KW - NF- Kappa B protein KW - tumor necrosis factor- alpha KW - Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - NF-B protein KW - tumor necrosis factor-a KW - NF-^KB protein KW - tumor necrosis factor-^a KW - Macrophages KW - Immunodeficiency KW - Lymph nodes KW - Opportunist infection KW - Tumor necrosis factor-^a KW - Immune response KW - J 02845:Ear, nose and respiratory tract KW - V 22003:AIDS: Immunological aspects KW - F 06800:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17635192?accountid=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+Leukocyte+Biology&rft.atitle=Permissive+factors+for+HIV-1+infection+of+macrophages&rft.au=Wahl%2C+S+M%3BGreenwell-Wild%2C+T%3BHale-Donze%2C+H%3BMoutsopoulos%2C+N%3BOrenstein%2C+J+M&rft.aulast=Wahl&rft.aufirst=S&rft.date=2000-09-01&rft.volume=68&rft.issue=3&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=Journal+of+Leukocyte+Biology&rft.issn=07415400&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Mycobacterium avium; Macrophages; Opportunist infection; Immunodeficiency; Lymph nodes; Immune response; NF-^KB protein; Tumor necrosis factor-^a ER - TY - JOUR T1 - Expression of green fluorescent protein in Streptococcus gordonii DL1 and its use as a species-specific marker in coadhesion with Streptococcus oralis 34 in saliva-conditioned biofilms in vitro AN - 17633322; 4784019 AB - Streptococcus gordonii is one of the predominant streptococci in the biofilm ecology of the oral cavity. It interacts with other bacteria through receptor-adhesin complexes formed between cognate molecules on the surfaces of the partner cells. To study the spatial organization of S. gordonii DL1 in oral biofilms, we used green fluorescent protein (GFP) as a species-specific marker to identify S. gordonii in a two-species in vitro oral biofilm flowcell system. To drive expression of gfp, we isolated and characterized an endogenous S. gordonii promoter, PhppA, which is situated upstream of the chromosomal hppA gene encoding an oligopeptide-binding lipoprotein. A chromosomal chloramphenicol acetyltransferase (cat) gene fusion with PhppA was constructed and used to demonstrate that PhppA was highly active throughout the growth of bacteria in batch culture. A promoterless 0.8-kb gfp ('gfp) cassette was PCR amplified from pBJ169 and subcloned to replace the cat cassette downstream of the S. gordonii-derived PhppA in pMH109-HPP, generating pMA1. Subsequently, the PhppA-'gfp cassette was PCR amplified from pMA1 and subcloned into pDL277 and pVA838 to generate the Escherichia coli-S. gordonii shuttle vectors pMA2 and pMA3, respectively. Each vector was transformed into S. gordonii DL1 aerobically to ensure GFP expression. Flow cytometric analyses of aerobically grown transformant cultures were performed over a 24-h period, and results showed that GFP could be successfully expressed in S. gordonii DL1 from PhppA and that S. gordonii DL1 transformed with the PhppA-'gfp fusion plasmid stably maintained the fluorescent phenotype. Fluorescent S. gordonii DL1 transformants were used to elucidate the spatial arrangement of S. gordonii DL1 alone in biofilms or with the coadhesion partner Streptococcus oralis 34 in two-species biofilms in a saliva-conditioned in vitro flowcell system. These results show for the first time that GFP expression in oral streptococci can be used as a species-specific marker in model oral biofilms. JF - Applied and Environmental Microbiology AU - Aspiras, M B AU - Kazmerzak, K M AU - Kolenbrander, P E AU - McNab, R AU - Hardegen, N AU - Jenkinson, H F AD - National Institutes of Health/NIDCR, Building 30, Room 310, 30 Convent Dr., MSC 4350, Bethesda, MD 20892-4350, USA, pkolenbrander@dir.nidcr.nih.gov Y1 - 2000/09// PY - 2000 DA - Sep 2000 SP - 4074 EP - 4083 VL - 66 IS - 9 SN - 0099-2240, 0099-2240 KW - PhppA promoter KW - gfp gene KW - hppA gene KW - Microbiology Abstracts B: Bacteriology KW - Flow cytometry KW - Gene expression KW - Streptococcus gordonii KW - Gene fusion KW - Green fluorescent protein KW - Escherichia coli KW - Saliva KW - Biofilms KW - Streptococcus oralis KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17633322?accountid=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=Applied+and+Environmental+Microbiology&rft.atitle=Expression+of+green+fluorescent+protein+in+Streptococcus+gordonii+DL1+and+its+use+as+a+species-specific+marker+in+coadhesion+with+Streptococcus+oralis+34+in+saliva-conditioned+biofilms+in+vitro&rft.au=Aspiras%2C+M+B%3BKazmerzak%2C+K+M%3BKolenbrander%2C+P+E%3BMcNab%2C+R%3BHardegen%2C+N%3BJenkinson%2C+H+F&rft.aulast=Aspiras&rft.aufirst=M&rft.date=2000-09-01&rft.volume=66&rft.issue=9&rft.spage=4074&rft.isbn=&rft.btitle=&rft.title=Applied+and+Environmental+Microbiology&rft.issn=00992240&rft_id=info:doi/10.1128%2FAEM.66.9.4074-4083.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus gordonii; Streptococcus oralis; Escherichia coli; Biofilms; Saliva; Green fluorescent protein; Gene expression; Gene fusion; Flow cytometry DO - http://dx.doi.org/10.1128/AEM.66.9.4074-4083.2000 ER - TY - JOUR T1 - Recovery and potential utility of YACs as circular YACs/BACs AN - 17632950; 4767350 AB - A method has been established to convert pYAC4-based linear yeast artificial chromosomes (YACs) into circular chromosomes that can also be propagated in Escherichia coli cells as bacterial artificial chromosomes (BACs). The circularization is based on use of a vector that contains a yeast dominant selectable marker (G418R), a BAC cassette and short targeting sequences adjacent to the edges of the insert in the pYAC4 vector. When it is introduced into yeast, the vector recombines with the YAC target sequences to form a circular molecule, retaining the insert but discarding most of the sequences of the YAC telomeric arms. YACs up to 670 kb can be efficiently circularized using this vector. Re-isolation of megabase-size YAC inserts as a set of overlapping circular YAC/BACs, based on the use of an Alu-containing targeting vector, is also described. We have shown that circular DNA molecules up to 250 kb can be efficiently and accurately transferred into E.coli cells by electroporation. Larger circular DNAs cannot be moved into bacterial cells, but can be purified away from linear yeast chromosomes. We propose that the described system for generation of circular YAC derivatives can facilitate sequencing as well as functional analysis of genomic regions. JF - Nucleic Acids Research AU - Cocchia, M AU - Kouprina, N AU - Kim, Sung-Jae AU - Larionov, V AU - Schlessinger, D AU - Nagaraja, R AD - Laboratory of Genetics, NIA, NIH, 333 Cassell Drive, Suite 4000, Baltimore, MD 21224, USA, nagarajar@grc.nia.nih.gov Y1 - 2000/09/01/ PY - 2000 DA - 2000 Sep 01 SP - 1 VL - 28 IS - 17 SN - 0305-1048, 0305-1048 KW - nucleotide sequence KW - Escherichia coli KW - bacterial artificial chromoosmes KW - bacterial artificial chromosomes KW - electroporation KW - recombination KW - yeast artificial chromosomes KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Bacterial artificial chromosomes KW - Cloning vectors KW - Yeast artificial chromosomes KW - G 07330:Fungal genetics KW - W3 33058:Cloning vectors KW - W 30965:Miscellaneous, Reviews KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17632950?accountid=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=Recovery+and+potential+utility+of+YACs+as+circular+YACs%2FBACs&rft.au=Cocchia%2C+M%3BKouprina%2C+N%3BKim%2C+Sung-Jae%3BLarionov%2C+V%3BSchlessinger%2C+D%3BNagaraja%2C+R&rft.aulast=Cocchia&rft.aufirst=M&rft.date=2000-09-01&rft.volume=28&rft.issue=17&rft.spage=e81&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 - Escherichia coli; Cloning vectors; Yeast artificial chromosomes; Bacterial artificial chromosomes ER - TY - JOUR T1 - Designer cancer vaccines are still in fashion AN - 17629834; 4773716 AB - The use of dendritic cells to immunize against tumor antigens is improving the prospects for cancer vaccines. However, caution must be taken to avoid activating autoimmunity against normal cells. JF - Nature Medicine AU - Biragyn, A AU - Kwak, L W AD - Department of Experimental, Transplantation & Immunology, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA, kwak@mail.ncifcrf.gov Y1 - 2000/09// PY - 2000 DA - Sep 2000 SP - 966 EP - 968 VL - 6 IS - 9 SN - 1078-8956, 1078-8956 KW - immunology KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Dendritic cells KW - Reviews KW - Autoimmunity KW - Vaccines KW - Cancer KW - F 06818:Cancer immunotherapy KW - W3 33350:Cancer vaccines KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17629834?accountid=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+Medicine&rft.atitle=Designer+cancer+vaccines+are+still+in+fashion&rft.au=Biragyn%2C+A%3BKwak%2C+L+W&rft.aulast=Biragyn&rft.aufirst=A&rft.date=2000-09-01&rft.volume=6&rft.issue=9&rft.spage=966&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/10.1038%2F79649 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cancer; Vaccines; Reviews; Dendritic cells; Autoimmunity DO - http://dx.doi.org/10.1038/79649 ER - TY - JOUR T1 - Expression and immunological analysis of the plasmid-borne mlp genes of Borrelia burgdorferi strain B31 AN - 17628161; 4764219 AB - A lipoprotein gene family first identified in Borrelia burgdorferi strain 297, designated 2.9 LP and recently renamed mlp, was found on circular and linear plasmids in the genome sequence of B. burgdorferi strain B31-M1. Sequence analyses of the B31 mlp genes and physically linked variant gene families indicated that mlp gene heterogeneity is unique and unrelated to location or linkage to divergent sequences. Evidence of recombination between B31 mlp alleles was also detected. Northern blot analysis of cultured strain B31 indicated that the mlp genes were not expressed at a temperature (23 degree C) characteristic of that of ticks in the environment. In striking contrast, expression of many mlp genes increased substantially when strain B31 was shifted to 35 degree C, a temperature change mimicking that occurring in the natural transmission cycle of the spirochete from tick to mammal. Primer extension analysis of the mlp mRNA transcripts suggested that sigma 70-like promoters are involved in mlp expression during temperature shift conditions. Antibodies were made against strain B31 Mlp proteins within the first 4 weeks after experimental mouse infection. Importantly, Lyme disease patients also had serum antibodies reactive with purified recombinant Mlp proteins from strain B31, a result indicating that humans are exposed to Mlp proteins during infection. Taken together, the data indicate that strain B31 mlp genes encode a diverse array of lipoproteins which may participate in early infection processes in the mammalian host. JF - Infection and Immunity AU - Porcella, S F AU - Fitzpatrick, CA AU - Bono, J L AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, 903 South 4th St., Hamilton, MT 59840, USA, sporcella@nih.gov Y1 - 2000/09// PY - 2000 DA - Sep 2000 SP - 4992 EP - 5001 VL - 68 IS - 9 SN - 0019-9567, 0019-9567 KW - mice KW - serum KW - Mlp protein KW - mlp gene KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Temperature effects KW - Borrelia burgdorferi KW - Nucleotide sequence KW - Plasmids KW - Infection KW - Gene families KW - Gene expression KW - Promoters KW - Recombination KW - Antibodies KW - Lipoproteins KW - G 07203:Plasmids KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17628161?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Expression+and+immunological+analysis+of+the+plasmid-borne+mlp+genes+of+Borrelia+burgdorferi+strain+B31&rft.au=Porcella%2C+S+F%3BFitzpatrick%2C+CA%3BBono%2C+J+L&rft.aulast=Porcella&rft.aufirst=S&rft.date=2000-09-01&rft.volume=68&rft.issue=9&rft.spage=4992&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.68.9.4992-5001.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Borrelia burgdorferi; Gene families; Nucleotide sequence; Recombination; Infection; Gene expression; Plasmids; Temperature effects; Promoters; Antibodies; Lipoproteins DO - http://dx.doi.org/10.1128/IAI.68.9.4992-5001.2000 ER - TY - JOUR T1 - Enhancement of clearance of bacteria from murine lungs by immunization with detoxified lipooligosaccharide from Moraxella catarrhalis conjugated to proteins AN - 17625606; 4764217 AB - Moraxella catarrhalis strain 25238 detoxified lipooligosaccharide (dLOS)-protein conjugates induced a significant rise of bactericidal anti-LOS antibodies in animals. This study reports the effect of active or passive immunization with the conjugates or their antiserum on pulmonary clearance of M. catarrhalis in an aerosol challenge mouse model. Mice were injected subcutaneously with dLOS-tetanus toxoid (dLOS-TT), dLOS-high-molecular-weight proteins (dLOS-HMP) from nontypeable Haemophilus influenzae (NTHi), or nonconjugated materials in Ribi adjuvant and then challenged with M. catarrhalis strain 25238 or O35E or NTHi strain 12. Immunization with dLOS-TT or dLOS-HMP generated a significant rise of serum anti-LOS immunoglobulin G and 68% and 35 to 41% reductions of bacteria in lungs compared with the control (P < 0.01) following challenge with homologous strain 25238 and heterologous strain O35E, respectively. Serum anti-LOS antibody levels correlated with its bactericidal titers against M. catarrhalis and bacterial CFU in lungs. Additionally, immunization with dLOS-HMP generated a 54% reduction of NTHi strain 12 compared with the control (P < 0.01). Passive immunization with a rabbit antiserum against dLOS-TT conferred a significant reduction of strain 25238 CFU in lungs in a dose- and time-dependent pattern compared with preimmune serum-treated mice. Kinetic examination of lung tissue sections demonstrated that antiserum-treated mice initiated and offset inflammatory responses more rapidly than preimmune serum-treated mice. These data indicate that LOS antibodies (whether active or passive) play a major role in the enhancement of pulmonary clearance of different test strains of M. catarrhalis in mice. In addition, dLOS-HMP is a potential candidate for a bivalent vaccine against M. catarrhalis and NTHi infections. JF - Infection and Immunity AU - Hu, W-G AU - Chen, J AU - Battey, J F AU - Gu, X-X AD - NIDCD, NIH, 5 Research Court, 2A31, Rockville, MD 20850, USA, guxx@nidcd.nih.gov Y1 - 2000/09// PY - 2000 DA - Sep 2000 SP - 4980 EP - 4985 VL - 68 IS - 9 SN - 0019-9567, 0019-9567 KW - animal models KW - mice KW - immunology KW - Haemophilus influenzae KW - Lipooligosaccharides KW - Moraxella catarrhalis KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Antibody response KW - Immunization KW - Lung KW - Lipopolysaccharides KW - Immunization (passive) KW - Vaccines KW - W3 33365:Vaccines (other) KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17625606?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Enhancement+of+clearance+of+bacteria+from+murine+lungs+by+immunization+with+detoxified+lipooligosaccharide+from+Moraxella+catarrhalis+conjugated+to+proteins&rft.au=Hu%2C+W-G%3BChen%2C+J%3BBattey%2C+J+F%3BGu%2C+X-X&rft.aulast=Hu&rft.aufirst=W-G&rft.date=2000-09-01&rft.volume=68&rft.issue=9&rft.spage=4980&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.68.9.4980-4985.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Moraxella catarrhalis; Haemophilus influenzae; Vaccines; Lipopolysaccharides; Antibody response; Immunization (passive); Lung; Immunization DO - http://dx.doi.org/10.1128/IAI.68.9.4980-4985.2000 ER - TY - JOUR T1 - Efficient Gene Transfer to Human Peripheral Blood Monocyte-Derived Dendritic Cells Using Human Immunodeficiency Virus Type 1-Based Lentiviral Vectors AN - 17624045; 4765363 AB - Dendritic cells (DCs) are potent antigen-presenting cells and are capable of activating naive T cells. Gene transfer of tumor antigen and cytokine genes into DCs could be an important strategy for immunotherapeutic applications. Dendritic cells derived from peripheral blood monocytes do not divide and are therefore poor candidates for gene transfer by Moloney murine leukemia virus (Mo-MuLV)-based retroviral vectors. Lentiviral vectors are emerging as a powerful tool for gene delivery into dividing and nondividing cells. A three-plasmid expression system pseudotyped with the envelope from vesicular stomatitis virus (VSV-G) was used to generate lentiviral vector particles expressing enhanced green fluorescent protein (EGFP). Peripheral blood monocyte-derived DCs were cultured in the presence of GM-CSF and IL-4 and transduced with lentiviral or Mo-MuLV-based vectors expressing EGFP. FACS analysis of lentiviral vector-transduced DCs derived either from normal healthy volunteers or from melanoma patients demonstrated transduction efficiency ranging from 70 to 90% compared with 2-8% using Mo-MuLV-based vectors pseudotyped with VSV-G. Comparison of lentiviral vectors expressing EGFP driven by CMV or human PGK promoters showed similar levels of transgene expression. Lentiviral vector preparations produced in the absence of HIV accessory proteins transduced DCs at efficiencies equal to vectors produced with accessory proteins. Alu-HIV-1 LTR PCR demonstrated the genomic integration of the lentiviral vector in the transduced DCs. Transduced cells showed characteristic dendritic cell phenotype and strong allostimulatory capacity and maintained the ability to respond to activation signals such as CD40 ligand and lipopolysaccharide. These results provide evidence that lentiviral vectors are efficient tools for gene transfer and expression in monocyte-derived DCs that could be useful for immunotherapeutic applications. JF - Human Gene Therapy AU - Chinnasamy, N AU - Chinnasamy, D AU - Toso, J F AU - Lapointe, R AU - Candotti, F AU - Morgan, R A AU - Hwu, P AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 2B42, Bethesda, MD 20892, USA, Patrick_Hwu@nih.gov Y1 - 2000/09/01/ PY - 2000 DA - 2000 Sep 01 SP - 1901 EP - 1909 VL - 11 IS - 13 SN - 1043-0342, 1043-0342 KW - transgenes KW - CD40 antigen KW - Murine leukemia virus KW - Vesicular stomatitis virus KW - dendritic cells KW - lipopolysaccharides KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Green fluorescent protein KW - Granulocyte-macrophage colony-stimulating factor KW - Peripheral blood KW - Melanoma KW - Gene expression KW - Expression vectors KW - Gene transfer KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17624045?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Efficient+Gene+Transfer+to+Human+Peripheral+Blood+Monocyte-Derived+Dendritic+Cells+Using+Human+Immunodeficiency+Virus+Type+1-Based+Lentiviral+Vectors&rft.au=Chinnasamy%2C+N%3BChinnasamy%2C+D%3BToso%2C+J+F%3BLapointe%2C+R%3BCandotti%2C+F%3BMorgan%2C+R+A%3BHwu%2C+P&rft.aulast=Chinnasamy&rft.aufirst=N&rft.date=2000-09-01&rft.volume=11&rft.issue=13&rft.spage=1901&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/10.1089%2F10430340050129512 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Murine leukemia virus; Vesicular stomatitis virus; Expression vectors; Gene transfer; Peripheral blood; Gene expression; Granulocyte-macrophage colony-stimulating factor; Melanoma; Green fluorescent protein DO - http://dx.doi.org/10.1089/10430340050129512 ER - TY - JOUR T1 - Retroviral integrase inhibitors year 2000: update and perspectives AN - 17612215; 4754317 AB - HIV-1 integrase is an essential enzyme for retroviral replication and a rational target for the design of anti-AIDS drugs. A number of inhibitors have been reported in the past 8 years. This review focuses on the recent developments in the past 2 years. There are now several inhibitors with known sites of actions and antiviral activity. The challenge is to convert these leads into drugs that will selectively target integrase in vivo, and can be added to our antiviral armamentarium. JF - Antiviral Research AU - Pommier, Y AU - Marchand, C AU - Neamati, N AD - Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, 20892-4255 Bethesda, MD USA Y1 - 2000/09/01/ PY - 2000 DA - 2000 Sep 01 SP - 139 EP - 148 PB - Elsevier VL - 47 IS - 3 SN - 0166-3542, 0166-3542 KW - HIV-1 KW - Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Acquired immune deficiency syndrome KW - Replication KW - Antiviral agents KW - Human immunodeficiency virus 1 KW - Inhibitors KW - Integrase KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01068:Antiviral & viricidal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17612215?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antiviral+Research&rft.atitle=Retroviral+integrase+inhibitors+year+2000%3A+update+and+perspectives&rft.au=Pommier%2C+Y%3BMarchand%2C+C%3BNeamati%2C+N&rft.aulast=Pommier&rft.aufirst=Y&rft.date=2000-09-01&rft.volume=47&rft.issue=3&rft.spage=139&rft.isbn=&rft.btitle=&rft.title=Antiviral+Research&rft.issn=01663542&rft_id=info:doi/10.1016%2FS0166-3542%2800%2900112-1 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Antiviral agents; Acquired immune deficiency syndrome; Integrase; Inhibitors; Replication DO - http://dx.doi.org/10.1016/S0166-3542(00)00112-1 ER - TY - JOUR T1 - A voltage-dependent channel involved in nutrient uptake by red blood cells infected with the malaria parasite AN - 1520380160; 13693458 AB - Growth of the malaria parasite in human red blood cells (RBCs) is accompanied by an increased uptake of many solutes including anions, sugars, purines, amino acids and organic cations. Although the pharmacological properties and selectivity of this uptake suggest that a chloride channel is involved, the precise mechanism has not been identified. Moreover, the location of this uptake in the infected RBC is unknown because tracer studies are complicated by possible uptake through fluid-phase pinocytosis or membranous ducts. Here we have studied the permeability ofinfected RBCs using the whole-cell voltage-clamp method. With this method, uninfected RBCs had ohmic whole-cell conductances of less than 100pS, consistent with their low tracer permeabilities. In contrast, trophozoite-infected RBCs exhibited voltage-dependent, non-saturating currents that were 150-fold larger, predominantly carried by anions and abruptly abolished by channel blockers. Patch-clamp measurements and spectral analysis confirmed that a small (<10pS) ion channel on the infected RBC surface, present at about 1,000 copies per cell, is responsible for these currents. Because its pharmacological properties and substrate selectivities match those seen with tracer studies, this channel accounts for the increased uptake of small solutes in infected RBCs. The surface location of this new channel and its permeability to organic solutes needed for parasite growth indicate that it may have a primary role in a sequential diffusive pathway for parasite nutrient acquisition. JF - Nature AU - Desai, Sanjay A AU - Bezrukov, Sergey M AU - Zimmerberg, Joshua AD - [1] The Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases [2] The Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Development, National Institutes of Health, Bethesda, Maryland 20892, USA Y1 - 2000/08/31/ PY - 2000 DA - 2000 Aug 31 SP - 1001 EP - 1005 PB - Nature Publishing Group, The Macmillan Building London N1 9XW UK VL - 406 IS - 6799 SN - 0028-0836, 0028-0836 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality KW - Parasites KW - Human diseases KW - Anions KW - Erythrocytes KW - Chloride channels KW - Nutrients KW - Malaria KW - Solutes KW - Tracers KW - Permeability KW - Growth KW - Pinocytosis KW - Ion channels KW - Nutrient uptake KW - Sugar KW - Amino acids KW - Endoparasites KW - purines KW - Cations KW - Uptake KW - Q1 08484:Species interactions: parasites and diseases KW - Q5 08524:Public health, medicines, dangerous organisms KW - K 03310:Genetics & Taxonomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1520380160?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=A+voltage-dependent+channel+involved+in+nutrient+uptake+by+red+blood+cells+infected+with+the+malaria+parasite&rft.au=Desai%2C+Sanjay+A%3BBezrukov%2C+Sergey+M%3BZimmerberg%2C+Joshua&rft.aulast=Desai&rft.aufirst=Sanjay&rft.date=2000-08-31&rft.volume=406&rft.issue=6799&rft.spage=1001&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/10.1038%2F35023000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2014-04-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Permeability; Tracers; Solutes; Human diseases; Growth; Anions; Erythrocytes; Uptake; Endoparasites; Sugar; Parasites; Amino acids; Chloride channels; Malaria; Nutrients; purines; Pinocytosis; Cations; Ion channels; Nutrient uptake DO - http://dx.doi.org/10.1038/35023000 ER - TY - JOUR T1 - Structure and function of mismatch repair proteins. AN - 71799525; 10946232 AB - DNA mismatch repair is required for maintaining genomic stability and is highly conserved from prokaryotes to eukaryotes. Errors made during DNA replication, such as deletions, insertions and mismatched basepairs, are substrates for mismatch repair. Mismatch repair is strand-specific and targets only the newly synthesized daughter strand. To initiate mismatch repair in Escherichia coli, three proteins are essential, MutS, for mismatch recognition, MutH, for introduction of a nick in the target strand, and MutL, for mediating the interactions between MutH and MutS. Homologues of MutS and MutL important for mismatch repair have been found in nearly all organisms. Mutations in MutS and MutL homologues have been linked to increased cancer susceptibility in both mice and humans. Here, we review the crystal structures of the MutH endonuclease, a conserved ATPase fragment of MutL (LN40), and complexes of LN40 with various nucleotides. Based on the crystal structure, the active site of MutH has been identified and an evolutionary relationship between MutH and type II restriction endonucleases established. Recent crystallographic and biochemical studies have revealed that MutL operates as a molecular switch with its interactions with MutH and MutS regulated by ATP binding and hydrolysis. These crystal structures also shed light on the general mechanism of mismatch repair and the roles of Mut proteins in preventing mutagenesis. JF - Mutation research AU - Yang, W AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. wei.yang@nih.gov Y1 - 2000/08/30/ PY - 2000 DA - 2000 Aug 30 SP - 245 EP - 256 VL - 460 IS - 3-4 SN - 0027-5107, 0027-5107 KW - Bacterial Proteins KW - 0 KW - DNA, Bacterial KW - DNA-Binding Proteins KW - Escherichia coli Proteins KW - Macromolecular Substances KW - MutL protein, E coli KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Endodeoxyribonucleases KW - EC 3.1.- KW - methyl-directed mismatch repair protein, E coli KW - EC 3.1.21.- KW - CAGCTG-specific type II deoxyribonucleases KW - EC 3.1.21.4 KW - Deoxyribonucleases, Type II Site-Specific KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - MutL Proteins KW - EC 3.6.1.3 KW - MutS DNA Mismatch-Binding Protein KW - MutS protein, E coli KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Magnesium KW - I38ZP9992A KW - Index Medicus KW - Animals KW - Models, Molecular KW - Magnesium -- physiology KW - Humans KW - Mice KW - Protein Binding KW - Hydrolysis KW - Evolution, Molecular KW - Structure-Activity Relationship KW - Binding Sites KW - Deoxyribonucleases, Type II Site-Specific -- metabolism KW - Adenosine Triphosphate -- physiology KW - Deoxyribonucleases, Type II Site-Specific -- chemistry KW - Allosteric Regulation KW - Crystallography, X-Ray KW - Cell Transformation, Neoplastic -- genetics KW - Protein Conformation KW - Endodeoxyribonucleases -- chemistry KW - DNA Repair KW - DNA-Binding Proteins -- chemistry KW - DNA Damage KW - Escherichia coli -- genetics KW - Escherichia coli -- enzymology KW - Endodeoxyribonucleases -- physiology KW - Bacterial Proteins -- chemistry KW - DNA, Bacterial -- chemistry KW - Base Pair Mismatch KW - DNA, Bacterial -- genetics KW - DNA, Bacterial -- metabolism KW - DNA-Binding Proteins -- physiology KW - Bacterial Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71799525?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Structure+and+function+of+mismatch+repair+proteins.&rft.au=Yang%2C+W&rft.aulast=Yang&rft.aufirst=W&rft.date=2000-08-30&rft.volume=460&rft.issue=3-4&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-13 N1 - Date created - 2000-11-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The use of sliding time windows for the exploratory analysis of temporal effects of smoking histories on lung cancer risk AN - 18153994; 4774066 AB - To examine the time-dependent effects of exposure histories on disease we use sliding time windows as an exploratory alternative to the analysis of variables like time since last exposure and duration of exposure. The method fits a series of risk models which contain total cumulative exposure and an additional covariate for exposures received during fixed time intervals. Characteristics of the fitted models provide insight into the influence of exposure increments at different times on disease risk. A simulation study is performed to check the validity of the approach. We apply the method to data from a recent German case-control study on smoking and lung cancer risk with about 4300 lung cancer cases and a similiar number of controls. The sliding time window approach indicates that the amount of cigarettes smoked from two to 11 years before disease incidence is most predicitive of lung cancer incidence. Among different smoking profiles that result in the same lifelong cumulative number of cigarettes smoked, those with a concentration of smoked cigarettes within 20 years before interview bear substantially larger risk than others. JF - Statistics in Medicine AU - Hauptmann, M AU - Lubin, J H AU - Rosenberg, P AU - Wellmann, J AU - Kreienbrock, L AD - National Cancer Institute, Division of Cancer Epidemiology and Genetics, 6120 Executive Blvd., EPS/7089, Bethesda, MD 20892, USA, hauptmann@nih.gov Y1 - 2000/08/30/ PY - 2000 DA - 2000 Aug 30 SP - 2185 EP - 2194 VL - 19 IS - 16 SN - 0277-6715, 0277-6715 KW - sliding time windows KW - man KW - Toxicology Abstracts KW - Risk assessment KW - Smoking KW - lung cancer KW - Mathematical models KW - Cigarette smoking KW - Cancer KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18153994?accountid=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=Statistics+in+Medicine&rft.atitle=The+use+of+sliding+time+windows+for+the+exploratory+analysis+of+temporal+effects+of+smoking+histories+on+lung+cancer+risk&rft.au=Hauptmann%2C+M%3BLubin%2C+J+H%3BRosenberg%2C+P%3BWellmann%2C+J%3BKreienbrock%2C+L&rft.aulast=Hauptmann&rft.aufirst=M&rft.date=2000-08-30&rft.volume=19&rft.issue=16&rft.spage=2185&rft.isbn=&rft.btitle=&rft.title=Statistics+in+Medicine&rft.issn=02776715&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 - Mathematical models; Cigarette smoking; lung cancer; Cancer; Risk assessment; Smoking ER - TY - JOUR T1 - Relative role of heme nitrosylation and beta-cysteine 93 nitrosation in the transport and metabolism of nitric oxide by hemoglobin in the human circulation. AN - 72216739; 10954746 AB - To quantify the reactions of nitric oxide (NO) with hemoglobin under physiological conditions and to test models of NO transport on hemoglobin, we have developed an assay to measure NO-hemoglobin reaction products in normal volunteers, under basal conditions and during NO inhalation. NO inhalation markedly raised total nitrosylated hemoglobin levels, with a significant arterial-venous gradient, supporting a role for hemoglobin in the transport and delivery of NO. The predominant species accounting for this arterial-venous gradient is nitrosyl(heme)hemoglobin. NO breathing increases S-nitrosation of hemoglobin beta-chain cysteine 93, however only to a fraction of the level of nitrosyl(heme)hemoglobin and without a detectable arterial-venous gradient. A strong correlation between methemoglobin and plasma nitrate formation was observed, suggesting that NO metabolism is a primary physiological cause of hemoglobin oxidation. Our results demonstrate that NO-heme reaction pathways predominate in vivo, NO binding to heme groups is a rapidly reversible process, and S-nitrosohemoglobin formation is probably not a primary transport mechanism for NO but may facilitate NO release from heme. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Gladwin, M T AU - Ognibene, F P AU - Pannell, L K AU - Nichols, J S AU - Pease-Fye, M E AU - Shelhamer, J H AU - Schechter, A N AD - Critical Care Medicine Department of the Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. mgladwin@nih.gov Y1 - 2000/08/29/ PY - 2000 DA - 2000 Aug 29 SP - 9943 EP - 9948 VL - 97 IS - 18 SN - 0027-8424, 0027-8424 KW - Hemoglobins KW - 0 KW - Nitrates KW - Nitrites KW - Nitroso Compounds KW - Nitric Oxide KW - 31C4KY9ESH KW - Heme KW - 42VZT0U6YR KW - Ozone KW - 66H7ZZK23N KW - Cysteine KW - K848JZ4886 KW - Potassium Cyanide KW - MQD255M2ZO KW - Index Medicus KW - Sensitivity and Specificity KW - Nitrites -- blood KW - Reproducibility of Results KW - Luminescent Measurements KW - Kinetics KW - Humans KW - Potassium Cyanide -- pharmacokinetics KW - Administration, Inhalation KW - Nitrates -- blood KW - Hemoglobins -- metabolism KW - Nitric Oxide -- pharmacokinetics KW - Heme -- chemistry KW - Nitric Oxide -- blood KW - Nitroso Compounds -- blood KW - Hemoglobins -- chemistry KW - Nitric Oxide -- administration & dosage KW - Heme -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72216739?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Relative+role+of+heme+nitrosylation+and+beta-cysteine+93+nitrosation+in+the+transport+and+metabolism+of+nitric+oxide+by+hemoglobin+in+the+human+circulation.&rft.au=Gladwin%2C+M+T%3BOgnibene%2C+F+P%3BPannell%2C+L+K%3BNichols%2C+J+S%3BPease-Fye%2C+M+E%3BShelhamer%2C+J+H%3BSchechter%2C+A+N&rft.aulast=Gladwin&rft.aufirst=M&rft.date=2000-08-29&rft.volume=97&rft.issue=18&rft.spage=9943&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 - 2000-10-05 N1 - Date created - 2000-10-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1999 Feb 26;274(9):5499-507 [10026163] Biochem Biophys Res Commun. 1998 Nov 27;252(3):535-40 [9837741] Biochim Biophys Acta. 1999 May 5;1411(2-3):290-309 [10320664] Biochim Biophys Acta. 1999 May 5;1411(2-3):370-7 [10320669] J Biol Chem. 1999 May 28;274(22):15487-92 [10336440] Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9027-32 [10430889] Am J Physiol. 1999 Aug;277(2 Pt 2):H676-82 [10444494] J Biol Chem. 1999 Aug 27;274(35):24742-8 [10455144] Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):9967-9 [10468537] J Biol Chem. 1999 Oct 1;274(40):28128-33 [10497164] J Biol Chem. 1999 Oct 8;274(41):28983-90 [10506146] J Clin Invest. 1999 Oct;104(7):937-45 [10510334] Nature. 1965 Nov 20;208(5012):760-2 [5868886] Biochem J. 1977 Jul 1;165(1):141-8 [889569] J Biol Chem. 1979 Nov 25;254(22):11467-74 [40982] Chem Res Toxicol. 1990 Jul-Aug;3(4):289-91 [2133073] Chem Res Toxicol. 1993 Jan-Feb;6(1):23-7 [8448345] Am J Physiol. 1994 May;266(5 Pt 1):C1400-5 [8203503] Chem Res Toxicol. 1994 Jul-Aug;7(4):519-25 [7981416] Nat Med. 1995 Aug;1(8):804-9 [7585184] J Biol Chem. 1995 Nov 24;270(47):28158-64 [7499306] Biochem Biophys Res Commun. 1996 Jan 26;218(3):749-52 [8579585] Nature. 1996 Mar 21;380(6571):205-6 [8637566] Nature. 1996 Mar 21;380(6571):221-6 [8637569] Nat Med. 1997 Apr;3(4):456-9 [9095182] Science. 1997 Jun 27;276(5321):2034-7 [9197264] Biochem Biophys Res Commun. 1997 Oct 9;239(1):284-6 [9345311] Br J Anaesth. 1997 Nov;79(5):631-40 [9422904] Nature. 1998 Jan 8;391(6663):169-73 [9428761] J Appl Physiol (1985). 1998 Jan;84(1):107-15 [9451624] Am J Physiol. 1998 Jan;274(1 Pt 2):H349-57 [9458886] Anal Biochem. 1998 May 1;258(2):322-30 [9570848] J Clin Invest. 1998 Jun 1;101(11):2497-505 [9616221] J Biol Chem. 1998 Aug 7;273(32):20323-33 [9685383] Am J Respir Crit Care Med. 1998 Sep;158(3):833-9 [9731013] Free Radic Biol Med. 1998 Sep;25(4-5):434-56 [9741580] Free Radic Biol Med. 1998 Sep;25(4-5):621-8 [9741600] Biochemistry. 1998 Sep 22;37(38):13194-202 [9748326] Biochim Biophys Acta. 1999 May 5;1411(2-3):250-62 [10320661] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inactivating mutation of the mouse tissue inhibitor of metalloproteinases-2(Timp-2) gene alters proMMP-2 activation. AN - 72195434; 10827176 AB - To understand the biologic function of TIMP-2, a member of the tissue inhibitors of metalloproteinases family, an inactivating mutation was introduced in the mouse Timp-2 gene by homologous recombination. Outbred homozygous mutants developed and procreated indistinguishably from wild type littermates, suggesting that fertility, development, and growth are not critically dependent on TIMP-2. Lack of functional TIMP-2, however, dramatically altered the activation of proMMP-2 both in vivo and in vitro. Fully functional TIMP-2 is essential for efficient activation of proMMP-2 in vivo. No evidence of successful functional compensation was observed. The results illustrate the duality of TIMP-2 function, i.e. at low concentrations, TIMP-2 exerts a "catalytic" or enhancing effect on cell-mediated proMMP-2 activation, whereas at higher concentrations, TIMP-2 inhibits the activation and/or activity of MMP-2. JF - The Journal of biological chemistry AU - Caterina, J J AU - Yamada, S AU - Caterina, N C AU - Longenecker, G AU - Holmbäck, K AU - Shi, J AU - Yermovsky, A E AU - Engler, J A AU - Birkedal-Hansen, H AD - NIDCR Matrix Metalloproteinase Unit and NIDCR Gene Targeting Research and Core Facility, National Institutes of Health, Bethesda, Maryland, 20892-4380, USA. jc239h@nih.gov Y1 - 2000/08/25/ PY - 2000 DA - 2000 Aug 25 SP - 26416 EP - 26422 VL - 275 IS - 34 SN - 0021-9258, 0021-9258 KW - Enzyme Precursors KW - 0 KW - Tissue Inhibitor of Metalloproteinase-2 KW - 127497-59-0 KW - Gelatinases KW - EC 3.4.24.- KW - Metalloendopeptidases KW - progelatinase KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Protein Structure, Secondary KW - Base Sequence KW - Enzyme Activation KW - Cells, Cultured KW - Recombination, Genetic KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Male KW - Female KW - Enzyme Precursors -- metabolism KW - Tissue Inhibitor of Metalloproteinase-2 -- metabolism KW - Metalloendopeptidases -- metabolism KW - Gelatinases -- metabolism KW - Tissue Inhibitor of Metalloproteinase-2 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72195434?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inactivating+mutation+of+the+mouse+tissue+inhibitor+of+metalloproteinases-2%28Timp-2%29+gene+alters+proMMP-2+activation.&rft.au=Caterina%2C+J+J%3BYamada%2C+S%3BCaterina%2C+N+C%3BLongenecker%2C+G%3BHolmb%C3%A4ck%2C+K%3BShi%2C+J%3BYermovsky%2C+A+E%3BEngler%2C+J+A%3BBirkedal-Hansen%2C+H&rft.aulast=Caterina&rft.aufirst=J&rft.date=2000-08-25&rft.volume=275&rft.issue=34&rft.spage=26416&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 - 2000-09-25 N1 - Date created - 2000-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conformationally constrained analogues of diacylglycerol (DAG). 17. Contrast between sn-1 and sn-2 DAG lactones in binding to protein kinase C. AN - 72226551; 10966739 AB - In previous work, we have obtained potent protein kinase C (PK-C) ligands with low-namomolar binding affinities by constructing diacylglycerol (DAG) mimetics in which the sn-2 carbonyl of DAG was constrained into a lactone ring. An additional structural element that helped achieve high binding affinity was the presence of branched acyl or alpha-alkylidene chains. In the present study, the effects of similarly branched chains on a different lactone system, where the lactone carbonyl is now equivalent to the sn-1 carbonyl of DAG, are investigated. In this new lactone template, the two chiral centers must have the S-configuration for enzyme recognition. As with the sn-2 DAG lactones, the branched chains were designed to optimize van der Waals contacts with a group of conserved hydrophobic amino acids located on the rim of the C1 domain of PK-C. The acyl and alpha-alkylidene chains were also designed to be lipophilically equivalent (8 carbons each). Eight new compounds (7-14) representing all possible combinations of linear and branched acyl and alpha-alkylidene were synthesized and evaluated. The sn-1 DAG lactones were less effective as PK-C ligands than the sn-2 DAG lactones despite having a similar array of linear or branched acyl and alpha-alkylidene chains JF - Journal of medicinal chemistry AU - Tamamura, H AU - Bienfait, B AU - Nacro, K AU - Lewin, N E AU - Blumberg, P M AU - Marquez, V E AD - Laboratories of Medicinal Chemistry and of Cellular Carcinogenesis and Tumor Promotion, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/08/24/ PY - 2000 DA - 2000 Aug 24 SP - 3209 EP - 3217 VL - 43 IS - 17 SN - 0022-2623, 0022-2623 KW - Diglycerides KW - 0 KW - Isoenzymes KW - Lactones KW - Ligands KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Stereoisomerism KW - Molecular Mimicry KW - Protein Binding KW - Isoenzymes -- metabolism KW - Structure-Activity Relationship KW - Protein Kinase C -- metabolism KW - Diglycerides -- chemistry KW - Diglycerides -- chemical synthesis KW - Lactones -- chemistry KW - Lactones -- chemical synthesis KW - Lactones -- metabolism KW - Diglycerides -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72226551?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Conformationally+constrained+analogues+of+diacylglycerol+%28DAG%29.+17.+Contrast+between+sn-1+and+sn-2+DAG+lactones+in+binding+to+protein+kinase+C.&rft.au=Tamamura%2C+H%3BBienfait%2C+B%3BNacro%2C+K%3BLewin%2C+N+E%3BBlumberg%2C+P+M%3BMarquez%2C+V+E&rft.aulast=Tamamura&rft.aufirst=H&rft.date=2000-08-24&rft.volume=43&rft.issue=17&rft.spage=3209&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=00222623&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-21 N1 - Date created - 2000-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ischemic preconditioning activates phosphatidylinositol-3-kinase upstream of protein kinase C. AN - 71775162; 10948065 AB - The present study is designed to test whether phosphatidylinositol 3-kinase (PI3-kinase) has a role in the signaling pathway in ischemic preconditioning (PC) and whether it is proximal or distal to protein kinase C (PKC). Before 20 minutes of global ischemia, Langendorff-perfused rat hearts were perfused for 20 minutes (control); preconditioned with 4 cycles of 5-minute ischemia and 5-minute reflow (PC); treated with either wortmannin (WM) or LY 294002 (LY), each of which is a PI3-kinase inhibitor, for 5 minutes before and throughout PC; treated with 1,2-dioctanoyl-sn-glycerol (DOG), an activator of PKC for 10 minutes (DOG); treated identically to the DOG group except with WM added 10 minutes before and during perfusion with DOG; or treated with either WM or LY for 25 minutes. Recovery of left ventricular developed pressure (LVDP; percentage of initial preischemic LVDP), measured after 30 minutes of reflow, was improved by PC (72+/-2% versus 36+/-4% in control; P0.05 compared with DOG; P<0.05 compared with control). PC induced phosphorylation of protein kinase B and translocation of PKC epsilon, and it increased NO production, and these effects were blocked by WM, which suggests a role for PI3-kinase in PC upstream of PKC and NO. JF - Circulation research AU - Tong, H AU - Chen, W AU - Steenbergen, C AU - Murphy, E AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. tong@niehs.nih.gov Y1 - 2000/08/18/ PY - 2000 DA - 2000 Aug 18 SP - 309 EP - 315 VL - 87 IS - 4 SN - 0009-7330, 0009-7330 KW - Androstadienes KW - 0 KW - Chromones KW - Diglycerides KW - Enzyme Inhibitors KW - Isoenzymes KW - Morpholines KW - Phosphodiesterase Inhibitors KW - Proto-Oncogene Proteins KW - 1,2-dioctanoylglycerol KW - 1069-87-0 KW - Nitric Oxide KW - 31C4KY9ESH KW - 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one KW - 31M2U1DVID KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Glycogen KW - 9005-79-2 KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Prkce protein, rat KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-akt KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-epsilon KW - wortmannin KW - XVA4O219QW KW - Index Medicus KW - Coronary Circulation -- physiology KW - Phosphodiesterase Inhibitors -- pharmacology KW - Animals KW - Hydrogen-Ion Concentration KW - Morpholines -- pharmacology KW - Proto-Oncogene Proteins -- metabolism KW - Androstadienes -- pharmacology KW - Nitric Oxide -- metabolism KW - Recovery of Function -- physiology KW - Recovery of Function -- drug effects KW - Coronary Circulation -- drug effects KW - Isoenzymes -- metabolism KW - Rats KW - Rats, Sprague-Dawley KW - Diglycerides -- pharmacology KW - Phosphorylation KW - Chromones -- pharmacology KW - Glycogen -- metabolism KW - Adenosine Triphosphate -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Male KW - Protein Kinase C -- metabolism KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Myocardium -- enzymology KW - Myocardial Reperfusion Injury -- metabolism KW - Ischemic Preconditioning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71775162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation+research&rft.atitle=Ischemic+preconditioning+activates+phosphatidylinositol-3-kinase+upstream+of+protein+kinase+C.&rft.au=Tong%2C+H%3BChen%2C+W%3BSteenbergen%2C+C%3BMurphy%2C+E&rft.aulast=Tong&rft.aufirst=H&rft.date=2000-08-18&rft.volume=87&rft.issue=4&rft.spage=309&rft.isbn=&rft.btitle=&rft.title=Circulation+research&rft.issn=00097330&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-12 N1 - Date created - 2000-09-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vaccines against intracellular infections requiring cellular immunity AN - 762271900; 13742834 AB - Vaccines against a variety of infectious diseases represent one of the great triumphs of medicine. The immune correlates of protection induced by most current vaccines seem to be mediated by long-lived humoral immune responses. By contrast, there are no currently available vaccines that are uniformly effective for diseases such as HIV, malaria and tuberculosis, in which the cellular immune response might be crucial in mediating protection. Here we examine the mechanisms by which long-lived cellular immune responses are generated and maintained in vivo. We then discuss current approaches for vaccination against diseases in which cellular immune responses are important for protection. JF - Nature AU - Seder, Robert A AU - Hill, Adrian VS AD - Clinical Immunology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA Y1 - 2000/08/17/ PY - 2000 DA - 2000 Aug 17 SP - 793 EP - 798 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 406 IS - 6797 SN - 0028-0836, 0028-0836 KW - Immunology Abstracts; ASFA 3: Aquatic Pollution & Environmental Quality; ASFA 1: Biological Sciences & Living Resources KW - Human diseases KW - Mycobacterium KW - Disease control KW - Malaria KW - Immunity KW - Infection KW - Defence mechanisms KW - Vaccination KW - Public health KW - Immunity (cell-mediated) KW - Infectious diseases KW - Human immunodeficiency virus KW - Tuberculosis KW - Immune response KW - Vaccines KW - Immune response (humoral) KW - Q1 08423:Behaviour KW - F 06910:Microorganisms & Parasites KW - Q5 08524:Public health, medicines, dangerous organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/762271900?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Vaccines+against+intracellular+infections+requiring+cellular+immunity&rft.au=Seder%2C+Robert+A%3BHill%2C+Adrian+VS&rft.aulast=Seder&rft.aufirst=Robert&rft.date=2000-08-17&rft.volume=406&rft.issue=6797&rft.spage=793&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/10.1038%2F35021239 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-11-01 N1 - Last updated - 2016-10-12 N1 - SubjectsTermNotLitGenreText - Human diseases; Infectious diseases; Disease control; Tuberculosis; Immunity; Vaccines; Defence mechanisms; Vaccination; Public health; Immunity (cell-mediated); Malaria; Immune response; Immune response (humoral); Infection; Mycobacterium; Human immunodeficiency virus DO - http://dx.doi.org/10.1038/35021239 ER - TY - JOUR T1 - 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, a carcinogen in high-temperature-cooked meat, and breast cancer risk. AN - 71774387; 10944558 JF - Journal of the National Cancer Institute AU - Sinha, R AU - Gustafson, D R AU - Kulldorff, M AU - Wen, W Q AU - Cerhan, J R AU - Zheng, W AD - Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. sinhar@nih.gov Y1 - 2000/08/16/ PY - 2000 DA - 2000 Aug 16 SP - 1352 EP - 1354 VL - 92 IS - 16 SN - 0027-8874, 0027-8874 KW - Carcinogens KW - 0 KW - Imidazoles KW - Mutagens KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Risk KW - Mutagens -- adverse effects KW - Humans KW - Female KW - Meat KW - Hot Temperature KW - Cooking KW - Breast Neoplasms -- etiology KW - Breast Neoplasms -- chemically induced KW - Imidazoles -- adverse effects KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71774387?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine%2C+a+carcinogen+in+high-temperature-cooked+meat%2C+and+breast+cancer+risk.&rft.au=Sinha%2C+R%3BGustafson%2C+D+R%3BKulldorff%2C+M%3BWen%2C+W+Q%3BCerhan%2C+J+R%3BZheng%2C+W&rft.aulast=Sinha&rft.aufirst=R&rft.date=2000-08-16&rft.volume=92&rft.issue=16&rft.spage=1352&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-20 N1 - Date created - 2000-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeted disruption of the epidermal growth factor receptor inhibits development of papillomas and carcinomas from human papillomavirus-immortalized keratinocytes. AN - 72220568; 10969784 AB - The epidermal growth factor receptor (EGF-R) is frequently overexpressed in human papillomavirus (HPV)-associated dysplasias and carcinomas, implying that it is important for the progression of keratinocytes to malignancy. We used mice with a targeted disruption of the EGF-R gene to directly examine its role in cell immortalization and tumor development. Epidermal keratinocytes were cultured from EGF-R knockout, heterozygous, and wild-type mice, infected with retroviruses encoding HPV-16 E6 and E7 oncogenes, and grafted to nude mice. E6/E7 induced immortalization of EGF-R wild-type cells 5-fold more efficiently than null cells. Immortal EGF-R null cells grew more slowly, achieved a lower saturation density, and were more sensitive to apoptosis than the immortalized wild-type or heterozygous cells. Analyses using cDNA expression arrays showed that EGF-R null cells expressed increased levels of RNAs encoding p21waf and insulin-like growth factor-binding protein-2. EGF-R-positive immortal keratinocytes formed papillomas in 17% (15 of 90) of skin grafts, and seven grafts progressed to squamous carcinoma after 6-12 months. EGF-R null keratinocytes did not form papillomas, but 1 of 96 grafts progressed to a squamous carcinoma after 1 year. However, treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate induced tumors in 18 and 35% of grafts containing EGF-R null or EGF-R-positive cells, respectively. Transduction with an activated v-Ha-ras gene, which signals downstream of the EGF-R, induced rapidly growing carcinomas in all grafts regardless of EGF-R genotype. These results directly show that the EGF-R is important, but not essential, for immortalization by HPV and for progression of immortal cells to papillomas and carcinomas. JF - Cancer research AU - Woodworth, C D AU - Gaiotti, D AU - Michael, E AU - Hansen, L AU - Nees, M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. woodworth@clarkson.edu Y1 - 2000/08/15/ PY - 2000 DA - 2000 Aug 15 SP - 4397 EP - 4402 VL - 60 IS - 16 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - E6 protein, Human papillomavirus type 16 KW - Oncogene Proteins, Viral KW - Papillomavirus E7 Proteins KW - Repressor Proteins KW - oncogene protein E7, Human papillomavirus type 16 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Cocarcinogenesis KW - Humans KW - Disease Progression KW - Gene Expression KW - Mice, Nude KW - Mice KW - Mice, Inbred BALB C KW - Genotype KW - Genes, ras -- genetics KW - Oncogene Proteins, Viral -- genetics KW - Cell Line, Transformed KW - Mutation KW - Cell Transformation, Viral KW - Keratinocytes -- transplantation KW - Papilloma -- prevention & control KW - Carcinoma, Squamous Cell -- chemically induced KW - Papillomaviridae -- genetics KW - Receptor, Epidermal Growth Factor -- physiology KW - Skin Neoplasms -- prevention & control KW - Skin Neoplasms -- virology KW - Carcinoma, Squamous Cell -- virology KW - Receptor, Epidermal Growth Factor -- genetics KW - Papilloma -- virology KW - Carcinoma, Squamous Cell -- prevention & control KW - Keratinocytes -- pathology KW - Keratinocytes -- virology KW - Papilloma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72220568?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Targeted+disruption+of+the+epidermal+growth+factor+receptor+inhibits+development+of+papillomas+and+carcinomas+from+human+papillomavirus-immortalized+keratinocytes.&rft.au=Woodworth%2C+C+D%3BGaiotti%2C+D%3BMichael%2C+E%3BHansen%2C+L%3BNees%2C+M&rft.aulast=Woodworth&rft.aufirst=C&rft.date=2000-08-15&rft.volume=60&rft.issue=16&rft.spage=4397&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 - 2000-09-14 N1 - Date created - 2000-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunoactive cannabinoids: therapeutic prospects for marijuana constituents. AN - 71763700; 10931962 JF - Proceedings of the National Academy of Sciences of the United States of America AU - Straus, S E AD - National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, MD 20892-2182, USA. Y1 - 2000/08/15/ PY - 2000 DA - 2000 Aug 15 SP - 9363 EP - 9364 VL - 97 IS - 17 SN - 0027-8424, 0027-8424 KW - Ligands KW - 0 KW - Receptors, Cannabinoid KW - Receptors, Drug KW - Cannabidiol KW - 19GBJ60SN5 KW - Index Medicus KW - Complementary Therapies -- trends KW - Animals KW - Receptors, Drug -- metabolism KW - Receptors, Drug -- agonists KW - Mice KW - Receptors, Drug -- antagonists & inhibitors KW - Phytotherapy KW - Cannabidiol -- therapeutic use KW - Arthritis -- pathology KW - Cannabis -- chemistry KW - Cannabis -- therapeutic use KW - Cannabis -- immunology KW - Arthritis -- chemically induced KW - Cannabidiol -- chemistry KW - Immune System -- immunology KW - Immune System -- metabolism KW - Arthritis -- immunology KW - Cannabidiol -- immunology KW - Arthritis -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71763700?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Immunoactive+cannabinoids%3A+therapeutic+prospects+for+marijuana+constituents.&rft.au=Straus%2C+S+E&rft.aulast=Straus&rft.aufirst=S&rft.date=2000-08-15&rft.volume=97&rft.issue=17&rft.spage=9363&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 - 2000-09-19 N1 - Date created - 2000-09-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: JAMA. 1998 Nov 11;280(18):1569-75 [9820257] J Neuroimmunol. 1998 Mar 15;83(1-2):102-15 [9610678] Immunopharmacology. 1998 Nov;40(3):179-85 [9858061] Life Sci. 1999;65(6-7):573-95 [10462059] Gastroenterology. 1999 Dec;117(6):1433-7 [10579985] Cancer Epidemiol Biomarkers Prev. 1999 Dec;8(12):1071-8 [10613339] Annu Rev Med. 2000;51:207-29 [10774461] Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9561-6 [10920191] Science. 1970 Jun 5;168(3936):1159-66 [4910003] J Environ Pathol Toxicol. 1980 Aug;4(1):471-82 [6255054] Toxicol Appl Pharmacol. 1981 Mar 30;58(1):118-31 [6262948] Pharmacol Rev. 1986 Jun;38(2):75-149 [3018800] Nature. 1990 Aug 9;346(6284):561-4 [2165569] Int J Immunopharmacol. 1991;13(8):1091-7 [1667651] Nature. 1993 Sep 2;365(6441):61-5 [7689702] Comment On: Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9561-6 [10920191] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of modified hepatitis C virus E2 proteins expressed on the cell surface. AN - 71758708; 10936090 AB - The envelope proteins of hepatitis C virus (HCV) are the likely targets of neutralizing antibodies and their molecular and functional characterization is relevant for vaccine development. We previously showed that surface-expressed E2 is a better immunogen than intracellular E2 and, therefore, we were interested in exploring more efficient ways to present E2 protein on the cell surface. We found that E2 targeted to the cell surface by replacement of its transmembrane domain did not bring E1 to the surface although E1 could be expressed independently on the cell surface if its transmembrane domain was similarly replaced. FACS analysis suggested that E2 expressed on the cell surface acquired its native conformation more efficiently when truncated at aa 661 than when truncated at aa 715. The shorter form of truncated E2 better retained the ability to bind the second extracellular loop (EC2) of CD81, the putative HCV receptor. Interestingly, deletion of the hypervariable region 1 (HVR1) did not perceptibly alter E2 structure; cell-surface forms of E2 lacking the HVR1 remained reactive with conformation-sensitive MAbs and were able to bind recombinant EC2 of CD81. Copyright 2000 Academic Press. JF - Virology AU - Forns, X AU - Allander, T AU - Rohwer-Nutter, P AU - Bukh, J AD - Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. XFORNS@clinic.ub.es Y1 - 2000/08/15/ PY - 2000 DA - 2000 Aug 15 SP - 75 EP - 85 VL - 274 IS - 1 SN - 0042-6822, 0042-6822 KW - Amino Acids KW - 0 KW - Antigens, CD KW - Antigens, CD81 KW - CD81 protein, human KW - Cd81 protein, mouse KW - E1 protein, Hepatitis C virus KW - HVR1 protein, Hepatitis C virus KW - Membrane Proteins KW - Receptors, Virus KW - Recombinant Fusion Proteins KW - Viral Envelope Proteins KW - Viral Proteins KW - glycoprotein E2, Hepatitis C virus KW - 157184-61-7 KW - Index Medicus KW - Viral Proteins -- genetics KW - Animals KW - Humans KW - Membrane Proteins -- metabolism KW - Biological Transport KW - Gene Expression KW - Antigens, CD -- genetics KW - Receptors, Virus -- metabolism KW - Receptors, Virus -- genetics KW - Rabbits KW - Mice KW - Membrane Proteins -- genetics KW - Protein Binding KW - Mutagenesis KW - Recombinant Fusion Proteins -- metabolism KW - Tumor Cells, Cultured KW - Recombinant Fusion Proteins -- genetics KW - Antigens, CD -- metabolism KW - Viral Proteins -- metabolism KW - Cell Membrane -- metabolism KW - Protein Conformation KW - Hepacivirus -- metabolism KW - Viral Envelope Proteins -- chemistry KW - Hepacivirus -- genetics KW - Viral Envelope Proteins -- biosynthesis KW - Viral Envelope Proteins -- metabolism KW - Viral Envelope Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71758708?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virology&rft.atitle=Characterization+of+modified+hepatitis+C+virus+E2+proteins+expressed+on+the+cell+surface.&rft.au=Forns%2C+X%3BAllander%2C+T%3BRohwer-Nutter%2C+P%3BBukh%2C+J&rft.aulast=Forns&rft.aufirst=X&rft.date=2000-08-15&rft.volume=274&rft.issue=1&rft.spage=75&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-25 N1 - Date created - 2000-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia. AN - 71738134; 10934283 AB - Inflammation in the brain has been increasingly associated with the development of a number of neurological diseases. The hallmark of neuroinflammation is the activation of microglia, the resident brain immune cells. Injection of bacterial endotoxin lipopolysaccharide (LPS) into the hippocampus, cortex, or substantia nigra of adult rats produced neurodegeneration only in the substantia nigra. Although LPS appeared to impact upon mesencephalic neurons in general, an extensive loss of dopaminergic neurons was observed. Analysis of the abundance of microglia revealed that the substantia nigra had the highest density of microglia. When mixed neuron-glia cultures derived from the rat hippocampus, cortex, or mesencephalon were treated with LPS, mesencephalic cultures became sensitive to LPS at a concentration as low as 10 ng/ml and responded in a dose-dependent manner with the production of inflammatory factors and a loss of dopaminergic and other neurons. In contrast, hippocampal or cortical cultures remained insensitive to LPS treatment at concentrations as high as 10 microg/ml. Consistent with in vivo observations, mesencephalic cultures had fourfold to eightfold more microglia than cultures from other regions. The positive correlation between abundance of microglia and sensitivity to LPS-induced neurotoxicity was further supported by the observation that supplementation with enriched microglia derived from mesencephalon or cortex rendered LPS-insensitive cortical neuron-glia cultures sensitive to LPS-induced neurotoxicity. These data indicate that the region-specific differential susceptibility of neurons to LPS is attributable to differences in the number of microglia present within the system and may reflect levels of inflammation-related factors produced by these cells. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Kim, W G AU - Mohney, R P AU - Wilson, B AU - Jeohn, G H AU - Liu, B AU - Hong, J S AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000/08/15/ PY - 2000 DA - 2000 Aug 15 SP - 6309 EP - 6316 VL - 20 IS - 16 SN - 0270-6474, 0270-6474 KW - Lipopolysaccharides KW - 0 KW - Neurotoxins KW - Tumor Necrosis Factor-alpha KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Animals KW - Cerebral Cortex -- drug effects KW - Neurons -- metabolism KW - Cell Count KW - Neurons -- drug effects KW - Substantia Nigra -- drug effects KW - Nitric Oxide -- biosynthesis KW - Tumor Necrosis Factor-alpha -- secretion KW - Pregnancy KW - Neurons -- pathology KW - Cerebral Cortex -- physiopathology KW - Hippocampus -- drug effects KW - Rats KW - Substantia Nigra -- physiopathology KW - Rats, Inbred F344 KW - Cell Survival -- drug effects KW - Substantia Nigra -- pathology KW - Cells, Cultured KW - Tumor Necrosis Factor-alpha -- drug effects KW - Cerebral Cortex -- pathology KW - Hippocampus -- physiopathology KW - Hippocampus -- pathology KW - Male KW - Cell Survival -- physiology KW - Female KW - Inflammation -- physiopathology KW - Nerve Degeneration -- physiopathology KW - Brain -- drug effects KW - Inflammation -- chemically induced KW - Nerve Degeneration -- chemically induced KW - Neurotoxins -- toxicity KW - Brain -- physiopathology KW - Brain -- pathology KW - Nerve Degeneration -- pathology KW - Lipopolysaccharides -- toxicity KW - Microglia -- drug effects KW - Microglia -- pathology KW - Inflammation -- pathology KW - Microglia -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71738134?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regional+difference+in+susceptibility+to+lipopolysaccharide-induced+neurotoxicity+in+the+rat+brain%3A+role+of+microglia.&rft.au=Kim%2C+W+G%3BMohney%2C+R+P%3BWilson%2C+B%3BJeohn%2C+G+H%3BLiu%2C+B%3BHong%2C+J+S&rft.aulast=Kim&rft.aufirst=W&rft.date=2000-08-15&rft.volume=20&rft.issue=16&rft.spage=6309&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=02706474&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-31 N1 - Date created - 2000-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficacy and safety of troglitazone in the treatment of lipodystrophy syndromes. AN - 71256323; 10929166 AB - Troglitazone promotes adipocyte differentiation in vitro and increases insulin sensitivity in vivo. Therefore, troglitazone may have therapeutic benefit in lipoatrophic diabetes. To determine whether troglitazone ameliorates hyperglycemia and hypertriglyceridemia or increases fat mass in lipoatrophic patients. Open-labeled prospective study. United States and Canada. 20 patients with various syndromes associated with lipoatrophy or lipodystrophy. 6 months of therapy with troglitazone, 200 to 600 mg/d. Levels of hemoglobin A1c triglycerides, free fatty acids, and insulin; respiratory quotient; percentage of body fat; liver volume; and regional fat mass. In the 13 patients with diabetes who completed 6 months of troglitazone therapy, hemoglobin A1c levels decreased by a mean of 2.8% (95% CI, 1.9% to 3.7%; P < 0.001). In all 19 study patients, fasting triglyceride levels decreased by 2.6 mmol/L (230 mg/dL) (CI, 0.7 to 4.5 mmol/L [62 to 398 mg/dL]; P = 0.019) and free fatty acid levels decreased by 325 micromol/L (CI, 135 to 515 micromol/L; P = 0.035). The respiratory quotient decreased by a mean of 0.12 (CI, 0.08 to 0.16; P < 0.001), suggesting that troglitazone promoted oxidation of fat. Body fat increased by a mean of 2.4 percentage points (CI, 1.3 to 4.5 percentage points; P = 0.044). Magnetic resonance imaging showed an increase in subcutaneous adipose tissue but not in visceral fat. In one patient, the serum alanine aminotransferase level increased eightfold during the 10th months of troglitazone treatment but normalized 3 months after discontinuation of treatment Liver biopsy revealed an eosinophilic infiltrate, suggesting hypersensitivity reaction as a cause of hepatotoxicity. Troglitazone therapy improved metabolic control and increased body fat in patients with lipoatrophic diabetes. The substantial benefits of troglitazone must be balanced against the risk for hepatotoxicity, which can occur relatively late in the treatment course. JF - Annals of internal medicine AU - Arioglu, E AU - Duncan-Morin, J AU - Sebring, N AU - Rother, K I AU - Gottlieb, N AU - Lieberman, J AU - Herion, D AU - Kleiner, D E AU - Reynolds, J AU - Premkumar, A AU - Sumner, A E AU - Hoofnagle, J AU - Reitman, M L AU - Taylor, S I AD - Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. elif_arioglu@nih.gov Y1 - 2000/08/15/ PY - 2000 DA - 2000 Aug 15 SP - 263 EP - 274 VL - 133 IS - 4 SN - 0003-4819, 0003-4819 KW - Chromans KW - 0 KW - Fatty Acids, Nonesterified KW - Hemoglobin A, Glycosylated KW - Hypoglycemic Agents KW - Insulin KW - Thiazoles KW - Thiazolidinediones KW - Triglycerides KW - troglitazone KW - I66ZZ0ZN0E KW - Abridged Index Medicus KW - Index Medicus KW - Respiratory Function Tests KW - Triglycerides -- blood KW - Liver -- anatomy & histology KW - Drug Administration Schedule KW - Insulin -- blood KW - Humans KW - Aged KW - Child KW - Insulin Resistance -- physiology KW - Chemical and Drug Induced Liver Injury -- etiology KW - Prospective Studies KW - Liver -- drug effects KW - Adipose Tissue -- anatomy & histology KW - Syndrome KW - Hemoglobin A, Glycosylated -- metabolism KW - Adult KW - Adipose Tissue -- drug effects KW - Middle Aged KW - Fatty Acids, Nonesterified -- blood KW - Body Composition -- drug effects KW - Statistics, Nonparametric KW - Male KW - Female KW - Hypoglycemic Agents -- therapeutic use KW - Lipodystrophy -- physiopathology KW - Hypoglycemic Agents -- adverse effects KW - Chromans -- therapeutic use KW - Thiazoles -- adverse effects KW - Lipodystrophy -- drug therapy KW - Thiazoles -- therapeutic use KW - Chromans -- adverse effects KW - Lipodystrophy -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71256323?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+internal+medicine&rft.atitle=Efficacy+and+safety+of+troglitazone+in+the+treatment+of+lipodystrophy+syndromes.&rft.au=Arioglu%2C+E%3BDuncan-Morin%2C+J%3BSebring%2C+N%3BRother%2C+K+I%3BGottlieb%2C+N%3BLieberman%2C+J%3BHerion%2C+D%3BKleiner%2C+D+E%3BReynolds%2C+J%3BPremkumar%2C+A%3BSumner%2C+A+E%3BHoofnagle%2C+J%3BReitman%2C+M+L%3BTaylor%2C+S+I&rft.aulast=Arioglu&rft.aufirst=E&rft.date=2000-08-15&rft.volume=133&rft.issue=4&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=Annals+of+internal+medicine&rft.issn=00034819&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-11 N1 - Date created - 2000-08-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Ann Intern Med. 2001 May 15;134(10):1008 [11352703] Ann Intern Med. 2000 Aug 15;133(4):304-6 [10929174] Ann Intern Med. 2001 Jun 19;134(12):1153-4 [11412067] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A pilot study investigating the role of NAT1 and NAT2 polymorphisms in gastric adenocarcinoma. AN - 71245425; 10918189 AB - In humans, aromatic and heterocyclic amine carcinogens may be acetylated by the expression products of either of the N-acetyltransferase genes, NAT1 or NAT2. This conjugation reaction can result in either activation or detoxication of these carcinogens depending on the tissue involved. Recent studies suggest that polymorphisms in NAT1 or NAT2 may modulate cancer risk. To determine if genetic differences in NAT1 and NAT2 could alter risk of gastric cancer, we tested for the presence of polymorphic N-acetyltransferase alleles (both NAT1 and NAT2) in a preliminary study of 94 gastric adenocarcinoma patients and 112 control subjects from North Staffordshire, England. We used established PCR protocols to genotype for NAT2 and NAT1 alleles (NAT2*4, NAT2*5, NAT2*6, NAT2*7, NAT2*14; NAT1*3, NAT1* 4, NAT1*10, and NAT1*11), and implemented an oligonucleotide ligation assay (OLA) to test for low-activity NAT1 alleles [NAT1*14 (G560A), NAT1*15 (C559T), and NAT1*17 (C190T)]. No significant increased risk was observed for NAT2 acetylation genotypes. However, among all cases, we found that individuals inheriting a variant NAT1 allele, NAT1*10, have a significantly elevated risk for gastric cancer (OR = 2.2, 95% CI 1. 2-3.9, P < 0.01). Interestingly, the risk observed for NAT1*10 appears to be solely associated with advanced-stage tumors (OR = 4.8, P < 0.001), suggesting a possible role in progression to advanced disease. This preliminary finding needs confirmation in a larger, detailed epidemiological study. Copyright 2000 Wiley-Liss, Inc. JF - International journal of cancer AU - Boissy, R J AU - Watson, M A AU - Umbach, D M AU - Deakin, M AU - Elder, J AU - Strange, R C AU - Bell, D A AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709-2233, USA. Y1 - 2000/08/15/ PY - 2000 DA - 2000 Aug 15 SP - 507 EP - 511 VL - 87 IS - 4 SN - 0020-7136, 0020-7136 KW - Isoenzymes KW - 0 KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - N-acetyltransferase 1 KW - NAT2 protein, human KW - Index Medicus KW - Homozygote KW - Humans KW - Aged KW - Pilot Projects KW - Genotype KW - Acetylation KW - Alleles KW - Polymorphism, Genetic -- physiology KW - Risk Factors KW - Middle Aged KW - Genetic Predisposition to Disease KW - Female KW - Male KW - Adenocarcinoma -- enzymology KW - Stomach Neoplasms -- genetics KW - Adenocarcinoma -- genetics KW - Stomach Neoplasms -- enzymology KW - Isoenzymes -- genetics KW - Arylamine N-Acetyltransferase -- metabolism KW - Isoenzymes -- metabolism KW - Arylamine N-Acetyltransferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71245425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+pilot+study+investigating+the+role+of+NAT1+and+NAT2+polymorphisms+in+gastric+adenocarcinoma.&rft.au=Boissy%2C+R+J%3BWatson%2C+M+A%3BUmbach%2C+D+M%3BDeakin%2C+M%3BElder%2C+J%3BStrange%2C+R+C%3BBell%2C+D+A&rft.aulast=Boissy&rft.aufirst=R&rft.date=2000-08-15&rft.volume=87&rft.issue=4&rft.spage=507&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 - 2000-08-18 N1 - Date created - 2000-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis AN - 17720969; 4783145 AB - Ethionamide (ETA) is an important component of second-line therapy for the treatment of multidrug-resistant tuberculosis. Synthesis of radiolabeled ETA and an examination of drug metabolites formed by whole cells of Mycobacterium tuberculosis (MTb) have allowed us to demonstrate that ETA is activated by S-oxidation before interacting with its cellular target. ETA is metabolized by MTb to a 4-pyridylmethanol product remarkably similar in structure to that formed by the activation of isoniazid by the catalase-peroxidase KatG. We have demonstrated that overproduction of Rv3855 (EtaR), a putative regulatory protein from MTb, confers ETA resistance whereas overproduction of an adjacent, clustered monooxygenase (Rv3854c, EtaA) confers ETA hypersensitivity. Production of EtaA appears to be negatively regulated by EtaR and correlates directly with [ super(14)C]ETA metabolism, suggesting that EtaA is the activating enzyme responsible for thioamide oxidation and subsequent toxicity. Coding sequence mutations in EtaA were found in 11 of 11 multidrug- resistant MTb patient isolates from Cape Town, South Africa. These isolates showed broad cross- resistance to thiocarbonyl containing drugs including ETA, thiacetazone, and thiocarlide. JF - Proceedings of the National Academy of Sciences, USA AU - DeBarber, A E AU - Mdluli, K AU - Bosman, M AU - Bekker, L AU - Barry 3rd, CE AD - Tuberculosis Research Section, Laboratory of Host Defenses, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Rockville, MD 20852, clifton_barry@nih.gov Y1 - 2000/08/15/ PY - 2000 DA - 2000 Aug 15 SP - 9677 EP - 9682 VL - 97 IS - 17 SN - 0027-8424, 0027-8424 KW - activation KW - sensitivity KW - ethionamide KW - Microbiology Abstracts B: Bacteriology KW - Drug resistance KW - Antitubercular agents KW - Mycobacterium tuberculosis KW - J 02814:Drug resistance KW - J 02812:Antibacterial Agents: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17720969?accountid=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=Ethionamide+activation+and+sensitivity+in+multidrug-resistant+Mycobacterium+tuberculosis&rft.au=DeBarber%2C+A+E%3BMdluli%2C+K%3BBosman%2C+M%3BBekker%2C+L%3BBarry+3rd%2C+CE&rft.aulast=DeBarber&rft.aufirst=A&rft.date=2000-08-15&rft.volume=97&rft.issue=17&rft.spage=9677&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&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 - Mycobacterium tuberculosis; Antitubercular agents; Drug resistance ER - TY - JOUR T1 - Characterization of a novel degradation product of 2,2'-dithiobis[N-isoleucylbenzamide], an inhibitor of HIV nucleocapsid protein zinc fingers AN - 17565974; 4750568 AB - Zinc finger motifs have been found to be important in a variety of protein structures including transcription factors and viral nucleocapsid proteins. Recently, it was demonstrated that various aromatic disulfides effectively remove the metal ion from the zinc finger, resulting in an alteration of tertiary structure in this region of the protein, thereby inhibiting transcription. Among these compounds, 2,2'-dithiobis[N-isoleucylbenzamide] exhibits activity against human immunodeficiency virus (HIV)-type 1 in vitro and has been selected for preclinical development as an anti-HIV agent. Analysis of this agent by reversed-phase high-performance liquid chromatography (HPLC) indicated a significant quantity of two additional compounds. Identifying the parent disulfide was accomplished by scanning eluting peaks with positive ion thermospray ionization (TSP) mass spectrometry (MS). Solution-induced disproportionation of the disulfide into its sulfydryl monomer was demonstrated by treating the drug with dithiothreitol (DTT) prior to HPLC analysis. TSP-MS analysis of the remaining chromatographic peak suggested a molecular weight of 265, which, with super(1)H-nuclear magnetic resonance (NMR) data of the isolated material, allowed us to elucidate the chemical structure as N-isoleucyl-benzisothiazolone. Contact with stainless steel, such as that employed in an HPLC system, was found to accelerate degradation of the parent disulfide to the benzisothiazolone. JF - Journal of Pharmaceutical and Biomedical Analysis AU - Phillips, L R AU - Malspeis, L AU - Tubbs, E K AU - Supko, J G AD - Laboratory of Drug Discovery, Research, and Development, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, MD 21701, USA Y1 - 2000/08/15/ PY - 2000 DA - 2000 Aug 15 SP - 395 EP - 402 VL - 23 IS - 2-3 SN - 0731-7085, 0731-7085 KW - HIV KW - 2,2'-Dithiobis[N-isoleucylbenzamide] KW - N-Isoleucyl-benzisothiazolone KW - nucleocapsid protein KW - stainless steel KW - zinc finger KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - Degradation KW - Antiviral agents KW - Human immunodeficiency virus KW - Transcription factors KW - N.M.R. KW - Dithiothreitol KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01068:Antiviral & viricidal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17565974?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Pharmaceutical+and+Biomedical+Analysis&rft.atitle=Characterization+of+a+novel+degradation+product+of+2%2C2%27-dithiobis%5BN-isoleucylbenzamide%5D%2C+an+inhibitor+of+HIV+nucleocapsid+protein+zinc+fingers&rft.au=Phillips%2C+L+R%3BMalspeis%2C+L%3BTubbs%2C+E+K%3BSupko%2C+J+G&rft.aulast=Phillips&rft.aufirst=L&rft.date=2000-08-15&rft.volume=23&rft.issue=2-3&rft.spage=395&rft.isbn=&rft.btitle=&rft.title=Journal+of+Pharmaceutical+and+Biomedical+Analysis&rft.issn=07317085&rft_id=info:doi/10.1016%2FS0731-7085%2800%2900311-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; Antiviral agents; Dithiothreitol; N.M.R.; Transcription factors; Degradation DO - http://dx.doi.org/10.1016/S0731-7085(00)00311-3 ER - TY - JOUR T1 - Chimeric Langat/Dengue Viruses Protect Mice from Heterologous Challenge with the Highly Virulent Strains of Tick-Borne Encephalitis Virus AN - 17561006; 4745503 AB - Langat virus (LGT), a tick-borne flavivirus, is naturally attenuated for humans but it is very virulent in SCID mice. In contrast, viable recombinant chimeras of LGT (preM and E genes) and dengue type 4 virus (all other sequences) recovered in mosquito cell culture were completely attenuated in SCID mice but still capable of providing protection against LGT. To develop the chimeras into vaccine candidates, we adapted them to replicate efficiently in simian Vero cells, a satisfactory substrate for human vaccines. The adapted chimeras remained completely attenuated for SCID mice and, significantly, provided protection in immunocompetent mice against tick-borne encephalitis virus, the most virulent of the tick-borne flaviviruses. JF - Virology AU - Pletnev, A G AU - Karganova, G G AU - Dzhivanyan, TI AU - Lashkevich, V A AU - Bray, M AD - Building 7, Room 236, NIAID, NIH, 7 Center Dr. MSC 0740, Bethesda, MD 20892., apletnev@niaid.nih.gov Y1 - 2000/08/15/ PY - 2000 DA - 2000 Aug 15 SP - 26 EP - 31 PB - Academic Press VL - 274 IS - 1 SN - 0042-6822, 0042-6822 KW - simian Vero cells KW - mice KW - SCID mice KW - Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Dengue virus 4 KW - Langat virus KW - Attenuation KW - Flavivirus KW - Chimeras KW - Vaccines KW - Tick-borne encephalitis virus KW - V 22097:Immunization: Vaccines & vaccination: Human KW - A 01097:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17561006?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virology&rft.atitle=Chimeric+Langat%2FDengue+Viruses+Protect+Mice+from+Heterologous+Challenge+with+the+Highly+Virulent+Strains+of+Tick-Borne+Encephalitis+Virus&rft.au=Pletnev%2C+A+G%3BKarganova%2C+G+G%3BDzhivanyan%2C+TI%3BLashkevich%2C+V+A%3BBray%2C+M&rft.aulast=Pletnev&rft.aufirst=A&rft.date=2000-08-15&rft.volume=274&rft.issue=1&rft.spage=26&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&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 - Flavivirus; Tick-borne encephalitis virus; Langat virus; Dengue virus 4; Vaccines; Attenuation; Chimeras ER - TY - JOUR T1 - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced complex I inhibition is reversed by disulfide reductant, dithiothreitol in mouse brain. AN - 72210021; 10961666 AB - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes dopaminergic cell loss in mice by inhibiting mitochondrial complex-I through its metabolite, MPP+, which binds to specific sites on complex-I. Since complex-I is highly vulnerable to oxidative stress, we have examined the nature of inhibition of complex-I by MPTP. Both MPTP and MPP+ inhibited complex-I activity, in vitro, in mouse brain slices, which was abolished by prior exposure of brain slices to glutathione. Further, the inhibited complex-I activity rebounded after incubation with disulfide reductant, dithiothreitol. Systemic administration of MPTP to mice resulted in inhibition of complex-I in striatum and midbrain which was also reversed by treatment of mitochondria with dithiothreitol. Inhibition of complex I activity by MPTP may be due to oxidation of thiol group(s) in complex-I, which may be reversed by thiol antioxidants. JF - Neuroscience letters AU - Annepu, J AU - Ravindranath, V AD - Department of Neurochemistry, National Institute of Mental Health & Neurosciences, Bangalore, India. Y1 - 2000/08/11/ PY - 2000 DA - 2000 Aug 11 SP - 209 EP - 212 VL - 289 IS - 3 SN - 0304-3940, 0304-3940 KW - Neuroprotective Agents KW - 0 KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - NADH, NADPH Oxidoreductases KW - EC 1.6.- KW - Electron Transport Complex I KW - EC 1.6.5.3 KW - Glutathione KW - GAN16C9B8O KW - 1-Methyl-4-phenylpyridinium KW - R865A5OY8J KW - Dithiothreitol KW - T8ID5YZU6Y KW - Index Medicus KW - Animals KW - Oxidation-Reduction -- drug effects KW - Glutathione -- metabolism KW - Nerve Degeneration -- physiopathology KW - Mice KW - Glutathione -- drug effects KW - Glutathione -- pharmacology KW - Neuroprotective Agents -- pharmacology KW - Nerve Degeneration -- drug therapy KW - Oxidative Stress -- physiology KW - Oxidative Stress -- drug effects KW - Nerve Degeneration -- enzymology KW - Male KW - 1-Methyl-4-phenylpyridinium -- pharmacology KW - Brain -- physiopathology KW - NADH, NADPH Oxidoreductases -- drug effects KW - Brain -- enzymology KW - Parkinsonian Disorders -- physiopathology KW - Mitochondria -- enzymology KW - Brain -- drug effects KW - Mitochondria -- pathology KW - Mitochondria -- drug effects KW - Dithiothreitol -- pharmacology KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- pharmacology KW - NADH, NADPH Oxidoreductases -- metabolism KW - Parkinsonian Disorders -- enzymology KW - Parkinsonian Disorders -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72210021?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience+letters&rft.atitle=1-Methyl-4-phenyl-1%2C2%2C3%2C6-tetrahydropyridine-induced+complex+I+inhibition+is+reversed+by+disulfide+reductant%2C+dithiothreitol+in+mouse+brain.&rft.au=Annepu%2C+J%3BRavindranath%2C+V&rft.aulast=Annepu&rft.aufirst=J&rft.date=2000-08-11&rft.volume=289&rft.issue=3&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Neuroscience+letters&rft.issn=03043940&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-31 N1 - Date created - 2000-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potentiated and preferential effects of combined paraquat and maneb on nigrostriatal dopamine systems: environmental risk factors for Parkinson's disease? AN - 71733138; 10930548 AB - The absence of any compelling basis for a heritable basis of idiopathic Parkinson's disease (PD) has focused attention on environmental exposures as causative agents. While the herbicide paraquat has repeatedly been implicated, its impact on dopamine systems following systemic exposures is equivocal. The restricted focus on paraquat also ignores the extensive geographical overlap of its use with other agrichemicals known to adversely impact dopamine systems, including ethylenebisdithiocarbamate fungicides such as maneb. The present study sought to determine whether combined exposures to paraquat and maneb would produce additive effects and support a multiple-hit environmental contribution to PD. C57BL/6 mice were exposed to either paraquat (5-10 mg/kg) or maneb (15-30 mg/kg) i.p. alone or in combination once a week for 4 weeks. Sustained decreases in motor activity immediately following injections were consistently observed only with combined exposures, with activity levels returning to control values 24 h later. Concurrently, levels of dopamine and metabolites and dopamine turnover were increased immediately post-injection only by combined exposures, and returned to control levels or below within 48 h. Reductions in tyrosine hydroxylase immunoreactivity, measured 3 days after the last injection, resulted only from combined exposure and were detected in dorsal striatum, but not in the nucleus accumbens. The fact that combined exposures resulted in potentiated effects that appear to target nigrostriatal dopamine systems suggests that these combinations may be important environmental risk factors for Parkinsonism. These findings also raise questions about the adequacy of current risk assessment guidelines for these chemicals which are based on effect levels derived from exposures to single agents. JF - Brain research AU - Thiruchelvam, M AU - Brockel, B J AU - Richfield, E K AU - Baggs, R B AU - Cory-Slechta, D A AD - Departments of Environmental Medicine, Pathology and Laboratory Medicine, Laboratory Animal Medicine and the NIEHS Environmental Health Sciences Center, University of Rochester School of Medicine, Rochester, NY 14642, USA. Y1 - 2000/08/11/ PY - 2000 DA - 2000 Aug 11 SP - 225 EP - 234 VL - 873 IS - 2 SN - 0006-8993, 0006-8993 KW - Maneb KW - 12427-38-2 KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Paraquat KW - PLG39H7695 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Tyrosine 3-Monooxygenase -- metabolism KW - Dose-Response Relationship, Drug KW - Neurons -- drug effects KW - Body Weight -- physiology KW - Dopamine -- metabolism KW - Motor Activity -- physiology KW - Mice KW - Lung -- pathology KW - Drug Interactions -- physiology KW - Risk Factors KW - Body Weight -- drug effects KW - Lung -- drug effects KW - Mice, Inbred C57BL KW - Neurons -- enzymology KW - Motor Activity -- drug effects KW - Lung -- physiopathology KW - Time Factors KW - Male KW - Neural Pathways -- physiopathology KW - Parkinsonian Disorders -- physiopathology KW - Parkinsonian Disorders -- chemically induced KW - Substantia Nigra -- drug effects KW - Neostriatum -- physiopathology KW - Parkinsonian Disorders -- enzymology KW - Neural Pathways -- drug effects KW - Paraquat -- toxicity KW - Substantia Nigra -- enzymology KW - Substantia Nigra -- physiopathology KW - Neostriatum -- drug effects KW - Environmental Exposure -- adverse effects KW - Neural Pathways -- enzymology KW - Neostriatum -- enzymology KW - Maneb -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71733138?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Potentiated+and+preferential+effects+of+combined+paraquat+and+maneb+on+nigrostriatal+dopamine+systems%3A+environmental+risk+factors+for+Parkinson%27s+disease%3F&rft.au=Thiruchelvam%2C+M%3BBrockel%2C+B+J%3BRichfield%2C+E+K%3BBaggs%2C+R+B%3BCory-Slechta%2C+D+A&rft.aulast=Thiruchelvam&rft.aufirst=M&rft.date=2000-08-11&rft.volume=873&rft.issue=2&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-28 N1 - Date created - 2000-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional analysis of tail domains of Acanthamoeba myosin IC by characterization of truncation and deletion mutants. AN - 71274915; 10840041 AB - Acanthamoeba myosin IC has a single 129-kDa heavy chain and a single 17-kDa light chain. The heavy chain comprises a 75-kDa catalytic head domain with an ATP-sensitive F-actin-binding site, a 3-kDa neck domain, which binds a single 17-kDa light chain, and a 50-kDa tail domain, which binds F-actin in the presence or absence of ATP. The actin-activated MgATPase activity of myosin IC exhibits triphasic actin dependence, apparently as a consequence of the two actin-binding sites, and is regulated by phosphorylation of Ser-329 in the head. The 50-kDa tail consists of a basic domain, a glycine/proline/alanine-rich (GPA) domain, and a Src homology 3 (SH3) domain, often referred to as tail homology (TH)-1, -2, and -3 domains, respectively. The SH3 domain divides the TH-3 domain into GPA-1 and GPA-2. To define the functions of the tail domains more precisely, we determined the properties of expressed wild type and six mutant myosins, an SH3 deletion mutant and five mutants truncated at the C terminus of the SH3, GPA-2, TH-1, neck and head domains, respectively. We found that both the TH-1 and GPA-2 domains bind F-actin in the presence of ATP. Only the mutants that retained an actin-binding site in the tail exhibited triphasic actin-dependent MgATPase activity, in agreement with the F-actin-cross-linking model, but truncation reduced the MgATPase activity at both low and high actin concentrations. Deletion of the SH3 domain had no effect. Also, none of the tail domains, including the SH3 domain, affected either the K(m) or V(max) for the phosphorylation of Ser-329 by myosin I heavy chain kinase. JF - The Journal of biological chemistry AU - Liu, X AU - Brzeska, H AU - Korn, E D AD - Laboratory of Cell Biology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/08/11/ PY - 2000 DA - 2000 Aug 11 SP - 24886 EP - 24892 VL - 275 IS - 32 SN - 0021-9258, 0021-9258 KW - Actins KW - 0 KW - Protozoan Proteins KW - Recombinant Proteins KW - Ca(2+) Mg(2+)-ATPase KW - EC 3.6.1.- KW - Myosin Heavy Chains KW - EC 3.6.4.1 KW - Myosins KW - Index Medicus KW - Protozoan Proteins -- metabolism KW - Animals KW - Protozoan Proteins -- genetics KW - Actins -- metabolism KW - Rabbits KW - Myosin Heavy Chains -- metabolism KW - Binding Sites KW - Cloning, Molecular KW - Mutagenesis KW - Protozoan Proteins -- chemistry KW - Myosin Heavy Chains -- chemistry KW - Myosin Heavy Chains -- genetics KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Recombinant Proteins -- chemistry KW - Ca(2+) Mg(2+)-ATPase -- metabolism KW - Sequence Deletion KW - Myosins -- metabolism KW - Acanthamoeba -- metabolism KW - Acanthamoeba -- genetics KW - Myosins -- chemistry KW - Myosins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71274915?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Functional+analysis+of+tail+domains+of+Acanthamoeba+myosin+IC+by+characterization+of+truncation+and+deletion+mutants.&rft.au=Liu%2C+X%3BBrzeska%2C+H%3BKorn%2C+E+D&rft.aulast=Liu&rft.aufirst=X&rft.date=2000-08-11&rft.volume=275&rft.issue=32&rft.spage=24886&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 - 2000-09-14 N1 - Date created - 2000-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - G13alpha-mediated PYK2 activation. PYK2 is a mediator of G13alpha -induced serum response element-dependent transcription. AN - 71271143; 10821841 AB - G(12)alpha/G(13)alpha transduces signals from G-protein-coupled receptors to stimulate growth-promoting pathways and the early response gene c-fos. Within the c-fos promoter lies a key regulatory site, the serum response element (SRE). Here we show a critical role for the tyrosine kinase PYK2 in muscarinic receptor type 1 and G(12)alpha/G(13)alpha signaling to an SRE reporter gene. A kinase-inactivate form of PYK2 (PYK2 KD) inhibits muscarinic receptor type 1 signaling to the SRE and PYK2 itself triggers SRE reporter gene activation through a RhoA-dependent pathway. Placing PYK2 downstream of G-protein activation but upstream of RhoA, the expression of PYK2 KD blocks the activation of an SRE reporter gene by GTPase-deficient forms of G(12)alpha or G(13)alpha but not by RhoA. The GTPase-deficient form of G(13)alpha triggers PYK2 kinase activity and PYK2 tyrosine phosphorylation, and co-expression of the RGS domain of p115 RhoGEF inhibits both responses. Finally, we show that in vivo G(13)alpha, although not G(12)alpha, readily associates with PYK2. Thus, G-protein-coupled receptors via G(13)alpha activation can use PYK2 to link to SRE-dependent gene expression. JF - The Journal of biological chemistry AU - Shi, C S AU - Sinnarajah, S AU - Cho, H AU - Kozasa, T AU - Kehrl, J H AD - BCell Molecular Immunology Section, Laboratory of Immunoregulation, NIAID, National Institutes of Health, Bethesda, Maryland 20892-1876, USA. Y1 - 2000/08/11/ PY - 2000 DA - 2000 Aug 11 SP - 24470 EP - 24476 VL - 275 IS - 32 SN - 0021-9258, 0021-9258 KW - Recombinant Proteins KW - 0 KW - Luciferases KW - EC 1.13.12.- KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Focal Adhesion Kinase 2 KW - EC 2.7.10.2 KW - GTP Phosphohydrolases KW - EC 3.6.1.- KW - GTP-Binding Protein alpha Subunits, G12-G13 KW - EC 3.6.5.1 KW - Heterotrimeric GTP-Binding Proteins KW - rhoA GTP-Binding Protein KW - EC 3.6.5.2 KW - Index Medicus KW - rhoA GTP-Binding Protein -- metabolism KW - Animals KW - COS Cells KW - HeLa Cells KW - Humans KW - Transcription, Genetic KW - Mutagenesis, Site-Directed KW - Phosphorylation KW - Transfection KW - Recombinant Proteins -- metabolism KW - GTP Phosphohydrolases -- metabolism KW - Genes, Reporter KW - Luciferases -- genetics KW - Amino Acid Substitution KW - Sequence Deletion KW - Protein-Tyrosine Kinases -- genetics KW - Heterotrimeric GTP-Binding Proteins -- metabolism KW - Heterotrimeric GTP-Binding Proteins -- chemistry KW - Protein-Tyrosine Kinases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71271143?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=G13alpha-mediated+PYK2+activation.+PYK2+is+a+mediator+of+G13alpha+-induced+serum+response+element-dependent+transcription.&rft.au=Shi%2C+C+S%3BSinnarajah%2C+S%3BCho%2C+H%3BKozasa%2C+T%3BKehrl%2C+J+H&rft.aulast=Shi&rft.aufirst=C&rft.date=2000-08-11&rft.volume=275&rft.issue=32&rft.spage=24470&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 - 2000-09-14 N1 - Date created - 2000-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adenoviral vector cytotoxicity depends in part on the transgene encoded. AN - 71262464; 10924352 AB - First-generation adenoviral vectors induce G(2)/M arrest and cell death at high multiplicities of infection (m.o.i.'s) in vitro. It is unclear whether this cytotoxicity is entirely adenoviral gene related or influenced in part by the encoded transgene. We examined this question in epithelial cells using seven vectors at relatively low (50) or higher (200) m.o.i.'s. The vectors contained no transgene (+/-promoter), transgenes encoding a cytoplasmic reporter protein (two luciferase constructs; beta-galactosidase), or transgenes encoding a secretory protein (alpha1-antitrypsin; growth hormone). After 24 h with a m.o.i. of 50, vectors encoding cytoplasmic reporter proteins led to greatest cytotoxicity (approximately 35-40% cells in G(2)/M). Vectors without a transgene resulted in lower cytotoxicity (approximately 15%, minus, or 23%, plus promoter, cells in G(2)/M). Vectors encoding secretory proteins led to approximately 22-25% cells in G(2)/M. A similar pattern resulted when cell number was measured. Results were unrelated to the steady-state levels of transgene product. At the higher m.o.i., all vectors caused substantial growth retardation. This is the first demonstration that adenoviral vector-induced cytotoxic effects are in part related to the transgene encoded. Copyright 2000 Academic Press. JF - Biochemical and biophysical research communications AU - Zheng, C AU - Goldsmith, C M AU - O'Connell, B C AU - Baum, B J AD - Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, Bethesda, Maryland, 20892-1190, USA. Y1 - 2000/08/11/ PY - 2000 DA - 2000 Aug 11 SP - 767 EP - 771 VL - 274 IS - 3 SN - 0006-291X, 0006-291X KW - alpha 1-Antitrypsin KW - 0 KW - Growth Hormone KW - 9002-72-6 KW - Luciferases KW - EC 1.13.12.- KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - Growth Hormone -- genetics KW - Epithelial Cells KW - alpha 1-Antitrypsin -- toxicity KW - Luciferases -- toxicity KW - Humans KW - alpha 1-Antitrypsin -- genetics KW - beta-Galactosidase -- toxicity KW - beta-Galactosidase -- genetics KW - Luciferases -- genetics KW - Cell Line KW - Growth Hormone -- toxicity KW - Adenoviridae KW - Gene Transfer Techniques KW - Genetic Vectors -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71262464?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Adenoviral+vector+cytotoxicity+depends+in+part+on+the+transgene+encoded.&rft.au=Zheng%2C+C%3BGoldsmith%2C+C+M%3BO%27Connell%2C+B+C%3BBaum%2C+B+J&rft.aulast=Zheng&rft.aufirst=C&rft.date=2000-08-11&rft.volume=274&rft.issue=3&rft.spage=767&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 - 2000-09-15 N1 - Date created - 2000-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural basis of DNA bridging by barrier-to-autointegration factor. AN - 71267848; 10924106 AB - Barrier-to-autointegration factor (BAF) is a host cell protein that plays a crucial role in retroviral integration. Preintegration complexes (PICs) stripped of BAF lose their normal integration activity, which can be restored by incubation with purified BAF. BAF bridges double-stranded DNA both intra- and intermolecularly in a non-sequence-specific manner, leading to the formation of a nucleoprotein network. BAF also binds to the nuclear protein lamina-associated polypeptide 2 (LAP2), and is localized with chromatin during interphase and mitosis. The crystal structure of homodimeric human BAF has been determined to 1.9 A resolution. The fold of the BAF monomer resembles that of the second domain of RuvA. This comparison revealed the presence of the helix-hairpin-helix (HhH) nonspecific DNA binding motif within BAF. A novel feature of BAF's HhH motif is the occupation of the metal binding site by the epsilon-amino group of Lys 6, providing an alternative means of sequestering positive charge. Mutational analysis corroborates the HhH motif's prominent role in DNA binding and argues against a previously proposed helix-turn-helix (HTH) binding site located in another region of the monomer. A model of BAF bridging DNA via the HhH motif is proposed. JF - Biochemistry AU - Umland, T C AU - Wei, S Q AU - Craigie, R AU - Davies, D R AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2000/08/08/ PY - 2000 DA - 2000 Aug 08 SP - 9130 EP - 9138 VL - 39 IS - 31 SN - 0006-2960, 0006-2960 KW - BANF1 protein, human KW - 0 KW - DNA-Binding Proteins KW - Nuclear Proteins KW - Solutions KW - DNA KW - 9007-49-2 KW - Selenomethionine KW - 964MRK2PEL KW - Index Medicus KW - Selenomethionine -- chemistry KW - Computer Simulation KW - Models, Molecular KW - DNA Mutational Analysis KW - Dimerization KW - Humans KW - Amino Acid Sequence KW - Moloney murine leukemia virus -- chemistry KW - Mutagenesis, Site-Directed KW - Nuclear Magnetic Resonance, Biomolecular KW - Protein Folding KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Moloney murine leukemia virus -- genetics KW - Binding Sites -- genetics KW - Helix-Turn-Helix Motifs -- genetics KW - DNA-Binding Proteins -- chemistry KW - DNA-Binding Proteins -- genetics KW - DNA -- chemistry KW - Virus Integration UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71267848?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Structural+basis+of+DNA+bridging+by+barrier-to-autointegration+factor.&rft.au=Umland%2C+T+C%3BWei%2C+S+Q%3BCraigie%2C+R%3BDavies%2C+D+R&rft.aulast=Umland&rft.aufirst=T&rft.date=2000-08-08&rft.volume=39&rft.issue=31&rft.spage=9130&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-07 N1 - Date created - 2000-09-07 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - R1CI4SF; PDB; 1CI4 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Escherichia coli NifS-like Proteins Provide Selenium in the Pathway for the Biosynthesis of Selenophosphate AN - 17634642; 4780928 AB - Selenophosphate synthetase (SPS), the selD gene product from Escherichia coli, catalyzes the biosynthesis of monoselenophosphate, AMP, and orthophosphate in a 1:1:1 ratio from selenide and ATP. Kinetic characterization revealed the K sub(m) value for selenide approached levels that are toxic to the cell. Our previous demonstration that a Se super(0)-generating system consisting of L-selenocysteine and the Azotobacter vinelandii NifS protein can replace selenide for selenophosphate biosynthesis in vitro suggested a mechanism whereby cells can overcome selenide toxicity. Recently, three E. coli NifS-like proteins, CsdB, CSD, and IscS, have been overexpressed and characterized. All three enzymes act on selenocysteine and cysteine to produce Se super(0) and S super(0), respectively. In the present study, we demonstrate the ability of each E. coli NifS-like protein to function as a selenium delivery protein for the in vitro biosynthesis of selenophosphate by E. coli wild-type SPS. Significantly, the SPS (C17S) mutant, which is inactive in the standard in vitro assay with selenide as substrate, was found to exhibit detectable activity in the presence of CsdB, CSD, or IscS and L-selenocysteine. Taken together the ability of the NifS-like proteins to generate a selenium substrate for SPS and the activation of the SPS (C17S) mutant suggest a selenium delivery function for the proteins in vivo. JF - Journal of Biological Chemistry AU - Lacourciere, G M AU - Mihara, H AU - Kurihara, T AU - Esaki, N AU - Stadtman, T C AD - Laboratory of Biochemistry, NHLBI, National Institutes of Health, Bethesda, Maryland 20892 and the Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan, lacourcg@nhlbi.nih.gov Y1 - 2000/08/04/ PY - 2000 DA - 2000 Aug 04 SP - 23769 EP - 23773 VL - 275 IS - 31 SN - 0021-9258, 0021-9258 KW - CSD protein KW - CsdB protein KW - IscS protein KW - NifS protein KW - selD gene KW - selenophosphate KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Selenium KW - Escherichia coli KW - G 07320:Bacterial genetics KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17634642?accountid=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=Escherichia+coli+NifS-like+Proteins+Provide+Selenium+in+the+Pathway+for+the+Biosynthesis+of+Selenophosphate&rft.au=Lacourciere%2C+G+M%3BMihara%2C+H%3BKurihara%2C+T%3BEsaki%2C+N%3BStadtman%2C+T+C&rft.aulast=Lacourciere&rft.aufirst=G&rft.date=2000-08-04&rft.volume=275&rft.issue=31&rft.spage=23769&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/10.1074%2Fjbc.M000926200 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Selenium DO - http://dx.doi.org/10.1074/jbc.M000926200 ER - TY - JOUR T1 - Molecular classification of cutaneous malignant melanoma by gene expression profiling AN - 856753917; 13742731 AB - The most common human cancers are malignant neoplasms of the skin. Incidence of cutaneous melanoma is rising especially steeply, with minimal progress in non-surgical treatment of advanced disease. Despite significant effort to identify independent predictors of melanoma outcome, no accepted histopathological, molecular or immunohistochemical marker defines subsets of this neoplasm. Accordingly, though melanoma is thought to present with different 'taxonomic' forms, these are considered part of a continuous spectrum rather than discrete entities. Here we report the discovery of a subset of melanomas identified by mathematical analysis of gene expression in a series of samples. Remarkably, many genes underlying the classification of this subset are differentially regulated in invasive melanomas that form primitive tubular networks in vitro, a feature of some highly aggressive metastatic melanomas. Global transcript analysis can identify unrecognized subtypes of cutaneous melanoma and predict experimentally verifiable phenotypic characteristics that may be of importance to disease progression. JF - Nature AU - Bittner, M AU - Meltzer, P AU - Chen, Y AU - Jiang, Y AU - Seftor, E AU - Hendrix, M AU - Radmacher, M AU - Simon, R AU - Yakhini, Z AU - Ben-Dor, A AU - Sampas, N AU - Dougherty, E AU - Wang, E AU - Marincola, F AU - Gooden, C AU - Lueders, J AU - Glatfelter, A AU - Pollock, P AU - Carpten, J AU - Gillanders, E AU - Leja, D AU - Dietrich, K AU - Beaudry, C AU - Berens, M AU - Alberts, D AU - Sondak, V AU - Hayward, N AU - Trent, J AD - Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA PY - 2000 SP - 536 EP - 540 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 406 IS - 6795 SN - 0028-0836, 0028-0836 KW - Genetics Abstracts; Aqualine Abstracts; Water Resources Abstracts KW - Skin KW - Mathematical Analysis KW - Transcription KW - Cancer KW - Melanoma KW - Gene expression KW - Metastases KW - Classification KW - Networks KW - Diseases KW - AQ 00001:Water Resources and Supplies KW - G 07720:Immunogenetics KW - SW 0540:Properties of water UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/856753917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aaqualine&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Molecular+classification+of+cutaneous+malignant+melanoma+by+gene+expression+profiling&rft.au=Bittner%2C+M%3BMeltzer%2C+P%3BChen%2C+Y%3BJiang%2C+Y%3BSeftor%2C+E%3BHendrix%2C+M%3BRadmacher%2C+M%3BSimon%2C+R%3BYakhini%2C+Z%3BBen-Dor%2C+A%3BSampas%2C+N%3BDougherty%2C+E%3BWang%2C+E%3BMarincola%2C+F%3BGooden%2C+C%3BLueders%2C+J%3BGlatfelter%2C+A%3BPollock%2C+P%3BCarpten%2C+J%3BGillanders%2C+E%3BLeja%2C+D%3BDietrich%2C+K%3BBeaudry%2C+C%3BBerens%2C+M%3BAlberts%2C+D%3BSondak%2C+V%3BHayward%2C+N%3BTrent%2C+J&rft.aulast=Bittner&rft.aufirst=M&rft.date=2000-08-03&rft.volume=406&rft.issue=6795&rft.spage=536&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/10.1038%2F35020115 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-03-01 N1 - Last updated - 2015-12-23 N1 - SubjectsTermNotLitGenreText - Metastases; Gene expression; Skin; Classification; Transcription; Cancer; Melanoma; Networks; Mathematical Analysis; Diseases DO - http://dx.doi.org/10.1038/35020115 ER - TY - JOUR T1 - A chromatin remodelling complex involved in transcription and DNA processing AN - 762282083; 13742732 AB - The packaging of the eukaryotic genome in chromatin presents barriers that restrict the access of enzymes that process DNA. To overcome these barriers, cells possess a number of multi-protein, ATP-dependent chromatin remodelling complexes, each containing an ATPase subunit from the SNF2/SWI2 superfamily. Chromatin remodelling complexes function by increasing nucleosome mobility and are clearly implicated in transcription. Here we have analysed SNF2/SWI2- and ISWI-related proteins to identify remodelling complexes that potentially assist other DNA transactions. We purified a complex from Saccharomyces cerevisiae that contains the Ino80 ATPase. The INO80 complex contains about 12 polypeptides including two proteins related to the bacterial RuvB DNA helicase, which catalyses branch migration of Holliday junctions. The purified complex remodels chromatin, facilitates transcription in vitro and displays 3' to 5' DNA helicase activity. Mutants of ino80 show hypersensitivity to agents that cause DNA damage, in addition to defects in transcription. These results indicate that chromatin remodelling driven by the Ino80 ATPase may be connected to transcription as well as DNA damage repair. JF - Nature AU - Shen, Xuetong AU - Mizuguchi, Gaku AU - Hamiche, Ali AU - Wu, Carl AD - Laboratory of Molecular Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA PY - 2000 SP - 541 EP - 544 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 406 IS - 6795 SN - 0028-0836, 0028-0836 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Water Resources Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Aqualine Abstracts KW - Genomes KW - Barriers KW - Mobility KW - Migration KW - Hypersensitivity KW - Nucleosomes KW - Damage KW - Holliday junctions KW - Adenosinetriphosphatase KW - Chromatin remodeling KW - Enzymes KW - Transcription KW - Saccharomyces cerevisiae KW - DNA damage KW - Proteins KW - DNA helicase KW - Catalysis KW - N 14820:DNA Metabolism & Structure KW - SW 0540:Properties of water KW - AQ 00005:Underground Services and Water Use KW - A 01300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/762282083?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aaqualine&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=A+chromatin+remodelling+complex+involved+in+transcription+and+DNA+processing&rft.au=Shen%2C+Xuetong%3BMizuguchi%2C+Gaku%3BHamiche%2C+Ali%3BWu%2C+Carl&rft.aulast=Shen&rft.aufirst=Xuetong&rft.date=2000-08-03&rft.volume=406&rft.issue=6795&rft.spage=541&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/10.1038%2F35020123 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-11-01 N1 - Last updated - 2015-12-23 N1 - SubjectsTermNotLitGenreText - Genomes; Holliday junctions; Adenosinetriphosphatase; Chromatin remodeling; Mobility; Transcription; Enzymes; Migration; DNA damage; Nucleosomes; Hypersensitivity; DNA helicase; Catalysis; Damage; Barriers; Proteins; Saccharomyces cerevisiae DO - http://dx.doi.org/10.1038/35020123 ER - TY - JOUR T1 - Cocaine effects on gene regulation in the striatum and behavior: increased sensitivity in D3 dopamine receptor-deficient mice. AN - 71771596; 10943692 AB - Central effects of psychostimulants such as cocaine are predominantly mediated by dopamine receptors. We have used mice with a targeted deletion of the D3 dopamine receptor subtype to investigate the role of this receptor in the regulation of gene expression in striatal neurons and behavior by acute and repeated treatment with cocaine (25 mg/kg). In mice lacking D3 receptors, acute administration of cocaine has more pronounced stimulatory effects on c-fos and dynorphin expression in the dorsal and ventral striatum. The behavioral response to cocaine is also increased in these mice. These findings indicate that the D3 receptor plays an inhibitory role in the action of cocaine on behavior and gene regulation in the striatum. JF - Neuroreport AU - Carta, A R AU - Gerfen, C R AU - Steiner, H AD - Laboratory of Systems Neuroscience, National Institute of Mental Health, Bethesda, MD 20892, USA. Y1 - 2000/08/03/ PY - 2000 DA - 2000 Aug 03 SP - 2395 EP - 2399 VL - 11 IS - 11 SN - 0959-4965, 0959-4965 KW - Drd3 protein, mouse KW - 0 KW - Proto-Oncogene Proteins c-fos KW - RNA, Messenger KW - Receptors, Dopamine D2 KW - Receptors, Dopamine D3 KW - Dynorphins KW - 74913-18-1 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Animals KW - Stereotyped Behavior -- physiology KW - Proto-Oncogene Proteins c-fos -- metabolism KW - Neurons -- metabolism KW - Head Movements -- physiology KW - Neurons -- drug effects KW - RNA, Messenger -- drug effects KW - Stereotyped Behavior -- drug effects KW - Mice KW - Motor Activity -- physiology KW - Mice, Knockout KW - Proto-Oncogene Proteins c-fos -- drug effects KW - Phenotype KW - RNA, Messenger -- metabolism KW - Cocaine-Related Disorders -- pathology KW - Neurons -- cytology KW - Cocaine-Related Disorders -- physiopathology KW - Motor Activity -- drug effects KW - Cocaine-Related Disorders -- metabolism KW - Dynorphins -- genetics KW - Head Movements -- drug effects KW - Receptors, Dopamine D2 -- deficiency KW - Nucleus Accumbens -- drug effects KW - Behavior, Animal -- drug effects KW - Neostriatum -- metabolism KW - Gene Expression Regulation -- physiology KW - Neostriatum -- drug effects KW - Receptors, Dopamine D2 -- drug effects KW - Behavior, Animal -- physiology KW - Neostriatum -- cytology KW - Nucleus Accumbens -- metabolism KW - Gene Expression Regulation -- drug effects KW - Receptors, Dopamine D2 -- genetics KW - Nucleus Accumbens -- cytology KW - Cocaine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71771596?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroreport&rft.atitle=Cocaine+effects+on+gene+regulation+in+the+striatum+and+behavior%3A+increased+sensitivity+in+D3+dopamine+receptor-deficient+mice.&rft.au=Carta%2C+A+R%3BGerfen%2C+C+R%3BSteiner%2C+H&rft.aulast=Carta&rft.aufirst=A&rft.date=2000-08-03&rft.volume=11&rft.issue=11&rft.spage=2395&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-04 N1 - Date created - 2000-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer surveillance series: non-Hodgkin's lymphoma incidence by histologic subtype in the United States from 1978 through 1995. AN - 71260601; 10922409 AB - Clinical investigations have shown prognostic heterogeneity within the non-Hodgkin's lymphomas (NHLs) according to histology, but few descriptive studies have considered NHLs by subgroup. Our purpose is to assess the demographic patterns and any notable increases in population-based rates of different histologic subgroups of NHL. Using data collected by the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute, we calculated incidence rates for the major clinicopathologic categories of NHL by age, race, sex, geographic area, and time period. Among the 60 057 NHL cases diagnosed during the period from 1978 through 1995, total incidence (per 100 000 person-years) was 17.1 and 11.5 among white males and females, respectively, and 12.6 and 7.4 among black males and females, respectively. However, rates for follicular NHLs were two to three times greater among whites than among blacks, with little sex variation. Blacks demonstrated much higher incidence than whites for peripheral T-cell NHL, with the incidence rates higher in males than in females. For other NHL subgroups, the incidence rates for persons less than 60 years of age were generally higher among males than among females, with little racial difference; at older ages, the rates were higher among whites than among blacks, with little sex difference. High-grade NHL was the most rapidly rising subtype, particularly among males. Follicular NHL increased more rapidly in black males than in the other three race/sex groups. Overall, the broad categories of small lymphocytic, follicular, diffuse, high-grade, and peripheral T-cell NHL emerged as distinct entities with specific age, sex, racial, temporal, and geographic variations in rates. Findings from our large, population-based study reveal differing demographic patterns and incidence trends according to histologic group. Future descriptive and analytic investigations should evaluate NHL risks according to subtype, as defined by histology and new classification criteria. JF - Journal of the National Cancer Institute AU - Groves, F D AU - Linet, M S AU - Travis, L B AU - Devesa, S S AD - Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. Y1 - 2000/08/02/ PY - 2000 DA - 2000 Aug 02 SP - 1240 EP - 1251 VL - 92 IS - 15 SN - 0027-8874, 0027-8874 KW - Pesticides KW - 0 KW - Index Medicus KW - Humans KW - SEER Program KW - African Americans -- statistics & numerical data KW - Aged KW - European Continental Ancestry Group -- statistics & numerical data KW - Pesticides -- adverse effects KW - Life Style KW - Blood Transfusion -- adverse effects KW - Risk Factors KW - Adult KW - Incidence KW - Middle Aged KW - Adolescent KW - Environmental Exposure -- adverse effects KW - United States -- epidemiology KW - Female KW - Male KW - Lymphoma, Non-Hodgkin -- genetics KW - Lymphoma, Non-Hodgkin -- epidemiology KW - Lymphoma, Non-Hodgkin -- classification KW - Lymphoma, Non-Hodgkin -- etiology KW - Lymphoma, Non-Hodgkin -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71260601?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Cancer+surveillance+series%3A+non-Hodgkin%27s+lymphoma+incidence+by+histologic+subtype+in+the+United+States+from+1978+through+1995.&rft.au=Groves%2C+F+D%3BLinet%2C+M+S%3BTravis%2C+L+B%3BDevesa%2C+S+S&rft.aulast=Groves&rft.aufirst=F&rft.date=2000-08-02&rft.volume=92&rft.issue=15&rft.spage=1240&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-29 N1 - Date created - 2000-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced Activation of T Cells by Dendritic Cells Engineered to Hyperexpress a Triad of Costimulatory Molecules AN - 17557706; 4751205 AB - Activation and proliferation of T cells are essential for a successful cellular immune response to an antigen. Antigen-presenting cells (APCs) activate T cells through a two-signal mechanism. The first signal is antigen specific and causes T cells to enter the cell cycle. The second signal involves a costimulatory molecule that interacts with a ligand on the T-cell surface and leads to T-cell cytokine production and their proliferation. Dendritic cells express several costimulatory molecules and are believed to be the most potent APCs. Two recombinant poxvirus vectors (replication-defective avipox [fowlpox; rF] and a replication-competent vaccinia [rV]) have been engineered to express a triad of costimulatory molecules (B7-1, intercellular adhesion molecule-1, and leukocyte function-associated antigen-3; designated TRICOM). This study was designed to determine if dendritic cells infected with these vectors would have an enhanced capacity to stimulate T-cell responses. Murine dendritic cells (of both intermediate maturity and full maturity) were infected with rF-TRICOM or rV-TRICOM and were used in vitro to stimulate naive T cells with the use of a pharmacologic agent as signal 1, to stimulate T cells in allospecific mixed lymphocyte cultures, and to stimulate CD8 super(+) T cells specific for a peptide from the ovalbumin (OVA) protein. In addition, dendritic cells infected with TRICOM vectors were pulsed with OVA peptide and used to vaccinate mice to examine T-cell responses in vivo. All statistical tests were two-sided. Dendritic cells infected with either rF-TRICOM or rV-TRICOM were found to greatly enhance naive T-cell activation (P<.001), allogeneic responses of T cells (P<.001), and peptide-specific T-cell stimulation in vitro (P<.001). Peptide-pulsed dendritic cells infected with rF-TRICOM or rV-TRICOM induced cytotoxic T-lymphocyte activity in vivo to a markedly greater extent than peptide-pulsed dendritic cells (P = .001 in both). The ability of dendritic cells to activate both naive and effector T cells in vitro and in vivo can be enhanced with the use of poxvirus vectors that potentiate the hyperexpression of a triad of costimulatory molecules. Use of either rF-TRICOM or rV-TRICOM vectors significantly improved the efficacy of dendritic cells in priming specific immune responses. These studies have implications in vaccine strategies for both cancer and infectious diseases. JF - Journal of the National Cancer Institute AU - Hodge, J W AU - Rad, AN AU - Grosenbach, D W AU - Sabzevari, H AU - Yafal, A G AU - Gritz, L AU - Schlom, J AD - National Institutes of Health, 10 Center Dr., Rm. 8B09, Bethesda, MD 20892-1750, USA, js141c@nih.gov Y1 - 2000/08/02/ PY - 2000 DA - 2000 Aug 02 SP - 1228 EP - 1239 VL - 92 IS - 15 SN - 0027-8874, 0027-8874 KW - mice KW - poxvirus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Dendritic cells KW - Infectious diseases KW - Cloning vectors KW - Lymphocytes T KW - Cytokines KW - Cancer KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17557706?accountid=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+the+National+Cancer+Institute&rft.atitle=Enhanced+Activation+of+T+Cells+by+Dendritic+Cells+Engineered+to+Hyperexpress+a+Triad+of+Costimulatory+Molecules&rft.au=Hodge%2C+J+W%3BRad%2C+AN%3BGrosenbach%2C+D+W%3BSabzevari%2C+H%3BYafal%2C+A+G%3BGritz%2C+L%3BSchlom%2C+J&rft.aulast=Hodge&rft.aufirst=J&rft.date=2000-08-02&rft.volume=92&rft.issue=15&rft.spage=1228&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Lymphocytes T; Dendritic cells; Cytokines; Cloning vectors; Cancer; Infectious diseases ER - TY - JOUR T1 - Risk of ovarian cancer in relation to use of phenolphthalein-containing laxatives AN - 899138034; 13758024 AB - We examined ovarian cancer risk in relation to use of phenolphthalein-containing laxatives in 410 epithelial ovarian cancer cases and 713 controls. Compared to women who never used a laxative, ever use of a phenolphthalein-containing laxative was not associated with an increased risk of ovarian cancer (odds ratio, OR, 1.1, 95% confidence interval, CI, 0.9-1.4). Risk was slightly, but not significantly, higher with more frequent use (OR 1.2 for 75 or more days of use). When women who used non-phenolphthalein containing laxatives was used as the reference group, the associations were slightly, but not significantly larger (OR 1.4 for any use of phenolphthalein-containing laxatives and OR 1.5 for 75 or more days of use) [copy 2000 Cancer Research Campaign JF - British Journal of Cancer AU - Cooper, G S AU - Longnecker, M P AU - Sandler, D P AU - Ness, R B AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, 27709, USA Y1 - 2000/08// PY - 2000 DA - Aug 2000 SP - 404 EP - 406 PB - Nature Publishing Group, The Macmillan Building London N1 9XW UK VL - 83 IS - 3 SN - 0007-0920, 0007-0920 KW - Risk Abstracts KW - ovarian carcinoma KW - Cancer KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/899138034?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+Journal+of+Cancer&rft.atitle=Risk+of+ovarian+cancer+in+relation+to+use+of+phenolphthalein-containing+laxatives&rft.au=Cooper%2C+G+S%3BLongnecker%2C+M+P%3BSandler%2C+D+P%3BNess%2C+R+B&rft.aulast=Cooper&rft.aufirst=G&rft.date=2000-08-01&rft.volume=83&rft.issue=3&rft.spage=404&rft.isbn=&rft.btitle=&rft.title=British+Journal+of+Cancer&rft.issn=00070920&rft_id=info:doi/10.1054%2Fbjoc.2000.1250 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-10-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - ovarian carcinoma; Cancer DO - http://dx.doi.org/10.1054/bjoc.2000.1250 ER - TY - JOUR T1 - Otoacoustic emission in patients with neurological disorders who have auditory brainstem response abnormality. AN - 85343915; pmid-10891641 AB - Otoacoustic emissions (OAEs) were evaluated in 51 ears of 30 patients with a severe auditory brainstem response (ABR) waveform abnormality. Thirteen ears showed no ABR to click sound of higher intensity than 100 dBSPL (group 1). Fourteen ears exhibited only wave V or a decreased amplitude pattern of ABR (group 2). Twenty-four ears showed a predominant wave I or no wave III pattern (group 3). Almost all the ears with absent ABR showed no OAE, which strongly suggested hearing loss of cochlear origin, although one patient with alternating hemiplegia of childhood exhibited definite OAEs and auditory reactions without ABR. One patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) and her mother in group 2 had OAE abnormalities, which also suggested mild to severe hearing impairment. When OAEs are present, an accompanying ABR abnormality may be produced by brainstem dysfunction of the underlying disorder such as Pelizaeus-Merzbacher disease. There was a significant relationship (chi-square test P<0.001) between the positivity of the distortion product OAE response and the clinical auditory reactions in 24 patients, although their ABR abnormalities did not reflect hearing impairment directly. Careful examination of both audiometry and OAEs might be necessary for further assessment of the hearing function in pediatric patients with neurological disorders and specific auditory nerve disease. JF - Brain & development AU - Kon, K AU - Inagaki, M AU - Kaga, M AU - Sasaki, M AU - Hanaoka, S AD - Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry (NCNP),1-7-3 Kohnodai, 272-0827, Ichikawa, Japan. Y1 - 2000/08// PY - 2000 DA - Aug 2000 SP - 327 EP - 335 VL - 22 IS - 5 SN - 0387-7604, 0387-7604 KW - Index Medicus KW - National Library of Medicine KW - Neurodegenerative Diseases -- physiopathology KW - Humans KW - Child KW - Brain Stem -- physiopathology KW - Deafness -- physiopathology KW - Child, Preschool KW - Infant KW - Adult KW - Acoustic Stimulation KW - Adolescent KW - Female KW - Male KW - Reaction Time KW - Otoacoustic Emissions, Spontaneous KW - Evoked Potentials, Auditory, Brain Stem KW - Nervous System Diseases -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85343915?accountid=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=Otoacoustic+emission+in+patients+with+neurological+disorders+who+have+auditory+brainstem+response+abnormality.&rft.au=Kon%2C+K%3BInagaki%2C+M%3BKaga%2C+M%3BSasaki%2C+M%3BHanaoka%2C+S&rft.aulast=Kon&rft.aufirst=K&rft.date=2000-08-01&rft.volume=22&rft.issue=5&rft.spage=327&rft.isbn=&rft.btitle=&rft.title=Brain+%26+development&rft.issn=03877604&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - Two distinct Ca(2+)-dependent signaling pathways regulate the motor output of cochlear outer hair cells. AN - 85222221; pmid-10934241 AB - The outer hair cells (OHCs) of the cochlea have an electromotility mechanism, based on conformational changes of voltage-sensitive "motor" proteins in the lateral plasma membrane. The translocation of electrical charges across the membrane that accompanies electromotility imparts a voltage dependency to the membrane capacitance. We used capacitance measurements to investigate whether electromotility may be influenced by different manipulations known to affect intracellular Ca(2+) or Ca(2+)-dependent protein phosphorylation. Application of acetylcholine (ACh) to the synaptic pole of isolated OHCs evoked a Ca(2+)-activated apamin-sensitive outward K(+) current. It also enhanced electromotility, probably because of a phosphorylation-dependent decrease of the cell's axial stiffness. However, ACh did not change the voltage-dependent capacitance either in conventional whole-cell experiments or under perforated-patch conditions. The effects produced by the Ca(2+) ionophore ionomycin mimicked those produced by ACh. Hyperpolarizing shifts of the voltage dependence of capacitance and electromotility were induced by okadaic acid, a promoter of protein phosphorylation, whereas trifluoperazine and W-7, antagonists of calmodulin, caused opposite depolarizing shifts. Components of the protein phosphorylation cascade-IP(3) receptors and calmodulin-dependent protein kinase type IV-were immunolocalized to the lateral wall of the OHC. Our results suggest that two different Ca(2+)-dependent pathways may control the OHC motor output. The first pathway modulates cytoskeletal stiffness and can be activated by ACh. The second pathway shifts the voltage sensitivity of the OHC electromotile mechanism and may be activated by the release of Ca(2+) from intracellular stores located in the proximity of the lateral plasma membrane. JF - The Journal of Neuroscience AU - Frolenkov, G I AU - Mammano, F AU - Belyantseva, I A AU - Coling, Donald E AU - Kachar Bechara AD - Section on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892-4163, USA.; Department of Communicative Disorders and Sciences, College of Arts and Sciences, State University of New York at Buffalo; National Institute on Deafness and Other Communication Disorders PY - 2000 SP - 5940 EP - 5948 VL - 20 IS - 16 SN - 0270-6474, 0270-6474 KW - Cell Movement KW - Guinea Pigs KW - Animal KW - Ca(2+)-Calmodulin Dependent Protein Kinase KW - Electrophysiology KW - Calcium Channels KW - Patch-Clamp Techniques KW - Phosphorylation KW - Cells, Cultured KW - Hair Cells, Outer KW - Ionomycin KW - Cell Membrane KW - Proteins KW - Support, Non-U.S. Gov't KW - Acetylcholine KW - Calcium Signaling KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85222221?accountid=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+Neuroscience&rft.atitle=Two+distinct+Ca%282%2B%29-dependent+signaling+pathways+regulate+the+motor+output+of+cochlear+outer+hair+cells.&rft.au=Frolenkov%2C+G+I%3BMammano%2C+F%3BBelyantseva%2C+I+A%3BColing%2C+Donald+E%3BKachar+Bechara&rft.aulast=Frolenkov&rft.aufirst=G&rft.date=2000-08-01&rft.volume=20&rft.issue=16&rft.spage=5940&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Neuroscience&rft.issn=02706474&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Molecular mechanism of vectorial proton translocation by bacteriorhodopsin AN - 762280734; 13742782 AB - Bacteriorhodopsin, a membrane protein with a relative molecular mass of 27,000, is a light driven pump which transports protons across the cell membrane of the halophilic organism Halobacterium salinarum. The chromophore retinal is covalently attached to the protein via a protonated Schiff base. Upon illumination, retinal is isomerized. The Schiff base then releases a proton to the extracellular medium, and is subsequently reprotonated from the cytoplasm. An atomic model for bacteriorhodopsin was first determined by Henderson et al, and has been confirmed and extended by work in a number of laboratories in the last few years. Here we present an atomic model for structural changes involved in the vectorial, light-driven transport of protons by bacteriorhodopsin. A 'switch' mechanism ensures the vectorial nature of pumping. First, retinal unbends, triggered by loss of the Schiff base proton, and second, a protein conformational change occurs. This conformational change, which we have determined by electron crystallography at atomic (3.2 aa in-plane and 3.6 aa vertical) resolution, is largely localized to helices F and G, and provides an 'opening' of the protein to protons on the cytoplasmic side of the membrane. JF - Nature AU - Subramaniam, Sriram AU - Henderson, Richard AD - [1] MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, UK [2] Laboratory of Biochemistry, National Cancer Institute, Bethesda, Maryland 20892, USA PY - 2000 SP - 653 EP - 657 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 406 IS - 6796 SN - 0028-0836, 0028-0836 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Water Resources Abstracts; Aqualine Abstracts; ASFA 1: Biological Sciences & Living Resources KW - Molecular modelling KW - Retina KW - Membrane proteins KW - Cell membranes KW - Molecular weight KW - Cytoplasm KW - Halobacterium salinarum KW - Crystallography KW - Pumping KW - Translocation KW - Bacteria KW - Membranes KW - Protons KW - Retinas KW - Laboratories KW - Bases KW - Chromophores KW - Model Studies KW - Light effects KW - Bacteriorhodopsin KW - Illumination KW - Proteins KW - Pumps KW - AQ 00001:Water Resources and Supplies KW - SW 6030:Hydraulic machinery KW - Q1 08481:Productivity KW - A 01300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/762280734?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aaqualine&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Molecular+mechanism+of+vectorial+proton+translocation+by+bacteriorhodopsin&rft.au=Subramaniam%2C+Sriram%3BHenderson%2C+Richard&rft.aulast=Subramaniam&rft.aufirst=Sriram&rft.date=2000-08-01&rft.volume=406&rft.issue=6796&rft.spage=653&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/10.1038%2F35020614 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-11-01 N1 - Last updated - 2015-12-23 N1 - SubjectsTermNotLitGenreText - Cell membranes; Retinas; Cytoplasm; Molecular weight; Pumping; Molecular modelling; Illumination; Retina; Bacteriorhodopsin; Protons; Crystallography; Chromophores; Membrane proteins; Translocation; Light effects; Membranes; Laboratories; Bases; Proteins; Pumps; Model Studies; Bacteria; Halobacterium salinarum DO - http://dx.doi.org/10.1038/35020614 ER - TY - JOUR T1 - Learning disabilities association-sponsored symposium on chemical hormone impostors and child development. AN - 72549725; 10964800 JF - Environmental health perspectives AU - Heindel, J AD - Division of Extramural Research and Training, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. heindelj@niehs.nih.gov Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 785 EP - 786 VL - 108 IS - 8 SN - 0091-6765, 0091-6765 KW - Environmental Pollutants KW - 0 KW - Hormones KW - Index Medicus KW - Humans KW - Child KW - Congresses as Topic KW - Child Development KW - Learning Disorders -- etiology KW - Environmental Pollutants -- adverse effects KW - Hormones -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72549725?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Learning+disabilities+association-sponsored+symposium+on+chemical+hormone+impostors+and+child+development.&rft.au=Heindel%2C+J&rft.aulast=Heindel&rft.aufirst=J&rft.date=2000-08-01&rft.volume=108&rft.issue=8&rft.spage=785&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 - 2001-08-16 N1 - Date created - 2001-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuroprotective role for the p50 subunit of NF-kappaB in an experimental model of Huntington's disease. AN - 72549609; 11211235 AB - Prototypical NF-kappaB consists of a transcription factor dimer of p50 and p65, and an inhibitory subunit called I-kappaB. NF-kappaB is activated in neurons in response to excitotoxic, metabolic, and oxidative stress. Cell-culture data suggest that activation of NF-kappaB can prevent neuronal apoptosis, but its role in vivo is unclear and the specific kappaB subunits involved are unknown. In Huntington's disease (HD), striatal neurons degenerate, and a similar pattern of neuronal vulnerability occurs in rats and mice following exposure to the mitochondrial toxin 3-nitropropionic acid (3NP). We report that mice lacking the p50 subunit of NF-kappaB exhibit increased damage to striatal neurons following administration of 3NP. The neuronal death occurs by apoptosis as indicated by increased caspase activation and DNA fragmentation into oligonucleosomes. NF-kappaB activity is markedly increased in striatum 24-72 h following 3NP administration in wild-type mice, but not in mice lacking p50, indicating that p50 is necessary for the vast majority of 3NP-induced NF-kappaB DNA-binding activity in striatum. Cultured striatal neurons from p50-/- mice exhibited enhanced oxidative stress, perturbed calcium regulation, and increased cell death following exposure to 3NP, suggesting a direct adverse effect of p50 deficiency in striatal neurons. JF - Journal of molecular neuroscience : MN AU - Yu, Z AU - Zhou, D AU - Cheng, G AU - Mattson, M P AD - Sanders-Brown Research Center on Aging, National Institute on Aging Gerontology Research Center, Baltimore, MD 21224, USA. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 31 EP - 44 VL - 15 IS - 1 SN - 0895-8696, 0895-8696 KW - Convulsants KW - 0 KW - NF-kappa B KW - Nitro Compounds KW - Propionates KW - 3-nitropropionic acid KW - QY4L0FOX0D KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Convulsants -- pharmacology KW - Propionates -- pharmacology KW - Disease Models, Animal KW - Cells, Cultured -- drug effects KW - Mice KW - Homeostasis -- physiology KW - Homeostasis -- drug effects KW - Neurons -- pathology KW - Mice, Knockout KW - Calcium -- metabolism KW - Oxidative Stress -- physiology KW - Neostriatum -- metabolism KW - Cells, Cultured -- metabolism KW - Neostriatum -- drug effects KW - Oxidative Stress -- drug effects KW - Mice, Inbred C57BL KW - Neostriatum -- pathology KW - Female KW - Huntington Disease -- physiopathology KW - Apoptosis -- genetics KW - Cell Survival -- genetics KW - Nerve Degeneration -- physiopathology KW - Huntington Disease -- chemically induced KW - Nerve Degeneration -- genetics KW - NF-kappa B -- genetics KW - NF-kappa B -- metabolism KW - Huntington Disease -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72549609?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+molecular+neuroscience+%3A+MN&rft.atitle=Neuroprotective+role+for+the+p50+subunit+of+NF-kappaB+in+an+experimental+model+of+Huntington%27s+disease.&rft.au=Yu%2C+Z%3BZhou%2C+D%3BCheng%2C+G%3BMattson%2C+M+P&rft.aulast=Yu&rft.aufirst=Z&rft.date=2000-08-01&rft.volume=15&rft.issue=1&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+neuroscience+%3A+MN&rft.issn=08958696&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-12 N1 - Date created - 2001-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assessing overall risk in reproductive experiments. AN - 72357586; 11051068 AB - Toxicologists are often interested in assessing the joint effect of an exposure on multiple reproductive endpoints, including early loss, fetal death, and malformation. Exposures that occur prior to mating or extremely early in development can adversely affect the number of implantation sites or fetuses that form within each dam and may even prevent pregnancy. A simple approach for assessing overall adverse effects in such studies is to consider fetuses or implants that fail to develop due to exposure as missing data. The missing data can be imputed, and standard methods for the analysis of quantal response data can then be used for quantitative risk assessment or testing. In this article, a new bias-corrected imputation procedure is proposed and evaluated. The procedure is straightforward to implement in standard statistical packages and has excellent operating characteristics when used in combination with a marginal model fit with generalized estimating equations. The methods are applied to data from a reproductive toxicity study of Nitrofurazone conducted by the National Toxicology Program. JF - Risk analysis : an official publication of the Society for Risk Analysis AU - Dunson, D B AD - Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. dunson1@niehs.nih.gov Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 429 EP - 437 VL - 20 IS - 4 SN - 0272-4332, 0272-4332 KW - Anti-Infective Agents, Local KW - 0 KW - Nitrofurazone KW - X8XI70B5Z6 KW - Index Medicus KW - Animals KW - Nitrofurazone -- toxicity KW - Dose-Response Relationship, Drug KW - Algorithms KW - Models, Statistical KW - Mice KW - Monte Carlo Method KW - Models, Biological KW - Pregnancy KW - Embryonic and Fetal Development -- drug effects KW - Abortion, Spontaneous -- chemically induced KW - Anti-Infective Agents, Local -- toxicity KW - Confidence Intervals KW - Abnormalities, Drug-Induced -- etiology KW - Fetal Death -- chemically induced KW - Female KW - Male KW - Fetus -- drug effects KW - Toxicology KW - Risk Assessment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72357586?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Risk+analysis+%3A+an+official+publication+of+the+Society+for+Risk+Analysis&rft.atitle=Assessing+overall+risk+in+reproductive+experiments.&rft.au=Dunson%2C+D+B&rft.aulast=Dunson&rft.aufirst=D&rft.date=2000-08-01&rft.volume=20&rft.issue=4&rft.spage=429&rft.isbn=&rft.btitle=&rft.title=Risk+analysis+%3A+an+official+publication+of+the+Society+for+Risk+Analysis&rft.issn=02724332&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-14 N1 - Date created - 2000-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional interactions between the extracellular domain and the seven-transmembrane domain in Ca2+ receptor activation. AN - 72355673; 11051048 AB - We studied the activity of mutants involving the aminoterminal extracellular, seven-transmembrane (7TM) and carboxy-terminal tail domains of the human Ca2+ receptor to gain insight into the functional interactions between these domains during receptor activation. Missense mutations of highly conserved residues, D190 and E297, in the extracellular domain (ECD), and a mutation within part of the proximal carboxyterminal tail, A877-880E, resulted in receptors with severely reduced response to Ca2+ despite adequate cell surface expression. Coexpression of either D190A or E297K mutants with A877-880E led to significant reconstitution of function. No such reconstitution occurred when D190A or E297K mutants were coexpressed with a truncation mutant possessing an intact amino-terminal extracellular and first transmembrane domain, despite evidence for heterodimerization and cell surface expression of the respective mutant receptors. In addition, no reconstitution of function was observed when D190A was coexpressed with a deletion Ca2+ receptor mutant lacking only a cysteine-rich region located in the ECD of the Ca2+ receptor (Ca-//-Ca). Moreover, coexpression of this Ca-//-Ca with A877-880E did not recover function. The results show that Ca2+ receptor extracellular and 7TM domains are discrete entities that can communicate within the context of a heterodimer composed of complementary mutant receptors. Two intact 7TM domains and two intact cysteine-rich regions appear to be required for such communication to occur. The results are discussed in the context of a speculative model of receptor structure and function. JF - Endocrine AU - Hauache, O M AU - Hu, J AU - Ray, K AU - Spiegel, A M AD - Metabolic Diseases Branch, NIDDK, NIH, Bethesda, MD, USA. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 63 EP - 70 VL - 13 IS - 1 SN - 1355-008X, 1355-008X KW - Calcium-Binding Proteins KW - 0 KW - Phosphatidylinositols KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Phosphatidylinositols -- metabolism KW - Dimerization KW - Humans KW - Gene Expression KW - Amino Acid Sequence KW - Calcium -- pharmacology KW - Hydrolysis KW - Biotinylation KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Transfection KW - Molecular Sequence Data KW - Immunosorbent Techniques KW - Cell Membrane -- metabolism KW - Cell Line KW - Calcium-Binding Proteins -- physiology KW - Calcium-Binding Proteins -- genetics KW - Calcium-Binding Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72355673?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrine&rft.atitle=Functional+interactions+between+the+extracellular+domain+and+the+seven-transmembrane+domain+in+Ca2%2B+receptor+activation.&rft.au=Hauache%2C+O+M%3BHu%2C+J%3BRay%2C+K%3BSpiegel%2C+A+M&rft.aulast=Hauache&rft.aufirst=O&rft.date=2000-08-01&rft.volume=13&rft.issue=1&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Endocrine&rft.issn=1355008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-01 N1 - Date created - 2001-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Research perspectives on alcohol craving: an overview. AN - 72286713; 11002901 AB - This overview of the Addiction supplement on 'Research Perspectives on Alcohol Craving' has three objectives. The first is to familiarize readers with the variety of theoretical models relevant to craving and the definitions of craving generated by them that are discussed in the supplement. These include phenomenological models, classical and operant conditioning models, the incentive-sensitization theory, a tonic-phasic model of dopamine system regulation, cognitive social learning theory and the cognitive processing theory of craving. The second objective is to provide a brief summary of the methodological articles which focus as a whole more on what can be done than on what has been done in alcohol craving research. The final objective is to emphasize the potential importance of transdisciplinary research--research that integrates components of different theoretical models--for delineating the role of alcohol and drug craving in the complex biobehavioral process known as addiction. It is the hope of the guest editors (the authors of this overview) that the Addiction supplement and this introduction to it will contribute to development of a framework for future transdisciplinary research on alcohol craving. JF - Addiction (Abingdon, England) AU - Lowman, C AU - Hunt, W A AU - Litten, R Z AU - Drummond, D C AD - Division of Clinical Prevention Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-7003, USA. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - S45 EP - S54 VL - 95 Suppl 2 SN - 0965-2140, 0965-2140 KW - Index Medicus KW - Animals KW - Models, Psychological KW - Conditioning (Psychology) KW - Humans KW - Research KW - Alcohol-Related Disorders -- physiopathology KW - Behavior, Addictive -- psychology KW - Alcohol-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72286713?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Research+perspectives+on+alcohol+craving%3A+an+overview.&rft.au=Lowman%2C+C%3BHunt%2C+W+A%3BLitten%2C+R+Z%3BDrummond%2C+D+C&rft.aulast=Lowman&rft.aufirst=C&rft.date=2000-08-01&rft.volume=95+Suppl+2&rft.issue=&rft.spage=S45&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 - 2000-10-05 N1 - Date created - 2000-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Small molecule inhibitor of HIV-1 nuclear import suppresses HIV-1 replication in human lymphoid tissue ex vivo: a potential addition to current anti-HIV drug repertoire. AN - 72274322; 10996396 AB - Despite recent progress in anti-HIV therapy, which has to do mainly with introduction of protease inhibitors into clinical practice, drug toxicity and emergence of drug-resistant isolates during the long-term treatment of the patients necessitates search for new drugs that can be added to currently used components of a multi-drug cocktail in highly active anti-retroviral therapy (HAART). Recently, we described a class of arylene bis(methylketone) compounds that inhibit nuclear import of HIV-1 pre-integration complexes and suppress viral replication in macrophages and PBMC in vitro. In this report, we demonstrate that one of these compounds, CNI-H1194, inhibited HIV-1 replication in primary lymphoid tissue ex vivo. The compound did not antagonize the activity of currently used anti-HIV drugs that inhibit viral reverse transcriptase or protease. These results suggest that arylene bis(methylketone) compounds might be a valuable addition to HAART. JF - Antiviral research AU - Glushakova, S AU - Dubrovsky, L AU - Grivel, J AU - Haffar, O AU - Bukrinsky, M AD - The Laboratory of Cellular and Molecular Biophysics, NICHD, NIH, Bethesda, MD 20892, USA. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 89 EP - 95 VL - 47 IS - 2 SN - 0166-3542, 0166-3542 KW - Aniline Compounds KW - 0 KW - Anti-HIV Agents KW - HIV Protease Inhibitors KW - Pyrimidines KW - Reverse Transcriptase Inhibitors KW - CNI H1194 KW - 180741-00-8 KW - Zidovudine KW - 4B9XT59T7S KW - Nelfinavir KW - HO3OGH5D7I KW - Index Medicus KW - Drug Interactions KW - Reverse Transcriptase Inhibitors -- pharmacology KW - Humans KW - Zidovudine -- pharmacology KW - Cell Culture Techniques KW - Macrophages -- virology KW - CD4-CD8 Ratio KW - Virus Replication -- drug effects KW - Anti-HIV Agents -- pharmacology KW - CD4-Positive T-Lymphocytes -- virology KW - Antiretroviral Therapy, Highly Active KW - HIV Protease Inhibitors -- pharmacology KW - Nelfinavir -- pharmacology KW - Organ Culture Techniques KW - Aniline Compounds -- pharmacology KW - Pyrimidines -- pharmacology KW - Palatine Tonsil -- immunology KW - HIV-1 -- enzymology KW - HIV-1 -- physiology KW - HIV-1 -- drug effects KW - Palatine Tonsil -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72274322?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antiviral+research&rft.atitle=Small+molecule+inhibitor+of+HIV-1+nuclear+import+suppresses+HIV-1+replication+in+human+lymphoid+tissue+ex+vivo%3A+a+potential+addition+to+current+anti-HIV+drug+repertoire.&rft.au=Glushakova%2C+S%3BDubrovsky%2C+L%3BGrivel%2C+J%3BHaffar%2C+O%3BBukrinsky%2C+M&rft.aulast=Glushakova&rft.aufirst=S&rft.date=2000-08-01&rft.volume=47&rft.issue=2&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Antiviral+research&rft.issn=01663542&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-07 N1 - Date created - 2000-10-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relationships between age of onset, antisocial history and general psychopathological traits in Japanese alcoholics. AN - 72269214; 10997857 AB - This study investigated the relationships of age of onset, antisocial history and general psychopathological traits measured by the Minnesota Multiphasic Personality Inventory (MMPI) in Japanese alcoholics (n = 84). A 2 (earlier vs later onset) x 2 (antisocial vs non-antisocial) multivariate analysis of covariance showed that age of onset had a significant correlation with some subscales of the MMPI such as L (lie), Sc (schizophrenia), and Si (social introversion), whereas history of antisocial behavior had no significant correlation with any MMPI clinical subscales. This result indicated that age of onset was a more significant variable than was antisocial history with regard to the current general psychopathological traits on MMPI in Japanese alcoholics. JF - Psychiatry and clinical neurosciences AU - Matsuoka, K AU - Kim, Y AU - Toshida, S AU - Ohshima, N AD - Division of Adult Mental Health, National Institute of Mental Health, National Center of Psychiatry and Neurology, Ichikawa, Chiba, Japan. HQL01005@nifty.ne.jp Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 413 EP - 417 VL - 54 IS - 4 SN - 1323-1316, 1323-1316 KW - Index Medicus KW - Japan -- epidemiology KW - Reproducibility of Results KW - Hospitalization KW - Age of Onset KW - Humans KW - MMPI KW - Adult KW - Middle Aged KW - Male KW - Catchment Area (Health) KW - Alcoholism -- rehabilitation KW - Alcoholism -- epidemiology KW - Antisocial Personality Disorder -- diagnosis KW - Antisocial Personality Disorder -- psychology KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72269214?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychiatry+and+clinical+neurosciences&rft.atitle=Relationships+between+age+of+onset%2C+antisocial+history+and+general+psychopathological+traits+in+Japanese+alcoholics.&rft.au=Matsuoka%2C+K%3BKim%2C+Y%3BToshida%2C+S%3BOhshima%2C+N&rft.aulast=Matsuoka&rft.aufirst=K&rft.date=2000-08-01&rft.volume=54&rft.issue=4&rft.spage=413&rft.isbn=&rft.btitle=&rft.title=Psychiatry+and+clinical+neurosciences&rft.issn=13231316&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-26 N1 - Date created - 2001-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Control of transfer RNA maturation by phosphorylation of the human La antigen on serine 366. AN - 72248501; 10983981 AB - Conversion of a nascent precursor tRNA to a mature functional species is a multipartite process that involves the sequential actions of several processing and modifying enzymes. La is the first protein to interact with pre-tRNAs in eukaryotes. An opal suppressor tRNA served as a functional probe to examine the activities of yeast and human (h)La proteins in this process in fission yeast. An RNA recognition motif and Walker motif in the metazoan-specific C-terminal domain (CTD) of hLa maintain pre-tRNA in an unprocessed state by blocking the 5'-processing site, impeding an early step in the pathway. Faithful phosphorylation of hLa on serine 366 reverses this block and promotes tRNA maturation. The results suggest that regulation of tRNA maturation at the level of RNase P cleavage may occur via phosphorylation of serine 366 of hLa. JF - Molecular cell AU - Intine, R V AU - Sakulich, A L AU - Koduru, S B AU - Huang, Y AU - Pierstorff, E AU - Goodier, J L AU - Phan, L AU - Maraia, R J AD - Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 339 EP - 348 VL - 6 IS - 2 SN - 1097-2765, 1097-2765 KW - Autoantigens KW - 0 KW - RNA Precursors KW - RNA, Transfer, Ser KW - Ribonucleoproteins KW - SS-B antigen KW - Transcription Factors KW - Phosphotyrosine KW - 21820-51-9 KW - Serine KW - 452VLY9402 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Phosphorylation KW - Transcription Factors -- metabolism KW - Models, Molecular KW - Humans KW - Transcription Factors -- chemistry KW - Molecular Sequence Data KW - Nucleic Acid Conformation KW - RNA Precursors -- metabolism KW - Schizosaccharomyces -- genetics KW - Ribonucleoproteins -- chemistry KW - RNA, Transfer, Ser -- chemistry KW - Ribonucleoproteins -- metabolism KW - Autoantigens -- metabolism KW - RNA Precursors -- genetics KW - RNA, Transfer, Ser -- genetics KW - Autoantigens -- chemistry KW - Schizosaccharomyces -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72248501?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Control+of+transfer+RNA+maturation+by+phosphorylation+of+the+human+La+antigen+on+serine+366.&rft.au=Intine%2C+R+V%3BSakulich%2C+A+L%3BKoduru%2C+S+B%3BHuang%2C+Y%3BPierstorff%2C+E%3BGoodier%2C+J+L%3BPhan%2C+L%3BMaraia%2C+R+J&rft.aulast=Intine&rft.aufirst=R&rft.date=2000-08-01&rft.volume=6&rft.issue=2&rft.spage=339&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 - 2000-09-28 N1 - Date created - 2000-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Improved titers of HIV-based lentiviral vectors using the SRV-1 constitutive transport element. AN - 72240382; 10981670 AB - The development of lentiviral vectors that use Rev-independent mechanisms of nuclear export for their genomic RNA could facilitate the construction of novel anti-HIV vectors. We have improved the titers of Rev-independent lentiviral vectors having the SRV-1 CTE by mutating the major splice donor and acceptor sites present in the vector and by relocalization of the CTE sequences adjacent to the HIV-1 3'LTR. These two modifications have additive beneficial effects on vector titers and packaging efficiency. Packaging these CTE+ vectors expressing marker genes with a Rev-dependent HIV-1 helper vector yields higher titers than are obtained using a Rev-dependent lentiviral vector. JF - Gene therapy AU - Mautino, M R AU - Keiser, N AU - Morgan, R A AD - Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-1851, USA. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 1421 EP - 1424 VL - 7 IS - 16 SN - 0969-7128, 0969-7128 KW - Gene Products, rev KW - 0 KW - rev Gene Products, Human Immunodeficiency Virus KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Humans KW - Acquired Immunodeficiency Syndrome -- therapy KW - Retroviruses, Simian -- genetics KW - Genetic Therapy -- methods KW - Genetic Vectors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72240382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+therapy&rft.atitle=Improved+titers+of+HIV-based+lentiviral+vectors+using+the+SRV-1+constitutive+transport+element.&rft.au=Mautino%2C+M+R%3BKeiser%2C+N%3BMorgan%2C+R+A&rft.aulast=Mautino&rft.aufirst=M&rft.date=2000-08-01&rft.volume=7&rft.issue=16&rft.spage=1421&rft.isbn=&rft.btitle=&rft.title=Gene+therapy&rft.issn=09697128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-26 N1 - Date created - 2000-09-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Employment as butcher and cancer risk in a record-linkage study from Sweden. AN - 72238081; 10977107 AB - To investigate the risk of cancer among butchers and other meat workers in a large record-linkage study from Sweden. The Swedish Cancer Environment Register III contains nationwide data on cancer incidence during 1971-1989 for all residents, by occupation and industry of employment as reported at the 1960 and 1970 censuses. We identified 25,049 men classified as butchers or meat workers at either census. We used as a comparison group the remaining part of the active male population, after exclusion of workers with direct contact with animals. Butchers in the meat industry had a slight increase in the risk of cancer (relative risk [RR] 1.1, 95% confidence interval [CI] 1.0-1.3), which was due to an increased risk of cancers of the oral cavity and pharynx (RR 1.6, 95% CI 1.0-2.7), stomach (RR 1.6, 95% CI 1.1-2.7), larynx (RR 1.4, 95% CI 0.6-3.4), and lung (RR 1.4, 95% CI 1.1-1.9). The risk of stomach cancer was highest during the first 5 years of the study, and among butchers from urban areas. No temporal or geographic variations were seen for lung cancer risk, with elevations restricted to squamous cell carcinoma. An increased risk of stomach, laryngeal and lung cancers was present in butchers and meat workers outside the meat industry. There was no clear indication of an increased risk of other neoplasms. The increased risk of oral, laryngeal, lung and stomach cancers among Swedish butchers may be at least partly due to confounding by tobacco smoking, alcohol drinking, and other lifestyle factors. However, exposures in the meat industry (e.g., viruses, nitrosamines, polycyclic aromatic hydrocarbons) may contribute the elevated cancer risks. JF - Cancer causes & control : CCC AU - Boffetta, P AU - Gridley, G AU - Gustavsson, P AU - Brennan, P AU - Blair, A AU - Ekström, A M AU - Fraumeni, J F AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. boffetta@iarc.fr Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 627 EP - 633 VL - 11 IS - 7 SN - 0957-5243, 0957-5243 KW - Hydrocarbons, Aromatic KW - 0 KW - Nitrosamines KW - Index Medicus KW - Humans KW - Hydrocarbons, Aromatic -- adverse effects KW - Nitrosamines -- adverse effects KW - Aged KW - Otorhinolaryngologic Neoplasms -- etiology KW - Life Style KW - Otorhinolaryngologic Neoplasms -- epidemiology KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - Risk Factors KW - Mouth Neoplasms -- etiology KW - Adult KW - Sweden -- epidemiology KW - Incidence KW - Middle Aged KW - Stomach Neoplasms -- epidemiology KW - Stomach Neoplasms -- etiology KW - Adolescent KW - Male KW - Mouth Neoplasms -- epidemiology KW - Occupational Diseases -- etiology KW - Neoplasms -- epidemiology KW - Meat-Packing Industry KW - Occupational Exposure -- adverse effects KW - Occupational Diseases -- epidemiology KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72238081?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Employment+as+butcher+and+cancer+risk+in+a+record-linkage+study+from+Sweden.&rft.au=Boffetta%2C+P%3BGridley%2C+G%3BGustavsson%2C+P%3BBrennan%2C+P%3BBlair%2C+A%3BEkstr%C3%B6m%2C+A+M%3BFraumeni%2C+J+F&rft.aulast=Boffetta&rft.aufirst=P&rft.date=2000-08-01&rft.volume=11&rft.issue=7&rft.spage=627&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-08 N1 - Date created - 2001-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of glioma cells in vitro and in vivo using a recombinant adenoviral vector containing an astrocyte-specific promoter. AN - 72233595; 10975672 AB - Gene therapy using the herpes simplex virus thymidine kinase (HSV-TK) gene in combination with the drug ganciclovir (GCV) is a promising approach for the treatment of cancer-inducing gliomas, a tumor with a poor prognosis. In an attempt to limit the toxic effects on normal tissues, we constructed a recombinant adenoviral vector, Adgfa2TK, in which the HSV-TK gene is driven by the promoter for the gene encoding glial fibrillary acidic protein, an intermediate filament protein expressed primarily in astrocytes. Infection by Adgfa2TK of a glial cell line (C6) and a non-glial cell line (MDA-MB-231) revealed markedly increased expression of HSV-TK in glial cells as determined by Western blot. In comparison, high HSV-TK protein levels were produced in both cell lines after infection with a control virus, AdCMVTK, in which the constitutive cytomegalovirus viral promoter was used to direct HSV-TK expression. Infection of two glial cell lines (C6, U251) and two non-glial cell lines (HepG2, MDA-MB-231) with Adgfa2TK followed by GCV treatment revealed high toxicity in glial cell lines (50% growth inhibitory concentration: 75 microg/mL) in the non-glial cell lines. In vivo, injection of Adgfa2TK into C6 tumors grown in nude mice followed by intraperitoneal GCV treatment significantly repressed tumor growth compared with the controls. Adgfa2TK may be useful for directing expression of the HSV-TK gene to gliomas. JF - Cancer gene therapy AU - Vandier, D AU - Rixe, O AU - Besnard, F AU - Kim, M AU - Rikiyama, T AU - Goldsmith, M AU - Brenner, M AU - Gouyette, A AU - Cowan, K H AD - Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 1120 EP - 1126 VL - 7 IS - 8 SN - 0929-1903, 0929-1903 KW - Antiviral Agents KW - 0 KW - DNA Primers KW - Glial Fibrillary Acidic Protein KW - Ganciclovir KW - P9G3CKZ4P5 KW - Index Medicus KW - Rats KW - Animals KW - Base Sequence KW - Tumor Cells, Cultured KW - Humans KW - Antiviral Agents -- pharmacology KW - Recombination, Genetic KW - In Vitro Techniques KW - Mice, Nude KW - Mice KW - Glial Fibrillary Acidic Protein -- genetics KW - Ganciclovir -- pharmacology KW - Brain Neoplasms -- pathology KW - Promoter Regions, Genetic KW - Glioma -- pathology KW - Genetic Vectors KW - Astrocytes -- pathology KW - Adenoviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72233595?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+gene+therapy&rft.atitle=Inhibition+of+glioma+cells+in+vitro+and+in+vivo+using+a+recombinant+adenoviral+vector+containing+an+astrocyte-specific+promoter.&rft.au=Vandier%2C+D%3BRixe%2C+O%3BBesnard%2C+F%3BKim%2C+M%3BRikiyama%2C+T%3BGoldsmith%2C+M%3BBrenner%2C+M%3BGouyette%2C+A%3BCowan%2C+K+H&rft.aulast=Vandier&rft.aufirst=D&rft.date=2000-08-01&rft.volume=7&rft.issue=8&rft.spage=1120&rft.isbn=&rft.btitle=&rft.title=Cancer+gene+therapy&rft.issn=09291903&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-22 N1 - Date created - 2000-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Systemic administration of the propargylamine CGP 3466B prevents behavioural and morphological deficits in rats with 6-hydroxydopamine-induced lesions in the substantia nigra. AN - 72231973; 10971644 AB - The ability of CGP 3466B to attenuate the behavioural and morphological consequences of experimentally induced cell death was investigated in a recently updated animal model of Parkinson's disease. 6-Hydroxydopamine was infused bilaterally into the substantia nigra pars compacta of rats that were pretreated with desimipramine. Treatment with CGP 3466B (0.0014-1.4 mg/kg, injected subcutaneously) or its solvent was begun 2 h after the 6-OHDA injection, and maintained twice daily for 14 days. After a washout period of 14 days, changes in motor behaviour were evaluated, using the open field test (analysis of normal and abnormal stepping, e.g.) and the paw test (analysis of retraction time of limbs). Changes in learning and memory were evaluated with the help of the Morris water maze task. Following immunocytochemical staining of tyrosine hydroxylase, the extent of the lesion was quantified using a computerized system. CGP 3466B prevented all deficits produced by 6-hydroxydopamine (6-OHDA), though at different doses. It prevented: abnormal stepping (0.0014-0.014 mg/kg); increased forelimb and hindlimb retraction time (0.014-0.14 mg/kg and 0.0014-0.14 mg/kg, respectively); delayed learning (1.4 mg/kg); and reduced tyrosine hydroxylase immunoreactivity in the substantia nigra (0.0014-0.014 mg/kg). CGP 3466B (0.0014-0.14 mg/kg) induced no deficits in sham-treated rats. CGP 3466B (1.4 mg/kg), however, did not show any benefit on motor deficits in 6-OHDA-lesioned rats, and induced abnormal movements and decreased the tyrosine hydroxylase immunoreactivity in the substantia nigra pars compacta and the ventral tegmental area of sham-lesioned animals. It is concluded that CGP 3466B prevents all 6-OHDA-induced behavioural and immunocytochemical deficits, though at different doses. CGP 3466B is suggested to be a valuable agent for inhibiting the dopaminergic degeneration in patients with Parkinson's disease. JF - The European journal of neuroscience AU - Andringa, G AU - van Oosten, R V AU - Unger, W AU - Hafmans, T G AU - Veening, J AU - Stoof, J C AU - Cools, A R AD - Department of Psychoneuropharmacology, University of Nijmegen, Nijmegen, The Netherlands. AndringaG@ninds.nih.gov Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 3033 EP - 3043 VL - 12 IS - 8 SN - 0953-816X, 0953-816X KW - Antibodies KW - 0 KW - Oxepins KW - Propylamines KW - Sympatholytics KW - dibenzo(b,f)oxepin-10-ylmethyl-methyl-prop-2-ynyl-amine KW - propargylamine KW - 2450-71-7 KW - Oxidopamine KW - 8HW4YBZ748 KW - Pargyline KW - 9MV14S8G3E KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Maze Learning -- drug effects KW - Dopamine -- physiology KW - Nerve Degeneration -- chemically induced KW - Denervation KW - Rats KW - Body Weight KW - Nerve Degeneration -- drug therapy KW - Tyrosine 3-Monooxygenase -- immunology KW - Tyrosine 3-Monooxygenase -- analysis KW - Exploratory Behavior -- drug effects KW - Nerve Degeneration -- pathology KW - Apoptosis -- drug effects KW - Rats, Wistar KW - Neurons -- enzymology KW - Gait -- drug effects KW - Male KW - Parkinson Disease, Secondary -- chemically induced KW - Behavior, Animal -- drug effects KW - Substantia Nigra -- physiopathology KW - Parkinson Disease, Secondary -- pathology KW - Oxepins -- pharmacology KW - Substantia Nigra -- pathology KW - Pargyline -- pharmacology KW - Substantia Nigra -- drug effects KW - Propylamines -- pharmacology KW - Pargyline -- analogs & derivatives KW - Parkinson Disease, Secondary -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72231973?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+European+journal+of+neuroscience&rft.atitle=Systemic+administration+of+the+propargylamine+CGP+3466B+prevents+behavioural+and+morphological+deficits+in+rats+with+6-hydroxydopamine-induced+lesions+in+the+substantia+nigra.&rft.au=Andringa%2C+G%3Bvan+Oosten%2C+R+V%3BUnger%2C+W%3BHafmans%2C+T+G%3BVeening%2C+J%3BStoof%2C+J+C%3BCools%2C+A+R&rft.aulast=Andringa&rft.aufirst=G&rft.date=2000-08-01&rft.volume=12&rft.issue=8&rft.spage=3033&rft.isbn=&rft.btitle=&rft.title=The+European+journal+of+neuroscience&rft.issn=0953816X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-19 N1 - Date created - 2000-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Stress-induced relapse to heroin and cocaine seeking in rats: a review. AN - 72231234; 10967352 AB - Studies in humans suggest that exposure to stress increases the probability of relapse to drug use, but until recently there has been no animal model to study the mechanisms that mediate this effect. We have developed a reinstatement procedure that allows us to study the effect of stress on relapse to drug seeking in rats. Using this procedure, we have shown that exposure to intermittent footshock stress reliably reinstates heroin and cocaine seeking after prolonged drug-free periods. In the present paper, we summarize results from several studies on stress-induced reinstatement of heroin and cocaine seeking in rats. We first assess the degree to which the phenomenon of stress-induced relapse generalizes to other stressors, to behaviors controlled by other drugs of abuse, and to behaviors controlled by non-drug reinforcers. We then review evidence from studies concerned with the neurotransmitters, the brain sites, and the neural systems involved in stress-induced reinstatement of drug seeking. Finally, we consider the mechanisms that might underlie stress-induced relapse to drug seeking and the possible implications of the findings for the treatment of relapse to drug use in humans. JF - Brain research. Brain research reviews AU - Shaham, Y AU - Erb, S AU - Stewart, J AD - Behavioral Neuroscience Branch, IRP/NIDA/NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. yshaham@intra.nida.nih.gov Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 13 EP - 33 VL - 33 IS - 1 KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Recurrence KW - Stress, Physiological -- complications KW - Heroin Dependence -- etiology KW - Heroin Dependence -- physiopathology KW - Cocaine-Related Disorders -- physiopathology KW - Cocaine-Related Disorders -- etiology KW - Stress, Physiological -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72231234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research.+Brain+research+reviews&rft.atitle=Stress-induced+relapse+to+heroin+and+cocaine+seeking+in+rats%3A+a+review.&rft.au=Shaham%2C+Y%3BErb%2C+S%3BStewart%2C+J&rft.aulast=Shaham&rft.aufirst=Y&rft.date=2000-08-01&rft.volume=33&rft.issue=1&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Brain+research+reviews&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-28 N1 - Date created - 2000-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Contributions of behavioral science to alcohol research: understanding who is at risk and why. AN - 72230453; 10975614 AB - Behavioral science has been an active participant in alcohol research progress over the past 30 years, particularly in the areas of prevention and treatment methodology. However, alcoholism results from the interaction between complex biological and behavioral systems, and in recent years, combined behavioral and biological studies, primarily of alcohol effects on the brain and of the genetics of alcoholism, have begun the much more complex process of elucidating the links between biology and specific alcohol use behaviors. It is this combined research that ultimately will produce the pharmacological and behavioral interventions that will improve the efficiency and effectiveness of alcohol prevention and treatment methods. JF - Experimental and clinical psychopharmacology AU - Gordis, E AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA. bhewitt@willco.niaaa.nih.gov Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 264 EP - 270 VL - 8 IS - 3 SN - 1064-1297, 1064-1297 KW - Central Nervous System Depressants KW - 0 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Central Nervous System Depressants -- pharmacology KW - Animals KW - Ethanol -- pharmacology KW - Risk Factors KW - Humans KW - Behavioral Sciences KW - Alcoholism -- therapy KW - Alcoholism -- genetics KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72230453?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+and+clinical+psychopharmacology&rft.atitle=Contributions+of+behavioral+science+to+alcohol+research%3A+understanding+who+is+at+risk+and+why.&rft.au=Gordis%2C+E&rft.aulast=Gordis&rft.aufirst=E&rft.date=2000-08-01&rft.volume=8&rft.issue=3&rft.spage=264&rft.isbn=&rft.btitle=&rft.title=Experimental+and+clinical+psychopharmacology&rft.issn=10641297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-09 N1 - Date created - 2001-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Placebo cigarettes in smoking research. AN - 72229995; 10975620 AB - This review outlines the development and use of placebo cigarettes in smoking research. Research on effects of smoking has been disadvantaged by the lack of an adequate placebo condition. Recently, tobacco-based denicotinized cigarettes have been used in smoking research to distinguish effects of smoking due to the delivery of nicotine, other components of tobacco smoke, and the sensory process of smoking. Placebo cigarettes do not increase heart rate and blood pressure or produce electroencephalogram changes ordinarily associated with nicotine. However, placebo cigarettes reduce subjective measures of tobacco craving, desire to smoke, and tobacco withdrawal. These findings indicate that the effects of cigarette smoking are dependent on the delivery of nicotine, tar, other compounds of tobacco smoke, and the sensory stimuli. The next generation of research may begin to investigate the mechanisms that modulate these placebo effects. JF - Experimental and clinical psychopharmacology AU - Robinson, M L AU - Houtsmuller, E J AU - Moolchan, E T AU - Pickworth, W B AD - National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland 21224, USA. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 326 EP - 332 VL - 8 IS - 3 SN - 1064-1297, 1064-1297 KW - Placebos KW - 0 KW - Index Medicus KW - Plants, Toxic KW - Behavior KW - Humans KW - Tobacco KW - Smoking -- physiopathology KW - Placebos -- therapeutic use KW - Smoking -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72229995?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+and+clinical+psychopharmacology&rft.atitle=Placebo+cigarettes+in+smoking+research.&rft.au=Robinson%2C+M+L%3BHoutsmuller%2C+E+J%3BMoolchan%2C+E+T%3BPickworth%2C+W+B&rft.aulast=Robinson&rft.aufirst=M&rft.date=2000-08-01&rft.volume=8&rft.issue=3&rft.spage=326&rft.isbn=&rft.btitle=&rft.title=Experimental+and+clinical+psychopharmacology&rft.issn=10641297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-09 N1 - Date created - 2001-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A behavioral economic analysis of the relative persistence of behavior: comment on Meisch (2000) AN - 72229492; 10975625 AB - This commentary examines and reinterprets the concept of relative persistence in drug self-administration studies, described by R. A. Meisch (2000), in behavioral economic terms. Over the past several years, investigators in the behavioral sciences have successfully applied consumer demand theory to the study of drug abuse and addiction. The economic concept of demand elasticity (i.e., the changes in the amount of a commodity demanded as a function of changes in price) and the concept of unit price are described in detail, and this commentary shows these concepts provide an alternative interpretation to the relative persistence of behavior. The application of the behavioral economic approach to understanding abuse potential of putative drugs of abuse, in development of medications for drug addiction and in characterizing the transition from drug use to drug addiction, is discussed. JF - Experimental and clinical psychopharmacology AU - Shurtleff, D AD - Division of Neuroscience and Behavioral Research, National Institute on Drug Abuse, Bethesda, Maryland 20892-9555, USA. dshurtle@nida.nih.gov Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 357 EP - 9; discussion 362-5 VL - 8 IS - 3 SN - 1064-1297, 1064-1297 KW - Index Medicus KW - Animals KW - Humans KW - Substance-Related Disorders -- psychology KW - Models, Economic KW - Conditioning, Operant -- drug effects KW - Behavior, Animal -- drug effects KW - Reinforcement (Psychology) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72229492?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+and+clinical+psychopharmacology&rft.atitle=A+behavioral+economic+analysis+of+the+relative+persistence+of+behavior%3A+comment+on+Meisch+%282000%29&rft.au=Shurtleff%2C+D&rft.aulast=Shurtleff&rft.aufirst=D&rft.date=2000-08-01&rft.volume=8&rft.issue=3&rft.spage=357&rft.isbn=&rft.btitle=&rft.title=Experimental+and+clinical+psychopharmacology&rft.issn=10641297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-09 N1 - Date created - 2001-01-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Exp Clin Psychopharmacol. 2000 Aug;8(3):333-49 [10975621] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - National Institute of Mental Health goals for behavioral science. AN - 72229396; 10975615 AB - Because all health conditions for which the National Institute of Mental Health (NIMH) is responsible manifest at the level of behavior, and all interventions must have an impact at the behavioral level, NIMH is firmly committed to the support of behavioral science. In an era in which research in areas that some view as reductionist--for example, genomics, genetics, functional genomics and proteomics, and molecular science--is especially promising, NIMH is striving to maintain a balance in its portfolio with studies that explore integrative aspects of biology, including behavior. Without this perspective, new information about fundamental processes will prove ultimately to be shallow. This commentary discusses how understanding of brain and behavior in mental illness and health calls for integrating bottom-up research that studies brain and behavior through genes and molecules, with top-down research that examines the impact of environment. JF - Experimental and clinical psychopharmacology AU - Hyman, S E AD - National Institute of Mental Health, Bethesda, Maryland 20892, USA. shyman@nih.gov Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 271 EP - 272 VL - 8 IS - 3 SN - 1064-1297, 1064-1297 KW - Index Medicus KW - United States KW - Goals KW - Genetics, Behavioral KW - Substance-Related Disorders -- therapy KW - Cognitive Science KW - Behavioral Sciences -- trends KW - National Institute of Mental Health (U.S.) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72229396?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+and+clinical+psychopharmacology&rft.atitle=National+Institute+of+Mental+Health+goals+for+behavioral+science.&rft.au=Hyman%2C+S+E&rft.aulast=Hyman&rft.aufirst=S&rft.date=2000-08-01&rft.volume=8&rft.issue=3&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Experimental+and+clinical+psychopharmacology&rft.issn=10641297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-09 N1 - Date created - 2001-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - National Institute on Drug Abuse's behavioral research agenda. AN - 72226046; 10975616 AB - Basic behavioral research continues to play an integral role in the National Institute on Drug Abuse's (NIDA's) search for solutions to the complex social and public health problems posed by drug abuse and addiction. Along with NIDA's basic molecular and neuroscience research programs, behavioral research has played an important role in increasing clinician's understanding of the mechanisms and processes that underlie addiction. Much has been learned about the ways in which animals and humans respond to their environment and the role these basic behavioral processes play in drug abuse and other drug-abuse-related phenomena, such as withdrawal, craving, and relapse, but there is still much more to be known. The author discusses how NIDA will continue to build and promote its behavioral research agenda and ensure that behavioral research findings are applied in real-life settings when applicable. JF - Experimental and clinical psychopharmacology AU - Leshner, A I AD - National Institute on Drug Abuse, Bethesda, Maryland 20892, USA. leshner@nih.gov Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 273 EP - 275 VL - 8 IS - 3 SN - 1064-1297, 1064-1297 KW - Index Medicus KW - United States KW - Genetics, Behavioral KW - Animals KW - Cognitive Science KW - Humans KW - National Institutes of Health (U.S.) KW - Disease Models, Animal KW - Substance-Related Disorders -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72226046?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+and+clinical+psychopharmacology&rft.atitle=National+Institute+on+Drug+Abuse%27s+behavioral+research+agenda.&rft.au=Leshner%2C+A+I&rft.aulast=Leshner&rft.aufirst=A&rft.date=2000-08-01&rft.volume=8&rft.issue=3&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=Experimental+and+clinical+psychopharmacology&rft.issn=10641297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-09 N1 - Date created - 2001-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Women and alcohol problems: a critical analysis of the literature and unanswered questions. AN - 72222289; 10968672 AB - The evaluation of alcohol treatment services for women that emerged from the deliberations of the expert panel and RSA roundtable clearly documents the importance of interdisciplinary research. This research considers the particular social and physical context of women's lives and uses measurement tools and outcome measures appropriate for women. Development of gender-tested measurements, gender-relevant treatment services, and gender-appropriate outcome evaluations is necessary to ensure that women receive the services they need. The inclusion of women from geographically and ethnically diverse subject populations, as well as from subgroups who have traditionally been excluded from health research, is critical in the development of scientifically sound, research-based knowledge of the treatment of women with alcohol problems. The papers that follow include critical reviews of the literature by members of the expert panel, and these reviews were enriched by the roundtable discussion at RSA. Schmidt and McCarty evaluate the research on women supported on welfare. The unique challenges for pregnant women on Medicaid are discussed by Hankin, McCaul, and Heussner. The research on alcohol treatment specific to older women is critiqued by Blow, and the barriers and need for alcohol service for women in rural populations are discussed by Booth and McLaughlin. The relationships between substance abuse and violence are assessed by Miller, Wilsnack, and Cunradi. Finally, Sinha and O'Malley discuss critical gaps in understanding the impact on treatment outcomes of co-occurring disorders such as depression, anxiety, and eating disorders. JF - Alcoholism, clinical and experimental research AU - Smith, W B AU - Weisner, C AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-7003, USA. wsmith@willco.niaaa.nih.gov Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 1320 EP - 1321 VL - 24 IS - 8 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Women's Health Services KW - Humans KW - Research KW - Female KW - Women's Health KW - Alcoholism -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72222289?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Women+and+alcohol+problems%3A+a+critical+analysis+of+the+literature+and+unanswered+questions.&rft.au=Smith%2C+W+B%3BWeisner%2C+C&rft.aulast=Smith&rft.aufirst=W&rft.date=2000-08-01&rft.volume=24&rft.issue=8&rft.spage=1320&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-22 N1 - Date created - 2000-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Eukaryote-specific domains in translation initiation factors: implications for translation regulation and evolution of the translation system. AN - 72213032; 10958635 AB - Computational analysis of sequences of proteins involved in translation initiation in eukaryotes reveals a number of specific domains that are not represented in bacteria or archaea. Most of these eukaryote-specific domains are known or predicted to possess an alpha-helical structure, which suggests that such domains are easier to invent in the course of evolution than are domains of other structural classes. A previously undetected, conserved region predicted to form an alpha-helical domain is delineated in the initiation factor eIF4G, in Nonsense-mediated mRNA decay 2 protein (NMD2/UPF2), in the nuclear cap-binding CBP80, and in other, poorly characterized proteins, which is named the NIC (NMD2, eIF4G, CBP80) domain. Biochemical and mutagenesis data on NIC-containing proteins indicate that this predicted domain is one of the central adapters in the regulation of mRNA processing, translation, and degradation. It is demonstrated that, in the course of eukaryotic evolution, initiation factor eIF4G, of which NIC is the core, conserved portion, has accreted several additional, distinct predicted domains such as MI (MA-3 and eIF4G ) and W2, which probably was accompanied by acquisition of new regulatory interactions. JF - Genome research AU - Aravind, L AU - Koonin, E V AD - National Center for Biotechnology Information, National Library of Medicine, National Institute of Health, Bethesda, MD 20894, USA. aravind@ncbi.nlm.nih.gov Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 1172 EP - 1184 VL - 10 IS - 8 SN - 1088-9051, 1088-9051 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Fungal Proteins KW - NMD2 protein, S cerevisiae KW - Peptide Initiation Factors KW - Saccharomyces cerevisiae Proteins KW - Trans-Activators KW - eIF-4gamma KW - Index Medicus KW - Space life sciences KW - Phylogeny KW - Animals KW - Humans KW - Trans-Activators -- chemistry KW - Amino Acid Sequence KW - Fungal Proteins -- genetics KW - Fungal Proteins -- chemistry KW - Conserved Sequence KW - Trans-Activators -- genetics KW - Databases, Factual KW - Molecular Sequence Data KW - Protein Structure, Tertiary KW - Protein Biosynthesis KW - Eukaryotic Cells -- chemistry KW - Peptide Initiation Factors -- genetics KW - Peptide Initiation Factors -- chemistry KW - Eukaryotic Cells -- physiology KW - Evolution, Molecular UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72213032?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genome+research&rft.atitle=Eukaryote-specific+domains+in+translation+initiation+factors%3A+implications+for+translation+regulation+and+evolution+of+the+translation+system.&rft.au=Aravind%2C+L%3BKoonin%2C+E+V&rft.aulast=Aravind&rft.aufirst=L&rft.date=2000-08-01&rft.volume=10&rft.issue=8&rft.spage=1172&rft.isbn=&rft.btitle=&rft.title=Genome+research&rft.issn=10889051&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-17 N1 - Date created - 2000-10-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1999 Mar;19(3):2389-99 [10022925] Nature. 1998 Apr 2;392(6675):520-3 [9548260] J Mol Evol. 1999 Mar;48(3):291-302 [10093218] J Biol Chem. 1999 Apr 9;274(15):10603-8 [10187856] Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4342-7 [10200264] Trends Genet. 1999 Mar;15(3):98-103 [10203806] Trends Biochem Sci. 1999 Mar;24(3):85-7 [10203752] J Mol Biol. 1999 Apr 16;287(5):1023-40 [10222208] Biochem Cell Biol. 1999;77(4):277-91 [10546891] Trends Biochem Sci. 1999 Oct;24(10):398-403 [10500305] Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):14037-42 [10570194] Mol Cell Biol. 2000 Jan;20(2):468-77 [10611225] Mol Cell Biol. 2000 Jan;20(2):496-506 [10611228] Nature. 2000 Jan 20;403(6767):332-5 [10659855] Mol Cell. 2000 Jan;5(1):109-19 [10678173] Curr Opin Struct Biol. 2000 Feb;10(1):78-86 [10679461] Biochimie. 1991 Dec;73(12):1557-66 [1805969] Nucleic Acids Res. 1998 May 15;26(10):2433-41 [9580697] Protein Sci. 1998 May;7(5):1250-4 [9605331] Gene. 1998 May 12;211(2):187-94 [9602122] Science. 1998 Jun 12;280(5370):1757-60 [9624054] Trends Biochem Sci. 1998 Jun;23(6):204-5 [9644972] J Biol Chem. 1998 Jul 17;273(29):18573-85 [9660829] Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10419-24 [9724718] Nature. 1998 Aug 27;394(6696):854-9 [9732867] Structure. 1998 Sep 15;6(9):1207-14 [9753699] J Biol Chem. 1999 Jan 1;274(1):249-56 [9867837] J Mol Biol. 1999 Jun 18;289(4):729-45 [10369758] Mol Cell. 1999 Jun;3(6):707-16 [10394359] Mol Cell Biol. 1999 Aug;19(8):5557-64 [10409745] Genome Res. 1999 Jul;9(7):608-28 [10413400] RNA. 1999 Aug;5(8):1055-70 [10445880] Genome Res. 1999 Aug;9(8):689-710 [10447505] EMBO J. 1999 Sep 1;18(17):4865-74 [10469664] J Biol Chem. 1999 Sep 17;274(38):26720-6 [10480875] Mol Cell Biol. 1999 Oct;19(10):6543-53 [10490594] J Mol Biol. 1999 Sep 17;292(2):195-202 [10493868] Mol Cell Biol. 1993 Aug;13(8):4860-74 [8336723] J Mol Biol. 1993 Jul 20;232(2):584-99 [8345525] Cell. 1994 Aug 26;78(4):657-68 [8069914] Nucleic Acids Res. 1994 Nov 11;22(22):4673-80 [7984417] Genes Dev. 1995 Feb 15;9(4):423-36 [7883167] J Biol Chem. 1995 Sep 15;270(37):21975-83 [7665619] Protein Sci. 1995 Aug;4(8):1608-17 [8520487] Gene. 1995 Dec 12;166(2):297-301 [8543179] Methods Enzymol. 1996;266:554-71 [8743706] Biochimie. 1996;78(7):577-89 [8955901] Genes Dev. 1997 Feb 1;11(3):321-33 [9030685] Mol Cell Biol. 1997 Mar;17(3):1580-94 [9032286] Mol Cell Biol. 1997 Mar;17(3):1615-25 [9032289] EMBO J. 1997 Feb 17;16(4):817-25 [9049310] EMBO J. 1997 Mar 17;16(6):1436-43 [9135158] Genetics. 1997 May;146(1):227-38 [9136012] Biochimie. 1997;79(1):7-11 [9195040] Cell. 1997 Jun 13;89(6):951-61 [9200613] Dev Genet. 1997;20(4):307-19 [9254905] Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 [9254694] Nat Struct Biol. 1997 Sep;4(9):717-24 [9302999] Mol Cell Biol. 1997 Dec;17(12):6940-7 [9372926] EMBO J. 1999 Mar 15;18(6):1673-88 [10075937] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reevaluation of ascorbate in cancer treatment: emerging evidence, open minds and serendipity. AN - 72212584; 10963459 AB - Some clinicians and alternative therapy practitioners advocate megadose intravenous and oral ascorbate treatment of cancer. Randomized control studies using oral ascorbate showed no benefit. Recent data show that intravenous but not oral administration of ascorbate can produce millimolar plasma concentrations, which are toxic to many cancer cell lines. We propose that ascorbate treatment of cancer should be reexamined by rigorous scientific scrutiny in the light of new evidence. JF - Journal of the American College of Nutrition AU - Padayatty, S J AU - Levine, M AD - Molecular and Clinical Nutrition Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 423 EP - 425 VL - 19 IS - 4 SN - 0731-5724, 0731-5724 KW - Antioxidants KW - 0 KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Index Medicus KW - Administration, Oral KW - Injections, Intravenous KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Neoplasms -- drug therapy KW - Ascorbic Acid -- administration & dosage KW - Antioxidants -- pharmacology KW - Ascorbic Acid -- blood KW - Ascorbic Acid -- pharmacology KW - Antioxidants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72212584?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+College+of+Nutrition&rft.atitle=Reevaluation+of+ascorbate+in+cancer+treatment%3A+emerging+evidence%2C+open+minds+and+serendipity.&rft.au=Padayatty%2C+S+J%3BLevine%2C+M&rft.aulast=Padayatty&rft.aufirst=S&rft.date=2000-08-01&rft.volume=19&rft.issue=4&rft.spage=423&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+College+of+Nutrition&rft.issn=07315724&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-11 N1 - Date created - 2000-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevention of carcinogen-induced mouse skin papilloma by whole fruit aqueous extract of Momordica charantia. AN - 72202718; 10958332 AB - The anticarcinogenic effect of aqueous extract of fruit of Momordica charantia (bitter gourd), which is widely used as a vegetable in India, was studied in a two-step skin carcinogenesis model in mice. The possible mode of action was also investigated. Oral administration of the fruit extract was found to have an adverse effect on the general health and lifespan of the animals when used at a high concentration. But when this dose was reduced by half, the test extract afforded protection from the development of skin tumour and increased life expectancy. Carcinogen-induced lipid peroxidation in liver and DNA damage in lymphocytes were found to be reduced following treatment with Momordica. The fruit extract was found to significantly activate the liver enzymes glutathione-S-transferase, glutathione peroxidase and catalase (P < 0.001), which showed a depression following exposure to the carcinogen. The results suggest a preventive role of water-soluble constituents of M. charantia fruit during carcinogenesis, which is mediated possibly by their modulatory effect on enzymes of the biotransformation and detoxification system of the host. JF - European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) AU - Ganguly, C AU - De, S AU - Das, S AD - Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 283 EP - 288 VL - 9 IS - 4 SN - 0959-8278, 0959-8278 KW - Anticarcinogenic Agents KW - 0 KW - Carcinogens KW - Plant Extracts KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Croton Oil KW - 8001-28-3 KW - Index Medicus KW - Animals KW - Cocarcinogenesis KW - DNA Damage KW - Liver -- metabolism KW - Mice KW - Lymphocytes -- drug effects KW - Lipid Peroxidation KW - Female KW - India KW - Plant Extracts -- pharmacology KW - Papilloma -- prevention & control KW - Skin Neoplasms -- chemically induced KW - Anticarcinogenic Agents -- pharmacology KW - Fruit KW - Skin Neoplasms -- prevention & control KW - Papilloma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72202718?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+cancer+prevention+%3A+the+official+journal+of+the+European+Cancer+Prevention+Organisation+%28ECP%29&rft.atitle=Prevention+of+carcinogen-induced+mouse+skin+papilloma+by+whole+fruit+aqueous+extract+of+Momordica+charantia.&rft.au=Ganguly%2C+C%3BDe%2C+S%3BDas%2C+S&rft.aulast=Ganguly&rft.aufirst=C&rft.date=2000-08-01&rft.volume=9&rft.issue=4&rft.spage=283&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+prevention+%3A+the+official+journal+of+the+European+Cancer+Prevention+Organisation+%28ECP%29&rft.issn=09598278&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-25 N1 - Date created - 2000-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I-II study of isolated hepatic perfusion using melphalan with or without tumor necrosis factor for patients with ocular melanoma metastatic to liver. AN - 72199501; 10955785 AB - There are no satisfactory treatment options for patients with ocular melanoma metastatic to liver, and after liver metastases are identified, median survival is only between 2 and 7 months. Because liver metastases are the sole or life-limiting component of disease in the vast majority of patients who recur, we reasoned that complete vascular isolation and perfusion of the liver might result in clinically meaningful regression of disease. Between September 1994 and July 1999, 22 patients (13 women and 9 men; mean age, 49 years) with ocular melanoma metastatic to liver were treated with a 60-min hyperthermic isolated hepatic perfusion (IHP) using melphalan alone (1.5-2.5 mg/kg, n = 11) or with tumor necrosis factor (TNF, 1.0 mg, n = 11). Via a laparotomy, IHP inflow was via the hepatic artery alone (n = 17) or hepatic artery and portal vein (n = 5) and outflow from an isolated segment of inferior vena cava. Most patients had advanced tumor burden with a mean percentage of hepatic replacement of 25% (range, 10-75%) and a median number of metastatic nodules of 25 (range, 5 to >50). Complete vascular isolation was confirmed in all patients using a continuous intraoperative leak monitoring technique with 131I radiolabeled albumin. There was one treatment mortality (5%). The overall response rate in 21 patients was 62% including 2 radiographic complete responses (9.5%) and 11 partial responses (52%). The overall median duration of response was 9 months (range, 5-50) and was significantly longer in those treated with TNF than without (14 versus 6 months, respectively; P = 0.04). Overall median survival in 22 patients was 11 months. These data indicate that a single 60-min IHP can result in significant regression of advanced hepatic metastases from ocular melanoma. TNF appears to significantly prolong the duration of response. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Alexander, H R AU - Libutti, S K AU - Bartlett, D L AU - Puhlmann, M AU - Fraker, D L AU - Bachenheimer, L C AD - Surgical Metabolism Section, Surgery Branch, Division of Clinical Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 3062 EP - 3070 VL - 6 IS - 8 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Tumor Necrosis Factor-alpha KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Disease-Free Survival KW - Infusions, Intra-Arterial KW - Hepatic Artery KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Infusions, Intravenous KW - Chemotherapy, Cancer, Regional Perfusion KW - Humans KW - Aged KW - Portal Vein KW - Tumor Necrosis Factor-alpha -- adverse effects KW - Adult KW - Middle Aged KW - Female KW - Male KW - Melphalan -- administration & dosage KW - Melanoma -- secondary KW - Liver Neoplasms -- drug therapy KW - Melphalan -- adverse effects KW - Melanoma -- drug therapy KW - Eye Neoplasms -- drug therapy KW - Antineoplastic Agents, Alkylating -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Antineoplastic Agents, Alkylating -- administration & dosage KW - Eye Neoplasms -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Liver Neoplasms -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72199501?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=A+phase+I-II+study+of+isolated+hepatic+perfusion+using+melphalan+with+or+without+tumor+necrosis+factor+for+patients+with+ocular+melanoma+metastatic+to+liver.&rft.au=Alexander%2C+H+R%3BLibutti%2C+S+K%3BBartlett%2C+D+L%3BPuhlmann%2C+M%3BFraker%2C+D+L%3BBachenheimer%2C+L+C&rft.aulast=Alexander&rft.aufirst=H&rft.date=2000-08-01&rft.volume=6&rft.issue=8&rft.spage=3062&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 - 2000-12-28 N1 - Date created - 2000-11-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of growth hormone and prolactin on hematopoiesis. AN - 71761178; 10953965 AB - The use of the neuroendocrine hormones growth hormone (GH) and prolactin (PRL) in preclinical models, demonstrating promotion of hematopoietic recovery and immune function, offers promise for several clinical situations. These hormones do not appear to produce the same extent of immune/hematopoietic effects when compared to conventional hematopoietic and immune stimulating cytokines (i.e. G-CSF or interleukin-2). However, their pleiotropic effects and limited toxicity after systemic administration makes them attractive to test in myeloablative situations. More work needs to be performed to understand the mechanism(s) of GH and PRL action, particularly with regard to hematopoietic progenitor cell expansion and differentiation both in normal and pathologic situations. JF - Leukemia & lymphoma AU - Welniak, L A AU - Tian, Z G AU - Sun, R AU - Keller, J R AU - Richards, S AU - Ruscetti, F W AU - Murphy, W J AD - Laboratory of Leukocyte Biology, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 435 EP - 445 VL - 38 IS - 5-6 SN - 1042-8194, 1042-8194 KW - Prolactin KW - 9002-62-4 KW - Growth Hormone KW - 9002-72-6 KW - Index Medicus KW - Animals KW - Humans KW - Signal Transduction KW - Hematopoiesis -- physiology KW - Prolactin -- physiology KW - Hematopoiesis -- drug effects KW - Growth Hormone -- physiology KW - Prolactin -- pharmacology KW - Growth Hormone -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71761178?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+growth+hormone+and+prolactin+on+hematopoiesis.&rft.au=Welniak%2C+L+A%3BTian%2C+Z+G%3BSun%2C+R%3BKeller%2C+J+R%3BRichards%2C+S%3BRuscetti%2C+F+W%3BMurphy%2C+W+J&rft.aulast=Welniak&rft.aufirst=L&rft.date=2000-08-01&rft.volume=38&rft.issue=5-6&rft.spage=435&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 - 2001-01-26 N1 - Date created - 2001-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Therapeutic studies. AN - 71758819; 10949777 AB - This article discusses the problems in basic design, conduct, and interpretation associated with phases I, II, and III of the cancer clinical trials and explains the various statistical solutions to these problems. The fundamental problem common to all three trials is achieving a correct and precise answer to the question posed to inform future testing and treatment while protecting trial patients from receiving treatment that has demonstrated excessive toxicity or lack of clinical efficacy. This shared problem gives rise to statistical designs with basic similarities across the three trial types. JF - Hematology/oncology clinics of North America AU - Rubinstein, L V AD - Biometric Research Branch, National Cancer Institute, Bethesda, Maryland, USA. rubinsteinl@ctep.nci.nih.gov Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 849 EP - 76, ix VL - 14 IS - 4 SN - 0889-8588, 0889-8588 KW - Antineoplastic Agents KW - 0 KW - Biomarkers KW - Index Medicus KW - United States KW - Clinical Trials, Phase I as Topic -- methods KW - Information Services KW - Antineoplastic Agents -- administration & dosage KW - Area Under Curve KW - Controlled Clinical Trials as Topic -- methods KW - Endpoint Determination KW - Random Allocation KW - Dose-Response Relationship, Drug KW - Humans KW - Stochastic Processes KW - Bayes Theorem KW - Research Design KW - Clinical Trials, Phase II as Topic -- methods KW - Antineoplastic Agents -- adverse effects KW - Prospective Studies KW - Logistic Models KW - Treatment Outcome KW - Multicenter Studies as Topic -- statistics & numerical data KW - Guidelines as Topic KW - Forecasting KW - Antineoplastic Agents -- therapeutic use KW - Randomized Controlled Trials as Topic -- methods KW - Neoplasms -- drug therapy KW - Clinical Trials as Topic -- standards KW - Neoplasms -- therapy KW - Clinical Trials as Topic -- methods KW - Clinical Trials as Topic -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71758819?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Therapeutic+studies.&rft.au=Rubinstein%2C+L+V&rft.aulast=Rubinstein&rft.aufirst=L&rft.date=2000-08-01&rft.volume=14&rft.issue=4&rft.spage=849&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 - 2001-01-18 N1 - Date created - 2000-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intermediate markers as surrogate endpoints in cancer research. AN - 71758514; 10949779 AB - Because studies with surrogate cancer endpoints can be smaller, faster, and substantially less expensive than those with frank cancer outcomes, the use of surrogate endpoints is undeniably attractive. This attractiveness is likely to grow in coming years as the rapidly advancing discoveries in cell and molecular biology generate new therapies requiring testing and new markers that could plausibly serve as surrogates for cancer. Surrogate endpoint studies can certainly be suggestive. They continue to play a legitimate role in phase II studies, and they may give the right answers about intervention effects on or exposure associations with cancer. The problem is the uncertainty attached to most potential surrogates. Except for those few surrogates that are both necessary for and developmentally relatively close to cancer, the existence of plausible alternative pathways makes inferences about cancer from many surrogates problematic. Merely being on the causal pathway to cancer does not in itself constitute surrogate validity. It is the totality of causal connections that is critical. There is, unfortunately, a fairly extensive history of quite plausible surrogate markers giving the wrong answer about various chronic disease therapies. There is no reason to believe that cancer surrogacy is immune to such inferential difficulties. This article is, in part, an invitation, even a plea, for researchers to carry out the investigations necessary to evaluate potential surrogates, particularly surrogate-cancer studies and intervention or exposure-surrogate-cancer mediation analyses. Such studies are needed to generalize from surrogate endpoint findings to cancer. There is, however, an implicit and perhaps unavoidable irony here: the large, long, expensive studies required to evaluate potential surrogates fully are precisely the studies that surrogates were designed to replace. The exposure dependence alluded to earlier complicates matters further: establishing validity for a given surrogate for one intervention or exposure vis-à-vis cancer does not necessarily translate into validity for another intervention or exposure. One can enhance the inferential strength of surrogacy by using further "downstream" markers. Results of trials with CIN3 as an endpoint are arguably more persuasive than those from intervention studies with HPV infection endpoints. Similarly, one could consider only the advanced adenoma (> or = 1 cm, villous elements, or high-grade dysplasia) as the primary endpoint in adenoma recurrence trials. The inferential gain, however, comes with substantial costs: studies with CIN3 endpoints must be much larger than those with HPV infection endpoints; adenoma recurrence trials with sufficient rates of recurrence of advanced adenomas must be five or six times larger than trials with any recurrent adenomas as endpoints. A law emerges here: in using surrogate endpoints, inferential certainty is directly associated with study cost. In other words, one gets what one pays for. The problems inherent in using surrogate endpoints need not be regarded as a cause for pessimism in cancer research. If anything, the limitations of surrogacy are reminders of the complexity of cancer causation and affirm the continued importance of large clinical trials and observational epidemiologic studies with explicit cancer endpoints. JF - Hematology/oncology clinics of North America AU - Schatzkin, A AD - Nutritional Epidemiology Branch, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 887 EP - 905 VL - 14 IS - 4 SN - 0889-8588, 0889-8588 KW - Biomarkers KW - 0 KW - Index Medicus KW - Uterine Cervical Neoplasms -- etiology KW - Causality KW - Reproducibility of Results KW - Humans KW - Colonic Polyps -- epidemiology KW - Disease Progression KW - Risk KW - Adenocarcinoma -- epidemiology KW - Colonic Neoplasms -- epidemiology KW - Uterine Cervical Neoplasms -- epidemiology KW - Colonic Neoplasms -- etiology KW - Adenocarcinoma -- etiology KW - Adenoma -- epidemiology KW - Environmental Exposure KW - Incidence KW - Adenocarcinoma -- prevention & control KW - Colonic Neoplasms -- prevention & control KW - Male KW - Female KW - Models, Theoretical KW - Cell Division KW - Neoplasms -- epidemiology KW - Clinical Trials as Topic -- standards KW - Neoplasms -- prevention & control KW - Neoplasms -- etiology KW - Clinical Trials as Topic -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71758514?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Intermediate+markers+as+surrogate+endpoints+in+cancer+research.&rft.au=Schatzkin%2C+A&rft.aulast=Schatzkin&rft.aufirst=A&rft.date=2000-08-01&rft.volume=14&rft.issue=4&rft.spage=887&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 - 2001-01-18 N1 - Date created - 2000-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of the E1B 55 kDa gene product in oncolytic adenoviral vectors expressing herpes simplex virus-tk: assessment of antitumor efficacy and toxicity. AN - 71748748; 10945625 AB - In this study, we evaluated three herpes simplex virus-1 thymidine kinase (HSV-tk) carrying replication-competent adenoviral vectors with and without the Ad5 E1B 55 kDa gene to assess whether this gene product has an influence on their antitumor efficacy, replication kinetics, and potential hepatotoxicity. Furthermore, we assessed the efficacy of these vectors in combination with ganciclovir (GCV). When compared with wild-type adenovirus, the recombinant vectors, in particular the E1B 55 kDa-deleted vector Ad.TK(RC)(II), generated a more efficiently cytopathic effect in proliferating cells, independently of their p53 phenotype. In a s.c. A549 lung cancer xenograft model, the cytoreductive effect of Ad.TK(RC)(II) was enhanced when followed by GCV treatment. In contrast, the efficacy of both E1B 55 kDa-positive vectors could not be further improved by GCV. In an i.p. MDAH 2774 ovarian cancer xenograft tumor model, the survival of animals treated with a prototypical replication-deficient adenovirus expressing HSV-tk (Ad.TK) was improved compared to controls when followed by GCV. In contrast, the cytoreductive efficacy of the replication-competent vectors was diminished when combined with the virostatic GCV. However, the antitumor effect of all replication-competent vectors was superior to combination chemotherapy with paclitaxel and carboplatin. In both tumor models, the oncolytic effect of the E1B 55 kDa-positive vectors was greater than that of Ad.TK(RC)(II). In an attempt to assess the toxicity of these vectors in a nonpermissive host, the viruses were administered systemically to immunocompetent and immunodeficient mice. Greater hepatotoxicity was seen with i.v. administration of the replication-competent viruses than with Ad.TK and in immunocompetent hosts, suggesting involvement of the immune system in the induction of tissue damage. The E1B 55 kDa gene had no significant influence on the liver toxicity of the vectors in this system. At therapeutic doses, intratumoral or i.p. injection of all vectors was well tolerated. Importantly, these replication-competent HSV-tk-expressing vectors were highly susceptible to GCV, representing an effective fail-safe mechanism to abolish viral replication in a clinical setting. Controllable intratumoral viral replication holds promise as a new treatment modality for cancer. JF - Cancer research AU - Wildner, O AU - Morris, J C AD - Clinical Gene Therapy Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA. wildner@rrk-berlin.de Y1 - 2000/08/01/ PY - 2000 DA - 2000 Aug 01 SP - 4167 EP - 4174 VL - 60 IS - 15 SN - 0008-5472, 0008-5472 KW - Adenovirus E1B Proteins KW - 0 KW - Antiviral Agents KW - Prodrugs KW - Thymidine Kinase KW - EC 2.7.1.21 KW - Ganciclovir KW - P9G3CKZ4P5 KW - Index Medicus KW - Animals KW - HeLa Cells -- virology KW - Ganciclovir -- pharmacokinetics KW - Humans KW - Lung Neoplasms -- therapy KW - Prodrugs -- pharmacokinetics KW - Mice, Nude KW - Mice KW - Virus Replication -- physiology KW - Mice, Inbred BALB C KW - Ovarian Neoplasms -- therapy KW - Neoplasm Transplantation KW - Antiviral Agents -- pharmacokinetics KW - Virus Replication -- drug effects KW - Prodrugs -- pharmacology KW - Antiviral Agents -- pharmacology KW - Liver Diseases -- pathology KW - Mice, Inbred C57BL KW - Genetic Therapy -- methods KW - Liver Diseases -- virology KW - Female KW - Ganciclovir -- pharmacology KW - Herpes Simplex -- genetics KW - Adenovirus E1B Proteins -- biosynthesis KW - Adenoviruses, Human -- genetics KW - Thymidine Kinase -- metabolism KW - Thymidine Kinase -- therapeutic use KW - Adenovirus E1B Proteins -- physiology KW - Genetic Vectors -- toxicity KW - Genetic Vectors -- pharmacology KW - Adenovirus E1B Proteins -- genetics KW - Herpes Simplex -- enzymology KW - Adenoviruses, Human -- physiology KW - Genetic Vectors -- genetics KW - Adenoviruses, Human -- enzymology KW - Thymidine Kinase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71748748?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=The+role+of+the+E1B+55+kDa+gene+product+in+oncolytic+adenoviral+vectors+expressing+herpes+simplex+virus-tk%3A+assessment+of+antitumor+efficacy+and+toxicity.&rft.au=Wildner%2C+O%3BMorris%2C+J+C&rft.aulast=Wildner&rft.aufirst=O&rft.date=2000-08-01&rft.volume=60&rft.issue=15&rft.spage=4167&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 - 2000-08-31 N1 - Date created - 2000-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Constitutive achaete-scute homologue-1 promotes airway dysplasia and lung neuroendocrine tumors in transgenic mice. AN - 71747767; 10945598 AB - The transcription factor achaete-scute homologue-1 (ASH1) is essential for neural differentiation during fetal development and is a cardinal feature of neuroendocrine (NE) tumors such as small cell lung cancer. To explore the potential of ASH1 to promote NE differentiation and tumorigenesis in the lung, we constitutively expressed the factor in nonendocrine airway epithelial cells using transgenic mice. Progressive airway hyperplasia and metaplasia developed beginning at 3 weeks of life. ASH1 potently enhanced the tumorigenic effect of SV40 large T antigen in airway epithelium. These doubly transgenic animals developed massive NE lung tumors, implying that ASH1 may cooperate with defects in p53, pRb, or related pathways in promoting NE lung carcinogenesis. JF - Cancer research AU - Linnoila, R I AU - Zhao, B AU - DeMayo, J L AU - Nelkin, B D AU - Baylin, S B AU - DeMayo, F J AU - Ball, D W AD - Cell and Cancer Biology Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, NIH, Rockville, Maryland 20817, USA. Y1 - 2000/08/01/ PY - 2000 DA - 2000 Aug 01 SP - 4005 EP - 4009 VL - 60 IS - 15 SN - 0008-5472, 0008-5472 KW - ASCL1 protein, human KW - 0 KW - Antigens, Polyomavirus Transforming KW - Ascl1 protein, mouse KW - Basic Helix-Loop-Helix Transcription Factors KW - DNA-Binding Proteins KW - Retinoblastoma Protein KW - Transcription Factors KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Animals KW - Antigens, Polyomavirus Transforming -- toxicity KW - Tumor Suppressor Protein p53 -- physiology KW - Mice, Inbred ICR KW - Cocarcinogenesis KW - Humans KW - Cell Division -- physiology KW - Retinoblastoma Protein -- physiology KW - Rabbits KW - Mice KW - Metaplasia -- genetics KW - Lung -- pathology KW - Mice, Transgenic KW - Metaplasia -- etiology KW - Antigens, Polyomavirus Transforming -- genetics KW - Bronchi -- pathology KW - Cell Differentiation -- physiology KW - Hyperplasia -- genetics KW - Epithelial Cells -- pathology KW - Hyperplasia -- etiology KW - Neurosecretory Systems -- cytology KW - Neurosecretory Systems -- physiology KW - Female KW - Neuroendocrine Tumors -- pathology KW - Carcinoma, Non-Small-Cell Lung -- genetics KW - Transcription Factors -- toxicity KW - DNA-Binding Proteins -- genetics KW - Transcription Factors -- genetics KW - Carcinoma, Non-Small-Cell Lung -- etiology KW - Carcinoma, Non-Small-Cell Lung -- pathology KW - Lung Neoplasms -- etiology KW - Neuroendocrine Tumors -- genetics KW - Lung Neoplasms -- genetics KW - DNA-Binding Proteins -- toxicity KW - Neuroendocrine Tumors -- etiology KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71747767?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Constitutive+achaete-scute+homologue-1+promotes+airway+dysplasia+and+lung+neuroendocrine+tumors+in+transgenic+mice.&rft.au=Linnoila%2C+R+I%3BZhao%2C+B%3BDeMayo%2C+J+L%3BNelkin%2C+B+D%3BBaylin%2C+S+B%3BDeMayo%2C+F+J%3BBall%2C+D+W&rft.aulast=Linnoila&rft.aufirst=R&rft.date=2000-08-01&rft.volume=60&rft.issue=15&rft.spage=4005&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 - 2000-08-31 N1 - Date created - 2000-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human papillomavirus type 16 E6 and E7 proteins inhibit differentiation-dependent expression of transforming growth factor-beta2 in cervical keratinocytes. AN - 71745836; 10945644 AB - Infection with high-risk human papillomaviruses (HPVs) represents a major risk factor for the development of cervical cancer. The HPV-16 E6 and E7 proteins are highly expressed in differentiating keratinocytes, where they inactivate the p53 and retinoblastoma (pRb) proteins, two important transcriptional regulators. We have used cDNA expression arrays to identify global alterations in gene expression induced by E6 and E7 in differentiating cultures of human cervical keratinocytes. We show that E6 and E7 decrease expression of TGF-beta2 mRNA and alter expression of multiple TGF-beta-responsive genes involved in cell cycle regulation, apoptosis, and tissue remodeling. E6 and E7 inhibited expression of TGF-beta2 RNA 7-fold (relative effectiveness, E6/ E7 > E6 > E7 > control) and decreased secretion of biologically active TGF-beta2 by 70-80% (reduced from 70 to 10 pg/10(6) cells/24 h). Downregulation occurred through p53- and pRb-dependent pathways. In contrast, E6 and E7 did not alter expression of TGF-beta1 and TGF-beta3. Down-regulation of TGF-beta2 was biologically relevant because the addition of recombinant cytokine (10-200 pg/ml) to E6/E7-expressing cells restored expression of TGF-P-responsive genes, inhibited growth of keratinocytes, and decreased immortalization by E6 and E7. These results suggest that TGF-32- and TGF-3-responsive genes are important targets for the HPV-16 E6 and E7 oncoproteins in differentiating cervical keratinocytes. JF - Cancer research AU - Nees, M AU - Geoghegan, J M AU - Munson, P AU - Prabhu, V AU - Liu, Y AU - Androphy, E AU - Woodworth, C D AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 2000/08/01/ PY - 2000 DA - 2000 Aug 01 SP - 4289 EP - 4298 VL - 60 IS - 15 SN - 0008-5472, 0008-5472 KW - E6 protein, Human papillomavirus type 16 KW - 0 KW - Oncogene Proteins, Viral KW - Papillomavirus E7 Proteins KW - Repressor Proteins KW - Transforming Growth Factor beta KW - Tumor Suppressor Protein p53 KW - oncogene protein E7, Human papillomavirus type 16 KW - Index Medicus KW - Blotting, Northern KW - Gene Silencing KW - Humans KW - Cell Division -- physiology KW - Reverse Transcriptase Polymerase Chain Reaction KW - Tumor Suppressor Protein p53 -- metabolism KW - Down-Regulation -- physiology KW - Cell Differentiation -- physiology KW - Genes, p53 KW - Cells, Cultured KW - Genes, Retinoblastoma KW - Tumor Suppressor Protein p53 -- genetics KW - Retroviridae -- genetics KW - Cell Transformation, Viral KW - Female KW - Transforming Growth Factor beta -- biosynthesis KW - Cervix Uteri -- metabolism KW - Transforming Growth Factor beta -- secretion KW - Oncogene Proteins, Viral -- genetics KW - Keratinocytes -- cytology KW - Cervix Uteri -- virology KW - Cervix Uteri -- cytology KW - Papillomaviridae -- genetics KW - Oncogene Proteins, Viral -- physiology KW - Keratinocytes -- virology KW - Keratinocytes -- metabolism KW - Oncogene Proteins, Viral -- metabolism KW - Transforming Growth Factor beta -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71745836?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Human+papillomavirus+type+16+E6+and+E7+proteins+inhibit+differentiation-dependent+expression+of+transforming+growth+factor-beta2+in+cervical+keratinocytes.&rft.au=Nees%2C+M%3BGeoghegan%2C+J+M%3BMunson%2C+P%3BPrabhu%2C+V%3BLiu%2C+Y%3BAndrophy%2C+E%3BWoodworth%2C+C+D&rft.aulast=Nees&rft.aufirst=M&rft.date=2000-08-01&rft.volume=60&rft.issue=15&rft.spage=4289&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 - 2000-08-31 N1 - Date created - 2000-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of the Ebola virus glycoprotein as the main viral determinant of vascular cell cytotoxicity and injury. AN - 71737793; 10932225 AB - Here we defined the main viral determinant of Ebola virus pathogenicity; synthesis of the virion glycoprotein (GP) of Ebola virus Zaire induced cytotoxic effects in human endothelial cells in vitro and in vivo. This effect mapped to a serine-threonine-rich, mucin-like domain of this type I transmembrane glycoprotein, one of seven gene products of the virus. Gene transfer of GP into explanted human or porcine blood vessels caused massive endothelial cell loss within 48 hours that led to a substantial increase in vascular permeability. Deletion of the mucin-like region of GP abolished these effects without affecting protein expression or function. GP derived from the Reston strain of virus, which causes disease in nonhuman primates but not in man, did not disrupt the vasculature of human blood vessels. In contrast, the Zaire GP induced endothelial cell disruption and cytotoxicity in both nonhuman primate and human blood vessels, and the mucin domain was required for this effect. These findings indicate that GP, through its mucin domain, is the viral determinant of Ebola pathogenicity and likely contributes to hemorrhage during infection. JF - Nature medicine AU - Yang, Z Y AU - Duckers, H J AU - Sullivan, N J AU - Sanchez, A AU - Nabel, E G AU - Nabel, G J AD - Vaccine Research Center, National Institutes of Health, 40 Convent Drive, Bethesda, Maryland 20892-3005, USA. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 886 EP - 889 VL - 6 IS - 8 SN - 1078-8956, 1078-8956 KW - Glycoproteins KW - 0 KW - Viral Envelope Proteins KW - Index Medicus KW - Animals KW - Endothelium, Vascular -- drug effects KW - Virulence -- physiology KW - Transfection KW - Virulence -- genetics KW - Humans KW - Cell Line KW - Endothelium, Vascular -- injuries KW - Glycoproteins -- toxicity KW - Viral Envelope Proteins -- physiology KW - Hemorrhagic Fever, Ebola -- pathology KW - Ebolavirus -- genetics KW - Ebolavirus -- pathogenicity KW - Viral Envelope Proteins -- toxicity KW - Hemorrhagic Fever, Ebola -- etiology KW - Ebolavirus -- physiology KW - Glycoproteins -- genetics KW - Hemorrhagic Fever, Ebola -- virology KW - Viral Envelope Proteins -- genetics KW - Glycoproteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71737793?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+medicine&rft.atitle=Identification+of+the+Ebola+virus+glycoprotein+as+the+main+viral+determinant+of+vascular+cell+cytotoxicity+and+injury.&rft.au=Yang%2C+Z+Y%3BDuckers%2C+H+J%3BSullivan%2C+N+J%3BSanchez%2C+A%3BNabel%2C+E+G%3BNabel%2C+G+J&rft.aulast=Yang&rft.aufirst=Z&rft.date=2000-08-01&rft.volume=6&rft.issue=8&rft.spage=886&rft.isbn=&rft.btitle=&rft.title=Nature+medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-28 N1 - Date created - 2000-08-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human homologue of maid: A dominant inhibitory helix-loop-helix protein associated with liver-specific gene expression. AN - 71279742; 10915743 AB - The helix-loop-helix (HLH) family of transcriptional regulatory proteins are key regulators in numerous developmental processes. The class I HLH proteins, such as E12 are ubiquitously expressed. Class II HLH proteins, such as MyoD, are expressed in a tissue-specific manner. Class I and II heterodimers can bind to E-boxes (CANNTG) and regulate lineage commitments of embryonic cells. In an attempt to identify partners for the E12 protein that may exert control during liver development, we performed the yeast 2-hybrid screen using an expression complementary DNA library from human fetal liver. A novel dominant inhibitory HLH factor, designated HHM (human homologue of maid), was isolated and characterized. HHM is structurally related to the Id family and was highly expressed in brain, pituitary gland, lung, heart, placenta, fetal liver, and bone marrow. HHM physically interacted with E12 in vitro and in mammalian cells. Comparison of the dominant inhibitory effects of HHM and Id2 on the binding of E12/MyoD dimer to an E-box element revealed a weaker inhibition by HHM. However, HHM but not Id2 specifically inhibited the luciferase gene activation induced by hepatic nuclear factor 4 (HNF4) promoter. The HHM was transiently expressed during stem-cell-driven regeneration of the liver at the stage in which the early basophilic foci of hepatocytes started to appear. These results suggest that HHM is a novel type of dominant inhibitory HLH protein that might modulate liver-specific gene expression. JF - Hepatology (Baltimore, Md.) AU - Terai, S AU - Aoki, H AU - Ashida, K AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 357 EP - 366 VL - 32 IS - 2 SN - 0270-9139, 0270-9139 KW - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors KW - 0 KW - CCNDBP1 protein, human KW - DNA-Binding Proteins KW - Hepatocyte Nuclear Factor 4 KW - MLX protein, human KW - MyoD Protein KW - Phosphoproteins KW - RNA, Messenger KW - TCF Transcription Factors KW - TCF7L1 protein, human KW - Transcription Factor 7-Like 1 Protein KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Phosphoproteins -- genetics KW - DNA -- metabolism KW - Humans KW - RNA, Messenger -- analysis KW - Amino Acid Sequence KW - Liver Regeneration KW - Transcriptional Activation KW - Rats KW - Rats, Inbred F344 KW - Promoter Regions, Genetic KW - Molecular Sequence Data KW - Male KW - Transcription Factors -- physiology KW - Helix-Loop-Helix Motifs KW - Liver -- metabolism KW - Gene Expression Regulation KW - DNA-Binding Proteins -- physiology KW - Transcription Factors -- genetics KW - MyoD Protein -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71279742?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Human+homologue+of+maid%3A+A+dominant+inhibitory+helix-loop-helix+protein+associated+with+liver-specific+gene+expression.&rft.au=Terai%2C+S%3BAoki%2C+H%3BAshida%2C+K%3BThorgeirsson%2C+S+S&rft.aulast=Terai&rft.aufirst=S&rft.date=2000-08-01&rft.volume=32&rft.issue=2&rft.spage=357&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 - 2000-08-24 N1 - Date created - 2000-08-24 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF113535; GENBANK; AF082569; AF127800 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Choosing a retrospective design to assess joint genetic and environmental contributions to risk. AN - 71274396; 10933265 AB - The authors consider issues that should be weighed when designing a retrospective study in which a focus of interest is the joint role of genetic and environmental factors in causing a disease. In place of the classical case-control design, in which controls are sampled from the same population that gives rise to the cases, one could study cases only. The case-only approach can be usefully extended by genotyping the two biologic parents of each case and in effect letting the parental genotype data provide the genetic control. Alternatively, one could carry out a case-control study in which the controls are siblings or cousins of the cases and inference is based on within-family parameters. The authors compare and contrast the parameters that can be estimated and the assumptions that must be made when each of these designs is used. The investigator must also consider certain practical issues, such as the availability of parents or sibling controls. JF - American journal of epidemiology AU - Weinberg, C R AU - Umbach, D M AD - Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. weinberg@niehs.nih.gov Y1 - 2000/08/01/ PY - 2000 DA - 2000 Aug 01 SP - 197 EP - 203 VL - 152 IS - 3 SN - 0002-9262, 0002-9262 KW - Index Medicus KW - Breast Neoplasms -- genetics KW - Causality KW - Polymorphism, Genetic KW - Humans KW - Linkage Disequilibrium KW - Environmental Monitoring KW - Logistic Models KW - Risk Factors KW - Breast Neoplasms -- etiology KW - Case-Control Studies KW - Bias (Epidemiology) KW - Female KW - Male KW - Retrospective Studies KW - Epidemiologic Research Design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71274396?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Choosing+a+retrospective+design+to+assess+joint+genetic+and+environmental+contributions+to+risk.&rft.au=Weinberg%2C+C+R%3BUmbach%2C+D+M&rft.aulast=Weinberg&rft.aufirst=C&rft.date=2000-08-01&rft.volume=152&rft.issue=3&rft.spage=197&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 - 2000-08-17 N1 - Date created - 2000-08-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Epidemiol. 2001 Jan 15;153(2):205-6 [11159168] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cyclooxygenase regulates human oropharyngeal carcinomas via the proinflammatory cytokine IL-6: a general role for inflammation? AN - 71271628; 10928984 AB - High levels of prostaglandins are produced in human oropharyngeal carcinoma (OPC). Five human OPC cell lines tested expressed both isoforms of cyclooxygenases (COX). The pan-COX inhibitor ketorolac continuously and significantly decreased PGE(2) production and IL-6 and IL-8 levels in all OPC cell lines tested, but did not affect IL-1alpha, GM-CSF levels, or in vitro tumor cell growth. In contrast, ketorolac reduced OPC growth in vivo. The OPC cell lines used express the IL-6 receptor, and IL-6 stimulation of these cells causes transduction to occur via STAT3 pathway activation. Coincubation with OPC cell lines with conditioned medium from a TPA-exposed HL-60 cells stimulated growth proportional to the IL-6 levels measured in the conditioned medium. This growth effect was specifically inhibited by anti-IL-6 antibody. These results are consistent with cytokine products of inflammatory cells having paracrine growth effects on OPC. If chronic inflammation plays a role in promoting the development of OPC, this mechanism may also apply to other epithelial tumor systems modulated by COX activity. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Hong, S H AU - Ondrey, F G AU - Avis, I M AU - Chen, Z AU - Loukinova, E AU - Cavanaugh, P F AU - Van Waes, C AU - Mulshine, J L AD - Intervention Section, Cell and Cancer Biology Department, Medicine Branch, Division of Clinical Science, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 1499 EP - 1507 VL - 14 IS - 11 SN - 0892-6638, 0892-6638 KW - Antibodies KW - 0 KW - Culture Media, Conditioned KW - Cyclooxygenase Inhibitors KW - DNA-Binding Proteins KW - Interleukin-1 KW - Interleukin-6 KW - Interleukin-8 KW - Isoenzymes KW - RNA, Messenger KW - Receptors, Interleukin-6 KW - STAT3 Transcription Factor KW - STAT3 protein, human KW - Stat3 protein, mouse KW - Trans-Activators KW - Arachidonic Acid KW - 27YG812J1I KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Prostaglandin-Endoperoxide Synthases KW - EC 1.14.99.1 KW - Dinoprostone KW - K7Q1JQR04M KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Ketorolac KW - YZI5105V0L KW - Index Medicus KW - Culture Media, Conditioned -- pharmacology KW - Trans-Activators -- metabolism KW - Animals KW - Interleukin-1 -- pharmacology KW - Humans KW - Ketorolac -- pharmacology KW - RNA, Messenger -- genetics KW - Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology KW - Mice, Inbred BALB C KW - Models, Biological KW - Interleukin-8 -- pharmacology KW - Isoenzymes -- metabolism KW - Tumor Cells, Cultured KW - Antibodies -- pharmacology KW - Interleukin-8 -- metabolism KW - Granulocyte-Macrophage Colony-Stimulating Factor -- metabolism KW - DNA-Binding Proteins -- metabolism KW - Antibodies -- immunology KW - Clinical Trials, Phase II as Topic KW - HL-60 Cells KW - Cell Division -- drug effects KW - Mice KW - Culture Media, Conditioned -- metabolism KW - Arachidonic Acid -- metabolism KW - Cyclooxygenase Inhibitors -- pharmacology KW - Isoenzymes -- antagonists & inhibitors KW - Interleukin-1 -- metabolism KW - RNA, Messenger -- metabolism KW - Dinoprostone -- metabolism KW - Signal Transduction -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Paracrine Communication -- drug effects KW - Receptors, Interleukin-6 -- metabolism KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Interleukin-6 -- antagonists & inhibitors KW - Oropharyngeal Neoplasms -- enzymology KW - Interleukin-6 -- metabolism KW - Interleukin-6 -- immunology KW - Interleukin-6 -- pharmacology KW - Inflammation -- metabolism KW - Oropharyngeal Neoplasms -- pathology KW - Oropharyngeal Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71271628?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cyclooxygenase+regulates+human+oropharyngeal+carcinomas+via+the+proinflammatory+cytokine+IL-6%3A+a+general+role+for+inflammation%3F&rft.au=Hong%2C+S+H%3BOndrey%2C+F+G%3BAvis%2C+I+M%3BChen%2C+Z%3BLoukinova%2C+E%3BCavanaugh%2C+P+F%3BVan+Waes%2C+C%3BMulshine%2C+J+L&rft.aulast=Hong&rft.aufirst=S&rft.date=2000-08-01&rft.volume=14&rft.issue=11&rft.spage=1499&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=08926638&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-25 N1 - Date created - 2000-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemopreventive activity of quercetin during carcinogenesis in cervix uteri in mice. AN - 71265502; 10925400 AB - The chemopreventive action of quercetin was examined during 20-methyl cholanthrene induced cervical neoplasia in virgin Swiss albino mice. The effects were evaluated on the basis of histopathological observation of the cervical epithelium, micronucleus frequency in vaginal exfoliated cells and some biochemical parameters in the host liver. Quercetin was found to arrest or reverse the progression of cervical neoplasia. The micronucleus frequency was reduced following its administration. The potential anti-carcinogenic effect of quercetin noted in this study is attributed to its antioxidant property which was reflected in the lipid peroxides and their role in the host detoxification system, as expressed in liver glutathione level, glutathione-S-transferase, glutathione peroxidase, catalase and superoxide dismutase activity. As an integral part of the diet quercetin may offer protection to the epithelium from the damaging effects of carcinogenic chemicals. Copyright 2000 John Wiley & Sons, Ltd. JF - Phytotherapy research : PTR AU - De, S AU - Chakraborty, J AU - Chakraborty, R N AU - Das, S AD - Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 347 EP - 351 VL - 14 IS - 5 SN - 0951-418X, 0951-418X KW - Anticarcinogenic Agents KW - 0 KW - Benz(a)Anthracenes KW - Carcinogens KW - cholanthrene KW - 429L45KABE KW - Quercetin KW - 9IKM0I5T1E KW - Index Medicus KW - Animals KW - Liver -- enzymology KW - Liver -- drug effects KW - Lipid Peroxidation -- drug effects KW - Disease Models, Animal KW - Mice KW - Female KW - Uterine Cervical Neoplasms -- prevention & control KW - Anticarcinogenic Agents -- therapeutic use KW - Quercetin -- therapeutic use KW - Anticarcinogenic Agents -- pharmacology KW - Uterine Cervical Neoplasms -- diagnosis KW - Uterine Cervical Neoplasms -- chemically induced KW - Quercetin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71265502?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Phytotherapy+research+%3A+PTR&rft.atitle=Chemopreventive+activity+of+quercetin+during+carcinogenesis+in+cervix+uteri+in+mice.&rft.au=De%2C+S%3BChakraborty%2C+J%3BChakraborty%2C+R+N%3BDas%2C+S&rft.aulast=De&rft.aufirst=S&rft.date=2000-08-01&rft.volume=14&rft.issue=5&rft.spage=347&rft.isbn=&rft.btitle=&rft.title=Phytotherapy+research+%3A+PTR&rft.issn=0951418X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-24 N1 - Date created - 2000-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A DNA polymerase epsilon mutant that specifically causes +1 frameshift mutations within homonucleotide runs in yeast. AN - 71264737; 10924461 AB - The DNA polymerases delta and epsilon are the major replicative polymerases in the yeast Saccharomyces cerevisiae that possess 3' --> 5' exonuclease proofreading activity. Many errors arising during replication are corrected by these exonuclease activities. We have investigated the contributions of regions of Polepsilon other than the proofreading motifs to replication accuracy. An allele, pol2-C1089Y, was identified in a screen of Polepsilon mutants that in combination with an exonuclease I (exo1) mutation could cause a synergistic increase in mutations within homonucleotide runs. In contrast to other polymerase mutators, this allele specifically results in insertion frameshifts. When pol2-C1089Y was combined with deletions of EXO1 or RAD27 (homologue of human FEN1), mutation rates were increased for +1 frameshifts while there was almost no effect on -1 frameshifts. On the basis of genetic analysis, the pol2-C1089Y mutation did not cause a defect in proofreading. In combination with a deletion of the mismatch repair gene MSH2, the +1 frameshift mutation rate for a short homonucleotide run was increased nearly 100-fold whereas the -1 frameshift rate was unchanged. This suggests that the Pol2-C1089Y protein makes +1 frameshift errors during replication of homonucleotide runs and that these errors can be corrected by either mismatch repair (MMR) or proofreading (in short runs). This is the first report of a +1-specific mutator for homonucleotide runs in vivo. The pol2-C1089Y mutation defines a functionally important residue in Polepsilon. JF - Genetics AU - Kirchner, J M AU - Tran, H AU - Resnick, M A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 1623 EP - 1632 VL - 155 IS - 4 SN - 0016-6731, 0016-6731 KW - Saccharomyces cerevisiae Proteins KW - 0 KW - DNA Polymerase II KW - EC 2.7.7.- KW - EXO1 protein, human KW - EC 3.1.- KW - Endodeoxyribonucleases KW - Exodeoxyribonucleases KW - Flap Endonucleases KW - FEN1 protein, human KW - EC 3.1.11.- KW - exodeoxyribonuclease I KW - EC 3.1.11.1 KW - RAD27 protein, S cerevisiae KW - EC 3.1.11.5 KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Plasmids -- genetics KW - Endodeoxyribonucleases -- genetics KW - Amino Acid Sequence KW - Exodeoxyribonucleases -- genetics KW - Sequence Analysis, DNA KW - Gene Deletion KW - Mutagenesis KW - DNA Repair -- genetics KW - Alleles KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Protein Structure, Tertiary KW - Saccharomyces cerevisiae -- genetics KW - Frameshift Mutation KW - Genes, Fungal KW - DNA Polymerase II -- genetics KW - DNA Polymerase II -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71264737?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=A+DNA+polymerase+epsilon+mutant+that+specifically+causes+%2B1+frameshift+mutations+within+homonucleotide+runs+in+yeast.&rft.au=Kirchner%2C+J+M%3BTran%2C+H%3BResnick%2C+M+A&rft.aulast=Kirchner&rft.aufirst=J&rft.date=2000-08-01&rft.volume=155&rft.issue=4&rft.spage=1623&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-10 N1 - Date created - 2000-10-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1988 Oct 15;263(29):14784-9 [3049589] Mol Cell Biol. 1999 Aug;19(8):5373-82 [10409728] EMBO J. 1991 Aug;10(8):2165-70 [1648480] Yeast. 1991 Apr;7(3):253-63 [1882550] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9473-7 [1658784] Yeast. 1991 Aug-Sep;7(6):609-15 [1767589] J Biol Chem. 1992 Sep 15;267(26):18251-4 [1526964] J Biol Chem. 1993 May 15;268(14):10238-45 [8486689] J Biol Chem. 1993 Nov 15;268(32):23762-5 [8226906] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6830-4 [8041704] Annu Rev Biochem. 1994;63:777-822 [7526780] Science. 1995 Jul 14;269(5221):238-40 [7618086] Trends Biochem Sci. 1995 Aug;20(8):319-23 [7667891] Mol Cell Biol. 1995 Oct;15(10):5607-17 [7565712] Biochemistry. 1996 Jan 23;35(3):1046-53 [8547240] Genes Dev. 1996 Jun 15;10(12):1433-42 [8666228] Bioessays. 1997 Mar;19(3):233-40 [9080773] Mol Cell Biol. 1997 May;17(5):2764-73 [9111347] Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7487-92 [9207118] Mutat Res. 1997 Sep;384(3):157-67 [9330612] Nucleic Acids Res. 1997 Dec 15;25(24):5041-6 [9396813] Science. 1998 Feb 6;279(5352):853-6 [9452383] Mol Cell Biol. 1998 May;18(5):2779-88 [9566897] J Mol Biol. 1998 Apr 24;278(1):135-46 [9571039] Curr Genet. 1998 Jul;34(1):21-9 [9683672] Mutat Res. 1998 May 25;400(1-2):45-58 [9685581] Cancer Res. 1998 Sep 15;58(18):4040-3 [9751605] Chromosoma. 1998 Sep;107(4):218-27 [9745046] Biochim Biophys Acta. 1998 Nov 26;1443(1-2):23-39 [9838028] Cold Spring Harb Symp Quant Biol. 1966;31:77-84 [5237214] J Biol Chem. 1987 Nov 25;262(33):16212-23 [3316214] J Biol Chem. 1996 Oct 4;271(40):24954-61 [8798775] Genetics. 1996 Aug;143(4):1579-87 [8844147] Cell. 1997 Jan 24;88(2):253-63 [9008166] Gastroenterology. 1999 Jan;116(1):58-63 [9869603] Nucleic Acids Res. 1999 Feb 1;27(3):736-42 [9889267] Am J Hum Genet. 1999 Feb;64(2):378-84 [9973276] Mol Cell Biol. 1999 Mar;19(3):2000-7 [10022887] Biochemistry. 1999 Mar 2;38(9):2661-8 [10052936] Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2204-9 [10051619] Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2970-5 [10077621] Biochem J. 1999 May 1;339 ( Pt 3):657-65 [10215605] Genetics. 1999 May;152(1):47-59 [10224242] J Biol Chem. 1999 May 21;274(21):14602-8 [10329652] Mol Cell Biol. 1999 Jun;19(6):4143-52 [10330154] Biochim Biophys Acta. 1999 Jun 9;1445(3):363-71 [10366722] J Mol Biol. 1999 Jun 18;289(4):835-50 [10369765] Cell. 1990 Sep 21;62(6):1143-51 [2169349] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bacterial-type DNA holliday junction resolvases in eukaryotic viruses. AN - 71259713; 10890916 AB - Homologous DNA recombination promotes genetic diversity and the maintenance of genome integrity, yet no enzymes with specificity for the Holliday junction (HJ)-a key DNA recombination intermediate-have been purified and characterized from metazoa or their viruses. Here we identify critical structural elements of RuvC, a bacterial HJ resolvase, in uncharacterized open reading frames from poxviruses and an iridovirus. The putative vaccinia virus resolvase was expressed as a recombinant protein, affinity purified, and shown to specifically bind and cleave a synthetic HJ to yield nicked duplex molecules. Mutation of either of two conserved acidic amino acids abrogated the catalytic activity of the A22R protein without affecting HJ binding. The presence of bacterial-type enzymes in metazoan viruses raises evolutionary questions. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Garcia, A D AU - Aravind, L AU - Koonin, E V AU - Moss, B AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, and National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2000/08/01/ PY - 2000 DA - 2000 Aug 01 SP - 8926 EP - 8931 VL - 97 IS - 16 SN - 0027-8424, 0027-8424 KW - DNA Primers KW - 0 KW - DNA, Bacterial KW - Recombinant Proteins KW - Recombinases KW - Transposases KW - EC 2.7.7.- KW - Index Medicus KW - Amino Acid Sequence KW - Recombinant Proteins -- genetics KW - Hydrolysis KW - Chromatography, Affinity KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Substrate Specificity KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Transposases -- chemistry KW - Transposases -- metabolism KW - Transposases -- genetics KW - DNA, Bacterial -- chemistry KW - Poxviridae -- enzymology KW - Transposases -- isolation & purification KW - Iridovirus -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71259713?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Bacterial-type+DNA+holliday+junction+resolvases+in+eukaryotic+viruses.&rft.au=Garcia%2C+A+D%3BAravind%2C+L%3BKoonin%2C+E+V%3BMoss%2C+B&rft.aulast=Garcia&rft.aufirst=A&rft.date=2000-08-01&rft.volume=97&rft.issue=16&rft.spage=8926&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 - 2000-09-05 N1 - Date created - 2000-09-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Gene. 1987;56(1):125-35 [3315856] J Biol Chem. 1987 Oct 25;262(30):14826-36 [3667607] J Mol Biol. 1988 Feb 5;199(3):399-413 [3351934] J Virol. 1989 Apr;63(4):1595-603 [2926864] J Virol. 1989 May;63(5):2030-5 [2704074] J Virol. 1989 Jun;63(6):2437-44 [2724409] Nucleic Acids Res. 1989 Jun 26;17(12):4713-30 [2546125] Proteins. 1991;9(3):180-90 [2006136] Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6063-7 [1829835] EMBO J. 1991 Dec;10(13):4381-9 [1661673] Nature. 1991 Dec 19-26;354(6354):506-10 [1758493] J Virol. 1992 Mar;66(3):1551-63 [1738203] EMBO J. 1992 Feb;11(2):699-704 [1537343] J Mol Biol. 1993 Jul 20;232(2):584-99 [8345525] J Biol Chem. 1994 Feb 18;269(7):5195-201 [8106501] Cell. 1994 Sep 23;78(6):1063-72 [7923356] EMBO J. 1994 Dec 15;13(24):6133-42 [7813450] Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7470-4 [7638215] Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):785-9 [8570635] J Mol Biol. 1997 Jul 18;270(3):471-80 [9237912] Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 [9254694] J Mol Biol. 1997 Oct 3;272(4):509-22 [9325108] Mol Cell Biol. 1997 Nov;17(11):6465-71 [9343409] Nucleic Acids Res. 1997 Dec 15;25(24):4876-82 [9396791] J Biol Chem. 1998 Dec 18;273(51):34151-6 [9852075] J Mol Biol. 1999 Mar 19;287(1):9-20 [10074403] J Mol Biol. 1999 Apr 16;287(5):1023-40 [10222208] Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8873-8 [10430863] J Mol Biol. 1999 Sep 17;292(2):195-202 [10493868] Nat Struct Biol. 1999 Oct;6(10):913-7 [10504723] J Virol. 1976 Jun;18(3):1000-15 [775128] Cell. 1981 Dec;27(2 Pt 1):391-401 [6277506] J Mol Biol. 1987 Aug 5;196(3):541-58 [2824785] Cell. 1982 Feb;28(2):315-24 [7060133] Cell. 1982 Jun;29(2):357-65 [6288255] Cold Spring Harb Symp Quant Biol. 1983;47 Pt 2:723-9 [6574869] J Mol Biol. 1974 Oct 5;88(4):785-96 [4427382] J Virol. 1985 Mar;53(3):935-43 [3871865] Cell. 1986 Jun 20;45(6):879-84 [3085958] J Virol. 1986 Aug;59(2):249-59 [3016294] J Mol Biol. 1987 Jan 20;193(2):359-76 [3037087] Comment In: Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9351-3 [10944205] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of aromatase activity and expression in MCF-7 cells by the chemopreventive retinoid N-(4-hydroxy-phenyl)-retinamide. AN - 71258587; 10917548 AB - The effect of the chemopreventive synthetic retinoid N-(4-hydroxyphenyl)-retinamide (4-HPR) on aromatase activity and expression was examined. 4-HPR caused a dose-dependent inhibition of aromatase activity in microsomes isolated from JEG-3 human placental carcinoma cells. The kinetics of inhibition were analysed by double-reciprocal plot. The Km of the substrate increased and the Vmax of the reaction decreased in the presence of 4-HPR, indicating that enzyme inhibition involved both competition for the substrate-binding site and non-competitive mechanisms. To determine whether 4-HPR would also inhibit aromatase activity in intact cells, MCF-7 human breast cancer cells were incubated with or without cAMP in the presence of 4-HPR. 4-HPR inhibited both basal and cAMP-induced aromatase activity in intact MCF-7 cells. The induction of aromatase mRNA expression in MCF-7 cells by cAMP was inhibited in cells treated with 4-HPR. These results indicate that 4-HPR inhibits both the enzymatic activity and expression of aromatase. These activities may play an important role in the known chemopreventive effect of 4-HPR towards breast cancer. JF - British journal of cancer AU - Ciolino, H P AU - Wang, T T AU - Sathyamoorthy, N AD - Cellular Defense and Carcinogenesis Section, Basic Research Laboratory, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21701-1201, USA. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 333 EP - 337 VL - 83 IS - 3 SN - 0007-0920, 0007-0920 KW - Anticarcinogenic Agents KW - 0 KW - Aromatase Inhibitors KW - RNA, Messenger KW - RNA, Neoplasm KW - Fenretinide KW - 187EJ7QEXL KW - Aromatase KW - EC 1.14.14.1 KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Gene Expression Regulation, Enzymologic KW - Tumor Cells, Cultured KW - Enzyme Induction -- drug effects KW - Humans KW - RNA, Messenger -- analysis KW - Aromatase -- genetics KW - Microsomes -- enzymology KW - RNA, Neoplasm -- analysis KW - Female KW - Pregnancy KW - Breast Neoplasms -- drug therapy KW - Choriocarcinoma -- enzymology KW - Uterine Neoplasms -- drug therapy KW - Fenretinide -- pharmacology KW - Choriocarcinoma -- drug therapy KW - Anticarcinogenic Agents -- pharmacology KW - Uterine Neoplasms -- enzymology KW - Breast Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71258587?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+cancer&rft.atitle=Inhibition+of+aromatase+activity+and+expression+in+MCF-7+cells+by+the+chemopreventive+retinoid+N-%284-hydroxy-phenyl%29-retinamide.&rft.au=Ciolino%2C+H+P%3BWang%2C+T+T%3BSathyamoorthy%2C+N&rft.aulast=Ciolino&rft.aufirst=H&rft.date=2000-08-01&rft.volume=83&rft.issue=3&rft.spage=333&rft.isbn=&rft.btitle=&rft.title=British+journal+of+cancer&rft.issn=00070920&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-03 N1 - Date created - 2000-08-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Br J Cancer. 1976 Jan;33(1):116-8 [1252327] Breast Cancer Res Treat. 1997 Nov-Dec;46(2-3):181-9 [9478273] J Clin Endocrinol Metab. 1981 Mar;52(3):447-50 [6970203] J Natl Cancer Inst. 1985 Nov;75(5):871-5 [2932587] Cancer Res. 1989 Nov 1;49(21):6149-52 [2529028] Cancer Res. 1990 Jun 15;50(12):3652-6 [2340513] J Cell Biochem Suppl. 1997;27:92-9 [9591198] Br J Cancer. 1998 Jun;77(12):2138-47 [9649125] J Steroid Biochem Mol Biol. 1998 Apr;65(1-6):169-74 [9699870] Endocr Rev. 1998 Oct;19(5):593-607 [9793759] Carcinogenesis. 1999 May;20(5):879-83 [10334206] J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):205-10 [10418994] J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):293-7 [10419005] Cancer Res. 1990 Nov 1;50(21):6949-54 [2208160] J Clin Oncol. 1993 Oct;11(10):2036-42 [8410127] Cancer Res. 1994 Apr 1;54(7 Suppl):2032s-2037s [8137334] Leukemia. 1994 Oct;8(10):1785-90 [7934176] Eur J Pharmacol. 1995 Apr 28;289(2):217-22 [7621894] J Cell Biochem Suppl. 1995;22:1-10 [8538183] Br J Cancer. 1996 Feb;73(4):415-7 [8595151] J Biol Chem. 1996 Jun 21;271(25):15194-202 [8662988] Biochem Mol Biol Int. 1996 May;39(1):109-16 [8799333] J Steroid Biochem Mol Biol. 1996 Jul;58(4):411-5 [8903425] Cancer Lett. 1996 Oct 1;107(1):65-71 [8913268] IARC Sci Publ. 1996;(139):47-59 [8923019] Endocrinology. 1996 Dec;137(12):5739-42 [8940410] J Clin Endocrinol Metab. 1997 Jan;82(1):200-8 [8989259] FASEB J. 1997 Jan;11(1):29-36 [9034163] Trends Pharmacol Sci. 1997 Jul;18(7):245-51 [9253856] J Steroid Biochem Mol Biol. 1997 Apr;61(3-6):281-6 [9365202] J Steroid Biochem Mol Biol. 1997 Nov-Dec;63(4-6):317-28 [9459198] Anal Biochem. 1976 May 7;72:248-54 [942051] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CD40 ligand trimer and IL-12 enhance peripheral blood mononuclear cells and CD4+ T cell proliferation and production of IFN-gamma in response to p24 antigen in HIV-infected individuals: potential contribution of anergy to HIV-specific unresponsiveness. AN - 71258207; 10903780 AB - It has been suggested that CD4+ T cell proliferative responses to HIV p24 Ag may be important in the control of HIV infection. However, these responses are minimal or absent in many HIV-infected individuals. Furthermore, while in vitro and in vivo responses to non-HIV recall Ags improve upon administration of highly active antiretroviral therapy, there does not appear to be a commensurate enhancement of HIV-specific immune responses. It is possible that CD4+ p24-specific T cells are deleted early in the course of infection. However, it is also possible that a discrete unresponsiveness, or anergy, contributes to the lack of proliferation to p24. To evaluate the possible contribution of unresponsiveness to the lack of CD4+ T cell proliferation to p24 in HIV-infected individuals, we attempted to overcome unresponsiveness. CD40 ligand trimer (CD40LT) and IL-12 significantly increased PBMC and CD4+ T cell proliferative responses to p24 Ag in HIV-infected, but not uninfected, individuals. No increase in proliferative response to CMV Ag was observed. CD40LT exerted its effect through B7-CD28-dependent and IL-12- and IL-15-independent mechanisms. Finally, the increase in proliferation with CD40LT and IL-12 was associated with an augmented production of IFN-gamma in most, but not all, individuals. These data suggest the possible contribution of HIV-specific unresponsiveness to the lack of CD4+ T cell proliferation to p24 Ag in HIV-infected individuals and that clonal deletion alone does not explain this phenomenon. They also indicate the potential for CD40LT and IL-12 as immune-based therapies for HIV infection. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Dybul, M AU - Mercier, G AU - Belson, M AU - Hallahan, C W AU - Liu, S AU - Perry, C AU - Herpin, B AU - Ehler, L AU - Davey, R T AU - Metcalf, J A AU - Mican, J M AU - Seder, R A AU - Fauci, A S AD - Laboratory of Immunoregulation and Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, and Warren Magneson Clinical Research Center, National Institutes of Health, Bethesda, MD 20892, USA. mdybul@nih.gov Y1 - 2000/08/01/ PY - 2000 DA - 2000 Aug 01 SP - 1685 EP - 1691 VL - 165 IS - 3 SN - 0022-1767, 0022-1767 KW - Adjuvants, Immunologic KW - 0 KW - Anti-HIV Agents KW - Antigens, CD28 KW - Antigens, CD40 KW - Antigens, CD80 KW - Epitopes KW - HIV Core Protein p24 KW - Interleukin-15 KW - Ligands KW - Membrane Glycoproteins KW - CD40 Ligand KW - 147205-72-9 KW - Interleukin-12 KW - 187348-17-0 KW - Interferon-gamma KW - 82115-62-6 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Antigens, CD80 -- physiology KW - HIV Infections -- virology KW - Humans KW - Antigens, CD28 -- physiology KW - Leukocytes, Mononuclear -- immunology KW - Anti-HIV Agents -- therapeutic use KW - Leukocytes, Mononuclear -- virology KW - Cells, Cultured KW - Interleukin-15 -- physiology KW - Dose-Response Relationship, Immunologic KW - HIV Infections -- immunology KW - Leukocytes, Mononuclear -- metabolism KW - HIV Infections -- drug therapy KW - Drug Synergism KW - Epitopes -- immunology KW - Clonal Anergy -- immunology KW - CD4-Positive T-Lymphocytes -- metabolism KW - Adjuvants, Immunologic -- physiology KW - Membrane Glycoproteins -- physiology KW - Lymphocyte Activation -- immunology KW - Interleukin-12 -- physiology KW - CD4-Positive T-Lymphocytes -- virology KW - Membrane Glycoproteins -- therapeutic use KW - Interferon-gamma -- biosynthesis KW - CD4-Positive T-Lymphocytes -- immunology KW - Interleukin-12 -- therapeutic use KW - HIV Core Protein p24 -- immunology KW - Antigens, CD40 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71258207?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=CD40+ligand+trimer+and+IL-12+enhance+peripheral+blood+mononuclear+cells+and+CD4%2B+T+cell+proliferation+and+production+of+IFN-gamma+in+response+to+p24+antigen+in+HIV-infected+individuals%3A+potential+contribution+of+anergy+to+HIV-specific+unresponsiveness.&rft.au=Dybul%2C+M%3BMercier%2C+G%3BBelson%2C+M%3BHallahan%2C+C+W%3BLiu%2C+S%3BPerry%2C+C%3BHerpin%2C+B%3BEhler%2C+L%3BDavey%2C+R+T%3BMetcalf%2C+J+A%3BMican%2C+J+M%3BSeder%2C+R+A%3BFauci%2C+A+S&rft.aulast=Dybul&rft.aufirst=M&rft.date=2000-08-01&rft.volume=165&rft.issue=3&rft.spage=1685&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 - 2000-08-22 N1 - Date created - 2000-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of fluconazole and clarithromycin on rifabutin and 25-O-desacetylrifabutin pharmacokinetics. AN - 71247984; 10898693 AB - Ten human immunodeficiency virus-infected patients were given rifabutin in addition to fluconazole and clarithromycin. There was a 76% increase in the area under the concentration-time curve of rifabutin when either fluconazole or clarithromycin was given alone and a 152% increase when both drugs were given together with rifabutin. Patients should be monitored for adverse effects of rifabutin administered concomitantly with clarithromycin and/or fluconazole. JF - Antimicrobial agents and chemotherapy AU - Jordan, M K AU - Polis, M A AU - Kelly, G AU - Narang, P K AU - Masur, H AU - Piscitelli, S C AD - Department of Pharmacy, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 2170 EP - 2172 VL - 44 IS - 8 SN - 0066-4804, 0066-4804 KW - Anti-Bacterial Agents KW - 0 KW - Antibiotics, Antitubercular KW - Antifungal Agents KW - 25-desacetylrifabutin KW - 100324-63-8 KW - Rifabutin KW - 1W306TDA6S KW - Fluconazole KW - 8VZV102JFY KW - Clarithromycin KW - H1250JIK0A KW - Index Medicus KW - AIDS/HIV KW - Drug Therapy, Combination KW - Drug Interactions KW - Antifungal Agents -- pharmacology KW - Humans KW - Antibiotics, Antitubercular -- adverse effects KW - Adult KW - Anti-Bacterial Agents -- pharmacology KW - Middle Aged KW - Antibiotics, Antitubercular -- blood KW - Antibiotics, Antitubercular -- pharmacokinetics KW - Male KW - Female KW - Rifabutin -- adverse effects KW - Rifabutin -- blood KW - Rifabutin -- analogs & derivatives KW - HIV Infections -- blood KW - Clarithromycin -- pharmacology KW - HIV Infections -- metabolism KW - Fluconazole -- pharmacology KW - Rifabutin -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71247984?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Effects+of+fluconazole+and+clarithromycin+on+rifabutin+and+25-O-desacetylrifabutin+pharmacokinetics.&rft.au=Jordan%2C+M+K%3BPolis%2C+M+A%3BKelly%2C+G%3BNarang%2C+P+K%3BMasur%2C+H%3BPiscitelli%2C+S+C&rft.aulast=Jordan&rft.aufirst=M&rft.date=2000-08-01&rft.volume=44&rft.issue=8&rft.spage=2170&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-05 N1 - Date created - 2000-10-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Ann Intern Med. 1996 Mar 15;124(6):573-6 [8597321] Clin Infect Dis. 1996 Apr;22 Suppl 1:S15-21; discussion S21-2 [8785251] N Engl J Med. 1996 Aug 8;335(6):377-83 [8676931] J Chromatogr B Biomed Appl. 1996 Feb 9;676(1):125-30 [8852052] MMWR Recomm Rep. 1999 Aug 20;48(RR-10):1-59, 61-6 [10499670] Antimicrob Agents Chemother. 1998 Mar;42(3):631-9 [9517944] Clin Pharmacol Ther. 1998 Apr;63(4):414-21 [9585795] Antimicrob Agents Chemother. 1999 Mar;43(3):647-50 [10049281] Biopharm Drug Dispos. 1996 Apr;17(3):223-36 [8983397] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of apoptosis in p16INK4A mutant cell lines by adenovirus-mediated overexpression of p16INK4A protein. AN - 71246799; 10918444 AB - The tumor suppressor gene p16INK4A is a cyclin-dependent kinase inhibitor (CDKI) and an important cell cycle regulator. We have previously constructed a recombinant adenovirus which expresses p16 (Adp16) and shown that infection in a variety of human tumor cell lines with this recombinant virus results in high levels of p16INK4A protein expression resulting in cell cycle arrest and loss of cyclin-cdk activity. Furthermore, adenoviral-mediated overexpression of wild-type p16INK4A is more toxic in cancer cells which express mutant forms of p16INK4A compared to cancer cell lines containing endogenous wild-type p16. TUNEL assay and DAPI staining following infection of MDA-MB 231 breast cancer cells with Adp16 indicate that p16INK4A-mediated cytotoxicity was associated with apoptosis. This is supported by studies demonstrating a decrease in cpp32 and cyclinB1 protein levels and induction of poly (ADP-ribose) polymerase (PARP) cleavage following infection of MDA-MB-231 cells with Adp16. These results suggest that gene therapy using Adp16 may be a promising treatment option for human cancers containing alterations in p16 expression. JF - Cell death and differentiation AU - Kim, M AU - Katayose, Y AU - Rojanala, L AU - Shah, S AU - Sgagias, M AU - Jang, L AU - Jung, Y J AU - Lee, S H AU - Hwang, S G AU - Cowan, K H AD - Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland, MD 20892, USA. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 706 EP - 711 VL - 7 IS - 8 SN - 1350-9047, 1350-9047 KW - Carrier Proteins KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p16 KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - CASP3 protein, human KW - EC 3.4.22.- KW - Caspase 3 KW - Caspases KW - Index Medicus KW - Adenoviridae KW - Tumor Cells, Cultured KW - Humans KW - Genetic Vectors KW - Gene Expression KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Cell Line KW - Caspases -- metabolism KW - Mutagenesis KW - Apoptosis KW - Carrier Proteins -- genetics KW - Carrier Proteins -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71246799?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+death+and+differentiation&rft.atitle=Induction+of+apoptosis+in+p16INK4A+mutant+cell+lines+by+adenovirus-mediated+overexpression+of+p16INK4A+protein.&rft.au=Kim%2C+M%3BKatayose%2C+Y%3BRojanala%2C+L%3BShah%2C+S%3BSgagias%2C+M%3BJang%2C+L%3BJung%2C+Y+J%3BLee%2C+S+H%3BHwang%2C+S+G%3BCowan%2C+K+H&rft.aulast=Kim&rft.aufirst=M&rft.date=2000-08-01&rft.volume=7&rft.issue=8&rft.spage=706&rft.isbn=&rft.btitle=&rft.title=Cell+death+and+differentiation&rft.issn=13509047&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-20 N1 - Date created - 2000-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lactic acidosis and hepatic steatosis associated with use of stavudine: report of four cases. AN - 71237541; 10906833 AB - An association between use of zidovudine and didanosine and a rare but life-threatening syndrome of hepatic steatosis, lactic acidosis, and myopathy has been reported. To describe the syndrome of hepatic steatosis, lactic acidosis, and myopathy in four patients taking stavudine. Case series. A community hospital in Washington, D.C., and National Institutes of Health Clinical Center, Bethesda, Maryland. Two men and two women with HIV-1 infection who were taking stavudine presented with lactic acidosis and elevated levels of aminotransferases. All patients required intensive care. Levels of lactic acid, alanine aminotransferase, aspartate aminotransferase, amylase, and lipase; computed tomography of the abdomen; liver biopsy (two patients); and muscle biopsy (two patients). Histologic findings consistent with mitochondrial injury confirmed the diagnosis of hepatic or muscle abnormality. Because hepatic steatosis may be life-threatening, physicians should consider it as a possible cause of elevated hepatic aminotransferase levels among patients taking stavudine. JF - Annals of internal medicine AU - Miller, K D AU - Cameron, M AU - Wood, L V AU - Dalakas, M C AU - Kovacs, J A AD - Warren Grant Magnuson Clinical Center, National Institute of Allergy and Infectious Diseases Intramural AIDS Program. National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/08/01/ PY - 2000 DA - 2000 Aug 01 SP - 192 EP - 196 VL - 133 IS - 3 SN - 0003-4819, 0003-4819 KW - Anti-HIV Agents KW - 0 KW - Stavudine KW - BO9LE4QFZF KW - Aspartate Aminotransferases KW - EC 2.6.1.1 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Tomography, X-Ray Computed KW - Mitochondrial Myopathies -- chemically induced KW - Biopsy KW - Muscle, Skeletal -- enzymology KW - Drug Therapy, Combination KW - Aspartate Aminotransferases -- blood KW - Alanine Transaminase -- blood KW - Syndrome KW - Adult KW - HIV Infections -- drug therapy KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Fatty Liver -- chemically induced KW - Acidosis, Lactic -- chemically induced KW - Anti-HIV Agents -- adverse effects KW - Stavudine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71237541?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+internal+medicine&rft.atitle=Lactic+acidosis+and+hepatic+steatosis+associated+with+use+of+stavudine%3A+report+of+four+cases.&rft.au=Miller%2C+K+D%3BCameron%2C+M%3BWood%2C+L+V%3BDalakas%2C+M+C%3BKovacs%2C+J+A&rft.aulast=Miller&rft.aufirst=K&rft.date=2000-08-01&rft.volume=133&rft.issue=3&rft.spage=192&rft.isbn=&rft.btitle=&rft.title=Annals+of+internal+medicine&rft.issn=00034819&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-01 N1 - Date created - 2000-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Signaling and transcriptional regulation in early mammalian eye development: a link between FGF and MITF. AN - 71229975; 10903182 AB - During vertebrate eye development, the optic vesicle is partitioned into a domain at its distal tip that will give rise to the neuroretina, and another at its proximal base that will give rise to the pigmented epithelium. Both domains are initially bipotential, each capable of giving rise to either neuroretina or pigmented epithelium. The partitioning depends on extrinsic signals, notably fibroblast growth factors, which emanate from the overlying surface ectoderm and induce the adjacent neuroepithelium to assume the neuroretinal fate. Using explant cultures of mouse optic vesicles, we demonstrate that bipotentiality of the optic neuroepithelium is associated with the initial coexpression of the basic-helix-loop-helix-zipper transcription factor MITF, which is later needed solely in the pigmented epithelium, and a set of distinct transcription factors that become restricted to the neuroretina. Implantation of fibroblast growth factor-coated beads close to the base of the optic vesicle leads to a rapid downregulation of MITF and the development of an epithelium that, by morphology, gene expression, and lack of pigmentation, resembles the future neuroretina. Conversely, the removal of the surface ectoderm results in the maintenance of MITF in the distal optic epithelium, lack of expression of the neuroretinal-specific CHX10 transcription factor, and conversion of this epithelium into a pigmented monolayer. This phenomenon can be prevented by the application of fibroblast growth factor alone. In Mitf mutant embryos, parts of the future pigment epithelium become thickened, lose expression of a number of pigment epithelium transcription factors, gain expression of neuroretinal transcription factors, and eventually transdifferentiate into a laminated second retina. The results support the view that the bipotential optic neuroepithelium is characterized by overlapping gene expression patterns and that selective gene repression, brought about by local extrinsic signals, leads to the separation into discrete expression domains and, hence, to domain specification. JF - Development (Cambridge, England) AU - Nguyen, M AU - Arnheiter, H AD - Laboratory of Developmental Neurogenetics, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/08// PY - 2000 DA - August 2000 SP - 3581 EP - 3591 VL - 127 IS - 16 SN - 0950-1991, 0950-1991 KW - DNA-Binding Proteins KW - 0 KW - Microphthalmia-Associated Transcription Factor KW - Mitf protein, mouse KW - Transcription Factors KW - Fibroblast Growth Factors KW - 62031-54-3 KW - Index Medicus KW - Animals KW - Mammals KW - Ectoderm KW - Pigment Epithelium of Eye -- metabolism KW - Transcription, Genetic KW - Mice KW - Pigment Epithelium of Eye -- embryology KW - Leucine Zippers KW - Mutagenesis KW - Helix-Loop-Helix Motifs KW - Down-Regulation KW - Mice, Inbred C57BL KW - DNA-Binding Proteins -- genetics KW - Fibroblast Growth Factors -- metabolism KW - Eye -- embryology KW - Transcription Factors -- genetics KW - Signal Transduction KW - Gene Expression Regulation, Developmental UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71229975?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Development+%28Cambridge%2C+England%29&rft.atitle=Signaling+and+transcriptional+regulation+in+early+mammalian+eye+development%3A+a+link+between+FGF+and+MITF.&rft.au=Nguyen%2C+M%3BArnheiter%2C+H&rft.aulast=Nguyen&rft.aufirst=M&rft.date=2000-08-01&rft.volume=127&rft.issue=16&rft.spage=3581&rft.isbn=&rft.btitle=&rft.title=Development+%28Cambridge%2C+England%29&rft.issn=09501991&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-19 N1 - Date created - 2000-09-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association between GSTM1*0 and squamous dysplasia of the esophagus in the high risk region of Linxian, China. AN - 71162632; 10840162 AB - Individuals with specific phase I and phase II enzyme polymorphisms may be at increased risk for squamous cell carcinoma of the esophagus. However, to our knowledge there has been only one previous report that evaluates a potential role for these polymorphisms in increasing risk for preneoplastic squamous lesions of the esophagus. To explore this further, we examined polymorphisms in CYP1A1, CYP2E1, GSTM1 and GSTT1, both independently and in combination, for potential associations with the risk of biopsy-proven squamous dysplasia of the esophagus in asymptomatic adults from Linxian, a high risk region in China. Cases consisted of 56 individuals from an esophageal cancer screening study with an endoscopic biopsy diagnosis of mild or moderate squamous dysplasia. Each case was matched on age (+/- 1 year) and gender to a control. Controls were defined as screening study participants with an endoscopic biopsy diagnosis of normal mucosa or esophagitis. DNA was extracted from frozen cell samples obtained by cytologic balloon examination and genotyped using standard methods. Individuals who were GSTM1 null (homozygous for GSTM1*0) were found to have a tendency for an increased risk of esophageal squamous dysplasia (odds ratio=2.6, 95% CI, 0.9-7.4). No excess risks were observed for inheritance of other putative at risk genotypes CYP1A1*2B, CYP2E1*6 or GSTT1*0. The risk associated with the inheritance of combined genotypes was not significantly different than the risk estimates from the univariate analysis. These results are consistent with the notion that exposure to environmental carcinogens that are detoxified by GSTM1, such as polycyclic aromatic hydrocarbons, may contribute to the etiology of esophageal cancer in Linxian. JF - Cancer letters AU - Roth, M J AU - Dawsey, S M AU - Wang, G AU - Tangrea, J A AU - Zhou, B AU - Ratnasinghe, D AU - Woodson, K G AU - Olivero, O A AU - Poirier, M C AU - Frye, B L AU - Taylor, P R AU - Weston, A AD - The Cancer Prevention Studies Branch, Division of Clinical Sciences, National Cancer Institute NIH, Bethesda, MD 20892, USA. mr166i@nih.gov Y1 - 2000/08/01/ PY - 2000 DA - 2000 Aug 01 SP - 73 EP - 81 VL - 156 IS - 1 SN - 0304-3835, 0304-3835 KW - Isoenzymes KW - 0 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Genotype KW - Risk KW - Humans KW - Carcinoma, Squamous Cell -- enzymology KW - Precancerous Conditions -- genetics KW - Carcinoma, Squamous Cell -- etiology KW - Esophageal Neoplasms -- enzymology KW - Precancerous Conditions -- etiology KW - Esophageal Neoplasms -- genetics KW - Carcinoma, Squamous Cell -- genetics KW - Glutathione Transferase -- genetics KW - Esophageal Neoplasms -- etiology KW - Isoenzymes -- genetics KW - Precancerous Conditions -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71162632?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Association+between+GSTM1*0+and+squamous+dysplasia+of+the+esophagus+in+the+high+risk+region+of+Linxian%2C+China.&rft.au=Roth%2C+M+J%3BDawsey%2C+S+M%3BWang%2C+G%3BTangrea%2C+J+A%3BZhou%2C+B%3BRatnasinghe%2C+D%3BWoodson%2C+K+G%3BOlivero%2C+O+A%3BPoirier%2C+M+C%3BFrye%2C+B+L%3BTaylor%2C+P+R%3BWeston%2C+A&rft.aulast=Roth&rft.aufirst=M&rft.date=2000-08-01&rft.volume=156&rft.issue=1&rft.spage=73&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 - 2000-07-31 N1 - Date created - 2000-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hypothalamic-Pituitary-Adrenal Axis Activity during Exercise in African American and Caucasian Women AN - 18331895; 5384516 AB - African American women have a greater prevalence of obesity than Caucasian women, but the reasons for this difference are not known. We have investigated whether activity of the hypothalamic-pituitary adrenal axis plays a role in this phenomenon. Previous studies have shown that plasma ACTH immunoreactivity (ACTH-IR) of African American women, measured after ovine CRH (oCRH) stimulation, is significantly greater than ACTH-IR of Caucasian women, but is not accompanied by greater plasma cortisol concentrations. Analysis by high pressure liquid chromatography has demonstrated that after oCRH stimulation, the plasma ACTH-IR of African American women contains many nonintact ACTH fragments not found in Caucasians. To determine whether these racial differences in ACTH-IR secretion are an artifact of exogenous oCRH administration or are also found after a physiological stimulus for ACTH secretion, we measured hormones of the hypothalamic-pituitary adrenal axis before and after a standardized, maximal exercise treadmill test in 16 African American and 19 Caucasian healthy women matched for age, socioeconomic status, and body mass index. The intensity of exercise performed was similar in the two groups, as determined by duration of exercise, perceived intensity of exertion, plasma lactate, maximal heart rate, and maximum oxygen uptake. Basal ACTH-IR measured by RIA or immunoradiometric assay and cortisol were similar in African Americans and Caucasians. Plasma ACTH-IR, measured 10 min after completion of exercise, was significantly greater in African Americans than in Caucasians [by RIA: mean plus or minus SD ACTH-IR, 47.1 plus or minus 30.9 vs. 25.4 plus or minus 16.7 pmol/L (P < 0.01); by immunoradiometric assay: ACTH-IR, 45.9 plus or minus 43.2 vs. 21.1 plus or minus 14.6 pmol/L (P < 0.05)]. However, plasma cortisol after exercise was not different (450.2 plus or minus 157.7 vs. 483.6 plus or minus 180.4 nmol/L; P = 0.57). We conclude that ACTH-IR is significantly greater in African American than in Caucasian women after intense exercise. The ACTH-IR of African Americans and Caucasians does not appear to be equipotent at adrenal melanocortin-2 receptors, because the greater ACTH-IR of African Americans does not lead to greater cortisol secretion. Whether some components of the ACTH-IR detected in African Americans affect signal transduction of the hypothalamic melanocortin-4 receptors implicated in body weight regulation and thus predispose African American women to weight gain without altering plasma cortisol remains to be determined. JF - Journal of Clinical Endocrinology and Metabolism AU - Yanovski, JA AU - Yanovski, S Z AU - Boyle, A J AU - Gold, P W AU - Sovik, K N AU - Sebring, NG AU - Drinkard, B AD - Unit on Growth and Obesity, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, MSC 1862, Building 10, Room 10N262, Bethesda, Maryland 20892-1862, USA, JYISi@NIH.Gov Y1 - 2000/08// PY - 2000 DA - Aug 2000 SP - 2660 EP - 2663 VL - 85 IS - 8 SN - 0021-972X, 0021-972X KW - Physical Education Index KW - Blacks KW - Physiological responses KW - Women KW - Brain KW - Exercise (effects) KW - Endocrine system KW - Hormones KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18331895?accountid=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+Clinical+Endocrinology+and+Metabolism&rft.atitle=Hypothalamic-Pituitary-Adrenal+Axis+Activity+during+Exercise+in+African+American+and+Caucasian+Women&rft.au=Yanovski%2C+JA%3BYanovski%2C+S+Z%3BBoyle%2C+A+J%3BGold%2C+P+W%3BSovik%2C+K+N%3BSebring%2C+NG%3BDrinkard%2C+B&rft.aulast=Yanovski&rft.aufirst=JA&rft.date=2000-08-01&rft.volume=85&rft.issue=8&rft.spage=2660&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Endocrinology+and+Metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Brain; Women; Physiological responses; Exercise (effects); Endocrine system; Hormones; Blacks ER - TY - JOUR T1 - Control of plasmid DNA replication by iterons: no longer paradoxical AN - 18245106; 5308307 AB - Replication origins of a family of bacterial plasmids have multiple sites, called iterons, for binding a plasmid-specific replication initiator protein. The iteron-initiator interactions are essential for plasmid replication as well as for inhibition of plasmid over-replication. The inhibition increases with plasmid copy number and eventually shuts plasmid replication off completely. The mechanism of inhibition appears to be handcuffing, the coupling of origins via iteron-bound initiators that block origin function. The probability of a trans-reaction such as handcuffing is expected to increase with plasmid copy number and diminish with increases in cell volume, explaining how the copy number can be maintained in a growing cell. Control is also exerted at the level of initiator synthesis and activation by chaperones. We propose that increases in active initiators promote initiation by overcoming handcuffing, but handcuffing dominates when the copy number reaches a threshold. Handcuffing should be ultrasensitive to copy number, as the negative control by iterons can be stringent (switch-like). JF - Molecular Microbiology AU - Chattoraj, D K AD - Laboratory of Biochemistry, NCI, NIH, Bethesda, MD 20892-4255, USA., dhrubac@sunspot.nci.nih.gov Y1 - 2000/08// PY - 2000 DA - Aug 2000 SP - 467 EP - 476 PB - Blackwell Science Ltd VL - 37 IS - 3 SN - 0950-382X, 0950-382X KW - iterons KW - handcuffing KW - copy number KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Replication KW - Chaperones KW - Plasmids KW - J 02760:Plasmids KW - N 14650:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18245106?accountid=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=Control+of+plasmid+DNA+replication+by+iterons%3A+no+longer+paradoxical&rft.au=Chattoraj%2C+D+K&rft.aulast=Chattoraj&rft.aufirst=D&rft.date=2000-08-01&rft.volume=37&rft.issue=3&rft.spage=467&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2000.01986.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Replication; Plasmids; Chaperones DO - http://dx.doi.org/10.1046/j.1365-2958.2000.01986.x ER - TY - JOUR T1 - BBID: the biological biochemical image database AN - 17901551; 5143128 AB - The Biological Biochemical Image Database is a WWW accessible relational database of archived images from research articles that describe regulatory pathways of higher eukaryotes. Pathway information is annotated and can be queried in the study of complex gene expression. In this way, complex regulatory pathways can be tested empirically in an efficient manner in the context of large-scale gene-expression systems. http://bbid.grc.nia.nih.gov. JF - Bioinformatics AU - Becker, K G AU - White, S L AU - Muller, J AU - Engel, J AD - DNA Array Unit, RRB, beckerk@grc.nia.nih.gov Y1 - 2000/08// PY - 2000 DA - Aug 2000 SP - 745 EP - 746 VL - 16 IS - 8 SN - 1367-4803, 1367-4803 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene expression KW - Eukaryotes KW - Databases KW - Image processing KW - Bioinformatics KW - Computer applications KW - W3 33080:Bioinformatics and computer applications KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17901551?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioinformatics&rft.atitle=BBID%3A+the+biological+biochemical+image+database&rft.au=Becker%2C+K+G%3BWhite%2C+S+L%3BMuller%2C+J%3BEngel%2C+J&rft.aulast=Becker&rft.aufirst=K&rft.date=2000-08-01&rft.volume=16&rft.issue=8&rft.spage=745&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bioinformatics; Computer applications; Databases; Image processing; Eukaryotes; Gene expression ER - TY - JOUR T1 - ComboScreen facilitates the multiplex hybridization-based screening of high-density clone arrays AN - 17897890; 5143119 AB - The construction of physical maps based on bacterial clones [e.g. bacterial artificial chromosomes (BACs)] is valuable for a number of molecular genetics applications, including the high-resolution mapping of genomic regions of interest and the identification of clones suitable for systematic sequencing. A common approach for large-scale screening of bacterial clone libraries involves the hybridization of high-density arrays of immobilized, lysed colonies with collections of DNA probes. The use of a multiplex hybridization screening strategy, whereby pooled probes are analysed en masse, simplifies the effort by reducing the total number of parallel experiments required. However, this approach generates large amounts of hybridization-based data that must be carefully analysed, assimilated, and disambiguated in a careful but efficient manner. To facilitate the screening of high-density clone arrays by a multiplex hybridization approach, we have written a program called ComboScreen. This program provides an organizational framework and analytical tools required for the high-throughput hybridization screening of clone arrays with pools of probes. We have used this program extensively for constructing mouse sequence-ready BAC contig maps. ComboScreen is freely available at http://genome.nhgri.nih.gov/comboscreen. JF - Bioinformatics AU - Jamison, D C AU - Thomas, J W AU - Green, ED AD - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA, cjamison@informaxinc.com Y1 - 2000/08// PY - 2000 DA - Aug 2000 SP - 678 EP - 684 VL - 16 IS - 8 SN - 1367-4803, 1367-4803 KW - screening KW - bacterial artificial chromosomes KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - DNA probes KW - Bioinformatics KW - Computer applications KW - Hybridization analysis KW - W3 33080:Bioinformatics and computer applications KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17897890?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioinformatics&rft.atitle=ComboScreen+facilitates+the+multiplex+hybridization-based+screening+of+high-density+clone+arrays&rft.au=Jamison%2C+D+C%3BThomas%2C+J+W%3BGreen%2C+ED&rft.aulast=Jamison&rft.aufirst=D&rft.date=2000-08-01&rft.volume=16&rft.issue=8&rft.spage=678&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bioinformatics; Computer applications; Hybridization analysis; DNA probes ER - TY - JOUR T1 - The ykgA gene of Escherichia coli AN - 17831302; 4865061 JF - Molecular Microbiology AU - Martin, G R AU - Gillette, K W AU - Rosner, L J AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Building 5, Room 333, National Institutes of Health, Bethesda, MD 20892-0560, USA. Y1 - 2000/08// PY - 2000 DA - Aug 2000 SP - 978 EP - 979 PB - Blackwell Science Ltd VL - 37 IS - 4 SN - 0950-382X, 0950-382X KW - ykgA gene KW - Microbiology Abstracts B: Bacteriology KW - Escherichia coli KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17831302?accountid=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=The+ykgA+gene+of+Escherichia+coli&rft.au=Martin%2C+G+R%3BGillette%2C+K+W%3BRosner%2C+L+J&rft.aulast=Martin&rft.aufirst=G&rft.date=2000-08-01&rft.volume=37&rft.issue=4&rft.spage=978&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&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 ER - TY - JOUR T1 - Three temporal classes of gene expression during the Chlamydia trachomatis developmental cycle AN - 17831247; 4865056 AB - The obligate intracellular bacterium Chlamydia trachomatis has a unique developmental cycle that involves functionally and morphologically distinct cell types adapted for extracellular survival and intracellular multiplication. Infection is initiated by an environmentally resistant cell type called an elementary body (EB). Over the first several hours of infection, EBs differentiate into a larger replicative form, termed the reticulate body (RB). Late in the infectious process, RBs asynchronously begin to differentiate back to EBs, which accumulate within the lumen of the inclusion until released from the host cell for subsequent rounds of infection. In an effort to characterize temporal gene expression in relation to the chlamydial developmental cycle, we have used quantitative-competitive polymerase chain reaction (QC-PCR) and reverse transcription (RT)-PCR techniques. These analyses demonstrate that C. trachomatis double their DNA content every 2-3 h, with synthesis beginning between 2 and 4 h after infection. We determined the onset of transcription of specific temporal classes of developmentally expressed genes. RT-PCR analysis was performed on several genes encoding key enzymes or components of essential biochemical pathways and functions. This comparison encompassed approximately 8% of open reading frames on the C. trachomatis genome. In analysis of total RNA samples harvested at 2, 6, 12 and 20 h after infection, using conditions under which a single chlamydial transcript per infected cell is detected, three major temporal classes of gene expression were resolved. Initiation of transcription appears to occur in three temporal classes which we have operationally defined as: early, which are detected by 2 h after infection during the germination of EBs to RBs; mid-cycle, which appear between 6 and 12 h after infection and represent transcripts expressed during the growth and multiplication of RBs; or late, which appear between 12 and 20 h after infection and represent those genes transcribed during the terminal differentiation of RBs to EBs. Collectively, the data suggest that chlamydial early gene functions are weighted toward initiation of macromolecular synthesis and the establishment of their intracellular niche by modification of the inclusion membrane. Surprisingly, representative enzymes of intermediary metabolism and structural proteins do not appear to be transcribed until 10-12 h after infection; coinciding with the onset of observed binary fission of RBs. Late gene functions appear to be predominately those associated with the terminal differentiation of RBs back to EBs. JF - Molecular Microbiology AU - Shaw, I E AU - Dooley, A C AU - Fischer, R E AU - Scidmore, A M AU - Fields, A K AU - Hackstadt, T AD - ost-Parasite Interactions Section, Laboratory of Intracellular Parasites and Microscopy Branch, National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, MT 59840, USA. Y1 - 2000/08// PY - 2000 DA - Aug 2000 SP - 913 EP - 925 PB - Blackwell Science Ltd VL - 37 IS - 4 SN - 0950-382X, 0950-382X KW - early gene KW - elementary body KW - late gene KW - reticulate body KW - temporal effects KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Germination KW - Gene expression KW - Gene regulation KW - Cell cycle KW - Transcription KW - Chlamydia trachomatis KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17831247?accountid=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=Three+temporal+classes+of+gene+expression+during+the+Chlamydia+trachomatis+developmental+cycle&rft.au=Shaw%2C+I+E%3BDooley%2C+A+C%3BFischer%2C+R+E%3BScidmore%2C+A+M%3BFields%2C+A+K%3BHackstadt%2C+T&rft.aulast=Shaw&rft.aufirst=I&rft.date=2000-08-01&rft.volume=37&rft.issue=4&rft.spage=913&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&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 - Chlamydia trachomatis; Transcription; Gene expression; Gene regulation; Cell cycle; Germination ER - TY - JOUR T1 - Isolation and Characterization of Myrianthus holstii Lectin, a Potent HIV-1 Inhibitory Protein from the Plant Myrianthus holstii AN - 17766877; 4822988 AB - Aqueous extracts from the African plant Myrianthus holstii potently inhibited the infection of the T-lymphoblastoid cell line, CEM-SS, by human immunodeficiency virus-1 sub(RF) (HIV-1 sub(RF)). The active constituent, M. holstii lectin (MHL), was purified by LH-20 column chromatography and reversed phase HPLC. MHL, a 9284-Da cysteine-rich protein, was characterized by amino acid analysis, N-terminal sequencing, ESIMS, and matrix-assisted laser-desorption ionization-time-of-flight mass spectrometry. Pure MHL had anti-HIV activity, with an EC sub(50) value of 150 nM. Delaying the addition of MHL for up to 8 h after initial exposure of CEM-SS cells to virus did not result in loss of the antiviral activity; however, if addition of the compound was delayed for 16 h or more, there was a marked decrease in the antiviral activity. MHL bound to a virus-free, soluble form of the viral envelope protein gp 120 but did not inhibit the subsequent binding to a cell-free, soluble form of the cellular receptor CD4. JF - Journal of Natural Products AU - Charan, R D AU - Munro, MHG AU - O'Keefe, B R AU - Sowder, RC II AU - McKee, T C AU - Currens, MJ AU - Pannell, L K AU - Boyd, M R AD - Laboratory of Drug Discovery Research and Development, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick Cancer Research and Development Center, Building 1052, Room 121, Frederick, Maryland, 21702-1201, USA, boyd@dtpax2.ncifcrf.gov Y1 - 2000/08// PY - 2000 DA - Aug 2000 SP - 1170 EP - 1174 VL - 63 IS - 8 SN - 0163-3864, 0163-3864 KW - amino acid sequence KW - HIV-1 KW - CEM-SS cells KW - MHL KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - High-performance liquid chromatography KW - Column chromatography KW - Lectins KW - Mass spectroscopy KW - Antiviral agents KW - Myrianthus holstii KW - Human immunodeficiency virus 1 KW - Plant extracts KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01068:Antiviral & viricidal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17766877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Natural+Products&rft.atitle=Isolation+and+Characterization+of+Myrianthus+holstii+Lectin%2C+a+Potent+HIV-1+Inhibitory+Protein+from+the+Plant+Myrianthus+holstii&rft.au=Charan%2C+R+D%3BMunro%2C+MHG%3BO%27Keefe%2C+B+R%3BSowder%2C+RC+II%3BMcKee%2C+T+C%3BCurrens%2C+MJ%3BPannell%2C+L+K%3BBoyd%2C+M+R&rft.aulast=Charan&rft.aufirst=R&rft.date=2000-08-01&rft.volume=63&rft.issue=8&rft.spage=1170&rft.isbn=&rft.btitle=&rft.title=Journal+of+Natural+Products&rft.issn=01633864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Myrianthus holstii; Lectins; Antiviral agents; Plant extracts; Column chromatography; High-performance liquid chromatography; Mass spectroscopy ER - TY - JOUR T1 - Toxicokinetics of Phenolphthalein in Male and Female Rats and Mice AN - 17730048; 4796625 AB - Phenolphthalein (PTH), which has been used as the active ingredient in a number of prescription and over-the-counter laxative products, is a rodent chemical carcinogen in multiple organs in the NTP 2-year bioassay at doses of 291-2927 mg/kg. This paper describes the toxicokinetics and estimates the internal dose of PTH administered as a single iv or gavage dose, or ad libitum for 14 days in feed to F344 rats, B6C3F1 mice, p53 (+/-) mice, and C57BL mice at doses that bracketed those used in the bioassay. Plasma concentrations for free phenolphthalein (PTH-F) and phenolphthalein glucuronide (PTH-G) were obtained for each dose regimen. Total phenolphthalein (PTH-T) was calculated as the sum of the molar concentrations of PTH-F and PTH-G. Noncompartmental pharmacokinetic models were used to calculate the area under the curve (AUC) from 0 h to infinity (AUC arrow left ), clearance (Cl), and oral bioavailability (F) for PTH-F; and were used to calculate AUC arrow left , t super( one half ), and relative absorption (Q) for PTH-T. After iv administration, PTH-F rapidly declined in rats and mice; PTH-T rose rapidly to Cmax and slowly declined 6-8 h after dosing, with no sex-related differences for rats or mice. For feed studies, mean plasma concentration (C arrow left ) and 24-h area under the curve (AUC sub(24h)) values were calculated. Results from feed studies showed no dose response in rat plasma PTH-F above similar to 50 mg/kg. Rat PTH-T AUC sub(24h) and C arrow left were linear with doses up to similar to 650 mg/kg. In B6C3F1 mice, PTH-F and PTH-T AUC sub(24h) increased nonlinearly with doses above similar to 165 mg/kg. PTH is well absorbed and readily converted to PTH-G when administered in feed to rats and mice, except at the highest bioassay doses, where PTH absorption may be saturated. JF - Toxicological Sciences AU - Collins, B J AU - Grizzle, T B AU - Dunnick, J K AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709-2233, USA Y1 - 2000/08// PY - 2000 DA - Aug 2000 SP - 271 EP - 281 VL - 56 IS - 2 SN - 1096-6080, 1096-6080 KW - toxicokinetics KW - rats KW - mice KW - phenolphthalein KW - phenolphthalein glucuronide KW - Toxicology Abstracts KW - Laxatives KW - X 24114:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17730048?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Toxicokinetics+of+Phenolphthalein+in+Male+and+Female+Rats+and+Mice&rft.au=Collins%2C+B+J%3BGrizzle%2C+T+B%3BDunnick%2C+J+K&rft.aulast=Collins&rft.aufirst=B&rft.date=2000-08-01&rft.volume=56&rft.issue=2&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Laxatives ER - TY - JOUR T1 - Metals and Disorders of Cell Accumulation: Modulation of Apoptosis and Cell Proliferation AN - 17725379; 4796623 AB - As a class of agents, toxic metals are a concern of the highest priority for human exposure. The metals have a vast array of remarkably adverse effects, including those of carcinogenicity, neurotoxicity, and immunotoxicity. Apoptotic cell death should be considered as an ongoing, normal event in the control of cell populations. However, apoptosis can also be induced by a variety of toxicants, including many of the toxic inorganics, resulting in the loss of affected cell populations. Understanding the mechanisms by which metals induce disorders of cell accumulation will be important in defining their toxic potentials in exposed populations. In an attempt to illuminate some of the most recent developments in metal-induced disorders of cell accumulation, a symposium on this topic was held at the 1999 Annual Meeting of the Society of Toxicology. JF - Toxicological Sciences AU - Waalkes, M P AU - Fox, DA AU - States, J C AU - Patierno AU - McCabe, MJ Jr AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at National Institute of Environmental Health Sciences, 111 Alexander Drive, P.O. Box 12233, MD F0-09, Research Triangle Park, NC, USA Y1 - 2000/08// PY - 2000 DA - Aug 2000 SP - 255 EP - 261 VL - 56 IS - 2 SN - 1096-6080, 1096-6080 KW - Toxicology Abstracts KW - Immunotoxicity KW - Apoptosis KW - Carcinogenicity KW - Heavy metals KW - Neurotoxicity KW - Cell proliferation KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17725379?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Metals+and+Disorders+of+Cell+Accumulation%3A+Modulation+of+Apoptosis+and+Cell+Proliferation&rft.au=Waalkes%2C+M+P%3BFox%2C+DA%3BStates%2C+J+C%3BPatierno%3BMcCabe%2C+MJ+Jr&rft.aulast=Waalkes&rft.aufirst=M&rft.date=2000-08-01&rft.volume=56&rft.issue=2&rft.spage=255&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Heavy metals; Apoptosis; Cell proliferation; Carcinogenicity; Neurotoxicity; Immunotoxicity ER - TY - JOUR T1 - A potential mechanism for fumonisin B sub(1)-mediated hepatocarcinogenesis: cyclin D1 stabilization associated with activation of Akt and inhibition of GSK-3 beta activity AN - 17633495; 4768396 AB - Fumonisin B sub(1) (FB sub(1)) is a worldwide corn contaminant and has been epidemiologically linked to the high incidence of human esophageal cancer in South Africa and China. FB sub(1) is hepatocarcinogenic in rats by an unknown mechanism. Inhibition of ceramide synthase and disruption of membrane phospholipids have been shown to be mechanisms of toxicity. Here we show overexpression of cyclin D1 protein in both preneoplastic and neoplastic liver specimens obtained from a long-term feeding study of FB sub(1) in rats. In rats fed FB sub(1) short-term, cyclin D1 protein levels in liver were increased up to five-fold in a dose-responsive manner. Northern blot analysis demonstrated no increase in mRNA levels of cyclin D1. 2D electrophoresis of cyclin D1 protein in FB sub(1)-treated samples showed a distinct pattern of migration (presence of less negatively charged form of the protein) that differed from controls. Recently, it has been shown that phosphorylation of cyclin D1 by glycogen synthase kinase 3 beta (GSK-3 beta ) on a single threonine residue (Thr-286) positively regulates proteosomal degradation of cyclin D1. In FB sub(1)-treated samples we detected GSK-3 beta phosphorylated on serine 9; activated protein kinase B (Akt) appears to be responsible for this activity-inhibiting phosphorylation. These findings suggest that overexpression of cyclin D1 results from stabilization due to a lack of phosphorylation mediated by GSK-3 beta . We also observed an increase in cyclin dependent kinase 4 (Cdk4) complexes with cyclin D1 in FB sub(1)-treated samples; additionally, elevated Cdk4 activity was shown by increased phosphorylation of the retinoblastoma protein. In summary, the activation of Akt leads to increased survival, inhibition of GSK-3 beta activity and post-translational stabilization of cyclin D1, all events responsible for disruption of the cell cycle G sub(1)/S restriction point in hepatocytes. This is the first report suggesting the mechanism by which FB sub(1) acts as a carcinogen. JF - Carcinogenesis AU - Ramljak, D AU - Calvert, R J AU - Wiesenfeld, P W AU - Diwan, BA AU - Catipovic, B AU - Marasas, WFO AU - Victor, T C AU - Anderson, L M AU - Gelderblom, WCA AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Building 538, Room 205E, Frederick, MD 21702, USA Y1 - 2000/08// PY - 2000 DA - Aug 2000 SP - 1537 EP - 1546 VL - 21 IS - 8 SN - 0143-3334, 0143-3334 KW - rats KW - Akt gene KW - cyclin D1 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Toxicology Abstracts; Oncogenes & Growth Factors Abstracts KW - Cell cycle KW - Cancer KW - Mycotoxins KW - Phosphorylation KW - Carcinogenicity KW - Carcinogenesis KW - Liver KW - Proteins KW - Fumonisin B1 KW - Cyclin D KW - B 26242:Cyclins and cyclin-dependent kinases KW - K 03082:Mycotoxins KW - X 24171:Microbial UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17633495?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=A+potential+mechanism+for+fumonisin+B+sub%281%29-mediated+hepatocarcinogenesis%3A+cyclin+D1+stabilization+associated+with+activation+of+Akt+and+inhibition+of+GSK-3+beta+activity&rft.au=Ramljak%2C+D%3BCalvert%2C+R+J%3BWiesenfeld%2C+P+W%3BDiwan%2C+BA%3BCatipovic%2C+B%3BMarasas%2C+WFO%3BVictor%2C+T+C%3BAnderson%2C+L+M%3BGelderblom%2C+WCA&rft.aulast=Ramljak&rft.aufirst=D&rft.date=2000-08-01&rft.volume=21&rft.issue=8&rft.spage=1537&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycotoxins; Fumonisin B1; Carcinogenicity; Cell cycle; Liver; Cancer; Cyclin D; Proteins; Phosphorylation; Carcinogenesis ER - TY - JOUR T1 - Diverse chemical carcinogens fail to induce G sub(1) arrest in MCF-7 cells AN - 17633318; 4768404 AB - The effect of three reactive potent chemical carcinogens on the passage of MCF-7 cells through the cell cycle was investigated. While these cells, which express wild-type p53, were arrested in G sub(1) after treatment with actinomycin D (a positive control), treatment with anti-benzo[a]pyrene dihydrodiol epoxide, N-acetoxy-N-2-fluorenylacetamide or N-methyl-N'-nitro-N-nitrosoguanidine, at doses consistent with survival of significant numbers of cells, caused the cells to accumulate in S phase, with little increase in those in G sub(1). This property of these three reactive potent carcinogens, of diverse chemical types, to induce evasion of G sub(1) arrest (the stealth property) presumably increases the likelihood of malignant change, because DNA replication continues on a damaged template. This stealth characteristic may be a major contributor to the tumorigenicity of DNA-adducting chemical carcinogens in general. JF - Carcinogenesis AU - Khan, Q A AU - Dipple, A AD - Laboratory of Comparative Carcinogenesis and National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA Y1 - 2000/08// PY - 2000 DA - Aug 2000 SP - 1611 EP - 1618 VL - 21 IS - 8 SN - 0143-3334, 0143-3334 KW - MCF-7 cells KW - tumor cell lines KW - N-Acetoxy-N-2-fluorenylacetamide KW - N-Methyl-N'-nitro-N-nitrosoguanidine KW - benzo(a)pyrene-dihydrodiol epoxide KW - Toxicology Abstracts KW - DNA adducts KW - G phase KW - Carcinogens KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17633318?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Diverse+chemical+carcinogens+fail+to+induce+G+sub%281%29+arrest+in+MCF-7+cells&rft.au=Khan%2C+Q+A%3BDipple%2C+A&rft.aulast=Khan&rft.aufirst=Q&rft.date=2000-08-01&rft.volume=21&rft.issue=8&rft.spage=1611&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Carcinogens; G phase; DNA adducts ER - TY - JOUR T1 - Chronic methamphetamine exposure decreases high affinity uptake function in norepinephrine afferents in the cerebellar cortex: An electrophysiological and electrochemical study AN - 17631826; 4773277 AB - It has been reported that chronic methamphetamine (MA) treatment decreases monoamine release in different brain regions. However, the clearance of norepinephrine (NE) after chronic MA intake is not clear. In the present study, we administered MA to Sprague-Dawley rats for 1 month. The animals were later anesthetized with urethane for electrophysiological recording. Previous studies have indicated that gamma -aminobutyric acid (GABA)-induced electrophysiological responses are enhanced by norepinephrine (NE) acting via postsynaptic beta -adrenergic receptors. We found that local application of the NE high affinity uptake inhibitor desmethylimipramine (DMI) significantly potentiated GABA-induced electrophysiological depressions in cerebellar Purkinje neurons in control rats. In contrast, DMI did not augment GABA responses in rats chronically treated with MA for 1 month, or in rats withdrawn from MA for 7-14 days after a 1-month MA treatment. To further examine if DMI-induced GABA modulation is altered by post- or pre-synaptic mechanisms in chronic MA-treated rats, we examined the electrophysiological interaction of GABA and isoproterenol (ISO), a postsynaptic beta -adrenergic receptor agonist, in Purkinje neurons. We found that GABA-induced inhibition is potentiated by local application of ISO in both control and chronic MA rats, suggesting that the reduction in DMI/GABA interactions is probably not mediated through post-synaptic noradrenergic mechanisms. Presynaptic NE clearance was further examined using in vivo chronoamperometric methods. Extracellular NE levels in the cerebellar cortex were measured using Nafion-coated carbon fiber sensors. We found that local application of DMI inhibited NE clearance in control rats, but not in chronic MA animals, suggesting that presynaptic NE clearance is reduced after chronic MA treatment. In addition, NE levels in cerebellar tissue were measured using HPLC-ECD. The NE concentration was significantly decreased in chronic MA rats. Taken together, our data suggest that regulation of uptake by DMI at central noradrenergic nerve terminals is abnormal after chronic MA exposure. JF - Neuropharmacology AU - Wang, Y AU - Chou, J AU - Jeng, C-H AU - Morales, M AU - Wang, J Y AD - National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, ywang@intra.nida.nih.gov Y1 - 2000/08// PY - 2000 DA - Aug 2000 SP - 2112 EP - 2123 VL - 39 IS - 11 SN - 0028-3908, 0028-3908 KW - rats KW - chronic exposure KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Cerebellum KW - Adrenergic nerves KW - ^g-Aminobutyric acid KW - Methamphetamine KW - Nerve endings KW - Chronic exposure KW - Norepinephrine KW - Purkinje cells KW - N3 11106:Neurobiology of drug abuse KW - X 24112:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17631826?accountid=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=Neuropharmacology&rft.atitle=Chronic+methamphetamine+exposure+decreases+high+affinity+uptake+function+in+norepinephrine+afferents+in+the+cerebellar+cortex%3A+An+electrophysiological+and+electrochemical+study&rft.au=Wang%2C+Y%3BChou%2C+J%3BJeng%2C+C-H%3BMorales%2C+M%3BWang%2C+J+Y&rft.aulast=Wang&rft.aufirst=Y&rft.date=2000-08-01&rft.volume=39&rft.issue=11&rft.spage=2112&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=00283908&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 - Methamphetamine; Norepinephrine; Nerve endings; Adrenergic nerves; Cerebellum; Purkinje cells; Chronic exposure; ^g-Aminobutyric acid ER - TY - JOUR T1 - Serum carotenoids are associated with increased lung cancer risk among alcohol drinkers, but not among non-drinkers in a cohort of tin miners AN - 17622586; 4768745 AB - To examine the association between pre-diagnostic serum carotenoid levels and lung cancer risk and the effects of alcohol intake on the carotenoid-lung cancer relationship, we conducted a case-control study in an occupational cohort from the Yunnan Tin Corporation in China. During 6 years of follow-up, 339 cases of confirmed lung cancer were diagnosed. Among these cases, those who donated pre-diagnostic blood (n = 108) were eligible for this study. For each case, two individuals alive and free of cancer at the time of case diagnosis, matched on age, sex, and date of blood collection, were selected as controls. Serum beta -carotene (odds ratios (ORs) for tertiles: 1, 1.3, 2.0) and beta -cryptoxanthin (ORs for tertiles: 1, 1.8, 2.9) levels were positively associated with lung cancer risk after adjustment for tobacco use and radon exposure. Among alcohol drinkers, higher serum carotenoid levels were significantly associated with increased lung cancer risk ( alpha -carotene OR 2.2, 95% confidence interval (CI) 1.1-4.4, beta -carotene OR 7.6, 95% CI 3.1-18.6, lutein/zeaxanthin OR 2.3, 95% CI 1.2-6.6 and beta -cryptoxanthin OR 7.6, 95% CI 2.7-21.5). Conversely, risk estimates among non-drinkers suggest a possible protective association for higher carotenoid levels. JF - Alcohol and Alcoholism AU - Ratnasinghe, D AU - Forman, M R AU - Tangrea, JA AU - Qiao, Y AU - Yao, S-X AU - Gunter, E W AU - Barrett, MJ AU - Giffen, CA AU - Erozan, Y AU - Tockman AU - Taylor, PR AD - Cancer Prevention Studies Branch, DCS, NCI, 6006 Executive Blvd, Suite 321, Bethesda, MD 20892-7058, USA Y1 - 2000/08// PY - 2000 DA - Aug 2000 SP - 355 EP - 360 VL - 35 IS - 4 SN - 0735-0414, 0735-0414 KW - man KW - serum levels KW - alpha -Carotene KW - Toxicology Abstracts KW - ^a-Carotene KW - Risk assessment KW - ^b-Carotene KW - Lung KW - Carcinogenesis KW - Mining KW - Tin KW - Ethanol KW - X 24162:Chronic exposure KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17622586?accountid=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+and+Alcoholism&rft.atitle=Serum+carotenoids+are+associated+with+increased+lung+cancer+risk+among+alcohol+drinkers%2C+but+not+among+non-drinkers+in+a+cohort+of+tin+miners&rft.au=Ratnasinghe%2C+D%3BForman%2C+M+R%3BTangrea%2C+JA%3BQiao%2C+Y%3BYao%2C+S-X%3BGunter%2C+E+W%3BBarrett%2C+MJ%3BGiffen%2C+CA%3BErozan%2C+Y%3BTockman%3BTaylor%2C+PR&rft.aulast=Ratnasinghe&rft.aufirst=D&rft.date=2000-08-01&rft.volume=35&rft.issue=4&rft.spage=355&rft.isbn=&rft.btitle=&rft.title=Alcohol+and+Alcoholism&rft.issn=07350414&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 - ^b-Carotene; Ethanol; Risk assessment; Lung; Tin; Carcinogenesis; Mining ER - TY - JOUR T1 - Use of Polyethylenimine-Adenovirus Complexes to Examine Triplex Formation in Intact Cells AN - 17617925; 4761471 AB - Triplex-forming oligonucleotides (TFOs) show potential for sequence-specific DNA binding and inhibition of gene expression. We have applied this antigene strategy using a TFO incorporating an Auger-emitting radionucleotide, super(125)I, to study the production of double-strand breaks (dsb) in the rat aquaporin 5 (rAQP5) cDNA. super(125)I-TFO bound to the pCMVrAQP5 plasmid in vitro in a dose-dependent manner and formed stable triplexes up to 65 degree C and in the presence of 140 mM KCl. Further, super(125)I-TFO resulted in a predictable dsb when analyzed by Southern hybridization. To deliver TFOs to epithelial cells, we employed super(125)I-TFO-polyethyleneimine-adenovirus ( super(125)I-TFO-PEI-Ad) complexes. We hypothesized that these complexes would take advantage of adenoviral characteristics to transfer super(125)I-TFO to the cell nucleus. Adenovirus-containing complexes brought about greater uptake and nuclear localization of TFOs compared with delivery with super(125)I-TFO-PEI complexes alone. No significant degradation of super(125)I-TFO was found after delivery into cells using PEI-Ad complexes and freezing and thawing. We next used PEI-Ad complexes to deliver super(125)I-TFO and pCMVrAQP5 separately to epithelial cells to determine if triplexes can form de novo within cells, resulting in the specific dsb in the rAQP5 cDNA. After delivery, cell pellets were stored at -80 degree C for more than 60 days. Thereafter, plasmid DNA was isolated from cells and analyzed for dsb by Southern hybridization. However, none were detected. We conclude that under the experimental conditions employed, effective triplexes, with super(125)I-TFO and pCMVrAQP5, do not form de novo inside cells. JF - Antisense and Nucleic Acid Drug Development AU - Hoque, ATMS AU - Sedelnikova, O A AU - Luu, AN AU - Swaim, W D AU - Panyutin, I G AU - Baum, B J AD - GTTB, NIDCR, NIH, Building 10, Room 1N113, MSC-1190, Bethesda, MD 20892-1190, USA Y1 - 2000/08// PY - 2000 DA - Aug 2000 SP - 229 EP - 241 VL - 10 IS - 4 SN - 1087-2906, 1087-2906 KW - rats KW - triplexes KW - Adenovirus KW - Polyethyleneimine KW - Polyethylenimine KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Expression vectors KW - Epithelial cells KW - DNA damage KW - Gene manipulation KW - Oligonucleotides KW - W3 33243:Molecular methods KW - N 14250:Biological properties KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17617925?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antisense+and+Nucleic+Acid+Drug+Development&rft.atitle=Use+of+Polyethylenimine-Adenovirus+Complexes+to+Examine+Triplex+Formation+in+Intact+Cells&rft.au=Hoque%2C+ATMS%3BSedelnikova%2C+O+A%3BLuu%2C+AN%3BSwaim%2C+W+D%3BPanyutin%2C+I+G%3BBaum%2C+B+J&rft.aulast=Hoque&rft.aufirst=ATMS&rft.date=2000-08-01&rft.volume=10&rft.issue=4&rft.spage=229&rft.isbn=&rft.btitle=&rft.title=Antisense+and+Nucleic+Acid+Drug+Development&rft.issn=10872906&rft_id=info:doi/10.1089%2F108729000421411 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adenovirus; DNA damage; Oligonucleotides; Gene manipulation; Expression vectors; Epithelial cells DO - http://dx.doi.org/10.1089/108729000421411 ER - TY - JOUR T1 - DNA vaccines: a key for inducing long-term cellular immunity AN - 17604552; 4744295 AB - Over the past few years, major advances in several areas of immunology have provided a foundation for the rational design of vaccines against diseases requiring cellular immunity. Among these advances are the cellular mechanisms by which DNA vaccines can sustain long-term humoral and cellular immunity. JF - Current Opinion in Immunology AU - Gurunathan, S AU - Wu, C-Y AU - Freidag, B L AU - Seder, R A AD - Clinical Immunology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Room 10/11C215, Bethesda, MD 20892, USA, rseder@niaid.nih.gov Y1 - 2000/08// PY - 2000 DA - Aug 2000 SP - 442 EP - 447 VL - 12 IS - 4 SN - 0952-7915, 0952-7915 KW - immunology KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Immune response (cell-mediated) KW - DNA vaccines KW - Reviews KW - Vaccines KW - F 06807:Active immunization KW - W3 33345:DNA vaccines KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17604552?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Opinion+in+Immunology&rft.atitle=DNA+vaccines%3A+a+key+for+inducing+long-term+cellular+immunity&rft.au=Gurunathan%2C+S%3BWu%2C+C-Y%3BFreidag%2C+B+L%3BSeder%2C+R+A&rft.aulast=Gurunathan&rft.aufirst=S&rft.date=2000-08-01&rft.volume=12&rft.issue=4&rft.spage=442&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Immunology&rft.issn=09527915&rft_id=info:doi/10.1016%2FS0952-7915%2800%2900118-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA vaccines; Vaccines; Immune response (cell-mediated); Reviews DO - http://dx.doi.org/10.1016/S0952-7915(00)00118-7 ER - TY - JOUR T1 - Antibodies for the prevention and treatment of viral diseases AN - 17568016; 4764958 AB - This paper reviews current use and evolving role of polyclonal and monoclonal antibody products for the prevention and treatment of viral diseases. Antibodies continue to be indicated for prophylaxis either prior to an anticipated exposure especially in situations of travel, or more commonly following an exposure. The predominant indication for use of antibody products is to prevent infection. With the availability of vaccines for the prevention of chickenpox, hepatitis A, hepatitis B, measles, rabies and smallpox, the role of passive immunization is reserved for susceptible individuals and those at high risk for complications of infection. Risks of transmission of infections associated with use of human plasma-derived products have been reduced by improvements in donor screening and virus removal and inactivation procedures. An additional safety concern has been addressed by the removal of thimerosal as a preservative. Within the last 5 years, two antibodies have been licensed for a viral indication, RespiGam and Synagis both for prevention of respiratory syncytial virus infection. RespiGam is a human plasma derived antibody and Synagis is a humanized monoclonal antibody, the first such antibody to be licensed for an infectious disease indication. CytoGam registered for prevention of cytomegalovirus infection in kidney transplant patients has recently been granted an expanded indication to include use in lung, liver, pancreas and heart transplant patients. As the use of therapeutics becomes more sophisticated, researchers may find better ways of using antibody products. JF - Antiviral Research AU - Sawyer, LA AD - Virology Branch, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 6700B Rockledge Drive, MSC-7630, Bethesda, MD 20892-7630 USA Y1 - 2000/08/01/ PY - 2000 DA - 2000 Aug 01 SP - 57 EP - 77 PB - Elsevier VL - 47 IS - 2 SN - 0166-3542, 0166-3542 KW - viruses KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Transplantation KW - Monoclonal antibodies KW - Measles KW - Immunity (passive) KW - Smallpox KW - Respiratory syncytial virus KW - Antibodies KW - Infectious diseases KW - Reviews KW - Rabies KW - Polyclonal antibodies KW - Hepatitis B KW - Hepatitis A KW - Immunization (passive) KW - Varicella KW - W3 33375:Antibodies KW - V 22096:Immunization: Passive KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17568016?accountid=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=Antiviral+Research&rft.atitle=Antibodies+for+the+prevention+and+treatment+of+viral+diseases&rft.au=Sawyer%2C+LA&rft.aulast=Sawyer&rft.aufirst=LA&rft.date=2000-08-01&rft.volume=47&rft.issue=2&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=Antiviral+Research&rft.issn=01663542&rft_id=info:doi/10.1016%2FS0166-3542%2800%2900111-X LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Respiratory syncytial virus; Infectious diseases; Antibodies; Varicella; Hepatitis A; Smallpox; Hepatitis B; Measles; Rabies; Immunization (passive); Transplantation; Reviews; Polyclonal antibodies; Monoclonal antibodies; Immunity (passive) DO - http://dx.doi.org/10.1016/S0166-3542(00)00111-X ER - TY - JOUR T1 - Identification of Saliva-Regulated Genes of Streptococcus gordonii DL1 by Differential Display Using Random Arbitrarily Primed PCR AN - 17562332; 4746036 AB - Attachment of Streptococcus gordonii to the acquired pellicle of the tooth surface involves specific interactions between bacterial adhesins and adsorbed salivary components. To study saliva-regulated gene expression in S. gordonii, we used random arbitrarily primed PCR (RAP-PCR). Bacteria were incubated in either brain heart infusion medium or saliva. Total RNA from both conditions was purified and RAP fingerprinted and then PCR amplified with an arbitrary primer. The differentially displayed DNA fragments were cloned, sequenced, and analyzed using the BLAST search network service. Three DNA products were up-regulated. One was identified as that of the sspA and -B genes, which encode the salivary agglutinin glycoprotein-binding proteins SspA and SspB of S. gordonii; another had 79% identity with the Lactococcus lactis clpE gene, encoding a member of the Clp protease family; and the third product showed no significant homology to known genes. Five down-regulated genes were identified which encode proteins involved in bacterial metabolism. We have shown, for the first time, direct induction of sspA and -B in S. gordonii by human saliva. JF - Infection and Immunity AU - Du, L D AU - Kolenbrander, P E AD - National Institutes of Health/NIDCR, Bldg. 30, Room 310, 30 Convent Dr., MSC 4350, Bethesda, MD 20892-4350, USA, pkolenbrander@dir.nidcr.nih.gov Y1 - 2000/08// PY - 2000 DA - Aug 2000 SP - 4834 EP - 4837 VL - 68 IS - 8 SN - 0019-9567, 0019-9567 KW - SspA protein KW - SspB protein KW - sspA gene KW - sspB gene KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Streptococcus gordonii KW - Gene regulation KW - Saliva KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17562332?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Identification+of+Saliva-Regulated+Genes+of+Streptococcus+gordonii+DL1+by+Differential+Display+Using+Random+Arbitrarily+Primed+PCR&rft.au=Du%2C+L+D%3BKolenbrander%2C+P+E&rft.aulast=Du&rft.aufirst=L&rft.date=2000-08-01&rft.volume=68&rft.issue=8&rft.spage=4834&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.68.8.4834-4837.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus gordonii; Saliva; Gene regulation DO - http://dx.doi.org/10.1128/IAI.68.8.4834-4837.2000 ER - TY - JOUR T1 - Adeno-associated virus (AAV)-3-based vectors transduce haematopoietic cells not susceptible to transduction with AAV-2-based vectors AN - 17554004; 4736815 AB - Although adeno-associated virus (AAV)-2 has a broad tissue-host range and can transduce a wide variety of tissue types, some cells, such as erythro- megakaryoblastoid cells, are non-permissive and appear to lack the AAV-2 receptor. However, limited studies have been reported with the related dependovirus AAV-3. We have previously cloned this virus, characterized its genome and produced an infectious clone. In this study, the gene for green fluorescent protein (GFP) was inserted into AAV-2- and AAV-3-based plasmids and recombinant viruses were produced. These viruses were then used to transduce haematopoietic cells and the transduction efficiencies were compared. In contrast to recombinant (r) AAV-2, rAAV-3 successfully transduced erythroid and megakaryoblastoid cells, although rAAV- 2 was superior in transduction of lymphocyte-derived cell lines. Recently, it was reported that heparan sulphate can act as a receptor of AAV-2. The infectivity of rAAV-2 and rAAV-3 was tested with mutant cell lines of Chinese hamster ovary cells that were defective for heparin or heparan sulphate expression on the cell surface. There was no correlation between the ability of rAAV-2 or rAAV-3 to infect cells and the cell surface expression of heparan sulphate and, although heparin blocked both rAAV-2 and rAAV-3 transduction, the ID sub(50) of rAAV- 3 was higher than that of rAAV-2. In addition, virus- binding overlay assays indicated that AAV-2 and AAV-3 bound different membrane proteins. These results suggest not only that there are different cellular receptors for AAV-2 and AAV-3, but that rAAV-3 vectors may be preferred for transduction of some haematopoietic cell types. JF - Journal of General Virology AU - Handa, A AU - Muramatsu, S AU - Qiu, J AU - Mizukami, H AU - Brown, KE AD - Hematology Branch, National Heart, Lung and Blood Institute, Bldg 10/Rm 7C218, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-1652, USA, handaa@nih.gov Y1 - 2000/08// PY - 2000 DA - Aug 2000 SP - 2077 EP - 2084 VL - 81 IS - 8 SN - 0022-1317, 0022-1317 KW - receptors KW - adeno-associated virus 2 KW - green fluorescent protein KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Gene therapy KW - Receptors KW - Cloning vectors KW - Membrane proteins KW - Plasmids KW - Adeno-associated virus 2 KW - Adeno-associated virus 3 KW - Gene transfer KW - Hemopoiesis KW - Hemopoietic system KW - Transduction KW - Dependovirus KW - W3 33181:Gene therapy vectors KW - V 22050:Viral genetics including virus reactivation KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17554004?accountid=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+General+Virology&rft.atitle=Adeno-associated+virus+%28AAV%29-3-based+vectors+transduce+haematopoietic+cells+not+susceptible+to+transduction+with+AAV-2-based+vectors&rft.au=Handa%2C+A%3BMuramatsu%2C+S%3BQiu%2C+J%3BMizukami%2C+H%3BBrown%2C+KE&rft.aulast=Handa&rft.aufirst=A&rft.date=2000-08-01&rft.volume=81&rft.issue=8&rft.spage=2077&rft.isbn=&rft.btitle=&rft.title=Journal+of+General+Virology&rft.issn=00221317&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adeno-associated virus 3; Adeno-associated virus 2; Dependovirus; Cloning vectors; Transduction; Gene transfer; Hemopoiesis; Gene therapy; Plasmids; Hemopoietic system; Membrane proteins; Receptors ER - TY - JOUR T1 - Thymosinalpha1 is chemopreventive for lung adenoma formation in A/J mice. AN - 71136393; 10822126 AB - The effects of thymosin (THN) alpha1 were investigated using the urethane injection carcinogenesis A/J mouse model. Lung adenomas were observed 2.5, 3, and 4 months after urethane injection (400 mg/kg i.p.) into female A/J mice. Daily administration of THNalpha1 (0.4 mg/kg, s.c.) reduced lung adenoma multiplicity significantly, by approximately 45, 40, and 17%, respectively, 2.5, 3, and 4 months after urethane injection. Animals treated with THNalpha1 had a significantly greater white cell density than control A/J mice. Endogenous THNalpha1-like peptides were detected in the mouse lung. By radioimmunoassay and by Western blot, prothymosin alpha was detected in the mouse lung. By immunocytochemistry, THNalpha1-like peptides were detected in all lung compartments including the bronchus, adenoma, bronchioles, and alveoli. These results indicate that exogenous THNalpha1 prevents lung carcinogenesis in A/J mice. JF - Cancer letters AU - Moody, T W AU - Leyton, J AU - Zia, F AU - Tuthill, C AU - Badamchian, M AU - Goldstein, A L AD - Medicine Branch, National Cancer Institute, MD 20850, Rockville, MD 20850, USA. moodyt@bprb.nci.nih.gov Y1 - 2000/07/31/ PY - 2000 DA - 2000 Jul 31 SP - 121 EP - 127 VL - 155 IS - 2 SN - 0304-3835, 0304-3835 KW - Carcinogens KW - 0 KW - Urethane KW - 3IN71E75Z5 KW - Thymosin KW - 61512-21-8 KW - thymalfasin KW - W0B22ISQ1C KW - Index Medicus KW - Animals KW - Blood -- drug effects KW - Mice KW - Tissue Distribution KW - Radioimmunoassay KW - Blotting, Western KW - Pulmonary Alveoli -- metabolism KW - Lung -- drug effects KW - Bronchi -- metabolism KW - Immunohistochemistry KW - Time Factors KW - Female KW - Lung Neoplasms -- prevention & control KW - Adenoma -- prevention & control KW - Adenoma -- chemically induced KW - Thymosin -- analogs & derivatives KW - Lung Neoplasms -- chemically induced KW - Thymosin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71136393?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Thymosinalpha1+is+chemopreventive+for+lung+adenoma+formation+in+A%2FJ+mice.&rft.au=Moody%2C+T+W%3BLeyton%2C+J%3BZia%2C+F%3BTuthill%2C+C%3BBadamchian%2C+M%3BGoldstein%2C+A+L&rft.aulast=Moody&rft.aufirst=T&rft.date=2000-07-31&rft.volume=155&rft.issue=2&rft.spage=121&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 - 2000-07-19 N1 - Date created - 2000-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Genetic variability in susceptibility and response to toxicants AN - 17905244; 5166543 AB - Everyone has a unique combination of polymorphic traits that modify susceptibility and response to drugs, chemicals and carcinogenic exposures. The metabolism of exogenous and endogenous chemical toxins may be modified by inherited and induced variation in CYP (P450), acetyltransferase (NAT) and glutathione S-transferase (GST) genes. We observe that specific `at risk' genotypes for GSTM1 and NAT1/2 increase risk for bladder cancer among smokers. Genotypic and phenotypic variation in DNA repair may affect risk of somatic mutation and cancer. Variants of base excision and nucleotide excision repair genes (XRCC1 and XPD) appear to modify exposure-induced damage from cigarette smoke and radiation. We are currently engaged in discovering genetic variation in environmental response genes and determining if this variation has any effect on gene function or if it is associated with disease risk. These and other results are discussed in the context of evaluating inherited or acquired susceptibility risk factors for environmentally caused disease. JF - Toxicology Letters AU - Miller, M C AU - Mohrenweiser, H W AU - Bell, DA Y1 - 2000/07/27/ PY - 2000 DA - 2000 Jul 27 SP - 269 EP - 280 PB - Elsevier Science Ireland Ltd., Elsevier House, Brookvale Plaza East Park Shannon, Co. Clare Ireland VL - 116 IS - 1-2 KW - N-Acetyltransferase KW - Toxicology Abstracts KW - Genetic factors KW - Radiation KW - Cigarette smoke KW - Cytochrome P450 KW - Enzyme polymorphism KW - Xenobiotics KW - Glutathione transferase KW - DNA repair KW - Environmental factors KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17905244?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+Letters&rft.atitle=Genetic+variability+in+susceptibility+and+response+to+toxicants&rft.au=Miller%2C+M+C%3BMohrenweiser%2C+H+W%3BBell%2C+DA&rft.aulast=Miller&rft.aufirst=M&rft.date=2000-07-27&rft.volume=116&rft.issue=1-2&rft.spage=269&rft.isbn=&rft.btitle=&rft.title=Toxicology+Letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - CONF T1 - New models for assessing carcinogenesis: An ongoing process AN - 17905172; 5166535 AB - Traditionally, the use of rodent models in assessing the carcinogenic potential of chemicals has been expensive and lengthy, and the relevance of the carcinogenic effect to humans is often not fully understood. Today, however, with the rapid advances in molecular biology, genetically altered mice containing genes relevant to humans (e.g. oncogenes, tumor suppressor genes) and reporter genes (e.g. lacI) provide powerful tools for examining specific chemical-gene interactions thereby allowing a better understanding of the mechanisms of carcinogenesis in a shorter period of time. This paper will cover an overview of ongoing validation efforts, followed by examples of studies using several genetically engineered models including the p53 super(def) mouse model and the Big Blue registered transgenic mouse model. Specifically, examples where transgenic models were integrated into the testing program based on specific hypotheses dealing with genetic alterations in cancer genes and reporter genes will be discussed. The examples will highlight possible ways genetically altered mice may be integrated into a comprehensive research and testing strategy and thereby provide an improved estimation of human health risks. JF - Toxicology Letters AU - Sills, R C AU - French, JE AU - Cunningham, M L Y1 - 2000/07/27/ PY - 2000 DA - 2000 Jul 27 SP - 187 EP - 198 PB - Elsevier Science Ireland Ltd., Elsevier House, Brookvale Plaza East Park Shannon, Co. Clare Ireland VL - 116 IS - 1-2 KW - reporter gene KW - Toxicology Abstracts KW - Genetic engineering KW - Reviews KW - Carcinogenicity testing KW - Carcinogenesis KW - Animal models KW - Toxicity testing KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17905172?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+Letters&rft.atitle=New+models+for+assessing+carcinogenesis%3A+An+ongoing+process&rft.au=Sills%2C+R+C%3BFrench%2C+JE%3BCunningham%2C+M+L&rft.aulast=Sills&rft.aufirst=R&rft.date=2000-07-27&rft.volume=116&rft.issue=1-2&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Toxicology+Letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - CONF T1 - The use of gene knockout mice to unravel the mechanisms of toxicity and chemical carcinogenesis AN - 17901836; 5166536 AB - Metabolism of toxins and carcinogens is carried out by large groups of xenobiotic-metabolizing enzymes. These enzymes are generally considered to be required for elimination of xenobiotics such as drugs, dietary chemicals and environmental pollutants, and to be required for chemical toxicity and carcinogenicity. An important role for these enzymes in metabolism of endogenous chemicals has not been established. Mouse lines in which the genes encoding several xenobiotic-metabolizing enzymes were knocked out were produced and are being used to determine the role of metabolism in carcinogenesis, and acute and chronic toxicities in vivo. Mouse lines lacking the P450s CYP1A1, CYP1A2, CYP1B1 and CYP2E1, microsomal epoxide hydrolase (mEH), NADPH:quinone oxidoreductase and the glutathione S-transferase P1 have no deleterious phenotypes, indicating that these enzymes are not required for mammalian development and physiological homeostasis. However, when challenged with toxins and carcinogens, they respond differently from their wild-type (WT) counterparts. For example, mice lacking CYP1A2 and CYP2E1 are totally resistant to acetaminophen-induced hepatotoxicity. Mice lacking CYP1B1 or mEH are less responsive to tumorigenesis by 7,12-dimethybenz[a]anthracene. However, CYP1A2-null mice do not significantly differ from WT mice in their response to the hepatocarcinogen 4-aminobiphenyl. These and other studies indicate that the xenobiotic-metabolism null mice are of great value in the study of the mechanisms of chemical injury. JF - Toxicology Letters AU - Gonzalez, F J Y1 - 2000/07/27/ PY - 2000 DA - 2000 Jul 27 SP - 199 EP - 208 PB - Elsevier Science Ireland Ltd., Elsevier House, Brookvale Plaza East Park Shannon, Co. Clare Ireland VL - 116 IS - 1-2 KW - knockout mice KW - Toxicology Abstracts KW - Polycyclic aromatic hydrocarbons KW - Carcinogenesis KW - Animal models KW - Cytochrome P450 KW - Chemical pollution KW - Toxicity testing KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17901836?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+Letters&rft.atitle=The+use+of+gene+knockout+mice+to+unravel+the+mechanisms+of+toxicity+and+chemical+carcinogenesis&rft.au=Gonzalez%2C+F+J&rft.aulast=Gonzalez&rft.aufirst=F&rft.date=2000-07-27&rft.volume=116&rft.issue=1-2&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Toxicology+Letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Stem cells--hype and hope AN - 17611835; 4744642 AB - Studies of stem cells will help in understanding the development and function of organs in mammals. They may also offer a way of treating diseases ranging from liver failure to Parkinson's disease. JF - Nature AU - McKay, R AD - Natl. Inst. of Health, LMB/NINDS, Bethesda, MD 20892, USA, mckay@codon.nih.gov Y1 - 2000/07/27/ PY - 2000 DA - 2000 Jul 27 SP - 361 EP - 364 PB - Macmillan Journals Ltd. VL - 406 IS - 6794 SN - 0028-0836, 0028-0836 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Stem cells KW - Parkinson's disease KW - Reviews KW - Liver KW - W 30965:Miscellaneous, Reviews KW - W3 33000:General topics and reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17611835?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Stem+cells--hype+and+hope&rft.au=McKay%2C+R&rft.aulast=McKay&rft.aufirst=R&rft.date=2000-07-27&rft.volume=406&rft.issue=6794&rft.spage=361&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Stem cells; Liver; Parkinson's disease ER - TY - JOUR T1 - Measuring gene-specific nucleotide excision repair in human cells using quantitative amplification of long targets from nanogram quantities of DNA. AN - 71229057; 10882849 AB - We have been developing a rapid and convenient assay for the measurement of DNA damage and repair in specific genes using quantitative polymerase chain reaction (QPCR) methodology. Since the sensitivity of this assay is limited to the size of the DNA amplification fragment, conditions have been found for the quantitative generation of PCR fragments from human genomic DNA in the range of 6-24 kb in length. These fragments include: (1) a 16.2 kb product from the mitochondrial genome; (2) 6.2, 10.4 kb, and 15.4 kb products from the hprt gene, and (3) 13.5, 17.7, 24.2 kb products from the human beta-globin gene cluster. Exposure of SV40 transformed human fibroblasts to increasing fluences of ultraviolet light (UV) resulted in the linear production of photoproducts with 10 J/m(2) of UVC producing 0.085 and 0.079 lesions/kb in the hprt gene and the beta-globin gene cluster, respectively. Kinetic analysis of repair following 10 J/m(2) of UVC exposure indicated that the time necessary for the removal of 50% of the photoproducts, in the hprt gene and beta-globin gene cluster was 7.8 and 24.2 h, respectively. Studies using lymphoblastoid cell lines show very little repair in XPA cells in both the hprt gene and beta-globin locus. Preferential repair in the hprt gene was detected in XPC cells. Cisplatin lesions were also detected using this method and showed slower rates of repair than UV-induced photoproducts. These data indicate that the use of long targets in the gene-specific QPCR assay allows the measurement of biologically relevant lesion frequencies in 5-30 ng of genomic DNA. This assay will be useful for the measurement of human exposure to genotoxic agents and the determination of human repair capacity. JF - Mutation research AU - Van Houten, B AU - Cheng, S AU - Chen, Y AD - Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, TX, USA. vanhout1@niehs.nih.gov Y1 - 2000/07/25/ PY - 2000 DA - 2000 Jul 25 SP - 81 EP - 94 VL - 460 IS - 2 SN - 0027-5107, 0027-5107 KW - Cross-Linking Reagents KW - 0 KW - DNA Adducts KW - DNA, Mitochondrial KW - Oligodeoxyribonucleotides KW - Globins KW - 9004-22-2 KW - DNA KW - 9007-49-2 KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Sensitivity and Specificity KW - DNA Adducts -- genetics KW - Ultraviolet Rays KW - Hypoxanthine Phosphoribosyltransferase -- genetics KW - Simian virus 40 -- genetics KW - Cross-Linking Reagents -- pharmacology KW - Humans KW - Globins -- genetics KW - Oligodeoxyribonucleotides -- genetics KW - Dose-Response Relationship, Radiation KW - Fibroblasts KW - DNA Adducts -- analysis KW - Kinetics KW - Cisplatin -- pharmacology KW - Sample Size KW - Cell Line KW - Oligodeoxyribonucleotides -- analysis KW - DNA, Mitochondrial -- genetics KW - DNA Repair -- genetics KW - DNA Repair -- radiation effects KW - Polymerase Chain Reaction -- methods KW - DNA -- genetics KW - DNA -- analysis KW - DNA Damage -- radiation effects KW - DNA Damage -- genetics KW - DNA Repair -- drug effects KW - DNA Damage -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71229057?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Measuring+gene-specific+nucleotide+excision+repair+in+human+cells+using+quantitative+amplification+of+long+targets+from+nanogram+quantities+of+DNA.&rft.au=Van+Houten%2C+B%3BCheng%2C+S%3BChen%2C+Y&rft.aulast=Van+Houten&rft.aufirst=B&rft.date=2000-07-25&rft.volume=460&rft.issue=2&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-29 N1 - Date created - 2000-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Self-reported sensitivity to chemical exposures in five clinical populations and healthy controls. AN - 71240982; 10904124 AB - Two hundred and twenty-five subjects, including normal volunteers and patients with previously documented seasonal affective disorder (SAD), chronic fatigue syndrome (CFS), Cushing's syndrome, Addison's disease and obsessive-compulsive disorder (OCD), completed a self-rated inventory of reported sensitivity to various chemical exposures. Patients with CFS, Addison's disease and SAD self-reported more sensitivity to chemical exposures than normal controls. In addition, women reported more sensitivity than men. This report suggests that chemical sensitivity may be a relevant area to explore in certain medical and psychiatric populations. A possible relationship between reported chemical sensitivity and hypothalamic-pituitary-adrenal (HPA)-axis functioning is discussed. JF - Psychiatry research AU - Nawab, S S AU - Miller, C S AU - Dale, J K AU - Greenberg, B D AU - Friedman, T C AU - Chrousos, G P AU - Straus, S E AU - Rosenthal, N E AD - Section on Biological Rhythms, National Institute of Mental Health, Bethesda, MD 20892-1390, USA. ssnawab@hotmail.com Y1 - 2000/07/24/ PY - 2000 DA - 2000 Jul 24 SP - 67 EP - 74 VL - 95 IS - 1 SN - 0165-1781, 0165-1781 KW - Index Medicus KW - Hypothalamo-Hypophyseal System -- physiopathology KW - Humans KW - Pituitary-Adrenal System -- physiopathology KW - Adult KW - Middle Aged KW - Male KW - Female KW - Comorbidity KW - Cushing Syndrome -- psychology KW - Obsessive-Compulsive Disorder -- diagnosis KW - Seasonal Affective Disorder -- physiopathology KW - Addison Disease -- physiopathology KW - Addison Disease -- diagnosis KW - Fatigue Syndrome, Chronic -- psychology KW - Obsessive-Compulsive Disorder -- physiopathology KW - Seasonal Affective Disorder -- diagnosis KW - Cushing Syndrome -- diagnosis KW - Obsessive-Compulsive Disorder -- psychology KW - Fatigue Syndrome, Chronic -- diagnosis KW - Multiple Chemical Sensitivity -- psychology KW - Fatigue Syndrome, Chronic -- physiopathology KW - Multiple Chemical Sensitivity -- physiopathology KW - Seasonal Affective Disorder -- psychology KW - Cushing Syndrome -- physiopathology KW - Multiple Chemical Sensitivity -- diagnosis KW - Addison Disease -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71240982?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychiatry+research&rft.atitle=Self-reported+sensitivity+to+chemical+exposures+in+five+clinical+populations+and+healthy+controls.&rft.au=Nawab%2C+S+S%3BMiller%2C+C+S%3BDale%2C+J+K%3BGreenberg%2C+B+D%3BFriedman%2C+T+C%3BChrousos%2C+G+P%3BStraus%2C+S+E%3BRosenthal%2C+N+E&rft.aulast=Nawab&rft.aufirst=S&rft.date=2000-07-24&rft.volume=95&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Psychiatry+research&rft.issn=01651781&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-26 N1 - Date created - 2000-09-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Peroxynitrite targets the epidermal growth factor receptor, Raf-1, and MEK independently to activate MAPK. AN - 71241061; 10801894 AB - Activation of ERK-1 and -2 by H(2)O(2) in a variety of cell types requires epidermal growth factor receptor (EGFR) phosphorylation. In this study, we investigated the activation of ERK by ONOO(-) in cultured rat lung myofibroblasts. Western blot analysis using anti-phospho-ERK antibodies along with an ERK kinase assay using the phosphorylated heat- and acid-stable protein (PHAS-1) substrate demonstrated that ERK activation peaked within 15 min after ONOO(-) treatment and was maximally activated with 100 micrometer ONOO(-). Activation of ERK by ONOO(-) and H(2)O(2) was blocked by the antioxidant N-acetyl-l-cysteine. Catalase blocked ERK activation by H(2)O(2), but not by ONOO(-), demonstrating that the effect of ONOO(-) was not due to the generation of H(2)O(2). Both H(2)O(2) and ONOO(-) induced phosphorylation of EGFR in Western blot experiments using an anti-phospho-EGFR antibody. However, the EGFR tyrosine kinase inhibitor AG1478 abolished ERK activation by H(2)O(2), but not by ONOO(-). Both H(2)O(2) and ONOO(-) activated Raf-1. However, the Raf inhibitor forskolin blocked ERK activation by H(2)O(2), but not by ONOO(-). The MEK inhibitor PD98059 inhibited ERK activation by both H(2)O(2) and ONOO(-). Moreover, ONOO(-) or H(2)O(2) caused a cytotoxic response of myofibroblasts that was prevented by preincubation with PD98059. In a cell-free kinase assay, ONOO(-) (but not H(2)O(2)) induced autophosphorylation and nitration of a glutathione S-transferase-MEK-1 fusion protein. Collectively, these data indicate that ONOO(-) activates EGFR and Raf-1, but these signaling intermediates are not required for ONOO(-)-induced ERK activation. However, MEK-1 activation is required for ONOO(-)-induced ERK activation in myofibroblasts. In contrast, H(2)O(2)-induced ERK activation is dependent on EGFR activation, which then leads to downstream Raf-1 and MEK-1 activation. JF - The Journal of biological chemistry AU - Zhang, P AU - Wang, Y Z AU - Kagan, E AU - Bonner, J C AD - Laboratory of Pulmonary Pathobiology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000/07/21/ PY - 2000 DA - 2000 Jul 21 SP - 22479 EP - 22486 VL - 275 IS - 29 SN - 0021-9258, 0021-9258 KW - Nitrates KW - 0 KW - Oxidants KW - peroxynitric acid KW - 26404-66-0 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-raf KW - Index Medicus KW - Rats KW - Animals KW - Enzyme Activation KW - MAP Kinase Signaling System -- drug effects KW - Receptor, Epidermal Growth Factor -- metabolism KW - Protein-Serine-Threonine Kinases -- metabolism KW - Oxidants -- pharmacology KW - Receptor, Epidermal Growth Factor -- agonists KW - Signal Transduction -- drug effects KW - Nitrates -- metabolism KW - Nitrates -- pharmacology KW - Proto-Oncogene Proteins c-raf -- metabolism KW - Oxidants -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71241061?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Peroxynitrite+targets+the+epidermal+growth+factor+receptor%2C+Raf-1%2C+and+MEK+independently+to+activate+MAPK.&rft.au=Zhang%2C+P%3BWang%2C+Y+Z%3BKagan%2C+E%3BBonner%2C+J+C&rft.aulast=Zhang&rft.aufirst=P&rft.date=2000-07-21&rft.volume=275&rft.issue=29&rft.spage=22479&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 - 2000-08-24 N1 - Date created - 2000-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction between RNA Polymerase and RapA, a Bacterial Homolog of the SWI/SNF Protein Family AN - 17635863; 4780681 AB - Recently, we identified a novel Escherichia coli RNA polymerase (RNAP)-associated protein, an ATPase, called RapA (Sukhodolets, M. V., and Jin, D. J. (1998) J. Biol. Chem. 273, 7018-7023). RapA is a bacterial homolog of SWI2/SNF2. We showed that RapA forms a stable complex with RNAP holoenzyme and that binding to RNAP holoenzyme stimulates the ATPase activity of RapA. We have further analyzed the interactions between purified RapA and the two forms of RNAP: core RNAP and RNAP holoenzyme. We found that RapA interacts with either form of RNAP. However, RapA exhibits higher affinity for core RNAP than for RNAP holoenzyme. Chemical cross-linking of the RNAP-RapA complex indicated that the RapA-binding sites are located at the interface between the alpha and beta ' subunits of RNAP. Contrary to previously reported results (Muzzin, O., Campbell, E., A., Xia, L., Severinova, E., Darst, S. A., and Severinov, K. (1998) J. Biol. Chem. 273, 15157-15161), our in vivo analysis of a rapA null mutant suggested that RapA is not likely to be directly involved in DNA repair. JF - Journal of Biological Chemistry AU - Sukhodolets, M V AU - Jin, D J AD - Laboratory of Molecular Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892, djjin@helix.nih.gov Y1 - 2000/07/21/ PY - 2000 DA - 2000 Jul 21 SP - 22090 EP - 22097 VL - 275 IS - 29 SN - 0021-9258, 0021-9258 KW - null mutant KW - RNAP protein KW - RapA protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - DNA-directed RNA polymerase KW - Escherichia coli KW - DNA repair KW - N 14721:RNA polymerases KW - J 02726:RNA and ribosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17635863?accountid=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=Interaction+between+RNA+Polymerase+and+RapA%2C+a+Bacterial+Homolog+of+the+SWI%2FSNF+Protein+Family&rft.au=Sukhodolets%2C+M+V%3BJin%2C+D+J&rft.aulast=Sukhodolets&rft.aufirst=M&rft.date=2000-07-21&rft.volume=275&rft.issue=29&rft.spage=22090&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/10.1074%2Fjbc.M000056200 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA-directed RNA polymerase; DNA repair DO - http://dx.doi.org/10.1074/jbc.M000056200 ER - TY - JOUR T1 - Subjectifying quality of life as a medical rehabilitation outcome. AN - 85351123; pmid-10972351 AB - In the literature of health-status assessment, it has been argued that quality of life has distinct meaning only if it is conceptualized and assessed according to a subjective perspective. This paper applies that viewpoint to the conceptual components of disablement and to assessing subjective well-being (i.e. subjective quality of life) as medical rehabilitation outcomes. The definition and measurement of subjective well-being are discussed, and its correlates for people generally are reviewed. Findings for people with disabilities are summarized, and several substantive and methodological issues are highlighted that require additional investigation. JF - Disability and rehabilitation AU - Fuhrer, M J AD - National Institutes of Health, Bethesda, Maryland, USA. fuhrerm@mail.nih.gov Y1 - 2000/07/20/ PY - 2000 DA - 2000 Jul 20 SP - 481 EP - 489 VL - 22 IS - 11 SN - 0963-8288, 0963-8288 KW - Index Medicus KW - National Library of Medicine KW - Adaptation, Psychological KW - Humans KW - Personal Satisfaction KW - Health Status Indicators KW - Rehabilitation KW - Outcome Assessment (Health Care) -- methods KW - Quality of Life UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85351123?accountid=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=Disability+and+rehabilitation&rft.atitle=Subjectifying+quality+of+life+as+a+medical+rehabilitation+outcome.&rft.au=Fuhrer%2C+M+J&rft.aulast=Fuhrer&rft.aufirst=M&rft.date=2000-07-20&rft.volume=22&rft.issue=11&rft.spage=481&rft.isbn=&rft.btitle=&rft.title=Disability+and+rehabilitation&rft.issn=09638288&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - Treatment-associated leukemia following testicular cancer. AN - 71239249; 10904090 AB - Men with testicular cancer are at an increased risk of leukemia, but the relationship to prior treatments is not well characterized. The purpose of our study was to describe the risk of leukemia following radiotherapy and chemotherapy for testicular cancer. Within a population-based cohort of 18 567 patients diagnosed with testicular cancer (from 1970 through 1993), a case-control study of leukemia was undertaken. Radiation dose to active bone marrow and type and cumulative amount of cytotoxic drugs were compared between 36 men who developed leukemia and 106 matched control patients without leukemia. Conditional logistic regression was used to estimate the relative risk of leukemia associated with specific treatments. All P values are two-sided. Radiotherapy (mean dose to active bone marrow, 12.6 Gy) without chemotherapy was associated with a threefold elevated risk of leukemia. Risk increased with increasing dose of radiation to active bone marrow (P for trend =.02), with patients receiving radiotherapy to the chest as well as to the abdominal/pelvic fields accounting for much of the risk at higher doses. Radiation dose to active bone marrow and the cumulative dose of cisplatin (P for trend =.001) were both predictive of excess leukemia risk in a model adjusted for all treatment variables. The estimated relative risk of leukemia at a cumulative dose of 650 mg cisplatin, which is commonly administered in current testicular cancer treatment regimens, was 3.2 (95% confidence interval = 1.5-8.4); larger doses (1000 mg) were linked with statistically significant sixfold increased risks. Past treatments for testicular cancer are associated with an increased risk of leukemia, with evidence for dose-response relationships for both radiotherapy and cisplatin-based chemotherapy. Statistically nonsignificant excesses are estimated for current radiotherapy regimens limited to the abdomen and pelvis: Among 10 000 patients given a treatment dose of 25 Gy and followed for 15 years, an excess of nine leukemias is predicted; cisplatin-based chemotherapy (dose, 650 mg) might result in 16 cases of leukemia. The survival advantage provided by current radiotherapy and chemotherapy regimens for testicular cancer far exceeds the small absolute risk of leukemia. JF - Journal of the National Cancer Institute AU - Travis, L B AU - Andersson, M AU - Gospodarowicz, M AU - van Leeuwen, F E AU - Bergfeldt, K AU - Lynch, C F AU - Curtis, R E AU - Kohler, B A AU - Wiklund, T AU - Storm, H AU - Holowaty, E AU - Hall, P AU - Pukkala, E AU - Sleijfer, D T AU - Clarke, E A AU - Boice, J D AU - Stovall, M AU - Gilbert, E AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2000/07/19/ PY - 2000 DA - 2000 Jul 19 SP - 1165 EP - 1171 VL - 92 IS - 14 SN - 0027-8874, 0027-8874 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Index Medicus KW - Humans KW - Europe -- epidemiology KW - Radiotherapy, Adjuvant -- adverse effects KW - Chemotherapy, Adjuvant -- adverse effects KW - Registries KW - Risk KW - North America -- epidemiology KW - Radiotherapy Dosage KW - Adult KW - Case-Control Studies KW - Antineoplastic Agents, Alkylating -- adverse effects KW - Incidence KW - Middle Aged KW - Time Factors KW - Male KW - Testicular Neoplasms -- drug therapy KW - Testicular Neoplasms -- radiotherapy KW - Neoplasms, Second Primary -- epidemiology KW - Leukemia, Radiation-Induced -- epidemiology KW - Neoplasms, Second Primary -- etiology KW - Leukemia, Radiation-Induced -- etiology KW - Bone Marrow -- radiation effects KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71239249?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Treatment-associated+leukemia+following+testicular+cancer.&rft.au=Travis%2C+L+B%3BAndersson%2C+M%3BGospodarowicz%2C+M%3Bvan+Leeuwen%2C+F+E%3BBergfeldt%2C+K%3BLynch%2C+C+F%3BCurtis%2C+R+E%3BKohler%2C+B+A%3BWiklund%2C+T%3BStorm%2C+H%3BHolowaty%2C+E%3BHall%2C+P%3BPukkala%2C+E%3BSleijfer%2C+D+T%3BClarke%2C+E+A%3BBoice%2C+J+D%3BStovall%2C+M%3BGilbert%2C+E&rft.aulast=Travis&rft.aufirst=L&rft.date=2000-07-19&rft.volume=92&rft.issue=14&rft.spage=1165&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-25 N1 - Date created - 2000-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of cysteines in Plasmodium falciparum circumsporozoite protein: interactions with heparin can rejuvenate inactive protein mutants. AN - 71255613; 10890903 AB - Various pathogenic bacteria, viruses, and protozoan bind to glycosaminoglycan-based receptors on host cells and initiate an infection. Sporozoites of Plasmodium predominantly express circumsporozoite (CS) protein on their surface, which binds to heparan sulfate proteoglycans on liver cell surface that subsequently leads to malaria. Here we show that the interaction of free heparin with this parasite ligand has the potential to be a critical component of invasion. CS protein of P. falciparum contains four cysteines at positions 361, 365, 396, and 401. In this study, all four cysteine residues were mutagenized to alanine both individually and in different combinations. Conversion of cysteine 396 to alanine (protein CS3) led to a 10-fold increase in the binding activity of the protein to HepG2 cells. Replacement of cysteines at positions 361, 365, and 401 either alone or in different combinations led to a near total loss of binding. Surprisingly, activity in these inactive mutants could be effectively restored in the presence of submolar concentrations of heparin. Heparin also up-regulated binding of CS3 at submolar concentrations with respect to the protein but down-regulated binding when present in excess. Given the significantly different concentrations of heparin in different organs of the host and the in vitro results described here one can consider in vivo ramifications of this phenomenon for pathogen targeting of specific organs and for the functional effects of antigenic variation on receptor ligand interaction. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Rathore, D AU - McCutchan, T F AD - Growth and Development Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-0425, USA. Y1 - 2000/07/18/ PY - 2000 DA - 2000 Jul 18 SP - 8530 EP - 8535 VL - 97 IS - 15 SN - 0027-8424, 0027-8424 KW - Peptides KW - 0 KW - Protozoan Proteins KW - circumsporozoite protein, Protozoan KW - Heparin KW - 9005-49-6 KW - Heparin Lyase KW - EC 4.2.2.7 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Tumor Cells, Cultured KW - Heparin Lyase -- metabolism KW - Humans KW - Binding, Competitive KW - Molecular Sequence Data KW - Gene Expression KW - Peptides -- metabolism KW - Amino Acid Sequence KW - Amino Acid Substitution KW - Protozoan Proteins -- metabolism KW - Cysteine -- metabolism KW - Protozoan Proteins -- isolation & purification KW - Cysteine -- genetics KW - Protozoan Proteins -- genetics KW - Protozoan Proteins -- physiology KW - Heparin -- metabolism KW - Plasmodium falciparum KW - Cysteine -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71255613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+cysteines+in+Plasmodium+falciparum+circumsporozoite+protein%3A+interactions+with+heparin+can+rejuvenate+inactive+protein+mutants.&rft.au=Rathore%2C+D%3BMcCutchan%2C+T+F&rft.aulast=Rathore&rft.aufirst=D&rft.date=2000-07-18&rft.volume=97&rft.issue=15&rft.spage=8530&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 - 2000-08-24 N1 - Date created - 2000-08-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Infect Immun. 2000 Feb;68(2):740-3 [10639441] Science. 1998 Oct 16;282(5388):476-80 [9774275] J Immunol. 1984 Feb;132(2):909-13 [6317752] Science. 1984 Aug 10;225(4662):593-9 [6204383] J Cell Biol. 1986 Nov;103(5):1635-48 [2430973] J Exp Med. 1986 Dec 1;164(6):1915-22 [3023519] Exp Parasitol. 1988 Aug;66(2):171-82 [3294024] Nature. 1988 Jul 21;334(6179):258-60 [2456467] Nature. 1988 Sep 1;335(6185):79-82 [3045563] Nature. 1988 Sep 1;335(6185):82-5 [3045564] Exp Parasitol. 1989 Apr;68(3):365-8 [2564825] J Biol Chem. 1990 Feb 15;265(5):2852-5 [2303431] Science. 1990 Sep 28;249(4976):1574-7 [2120774] Cell. 1992 Sep 18;70(6):1021-33 [1326407] J Exp Med. 1993 May 1;177(5):1287-98 [8478608] EMBO J. 1993 Jul;12(7):2881-9 [8392935] J Cell Biol. 1993 Nov;123(3):759-66 [8227137] J Exp Med. 1994 Jul 1;180(1):297-306 [8006589] Infect Immun. 1995 Feb;63(2):456-66 [7822010] Mol Biochem Parasitol. 1995 Nov;74(2):129-41 [8719155] Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11889-94 [8876233] N Engl J Med. 1997 Jan 9;336(2):86-91 [8988885] Exp Parasitol. 1997 Feb;85(2):168-82 [9030667] Infect Immun. 1997 Aug;65(8):3024-31 [9234749] J Biol Chem. 1997 Aug 1;272(31):19205-13 [9235912] Bioessays. 1998 Feb;20(2):156-67 [9631661] Exp Parasitol. 1980 Jun;49(3):420-9 [6768578] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MDP-1: A novel eukaryotic magnesium-dependent phosphatase. AN - 71253337; 10889041 AB - We report here the purification, cloning, expression, and characterization of a novel phosphatase, MDP-1. In the course of investigating the reported acid phosphatase activity of carbonic anhydrase III preparations, several discrete phosphatases were discerned. One of these, a magnesium-dependent species of 18.6 kDa, was purified to homogeneity and yielded several peptide sequences from which the parent gene was identified by database searching. Although orthologous genes were identified in fungi and plants as well as mammalian species, there was no apparent homology to any known family of phosphatases. The enzyme was expressed in Escherichia coli with a fusion tag and purified by affinity methods. The recombinant enzyme showed magnesium-dependent acid phosphatase activity comparable to the originally isolated rabbit protein. The enzyme catalyzes the rapid hydrolysis of p-nitrophenyl phosphate, ribose-5-phosphate, and phosphotyrosine. The selectivity for phosphotyrosine over phosphoserine or phosphothreonine is considerable, but the enzyme did not show activity toward five phosphotyrosine-containing peptides. None of the various substrates assayed (including various nucleotide, sugar, amino acid and peptide phosphates, phosphoinositides, and phosphodiesters) exhibited K(M) values lower than 1 mM, and many showed negligible rates of hydrolysis. The enzyme is inhibited by vanadate and fluoride but not by azide, cyanide, calcium, lithium, or tartaric acid. Chemical labeling, refolding, dialysis, and mutagenesis experiments suggest that the enzymatic mechanism is not dependent on cysteine, histidine, or nonmagnesium metal ions. In recognition of these observations, the enzyme has been given the name magnesium-dependent phosphatase-1 (MDP-1). JF - Biochemistry AU - Selengut, J D AU - Levine, R L AD - Laboratory of Biochemistry, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-0320, USA. selengut@nih.gov Y1 - 2000/07/18/ PY - 2000 DA - 2000 Jul 18 SP - 8315 EP - 8324 VL - 39 IS - 28 SN - 0006-2960, 0006-2960 KW - Cations KW - 0 KW - Enzyme Inhibitors KW - Histidine KW - 4QD397987E KW - MDP-1 protein, mouse KW - EC 3.1.3.16 KW - Phosphoprotein Phosphatases KW - Protein Phosphatase 1 KW - Protein Phosphatase 2C KW - Magnesium KW - I38ZP9992A KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - Cysteine -- metabolism KW - Hydrogen-Ion Concentration KW - Rabbits KW - Amino Acid Sequence KW - Mice KW - Cloning, Molecular KW - Sequence Analysis, Protein KW - Chromatography, Affinity KW - Magnesium -- metabolism KW - Molecular Sequence Data KW - Enzyme Inhibitors -- pharmacology KW - Substrate Specificity KW - Sequence Homology, Amino Acid KW - Histidine -- metabolism KW - Catalysis KW - Phosphoprotein Phosphatases -- metabolism KW - Phosphoprotein Phosphatases -- genetics KW - Phosphoprotein Phosphatases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71253337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=MDP-1%3A+A+novel+eukaryotic+magnesium-dependent+phosphatase.&rft.au=Selengut%2C+J+D%3BLevine%2C+R+L&rft.aulast=Selengut&rft.aufirst=J&rft.date=2000-07-18&rft.volume=39&rft.issue=28&rft.spage=8315&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-16 N1 - Date created - 2000-08-16 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF230273; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Site-specific chemical modification with polyethylene glycol of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) improves antitumor activity and reduces animal toxicity and immunogenicity AN - 17679345; 4760624 AB - Chemical modification of proteins with polyethylene glycol (PEGylation) can increase plasma half-lives, stability, and therapeutic potency. To make a PEGylated recombinant immunotoxin with improved therapeutic properties, we prepared a mutant of anti-Tac(Fv)-PE38 (LMB-2), a recombinant immunotoxin composed of a single-chain Fv fragment of the anti-human Tac monoclonal antibody to the IL-2 receptor alpha subunit fused to a 38-kDa fragment of Pseudomonas exotoxin. For site-specific PEGylation of LMB-2, one cysteine residue was introduced into the peptide connector (ASGCGPE) between the Fv and the toxin. This mutant LMB-2 (cys1-LMB-2), which retained full cytotoxic activity, was then site-specifically conjugated with 5 or 20 kDa of polyethylene glycol-maleimide. When compared with unmodified LMB-2, both PEGylated immunotoxins showed similar cytotoxic activities in vitro but superior stability at 37 degree C in mouse serum, a 5- to 8-fold increase in plasma half-lives in mice, and a 3- to 4-fold increase in antitumor activity. This was accompanied by a substantial decrease in animal toxicity and immunogenicity. Site-specific PEGylation of recombinant immunotoxins may increase their therapeutic potency in humans. JF - Proceedings of the National Academy of Sciences, USA AU - Tsutsumi, Y AU - Onda, M AU - Nagata, S AU - Lee, B AU - Kreitman, R J AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Basic Science, National Cancer Institute, National Institutes of Health, Building 37, Room 4E16, 37 Convent Drive MSC 4255, Bethesda, MD 20892-4255, pasta@helix.nih.gov Y1 - 2000/07/18/ PY - 2000 DA - 2000 Jul 18 SP - 8548 EP - 8553 VL - 97 IS - 15 SN - 0027-8424, 0027-8424 KW - chemical modification KW - antitumor activity KW - man KW - toxicity KW - mice KW - immunology KW - Fv KW - LMB-2 protein KW - Tac antigen KW - polyethylene glycol KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Toxicology Abstracts KW - Monoclonal antibodies KW - Immunotherapy KW - Immunotoxins KW - W3 33375:Antibodies KW - F 06818:Cancer immunotherapy KW - X 24117:Biochemistry KW - F 06711:Monoclonal antibodies, hybridomas, antigens and antisera KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17679345?accountid=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=Site-specific+chemical+modification+with+polyethylene+glycol+of+recombinant+immunotoxin+anti-Tac%28Fv%29-PE38+%28LMB-2%29+improves+antitumor+activity+and+reduces+animal+toxicity+and+immunogenicity&rft.au=Tsutsumi%2C+Y%3BOnda%2C+M%3BNagata%2C+S%3BLee%2C+B%3BKreitman%2C+R+J%3BPastan%2C+I&rft.aulast=Tsutsumi&rft.aufirst=Y&rft.date=2000-07-18&rft.volume=97&rft.issue=15&rft.spage=8548&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&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 - Immunotoxins; Monoclonal antibodies; Immunotherapy ER - TY - JOUR T1 - Activation of protein kinase C alters p34(cdc2) phosphorylation state and kinase activity in early sea urchin embryos by abolishing intracellular Ca2+ transients. AN - 72524426; 10880348 AB - The p34(cdc2) protein kinase, a universal regulator of mitosis, is controlled positively and negatively by phosphorylation, and by association with B-type mitotic cyclins. In addition, activation and inactivation of p34(cdc2) are induced by Ca(2+) and prevented by Ca(2+) chelators in permeabilized cells and cell-free systems. This suggests that intracellular Ca(2+) transients may play an important physiological role in the control of p34(cdc2) kinase activity. We have found that activators of protein kinase C can be used to block cell cycle-related alterations in intracellular Ca(2+) concentration ([Ca(2+)](i)) in early sea urchin embryos without altering the normal resting level of Ca(2+). We have used this finding to investigate whether [Ca(2+)](i) transients control p34(cdc2) kinase activity in living cells via a mechanism that involves cyclin B or the phosphorylation state of p34(cdc2). In the present study we show that the elimination of [Ca(2+)](i) transients during interphase blocks p34(cdc2) activation and entry into mitosis, while the elimination of mitotic [Ca(2+)](i) transients prevents p34(cdc2) inactivation and exit from mitosis. Moreover, we find that [Ca(2+)](i) transients are not required for the synthesis of cyclin B, its binding to p34(cdc2) or its destruction during anaphase. However, in the absence of interphase [Ca(2+)](i) transients p34(cdc2) does not undergo the tyrosine dephosphorylation that is required for activation, and in the absence of mitotic [Ca(2+)](i) transients p34(cdc2) does not undergo threonine dephosphorylation that is normally associated with inactivation. These results provide evidence that intracellular [Ca(2+)](i) transients trigger the dephosphorylation of p34(cdc2) at key regulatory sites, thereby controlling the timing of mitosis entry and exit. JF - The Biochemical journal AU - Suprynowicz, F A AU - Groigno, L AU - Whitaker, M AU - Miller, F J AU - Sluder, G AU - Sturrock, J AU - Whalley, T AD - Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. Y1 - 2000/07/15/ PY - 2000 DA - 2000 Jul 15 SP - 489 EP - 499 VL - 349 SN - 0264-6021, 0264-6021 KW - Carcinogens KW - 0 KW - Cyclin B KW - Enzyme Activators KW - Protein Kinase C KW - EC 2.7.11.13 KW - CDC2 Protein Kinase KW - EC 2.7.11.22 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Carcinogens -- pharmacology KW - Animals KW - Phosphorylation KW - Enzyme Activation KW - Cyclin B -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Embryo, Nonmammalian -- cytology KW - Time Factors KW - Enzyme Activators -- pharmacology KW - Cell Cycle -- drug effects KW - Embryo, Nonmammalian -- enzymology KW - Protein Kinase C -- metabolism KW - Calcium -- metabolism KW - CDC2 Protein Kinase -- physiology KW - Sea Urchins -- metabolism KW - CDC2 Protein Kinase -- metabolism KW - Sea Urchins -- enzymology KW - Sea Urchins -- embryology KW - Mitosis -- drug effects KW - Mitosis -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72524426?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activation+of+protein+kinase+C+alters+p34%28cdc2%29+phosphorylation+state+and+kinase+activity+in+early+sea+urchin+embryos+by+abolishing+intracellular+Ca2%2B+transients.&rft.au=Suprynowicz%2C+F+A%3BGroigno%2C+L%3BWhitaker%2C+M%3BMiller%2C+F+J%3BSluder%2C+G%3BSturrock%2C+J%3BWhalley%2C+T&rft.aulast=Suprynowicz&rft.aufirst=F&rft.date=2000-07-15&rft.volume=349&rft.issue=&rft.spage=489&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 - 2001-07-05 N1 - Date created - 2001-01-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Biol. 1990 Jul;111(1):183-96 [2114410] Anal Biochem. 1989 Feb 15;177(1):138-43 [2472754] Development. 1990 Apr;108(4):525-42 [2167196] J Biol Chem. 1990 Oct 15;265(29):17941-5 [2211670] Cell. 1991 Apr 5;65(1):163-74 [1849458] EMBO J. 1991 Nov;10(11):3311-9 [1833185] EMBO J. 1991 Dec;10(12):3769-75 [1834459] Methods Enzymol. 1991;201:110-49 [1943760] Methods Enzymol. 1991;201:149-52 [1943761] EMBO J. 1991 Dec;10(13):4311-20 [1836759] J Biol Chem. 1992 Jan 25;267(3):1496-501 [1370476] Mol Biol Cell. 1992 Jan;3(1):13-27 [1532335] J Cell Biol. 1992 Apr;117(1):213-24 [1532584] J Cell Biol. 1992 May;117(4):799-811 [1577859] New Biol. 1992 Apr;4(4):323-9 [1622929] EMBO J. 1992 Jul;11(7):2381-90 [1321030] Biol Reprod. 1992 Jul;47(1):118-25 [1637939] Annu Rev Biochem. 1992;61:441-70 [1497317] Cell Signal. 1992 Jul;4(4):393-403 [1419482] J Exp Zool. 1992 Nov 1;264(2):206-13 [1431782] Science. 1993 Jul 16;261(5119):348-52 [8392748] Nature. 1993 Nov 18;366(6452):270-3 [8232587] J Cell Sci. 1993 Oct;106 ( Pt 2):523-34 [8282759] Nature. 1994 Apr 28;368(6474):875-8 [8159248] Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6176-80 [8016134] Mol Biol Cell. 1994 Aug;5(8):921-32 [7803859] Curr Opin Cell Biol. 1994 Dec;6(6):877-82 [7880537] Adv Second Messenger Phosphoprotein Res. 1995;30:299-310 [7695995] J Cell Sci. 1995 Nov;108 ( Pt 11):3557-68 [8586667] J Cell Biol. 1996 Oct;135(1):191-9 [8858173] Mol Reprod Dev. 1997 Oct;48(2):292-9 [9291480] Cell. 1998 Jan 23;92(2):193-204 [9458044] J Cell Biol. 1989 Aug;109(2):627-36 [2668300] EMBO J. 1989 Aug;8(8):2275-82 [2551679] Curr Biol. 1998 Jun 4;8(12):692-9 [9637920] J Biol Chem. 1999 Mar 19;274(12):7958-68 [10075693] Development. 1999 May;126(10):2273-84 [10207151] J Biol Chem. 1990 Apr 25;265(12):7009-15 [2108964] Exp Cell Res. 1969 Dec;58(2):312-8 [5408617] Methods Enzymol. 1974;30:563-90 [4212117] Methods Enzymol. 1983;99:387-402 [6196603] Nature. 1984 Apr 19-25;308(5961):693-8 [6232463] Nature. 1985 Mar 21-27;314(6008):274-7 [2984569] Nature. 1985 May 9-15;315(6015):147-9 [3838803] Exp Cell Res. 1986 Aug;165(2):507-17 [3013665] Exp Cell Res. 1986 Sep;166(1):23-30 [3017737] J Cell Biol. 1986 Nov;103(5):1873-81 [3782286] Science. 1987 Dec 18;238(4834):1726-8 [3686012] Nature. 1988 Mar 24;332(6162):364-6 [3127727] Nature. 1988 Mar 24;332(6162):366-9 [3127728] Mol Cell Biol. 1988 Jun;8(6):2302-8 [3136317] Dev Biol. 1989 Jan;131(1):11-26 [2491818] Comp Biochem Physiol B. 1989;92(2):251-4 [2924534] Nature. 1989 May 25;339(6222):280-6 [2566918] Dev Biol. 1990 Aug;140(2):272-80 [2373253] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of trans-acting factors and DNA-bending in the silencing of human beta-globin gene expression. AN - 71272754; 10908341 AB - The molecular mechanisms which govern the develop-mental specificity of human beta-globin gene transcription have been studied in K562 cells, a human eyrthroleukemia line that expresses minimal beta-globin. Protein-binding analysis reveals that the 5' region contains three elements bound by trans-acting factors, beta-protein 1 (BP1) and beta-protein 2 (BP2). In vitro mutagenesis of each individual element in a beta-globin vector containing chloramphenicol acetyl-transferase (pCAT) followed by transient transfection into K562 cells increased levels of CAT activity 5. 5-fold higher than wild-type (wt) betaCAT, consistent with their silencing role. Mutagenesis of all three elements, however, resulted in activity significantly lower than wt betaCAT. BP1 and BP2 motifs have overlapping binding sites for high mobility group proteins (HMG1+2), DNA-bending factors, shown here to extrinsically bend the beta-globin promoter. Theoretically, mutations in all beta-protein binding sites could affect the binding of HMG1+2 sufficiently to impede DNA-protein and/or protein-protein interactions needed to facilitate constitutive gene expression. Placing two turns of DNA between BP1 and BP2 motifs also increased expression 3-fold, indicative of spatial constraints required for optimal silencing. However, insertion of the HMG1+2 DNA-bending motif (also equivalent to two turns) facilitates beta-silencing by re-establishment of BP1-BP2 proximity. Thus a combination of general DNA-bending and specific transcriptional factors appear to be involved in beta-globin silencing in the embryonic/fetal erythroid stage. JF - Nucleic acids research AU - Drew, L R AU - Tang, D C AU - Berg, P E AU - Rodgers, G P AD - Molecular and Clinical Hematology Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Building 10, Room 9N115, 10 Center Drive, Bethesda, MD 20892, USA. Y1 - 2000/07/15/ PY - 2000 DA - 2000 Jul 15 SP - 2823 EP - 2830 VL - 28 IS - 14 KW - DNA-Binding Proteins KW - 0 KW - Recombinant Fusion Proteins KW - Trans-Activators KW - Globins KW - 9004-22-2 KW - DNA KW - 9007-49-2 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - Gene Silencing KW - Humans KW - Chloramphenicol O-Acetyltransferase -- metabolism KW - K562 Cells KW - Protein Binding KW - Nucleic Acid Conformation KW - Mutagenesis KW - Recombinant Fusion Proteins -- metabolism KW - Regulatory Sequences, Nucleic Acid -- genetics KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Base Sequence KW - Adult KW - Recombinant Fusion Proteins -- genetics KW - Binding Sites -- genetics KW - Mutation KW - DNA-Binding Proteins -- metabolism KW - Trans-Activators -- metabolism KW - DNA -- metabolism KW - Globins -- genetics KW - DNA -- genetics KW - DNA -- chemistry KW - Trans-Activators -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71272754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=The+role+of+trans-acting+factors+and+DNA-bending+in+the+silencing+of+human+beta-globin+gene+expression.&rft.au=Drew%2C+L+R%3BTang%2C+D+C%3BBerg%2C+P+E%3BRodgers%2C+G+P&rft.aulast=Drew&rft.aufirst=L&rft.date=2000-07-15&rft.volume=28&rft.issue=14&rft.spage=2823&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-07 N1 - Date created - 2000-09-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1998 Apr 24;273(17):10355-61 [9553091] Mol Cell Biol. 1998 May;18(5):2617-28 [9566881] Mol Endocrinol. 1998 May;12(5):664-74 [9605929] Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7322-6 [9636147] Keio J Med. 1998 Jun;47(2):73-7 [9659816] Ann N Y Acad Sci. 1998 Jun 30;850:64-9 [9668528] Mol Cell Biol. 1998 Aug;18(8):4471-87 [9671457] Am J Hematol. 1999 Jan;60(1):27-35 [9883803] J Biol Chem. 1999 Jan 15;274(3):1628-34 [9880542] Biochemistry. 1999 Jan 12;38(2):589-95 [9888798] Blood Cells Mol Dis. 1998 Sep;24(3):356-69 [10087993] Eur J Biochem. 1999 Mar;260(3):692-700 [10102997] Mol Endocrinol. 1999 Apr;13(4):632-43 [10194768] Protein Eng. 1999 Mar;12(3):235-42 [10235624] Nat Genet. 1999 Jul;22(3):215-7 [10391203] Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10051-5 [10468560] Blood. 1975 Mar;45(3):321-34 [163658] Proc Natl Acad Sci U S A. 1980 Jun;77(6):3509-13 [6932034] Proc Natl Acad Sci U S A. 1981 Jan;78(1):348-52 [6264439] Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 [6828386] Proc Natl Acad Sci U S A. 1983 Sep;80(18):5515-9 [6310580] Nature. 1984 Apr 5-11;308(5959):509-13 [6323997] Proc Natl Acad Sci U S A. 1984 Jul;81(14):4485-9 [6205398] Cell. 1987 Dec 24;51(6):975-85 [3690667] Nucleic Acids Res. 1988 Aug 11;16(15):7351-67 [3045756] Nucleic Acids Res. 1988 Oct 25;16(20):9687-705 [2972993] Proc Natl Acad Sci U S A. 1989 Apr;86(8):2554-8 [2704733] Nucleic Acids Res. 1989 Nov 11;17(21):8833-52 [2587218] Gene. 1989 Dec 21;85(1):15-23 [2533576] Nature. 1990 Mar 22;344(6264):309-13 [2314472] Nature. 1990 Apr 26;344(6269):830-6 [2330041] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10188-92 [1946439] EMBO J. 1992 Mar;11(3):1055-63 [1547772] Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5809-13 [1631062] Sci China B. 1993 Jan;36(1):81-8 [8503989] Genes Dev. 1993 Aug;7(8):1521-34 [8339930] Nucleic Acids Res. 1993 Jul 25;21(15):3427-36 [8346022] Eur J Biochem. 1995 Jul 15;231(2):271-81 [7635138] Curr Opin Cell Biol. 1995 Jun;7(3):362-70 [7662366] Mol Cell Biol. 1996 Mar;16(3):829-38 [8622684] DNA Cell Biol. 1996 May;15(5):347-52 [8924208] EMBO J. 1996 Dec 16;15(24):7079-87 [9003783] Blood. 1997 Jul 1;90(1):421-7 [9207479] Anal Biochem. 1997 Dec 1;254(1):1-8 [9398338] Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):969-74 [9448269] EMBO J. 1998 Feb 2;17(3):817-26 [9451006] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dietary heterocyclic amines and the risk of lung cancer among Missouri women. AN - 71269897; 10919646 AB - Heterocyclic amines (HCAs) such as 2-amino-3,8-dimethylimidazo[4,5f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx,), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are found in meats cooked at high temperatures. In rodents, MeIQx induces lung tumors. The purpose of this study was to investigate lung cancer risk posed by different HCAs in the diet. A population-based case-control study of 593 cases and 623 frequency-matched controls including both nonsmoking and smoking women was conducted in Missouri. An administered food frequency questionnaire with detailed questions on meat consumption, degrees of internal doneness, surface browning/charring, and cooking technique was linked to a database that provided exposure estimates of three HCAs. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. When comparing the 90th and 10th percentiles, significant excess risks were observed for MeIQx (OR, 1.5; CI, 1.1-2.0), but not for DiMeIQx (OR, 1.2; CI, 0.9-1.6) or PhIP (OR, 0.9; CI, 0.8-1.1). MeIQx consumption was associated with increased risk of lung cancer for nonsmokers (OR, 3.6; CI, 1.3-10.3) and light/moderate smokers (OR, 2.1; CI, 1.3-3.3), but not for heavy smokers (OR, 1.0; CI, 0.7-1.5). There was elevated risk with MeIQx intake for subjects with squamous cell carcinomas (OR, 1.9; CI, 1.2-3.1) and "other histological cell types" (OR, 1.6; CI, 1.1-2.5), but not for subjects with small cell carcinomas and adenocarcinomas. Neither DiMeIQx nor PhIP showed an association with smoking categories or lung cancer histology. In conclusion, MeIQx may be associated with lung cancer risk, but DiMeIQx and PhIP are probably not associated with lung cancer risk. JF - Cancer research AU - Sinha, R AU - Kulldorff, M AU - Swanson, C A AU - Curtin, J AU - Brownson, R C AU - Alavanja, M C AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. sinhar@nih.gov Y1 - 2000/07/15/ PY - 2000 DA - 2000 Jul 15 SP - 3753 EP - 3756 VL - 60 IS - 14 SN - 0008-5472, 0008-5472 KW - Heterocyclic Compounds KW - 0 KW - Imidazoles KW - Quinoxalines KW - 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline KW - 77500-04-0 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - 3,4,8-trimethylimidazo(4,5-f)quinoxalin-2-amine KW - YRA7G7WU6P KW - Index Medicus KW - Carcinoma, Squamous Cell -- etiology KW - Carcinoma, Small Cell -- etiology KW - Missouri KW - Humans KW - Aged KW - Imidazoles -- analysis KW - Multivariate Analysis KW - Smoking KW - Hot Temperature KW - Aged, 80 and over KW - Risk Factors KW - Quinoxalines -- analysis KW - Adenocarcinoma -- etiology KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Female KW - Lung Neoplasms -- etiology KW - Heterocyclic Compounds -- analysis KW - Diet UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71269897?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dietary+heterocyclic+amines+and+the+risk+of+lung+cancer+among+Missouri+women.&rft.au=Sinha%2C+R%3BKulldorff%2C+M%3BSwanson%2C+C+A%3BCurtin%2C+J%3BBrownson%2C+R+C%3BAlavanja%2C+M+C&rft.aulast=Sinha&rft.aufirst=R&rft.date=2000-07-15&rft.volume=60&rft.issue=14&rft.spage=3753&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 - 2000-08-24 N1 - Date created - 2000-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human mesothelioma samples overexpress both cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (NOS2): in vitro antiproliferative effects of a COX-2 inhibitor. AN - 71268973; 10919635 AB - Accumulating data demonstrate overexpression of both inducible NO synthase (NOS2) and cyclooxygenase-2 (COX2) in many epithelial neoplasias. In addition, cyclooxygenase inhibitors have been shown to have antineoplastic and prophylactic efficacy against human colon cancer and in mouse models of this disease. Mesothelioma arises in a context of asbestos exposure and chronic inflammation, which would be expected to enhance the expression of these inducible enzymes. This study demonstrates that both inducible enzymes were expressed in 30 human mesothelioma tissues but were not detectable in nonreactive mesothelial tissues from the same individuals. In contrast, areas of reactive mesothelial cells stained positively for these enzymes. In vitro exposure of human mesothelioma cell lines to the COX2 inhibitor, NS398, revealed dose- and time-dependent antiproliferative activity, whereas the NOS2 inhibitor, 1400W, had no detectable inhibitory effect. Surprisingly, nonmalignant human mesothelial isolates expressed both NOS2 and COX2 in vitro at the same level as mesothelioma cell lines but were less sensitive to NS398 inhibition. This finding indicates that these nonmalignant isolates may retain properties of reactive mesothelial cells and suggests that targets in addition to COX2 may be involved in the antiproliferative response of mesothelioma cell lines. These results have clinical significance because of the selective activity of the drug coupled with the therapeutic resistance and poor prognosis of mesothelioma. The findings presented here suggest that further preclinical studies of these inhibitors in animal models of mesothelioma would be of great interest. JF - Cancer research AU - Marrogi, A AU - Pass, H I AU - Khan, M AU - Metheny-Barlow, L J AU - Harris, C C AU - Gerwin, B I AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2000/07/15/ PY - 2000 DA - 2000 Jul 15 SP - 3696 EP - 3700 VL - 60 IS - 14 SN - 0008-5472, 0008-5472 KW - Amidines KW - 0 KW - Anti-Inflammatory Agents, Non-Steroidal KW - Benzylamines KW - Cyclooxygenase 2 Inhibitors KW - Cyclooxygenase Inhibitors KW - Enzyme Inhibitors KW - Isoenzymes KW - Membrane Proteins KW - N-(3-(aminomethyl)benzyl)acetamidine KW - Nitrobenzenes KW - Sulfonamides KW - N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide KW - 123653-11-2 KW - Asbestos KW - 1332-21-4 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 - Index Medicus KW - Benzylamines -- pharmacology KW - Nitrobenzenes -- pharmacology KW - Dose-Response Relationship, Drug KW - Humans KW - Cell Division -- drug effects KW - Aged KW - Lung -- metabolism KW - Cyclooxygenase Inhibitors -- pharmacology KW - Amidines -- pharmacology KW - Tumor Cells, Cultured KW - Sulfonamides -- pharmacology KW - Adult KW - Lung -- drug effects KW - Asbestos -- adverse effects KW - Enzyme Inhibitors -- pharmacology KW - Middle Aged KW - Time Factors KW - Immunohistochemistry KW - Male KW - Female KW - Lung Neoplasms -- enzymology KW - Lung Neoplasms -- drug therapy KW - Mesothelioma -- etiology KW - Prostaglandin-Endoperoxide Synthases -- pharmacology KW - Mesothelioma -- enzymology KW - Nitric Oxide Synthase -- biosynthesis KW - Isoenzymes -- antagonists & inhibitors KW - Mesothelioma -- drug therapy KW - Lung Neoplasms -- etiology KW - Isoenzymes -- biosynthesis KW - Mesothelioma -- mortality KW - Lung Neoplasms -- mortality KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis KW - Isoenzymes -- pharmacology KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71268973?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Human+mesothelioma+samples+overexpress+both+cyclooxygenase-2+%28COX-2%29+and+inducible+nitric+oxide+synthase+%28NOS2%29%3A+in+vitro+antiproliferative+effects+of+a+COX-2+inhibitor.&rft.au=Marrogi%2C+A%3BPass%2C+H+I%3BKhan%2C+M%3BMetheny-Barlow%2C+L+J%3BHarris%2C+C+C%3BGerwin%2C+B+I&rft.aulast=Marrogi&rft.aufirst=A&rft.date=2000-07-15&rft.volume=60&rft.issue=14&rft.spage=3696&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 - 2000-08-24 N1 - Date created - 2000-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Myeloid specific human CD33 is an inhibitory receptor with differential ITIM function in recruiting the phosphatases SHP-1 and SHP-2. AN - 71246819; 10887109 AB - CD33 is a myeloid specific member of the sialic acid-binding receptor family and is expressed highly on myeloid progenitor cells but at much lower levels in differentiated cells. Human CD33 has two tyrosine residues in its cytoplasmic domain (Y340 and Y358). When phosphorylated, these tyrosines could function as docking sites for the phosphatases, SHP-1 and/or SHP-2, enabling CD33 to function as an inhibitory receptor. Here we demonstrate that CD33 is tyrosine phosphorylated in the presence of the phosphatase inhibitor, pervanadate, and recruits SHP-1 and SHP-2. Co-expression studies suggest that the Src-family kinase Lck is effective at phosphorylating Y340, but not Y358, suggesting that these residues may function in the selective recruitment of adapter molecules and have distinct functions. Further support for overlapping, but nonredundant, roles for Y340 and Y358 comes from peptide-binding studies that revealed the recruitment of both SHP-1 and SHP-2 to Y340 but only SHP-2 to Y358. Analysis using mutants of SHP-1 demonstrated that binding Y340 of CD33 was primarily to the amino Src homology-2 domain of SHP-1. The potential of CD33 to function as an inhibitory receptor was demonstrated by its ability to down-regulate CD64-induced calcium mobilization in U937. The dependence of this inhibition on SHP-1 was demonstrated by blocking CD33-mediated effects with dominant negative SHP-1. This result implies that CD33 is an inhibitory receptor and also that SHP-1 phosphatase has a significant role in mediating CD33 function. Further studies are essential to identify the receptor(s) that CD33 inhibits in vivo and its function in myeloid lineage development. (Blood. 2000;96:483-490) JF - Blood AU - Paul, S P AU - Taylor, L S AU - Stansbury, E K AU - McVicar, D W AD - Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute, NCI-FCRDC, Frederick, Maryland 21702, USA. Y1 - 2000/07/15/ PY - 2000 DA - 2000 Jul 15 SP - 483 EP - 490 VL - 96 IS - 2 SN - 0006-4971, 0006-4971 KW - Antigens, CD KW - 0 KW - Antigens, Differentiation, Myelomonocytic KW - CD33 protein, human KW - Intracellular Signaling Peptides and Proteins KW - Peptide Fragments KW - Sialic Acid Binding Ig-like Lectin 3 KW - Phosphotyrosine KW - 21820-51-9 KW - PTPN11 protein, human KW - EC 3.1.3.48 KW - PTPN6 protein, human KW - Protein Tyrosine Phosphatase, Non-Receptor Type 11 KW - Protein Tyrosine Phosphatase, Non-Receptor Type 6 KW - Protein Tyrosine Phosphatases KW - Abridged Index Medicus KW - Index Medicus KW - Peptide Fragments -- metabolism KW - Gene Transfer Techniques KW - Humans KW - Phosphotyrosine -- metabolism KW - Gene Expression KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Blotting, Western KW - Peptide Fragments -- chemistry KW - Phosphorylation KW - Molecular Sequence Data KW - Immunosorbent Techniques KW - Cell Line KW - Antigens, CD -- physiology KW - Antigens, Differentiation, Myelomonocytic -- physiology KW - Protein Tyrosine Phosphatases -- metabolism KW - Antigens, CD -- chemistry KW - Antigens, Differentiation, Myelomonocytic -- chemistry KW - Antigens, CD -- genetics KW - Antigens, Differentiation, Myelomonocytic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71246819?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Myeloid+specific+human+CD33+is+an+inhibitory+receptor+with+differential+ITIM+function+in+recruiting+the+phosphatases+SHP-1+and+SHP-2.&rft.au=Paul%2C+S+P%3BTaylor%2C+L+S%3BStansbury%2C+E+K%3BMcVicar%2C+D+W&rft.aulast=Paul&rft.aufirst=S&rft.date=2000-07-15&rft.volume=96&rft.issue=2&rft.spage=483&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-17 N1 - Date created - 2000-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Maintenance of large numbers of virus-specific CD8+ T cells in HIV-infected progressors and long-term nonprogressors. AN - 71229874; 10878387 AB - The virus-specific CD8+ T cell responses of 21 HIV-infected patients were studied including a unique cohort of long-term nonprogressors with low levels of plasma viral RNA and strong proliferative responses to HIV Ags. HIV-specific CD8+ T cell responses were studied by a combination of standard cytotoxic T cell (CTL) assays, MHC tetramers, and TCR repertoire analysis. The frequencies of CD8+ T cells specific to the majority of HIV gene products were measured by flow cytometric detection of intracellular IFN-gamma in response to HIV-vaccinia recombinant-infected autologous B cells. Very high frequencies (0.8-18.0%) of circulating CD8+ T cells were found to be HIV specific. High frequencies of HIV-specific CD8+ T cells were not limited to long-term nonprogressors with restriction of plasma virus. No correlation was found between the frequency of HIV-specific CD8+ T cells and levels of plasma viremia. In each case, the vast majority of cells (up to 17.2%) responded to gag-pol. Repertoire analysis showed these large numbers of Ag-specific cells were scattered throughout the repertoire and in the majority of cases not contained within large monoclonal expansions. These data demonstrate that high numbers of HIV-specific CD8+ T cells exist even in patients with high-level viremia and progressive disease. Further, they suggest that other qualitative parameters of the CD8+ T cell response may differentiate some patients with very low levels of plasma virus and nonprogressive disease. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Gea-Banacloche, J C AU - Migueles, S A AU - Martino, L AU - Shupert, W L AU - McNeil, A C AU - Sabbaghian, M S AU - Ehler, L AU - Prussin, C AU - Stevens, R AU - Lambert, L AU - Altman, J AU - Hallahan, C W AU - de Quiros, J C AU - Connors, M AD - Laboratories ofImmunoregulation and Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2000/07/15/ PY - 2000 DA - 2000 Jul 15 SP - 1082 EP - 1092 VL - 165 IS - 2 SN - 0022-1767, 0022-1767 KW - Epitopes, T-Lymphocyte KW - 0 KW - HIV Antigens KW - Receptors, Antigen, T-Cell, alpha-beta KW - Interferon-gamma KW - 82115-62-6 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Lymphocyte Count KW - Interferon-gamma -- secretion KW - Humans KW - Receptors, Antigen, T-Cell, alpha-beta -- analysis KW - Adult KW - Molecular Sequence Data KW - Disease Progression KW - Cytotoxicity Tests, Immunologic KW - Middle Aged KW - Amino Acid Sequence KW - Receptors, Antigen, T-Cell, alpha-beta -- genetics KW - Male KW - Female KW - HIV Infections -- virology KW - Epitopes, T-Lymphocyte -- immunology KW - T-Lymphocytes, Cytotoxic -- immunology KW - HIV Infections -- pathology KW - HIV Antigens -- immunology KW - Epitopes, T-Lymphocyte -- analysis KW - T-Lymphocytes, Cytotoxic -- metabolism KW - Epitopes, T-Lymphocyte -- genetics KW - T-Lymphocytes, Cytotoxic -- secretion KW - Cytotoxicity, Immunologic KW - HIV Infections -- immunology KW - HIV Infections -- metabolism KW - T-Lymphocytes, Cytotoxic -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71229874?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Maintenance+of+large+numbers+of+virus-specific+CD8%2B+T+cells+in+HIV-infected+progressors+and+long-term+nonprogressors.&rft.au=Gea-Banacloche%2C+J+C%3BMigueles%2C+S+A%3BMartino%2C+L%3BShupert%2C+W+L%3BMcNeil%2C+A+C%3BSabbaghian%2C+M+S%3BEhler%2C+L%3BPrussin%2C+C%3BStevens%2C+R%3BLambert%2C+L%3BAltman%2C+J%3BHallahan%2C+C+W%3Bde+Quiros%2C+J+C%3BConnors%2C+M&rft.aulast=Gea-Banacloche&rft.aufirst=J&rft.date=2000-07-15&rft.volume=165&rft.issue=2&rft.spage=1082&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 - 2000-08-03 N1 - Date created - 2000-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Requirements for the Maintenance of Th1 Immunity In Vivo Following DNA Vaccination: A Potential Immunoregulatory Role for CD8 super(+) T Cells AN - 17598952; 4739770 AB - Protective immunity against Leishmania major generated by DNA encoding the LACK (Leishmania homologue of receptor for activated C kinase) Ag has been shown to be more durable than vaccination with LACK protein plus IL-12. One mechanism to account for this may be the selective ability of DNA vaccination to induce CD8 super(+) IFN- gamma -producing T cells. In this regard, we previously reported that depletion of CD8 super(+) T cells in LACK DNA-vaccinated mice abrogated protection when infectious challenge was done 2 wk postvaccination. In this study, we extend these findings to study the mechanism by which CD8 super(+) T cells induced by LACK DNA vaccination mediate both short- and long-term protective immunity against L. major. Mice vaccinated with LACK DNA and depleted of CD8 super(+) T cells at the time of vaccination or infection were unable to control infection when challenge was done 2 or 12 wk postvaccination. Remarkably, it was noted that depletion of CD8 super(+) T cells in LACK DNA-vaccinated mice was associated with a striking decrease in the frequency of LACK-specific CD4 super(+) IFN- gamma -producing T cells both before and after infection. Moreover, data are presented to suggest a mechanism by which CD8 super(+) T cells exert this regulatory role. Taken together, these data provide additional insight into how Th1 cells are generated and sustained in vivo and suggest a potentially novel immunoregulatory role for CD8 super(+) T cells following DNA vaccination. JF - Journal of Immunology AU - Gurunathan, S AU - Stobie, L AU - Prussin, C AU - Sacks, D L AU - Glaichenhaus, N AU - Fowell, D J AU - Locksley, R M AU - Chang, J T AU - Wu, C-Y AU - Seder, R A AD - Clinical Immunology Section, LCI, NIAID, 10 Center Drive, Room 10/11C215, Bethesda, MD 20892, USA, rseder@nih.gov Y1 - 2000/07/15/ PY - 2000 DA - 2000 Jul 15 SP - 915 EP - 924 VL - 165 IS - 2 SN - 0022-1767, 0022-1767 KW - mice KW - immunology KW - CD8 antigen KW - LACK antigen KW - Leishmania major KW - Biotechnology and Bioengineering Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Helper cells KW - DNA vaccines KW - Lymphocytes T KW - Vaccines KW - K 03086:Immunology & vaccination KW - F 06807:Active immunization KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17598952?accountid=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+Immunology&rft.atitle=Requirements+for+the+Maintenance+of+Th1+Immunity+In+Vivo+Following+DNA+Vaccination%3A+A+Potential+Immunoregulatory+Role+for+CD8+super%28%2B%29+T+Cells&rft.au=Gurunathan%2C+S%3BStobie%2C+L%3BPrussin%2C+C%3BSacks%2C+D+L%3BGlaichenhaus%2C+N%3BFowell%2C+D+J%3BLocksley%2C+R+M%3BChang%2C+J+T%3BWu%2C+C-Y%3BSeder%2C+R+A&rft.aulast=Gurunathan&rft.aufirst=S&rft.date=2000-07-15&rft.volume=165&rft.issue=2&rft.spage=915&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&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 - Leishmania major; Lymphocytes T; Helper cells; Vaccines; DNA vaccines ER - TY - JOUR T1 - Active site studies of bovine alpha1-->3-galactosyltransferase and its secondary structure prediction. AN - 72291662; 11004566 AB - The catalytic domain of bovine alpha1-->3-galactosyltransferase (alpha3GalT), residues 80-368, have been cloned and expressed, in Escherichia coli. Using a sequential purification protocol involving a Ni(2+) affinity column followed by a UDP-hexanolamine affinity column, we have obtained a pure and active protein from the soluble fraction which catalyzes the transfer of galactose (Gal) from UDP-Gal to N-acetyllactosamine (LacNAc) with a specific activity of 0.69 pmol/min/ng. The secondary structural content of alpha3GalT protein was analyzed by Fourier transform infrared (FTIR) spectroscopy, which shows that the enzyme has about 35% beta-sheet and 22% alpha-helix. This predicted secondary structure content by FTIR spectroscopy was used in the protein sequence analysis algorithm, developed by the Biomolecular Engineering Research Center at Boston University and Tasc Inc., for the assignment of secondary structural elements to the amino acid sequence of alpha3GalT. The enzyme appears to have three major and three minor helices and five sheet-like structures. The studies on the acceptor substrate specificity of the enzyme, alpha3GalT, show that in addition to LacNAc, which is the natural substrate, the enzyme accepts various other disaccharides as substrates such as lactose and Gal derivatives, beta-O-methylgalactose and beta-D-thiogalactopyranoside, albeit with lower specific activities. There is an absolute requirement for Gal to be at the non-reducing end of the acceptor molecule which has to be beta1-->4-linked to a second residue that can be more diverse in structure. The kinetic parameters for four acceptor molecules were determined. Lactose binds and functions in a similar way as LacNAc. However, beta-O-methylgalactose and Gal do not bind as tightly as LacNAc or lactose, as their K(ia) and K(A) values indicate, suggesting that the second monosaccharide is critical for holding the acceptor molecule in place. The 2' and 4' hydroxyl groups of the receiving Gal moiety are important in binding. Even though there is large structural variability associated with the second residue of the acceptor molecule, there are constraints which do not allow certain Gal-R sugars to be good acceptors for the enzyme. The beta1-->4-linked residue at the second position of the acceptor molecule is preferred, but the interactions between the enzyme and the second residue are likely to be non-specific. JF - Biochimica et biophysica acta AU - Shah, P S AU - Bizik, F AU - Dukor, R K AU - Qasba, P K AD - Structural Glycobiology Section, Laboratory of Experimental and Computational Biology, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 2000/07/14/ PY - 2000 DA - 2000 Jul 14 SP - 222 EP - 234 VL - 1480 IS - 1-2 SN - 0006-3002, 0006-3002 KW - DNA Primers KW - 0 KW - Metals KW - Recombinant Proteins KW - Galactosyltransferases KW - EC 2.4.1.- KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - Models, Molecular KW - Amino Acid Sequence KW - Recombinant Proteins -- genetics KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Base Sequence KW - Cattle KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Metals -- metabolism KW - Galactosyltransferases -- metabolism KW - Galactosyltransferases -- isolation & purification KW - Galactosyltransferases -- genetics KW - Galactosyltransferases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72291662?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=Active+site+studies+of+bovine+alpha1--%26gt%3B3-galactosyltransferase+and+its+secondary+structure+prediction.&rft.au=Shah%2C+P+S%3BBizik%2C+F%3BDukor%2C+R+K%3BQasba%2C+P+K&rft.aulast=Shah&rft.aufirst=P&rft.date=2000-07-14&rft.volume=1480&rft.issue=1-2&rft.spage=222&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-30 N1 - Date created - 2000-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibitory effects of nitric oxide and nitrosative stress on dopamine-beta-hydroxylase. AN - 71248275; 10887204 AB - Dopamine-beta-hydroxylase (DbetaH) is a copper-containing enzyme that uses molecular oxygen and ascorbate to catalyze the addition of a hydroxyl group on the beta-carbon of dopamine to form norepinephrine. While norepinephrine causes vasoconstriction following reflex sympathetic stimulation, nitric oxide (NO) formation results in vasodilatation via a guanylyl cyclase-dependent mechanism. In this report, we investigated the relationship between NO and DbetaH enzymatic activity. In the initial in vitro experiments, the activity of purified DbetaH was inhibited by the NO donor, diethylamine/NO (DEA/NO), with an IC(50) of 1 mm. The inclusion of either azide or GSH partially restored DbetaH activity, suggesting the involvement of the reactive nitrogen oxide species, N(2)O(3). Treatment of human neuroblastoma cells (SK-N-MC) with diethylamine/NO decreased cellular DbetaH activity without affecting their growth rate and was augmented by the depletion of intracellular GSH. Co-culture of the SK-N-MC cells with interferon-gamma and lipopolysaccharide-activated macrophages, which release NO, also reduced the DbetaH activity in the neuroblastoma cells. Our results are consistent with the hypothesis that nitrosative stress, mediated by N(2)O(3), can result in the inhibition of norepinephrine biosynthesis and may contribute to the regulation of neurotransmission and vasodilatation. JF - The Journal of biological chemistry AU - Zhou, X AU - Espey, M G AU - Chen, J X AU - Hofseth, L J AU - Miranda, K M AU - Hussain, S P AU - Wink, D A AU - Harris, C C AD - Laboratory of Human Carcinogenesis, Radiation Biology Branch, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/07/14/ PY - 2000 DA - 2000 Jul 14 SP - 21241 EP - 21246 VL - 275 IS - 28 SN - 0021-9258, 0021-9258 KW - Hydrazines KW - 0 KW - Lipopolysaccharides KW - Nitric Oxide Donors KW - Nitrogen Oxides KW - omega-N-Methylarginine KW - 27JT06E6GR KW - Nitric Oxide KW - 31C4KY9ESH KW - Interferon-gamma KW - 82115-62-6 KW - 1,1-diethyl-2-hydroxy-2-nitrosohydrazine KW - 86831-65-4 KW - Sodium Azide KW - 968JJ8C9DV KW - Dopamine beta-Hydroxylase KW - EC 1.14.17.1 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Animals KW - Coculture Techniques KW - Humans KW - Lipopolysaccharides -- pharmacology KW - Macrophage Activation KW - Macrophages -- physiology KW - Adrenal Glands -- enzymology KW - Interferon-gamma -- pharmacology KW - Mice KW - Macrophages -- drug effects KW - Glutathione -- pharmacology KW - Neuroblastoma KW - Sodium Azide -- pharmacology KW - Microglia -- enzymology KW - Cattle KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Kinetics KW - Microglia -- cytology KW - omega-N-Methylarginine -- pharmacology KW - Microglia -- drug effects KW - Nitric Oxide Donors -- pharmacology KW - Hydrazines -- pharmacology KW - Nitric Oxide -- pharmacology KW - Dopamine beta-Hydroxylase -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71248275?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibitory+effects+of+nitric+oxide+and+nitrosative+stress+on+dopamine-beta-hydroxylase.&rft.au=Zhou%2C+X%3BEspey%2C+M+G%3BChen%2C+J+X%3BHofseth%2C+L+J%3BMiranda%2C+K+M%3BHussain%2C+S+P%3BWink%2C+D+A%3BHarris%2C+C+C&rft.aulast=Zhou&rft.aufirst=X&rft.date=2000-07-14&rft.volume=275&rft.issue=28&rft.spage=21241&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 - 2000-08-16 N1 - Date created - 2000-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specific functional interaction of human cytohesin-1 and ADP-ribosylation factor domain protein (ARD1). AN - 71247609; 10748148 AB - Activation of ADP-ribosylation factors (ARFs) is mediated by guanine nucleotide-exchange proteins, which accelerate conversion of inactive ARF-GDP to active ARF-GTP. ARF domain protein (ARD1), a 64-kDa GTPase with a C-terminal ADP-ribosylation factor domain, is localized to lysosomes and the Golgi apparatus. When ARD1 was used as bait to screen a human liver cDNA library using the yeast two-hybrid system, a cDNA for cytohesin-1, a approximately 50-kDa protein with ARF guanine nucleotide-exchange protein activity, was isolated. In this system, ARD1-GDP interacted well with cytohesin-1 but very poorly with cytohesin-2. In agreement, cytohesin-1, but not cytohesin-2, markedly accelerated [(35)S]guanosine 5'-3-O-(thio)triphosphate binding to ARD1. The effector region of the ARF domain of ARD1 appeared to be critical for the specific interaction with cytohesin-1. Replacement of single amino acids in the Sec7 domains of cytohesin-1 and -2 showed that residue 30 is critical for specificity. In transfected COS-7 cells, overexpressed ARD1 and cytohesin-1 were partially colocalized, as determined by confocal fluorescence microscopy. It was concluded that cytohesin-1 is likely to be involved in ARD1 activation, consistent with a role for ARD1 in the regulation of vesicular trafficking. JF - The Journal of biological chemistry AU - Vitale, N AU - Pacheco-Rodriguez, G AU - Ferrans, V J AU - Riemenschneider, W AU - Moss, J AU - Vaughan, M AD - Pulmonary-Critical Care Medicine Branch and the Pathology Section, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/07/14/ PY - 2000 DA - 2000 Jul 14 SP - 21331 EP - 21339 VL - 275 IS - 28 SN - 0021-9258, 0021-9258 KW - Cell Adhesion Molecules KW - 0 KW - Guanine Nucleotide Exchange Factors KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - TRIM23 protein, human KW - cytohesin-1 KW - Guanosine Diphosphate KW - 146-91-8 KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - GTP Phosphohydrolases KW - EC 3.6.1.- KW - GTP-Binding Proteins KW - Index Medicus KW - Guanosine Diphosphate -- metabolism KW - Humans KW - Liver -- metabolism KW - Amino Acid Sequence KW - Saccharomyces cerevisiae KW - Cloning, Molecular KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Sequence Alignment KW - Transfection KW - Recombinant Proteins -- metabolism KW - GTP Phosphohydrolases -- metabolism KW - Kinetics KW - Point Mutation KW - Molecular Sequence Data KW - Guanosine 5'-O-(3-Thiotriphosphate) -- metabolism KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Amino Acid Substitution KW - Cell Line KW - Gene Library KW - GTP-Binding Proteins -- metabolism KW - GTP-Binding Proteins -- chemistry KW - Cell Adhesion Molecules -- metabolism KW - Cell Adhesion Molecules -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71247609?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Specific+functional+interaction+of+human+cytohesin-1+and+ADP-ribosylation+factor+domain+protein+%28ARD1%29.&rft.au=Vitale%2C+N%3BPacheco-Rodriguez%2C+G%3BFerrans%2C+V+J%3BRiemenschneider%2C+W%3BMoss%2C+J%3BVaughan%2C+M&rft.aulast=Vitale&rft.aufirst=N&rft.date=2000-07-14&rft.volume=275&rft.issue=28&rft.spage=21331&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 - 2000-08-16 N1 - Date created - 2000-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunologic and virologic effects of subcutaneous interleukin 2 in combination with antiretroviral therapy: A randomized controlled trial. AN - 71226235; 10889591 AB - While interleukin 2 (IL-2) is capable of inducing a marked expansion of the CD4 T-lymphocyte pool, limited data exist on whether IL-2 treatment can add significantly to the immunologic and virologic effects of potent antiretroviral therapy (ART). To determine the rate and magnitude of CD4 cell recovery and viral suppression when using a combination therapy of IL-2 and ART compared with ART alone. Randomized, controlled multicenter trial conducted from April 1996 through April 1998 at 8 clinical sites in the United States. Eighty-two adult outpatients who were infected with human immunodeficiency virus (HIV) and had baseline CD4 cell counts of 200 x 10(6)/L to 500 x 10(6)/L and baseline RNA levels of fewer than 10,000 copies/mL were randomized; 78 completed the study. Thirty-nine patients were randomly assigned to receive a combination therapy of subcutaneous IL-2 (administered in 5-day courses every 8 weeks at a starting dosage of 7.5 mIU twice per day) and ART; 43 were to receive ART therapy alone. Interleukin 2 safety and differential effects on CD4 cell counts, CD4 cell percentages, and plasma HIV RNA levels. The mean (SD) percentage increase in CD4 cell counts at 1 year for patients who received IL-2 was 112% (113%) compared with 18% (35%) in recipients of ART alone (P<.001). Both groups had mean (SD) increases in CD4 cell percentage: from 20.4% (6.3%) to 32.3% (12.4%) for the combination therapy group compared with 20.4% (5.1%) to 23.0% (7.2%) for recipients of ART alone (P<.001). Using a sensitive viral RNA assay, mean viral load changes were -0.28 and 0.09 log(10) copies for IL-2 recipients and control patients, respectively (P=.03). Twenty (67%) of 30 evaluable patients receiving IL-2 achieved final viral loads of fewer than 50 copies/mL compared with 13 (36%) of 36 control patients (P=.02). Toxic effects were common among patients who received IL-2 and were managed with antipyretics, hydration, rest, and dosage reduction as needed. Intermittent therapy with IL-2 and ART produced a substantially greater increase in CD4 cells and was associated with a larger decrease in viral load than ART alone. Clinical end-point trials will be necessary to determine whether the enhanced viral suppression and CD4 cell increases associated with IL-2 therapy will translate into improved clinical outcomes. JAMA. 2000;284:183-189 JF - JAMA AU - Davey, R T AU - Murphy, R L AU - Graziano, F M AU - Boswell, S L AU - Pavia, A T AU - Cancio, M AU - Nadler, J P AU - Chaitt, D G AU - Dewar, R L AU - Sahner, D K AU - Duliege, A M AU - Capra, W B AU - Leong, W P AU - Giedlin, M A AU - Lane, H C AU - Kahn, J O AD - National Institutes of Health, Bethesda, MD 20892-1880, USA. rdavey@niaid.nih.gov Y1 - 2000/07/12/ PY - 2000 DA - 2000 Jul 12 SP - 183 EP - 189 VL - 284 IS - 2 SN - 0098-7484, 0098-7484 KW - Anti-HIV Agents KW - 0 KW - Immunoglobulin G KW - Immunoglobulin M KW - Interleukin-2 KW - RNA, Viral KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - HIV-1 -- genetics KW - Analysis of Variance KW - Humans KW - Aged KW - Antibody Formation KW - CD4 Lymphocyte Count KW - Viral Load KW - Drug Therapy, Combination KW - Prospective Studies KW - Adult KW - Middle Aged KW - Immunoglobulin M -- biosynthesis KW - Immunoglobulin G -- biosynthesis KW - Female KW - Male KW - RNA, Viral -- blood KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - HIV Infections -- virology KW - Anti-HIV Agents -- therapeutic use KW - Interleukin-2 -- therapeutic use KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy KW - Anti-HIV Agents -- administration & dosage KW - Interleukin-2 -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71226235?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Immunologic+and+virologic+effects+of+subcutaneous+interleukin+2+in+combination+with+antiretroviral+therapy%3A+A+randomized+controlled+trial.&rft.au=Davey%2C+R+T%3BMurphy%2C+R+L%3BGraziano%2C+F+M%3BBoswell%2C+S+L%3BPavia%2C+A+T%3BCancio%2C+M%3BNadler%2C+J+P%3BChaitt%2C+D+G%3BDewar%2C+R+L%3BSahner%2C+D+K%3BDuliege%2C+A+M%3BCapra%2C+W+B%3BLeong%2C+W+P%3BGiedlin%2C+M+A%3BLane%2C+H+C%3BKahn%2C+J+O&rft.aulast=Davey&rft.aufirst=R&rft.date=2000-07-12&rft.volume=284&rft.issue=2&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-25 N1 - Date created - 2000-07-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 2000 Oct 25;284(16):2055-6 [11042746] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Current evidence and future directions for targeting HIV entry: therapeutic and prophylactic strategies. AN - 71221399; 10889596 AB - Great strides have been made in developing potent antiretroviral regimens that block human immunodeficiency virus (HIV) transcription and assembly. Despite these therapeutic advances, problems of drug resistance, latent viral reservoirs, and drug-induced toxic effects that compromise effective viral control point to the need for new classes of anti-HIV drugs with different modes of action. One promising approach involves blocking HIV entry into human cells, a complex process that involves multiple protein interactions. The process of HIV entry begins with binding of the viral envelope glycoprotein to both the CD4 receptor and one of several chemokine receptors and ends with fusion of viral and cell membranes. Conceptually, there are 3 steps in the HIV entry process that could serve as therapeutic targets: binding of the viral envelope glycoprotein with the CD4 receptor, binding of the envelope-CD4 complex to chemokine receptors, and fusion of the viral and cell membranes. Preclinical and clinical assessment of these entry inhibitors is ongoing and will determine if they possess properties required for drug licensure. Moreover, the worldwide epidemic is largely occurring in developing countries that cannot afford these drugs: a prophylactic vaccine is necessary and urgent. New knowledge of the HIV-envelope glycoprotein has also provided insight into possibilities for the design of novel HIV vaccines. JAMA. 2000;284:215-222 JF - JAMA AU - D'Souza, M P AU - Cairns, J S AU - Plaeger, S F AD - Vaccine Clinical Research Branch, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Room 4152, 6700-B Rockledge Dr, Bethesda, MD 20892, USA. pd6n@nih.gov Y1 - 2000/07/12/ PY - 2000 DA - 2000 Jul 12 SP - 215 EP - 222 VL - 284 IS - 2 SN - 0098-7484, 0098-7484 KW - AIDS Vaccines KW - 0 KW - Anti-HIV Agents KW - Antigens, CD4 KW - Receptors, Chemokine KW - Viral Envelope Proteins KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Pharmacology -- trends KW - Protein Binding -- drug effects KW - Humans KW - Receptors, Chemokine -- metabolism KW - Membrane Fusion -- drug effects KW - Forecasting KW - Viral Envelope Proteins -- metabolism KW - Drug Design KW - Antigens, CD4 -- metabolism KW - HIV -- drug effects KW - Anti-HIV Agents -- pharmacology KW - HIV Infections -- prevention & control KW - AIDS Vaccines -- pharmacology KW - HIV -- pathogenicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71221399?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Current+evidence+and+future+directions+for+targeting+HIV+entry%3A+therapeutic+and+prophylactic+strategies.&rft.au=D%27Souza%2C+M+P%3BCairns%2C+J+S%3BPlaeger%2C+S+F&rft.aulast=D%27Souza&rft.aufirst=M&rft.date=2000-07-12&rft.volume=284&rft.issue=2&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-25 N1 - Date created - 2000-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk of Cancer: Children With AIDS AN - 18343179; 5183616 AB - Population-based data on cancers associated with acquired immunodeficiency syndrome (AIDS) in children are lacking. To determine risk of pediatric AIDS-associated cancers. Using records from 11 locations in the United States for varying periods between 1978 and 1996, we linked data for children aged 14 years and younger at AIDS diagnosis to local cancer registry data. Cancer frequency and, in the 2-year post-AIDS onset period, cancer incidence and relative risk (RR; measured as standardized incidence ratio), by cancer type. Among 4954 children with AIDS, 124 (2.5%) were identified as having cancer before, at, or after AIDS onset, including 100 cases of non-Hodgkin lymphoma (NHL), 8 of Kaposi sarcoma (KS), 4 of leiomyosarcoma, and 2 of Hodgkin disease; there were 10 other or unspecified cancers. Expected numbers for all cancers identified in the study sample, based on population rates (using area-specific registry data), were less than 1. In the first 2 years after AIDS diagnosis (5485 person-years), NHL incidence was 510 per 100,000 person-years (RR, 651; 95% confidence interval [CI], 432-941). Median time for developing NHL after AIDS diagnosis was 14 months (range, 3-107 months). The most common type of NHL was Burkitt lymphoma. However, the risk of primary brain lymphoma (91 per 100,000 person-years)was especially high (RR, 7143; 95% CI, 2321-16,692), and 4 cases were diagnosed more than 2 years (range, 37-98 months) after AIDS onset. Leiomyosarcomas also tended to occur several years after AIDS onset, with 3 of the 4 cases occurring 33 to 76 months after AIDS diagnosis, whereas KS was reported only at or within 2 years of AIDS diagnosis. Hodgkin disease risk was also significantly increased (RR, 62; 95% CI, 2-342). The spectrum of AIDS-associated pediatric cancers resembled that seen in adults, with the addition of leiomyosarcoma. Both primary brain lymphomas and leiomyosarcomas tended to occur in children surviving several years after AIDS onset. Because the expected numbers of these cancers in this population were less than 1 and because of the small numbers of some types of observed cancers, the RR estimates are imprecise and caution is warranted in their interpretation. JF - Journal of the American Medical Association AU - Biggar, R J AU - Frisch, M AU - Goedert, J J AD - VEB/NCI, 6120 Executive Blvd, Room 8014, Bethesda, MD 20852, USA, Biggarb@epndce.nci.nih.gov Y1 - 2000/07/12/ PY - 2000 DA - 2000 Jul 12 SP - 205 EP - 209 VL - 284 IS - 2 SN - 0098-7484, 0098-7484 KW - man KW - HIV KW - leiomyosarcoma KW - Risk Abstracts; Virology & AIDS Abstracts KW - Risk assessment KW - Burkitt's lymphoma KW - Acquired immune deficiency syndrome KW - Hodgkin's disease KW - Kaposi's sarcoma KW - Human immunodeficiency virus KW - Brain KW - Children KW - Lymphoma KW - V 22004:AIDS: Clinical aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18343179?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Medical+Association&rft.atitle=Risk+of+Cancer%3A+Children+With+AIDS&rft.au=Biggar%2C+R+J%3BFrisch%2C+M%3BGoedert%2C+J+J&rft.aulast=Biggar&rft.aufirst=R&rft.date=2000-07-12&rft.volume=284&rft.issue=2&rft.spage=205&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Medical+Association&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; Risk assessment; Children; Acquired immune deficiency syndrome; Lymphoma; Kaposi's sarcoma; Hodgkin's disease; Burkitt's lymphoma; Brain ER - TY - JOUR T1 - Chronic combined exposure to cadmium and arsenic exacerbates nephrotoxicity, particularly in metallothionein-I/II null mice. AN - 71749385; 10924798 AB - Cadmium (Cd) and arsenic (As) are important inorganic toxicants in the environment. Humans certainly have the potential to be exposed to the mixtures of Cd and As, but the toxicological interactions of these inorganic mixtures are poorly defined. Metallothionein (MT) is a cysteine-rich, metal-binding protein that plays an important role in Cd detoxication, but its role in As toxicity is less certain. To examine the role of MT in Cd- and/or As-induced nephrotoxicity, MT-I/II-knockout (MT-null) mice and background-matched wild-type (WT) mice were fed CdCl(2) (100 ppm Cd) in the diet, NaAsO(2) (22.5 ppm As) in the drinking water, or Cd plus As for 4 months. Subsequently, nephrotoxicity was examined by morphological and biochemical techniques. Chronic exposure to Cd produced more renal toxicity than As, and the combination of Cd and As produced even more renal injury than caused by either of the chemicals given alone. In mice receiving Cd plus As, proximal tubule degeneration and atrophy, glomerular swelling and interstitial fibrosis were more severe than those produced by either inorganic. Furthermore, lack of MT rendered MT-null mice more sensitive than WT mice to the nephrotoxicity produced by chronic Cd- and/or As-exposure. MT-null mice were especially susceptible to the toxicity produced by the combination of Cd and As, as evidenced by decreased body weight, enzymuria, glucosuria, proteinuria and nephropathy. In conclusion, this study indicates that As may potentiate Cd nephrotoxicity during the long-term, combined exposure, and that intracellular MT plays a role in decreasing the nephropathy of combined exposure to Cd and As. JF - Toxicology AU - Liu, J AU - Liu, Y AU - Habeebu, S M AU - Waalkes, M P AU - Klaassen, C D AD - Laboratory of Comparative Carcinogenesis, NCI at NIEHS, Mail Drop F0-09, Research Triangle Park, NC 27709, USA. lieu6@niehs.nih.gov Y1 - 2000/07/05/ PY - 2000 DA - 2000 Jul 05 SP - 157 EP - 166 VL - 147 IS - 3 SN - 0300-483X, 0300-483X KW - Cadmium KW - 00BH33GNGH KW - Metallothionein KW - 9038-94-2 KW - Acetylglucosaminidase KW - EC 3.2.1.52 KW - Arsenic KW - N712M78A8G KW - Index Medicus KW - Administration, Oral KW - Animals KW - Liver -- anatomy & histology KW - Proteinuria -- urine KW - Drug Administration Schedule KW - Kidney -- metabolism KW - Kidney -- pathology KW - Kidney -- drug effects KW - Liver -- metabolism KW - Mice KW - Acetylglucosaminidase -- metabolism KW - Mice, Knockout KW - Body Weight -- drug effects KW - Glycosuria -- urine KW - Drug Synergism KW - Male KW - Organ Size -- drug effects KW - Kidney Diseases -- metabolism KW - Cadmium -- metabolism KW - Arsenic -- toxicity KW - Arsenic -- metabolism KW - Metallothionein -- physiology KW - Kidney Diseases -- urine KW - Cadmium -- toxicity KW - Metallothionein -- genetics KW - Metallothionein -- metabolism KW - Kidney Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71749385?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Chronic+combined+exposure+to+cadmium+and+arsenic+exacerbates+nephrotoxicity%2C+particularly+in+metallothionein-I%2FII+null+mice.&rft.au=Liu%2C+J%3BLiu%2C+Y%3BHabeebu%2C+S+M%3BWaalkes%2C+M+P%3BKlaassen%2C+C+D&rft.aulast=Liu&rft.aufirst=J&rft.date=2000-07-05&rft.volume=147&rft.issue=3&rft.spage=157&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-30 N1 - Date created - 2000-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nonreceptor tyrosine protein kinase pp60c-src in spatial learning: synapse-specific changes in its gene expression, tyrosine phosphorylation, and protein-protein interactions. AN - 71247398; 10884433 AB - c-src is a nonreceptor tyrosine protein kinase that is highly concentrated in synaptic regions, including synaptic vesicles and growth cones. Here, we report that the mRNA signal of pp60c-src is widely distributed in the rat brain with particularly high concentrations in the hippocampus. After spatial maze learning, up-regulation of c-src mRNA was observed in the CA3 region of the hippocampus, which was accompanied by increases in pp60c-src protein in hippocampal synaptosomal preparations. Training also triggered an increase in c-src protein tyrosine kinase activity that was correlated with its tyrosine dephosphorylation in the synaptic membrane fraction. After training, pp60c-src from hippocampus showed enhanced interactions with synaptic proteins such as synapsin I, synaptophysin, and the type 2 N-methyl-d-aspartate receptor, as well as the cytoskeletal protein actin. The association of pp60c-src with insulin receptor in the synaptic membrane fraction, however, was temporally decreased after training. Furthermore, in vitro results showed that Ca(2+) and protein kinase C might be involved in the regulation of protein-protein interactions of pp60c-src. These results suggest, therefore, that pp60c-src participates in the regulation of hippocampal synaptic activity during learning and memory. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Zhao, W AU - Cavallaro, S AU - Gusev, P AU - Alkon, D L AD - Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. zhaow@ninds.nih.gov Y1 - 2000/07/05/ PY - 2000 DA - 2000 Jul 05 SP - 8098 EP - 8103 VL - 97 IS - 14 SN - 0027-8424, 0027-8424 KW - Nerve Tissue Proteins KW - 0 KW - Phorbol Esters KW - RNA, Messenger KW - Receptor, Insulin KW - EC 2.7.10.1 KW - Proto-Oncogene Proteins pp60(c-src) KW - EC 2.7.10.2 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Space life sciences KW - Rats KW - Phorbol Esters -- pharmacology KW - Animals KW - Phosphorylation KW - Protein Binding -- drug effects KW - Rats, Wistar KW - Nerve Tissue Proteins -- metabolism KW - Calcium -- pharmacology KW - Up-Regulation KW - RNA, Messenger -- isolation & purification KW - Synaptosomes -- chemistry KW - Male KW - Receptor, Insulin -- metabolism KW - Space Perception -- physiology KW - Hippocampus -- physiology KW - Maze Learning -- physiology KW - Proto-Oncogene Proteins pp60(c-src) -- metabolism KW - Proto-Oncogene Proteins pp60(c-src) -- genetics KW - Memory -- physiology KW - Synaptic Transmission -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71247398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nonreceptor+tyrosine+protein+kinase+pp60c-src+in+spatial+learning%3A+synapse-specific+changes+in+its+gene+expression%2C+tyrosine+phosphorylation%2C+and+protein-protein+interactions.&rft.au=Zhao%2C+W%3BCavallaro%2C+S%3BGusev%2C+P%3BAlkon%2C+D+L&rft.aulast=Zhao&rft.aufirst=W&rft.date=2000-07-05&rft.volume=97&rft.issue=14&rft.spage=8098&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 - 2000-08-10 N1 - Date created - 2000-08-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1999 Dec 3;274(49):34893-902 [10574963] J Physiol. 1973 Jul;232(2):331-56 [4727084] Proc Natl Acad Sci U S A. 1981 Oct;78(10):6013-7 [6273838] Mol Cell Biol. 1983 Jun;3(6):1157-62 [6192323] Symp Soc Exp Biol. 1993;47:267-82 [8165570] Nature. 1994 May 19;369(6477):233-5 [7514272] Adv Second Messenger Phosphoprotein Res. 1994;29:31-45 [7848718] Biochim Biophys Acta. 1996 Jun 7;1287(2-3):121-49 [8672527] J Neurochem. 1996 Jul;67(1):194-200 [8666992] J Physiol. 1996 Apr 15;492 ( Pt 2):445-52 [9019541] Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):12168-73 [9342381] J Biol Chem. 1998 Jan 30;273(5):2851-7 [9446595] Cell. 1998 Jan 23;92(2):279-89 [9458051] Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4673-7 [9539797] Nat Neurosci. 1998 May;1(1):29-35 [10195105] Nat Neurosci. 1999 Apr;2(4):331-8 [10204539] Philos Trans R Soc Lond B Biol Sci. 1999 Feb 28;354(1381):269-79 [10212475] EMBO J. 1985 Jun;4(6):1471-7 [2411538] Nature. 1985 Aug 8-14;316(6028):554-7 [2412121] Cell. 1985 Oct;42(3):849-57 [2996780] Nature. 1986 Feb 27-Mar 5;319(6056):774-6 [2869411] J Neurosci Res. 1986;16(1):127-39 [2427734] Mol Cell Biol. 1986 Dec;6(12):4467-77 [2432403] Proc Natl Acad Sci U S A. 1988 Feb;85(3):762-6 [3124110] Cell. 1988 Mar 25;52(6):801-10 [2450676] Proc Natl Acad Sci U S A. 1988 May;85(10):3348-52 [2453056] Proc Natl Acad Sci U S A. 1988 Jun;85(12):4232-6 [2454466] Proc Natl Acad Sci U S A. 1988 Jul;85(14):5001-5 [2455889] Oncogene. 1989 Mar;4(3):317-24 [2468125] Science. 1989 Aug 25;245(4920):866-9 [2772638] J Cell Biol. 1990 Apr;110(4):1285-94 [2182650] Ciba Found Symp. 1990;150:57-69; discussion 69-78 [2115426] Oncogene. 1990 Jul;5(7):1019-24 [1695724] J Cell Biol. 1990 Nov;111(5 Pt 1):1959-70 [1699949] Cell. 1991 Feb 22;64(4):693-702 [1997203] J Cell Biol. 1992 Jun;117(5):1077-84 [1374414] J Neurobiol. 1992 Sep;23(7):803-13 [1279117] Epilepsy Res Suppl. 1992;7:151-7 [1334660] Science. 1992 Dec 18;258(5090):1903-10 [1361685] Science. 1993 Feb 5;259(5096):780-5 [8430330] J Neurocytol. 1993 Apr;22(4):244-58 [7683040] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of experimental (Trinitrobenzene sulfonic acid) colitis by intranasal administration of transforming growth factor (TGF)-beta1 plasmid: TGF-beta1-mediated suppression of T helper cell type 1 response occurs by interleukin (IL)-10 induction and IL-12 receptor beta2 chain downregulation. AN - 71240063; 10880525 AB - In this study, we show that a single intranasal dose of a plasmid encoding active transforming growth factor beta1 (pCMV-TGF-beta1) prevents the development of T helper cell type 1 (Th1)-mediated experimental colitis induced by the haptenating reagent, 2,4, 6-trinitrobenzene sulfonic acid (TNBS). In addition, such plasmid administration abrogates TNBS colitis after it has been established, whereas, in contrast, intraperitoneal administration of rTGF-beta1 protein does not have this effect. Intranasal pCMV-TGF-beta1 administration leads to the expression of TGF-beta1 mRNA in the intestinal lamina propria and spleen for 2 wk, as well as the appearance of TGF-beta1-producing T cells and macrophages in these tissues, and is not associated with the appearances of fibrosis. These cells cause marked suppression of interleukin (IL)-12 and interferon (IFN)-gamma production and enhancement of IL-10 production; in addition, they inhibit IL-12 receptor beta2 (IL-12Rbeta2) chain expression. Coadministration of anti-IL-10 at the time of pCMV-TGF-beta1 administration prevents the enhancement of IL-10 production and reverses the suppression of IL-12 but not IFN-gamma secretion. However, anti-IL-10 leads to increased tumor necrosis factor alpha production, especially in established colitis. Taken together, these studies show that TGF-beta1 inhibition of a Th1-mediated colitis is due to: (a) suppression of IL-12 secretion by IL-10 induction and (b) inhibition of IL-12 signaling via downregulation of IL-12Rbeta2 chain expression. In addition, TGF-beta1 may also have an inhibitory effect on IFN-gamma transcription. JF - The Journal of experimental medicine AU - Kitani, A AU - Fuss, I J AU - Nakamura, K AU - Schwartz, O M AU - Usui, T AU - Strober, W AD - Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/07/03/ PY - 2000 DA - 2000 Jul 03 SP - 41 EP - 52 VL - 192 IS - 1 SN - 0022-1007, 0022-1007 KW - Cytokines KW - 0 KW - Recombinant Proteins KW - Transforming Growth Factor beta KW - Trinitrobenzenesulfonic Acid KW - 8T3HQG2ZC4 KW - Index Medicus KW - AIDS/HIV KW - Injections, Intraperitoneal KW - Swine KW - Animals KW - Colon -- pathology KW - Cytokines -- biosynthesis KW - Mice KW - Cytomegalovirus KW - Mice, Inbred Strains KW - Administration, Intranasal KW - Intestinal Mucosa -- pathology KW - Male KW - Recombinant Proteins -- therapeutic use KW - Colitis -- prevention & control KW - Th1 Cells -- immunology KW - Colitis -- immunology KW - Th1 Cells -- drug effects KW - Colitis -- therapy KW - Genetic Therapy KW - Colitis -- chemically induced KW - Plasmids -- administration & dosage KW - Transforming Growth Factor beta -- genetics KW - Transforming Growth Factor beta -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71240063?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Treatment+of+experimental+%28Trinitrobenzene+sulfonic+acid%29+colitis+by+intranasal+administration+of+transforming+growth+factor+%28TGF%29-beta1+plasmid%3A+TGF-beta1-mediated+suppression+of+T+helper+cell+type+1+response+occurs+by+interleukin+%28IL%29-10+induction+and+IL-12+receptor+beta2+chain+downregulation.&rft.au=Kitani%2C+A%3BFuss%2C+I+J%3BNakamura%2C+K%3BSchwartz%2C+O+M%3BUsui%2C+T%3BStrober%2C+W&rft.aulast=Kitani&rft.aufirst=A&rft.date=2000-07-03&rft.volume=192&rft.issue=1&rft.spage=41&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 - 2000-08-15 N1 - Date created - 2000-08-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: EMBO J. 1992 Apr;11(4):1599-605 [1314170] J Exp Med. 1999 Oct 4;190(7):995-1004 [10510089] J Immunol. 1993 Dec 15;151(12):6853-61 [8258695] Int Immunol. 1993 Nov;5(11):1461-71 [7903159] J Exp Med. 1994 Feb 1;179(2):589-600 [7905019] J Immunol. 1994 Aug 15;153(4):1466-77 [8046226] Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2572-6 [7708687] J Exp Med. 1995 May 1;181(5):1755-62 [7722452] Eur J Gastroenterol Hepatol. 1995 Apr;7(4):341-7 [7600140] Immunity. 1994 Oct;1(7):553-62 [7600284] Nature. 1995 Jul 13;376(6536):177-80 [7603570] Gastroenterology. 1995 Oct;109(4):1344-67 [7557106] J Exp Med. 1995 Nov 1;182(5):1281-90 [7595199] J Immunol. 1995 Nov 15;155(10):4926-32 [7594497] Lab Invest. 1996 Jun;74(6):991-1003 [8667617] J Exp Med. 1996 Jun 1;183(6):2605-16 [8676081] J Exp Med. 1996 Jun 1;183(6):2669-74 [8676088] J Clin Invest. 1996 Jul 1;98(1):70-7 [8690806] Nature. 1996 Jul 11;382(6587):171-4 [8700208] Immunol Today. 1997 Feb;18(2):61-4 [9057354] J Exp Med. 1997 Mar 3;185(5):817-24 [9120387] J Exp Med. 1997 Mar 3;185(5):825-31 [9120388] Hum Gene Ther. 1997 May 20;8(8):929-34 [9195215] Eur J Immunol. 1997 Jul;27(7):1743-50 [9247586] J Clin Invest. 1997 Aug 15;100(4):768-76 [9259574] Nature. 1997 Oct 16;389(6652):737-42 [9338786] J Clin Invest. 1997 Dec 1;100(11):2766-76 [9389741] J Exp Med. 1998 Feb 16;187(4):537-46 [9463404] J Exp Med. 1998 Apr 20;187(8):1225-34 [9547334] Ann Intern Med. 1998 May 15;128(10):848-56 [9599198] Eur J Immunol. 1998 May;28(5):1719-26 [9603479] J Clin Invest. 1998 Jun 15;101(12):2615-21 [9637694] Gastroenterology. 1998 Jul;115(1):182-205 [9649475] J Clin Invest. 1998 Jul 15;102(2):438-44 [9664086] Biochim Biophys Acta. 1990 Jun 1;1032(1):79-87 [2194569] J Immunol. 1990 Nov 1;145(9):2938-45 [2145365] N Engl J Med. 1991 Sep 26;325(13):928-37 [1881418] J Immunol. 1991 Dec 1;147(11):3815-22 [1940369] J Exp Med. 1999 Nov 15;190(10):1479-92 [10562322] J Exp Med. 2000 Mar 6;191(5):847-58 [10704465] J Immunol Methods. 1987 Nov 5;103(2):161-7 [2889781] J Exp Med. 1998 Nov 16;188(10):1929-39 [9815270] J Immunol. 1999 Feb 15;162(4):1994-8 [9973470] Immunity. 1999 Mar;10(3):387-98 [10204494] J Exp Med. 1999 Apr 19;189(8):1169-80 [10209035] J Biol Chem. 1999 May 7;274(19):13586-93 [10224129] Immunol Rev. 1999 Jun;169:195-207 [10450518] J Immunol. 1999 Sep 1;163(5):2393-402 [10452973] Biotechniques. 1999 Sep;27(3):438-40 [10489600] Immunol Today. 1999 Oct;20(10):442-5 [10500290] J Exp Med. 1993 Jul 1;178(1):237-44 [8100269] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of dimethylaminosulfonates of alkane diols as a novel group of anticancer agents. AN - 71115543; 10814884 AB - A series of title compounds has been synthesized and evaluated by the cytotoxicity assays conducted in vitro in seven human tumor cell lines, initially in MT-4 and H-9, followed by U-937, PM-1, MCF-7, Hep-3B, and K-562. These compounds were simultaneously compared with the existing clinical drug, busulfan and also with an experimental drug, hepsulfam. IC(50) values of these agents in T-cell lymphoma and leukemic cell lines indicate that two of these agents hexsulfamyl and octsulfamyl (compounds 3 and 4) were significantly more potent than busulfan and were comparable in antileukemic activity with hepsulfam. In order to determine the effect of these agents on normal proliferating cells, the toxicity of 3 and 4 was also determined in vitro against human peripheral blood mononuclear cells (PBMC) and against murine bone marrow progenitor cells. PBMC assay data indicate that these agents were generally less toxic than hepsulfam. The results of the colony forming unit-erythroid (CFU-E) and granulocyte-macrophage colony forming unit (CFU-GM) assays, however, indicate that these agents were more toxic than hepsulfam to erythroid progenitor cells than to granulocyte-macrophage progenitors. The toxicity of octsulfamyl was further assessed in vivo in normal Swiss mice by measuring drug-induced changes in hematological parameters, femoral bone marrow cellularity and splenic cellularity as well as hepatotoxicity and nephrotoxicity on day 7 and 14 following drug treatment at the dose of 1.0 mg/kg body weight from days 1 to 5. The results indicate that the compound did not adversely affect hematopoiesis. Marginal bone marrow suppression was observed on day 7, which gradually tends to reach normalcy on day 14. The other parameters were within normal limit. JF - Cancer letters AU - Sanyal, U AU - Nanda, R AU - Samanta, S AU - Pain, A AU - Dutta, S AU - Verma, A S AU - Rider, B J AU - Agrawal, K C AD - Department of Anticancer Drug Development and Chemotherapy, Chittaranjan National Cancer Institute, Calcutta, India. cncinst@giasc101.vsnl.net.in Y1 - 2000/07/03/ PY - 2000 DA - 2000 Jul 03 SP - 89 EP - 97 VL - 155 IS - 1 SN - 0304-3835, 0304-3835 KW - Alkanes KW - 0 KW - Antineoplastic Agents KW - Antineoplastic Agents, Alkylating KW - Mesylates KW - Sulfones KW - Busulfan KW - G1LN9045DK KW - Index Medicus KW - Animals KW - Busulfan -- pharmacology KW - Antineoplastic Agents, Alkylating -- pharmacology KW - Humans KW - Mice KW - K562 Cells KW - Macrophages -- drug effects KW - Hematopoietic Stem Cells -- drug effects KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Granulocytes -- drug effects KW - Inhibitory Concentration 50 KW - Leukocytes, Mononuclear -- drug effects KW - Tumor Stem Cell Assay KW - Bone Marrow -- drug effects KW - Male KW - Sulfones -- pharmacology KW - Alkanes -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - Mesylates -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71115543?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Evaluation+of+dimethylaminosulfonates+of+alkane+diols+as+a+novel+group+of+anticancer+agents.&rft.au=Sanyal%2C+U%3BNanda%2C+R%3BSamanta%2C+S%3BPain%2C+A%3BDutta%2C+S%3BVerma%2C+A+S%3BRider%2C+B+J%3BAgrawal%2C+K+C&rft.aulast=Sanyal&rft.aufirst=U&rft.date=2000-07-03&rft.volume=155&rft.issue=1&rft.spage=89&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 - 2000-07-18 N1 - Date created - 2000-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Definitional Issues in Violence Against Women. Surveillance and Research from a Violence Research Perspective AN - 877591556; 13501929 AB - Issues relevant to defining Violence Against Women include the importance of severity of aggressive behavior in partner relationships, relationships among types of abusive behavior, and adequacy of explanatory models of partner violence. Severity of aggression is important for describing and understanding partner violence. Different types of abusive behavior should be assessed to account for variation in partner abuse. Constructs drawn from multiple domains are needed to adequately explain partner aggression across the range of severity of partner abuse. Standardized structured interviews to assess partner violence in high-risk surveillance would complement checklists for general population surveillance. JF - Violence Against Women AU - Gordon, Malcolm AD - National Institute of Mental Health Y1 - 2000/07// PY - 2000 DA - Jul 2000 SP - 747 EP - 783 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 6 IS - 7 SN - 1077-8012, 1077-8012 KW - Risk Abstracts KW - domestic violence KW - Standards KW - Females KW - aggressive behavior KW - Violence KW - R2 23110:Psychological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/877591556?accountid=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=Violence+Against+Women&rft.atitle=Definitional+Issues+in+Violence+Against+Women.+Surveillance+and+Research+from+a+Violence+Research+Perspective&rft.au=Gordon%2C+Malcolm&rft.aulast=Gordon&rft.aufirst=Malcolm&rft.date=2000-07-01&rft.volume=6&rft.issue=7&rft.spage=747&rft.isbn=&rft.btitle=&rft.title=Violence+Against+Women&rft.issn=10778012&rft_id=info:doi/10.1177%2F1077801200006007004 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - domestic violence; Standards; Females; aggressive behavior; Violence DO - http://dx.doi.org/10.1177/1077801200006007004 ER - TY - JOUR T1 - Conceptualizing Functional Neuroplasticity AN - 85526807; 200100128 AB - There are at least four major forms of functional neuroplasticity that can be studied in humans: homologous area adaptation, cross-modal reassignment, map expansion, & compensatory masquerade. Homologous area adaptation is the assumption of a particular cognitive process by a homologous region in the opposite hemisphere. Cross-modal reassignment occurs when structures previously devoted to processing a particular kind of sensory input now accepts input from a new sensory method. Map expansion is the enlargement of a functional brain region on the basis of performance. Compensatory masquerade is a novel allocation of a particular cognitive process to perform a task. By focusing on these four forms of functional neuroplasticity, several fundamental questions about how functional cooperation between brain regions is achieved can be addressed. 35 References. Adapted from the source document JF - Journal of Communication Disorders AU - Grafman, Jordan AD - Cognitive Neuroscience Section, NIH/NINDS, Bethesda, MD grafmanj@ninds.nih.gov Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 345 EP - 356 VL - 33 IS - 4 SN - 0021-9924, 0021-9924 KW - Cognitive Processes (12950) KW - Cerebral Dominance (11500) KW - Brain Damage (09400) KW - article KW - 4018: psycholinguistics; neurolinguistics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85526807?accountid=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+Communication+Disorders&rft.atitle=Conceptualizing+Functional+Neuroplasticity&rft.au=Grafman%2C+Jordan&rft.aulast=Grafman&rft.aufirst=Jordan&rft.date=2000-07-01&rft.volume=33&rft.issue=4&rft.spage=345&rft.isbn=&rft.btitle=&rft.title=Journal+of+Communication+Disorders&rft.issn=00219924&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 - JCDIAI N1 - SubjectsTermNotLitGenreText - Cognitive Processes (12950); Brain Damage (09400); Cerebral Dominance (11500) ER - TY - JOUR T1 - A Comparison of rCBF Patterns During Letter and Semantic Fluency AN - 85513128; 200101072 AB - To evaluate the functional neuroanatomies underlying letter & category fluency, 18 normal controls were studied with oxygen-15 water regional cerebral blood flow positron emission tomography. Three counterbalanced conditions each consisted of 6 trials (45 s each): letter fluency (generating words when cued with a particular letter), semantic fluency (generating words when cued with a particular category), & a control condition (generating days of the week & months of the year). Relative to the control, participants activated similar brain regions during both fluency tasks, including the anterior cingulate, left prefrontal regions, thalamus, & cerebellum; reductions were found in parietal & temporal regions. In a direct comparison of the 2 fluency tasks, inferior frontal cortex & temporoparietal cortex (hypothesized to participate in a phonologic loop for accessing word pronunciation) were activated more during letter than semantic fluency, whereas left temporal cortex (associated with access to semantic storage) was activated more during semantic than letter fluency. This study identifies subtle differences in the neural networks underlying letter & semantic fluency that may underlie the dissociation of these abilities in patients. 3 Tables, 41 References. [Copyright 2000 The American Psychological Association.] JF - Neuropsychology AU - Gourovitch, Monica L AU - Kirkby, Brenda S AU - Goldberg, Terry E AU - Weinberger, Daniel R AU - Gold, James M AU - Esposito, Giuseppe AU - Van Horn, John D AU - Berman, Karen Faith AD - c/o Berman-mailto:karen.berman@nih.gov Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 353 EP - 360 VL - 14 IS - 3 SN - 0894-4105, 0894-4105 KW - Cerebral Dominance (11500) KW - Letter Recognition (46400) KW - Neurolinguistics (57250) KW - Lexical Access (46630) KW - Semantic Processing (76760) KW - article KW - 4018: psycholinguistics; neurolinguistics KW - 4014: psycholinguistics; semantic processing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85513128?accountid=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=A+Comparison+of+rCBF+Patterns+During+Letter+and+Semantic+Fluency&rft.au=Gourovitch%2C+Monica+L%3BKirkby%2C+Brenda+S%3BGoldberg%2C+Terry+E%3BWeinberger%2C+Daniel+R%3BGold%2C+James+M%3BEsposito%2C+Giuseppe%3BVan+Horn%2C+John+D%3BBerman%2C+Karen+Faith&rft.aulast=Gourovitch&rft.aufirst=Monica&rft.date=2000-07-01&rft.volume=14&rft.issue=3&rft.spage=353&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 - Letter Recognition (46400); Semantic Processing (76760); Lexical Access (46630); Cerebral Dominance (11500); Neurolinguistics (57250) ER - TY - JOUR T1 - Burkitt's lymphoma: historical background and recent insights into classification and pathogenesis. AN - 85346134; pmid-10903055 AB - In this paper, the authors evaluate the historical evolution of the definition of Burkitt's lymphoma (BL) and of its clinicoepidemiological (endemic, sporadic, and acquired immunodeficiency syndrome-associated BL) and morphological variants. On the basis of the morphological, immunologic, genetic, and clinical characteristics of these tumors, the authors also emphasize the importance of precise disease definitions for biological and epidemiological studies. These principles were used in accordance with the Revised European-American classification of lymphoid neoplasms (REAL), which proposed that disease entities should be defined by a constellation of pathobiological and clinical features. JF - The Annals of otology, rhinology, and laryngology AU - Carbone, A AU - Canzonieri, V AU - Gloghini, A AU - Rinaldo, A AU - Gaidano, G AU - Ferlito, A AD - Division of Pathology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy. Y1 - 2000/07// PY - 2000 DA - Jul 2000 SP - 693 EP - 702 VL - 109 IS - 7 SN - 0003-4894, 0003-4894 KW - National Library of Medicine KW - Humans KW - Burkitt Lymphoma -- genetics KW - Burkitt Lymphoma -- classification KW - Burkitt Lymphoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85346134?accountid=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+Annals+of+otology%2C+rhinology%2C+and+laryngology&rft.atitle=Burkitt%27s+lymphoma%3A+historical+background+and+recent+insights+into+classification+and+pathogenesis.&rft.au=Carbone%2C+A%3BCanzonieri%2C+V%3BGloghini%2C+A%3BRinaldo%2C+A%3BGaidano%2C+G%3BFerlito%2C+A&rft.aulast=Carbone&rft.aufirst=A&rft.date=2000-07-01&rft.volume=109&rft.issue=7&rft.spage=693&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+otology%2C+rhinology%2C+and+laryngology&rft.issn=00034894&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - Audiovestibular phenotype associated with a COL11A1 mutation in Marshall syndrome. AN - 85346115; pmid-10889003 AB - BACKGROUND: Marshall syndrome is a dominant disorder characterized by craniofacial and skeletal abnormalities, sensorineural hearing loss, myopia, and cataracts, and is associated with splicing mutations in COL11A1. OBJECTIVE: To determine the auditory and vestibular phenotypes associated with a COL11A1 splicing. DESIGN: Clinical otolaryngologic, audiologic, vestibular, and radiologic evaluations of the auditory and vestibular systems. SUBJECTS: Three affected individuals from a family cosegregating Marshall syndrome and a COL11A1 splice site mutation. RESULTS: The study subjects have progressive sensorineural hearing loss that is predominantly cochlear in origin and asymptomatic dysfunction of the central and peripheral vestibular systems. Computed tomography detected no malformations of temporal bone structures. CONCLUSIONS: The observed auditory and vestibular abnormalities are not caused by defective morphogenesis of the osseous labyrinth, but by more direct effects of the COL11A1 mutation on the membranous labyrinth and the central nervous system. The onset and degree of hearing loss associated with COL11A1 mutations are useful clinical features to differentiate Marshall syndrome from the phenotypically similar Stickler syndrome. JF - Archives of otolaryngology--head & neck surgery AU - Griffith, A J AU - Gebarski, S S AU - Shepard, N T AU - Kileny, P R AD - Neuro-Otology Branch, NIDCD/NIH, Rockville, MD 20850, USA. Y1 - 2000/07// PY - 2000 DA - Jul 2000 SP - 891 EP - 894 VL - 126 IS - 7 SN - 0886-4470, 0886-4470 KW - National Library of Medicine KW - Phenotype KW - Audiometry, Pure-Tone KW - Syndrome KW - RNA Splicing KW - Humans KW - Electronystagmography KW - Temporal Bone -- radiography KW - Tomography, X-Ray Computed KW - Male KW - Female KW - Hearing Loss, Sensorineural -- genetics KW - Vestibular Diseases -- genetics KW - Craniofacial Abnormalities -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85346115?accountid=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=Archives+of+otolaryngology--head+%26+neck+surgery&rft.atitle=Audiovestibular+phenotype+associated+with+a+COL11A1+mutation+in+Marshall+syndrome.&rft.au=Griffith%2C+A+J%3BGebarski%2C+S+S%3BShepard%2C+N+T%3BKileny%2C+P+R&rft.aulast=Griffith&rft.aufirst=A&rft.date=2000-07-01&rft.volume=126&rft.issue=7&rft.spage=891&rft.isbn=&rft.btitle=&rft.title=Archives+of+otolaryngology--head+%26+neck+surgery&rft.issn=08864470&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - The motor and tail regions of myosin XV are critical for normal structure and function of auditory and vestibular hair cells. AN - 85291315; pmid-10915760 AB - Recessive mutations in myosin 15, a class XV unconventional myosin, cause profound congenital deafness in humans and both deafness and vestibular dysfunction in mice homozygous for the shaker 2 and shaker 2(J) alleles. The shaker 2 allele is a previously described missense mutation of a highly conserved residue in the motor domain of myosin XV. The shaker 2(J) lesion, in contrast, is a 14.7 kb deletion that removes the last six exons from the 3"-terminus of the Myo15 transcript. These exons encode a FERM (F, ezrin, radixin and moesin) domain that may interact with integral membrane proteins. Despite the deletion of six exons, Myo15 mRNA transcripts and protein are present in the post-natal day 1 shaker 2(J) inner ear, which suggests that the FERM domain is critical for the development of normal hearing and balance. Myo15 transcripts are first detectable at embryonic day 13.5 in wild-type mice. Myo15 transcripts in the mouse inner ear are restricted to the sensory epithelium of the developing cristae ampularis, macula utriculi and macula sacculi of the vestibular system as well as to the developing organ of Corti. Both the shaker 2 and shaker 2(J) alleles result in abnormally short hair cell stereocilia in the cochlear and vestibular systems. This suggests that Myo15 may be important for both the structure and function of these sensory epithelia. JF - Human Molecular Genetics AU - Anderson, D W AU - Probst, F J AU - Belyantseva, I A AU - Fridell, R A AU - Beyer, L AU - Martin, D M AU - Wu D AU - Kachar Bechara AU - Friedman, T B AU - Raphael, Y AU - Camper, S A AD - Laboratory of Molecular Genetics and Laboratory of Cell Biology, NIDCD, Rockville, MD 20850, USA.; National Institute on Deafness and Other Communication Disorders PY - 2000 SP - 1729 EP - 1738 VL - 9 IS - 12 SN - 0964-6906, 0964-6906 KW - Support, U.S. Gov't, P.H.S. KW - Myosins KW - Animal KW - Gene Expression KW - Mice KW - Binding Sites KW - Gene Deletion KW - RNA, Messenger KW - Alleles KW - Base Sequence KW - Mice, Mutant Strains KW - Hair Cells, Vestibular KW - Hair Cells, Inner KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Support, Non-U.S. Gov't UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85291315?accountid=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=Human+Molecular+Genetics&rft.atitle=The+motor+and+tail+regions+of+myosin+XV+are+critical+for+normal+structure+and+function+of+auditory+and+vestibular+hair+cells.&rft.au=Anderson%2C+D+W%3BProbst%2C+F+J%3BBelyantseva%2C+I+A%3BFridell%2C+R+A%3BBeyer%2C+L%3BMartin%2C+D+M%3BWu+D%3BKachar+Bechara%3BFriedman%2C+T+B%3BRaphael%2C+Y%3BCamper%2C+S+A&rft.aulast=Anderson&rft.aufirst=D&rft.date=2000-07-01&rft.volume=9&rft.issue=12&rft.spage=1729&rft.isbn=&rft.btitle=&rft.title=Human+Molecular+Genetics&rft.issn=09646906&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Statistical artifacts in diffusion tensor MRI (DT-MRI) caused by background noise. AN - 85275326; pmid-10893520 AB - This work helps elucidate how background noise introduces statistical artifacts in the distribution of the sorted eigenvalues and eigenvectors in diffusion tensor MRI (DT-MRI) data. Although it was known that sorting eigenvalues (principal diffusivities) by magnitude introduces a bias in their sample mean within a homogeneous region of interest (ROI), here it is shown that magnitude sorting also introduces a significant bias in the variance of the sample mean eigenvalues. New methods are presented to calculate the mean and variance of the eigenvectors of the diffusion tensor, based on a dyadic tensor representation of eigenvalue-eigenvector pairs. Based on their use it is shown that sorting eigenvalues by magnitude also introduces a bias in the mean and the variance of the sample eigenvectors (principal directions). This required the development of new methods to calculate the mean and variance of the eigenvectors of the diffusion tensor, based on a dyadic tensor representation of eigenvalue-eigenvector pairs. Moreover, a new approach is proposed to order these pairs within an ROI. To do this, a correspondence between each principal axis of the diffusion ellipsoid, an eigenvalue-eigenvector pair, and a dyadic tensor constructed from it is exploited. A measure of overlap between principal axes of diffusion ellipsoids in different voxels is defined that employs projections between these dyadic tensors. The optimal eigenvalue assignment within an ROI maximizes this overlap. Bias in the estimate of the mean and of the variance of the eigenvalues and of their corresponding eigenvectors is reduced in DT-MRI experiments and in Monte Carlo simulations of such experiments. Improvement is most significant in isotropic regions, but some is also observed in anisotropic regions. This statistical framework should enhance our ability to characterize microstructure and architecture of healthy tissue, and help to assess its changes in development, disease, and degeneration. Mitigating these artifacts should also improve the characterization of diffusion anisotropy and the elucidation of fiber-tract trajectories in the brain and in other fibrous tissues. Magn Reson Med 44:41-50, 2000. Published 2000 Wiley-Liss, Inc. JF - Magnetic Resonance in Medicine AU - Basser, P J AU - Pajevic, S AD - Section on Tissue Biophysics and Biomimetics, Laboratory of Integrative and Medical Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, 20892-5772, USA. PY - 2000 SP - 41 EP - 50 VL - 44 IS - 1 SN - 0740-3194, 0740-3194 KW - Magnetic Resonance Imaging KW - Monte Carlo Method KW - Artifacts KW - Statistics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85275326?accountid=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=Statistical+artifacts+in+diffusion+tensor+MRI+%28DT-MRI%29+caused+by+background+noise.&rft.au=Basser%2C+P+J%3BPajevic%2C+S&rft.aulast=Basser&rft.aufirst=P&rft.date=2000-07-01&rft.volume=44&rft.issue=1&rft.spage=41&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 - Noise reduction in 3D perfusion imaging by attenuating the static signal in arterial spin tagging (ASSIST). AN - 85268246; pmid-10893526 AB - Phase-encoded multishot SPIRAL approaches were used to acquire true 3D cerebral blood flow images of the human head using arterial spin tagging approaches. Multiple-inversion background suppression techniques, which suppress phase noise due to interacquisition fluctuations in the static magnetic field, reduced the temporal standard deviation of true 3D delta M images acquired using arterial spin tagging approaches by approximately 50%. Background suppressed arterial spin tagging (ASSIST) approaches were used to obtain high-resolution isotropic true 3D cerebral blood flow images, and to obtain true 3D activation images during cognitive (working memory) tasks. Magn Reson Med 44:92-100, 2000. Published 2000 Wiley-Liss, Inc. JF - Magnetic Resonance in Medicine AU - Ye, F Q AU - Frank, J A AU - Weinberger, D R AU - McLaughlin, A C AD - Clinical Brain Disorders Branch, NIMH, Bethesda, Maryland, USA. PY - 2000 SP - 92 EP - 100 VL - 44 IS - 1 SN - 0740-3194, 0740-3194 KW - Magnetic Resonance Imaging KW - Phantoms, Imaging KW - Artifacts KW - Human KW - Adult KW - Cerebrovascular Circulation KW - Time Factors KW - Cerebral Arteries KW - Female KW - Male KW - Spin Labels UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85268246?accountid=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=Noise+reduction+in+3D+perfusion+imaging+by+attenuating+the+static+signal+in+arterial+spin+tagging+%28ASSIST%29.&rft.au=Ye%2C+F+Q%3BFrank%2C+J+A%3BWeinberger%2C+D+R%3BMcLaughlin%2C+A+C&rft.aulast=Ye&rft.aufirst=F&rft.date=2000-07-01&rft.volume=44&rft.issue=1&rft.spage=92&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 - Examining noise sources at the single-molecule level: 1/f noise of an open maltoporin channel. AN - 85247831; pmid-10991194 AB - We have studied the phenomenological origin of 1/f noise in a solute-specific bacterial ion channel, maltoporin. We show that after excision of small, but resolvable stepwise changes in the recordings of the current through a single open channel, the 1/f noise component disappears and the channel exhibits noise that is "white" below 100 Hz. Combined with results of a recent noise study of several bacterial porins, our observations suggest that 1/f noise is caused by the equilibrium conductance fluctuations related to the conformational flexibility of the channel pore structural constituents. JF - Physical Review Letters AU - Bezrukov, S M AU - Winterhalter, M AD - Laboratory of Physical and Structural Biology, NICHD, NIH, Bethesda, Maryland 20892-0924, USA. PY - 2000 SP - 202 EP - 205 VL - 85 IS - 1 SN - 0031-9007, 0031-9007 KW - Bacterial Proteins KW - Receptors, Virus KW - Electric Conductivity KW - Oligosaccharides KW - Biological Transport KW - Electrophysiology KW - Ion Channel Gating KW - Artifacts KW - Models, Molecular UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85247831?accountid=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=Physical+Review+Letters&rft.atitle=Examining+noise+sources+at+the+single-molecule+level%3A+1%2Ff+noise+of+an+open+maltoporin+channel.&rft.au=Bezrukov%2C+S+M%3BWinterhalter%2C+M&rft.aulast=Bezrukov&rft.aufirst=S&rft.date=2000-07-01&rft.volume=85&rft.issue=1&rft.spage=202&rft.isbn=&rft.btitle=&rft.title=Physical+Review+Letters&rft.issn=00319007&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Additive analgesia without opioid side effects. AN - 72541499; 11199661 AB - Postoperative pain control is often inadequate because of insufficient pain relief or unacceptable side effects. Nonsteroidal antiinflammatory drugs (NSAIDs) are very efficacious for pain of dental origin, but their ceiling of efficacy does not result in greater peak analgesia if the dose is raised beyond recommended limits. Switching to an opioid combined with acetaminophen or aspirin does not result in greater analgesia, but increases the incidence of side effects such as drowsiness and nausea. Combining NSAIDs with opioids has been largely unsuccessful and still results in opioid side effects. The combination of NSAIDs with acetaminophen holds promise for greater analgesia than either drug alone, but without the increased side effects associated with opioids in ambulatory dental patients. JF - Compendium of continuing education in dentistry (Jamesburg, N.J. : 1995) AU - Dionne, R AD - National Institute of Dental and Craniofacial Research, Bethesda, Maryland, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 572 EP - 4, 576-7 VL - 21 IS - 7 SN - 1548-8578, 1548-8578 KW - Analgesics, Non-Narcotic KW - 0 KW - Analgesics, Opioid KW - Anti-Inflammatory Agents, Non-Steroidal KW - Drug Combinations KW - Acetaminophen KW - 362O9ITL9D KW - Dentistry KW - Nausea -- chemically induced KW - Analgesia KW - Dental Care KW - Pain, Postoperative -- prevention & control KW - Humans KW - Analgesics, Opioid -- therapeutic use KW - Analgesics, Opioid -- adverse effects KW - Analgesics, Opioid -- administration & dosage KW - Sleep Stages -- drug effects KW - Drug Synergism KW - Ambulatory Care KW - Acetaminophen -- administration & dosage KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Analgesics, Non-Narcotic -- therapeutic use KW - Acetaminophen -- therapeutic use KW - Anti-Inflammatory Agents, Non-Steroidal -- administration & dosage KW - Analgesics, Non-Narcotic -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72541499?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Compendium+of+continuing+education+in+dentistry+%28Jamesburg%2C+N.J.+%3A+1995%29&rft.atitle=Additive+analgesia+without+opioid+side+effects.&rft.au=Dionne%2C+R&rft.aulast=Dionne&rft.aufirst=R&rft.date=2000-07-01&rft.volume=21&rft.issue=7&rft.spage=572&rft.isbn=&rft.btitle=&rft.title=Compendium+of+continuing+education+in+dentistry+%28Jamesburg%2C+N.J.+%3A+1995%29&rft.issn=15488578&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-15 N1 - Date created - 2001-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Integration of deletion mutants of bovine rhodopsin into the membrane of the endoplasmic reticulum. AN - 72509773; 11128975 AB - Newly synthesized eukaryotic membrane proteins must be integrated into the membrane of the endoplasmic reticulum with the correct topology to enable the subsequent acquisition of the correctly folded, functional conformation. Here, an analysis is presented of N-terminal glycosylation and steady-state membrane orientation of a series of truncation mutants of the seven-helix protein rhodopsin expressed in COS-1 cells. Mutants containing one, three, or five N-terminal transmembrane segments of rhodopsin, as well as mutants containing only the first transmembrane segment, but with hydrophilic extensions at the C-terminus were studied. The findings demonstrate that the C-terminal transmembrane segments play a crucial role in determining the final orientation of rhodopsin, and that the commitment to the correct orientation occurs only after the synthesis of at least three transmembrane segments. The experiments also suggest that the molecular machinery involved in the integration of a newly synthesized seven-helix membrane protein into the endoplasmic reticulum membrane is sensitive to the overall hydrophobicity of the sequence that follows the first transmembrane segment. JF - Molecular membrane biology AU - Heymann, J A AU - Subramaniam, S AD - National Cancer Institute, NIH, Laboratory of Biochemistry, Bethesda, MD 20892, USA. heymannj@mail.nih.gov PY - 2000 SP - 165 EP - 174 VL - 17 IS - 3 SN - 0968-7688, 0968-7688 KW - Carbonates KW - 0 KW - Rhodopsin KW - 9009-81-8 KW - Trypsin KW - EC 3.4.21.4 KW - Index Medicus KW - Animals KW - Immunoblotting KW - COS Cells KW - Dose-Response Relationship, Drug KW - Electrophoresis, Polyacrylamide Gel KW - Amino Acid Sequence KW - Glycosylation KW - Models, Biological KW - Mutagenesis KW - Carbonates -- metabolism KW - Cattle KW - Transfection KW - Microsomes -- metabolism KW - Molecular Sequence Data KW - Trypsin -- pharmacology KW - Rhodopsin -- genetics KW - Endoplasmic Reticulum -- metabolism KW - Intracellular Membranes -- metabolism KW - Mutation KW - Rhodopsin -- biosynthesis KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72509773?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+membrane+biology&rft.atitle=Integration+of+deletion+mutants+of+bovine+rhodopsin+into+the+membrane+of+the+endoplasmic+reticulum.&rft.au=Heymann%2C+J+A%3BSubramaniam%2C+S&rft.aulast=Heymann&rft.aufirst=J&rft.date=2000-07-01&rft.volume=17&rft.issue=3&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Molecular+membrane+biology&rft.issn=09687688&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-01 N1 - Date created - 2000-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Air pollution in Calcutta elicits adverse pulmonary reaction in children. AN - 72291566; 11006657 AB - Pulmonary responses of children chronically exposed to ambient air pollution in Calcutta have been investigated. A total number of 153 children from Calcutta and 116 from rural West Bengal in the age group of 6-17 yr were included in this study. Respiratory symptom complex, sputum cytology and micronucleus (MN) count of buccal epithelial cells were evaluated. Blood smears were examined for WBC differential count and RBC morphology. Marked rise in respiratory symptoms (43% in urban vs 14% in rural) and sputum alveolar macrophage (AM) number was observed in urban children compared to their rural counterparts (14.2 +/- 1.4 AM/hpf vs 6.7 +/- 1.4 AM/hpf, mean +/- SE, P < 0.001). The urban group also demonstrated increased numbers of neutrophils, eosinophils and iron-laden AM in their sputum. Besides, buccal epithelial cells of urban children exhibited higher MN frequency than their rural counterparts (0.22 vs 0.17%, P < 0.05). While sputum neutrophilia and eosinophilia suggest inflammatory and allergic lung reactions, elevated MN count is indicative of greater genotoxic effect on the exposed tissues of urban children. Hypochromic red cells in peripheral blood smear was a common finding in both urban and rural groups, but eosinophils and monocytes were present in elevated frequencies in the rural children. The study demonstrated that children inhaling grossly polluted air of Calcutta suffer from adverse lung reactions and genetic abnormality in the exposed tissues. JF - The Indian journal of medical research AU - Lahiri, T AU - Roy, S AU - Basu, C AU - Ganguly, S AU - Ray, M R AU - Lahiri, P AD - Department of Neuroendocrinology, Chittaranjan National Cancer Institute, Calcutta. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 21 EP - 26 VL - 112 SN - 0971-5916, 0971-5916 KW - Air Pollutants KW - 0 KW - Index Medicus KW - Rural Population KW - Humans KW - Child KW - Adolescent KW - Urban Population KW - Male KW - Female KW - India KW - Lung -- drug effects KW - Lung -- physiopathology KW - Air Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72291566?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Indian+journal+of+medical+research&rft.atitle=Air+pollution+in+Calcutta+elicits+adverse+pulmonary+reaction+in+children.&rft.au=Lahiri%2C+T%3BRoy%2C+S%3BBasu%2C+C%3BGanguly%2C+S%3BRay%2C+M+R%3BLahiri%2C+P&rft.aulast=Lahiri&rft.aufirst=T&rft.date=2000-07-01&rft.volume=112&rft.issue=&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=The+Indian+journal+of+medical+research&rft.issn=09715916&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-13 N1 - Date created - 2000-10-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcription factor hierarchy in Waardenburg syndrome: regulation of MITF expression by SOX10 and PAX3. AN - 72244250; 10982026 AB - Waardenburg syndrome (WS) is associated with neural crest-derived melanocyte deficiency caused by mutations in either one of three transcription factors: MITF, PAX3, and SOX10. However, the hierarchical relationship of these transcription factors is largely unknown. We show that SOX10 is capable of transactivating the MITF promoter 100-fold, and that this transactivation is further stimulated by PAX3. Promoter deletion and mutational analyses indicate that SOX10 can activate MITF expression through binding to a region that is evolutionarily conserved between the mouse and human MITF promoters. A SOX10 mutant that models C-terminal truncations in WS can reduce wild-type SOX10 induction of MITF, suggesting these mutations may act in a dominant-negative fashion. Our data support a model in which the hypopigmentation in WS, of which these factors have been implicated, results from a disruption in function of the central melanocyte transcription factor MITF. JF - Human genetics AU - Potterf, S B AU - Furumura, M AU - Dunn, K J AU - Arnheiter, H AU - Pavan, W J AD - Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-4472, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 1 EP - 6 VL - 107 IS - 1 SN - 0340-6717, 0340-6717 KW - DNA-Binding Proteins KW - 0 KW - High Mobility Group Proteins KW - MITF protein, human KW - Microphthalmia-Associated Transcription Factor KW - Mitf protein, mouse KW - PAX3 Transcription Factor KW - PAX3 protein, human KW - Paired Box Transcription Factors KW - SOX10 protein, human KW - SOXE Transcription Factors KW - Sox10 protein, mouse KW - Transcription Factors KW - Pax3 protein, mouse KW - 138016-91-8 KW - Index Medicus KW - Animals KW - Sequence Homology, Nucleic Acid KW - HeLa Cells KW - Humans KW - Mice KW - Evolution, Molecular KW - Mutagenesis KW - Gene Deletion KW - Phenotype KW - Genotype KW - Promoter Regions, Genetic KW - Mice, Mutant Strains KW - Base Sequence KW - Conserved Sequence KW - Genes, Dominant KW - Transfection KW - Molecular Sequence Data KW - Mice, Inbred C3H KW - Mice, Inbred C57BL KW - Time Factors KW - Mutation KW - High Mobility Group Proteins -- biosynthesis KW - High Mobility Group Proteins -- genetics KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- biosynthesis KW - Gene Expression Regulation KW - Transcription Factors -- genetics KW - Waardenburg Syndrome -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72244250?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+genetics&rft.atitle=Transcription+factor+hierarchy+in+Waardenburg+syndrome%3A+regulation+of+MITF+expression+by+SOX10+and+PAX3.&rft.au=Potterf%2C+S+B%3BFurumura%2C+M%3BDunn%2C+K+J%3BArnheiter%2C+H%3BPavan%2C+W+J&rft.aulast=Potterf&rft.aufirst=S&rft.date=2000-07-01&rft.volume=107&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Human+genetics&rft.issn=03406717&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-21 N1 - Date created - 2000-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human polyomavirus JC variants in Papua New Guinea and Guam reflect ancient population settlement and viral evolution. AN - 72226227; 10967279 AB - The peopling of the Pacific was a complex sequence of events that is best reconstructed by reconciling insights from various disciplines. Here we analyze the human polyomavirus JC (JCV) in Highlanders of Papua New Guinea (PNG), in Austronesian-speaking Tolai people on the island of New Britain, and in nearby non-Austronesian-speaking Baining people. We also characterize JCV from the Chamorro of Guam, a Micronesian population. All JCV strains from PNG and Guam fall within the broad Asian group previously defined in the VP1 gene as Type 2 or Type 7, but the PNG strains were distinct from both genotypes. Among the Chamorro JCV samples, 8 strains (Guam-1) were like the Type 7 strains found in Southeast Asia, while nine strains (Guam-2) were distinct from both the mainland strains and most PNG strains. We identified three JCV variants within Papua New Guinea (PNG-1, PNG-2 and PNG-3), but none of the Southeast Asian (Type 7) strains. PNG-1 strains were present in all three populations (Highlanders and the Baining and Tolai of New Britain), but PNG-2 strains were restricted to the Highlanders. Their relative lack of DNA sequence variation suggests that they arose comparatively recently. The single PNG-3 strain, identified in an Austronesian-speaking Tolai individual, was closely related to the Chamorro variants (Guam-2), consistent with a common Austronesian ancestor. In PNG-2 variants a complex regulatory region mutation inserts a duplication into a nearby deletion, a change reminiscent of those seen in the brains of progressive multifocal leukoencephalopathy patients. This is the first instance of a complex JCV rearrangement circulating in a human population. JF - Microbes and infection AU - Ryschkewitsch, C F AU - Friedlaender, J S AU - Mgone, C S AU - Jobes, D V AU - Agostini, H T AU - Chima, S C AU - Alpers, M P AU - Koki, G AU - Yanagihara, R AU - Stoner, G L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 987 EP - 996 VL - 2 IS - 9 SN - 1286-4579, 1286-4579 KW - Capsid Proteins KW - 0 KW - VP1 protein, polyomavirus KW - Index Medicus KW - Genes, Duplicate KW - Population Dynamics KW - Humans KW - Evolution, Molecular KW - Gene Deletion KW - Genotype KW - Base Sequence KW - New Guinea KW - Replication Origin KW - Guam KW - Adult KW - Cohort Studies KW - Molecular Sequence Data KW - Mutation KW - JC Virus -- genetics KW - JC Virus -- chemistry KW - Capsid -- genetics KW - Genome, Viral KW - Capsid -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72226227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Microbes+and+infection&rft.atitle=Human+polyomavirus+JC+variants+in+Papua+New+Guinea+and+Guam+reflect+ancient+population+settlement+and+viral+evolution.&rft.au=Ryschkewitsch%2C+C+F%3BFriedlaender%2C+J+S%3BMgone%2C+C+S%3BJobes%2C+D+V%3BAgostini%2C+H+T%3BChima%2C+S+C%3BAlpers%2C+M+P%3BKoki%2C+G%3BYanagihara%2C+R%3BStoner%2C+G+L&rft.aulast=Ryschkewitsch&rft.aufirst=C&rft.date=2000-07-01&rft.volume=2&rft.issue=9&rft.spage=987&rft.isbn=&rft.btitle=&rft.title=Microbes+and+infection&rft.issn=12864579&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-12 N1 - Date created - 2000-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Emerging neuroprotective strategies for Alzheimer's disease: dietary restriction, telomerase activation, and stem cell therapy. AN - 72215508; 10959037 AB - The molecular, biochemical and cellular events that result in synaptic dysfunction and neuronal degeneration in the brain in Alzheimer's disease (AD) are becoming known. Age-related increases in cellular oxidative stress, and impairment of energy metabolism, result in disruption of neuronal calcium homeostasis and increased vulnerability of neurons to excitotoxicity and apoptosis. Inherited forms of AD that result from mutations in the beta-amyloid precursor protein (APP) and presenilins accelerate the neurodegenerative cascade by increasing production and deposition of neurotoxic forms of amyloid beta-peptide and by perturbing calcium homeostasis. Dietary restriction (DR; reduced calorie intake with maintained nutrition) extends life span of rodents and (probably) humans. DR increases resistance of neurons to dysfunction and degeneration, and improves behavioral outcome, in experimental models of AD and other age-related neurodegenerative disorders by a mechanism involving a mild stress response. Telomerase, a specialized reverse transcriptase, has been proposed to possess anti-aging properties. The catalytic subunit of telomerase (TERT) is expressed in neurons throughout the brain during development, but is absent from neurons in the adult brain. TERT exhibits neuroprotective properties in experimental models of neurodegenerative disorders suggesting that manipulations that induce telomerase in neurons may protect against age-related neurodegeneration. Finally, the exciting and exploding field of stem cell research suggests methods for replacing damaged or lost brain cells in an array of neurological disorders. JF - Experimental gerontology AU - Mattson, M P AD - Laboratory of Neurosciences - 4F01, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, MD 23224, USA. mattsonm@grc.nia.nih.gov Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 489 EP - 502 VL - 35 IS - 4 SN - 0531-5565, 0531-5565 KW - Telomerase KW - EC 2.7.7.49 KW - Index Medicus KW - Neurology -- trends KW - Enzyme Activation KW - Humans KW - Alzheimer Disease -- diet therapy KW - Alzheimer Disease -- therapy KW - Alzheimer Disease -- prevention & control KW - Telomerase -- metabolism KW - Stem Cell Transplantation KW - Alzheimer Disease -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72215508?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+gerontology&rft.atitle=Emerging+neuroprotective+strategies+for+Alzheimer%27s+disease%3A+dietary+restriction%2C+telomerase+activation%2C+and+stem+cell+therapy.&rft.au=Mattson%2C+M+P&rft.aulast=Mattson&rft.aufirst=M&rft.date=2000-07-01&rft.volume=35&rft.issue=4&rft.spage=489&rft.isbn=&rft.btitle=&rft.title=Experimental+gerontology&rft.issn=05315565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-22 N1 - Date created - 2000-12-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidative stress contributes to the anti-proliferative effects of flavone acetic acid on endothelial cells. AN - 72200720; 10953282 AB - The synthetic flavonoid flavone acetic acid (FAA) has anti-tumor activity against a variety of transplanted tumors in mice through mechanisms which likely involve effects on tumor vasculature and the host immune system. The aims of the present in vitro study were to compare the sensitivity of tumor and endothelial cells to FAA treatment and to assess if nitric oxide and superoxide are involved in the FAA-mediated suppression of cell proliferation. FAA at 1 mM concentration was approximately two times more effective in suppressing proliferation of endothelial than tumor cells. The anti-proliferative effect of 1 mM FAA on endothelial cells was partially blocked by inhibitors to various superoxide-producing enzymes (xanthine oxidase, cyclooxygenase, poly-ADP-ribose polymerase, ribonucleotide reductase) and completely inhibited by the direct scavengers of superoxide lucigenin and Tiron. In contrast, inhibitors of nitric oxide were unable to prevent the effects of FAA on proliferation. FAA induced apoptosis of endothelial cells, which was not affected by inhibitors of nitric oxide or superoxide. Our data imply that FAA inhibits proliferation of endothelial cells by a superoxide-dependent mechanism and induces apoptosis by a nitric oxide and superoxide-independent mechanism. JF - Anticancer research AU - Harris, S R AU - Panaro, N J AU - Thorgeirsson, U P AD - Tumor Biology and Carcinogenesis Section, National Cancer Institute, NIH, Bethesda, MD 20892, USA. PY - 2000 SP - 2249 EP - 2254 VL - 20 IS - 4 SN - 0250-7005, 0250-7005 KW - Antineoplastic Agents KW - 0 KW - Flavonoids KW - Superoxides KW - 11062-77-4 KW - flavone acetic acid KW - 87626-55-9 KW - Index Medicus KW - Rats KW - Animals KW - Superoxides -- metabolism KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Humans KW - Cell Division -- drug effects KW - Mice KW - Endothelium, Vascular -- drug effects KW - Endothelium, Vascular -- cytology KW - Oxidative Stress KW - Flavonoids -- pharmacology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72200720?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Oxidative+stress+contributes+to+the+anti-proliferative+effects+of+flavone+acetic+acid+on+endothelial+cells.&rft.au=Harris%2C+S+R%3BPanaro%2C+N+J%3BThorgeirsson%2C+U+P&rft.aulast=Harris&rft.aufirst=S&rft.date=2000-07-01&rft.volume=20&rft.issue=4&rft.spage=2249&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-31 N1 - Date created - 2000-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Promotion of hepatocarcinogenesis by phenobarbital in c-myc/TGF-alpha transgenic mice. AN - 71751995; 10942533 AB - Previous work has shown that phenobarbital (PB) can promote cell survival in double transgenic c-myc/transforming growth factor (TGF)-alpha mice. This was achieved through a suppression of cell death brought about, at least in part, by a general increase in the level of bcl-2 protein and a decrease in TGF-beta1 in treated versus untreated animals. No changes were found in TGF-beta type II receptor or in bcl-X(L) protein levels. In the present work, we followed these animals for up to 31 wk of age (28 wk of treatment), by which time numerous tumors could be observed. A PB-dependent decrease in tumor latency and a significant increase in multiplicity were seen. No statistically significant changes in the phenotype of foci, nodules, or neoplasms were observed after PB administration, and no effect on median tumor size was detected. Levels of the anti-apoptotic protein bcl-2 did not correlate with tumor formation in PB-treated animals. However, in untreated mice, bcl-2 was higher in tumors than in surrounding tissue in all tumors examined. We believe that the PB-dependent modification of tumorigenesis in the livers of c-myc/TGF-alpha mice was predominantly a result of the ability of this drug to block cell death during the early stages of tumor development. The effect of PB was exerted apparently by a pathway similar to, but separate from, that of TGF-alpha. However, these pathways appear to converge downstream, having common effectors in the form of bcl-2 family proteins. Mol. Carcinog. 28:168-173, 2000. Copyright 2000 Wiley-Liss, Inc. JF - Molecular carcinogenesis AU - Sanders, S AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 168 EP - 173 VL - 28 IS - 3 SN - 0899-1987, 0899-1987 KW - BCL2L1 protein, human KW - 0 KW - Bcl2l1 protein, mouse KW - Carcinogens KW - Neoplasm Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Proto-Oncogene Proteins c-myc KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor alpha KW - bcl-X Protein KW - Metallothionein KW - 9038-94-2 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 - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Receptors, Transforming Growth Factor beta -- genetics KW - Animals KW - Humans KW - Transgenes KW - Proto-Oncogene Proteins c-bcl-2 -- physiology KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Proto-Oncogene Proteins c-myc -- physiology KW - Metallothionein -- genetics KW - Genes, Synthetic KW - Mice KW - Mice, Transgenic KW - Precancerous Conditions -- pathology KW - Precancerous Conditions -- genetics KW - Mice, Inbred CBA KW - Neoplasm Proteins -- physiology KW - Precancerous Conditions -- chemically induced KW - Cell Transformation, Neoplastic -- chemically induced KW - Mice, Inbred C57BL KW - Crosses, Genetic KW - Genetic Predisposition to Disease KW - Cell Transformation, Neoplastic -- genetics KW - Liver Neoplasms, Experimental -- genetics KW - Apoptosis -- genetics KW - Transforming Growth Factor alpha -- genetics KW - Liver Neoplasms, Experimental -- pathology KW - Genes, myc KW - Transforming Growth Factor alpha -- physiology KW - Apoptosis -- drug effects KW - Carcinogens -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced KW - Phenobarbital -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71751995?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+carcinogenesis&rft.atitle=Promotion+of+hepatocarcinogenesis+by+phenobarbital+in+c-myc%2FTGF-alpha+transgenic+mice.&rft.au=Sanders%2C+S%3BThorgeirsson%2C+S+S&rft.aulast=Sanders&rft.aufirst=S&rft.date=2000-07-01&rft.volume=28&rft.issue=3&rft.spage=168&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-05 N1 - Date created - 2000-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - BRCA2-null embryonic survival is prolonged on the BALB/c genetic background. AN - 71751929; 10942534 AB - Women who inherit mutations in the BRCA2 cancer susceptibility gene have an 85% chance of developing breast cancer. The function of the BRCA2 gene remains elusive, but there is evidence to support its role in transcriptional transactivation, tumor suppression, and the maintenance of genomic integrity. Individuals with identical BRCA2 mutations display a different distribution of cancers, suggesting that there are low-penetrance genes that can modify disease outcome. We hypothesized that genetic background could influence embryonic survival of a Brca2 mutation in mice. Brca2-null embryos with a 129/SvEv genetic background (129(B2-/-)) died before embryonic day 8. 5. Transfer of this Brca2 mutation onto the BALB/cJ genetic background (BALB/c(B2-/-)) extended survival to embryonic day 10.5. These results indicate that the BALB/c background harbors genetic modifiers that can prolong Brca2-null embryonic survival. The extended survival of BALB/c(B2-/-) embryos enabled us to ask whether transcriptional regulation of the Brca1 and Brca2 genes is interdependent. The interdependence of Brca1 and Brca2 was evaluated by studying Brca2 gene expression in BALB/c(B1-/-) embryos and Brca1 gene expression in BALB/c(B2-/-) embryos. Nonisotopic in situ hybridization demonstrated that Brca2 transcript levels were comparable in BALB/c(B1-/-) embryos and wild-type littermates. Likewise, reverse transcriptase-polymerase chain reactions confirmed Brca1 mRNA expression in embryonic day 8.5 BALB/c(B2-/-) embryos that was comparable to Brca2-heterozygous littermates. Thus, the Brca1 and Brca2 transcripts are expressed independently of one another in Brca1- and Brca2-null embryos. Mol. Carcinog. 28:174-183, 2000. Copyright 2000 Wiley-Liss, Inc. JF - Molecular carcinogenesis AU - Bennett, L M AU - McAllister, K A AU - Blackshear, P E AU - Malphurs, J AU - Goulding, G AU - Collins, N K AU - Ward, T AU - Bunch, D O AU - Eddy, E M AU - Davis, B J AU - Wiseman, R W AD - Laboratory of Molecular Carcinogenesis, National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 174 EP - 183 VL - 28 IS - 3 SN - 0899-1987, 0899-1987 KW - BRCA1 Protein KW - 0 KW - BRCA2 Protein KW - Neoplasm Proteins KW - Transcription Factors KW - Index Medicus KW - Animals KW - Mice KW - Genes, BRCA1 KW - Mice, Knockout KW - Genotype KW - BRCA1 Protein -- deficiency KW - Base Sequence KW - BRCA1 Protein -- physiology KW - Embryonic and Fetal Development -- genetics KW - Molecular Sequence Data KW - Transcriptional Activation -- genetics KW - Genetic Predisposition to Disease KW - Genes, Lethal KW - Female KW - Transcription Factors -- physiology KW - Neoplasm Proteins -- physiology KW - Gene Expression Regulation, Developmental -- genetics KW - Fetal Death -- genetics KW - Neoplasm Proteins -- genetics KW - Mice, Inbred BALB C -- genetics KW - Neoplasm Proteins -- deficiency KW - Transcription Factors -- deficiency KW - Transcription Factors -- genetics KW - Mice, Inbred BALB C -- embryology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71751929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+carcinogenesis&rft.atitle=BRCA2-null+embryonic+survival+is+prolonged+on+the+BALB%2Fc+genetic+background.&rft.au=Bennett%2C+L+M%3BMcAllister%2C+K+A%3BBlackshear%2C+P+E%3BMalphurs%2C+J%3BGoulding%2C+G%3BCollins%2C+N+K%3BWard%2C+T%3BBunch%2C+D+O%3BEddy%2C+E+M%3BDavis%2C+B+J%3BWiseman%2C+R+W&rft.aulast=Bennett&rft.aufirst=L&rft.date=2000-07-01&rft.volume=28&rft.issue=3&rft.spage=174&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-05 N1 - Date created - 2000-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ki-ras and the characteristics of mouse lung tumors. AN - 71751848; 10942532 AB - Codon 12 mutations are frequent in the Ki-ras oncogene in human lung adenocarcinomas, but the effects of these alterations have not been well characterized in lung epithelial cells. Murine primary lung tumors derived from peripheral epithelial cells also may present Ki-ras mutations and are useful models for study of early phases of tumor development. One hypothesis is that Ki-ras mutation and/or a Ki-ras p21 increase could enhance Ki-ras p21-GTP and cell-cycle stimulation through raf-1 and extracellularly regulated protein kinases (Erks). We examined lung tumors 1-7 mm in largest dimension initiated in male Swiss mice by N-nitrosodimethylamine for pathologic type, Ki-ras mutations and levels of total Ki-ras p21, Ki-ras p21 bound to GTP, raf-1, Erk1 and Erk2 and their phosphorylated (activated) forms, and proliferating cell nuclear antigen. Total Ki-ras p21 and activated ras-GTP were not significantly greater in tumors than in normal lung or in tumors with versus those without Ki-ras mutations. Carcinomas with Ki-ras mutations were significantly smaller than those without mutations. Carcinomas were significantly larger than adenomas only for tumors without mutations. High levels of Erk2 and correlation of Erk2 amount with ras-GTP were specific characteristics of tumors with Ki-ras mutations. Size of all tumors correlated with ras-GTP but not with proliferating cell nuclear antigen. Raf-1 was expressed mainly in alveolar macrophages in normal lung but was focally upregulated in papillary areas of some tumors. The results indicate that Ki-ras influences the characteristics of lung tumors, but a linear ras-raf-Erk-cell-cycle control sequence does not adequately characterize tumorigenic events in this model. Mol. Carcinog. 28:156-167, 2000. Copyright 2000 Wiley-Liss, Inc. JF - Molecular carcinogenesis AU - Ramakrishna, G AU - Bialkowska, A AU - Perella, C AU - Birely, L AU - Fornwald, L W AU - Diwan, B A AU - Shiao, Y H AU - Anderson, L M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 156 EP - 167 VL - 28 IS - 3 SN - 0899-1987, 0899-1987 KW - Codon KW - 0 KW - DNA, Neoplasm KW - Neoplasm Proteins KW - Proliferating Cell Nuclear Antigen KW - Guanosine Triphosphate KW - 86-01-1 KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - Mitogen-Activated Protein Kinases KW - HRAS protein, human KW - EC 3.6.5.2 KW - Proto-Oncogene Proteins p21(ras) KW - Dimethylnitrosamine KW - M43H21IO8R KW - Index Medicus KW - Animals KW - Codon -- genetics KW - Mitogen-Activated Protein Kinases -- metabolism KW - DNA Mutational Analysis KW - Humans KW - Proto-Oncogene Proteins c-raf -- metabolism KW - Mice KW - Guanosine Triphosphate -- metabolism KW - Codon -- drug effects KW - Apoptosis -- genetics KW - Mitogen-Activated Protein Kinase 1 -- metabolism KW - Cell Transformation, Neoplastic -- chemically induced KW - DNA, Neoplasm -- genetics KW - Neoplasm Proteins -- analysis KW - Cell Cycle -- genetics KW - Species Specificity KW - Neoplasm Proteins -- metabolism KW - Proliferating Cell Nuclear Antigen -- metabolism KW - Male KW - Cell Transformation, Neoplastic -- genetics KW - Lung Neoplasms -- chemistry KW - Carcinoma -- chemistry KW - Genes, ras KW - Adenoma -- chemistry KW - Carcinoma -- pathology KW - Adenoma -- chemically induced KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- chemically induced KW - Adenoma -- genetics KW - Adenoma -- pathology KW - Proto-Oncogene Proteins p21(ras) -- physiology KW - Proto-Oncogene Proteins p21(ras) -- genetics KW - Lung Neoplasms -- pathology KW - Carcinoma -- chemically induced KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71751848?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+carcinogenesis&rft.atitle=Ki-ras+and+the+characteristics+of+mouse+lung+tumors.&rft.au=Ramakrishna%2C+G%3BBialkowska%2C+A%3BPerella%2C+C%3BBirely%2C+L%3BFornwald%2C+L+W%3BDiwan%2C+B+A%3BShiao%2C+Y+H%3BAnderson%2C+L+M&rft.aulast=Ramakrishna&rft.aufirst=G&rft.date=2000-07-01&rft.volume=28&rft.issue=3&rft.spage=156&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-05 N1 - Date created - 2000-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - T cell lysis of murine renal cancer: multiple signaling pathways for cell death via Fas. AN - 71277875; 10914493 AB - Activated T cells lyse the murine renal cancer Renca. We have examined the mechanism of tumor cell lysis with the use of T cells derived from C57BL/6, BALB/c, B6.gld, and B6.Pfp-/- mice. C57BL/6 and BALB/c T cells can lyse Renca cells through the use of both granule- and Fas ligand (FasL)-mediated pathways. However, B6.gld T cells predominantly use granule-mediated killing, whereas B6.Pfp-/- T cells use FasL. The lysis of Renca by Pfp-/- T cells is only partially inhibited by the caspase inhibitor ZVAD-FMK, suggesting that caspase-independent signaling is also important for Renca cell lysis. When the reactive oxygen scavenger butylated hydroxyanisole was used alone or in combination with ZVAD-FMK a substantial reduction of Renca lysis was observed. Therefore, the caspase-independent generation of reactive oxygen intermediates in Renca after Fas triggering contributes to the lysis of these cells. JF - Journal of leukocyte biology AU - Sayers, T J AU - Brooks, A D AU - Seki, N AU - Smyth, M J AU - Yagita, H AU - Blazar, B R AU - Malyguine, A M AD - Intramural Research Support Program, SAIC-Frederick, DBS, NCI-FCRDC, Maryland 21702-1201, USA. Sayers@mail.ncifcrf.gov Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 81 EP - 86 VL - 68 IS - 1 SN - 0741-5400, 0741-5400 KW - Amino Acid Chloromethyl Ketones KW - 0 KW - Antigens, CD95 KW - Apoptosis Regulatory Proteins KW - Dipeptides KW - Enzyme Inhibitors KW - FASLG protein, human KW - Fas Ligand Protein KW - Fasl protein, mouse KW - Free Radical Scavengers KW - Ketones KW - Membrane Glycoproteins KW - Reactive Oxygen Species KW - Recombinant Proteins KW - TNF-Related Apoptosis-Inducing Ligand KW - TNFSF10 protein, human KW - Tnfsf10 protein, mouse KW - Tumor Necrosis Factor-alpha KW - benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone KW - Butylated Hydroxyanisole KW - 25013-16-5 KW - Interferon-gamma KW - 82115-62-6 KW - MDL 201053 KW - 96922-64-4 KW - Caspases KW - EC 3.4.22.- KW - Index Medicus KW - Specific Pathogen-Free Organisms KW - Animals KW - Cytoplasmic Granules -- secretion KW - Humans KW - Interferon-gamma -- pharmacology KW - Mice, Inbred BALB C KW - Tumor Necrosis Factor-alpha -- genetics KW - Mice, Knockout KW - Lymphocyte Activation KW - Tumor Cells, Cultured KW - Caspases -- physiology KW - Free Radical Scavengers -- pharmacology KW - Dipeptides -- pharmacology KW - Butylated Hydroxyanisole -- pharmacology KW - Ketones -- pharmacology KW - Recombinant Proteins -- pharmacology KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Tumor Necrosis Factor-alpha -- physiology KW - Mice KW - Cytotoxicity, Immunologic KW - Transfection KW - Mice, Inbred C57BL KW - Enzyme Inhibitors -- pharmacology KW - Crosses, Genetic KW - Amino Acid Chloromethyl Ketones -- pharmacology KW - Carcinoma, Renal Cell -- pathology KW - Signal Transduction -- physiology KW - Kidney Neoplasms -- pathology KW - Antigens, CD95 -- genetics KW - Membrane Glycoproteins -- physiology KW - Apoptosis -- physiology KW - Antigens, CD95 -- physiology KW - T-Lymphocytes, Cytotoxic -- immunology KW - Carcinoma, Renal Cell -- immunology KW - Membrane Glycoproteins -- deficiency KW - Membrane Glycoproteins -- genetics KW - Kidney Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71277875?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+leukocyte+biology&rft.atitle=T+cell+lysis+of+murine+renal+cancer%3A+multiple+signaling+pathways+for+cell+death+via+Fas.&rft.au=Sayers%2C+T+J%3BBrooks%2C+A+D%3BSeki%2C+N%3BSmyth%2C+M+J%3BYagita%2C+H%3BBlazar%2C+B+R%3BMalyguine%2C+A+M&rft.aulast=Sayers&rft.aufirst=T&rft.date=2000-07-01&rft.volume=68&rft.issue=1&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Journal+of+leukocyte+biology&rft.issn=07415400&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-17 N1 - Date created - 2000-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anti-tumor activity of K1-LysPE38QQR, an immunotoxin targeting mesothelin, a cell-surface antigen overexpressed in ovarian cancer and malignant mesothelioma. AN - 71265593; 10916757 AB - Mesothelin, a differentiation antigen, is a 40-kD glycosylphosphatidylinositol-linked cell-surface glycoprotein, that is present on the surface of normal mesothelium and is overexpressed in many patients with epithelial ovarian cancer and malignant mesotheliomas. Monoclonal antibody K1 is a murine immunoglobulin G1 that recognizes mesothelin. LysPE38QQR is a truncated form of Pseudomonas exotoxin that lacks the cell-binding domain, but retains the translocation and adenosine diphosphate-ribosylation domains. It has a single lysine residue near the amino terminus that is available for conjugation to antibodies. To prevent chemical conjugation of the antibody to lysine residues at the C-terminus of Pseudomonas exotoxin, the two lysine residues at positions 590 and 606 were mutated to glutamine, and the lysine residue at position 613 was mutated to arginine. Monoclonal antibody K1 was chemically conjugated with LysPE38QQR, by modifying the antibody with sulfosuccinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate and coupling it with SPDP N-succinimidyl 3-(2-pyridyldithio)propionate-modified LysPE38QQR. The resulting immunotoxin K1-LysPE38QQR was highly toxic to A431-K5 cells (a human epidermoid carcinoma cell line transfected with a mesothelin expression plasmid) with a half-maximal inhibitory concentration of 3-6 ng/mL. The immunotoxin had negligible activity against A431 cells, which do not express mesothelin (median inhibitory concentration > 100 ng/mL). This immunotoxin also caused complete regression of tumors in nude mice that received xenografts of mesothelin-positive human carcinomas. These results show that immunotoxins directed against mesothelin are a therapeutic option that merits further investigation for the treatment of ovarian cancer and malignant mesotheliomas. JF - Journal of immunotherapy (Hagerstown, Md. : 1997) AU - Hassan, R AU - Viner, J L AU - Wang, Q C AU - Margulies, I AU - Kreitman, R J AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 2000 SP - 473 EP - 479 VL - 23 IS - 4 SN - 1524-9557, 1524-9557 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, Neoplasm KW - Bacterial Toxins KW - Exotoxins KW - GPI-Linked Proteins KW - Immunotoxins KW - Membrane Glycoproteins KW - Virulence Factors KW - mesothelin KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Antigens, Neoplasm -- isolation & purification KW - Humans KW - Mice, Nude KW - Mice KW - Antibodies, Monoclonal -- therapeutic use KW - Antigens, Neoplasm -- therapeutic use KW - Tumor Cells, Cultured KW - Immunotoxins -- immunology KW - Immunotoxins -- therapeutic use KW - Immunotoxins -- isolation & purification KW - Antigens, Neoplasm -- immunology KW - Mutation KW - Female KW - Mesothelioma -- therapy KW - Exotoxins -- genetics KW - Exotoxins -- immunology KW - Ovarian Neoplasms -- therapy KW - Mesothelioma -- immunology KW - Exotoxins -- isolation & purification KW - Membrane Glycoproteins -- therapeutic use KW - Exotoxins -- therapeutic use KW - Membrane Glycoproteins -- immunology KW - Ovarian Neoplasms -- immunology KW - Membrane Glycoproteins -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71265593?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.atitle=Anti-tumor+activity+of+K1-LysPE38QQR%2C+an+immunotoxin+targeting+mesothelin%2C+a+cell-surface+antigen+overexpressed+in+ovarian+cancer+and+malignant+mesothelioma.&rft.au=Hassan%2C+R%3BViner%2C+J+L%3BWang%2C+Q+C%3BMargulies%2C+I%3BKreitman%2C+R+J%3BPastan%2C+I&rft.aulast=Hassan&rft.aufirst=R&rft.date=2000-07-01&rft.volume=23&rft.issue=4&rft.spage=473&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.issn=15249557&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-22 N1 - Date created - 2000-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overexpression of Grb2 in inflammatory lesions and preneoplastic foci and tumors induced by N-nitrosodimethylamine in Helicobacter hepaticus-infected and -noninfected A/J mice. AN - 71264733; 10930041 AB - Growth factors bind to membrane receptor tyrosine kinases, resulting in autophosphorylation and subsequent binding to proteins with SH2 domains, including growth factor receptor-bound protein 2 (Grb2). Grb2 bridges receptors to tyrosine kinase substrates such as SHC and SOS, which in turn facilitate the activation of downstream signaling pathways, including Ras and mitogen-activated protein kinase (MAPK). Overexpression of Grb2 has been demonstrated in several types of neoplasia but has not been investigated in liver tumorigenesis. Here we investigated Grb2 expression in liver lesions in N-nitrosodimethylamine (NDMA)-treated Helicobacter hepaticus-infected and -noninfected A/J mice at 1 year of age. Previously, we reported (6) that infection promotes the development of these NDMA-initiated tumors. In controls, Grb2 immunostaining was absent from normal hepatic tissues, whereas the inflammatory lesions in infected livers were positive for cytoplasmic Grb2 in both hepatocytes and infiltrating leukocytes. All preneoplastic foci (7 of 7), 15 of 27 adenomas, and 3 of 7 carcinomas were positive for Grb2 by immunostaining in both infected and noninfected NDMA-initiated livers. Involvement of Grb2 was confirmed by immunoblotting of similarly infected mice at 9 to 18 months of age, showing a 2.5- to 3.3-fold increase in Grb2 protein in infected livers (p < 0.05 compared with uninfected controls) as well as in preneoplastic foci, adenomas, and carcinomas. These livers also showed a 2.5- to 2.8-fold increase in total Ras protein. The results suggest that upregulation of Grb2 is an early event in liver carcinogenesis, whether caused by the bacterial infection or by NDMA. Concomitant upregulation of Ras p21 would ensure transmission of amplified signal from growth factors via Grb2. JF - Toxicologic pathology AU - Diwan, B A AU - Ramakrishna, G AU - Anderson, L M AU - Ramljak, D AD - Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. bdiwan@mail.ncifcrf.gov PY - 2000 SP - 548 EP - 554 VL - 28 IS - 4 SN - 0192-6233, 0192-6233 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - GRB2 Adaptor Protein KW - Grb2 protein, mouse KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Oncogene Protein p21(ras) KW - EC 3.6.5.2 KW - Dimethylnitrosamine KW - M43H21IO8R KW - Index Medicus KW - Mice, Inbred A KW - Immunoblotting KW - Animals, Newborn KW - Animals KW - Oncogene Protein p21(ras) -- genetics KW - Oncogene Protein p21(ras) -- biosynthesis KW - Up-Regulation -- drug effects KW - Mice KW - Dimethylnitrosamine -- metabolism KW - Immunohistochemistry KW - Male KW - Protein Biosynthesis KW - Hepatitis A -- metabolism KW - Precancerous Conditions -- metabolism KW - Precancerous Conditions -- pathology KW - Receptor, Epidermal Growth Factor -- biosynthesis KW - Neoplasms -- pathology KW - Hepatitis A -- pathology KW - Inflammation -- metabolism KW - Helicobacter Infections -- pathology KW - Helicobacter Infections -- metabolism KW - Inflammation -- pathology KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71264733?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Overexpression+of+Grb2+in+inflammatory+lesions+and+preneoplastic+foci+and+tumors+induced+by+N-nitrosodimethylamine+in+Helicobacter+hepaticus-infected+and+-noninfected+A%2FJ+mice.&rft.au=Diwan%2C+B+A%3BRamakrishna%2C+G%3BAnderson%2C+L+M%3BRamljak%2C+D&rft.aulast=Diwan&rft.aufirst=B&rft.date=2000-07-01&rft.volume=28&rft.issue=4&rft.spage=548&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-08 N1 - Date created - 2001-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase 1 study in patients with metastatic melanoma of immunization with dendritic cells presenting epitopes derived from the melanoma-associated antigens MART-1 and gp100. AN - 71263328; 10916759 AB - Dendritic cells (DCs) have been shown to enhance anti-tumor immune responses in several preclinical models. Furthermore, DC-like function can be elicited from peripheral blood monocytes cultured in vitro with interleukin-4 and granulocyte-macrophage colony-stimulating factor. For this reason, a phase 1 study was initiated at the Surgery Branch of the National Cancer Institute to test the toxicity and biological activity of the intravenous administration of peripheral blood monocyte-derived DCs. The DCs were generated by 5- to 7-day incubation in interleukin-4 (1,000 U/mL) and granulocyte-macrophage colony-stimulating factor (1,000 U/mL) of peripheral blood monocytes obtained by leukapheresis. Before administration, the DCs were pulsed separately with the HLA-A*0201-associated melanoma epitopes MART-1(27-35) and gp-100-209-2M. The DCs were administered four times at 3-week intervals. A first cohort of patients (n = 3) was treated with 6 x 10(7) DCs and a second cohort (n = 5) with 2 x 10(8) DCs (in either case, one half of the DCs were pulsed with MART-1(27-35) and the other half was pulsed with gp-100-209-2M). In a final cohort under accrual (n = 2) 2 x 10(8) DCs were administered in combination with interleukin-2 (720,000 IU/kg every 8 hours). The recovery of DCs after in vitro culture ranged from 3% to 35% (mean, 15%) of the original peripheral blood monocytes. Administration of DCs caused no symptoms at any of the doses, and the concomitant administration of interleukin-2 did not cause toxicity other than that expected for interleukin-2 alone. Monitoring of patients' cytotoxic T lymphocyte reactivity before and after treatment revealed enhancement of cytotoxic T lymphocyte reactivity only in one of five patients tested. Of seven patients evaluated for response, one had a transient partial response with regression of pulmonary and cutaneous metastases. A relatively large number of DCs can be safely administered intravenously. The poor clinical outcome of this study perhaps could be explained by the type of protocol used for DC maturation, the route of administration, or both. For this reason, this clinical protocol was interrupted prematurely, whereas other strategies for DC preparation and route of administration are being investigated at the authors' institution. JF - Journal of immunotherapy (Hagerstown, Md. : 1997) AU - Panelli, M C AU - Wunderlich, J AU - Jeffries, J AU - Wang, E AU - Mixon, A AU - Rosenberg, S A AU - Marincola, F M AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1502, USA. PY - 2000 SP - 487 EP - 498 VL - 23 IS - 4 SN - 1524-9557, 1524-9557 KW - Antigens, Differentiation KW - 0 KW - Cancer Vaccines KW - Epitopes KW - Interleukin-2 KW - MART-1-Melan-A(27-35) epitope KW - Membrane Glycoproteins KW - Neoplasm Proteins KW - PMEL protein, human KW - Peptide Fragments KW - gp100 Melanoma Antigen KW - Index Medicus KW - Antigen Presentation KW - Cancer Vaccines -- adverse effects KW - Injections, Intravenous KW - Antigens, Differentiation -- analysis KW - Humans KW - Cancer Vaccines -- therapeutic use KW - Aged KW - T-Lymphocytes, Cytotoxic -- immunology KW - Cancer Vaccines -- immunology KW - Cells, Cultured KW - Interleukin-2 -- therapeutic use KW - Adult KW - Neoplasm Metastasis KW - Immunotherapy, Adoptive KW - Middle Aged KW - Male KW - Cell Line KW - Female KW - Dendritic Cells -- immunology KW - Neoplasm Proteins -- immunology KW - Dendritic Cells -- transplantation KW - Melanoma -- immunology KW - Peptide Fragments -- immunology KW - Peptide Fragments -- therapeutic use KW - Melanoma -- pathology KW - Membrane Glycoproteins -- therapeutic use KW - Neoplasm Proteins -- therapeutic use KW - Epitopes -- therapeutic use KW - Melanoma -- therapy KW - Epitopes -- immunology KW - Membrane Glycoproteins -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71263328?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.atitle=Phase+1+study+in+patients+with+metastatic+melanoma+of+immunization+with+dendritic+cells+presenting+epitopes+derived+from+the+melanoma-associated+antigens+MART-1+and+gp100.&rft.au=Panelli%2C+M+C%3BWunderlich%2C+J%3BJeffries%2C+J%3BWang%2C+E%3BMixon%2C+A%3BRosenberg%2C+S+A%3BMarincola%2C+F+M&rft.aulast=Panelli&rft.aufirst=M&rft.date=2000-07-01&rft.volume=23&rft.issue=4&rft.spage=487&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.issn=15249557&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-22 N1 - Date created - 2000-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mice heterozygous for a Brca1 or Brca2 mutation display distinct mammary gland and ovarian phenotypes in response to diethylstilbestrol. AN - 71262671; 10910057 AB - Women who inherit mutations in the breast cancer susceptibility genes, BRCA1 and BRCA2, are predisposed to the development of breast and ovarian cancer. We used mice with a Brca1 mutation on a BALB/cJ inbred background (BALB/cB1+/- mice) or a Brca2 genetic alteration on the 129/SvEv genetic background (129B2+/- mice) to investigate potential gene-environment interactions between defects in these genes and treatment with the highly estrogenic compound diethylstilbestrol (DES). Beginning at 3 weeks of age, BALB/cB1+/-, 129B2+/-, and wild-type female mice were fed a control diet or a diet containing 640 ppb DES for 26 weeks. DES treatment caused vaginal epithelial hyperplasia and hyperkeratosis, uterine inflammation, adenomyosis, and fibrosis, as well as oviductal smooth muscle hypertrophy. The severity of the DES response was mouse strain specific. The estrogen-responsive 129/SvEv strain exhibited an extreme response in the reproductive tract, whereas the effect in BALB/cJ and C3H/HeN(MMTV-) mice was less severe. The Brca1 and Brca2 genetic alterations influenced the phenotypic response of BALB/cJ and 129/SvEv inbred strains, respectively, to DES in the mammary gland and ovary. The mammary duct branching morphology was inhibited in DES-treated BALB/cB1+/- mice compared with similarly treated BALB/cB1+/+ littermates. In addition, the majority of BALB/cB1+/- mice had atrophied ovaries, whereas wild-type littermates were largely diagnosed with arrested follicular development. The mammary ductal architecture in untreated 129B2+/- mice revealed a subtle inhibited branching phenotype that was enhanced with DES treatment. However, no significant differences were observed in ovarian pathology between 129B2+/+ and 129B2+/- mice. These data suggest that estrogenic compounds may modulate mammary gland or ovarian morphology in BALB/cB1+/- and 129B2+/- mice. These observations are consistent with the hypothesis that compromised DNA repair processes in cells harboring Brca1 or Brca2 mutations lead to inhibited growth and differentiation compared with the proliferative response of wild-type cells to DES treatment. JF - Cancer research AU - Bennett, L M AU - McAllister, K A AU - Malphurs, J AU - Ward, T AU - Collins, N K AU - Seely, J C AU - Gowen, L C AU - Koller, B H AU - Davis, B J AU - Wiseman, R W AD - Laboratories of Molecular Carcinogenesis, NIH, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Bennett3@niehs.nih.gov Y1 - 2000/07/01/ PY - 2000 DA - 2000 Jul 01 SP - 3461 EP - 3469 VL - 60 IS - 13 SN - 0008-5472, 0008-5472 KW - BRCA2 Protein KW - 0 KW - Carcinogens KW - Genetic Markers KW - Neoplasm Proteins KW - Transcription Factors KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Animals KW - Fallopian Tubes -- pathology KW - Fallopian Tubes -- drug effects KW - Fibrosis -- chemically induced KW - Vagina -- pathology KW - Mice, Inbred BALB C KW - Mice, Transgenic KW - Phenotype KW - Chimera KW - Heterozygote KW - Mice, Inbred C3H KW - Vagina -- drug effects KW - Muscle, Smooth -- pathology KW - Carcinogens -- toxicity KW - Mice KW - Uterus -- drug effects KW - Inflammation KW - Hypertrophy KW - Epithelial Cells -- drug effects KW - Endometriosis -- pathology KW - Epithelial Cells -- pathology KW - Crosses, Genetic KW - Uterus -- pathology KW - Muscle, Smooth -- drug effects KW - Female KW - Mammary Glands, Animal -- drug effects KW - Ovary -- pathology KW - Genes, BRCA1 -- genetics KW - Mammary Glands, Animal -- pathology KW - Diethylstilbestrol -- toxicity KW - Ovary -- drug effects KW - Neoplasm Proteins -- genetics KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71262671?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mice+heterozygous+for+a+Brca1+or+Brca2+mutation+display+distinct+mammary+gland+and+ovarian+phenotypes+in+response+to+diethylstilbestrol.&rft.au=Bennett%2C+L+M%3BMcAllister%2C+K+A%3BMalphurs%2C+J%3BWard%2C+T%3BCollins%2C+N+K%3BSeely%2C+J+C%3BGowen%2C+L+C%3BKoller%2C+B+H%3BDavis%2C+B+J%3BWiseman%2C+R+W&rft.aulast=Bennett&rft.aufirst=L&rft.date=2000-07-01&rft.volume=60&rft.issue=13&rft.spage=3461&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 - 2000-08-17 N1 - Date created - 2000-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Convection-enhanced delivery of AAV vector in parkinsonian monkeys; in vivo detection of gene expression and restoration of dopaminergic function using pro-drug approach. AN - 71262219; 10877910 AB - Using an approach that combines gene therapy with aromatic l-amino acid decarboxylase (AADC) gene and a pro-drug (l-dopa), dopamine, the neurotransmitter involved in Parkinson's disease, can be synthesized and regulated. Striatal neurons infected with the AADC gene by an adeno-associated viral vector can convert peripheral l-dopa to dopamine and may therefore provide a buffer for unmetabolized l-dopa. This approach to treating Parkinson's disease may reduce the need for l-dopa/carbidopa, thus providing a better clinical response with fewer side effects. In addition, the imbalance in dopamine production between the nigrostriatal and mesolimbic dopaminergic systems can be corrected by using AADC gene delivery to the striatum. We have also demonstrated that a fundamental obstacle in the gene therapy approach to the central nervous system, i.e., the ability to deliver viral vectors in sufficient quantities to the whole brain, can be overcome by using convection-enhanced delivery. Finally, this study demonstrates that positron emission tomography and the AADC tracer, 6-[(18)F]fluoro-l-m-tyrosine, can be used to monitor gene therapy in vivo. Our therapeutic approach has the potential to restore dopamine production, even late in the disease process, at levels that can be maintained during continued nigrostriatal degeneration. Copyright 2000 Academic Press. JF - Experimental neurology AU - Bankiewicz, K S AU - Eberling, J L AU - Kohutnicka, M AU - Jagust, W AU - Pivirotto, P AU - Bringas, J AU - Cunningham, J AU - Budinger, T F AU - Harvey-White, J AD - Molecular Therapeutics Section, LMMN, NINDS, Bethesda, Maryland 20892, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 2 EP - 14 VL - 164 IS - 1 SN - 0014-4886, 0014-4886 KW - Drug Combinations KW - 0 KW - Fluorine Radioisotopes KW - Prodrugs KW - carbidopa, levodopa drug combination KW - 6-fluoro-3-tyrosine KW - 148613-12-1 KW - Tyrosine KW - 42HK56048U KW - Levodopa KW - 46627O600J KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Aromatic-L-Amino-Acid Decarboxylases KW - EC 4.1.1.28 KW - Carbidopa KW - MNX7R8C5VO KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Magnetic Resonance Imaging KW - Animals KW - Caudate Nucleus -- diagnostic imaging KW - Neurons -- drug effects KW - Aromatic-L-Amino-Acid Decarboxylases -- genetics KW - Drug Administration Routes KW - Neurons -- pathology KW - Prodrugs -- therapeutic use KW - Caudate Nucleus -- pathology KW - Carbidopa -- therapeutic use KW - Aromatic-L-Amino-Acid Decarboxylases -- metabolism KW - Macaca mulatta KW - Levodopa -- metabolism KW - Putamen -- drug effects KW - Tyrosine 3-Monooxygenase -- metabolism KW - Neurons -- metabolism KW - Aromatic-L-Amino-Acid Decarboxylases -- therapeutic use KW - Dopamine -- metabolism KW - Caudate Nucleus -- drug effects KW - Putamen -- diagnostic imaging KW - Putamen -- pathology KW - Tomography, Emission-Computed KW - Catheterization -- methods KW - Levodopa -- therapeutic use KW - Cell Line KW - Parkinson Disease, Secondary -- chemically induced KW - Genetic Vectors -- administration & dosage KW - Tyrosine -- pharmacokinetics KW - Dependovirus -- genetics KW - Genetic Therapy -- methods KW - Tyrosine -- analogs & derivatives KW - Parkinson Disease, Secondary -- therapy KW - Genetic Vectors -- pharmacokinetics KW - Genetic Vectors -- genetics KW - Parkinson Disease, Secondary -- genetics KW - Parkinson Disease, Secondary -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71262219?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Convection-enhanced+delivery+of+AAV+vector+in+parkinsonian+monkeys%3B+in+vivo+detection+of+gene+expression+and+restoration+of+dopaminergic+function+using+pro-drug+approach.&rft.au=Bankiewicz%2C+K+S%3BEberling%2C+J+L%3BKohutnicka%2C+M%3BJagust%2C+W%3BPivirotto%2C+P%3BBringas%2C+J%3BCunningham%2C+J%3BBudinger%2C+T+F%3BHarvey-White%2C+J&rft.aulast=Bankiewicz&rft.aufirst=K&rft.date=2000-07-01&rft.volume=164&rft.issue=1&rft.spage=2&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 - 2000-08-16 N1 - Date created - 2000-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quality of pharmacotherapy consultations provided by drug information centers in the United States. AN - 71260460; 10907973 AB - We evaluated the performance of 116 U.S. drug information centers in responding to specific questions about drugs. The primary measures were correctness of responses and extent of probing for patient data. Questions addressed the effect of ranitidine on blood alcohol concentrations, the potential interaction between didanosine and dapsone, prevention of nonsteroidal antiinflammatory drug (NSAID)-induced peptic ulcers, and use of erythromycin for diabetic gastroparesis. The percentages of centers providing correct overall responses were 70% for the ranitidine question, 90% for the didanosine-dapsone question, 8% for the NSAID question, and 20% for the erythromycin question. For the three patient-specific questions, the percentages of centers eliciting vital patient data were 27% for the didanosine-dapsone question, 86% for the NSAID question, and 5% for the erythromycin question. In providing pharmacotherapy consultations, drug information centers generally failed to obtain pertinent patient data, thereby risking incorrect responses and inappropriate recommendations. JF - Pharmacotherapy AU - Calis, K A AU - Anderson, D W AU - Auth, D A AU - Mays, D A AU - Turcasso, N M AU - Meyer, C C AU - Young, L R AD - Department of Pharmacy, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1196, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 830 EP - 836 VL - 20 IS - 7 SN - 0277-0008, 0277-0008 KW - Index Medicus KW - United States KW - Drug Interactions KW - Drug Therapy KW - Quality of Health Care KW - Humans KW - Drug-Related Side Effects and Adverse Reactions KW - Drug Information Services -- standards KW - Referral and Consultation -- standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71260460?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Quality+of+pharmacotherapy+consultations+provided+by+drug+information+centers+in+the+United+States.&rft.au=Calis%2C+K+A%3BAnderson%2C+D+W%3BAuth%2C+D+A%3BMays%2C+D+A%3BTurcasso%2C+N+M%3BMeyer%2C+C+C%3BYoung%2C+L+R&rft.aulast=Calis&rft.aufirst=K&rft.date=2000-07-01&rft.volume=20&rft.issue=7&rft.spage=830&rft.isbn=&rft.btitle=&rft.title=Pharmacotherapy&rft.issn=02770008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-30 N1 - Date created - 2000-11-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations of ras protooncogenes and p53 tumor suppressor gene in cardiac hemangiosarcomas from B6C3F1 mice exposed to 1,3-butadiene for 2 years. AN - 71256099; 10930038 AB - 1,3-Butadiene is a multisite carcinogen in rodents. Incidences of cardiac hemangiosarcomas were significantly increased in male and female B6C3F1 mice that inhaled 1,3-butadiene (BD) for 2 years. Eleven BD-induced cardiac hemangiosarcomas were examined for genetic alterations in ras protooncogenes and in the p53 tumor suppressor gene. Nine of 11 (82%) BD-induced hemangiosarcomas had K-ras mutations and 5 of 11 (46%) had H-ras mutations. All of the K-ras mutations were G-->C transversions (GGC-->CGC) at codon 13; this pattern is consistent with reported results in BD-induced lung neoplasms and lymphomas. Both K-ras codon 13 CGC mutations and H-ras codon 61 CGA mutations were detected in 5 of 9 (56%) hemangiosarcomas. The 11 hemangiosarcomas stained positive for p53 protein by immunohistochemistry and were analyzed for p53 mutations using cycle sequencing of polymerase chain reaction (PCR) amplified DNA isolated from paraffin-embedded sections. Mutations in exons 5 to 8 of the p53 gene were identified in 5 of 11 (46%) hemangiosarcomas, and all of these were from the 200- or 625-ppm exposure groups that also had K-ras codon 13 CGC mutations. Our data indicate that K-ras, H-ras, and p53 mutations in these hemangiosarcomas most likely occurred as a result of the genotoxic effects of BD and that these mutations may play a role in the pathogenesis of BD-induced cardiac hemangiosarcomas in the B6C3F1 mouse. JF - Toxicologic pathology AU - Hong, H H AU - Devereux, T R AU - Melnick, R L AU - Moomaw, C R AU - Boorman, G A AU - Sills, R C AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. hong@niehs.nih.gov PY - 2000 SP - 529 EP - 534 VL - 28 IS - 4 SN - 0192-6233, 0192-6233 KW - Butadienes KW - 0 KW - Mutagens KW - 1,3-butadiene KW - JSD5FGP5VD KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Mice KW - Immunohistochemistry KW - Male KW - Female KW - Cell Cycle -- drug effects KW - Genes, ras -- genetics KW - Genes, ras -- drug effects KW - Genes, p53 -- drug effects KW - Butadienes -- toxicity KW - Heart Neoplasms -- pathology KW - Hemangiosarcoma -- genetics KW - Hemangiosarcoma -- pathology KW - Heart Neoplasms -- genetics KW - Genes, p53 -- genetics KW - Mutagens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71256099?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Mutations+of+ras+protooncogenes+and+p53+tumor+suppressor+gene+in+cardiac+hemangiosarcomas+from+B6C3F1+mice+exposed+to+1%2C3-butadiene+for+2+years.&rft.au=Hong%2C+H+H%3BDevereux%2C+T+R%3BMelnick%2C+R+L%3BMoomaw%2C+C+R%3BBoorman%2C+G+A%3BSills%2C+R+C&rft.aulast=Hong&rft.aufirst=H&rft.date=2000-07-01&rft.volume=28&rft.issue=4&rft.spage=529&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-08 N1 - Date created - 2001-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunotoxins with increased activity against epidermal growth factor receptor vIII-expressing cells produced by antibody phage display. AN - 71255710; 10914732 AB - Recombinant immunotoxins are fusion proteins composed of Fv regions of antibodies and bacterial or plant toxins that are being developed for the targeted therapy of cancer. MR1(Fv)-PE38 is a single-chain recombinant immunotoxin that targets a mutant form of the epidermal growth factor receptor (EGFR), EGFRvIII, that is frequently overexpressed in malignant glioblastomas. We have used random complementarity determining region (CDR) mutagenesis to obtain mutants of MR1(Fv) with an increased affinity for EGFRvIII and an increased activity when converted to a recombinant immunotoxin. Initially, nine residues of heavy chain CDR3 were randomly mutagenized, and several mutants with increased binding affinity were isolated. All mutations were located at amino acids 98 and 99, which correspond to a DNA hot spot, a DNA sequence that mutates at high frequency during natural antibody maturation. A specific region of variable region of antibody light chain CDR3 was mutagenized that corresponded to a hot spot and a mutant (MR1-1) with an additional increase in affinity, and cytotoxic activity was isolated. These studies show that targeting hot spots in the CDRs of Fvs is an effective approach to obtaining Fvs with increased affinity. The increased affinity of MR1-1(Fv) makes it an attractive candidate for the targeted therapy of glioblastomas. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Beers, R AU - Chowdhury, P AU - Bigner, D AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 2835 EP - 2843 VL - 6 IS - 7 SN - 1078-0432, 1078-0432 KW - Bacterial Toxins KW - 0 KW - Exotoxins KW - Immunoglobulin Heavy Chains KW - Immunoglobulin Light Chains KW - Immunotoxins KW - Peptide Library KW - Recombinant Proteins KW - Virulence Factors KW - epidermal growth factor receptor VIII KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Surface Plasmon Resonance KW - Amino Acid Sequence KW - Immunoglobulin Light Chains -- chemistry KW - Immunoglobulin Heavy Chains -- genetics KW - Cloning, Molecular KW - Recombinant Proteins -- toxicity KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Cell Survival -- drug effects KW - Immunoglobulin Heavy Chains -- chemistry KW - Escherichia coli KW - Immunoglobulin Light Chains -- genetics KW - Recombinant Proteins -- chemistry KW - Cell Line KW - Immunotoxins -- chemistry KW - Immunotoxins -- toxicity KW - Receptor, Epidermal Growth Factor -- immunology KW - Receptor, Epidermal Growth Factor -- chemistry KW - Exotoxins -- toxicity KW - Exotoxins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71255710?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Immunotoxins+with+increased+activity+against+epidermal+growth+factor+receptor+vIII-expressing+cells+produced+by+antibody+phage+display.&rft.au=Beers%2C+R%3BChowdhury%2C+P%3BBigner%2C+D%3BPastan%2C+I&rft.aulast=Beers&rft.aufirst=R&rft.date=2000-07-01&rft.volume=6&rft.issue=7&rft.spage=2835&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 - 2000-11-16 N1 - Date created - 2000-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase II trial of paclitaxel by 96-hour continuous infusion in combination with cisplatin for patients with advanced non-small cell lung cancer. AN - 71254824; 10914708 AB - Our purpose was to determine the antitumor efficacy and safety profile of the combination of paclitaxel administered by 96-h continuous i.v. infusion followed by bolus cisplatin in patients with untreated advanced non-small cell lung cancer (NSCLC). Fifty-eight patients with untreated advanced or recurrent NSCLC were enrolled between October 1995 and December 1998. The median patient age was 60 years (age range, 34-75 years). Twenty-four patients were female. The majority of patients (n = 52) had an Eastern Cooperative Oncology Group performance status of 0/1. Twelve patients had stage IIIB NSCLC, 43 had stage IV disease, and 3 had recurrent disease after prior resection. Seven patients had received cranial irradiation for brain metastases, and 5 patients had received bone irradiation before enrollment. Patients were treated with paclitaxel (120 mg/m2/96 h) by continuous i.v. infusion followed by cisplatin (80 mg/m2) on day 5. Therapy was administered every 3 weeks as tolerated until disease progression or a maximum of six cycles. A total of 264 cycles of therapy were administered. Twenty-nine patients received all six cycles. Forty-six patients had measurable disease, with 20 patients achieving a partial response, and no complete responses were seen (overall response rate, 43%; 95% confidence interval, 29-60%). The median progression-free survival was 5.5 months. At a median potential follow-up of 27.2 months, the median survival for all 58 enrolled patients was 8.5 months, and the actuarial 1-year survival was 37% (95% confidence interval, 25.9-50.5%). This is the most extensive evaluation of prolonged continuous infusional paclitaxel in patients with advanced-stage cancer. In contrast to predictions from in vitro cytotoxicity models, the regimen does not appear to be obviously superior to shorter infusion times in the clinical setting. Additional trials of this regimen in patients with NSCLC are therefore of low priority. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Breathnach, O S AU - Georgiadis, M S AU - Schuler, B S AU - Pizzella, P AU - Llorens, V AU - Kasturi, V AU - Steinberg, S M AU - O'Neil, K AU - Takimoto, C H AU - Johnson, B E AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute/National Naval Medical Center, Bethesda, Maryland 20889, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 2670 EP - 2676 VL - 6 IS - 7 SN - 1078-0432, 1078-0432 KW - Paclitaxel KW - P88XT4IS4D KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Drug Administration Schedule KW - Disease-Free Survival KW - Survival Rate KW - Neoplasm Staging KW - Infusions, Intravenous KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - Male KW - Female KW - Paclitaxel -- administration & dosage KW - Paclitaxel -- adverse effects KW - Carcinoma, Non-Small-Cell Lung -- mortality KW - Lung Neoplasms -- drug therapy KW - Lung Neoplasms -- mortality KW - Cisplatin -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Carcinoma, Non-Small-Cell Lung -- drug therapy KW - Lung Neoplasms -- pathology KW - Cisplatin -- administration & dosage KW - Carcinoma, Non-Small-Cell Lung -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71254824?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phase+II+trial+of+paclitaxel+by+96-hour+continuous+infusion+in+combination+with+cisplatin+for+patients+with+advanced+non-small+cell+lung+cancer.&rft.au=Breathnach%2C+O+S%3BGeorgiadis%2C+M+S%3BSchuler%2C+B+S%3BPizzella%2C+P%3BLlorens%2C+V%3BKasturi%2C+V%3BSteinberg%2C+S+M%3BO%27Neil%2C+K%3BTakimoto%2C+C+H%3BJohnson%2C+B+E&rft.aulast=Breathnach&rft.aufirst=O&rft.date=2000-07-01&rft.volume=6&rft.issue=7&rft.spage=2670&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 - 2000-11-16 N1 - Date created - 2000-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Combination immunotherapy of relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma with rituximab and interferon-alpha-2a. AN - 71251813; 10914705 AB - Rituximab and IFN have each demonstrated single-agent activity in patients with low-grade non-Hodgkin's lymphoma (NHL). A single-arm, multicenter, Phase II trial was conducted to assess the safety and efficacy of combination therapy with rituximab and IFN-alpha-2a in 38 patients with relapsed or refractory, low-grade or follicular, B-cell NHL. IFN-alpha-2a [2.5 or 5 million units (MIU)] was administered s.c., three times weekly for 12 weeks. Starting on the fifth week of treatment, rituximab was administered by i.v. infusion (375 mg/m2) weekly for 4 doses. All 38 patients received four complete infusions of rituximab and were evaluable for efficacy, although 11 patients (29%) did not-receive all 36 injections of IFN. The mean number of IFN-alpha-2a injections was 31 doses; the mean total units received were 141 MIU (maximum, 180 MIU). The study treatment was reasonably well tolerated with no unexpected toxicities stemming from the combination therapy. No grade 4 events were reported. Frequent adverse events during the treatment period included asthenia (35 of 38 patients), chills (31 of 38), fever (30 of 38), headache (28 of 38), nausea (23 of 38), and myalgia (22 of 38). The overall response rate was 45% (17 of 38 patients); 11% had a complete response, and 34% had a partial response. The Kaplan-Meier estimates for the median response duration and the median time to progression in responders are 22.3 and 25.2 months, respectively. Further follow-up is needed to determine whether this treatment combination leads to a significantly longer time to progression than single-agent treatment with rituximab. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Davis, T A AU - Maloney, D G AU - Grillo-López, A J AU - White, C A AU - Williams, M E AU - Weiner, G J AU - Dowden, S AU - Levy, R AD - Cancer Therapy Evaluation Program, National Cancer Institute, Rockville, Maryland 20852, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 2644 EP - 2652 VL - 6 IS - 7 SN - 1078-0432, 1078-0432 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Murine-Derived KW - Antineoplastic Agents KW - Interferon-alpha KW - Recombinant Proteins KW - interferon alfa-2a KW - 47RRR83SK7 KW - Rituximab KW - 4F4X42SYQ6 KW - Index Medicus KW - Disease-Free Survival KW - Infusions, Intravenous KW - Neoplasm Staging KW - Humans KW - Disease Progression KW - Aged KW - Immunotherapy -- adverse effects KW - Adult KW - Middle Aged KW - Time Factors KW - Female KW - Male KW - Interferon-alpha -- therapeutic use KW - Lymphoma, Follicular -- pathology KW - Interferon-alpha -- administration & dosage KW - Lymphoma, Follicular -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antibodies, Monoclonal -- administration & dosage KW - Antibodies, Monoclonal -- therapeutic use KW - Antineoplastic Agents -- adverse effects KW - Interferon-alpha -- adverse effects KW - Lymphoma, B-Cell -- drug therapy KW - Lymphoma, B-Cell -- pathology KW - Antibodies, Monoclonal -- adverse effects KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71251813?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Combination+immunotherapy+of+relapsed+or+refractory+low-grade+or+follicular+non-Hodgkin%27s+lymphoma+with+rituximab+and+interferon-alpha-2a.&rft.au=Davis%2C+T+A%3BMaloney%2C+D+G%3BGrillo-L%C3%B3pez%2C+A+J%3BWhite%2C+C+A%3BWilliams%2C+M+E%3BWeiner%2C+G+J%3BDowden%2C+S%3BLevy%2C+R&rft.aulast=Davis&rft.aufirst=T&rft.date=2000-07-01&rft.volume=6&rft.issue=7&rft.spage=2644&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 - 2000-11-16 N1 - Date created - 2000-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protease inhibitor-induced apoptosis: accumulation of wt p53, p21WAF1/CIP1, and induction of apoptosis are independent markers of proteasome inhibition. AN - 71251374; 10914553 AB - Inhibitors of proteases are currently emerging as a potential anti-cancer modality. Nonselective protease inhibitors are cytotoxic to leukemia and cancer cell lines and we found that this cytotoxicity is correlated with their potency as inhibitors of the proteasome but not as inhibitors of calpain and cathepsin. Highly selective inhibitors of the proteasome were more cytotoxic and fast-acting than less selective inhibitors (PS341>>ALLN>>ALLM). Induction of wt p53 correlated with inhibition of the proteasome and antiproliferative effect in MCF7, a breast cancer cell line, which was resistant to apoptosis caused by proteasome inhibitors. In contrast, inhibitors of the proteasome induced apoptosis in four leukemia cell lines lacking wt p53. The order of sensitivity of leukemia cells was: Jurkat>HL60> or =U937>>K562. The highly selective proteasome inhibitor PS-341 induced cell death with an IC50 as low as 5 nM in apoptosis-prone leukemia cells. Cell death was preceded by p21WAF1/CIP1 accumulation, an alternative marker of proteasome inhibition, and by cleavage of PARP and Rb proteins and nuclear fragmentation. Inhibition of caspases abrogated PARP cleavage and nuclear fragmentation and delayed, but did not completely prevent cell death caused by PS-341. Reintroduction of wt p53 into p53-null PC3 prostate carcinoma cells did not increase their sensitivity to proteasome inhibitors. Likewise, comparison of parental and p21-deficient cells demonstrated that p21WAF1/CIP1 was dispensable for proteasome inhibitor-induced cytotoxicity. We conclude that accumulation of wt p53 and induction of apoptosis are independent markers of proteasome inhibition. JF - Leukemia AU - An, W G AU - Hwang, S G AU - Trepel, J B AU - Blagosklonny, M V AD - Medicine Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 1276 EP - 1283 VL - 14 IS - 7 SN - 0887-6924, 0887-6924 KW - Acrylates KW - 0 KW - Amino Acid Chloromethyl Ketones KW - Boronic Acids KW - CDKN1A protein, human KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Leupeptins KW - Multienzyme Complexes KW - Neoplasm Proteins KW - Oligopeptides KW - PD 150606 KW - Protease Inhibitors KW - Pyrazines KW - Tumor Suppressor Protein p53 KW - benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone KW - acetylleucyl-leucyl-norleucinal KW - 110044-82-1 KW - N-acetylleucyl-leucyl-methioninal KW - 110115-07-6 KW - lactacystin KW - 133343-34-7 KW - Bortezomib KW - 69G8BD63PP KW - Cathepsins KW - EC 3.4.- KW - Calpain KW - EC 3.4.22.- KW - Cysteine Endopeptidases KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Boronic Acids -- pharmacology KW - Tumor Cells, Cultured -- cytology KW - Boronic Acids -- toxicity KW - Leupeptins -- toxicity KW - Tumor Cells, Cultured -- drug effects KW - Jurkat Cells -- metabolism KW - Humans KW - Jurkat Cells -- drug effects KW - Leupeptins -- pharmacology KW - U937 Cells -- drug effects KW - Genes, p53 KW - Acrylates -- pharmacology KW - Calpain -- antagonists & inhibitors KW - Jurkat Cells -- cytology KW - Drug Synergism KW - Pyrazines -- toxicity KW - Tumor Cells, Cultured -- metabolism KW - Acetylcysteine -- analogs & derivatives KW - Pyrazines -- pharmacology KW - Acetylcysteine -- toxicity KW - Cell Division -- drug effects KW - Cathepsins -- antagonists & inhibitors KW - Acetylcysteine -- pharmacology KW - Acrylates -- toxicity KW - Oligopeptides -- toxicity KW - Neoplasms -- pathology KW - Amino Acid Chloromethyl Ketones -- toxicity KW - Oligopeptides -- pharmacology KW - Amino Acid Chloromethyl Ketones -- pharmacology KW - U937 Cells -- metabolism KW - U937 Cells -- cytology KW - Protease Inhibitors -- pharmacology KW - Multienzyme Complexes -- metabolism KW - Cysteine Endopeptidases -- metabolism KW - Neoplasm Proteins -- genetics KW - Apoptosis -- drug effects KW - Protease Inhibitors -- toxicity KW - Cyclins -- metabolism KW - Tumor Suppressor Protein p53 -- metabolism KW - Neoplasm Proteins -- metabolism KW - Cyclins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71251374?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia&rft.atitle=Protease+inhibitor-induced+apoptosis%3A+accumulation+of+wt+p53%2C+p21WAF1%2FCIP1%2C+and+induction+of+apoptosis+are+independent+markers+of+proteasome+inhibition.&rft.au=An%2C+W+G%3BHwang%2C+S+G%3BTrepel%2C+J+B%3BBlagosklonny%2C+M+V&rft.aulast=An&rft.aufirst=W&rft.date=2000-07-01&rft.volume=14&rft.issue=7&rft.spage=1276&rft.isbn=&rft.btitle=&rft.title=Leukemia&rft.issn=08876924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-10 N1 - Date created - 2000-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase II study of gemcitabine plus cisplatin chemotherapy in advanced bilharzial bladder carcinoma. AN - 71251368; 10908847 AB - Bilharzial bladder cancer represents a distinct clinicopathological entity. To investigate whether gemcitabine-cisplatin is also active against bladder cancer of bilharzial origin, we performed a phase II study of previously untreated patients with stage III/IV disease. Standard eligibility criteria were used. Patients received gemcitabine (1000 mg/m(2)) on days 1, 8 and 15 and cisplatin (70 mg/m(2)) on day 2 of every 28-day cycle. The 32 males and 5 females had a median age of 59 years (range: 29-81 years). Of 33 evaluable patients, 8 (24%) achieved complete responses, and 10 (30%) partial responses, for an overall response rate of 55%. 3 patients had minor responses. Responses were observed at all disease sites including lung and liver lesions. Myelosuppression was significant but manageable. Non-haematological toxicity was limited mainly to nausea and vomiting and raised liver enzymes. Thus, these data suggest that gemcitabine plus cisplatin induces high response rates in patients with bilharzial bladder cancer with a moderate toxicity profile. JF - European journal of cancer (Oxford, England : 1990) AU - Khaled, H M AU - Hamza, M R AU - Mansour, O AU - Gaafar, R AU - Zaghloul, M S AD - Department of Medical Oncology, National Cancer Institute, University, Cairo, Egypt. khaled@brainy1.ie-eg.com Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 34 EP - 37 VL - 36 Suppl 2 SN - 0959-8049, 0959-8049 KW - Deoxycytidine KW - 0W860991D6 KW - gemcitabine KW - B76N6SBZ8R KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Aged, 80 and over KW - Humans KW - Deoxycytidine -- analogs & derivatives KW - Adult KW - Treatment Outcome KW - Deoxycytidine -- administration & dosage KW - Aged KW - Middle Aged KW - Male KW - Female KW - Cisplatin -- administration & dosage KW - Schistosomiasis -- drug therapy KW - Urinary Bladder Neoplasms -- drug therapy KW - Schistosomiasis -- complications KW - Urinary Bladder Neoplasms -- parasitology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Carcinoma, Transitional Cell -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71251368?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.atitle=A+phase+II+study+of+gemcitabine+plus+cisplatin+chemotherapy+in+advanced+bilharzial+bladder+carcinoma.&rft.au=Khaled%2C+H+M%3BHamza%2C+M+R%3BMansour%2C+O%3BGaafar%2C+R%3BZaghloul%2C+M+S&rft.aulast=Khaled&rft.aufirst=H&rft.date=2000-07-01&rft.volume=36+Suppl+2&rft.issue=&rft.spage=34&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.issn=09598049&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-28 N1 - Date created - 2000-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ni(II) specifically cleaves the C-terminal tail of the major variant of histone H2A and forms an oxidative damage-mediating complex with the cleaved-off octapeptide. AN - 71249594; 10898594 AB - The acetyl-TESHHK-amide peptide, modeling a part of the C-terminal "tail" of histone H2A, was found previously by us to undergo at pH 7. 4 a Ni(II)-assisted hydrolysis of the E-S peptide bond with formation of a stronger Ni(II) complex with the SHHK-amide product [Bal, W., et al. (1998) Chem. Res. Toxicol. 11, 1014-1023]. To further characterize the hydrolysis and test the resulting Ni(II) complex for redox activity, bovine histone H2A and three peptides were investigated: acetyl-LLGKVTIAQGGVLPNIQAVLLPKKTESHHKAKGK (H2A(34)), modeling the entire "C-tail" of H2A; SHHKAKGK (H2A(8)), modeling the cutoff product of hydrolysis; and acetyl-KTESHKAKGK (H2A(10)), modeling a putative Ni(II) binding site in a minor variant H2A.4 of human histone H2A. The Ni(II)-assisted hydrolysis of H2A and H2A(34) was found to proceed approximately 7-fold faster than that of the Ni(II)-acetyl-TESHHK-amide complex under comparable conditions. In both cases, the Ni(II) complex with H2A(8) was the smaller product of the hydrolysis, indicating a high site specificity of the reaction. Of three other metals tested with H2A(34), only Cu(II) cleaved the E-S bond, although much less efficiently than Ni(II); Co(II) and Zn(II) had no effect whatsoever. The H2A(10) peptide appeared to be fully resistant to hydrolytic cleavage and did not exhibit any redox activity versus H(2)O(2) in the presence of Ni(II) at pH 7.4. Likewise, redox-inactive was the Ni(II)-H2A(34) complex. In contrast, the Ni(II)-H2A(8) complex promoted oxidative damage of pUC19 DNA by H(2)O(2), evidenced by a significant increase in the number of single strand breaks and nucleobase modifications typical for a hydroxyl radical-like species attack on DNA. Interestingly, instead of 8-oxopurines, the corresponding formamidopyrimidines were the major products of the damage. The difference in redox activity between the Ni(II)-H2A(34) and Ni(II)-H2A(8) complexes is most likely associated with their different geometries: octahedral and square planar, respectively. Incubation of the Ni(II)-H2A(8) complex with H(2)O(2) also resulted in degradation of the peptide ligand, especially at its Ser and His residues. Thus, binding of Ni(II) to the ESHHK motif of the histone H2A C-tail is damaging to the histone C-terminal tail and to histone-associated DNA. The results support a dual mechanism of Ni(II)-induced carcinogenesis, including both genotoxic and epigenetic effects. JF - Chemical research in toxicology AU - Bal, W AU - Liang, R AU - Lukszo, J AU - Lee, S H AU - Dizdaroglu, M AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, FCRDC, Frederick, Maryland 21702, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 616 EP - 624 VL - 13 IS - 7 SN - 0893-228X, 0893-228X KW - Histones KW - 0 KW - Oligopeptides KW - Nickel KW - 7OV03QG267 KW - DNA KW - 9007-49-2 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Index Medicus KW - Oxidation-Reduction KW - DNA Damage KW - DNA -- metabolism KW - Oxidative Stress KW - Hydrogen Peroxide -- pharmacology KW - Molecular Sequence Data KW - DNA -- chemistry KW - Amino Acid Sequence KW - Hydrolysis KW - Chromatography, High Pressure Liquid KW - DNA -- drug effects KW - Nickel -- pharmacology KW - Histones -- metabolism KW - Oligopeptides -- chemistry KW - Histones -- chemistry KW - Oligopeptides -- metabolism KW - Oligopeptides -- drug effects KW - Histones -- drug effects KW - Nickel -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71249594?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Ni%28II%29+specifically+cleaves+the+C-terminal+tail+of+the+major+variant+of+histone+H2A+and+forms+an+oxidative+damage-mediating+complex+with+the+cleaved-off+octapeptide.&rft.au=Bal%2C+W%3BLiang%2C+R%3BLukszo%2C+J%3BLee%2C+S+H%3BDizdaroglu%2C+M%3BKasprzak%2C+K+S&rft.aulast=Bal&rft.aufirst=W&rft.date=2000-07-01&rft.volume=13&rft.issue=7&rft.spage=616&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-12 N1 - Date created - 2000-09-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - poliota, a remarkably error-prone human DNA polymerase. AN - 71248672; 10887158 AB - The Saccharomyces cerevisiae RAD30 gene encodes DNA polymerase eta. Humans possess two Rad30 homologs. One (RAD30A/POLH) has previously been characterized and shown to be defective in humans with the Xeroderma pigmentosum variant phenotype. Here, we report experiments demonstrating that the second human homolog (RAD30B), also encodes a novel DNA polymerase that we designate poliota. poliota, is a distributive enzyme that is highly error-prone when replicating undamaged DNA. At template G or C, the average error frequency was approximately 1 x 10(-2). Our studies revealed, however, a striking asymmetry in misincorporation frequency at template A and T. For example, template A was replicated with the greatest accuracy, with misincorporation of G, A, or C occurring with a frequency of approximately 1 x 10(-4) to 2 x 10(-4). In dramatic contrast, most errors occurred at template T, where the misincorporation of G was, in fact, favored approximately 3:1 over the correct nucleotide, A, and misincorporation of T occurred at a frequency of approximately 6.7 x 10(-1). These findings demonstrate that poliota is one of the most error-prone eukaryotic polymerases reported to date and exhibits an unusual misincorporation spectrum in vitro. JF - Genes & development AU - Tissier, A AU - McDonald, J P AU - Frank, E G AU - Woodgate, R AD - Section on DNA Replication, Repair, and Mutagenesis, National Institute of Child Health and Human Development, Bethesda, MD 20892-2725, USA. Y1 - 2000/07/01/ PY - 2000 DA - 2000 Jul 01 SP - 1642 EP - 1650 VL - 14 IS - 13 SN - 0890-9369, 0890-9369 KW - DNA Primers KW - 0 KW - Isoenzymes KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Base Sequence KW - Humans KW - Mutation KW - DNA-Directed DNA Polymerase -- isolation & purification KW - Isoenzymes -- isolation & purification KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism KW - DNA-Directed DNA Polymerase -- genetics KW - DNA-Directed DNA Polymerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71248672?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+%26+development&rft.atitle=poliota%2C+a+remarkably+error-prone+human+DNA+polymerase.&rft.au=Tissier%2C+A%3BMcDonald%2C+J+P%3BFrank%2C+E+G%3BWoodgate%2C+R&rft.aulast=Tissier&rft.aufirst=A&rft.date=2000-07-01&rft.volume=14&rft.issue=13&rft.spage=1642&rft.isbn=&rft.btitle=&rft.title=Genes+%26+development&rft.issn=08909369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-04 N1 - Date created - 2000-08-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 1996 Apr 1;156(7):2642-52 [8786330] Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2941-6 [8610147] J Bacteriol. 1996 May;178(9):2559-63 [8626322] Science. 1996 Jun 14;272(5268):1646-9 [8658138] Mol Gen Genet. 1996 Jun 24;251(4):493-8 [8709953] Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7805-10 [8755557] Mutat Res. 1996 Oct 25;357(1-2):245-53 [8876701] Proc Natl Acad Sci U S A. 1997 May 27;94(11):5733-8 [9159142] J Biol Chem. 1997 Oct 31;272(44):27501-4 [9346877] J Bacteriol. 1997 Dec;179(23):7435-45 [9393709] Genetics. 1997 Dec;147(4):1557-68 [9409821] Immunol Rev. 1998 Apr;162:13-24 [9602348] J Exp Med. 1998 Jun 1;187(11):1735-43 [9607915] Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6953-8 [9618520] Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9755-60 [9707548] Mol Cell Biol. 1999 Jan;19(1):147-54 [9858539] Science. 1999 Feb 12;283(5404):1001-4 [9974380] Nucleic Acids Res. 1999 Nov 15;27(22):4468-75 [10536157] J Biol Chem. 1990 Feb 5;265(4):2338-46 [1688852] Mutat Res. 1992 Mar;281(3):221-5 [1371846] Mol Cell Biol. 1993 Jul;13(7):4276-83 [8321229] Nature. 1995 Jul 20;376(6537):225-9 [7617031] Annu Rev Biochem. 1995;64:171-200 [7574479] Methods Enzymol. 1995;262:232-56 [8594351] Methods Enzymol. 1995;262:270-80 [8594353] J Biol Chem. 1999 Nov 5;274(45):31763-6 [10542196] J Biol Chem. 1999 Dec 24;274(52):36835-8 [10601233] Genes Cells. 1999 Nov;4(11):607-18 [10620008] Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):565-70 [10639119] Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1166-71 [10655502] Trends Biochem Sci. 2000 Mar;25(3):143-7 [10694886] J Biol Chem. 2000 Mar 17;275(11):7447-50 [10713043] J Biol Chem. 2000 Mar 17;275(11):8233-9 [10713149] Science. 2000 Mar 24;287(5461):2185-95 [10731132] Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3094-9 [10725365] EMBO J. 2000 Apr 3;19(7):1731-42 [10747040] Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):3838-43 [10760255] Nature. 2000 Apr 27;404(6781):1011-3 [10801132] Nature. 2000 Apr 27;404(6781):1014-8 [10801133] Genes Dev. 2000 Jul 1;14(13):1589-94 [10887153] J Invest Dermatol. 1973 Jan;60(1):29-32 [4684158] Mol Gen Genet. 1977 Nov 14;156(2):121-31 [340898] Mol Gen Genet. 1978 Sep 20;165(1):87-93 [362169] Carcinogenesis. 1981;2(9):863-72 [7028309] J Biol Chem. 1987 Oct 25;262(30):14689-96 [3667598] J Biol Chem. 1989 Jul 5;264(19):11360-6 [2661558] J Biol Chem. 1989 Aug 25;264(24):14415-23 [2474545] Mutat Res. 1999 Mar;436(2):157-78 [10095138] Int Immunol. 1999 May;11(5):825-33 [10330287] J Biol Chem. 1999 Jun 4;274(23):15975-7 [10347143] J Immunol. 1999 Jun 1;162(11):6596-601 [10352276] J Pathol. 1999 Jan;187(2):158-63 [10365090] EMBO J. 1999 Jun 15;18(12):3491-501 [10369688] Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8919-24 [10430871] Genomics. 1999 Aug 15;60(1):20-30 [10458907] Genes Dev. 1999 Sep 1;13(17):2191-5 [10485842] Mol Cell. 1999 Aug;4(2):281-6 [10488344] Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):11922-7 [10518552] Nature. 1999 Jun 17;399(6737):700-4 [10385124] Science. 1999 Jul 9;285(5425):263-5 [10398605] Photodermatol Photoimmunol Photomed. 1999 Jun-Aug;15(3-4):127-32 [10404723] J Exp Med. 1999 Jul 5;190(1):21-30 [10429667] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lead interaction with human protamine (HP2) as a mechanism of male reproductive toxicity. AN - 71248512; 10898591 AB - During spermatogenesis, histones are replaced by protamines, which condense and protect sperm DNA. In humans, zinc contributes to sperm chromatin stability and binds to protamine P2 (HP2). Chemical interactions with nuclear protamines, which prevent normal sperm chromatin condensation, may induce changes in the sperm genome and thus affect fertility and offspring development. Since lead has a high affinity for zinc-containing proteins, we investigated lead interactions with HP2 as a novel mechanism of its toxicity to sperm. UV/vis and CD spectroscopy results indicated that HP2 binds Pb(2+) at two different sites, causing a conformational change in the protein. They also provided evidence that thiol groups are primarily involved in Zn(2+) and Pb(2+) binding to HP2 and that HP2 may have additional binding sites for Pb(2+) not related to Zn(2+). HP2 affinities for Pb(2+) and Zn(2+) were very similar, suggesting that Pb(2+) can compete with or replace Zn(2+) in HP2 in vivo. This interaction of lead with HP2 resulted in a dose-dependent decrease in the extent of HP2-DNA binding, although lead interaction with DNA also contributed to this effect. Therefore, the ability of lead to decrease the level of HP2-DNA interaction may result in alterations to sperm chromatin condensation, and thus in reduced fertility. JF - Chemical research in toxicology AU - Quintanilla-Vega, B AU - Hoover, D J AU - Bal, W AU - Silbergeld, E K AU - Waalkes, M P AU - Anderson, L D AD - National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. mquintan@mail.cinvestav.mx Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 594 EP - 600 VL - 13 IS - 7 SN - 0893-228X, 0893-228X KW - Protamines KW - 0 KW - protamine P2 KW - Lead KW - 2P299V784P KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Protein Binding -- drug effects KW - Humans KW - DNA -- metabolism KW - DNA -- chemistry KW - Circular Dichroism KW - Spectrophotometry KW - Male KW - Genitalia, Male -- metabolism KW - Protamines -- metabolism KW - Lead -- chemistry KW - Protamines -- chemistry KW - Lead -- pharmacology KW - Lead -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71248512?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Lead+interaction+with+human+protamine+%28HP2%29+as+a+mechanism+of+male+reproductive+toxicity.&rft.au=Quintanilla-Vega%2C+B%3BHoover%2C+D+J%3BBal%2C+W%3BSilbergeld%2C+E+K%3BWaalkes%2C+M+P%3BAnderson%2C+L+D&rft.aulast=Quintanilla-Vega&rft.aufirst=B&rft.date=2000-07-01&rft.volume=13&rft.issue=7&rft.spage=594&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-12 N1 - Date created - 2000-09-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel smad nuclear interacting protein, SNIP1, suppresses p300-dependent TGF-beta signal transduction. AN - 71246592; 10887155 AB - Members of the transforming growth factor-beta superfamily play critical roles in controlling cell growth and differentiation. Effects of TGF-beta family ligands are mediated by Smad proteins. To understand the mechanism of Smad function, we sought to identify novel interactors of Smads by use of a yeast two-hybrid system. A 396-amino acid nuclear protein termed SNIP1 was cloned and shown to harbor a nuclear localization signal (NLS) and a Forkhead-associated (FHA) domain. The carboxyl terminus of SNIP1 interacts with Smad1 and Smad2 in yeast two-hybrid as well as in mammalian overexpression systems. However, the amino terminus of SNIP1 harbors binding sites for both Smad4 and the coactivator CBP/p300. Interaction between endogenous levels of SNIP1 and Smad4 or CBP/p300 is detected in NMuMg cells as well as in vitro. Overexpression of full-length SNIP1 or its amino terminus is sufficient to inhibit multiple gene responses to TGF-beta and CBP/p300, as well as the formation of a Smad4/p300 complex. Studies in Xenopus laevis further suggest that SNIP1 plays a role in regulating dorsomedial mesoderm formation by the TGF-beta family member nodal. Thus, SNIP1 is a nuclear inhibitor of CBP/p300 and its level of expression in specific cell types has important physiological consequences by setting a threshold for TGF-beta-induced transcriptional activation involving CBP/p300. JF - Genes & development AU - Kim, R H AU - Wang, D AU - Tsang, M AU - Martin, J AU - Huff, C AU - de Caestecker, M P AU - Parks, W T AU - Meng, X AU - Lechleider, R J AU - Wang, T AU - Roberts, A B AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2000/07/01/ PY - 2000 DA - 2000 Jul 01 SP - 1605 EP - 1616 VL - 14 IS - 13 SN - 0890-9369, 0890-9369 KW - Carrier Proteins KW - 0 KW - Intracellular Signaling Peptides and Proteins KW - Nuclear Proteins KW - SNIP1 protein, human KW - Trans-Activators KW - Transforming Growth Factor beta KW - Index Medicus KW - Xenopus laevis KW - Animals KW - Two-Hybrid System Techniques KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Transcription, Genetic -- physiology KW - Cloning, Molecular KW - Signal Transduction -- physiology KW - Transforming Growth Factor beta -- physiology KW - Carrier Proteins -- chemistry KW - Carrier Proteins -- genetics KW - Carrier Proteins -- physiology KW - Trans-Activators -- physiology KW - Trans-Activators -- antagonists & inhibitors KW - Nuclear Proteins -- physiology KW - Nuclear Proteins -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71246592?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+%26+development&rft.atitle=A+novel+smad+nuclear+interacting+protein%2C+SNIP1%2C+suppresses+p300-dependent+TGF-beta+signal+transduction.&rft.au=Kim%2C+R+H%3BWang%2C+D%3BTsang%2C+M%3BMartin%2C+J%3BHuff%2C+C%3Bde+Caestecker%2C+M+P%3BParks%2C+W+T%3BMeng%2C+X%3BLechleider%2C+R+J%3BWang%2C+T%3BRoberts%2C+A+B&rft.aulast=Kim&rft.aufirst=R&rft.date=2000-07-01&rft.volume=14&rft.issue=13&rft.spage=1605&rft.isbn=&rft.btitle=&rft.title=Genes+%26+development&rft.issn=08909369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-04 N1 - Date created - 2000-08-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genes Cells. 1998 Sep;3(9):613-23 [9813111] Genes Dev. 1998 Jul 15;12(14):2114-9 [9679056] Cell. 1998 Dec 11;95(6):779-91 [9865696] Science. 1999 Feb 26;283(5406):1317-21 [10037600] Cell. 1999 Apr 2;97(1):29-39 [10199400] Science. 1999 Apr 16;284(5413):479-82 [10205054] Science. 1999 Apr 23;284(5414):606-9 [10213677] J Biol Chem. 1999 May 7;274(19):12971-4 [10224044] J Biol Chem. 1999 Jul 16;274(29):20489-98 [10400677] Nature. 1999 Aug 12;400(6745):687-93 [10458166] Genes Dev. 1999 Sep 1;13(17):2196-206 [10485843] J Biol Chem. 1999 Oct 1;274(40):28716-23 [10497242] Mol Cell. 1999 Sep;4(3):387-94 [10518219] Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12442-7 [10535941] J Biol Chem. 2000 Jan 21;275(3):2115-22 [10636916] Structure. 1999 Dec 15;7(12):1493-503 [10647180] Mol Cell Biol. 2000 Apr;20(8):2676-86 [10733570] Cell. 1992 Dec 11;71(6):1003-14 [1333888] Genes Dev. 1998 Jul 15;12(14):2153-63 [9679060] Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9506-11 [9689110] J Biol Chem. 1998 Sep 4;273(36):22865-8 [9722503] Nature. 1998 Aug 27;394(6696):909-13 [9732876] Annu Rev Biochem. 1998;67:753-91 [9759503] Genes Dev. 1998 Oct 1;12(19):3084-95 [9765209] Mol Cell. 1998 Oct;2(4):405-15 [9809062] Nature. 1996 Sep 26;383(6598):344-7 [8848048] Ultrastruct Pathol. 1996 Sep-Oct;20(5):477-90 [8883333] Nature. 1996 Oct 31;383(6603):832-6 [8893010] Cell. 1996 Nov 29;87(5):953-9 [8945521] Science. 1997 Jan 24;275(5299):523-7 [8999795] J Biol Chem. 1997 May 23;272(21):13690-6 [9153220] Nature. 1997 Jul 3;388(6637):82-7 [9214507] Nature. 1997 Jul 3;388(6637):87-93 [9214508] Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 [9254694] Biochim Biophys Acta. 1997 Oct 24;1333(2):F105-50 [9395284] Development. 1997 Nov;124(22):4467-80 [9409665] Annu Rev Cell Dev Biol. 1997;13:611-67 [9442883] Mol Cell Biol. 1998 Apr;18(4):2218-29 [9528793] Genes Dev. 1998 Jun 1;12(11):1587-92 [9620846] Curr Opin Cell Biol. 1998 Jun;10(3):373-83 [9640539] Mol Cell. 1998 Mar;1(4):611-7 [9660945] Nature. 1998 Jul 2;394(6688):92-6 [9665135] Mol Biol Cell. 1998 Dec;9(12):3309-19 [9843571] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potential endocrine-modulating effects of various phytoestrogens in the diet. AN - 71245560; 10906588 JF - Nutrition (Burbank, Los Angeles County, Calif.) AU - Jefferson, W N AU - Newbold, R R AD - Developmental Endocrinology Section, Environmental Toxicology Program, Laboratory of Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. jeffers1@niehs.nih.gov PY - 2000 SP - 658 EP - 662 VL - 16 IS - 7-8 SN - 0899-9007, 0899-9007 KW - Estrogens KW - 0 KW - Estrogens, Non-Steroidal KW - Isoflavones KW - Phytoestrogens KW - Plant Preparations KW - Diethylstilbestrol KW - 731DCA35BT KW - Genistein KW - DH2M523P0H KW - Index Medicus KW - Animals KW - Estrogens -- pharmacology KW - Genistein -- pharmacology KW - Humans KW - Plants KW - Diethylstilbestrol -- pharmacology KW - Endocrine Glands -- drug effects KW - Estrogens, Non-Steroidal -- administration & dosage KW - Diet KW - Estrogens, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71245560?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+%28Burbank%2C+Los+Angeles+County%2C+Calif.%29&rft.atitle=Potential+endocrine-modulating+effects+of+various+phytoestrogens+in+the+diet.&rft.au=Jefferson%2C+W+N%3BNewbold%2C+R+R&rft.aulast=Jefferson&rft.aufirst=W&rft.date=2000-07-01&rft.volume=16&rft.issue=7-8&rft.spage=658&rft.isbn=&rft.btitle=&rft.title=Nutrition+%28Burbank%2C+Los+Angeles+County%2C+Calif.%29&rft.issn=08999007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-24 N1 - Date created - 2000-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Extremely low-frequency magnetic fields and childhood acute lymphoblastic leukemia: an exploratory analysis of alternative exposure metrics. AN - 71243042; 10901326 AB - Data collected by the National Cancer Institute-Children's Cancer Group were utilized to explore various metrics of magnetic field levels and risk of acute lymphoblastic leukemia (ALL) in children. Cases were aged 0-14 years, were diagnosed with ALL during 1989-1993, were registered with the Children's Cancer Group, and resided in one home for at least 70 percent of the 5 years immediately prior to diagnosis. Controls were identified by using random digit dialing and met the same residential requirements. With 30-second ("spot") measurements and components of the 24-hour measurement obtained in the subject's bedroom, metrics evaluated included measures of central tendency, peak exposures, threshold values, and measures of short-term temporal variability. Measures of central tendency and the threshold measures showed good-to-high correlation, but these metrics correlated less well with the others. Small increases in risk (ranging from 1.02 to 1.69 for subjects in the highest exposure category) were associated with some measures of central tendency, but peak exposures, threshold values, measures of short-term variability, and spot measurements demonstrated little association with risk of childhood ALL. In general, risk estimates were slightly higher for the nighttime (10 p.m.-6 a.m.) interval than for the corresponding 24-hour period. JF - American journal of epidemiology AU - Auvinen, A AU - Linet, M S AU - Hatch, E E AU - Kleinerman, R A AU - Robison, L L AU - Kaune, W T AU - Misakian, M AU - Niwa, S AU - Wacholder, S AU - Tarone, R E AD - National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD 20892-7238, USA. Y1 - 2000/07/01/ PY - 2000 DA - 2000 Jul 01 SP - 20 EP - 31 VL - 152 IS - 1 SN - 0002-9262, 0002-9262 KW - Index Medicus KW - Infant KW - Humans KW - Environmental Exposure KW - Child KW - Adolescent KW - Male KW - Female KW - Child, Preschool KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- epidemiology KW - Electromagnetic Fields -- adverse effects KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71243042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Extremely+low-frequency+magnetic+fields+and+childhood+acute+lymphoblastic+leukemia%3A+an+exploratory+analysis+of+alternative+exposure+metrics.&rft.au=Auvinen%2C+A%3BLinet%2C+M+S%3BHatch%2C+E+E%3BKleinerman%2C+R+A%3BRobison%2C+L+L%3BKaune%2C+W+T%3BMisakian%2C+M%3BNiwa%2C+S%3BWacholder%2C+S%3BTarone%2C+R+E&rft.aulast=Auvinen&rft.aufirst=A&rft.date=2000-07-01&rft.volume=152&rft.issue=1&rft.spage=20&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 - 2000-08-09 N1 - Date created - 2000-08-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of cell cycle control allows selective microtubule-active drug-induced Bcl-2 phosphorylation and cytotoxicity in autonomous cancer cells. AN - 71240767; 10910051 AB - Lack of selectivity in the killing of tumor and normal cells is a major obstacle in cancer therapy. By inhibiting normal but not autonomous cell growth, we exploited the differences in cell cycle regulation to achieve a selective protection of nonautonomous cells against paclitaxel and other microtubule-active drugs. Tubulin polymerization, a primary effect of paclitaxel, can be dissociated from Bcl-2 phosphorylation and cytotoxicity in HL-60 cells. Growth arrest prevented paclitaxel-induced Bcl-2 phosphorylation and apoptosis without affecting paclitaxel-induced tubulin polymerization. We abrogated the effects of paclitaxel on MCF-10A immortalized breast cells, while preserving its effects on MCF-7 cancer cells. Unlike MCF-7 cells, MCF-10A cells were arrested by epidermal growth factor withdrawal, precluding paclitaxel-induced Bcl-2 phosphorylation. Furthermore, the inhibition of the epidermal growth factor receptor kinase with low doses of AG1478 arrested growth of MCF-10A but not MCF-7 cells. Pretreatment with AG1478 did not affect paclitaxel-induced Bcl-2/Raf-1 phosphorylation in MCF-7 but abrogated such phosphorylation in MCF-10A. Exploitation of growth factor dependency may allow the protection of normal cells from microtubule-active drugs. JF - Cancer research AU - Blagosklonny, M V AU - Bishop, P C AU - Robey, R AU - Fojo, T AU - Bates, S E AD - Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. mikhailb@box-m.nih.gov Y1 - 2000/07/01/ PY - 2000 DA - 2000 Jul 01 SP - 3425 EP - 3428 VL - 60 IS - 13 SN - 0008-5472, 0008-5472 KW - Enzyme Inhibitors KW - 0 KW - Proto-Oncogene Proteins c-bcl-2 KW - Quinazolines KW - Tubulin KW - Tyrphostins KW - tyrphostin AG 1478 KW - 170449-18-0 KW - Epidermal Growth Factor KW - 62229-50-9 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - HL-60 Cells KW - Humans KW - Enzyme Inhibitors -- toxicity KW - Cell Division -- drug effects KW - Tubulin -- metabolism KW - Breast Neoplasms KW - Epidermal Growth Factor -- pharmacology KW - Tubulin -- drug effects KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Phosphorylation KW - Apoptosis -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Mitosis -- drug effects KW - Female KW - Paclitaxel -- toxicity KW - Cell Cycle -- physiology KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - Tyrphostins -- toxicity KW - Microtubules -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71240767?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Loss+of+cell+cycle+control+allows+selective+microtubule-active+drug-induced+Bcl-2+phosphorylation+and+cytotoxicity+in+autonomous+cancer+cells.&rft.au=Blagosklonny%2C+M+V%3BBishop%2C+P+C%3BRobey%2C+R%3BFojo%2C+T%3BBates%2C+S+E&rft.aulast=Blagosklonny&rft.aufirst=M&rft.date=2000-07-01&rft.volume=60&rft.issue=13&rft.spage=3425&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 - 2000-08-17 N1 - Date created - 2000-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dysregulation of renal aquaporins and Na-Cl cotransporter in CCl4-induced cirrhosis. AN - 71239892; 10886566 AB - Severe hepatic cirrhosis is associated with abnormal renal water retention. Semiquantitative immunoblotting was employed to investigate the abundance of the major renal aquaporins (water channels) and sodium-dependent cotransporters in kidneys from control rats and rats with cirrhosis secondary to chronic CCl4 inhalation. The cirrhotic rats had ascites and manifested a water excretion defect detected by a standard water-loading test. The abundance of aquaporin-1 (the major aquaporin in the proximal tubule) was increased, an effect markedly accentuated in high-density membrane fractions prepared by differential centrifugation. Differential centrifugation studies demonstrated a redistribution of aquaporin-2 from high-density to low-density membranes, compatible with increased trafficking of aquaporin-2 to the plasma membrane. The abundance of aquaporin-3, but not aquaporin-2, was increased in collecting ducts of rats with CCl4-induced cirrhosis. The Na-K-2Cl cotransporter of the thick ascending limb showed no change in abundance. However, the abundance of the thiazide-sensitive Na-Cl cotransporter of the distal convoluted tubule was markedly suppressed in cirrhotic rats, possibly contributing to a defect in urinary dilution. In this model of cirrhosis, the development of a defect in urinary dilution may be multifactorial, with contributions from at least four abnormalities in transporter regulation: (1) an increase in the renal abundance of aquaporin-1, (2) a cellular redistribution of aquaporin-2 in the collecting duct compatible with trafficking to the plasma membrane without an increase in total cellular aquaporin-2, (3) an increase in the renal abundance of aquaporin-3, and (4) a decrease in the abundance of the thiazide-sensitive cotransporter of the distal convoluted tubule. JF - Kidney international AU - Fernández-Llama, P AU - Jimenez, W AU - Bosch-Marcé, M AU - Arroyo, V AU - Nielsen, S AU - Knepper, M A AD - Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1603, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 216 EP - 228 VL - 58 IS - 1 SN - 0085-2538, 0085-2538 KW - Aqp1 protein, rat KW - 0 KW - Aqp2 protein, rat KW - Aqp3 protein, rat KW - Aquaporin 2 KW - Aquaporin 6 KW - Aquaporins KW - Carrier Proteins KW - Chlorides KW - Sodium Chloride Symporters KW - Symporters KW - Aquaporin 1 KW - 146410-94-8 KW - Aquaporin 3 KW - 158801-98-0 KW - Sodium KW - 9NEZ333N27 KW - Carbon Tetrachloride KW - CL2T97X0V0 KW - Index Medicus KW - Kidney Tubules, Collecting -- metabolism KW - Animals KW - Immunoblotting KW - Chlorides -- metabolism KW - Kidney Tubules, Distal -- metabolism KW - Kidney Concentrating Ability -- physiology KW - Rats KW - Kidney Tubules, Proximal -- metabolism KW - Rats, Wistar KW - Male KW - Sodium -- metabolism KW - Liver Cirrhosis, Experimental -- chemically induced KW - Carrier Proteins -- metabolism KW - Aquaporins -- analysis KW - Liver Cirrhosis, Experimental -- metabolism KW - Kidney Tubules -- metabolism KW - Carrier Proteins -- analysis KW - Aquaporins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71239892?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Kidney+international&rft.atitle=Dysregulation+of+renal+aquaporins+and+Na-Cl+cotransporter+in+CCl4-induced+cirrhosis.&rft.au=Fern%C3%A1ndez-Llama%2C+P%3BJimenez%2C+W%3BBosch-Marc%C3%A9%2C+M%3BArroyo%2C+V%3BNielsen%2C+S%3BKnepper%2C+M+A&rft.aulast=Fern%C3%A1ndez-Llama&rft.aufirst=P&rft.date=2000-07-01&rft.volume=58&rft.issue=1&rft.spage=216&rft.isbn=&rft.btitle=&rft.title=Kidney+international&rft.issn=00852538&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-21 N1 - Date created - 2000-08-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - The epidermal growth factor receptor is required to maintain the proliferative population in the basal compartment of epidermal tumors. AN - 71238959; 10910032 AB - Previous studies using keratinocytes from epidermal growth factor receptor (EGFR)-deficient mice revealed that the EGFR is not required for papilloma formation initiated by a mutant rasHa gene, although the tumors that develop are very small (A. A. Dlugosz et aL, Cancer Res., 57: 3180-3188, 1997). The current study used a combination of bromodeoxyuridine pulse-chase, proliferating cell nuclear antigen distribution, and differentiation marker analysis to reveal the following: (a) the EGFR was required to maintain the proliferative population in the basal cell compartment of papillomas; (b) in the absence of EGFR, cycling tumor cells migrated into the suprabasal compartment and initiated the differentiation program prematurely; and (c) these changes were associated with cell cycle arrest. Further analysis of v-rasHa-transformed EGFR-deficient keratinocytes in vitro indicated that such cells migrated more on and attached less to extracellular matrix components. Together, these studies reveal that an essential function for the EGFR pathway in squamous tumors is to maintain a proliferative pool of basal cells and prevent premature terminal differentiation. JF - Cancer research AU - Hansen, L A AU - Woodson, R L AU - Holbus, S AU - Strain, K AU - Lo, Y C AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2000/07/01/ PY - 2000 DA - 2000 Jul 01 SP - 3328 EP - 3332 VL - 60 IS - 13 SN - 0008-5472, 0008-5472 KW - Fgf7 protein, mouse KW - 0 KW - Fibroblast Growth Factor 10 KW - Growth Substances KW - Fibroblast Growth Factor 7 KW - 126469-10-1 KW - Fibroblast Growth Factors KW - 62031-54-3 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Animals, Newborn KW - Animals KW - Growth Substances -- pharmacology KW - S Phase KW - Mice KW - Cell Transformation, Neoplastic KW - Mice, Knockout KW - Skin Neoplasms -- genetics KW - Genes, ras KW - Receptor, Epidermal Growth Factor -- genetics KW - Papilloma -- pathology KW - Keratinocytes -- drug effects KW - Cell Cycle -- physiology KW - Skin Neoplasms -- pathology KW - Keratinocytes -- cytology KW - Receptor, Epidermal Growth Factor -- physiology KW - Receptor, Epidermal Growth Factor -- deficiency KW - Papilloma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71238959?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=The+epidermal+growth+factor+receptor+is+required+to+maintain+the+proliferative+population+in+the+basal+compartment+of+epidermal+tumors.&rft.au=Hansen%2C+L+A%3BWoodson%2C+R+L%3BHolbus%2C+S%3BStrain%2C+K%3BLo%2C+Y+C%3BYuspa%2C+S+H&rft.aulast=Hansen&rft.aufirst=L&rft.date=2000-07-01&rft.volume=60&rft.issue=13&rft.spage=3328&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 - 2000-08-17 N1 - Date created - 2000-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential formation of beta-catenin/lymphoid enhancer factor-1 DNA binding complex induced by nitric oxide in mouse colonic epithelial cells differing in adenomatous polyposis coli (Apc) genotype. AN - 71238174; 10910042 AB - Increased cytoplasmic beta-catenin levels and the associated nuclear beta-catenin/T-cell factor (Tcf)-lymphoid enhancer factor (LEF) complex formation have been frequently found in colon cancer. In this context, overproduction of nitric oxide (NO) attributable to inflammatory stimuli in diseases such as ulcerative colitis and Crohn's disease may-contribute to colonic carcinogenesis. Therefore, we examined the modulation by NO of cytoplasmic beta-catenin levels and the formation of the nuclear beta-catenin/LEF-1 DNA binding complex in conditionally immortalized mouse colonic epithelial cells that differed in adenomatous polyposis coli (Apc) genotype, namely young adult mouse colon (YAMC; Apc+/+) and immortal mouse colon epithelium (IMCE; ApcMin/+). Unlike most colon cancer cell lines, this pair of cell lines has either nondetectable or low basal level of beta-catenin when they are cultured under nonpermissive and nonproliferative conditions. Using electrophoretic mobility shift assays, we found that NO-releasing agents (E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexeneamide and S-nitroso-N-acetylpenicillamine greatly enhanced the formation of beta-catenin/LEF-1 DNA binding complex in a concentration- and time-dependent fashion in YAMC and IMCE cells. Significantly, IMCE cells showed a markedly greater amount of nuclear beta-catenin/LEF-1 DNA binding complex in response to NO. Super shift by anti-beta-catenin antibody confirmed the presence of beta-catenin in the complex. Western blot analysis of the soluble cytoplasmic fractions demonstrated that these NO donors caused differential accumulation of cytoplasmic beta-catenin in YAMC and IMCE. In conclusion, this study indicates that the defective beta-catenin degradation machinery attributable to ApcMin/+ mutation in IMCE cells not only affects basal levels but also contributes to NO-induced dysregulation of cytoplasmic beta-catenin and nuclear beta-catenin/LEF-1 DNA binding complex formation. JF - Cancer research AU - Mei, J M AU - Hord, N G AU - Winterstein, D F AU - Donald, S P AU - Phang, J M AD - Metabolism and Cancer Susceptibility Section, Basic Research Laboratory, Division of Basic Sciences, National Cancer Institute, Frederick, Maryland 21702, USA. Mei@mail.ncifcrf.gov Y1 - 2000/07/01/ PY - 2000 DA - 2000 Jul 01 SP - 3379 EP - 3383 VL - 60 IS - 13 SN - 0008-5472, 0008-5472 KW - CTNNB1 protein, mouse KW - 0 KW - Cytoskeletal Proteins KW - DNA-Binding Proteins KW - Lymphoid Enhancer-Binding Factor 1 KW - Nitric Oxide Donors KW - Nitro Compounds KW - Trans-Activators KW - Transcription Factors KW - beta Catenin KW - methyl-2-hydroxyimino-5-nitro-6-methoxy-3-hexeneamide KW - Nitric Oxide KW - 31C4KY9ESH KW - S-Nitroso-N-Acetylpenicillamine KW - 79032-48-7 KW - Penicillamine KW - GNN1DV99GX KW - Index Medicus KW - Genotype KW - Animals KW - Cell Nucleus -- metabolism KW - Mice KW - Cell Line, Transformed KW - Penicillamine -- analogs & derivatives KW - Penicillamine -- pharmacology KW - Transcription Factors -- metabolism KW - Cytoskeletal Proteins -- isolation & purification KW - Colon -- drug effects KW - Intestinal Mucosa -- metabolism KW - Nitric Oxide -- physiology KW - Genes, APC KW - Nitric Oxide Donors -- pharmacology KW - Colon -- metabolism KW - Transcription Factors -- isolation & purification KW - Intestinal Mucosa -- drug effects KW - DNA-Binding Proteins -- isolation & purification KW - Cytoskeletal Proteins -- metabolism KW - Nitro Compounds -- pharmacology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71238174?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Differential+formation+of+beta-catenin%2Flymphoid+enhancer+factor-1+DNA+binding+complex+induced+by+nitric+oxide+in+mouse+colonic+epithelial+cells+differing+in+adenomatous+polyposis+coli+%28Apc%29+genotype.&rft.au=Mei%2C+J+M%3BHord%2C+N+G%3BWinterstein%2C+D+F%3BDonald%2C+S+P%3BPhang%2C+J+M&rft.aulast=Mei&rft.aufirst=J&rft.date=2000-07-01&rft.volume=60&rft.issue=13&rft.spage=3379&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 - 2000-08-17 N1 - Date created - 2000-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cyclophosphamide, methotrexate, and fluorouracil versus tamoxifen plus ovarian suppression as adjuvant treatment of estrogen receptor-positive pre-/perimenopausal breast cancer patients: results of the Italian Breast Cancer Adjuvant Study Group 02 randomized trial. boccardo@hp380.ist.unige.it. AN - 71237385; 10894871 AB - To compare the efficacy of chemotherapy versus that of tamoxifen plus ovarian suppression in pre-/perimenopausal estrogen receptor-positive patients with early breast cancer. Patients were randomly assigned to receive either six cycles of a standard regimen of cyclophosphamide 100 mg/m(2) orally days 1 to 14, methotrexate 40 mg/m(2) intravenously (IV) days 1 and 8, and fluorouracil 600 mg/m(2) IV days 1 and 8 (CMF), with all drugs restarted on day 29, or 5 years of tamoxifen, 30 mg/d, plus ovarian suppression with surgical oophorectomy, ovarian irradiation, or monthly goserelin 3.6-mg injections. Disease-free survival was the main study end point. Overall survival and toxicity were additional end points. Between 1989 and 1997, 120 patients were assigned to CMF and 124 to tamoxifen and ovarian suppression (oophorectomy, n = 6; ovarian irradiation, n = 31; and goserelin injections, n = 87). At the time of analysis (median follow-up time, 76 months; range, 9 to 121 months), 82 patients had relapsed and 39 had died. No difference between groups had emerged with respect to either disease-free or overall survival. Treatments were comparable even in respect to age, tumor size, and nodal status, although a nonsignificant trend favored patients with poorly differentiated tumors treated with CMF. Leukopenia, nausea, vomiting, stomatitis, and alopecia were significantly more common in patients treated with CMF. There were few patients who developed benign gynecologic changes in either group, and numbers were comparable. The combination of tamoxifen with ovarian suppression seems to be safe and to yield comparable results relative to standard CMF. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Boccardo, F AU - Rubagotti, A AU - Amoroso, D AU - Mesiti, M AU - Romeo, D AU - Sismondi, P AU - Giai, M AU - Genta, F AU - Pacini, P AU - Distante, V AU - Bolognesi, A AU - Aldrighetti, D AU - Farris, A AD - Professorial Unit of Medical Oncology and Biostatistics Unit, University and National Cancer Institute, Genoa, Italy. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 2718 EP - 2727 VL - 18 IS - 14 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents, Hormonal KW - 0 KW - Receptors, Estrogen KW - Tamoxifen KW - 094ZI81Y45 KW - Goserelin KW - 0F65R8P09N KW - Cyclophosphamide KW - 8N3DW7272P KW - Fluorouracil KW - U3P01618RT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Fluorouracil -- administration & dosage KW - Cyclophosphamide -- administration & dosage KW - Combined Modality Therapy KW - Premenopause KW - Humans KW - Adult KW - Ovariectomy KW - Middle Aged KW - Receptors, Estrogen -- metabolism KW - Methotrexate -- administration & dosage KW - Goserelin -- therapeutic use KW - Female KW - Survival Analysis KW - Breast Neoplasms -- drug therapy KW - Tamoxifen -- therapeutic use KW - Neoplasms, Hormone-Dependent -- metabolism KW - Neoplasms, Hormone-Dependent -- drug therapy KW - Breast Neoplasms -- metabolism KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Antineoplastic Agents, Hormonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71237385?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cyclophosphamide%2C+methotrexate%2C+and+fluorouracil+versus+tamoxifen+plus+ovarian+suppression+as+adjuvant+treatment+of+estrogen+receptor-positive+pre-%2Fperimenopausal+breast+cancer+patients%3A+results+of+the+Italian+Breast+Cancer+Adjuvant+Study+Group+02+randomized+trial.+boccardo%40hp380.ist.unige.it.&rft.au=Boccardo%2C+F%3BRubagotti%2C+A%3BAmoroso%2C+D%3BMesiti%2C+M%3BRomeo%2C+D%3BSismondi%2C+P%3BGiai%2C+M%3BGenta%2C+F%3BPacini%2C+P%3BDistante%2C+V%3BBolognesi%2C+A%3BAldrighetti%2C+D%3BFarris%2C+A&rft.aulast=Boccardo&rft.aufirst=F&rft.date=2000-07-01&rft.volume=18&rft.issue=14&rft.spage=2718&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 - 2000-08-01 N1 - Date created - 2000-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased p53 mutation load in noncancerous colon tissue from ulcerative colitis: a cancer-prone chronic inflammatory disease. AN - 71237316; 10910033 AB - Ulcerative colitis (UC) is a chronic inflammatory disease that produces reactive oxygen and nitrogen species and increases the risk of colorectal cancer (CRC). The p53 tumor suppressor gene is frequently mutated in UC-associated dysplastic lesions and CRC. We are exploring the hypothesis that p53 mutations in the nontumorous colonic tissue in noncancerous UC cases indicate genetic damage from exposure to exogenous and endogenous carcinogens and may identify individuals at increased cancer risk. We are reporting, for the first time, the frequency of specific p53 mutated alleles in nontumorous colon tissue from donors either with or without UC by using a highly sensitive genotypic mutation assay. Higher p53 mutation frequencies of both G:C to A:T transitions at the CpG site of codon 248 and C:G to T:A transitions at codon 247 were observed in colon from UC cases when compared with normal adult controls (P = 0.001 and P = 0.001, respectively). In the UC cases, higher p53 codon 247 and 248 mutation frequencies were observed in the inflamed lesional regions when compared with the nonlesional regions of their colon (P < 0.001 and P = 0.001). The colonic nitric oxide synthase-2 activity was higher in UC cases than in non-UC adult controls (P = 0.02). Our data are consistent with the hypothesis that a higher frequency of p53 mutant cells can be generated under oxidative stress in people with UC. The increased frequency of specific p53 mutated alleles in noncancerous UC colon tissue may confer susceptibility to the development of CRC in an inflammatory microenvironment. JF - Cancer research AU - Hussain, S P AU - Amstad, P AU - Raja, K AU - Ambs, S AU - Nagashima, M AU - Bennett, W P AU - Shields, P G AU - Ham, A J AU - Swenberg, J A AU - Marrogi, A J AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 2000/07/01/ PY - 2000 DA - 2000 Jul 01 SP - 3333 EP - 3337 VL - 60 IS - 13 SN - 0008-5472, 0008-5472 KW - Codon KW - 0 KW - Dinucleoside Phosphates KW - cytidylyl-3'-5'-guanosine KW - 2382-65-2 KW - NOS2 protein, human KW - EC 1.14.13.39 KW - Nitric Oxide Synthase KW - Nitric Oxide Synthase Type II KW - Index Medicus KW - Genotype KW - Dinucleoside Phosphates -- genetics KW - Reference Values KW - Colon -- pathology KW - Humans KW - Adult KW - Intestinal Mucosa -- pathology KW - Genetic Predisposition to Disease KW - Nitric Oxide Synthase -- analysis KW - Colonic Neoplasms -- genetics KW - Colitis, Ulcerative -- complications KW - Genes, p53 KW - Colonic Neoplasms -- etiology KW - Point Mutation KW - Colitis, Ulcerative -- pathology KW - Colitis, Ulcerative -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71237316?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Increased+p53+mutation+load+in+noncancerous+colon+tissue+from+ulcerative+colitis%3A+a+cancer-prone+chronic+inflammatory+disease.&rft.au=Hussain%2C+S+P%3BAmstad%2C+P%3BRaja%2C+K%3BAmbs%2C+S%3BNagashima%2C+M%3BBennett%2C+W+P%3BShields%2C+P+G%3BHam%2C+A+J%3BSwenberg%2C+J+A%3BMarrogi%2C+A+J%3BHarris%2C+C+C&rft.aulast=Hussain&rft.aufirst=S&rft.date=2000-07-01&rft.volume=60&rft.issue=13&rft.spage=3333&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 - 2000-08-17 N1 - Date created - 2000-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Changing patterns of tonsillar squamous cell carcinoma in the United States. AN - 71229282; 10880031 AB - Tonsillar squamous cell carcinoma (SCC) may differ etiologically from other oral cancers. The aim of this study was to provide a detailed description of the incidence patterns of tonsillar SCC in the United States. Population-based incidence data from the Connecticut Tumor Registry (period 1945-1994) and from the SEER program (period 1973-1995) were used to calculate age-standardized (US 1970) and age-specific incidence rates and confidence intervals (CIs). Linear regression was used to evaluate trends. The incidence of tonsillar SCC increased fourfold among white women in Connecticut during 1945-1994 but remained rather constant in white men. During 1973-1995, incidence rates per million person-years were considerably higher in blacks (31.6; 95% CI: 29.0-34.4 in men, and 9.6; 95% CI: 8.3-10.9 in women) than whites (14.8; 95% CI: 14.3 15.3 in men, and 6.1; 95% CI: 5.8-6.4 in women). Men, but not women, who were younger than 60 years experienced significant annual increases in tonsillar SCC incidence during 1973-1995 (2.7% in blacks and 1.9% in whites). No similar increases occurred for oral SCC at non-tonsillar sites. Incidence rates of tonsillar SCC vary considerably by sex, race and time in a way that cannot be explained by changes in tonsillectomy practices alone. Changes in environmental risk factors, including changes in smoking patterns and an increase in oral human papillomavirus infections, may have contributed. JF - Cancer causes & control : CCC AU - Frisch, M AU - Hjalgrim, H AU - Jaeger, A B AU - Biggar, R J AD - Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. mfr@ssi.dk Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 489 EP - 495 VL - 11 IS - 6 SN - 0957-5243, 0957-5243 KW - Index Medicus KW - Age Factors KW - Sex Factors KW - Humans KW - SEER Program KW - Linear Models KW - Smoking -- epidemiology KW - Marital Status KW - European Continental Ancestry Group KW - Adult KW - Connecticut -- epidemiology KW - Environmental Exposure KW - Incidence KW - Middle Aged KW - United States -- epidemiology KW - African Continental Ancestry Group KW - Female KW - Male KW - Carcinoma, Squamous Cell -- epidemiology KW - Tonsillar Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71229282?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Changing+patterns+of+tonsillar+squamous+cell+carcinoma+in+the+United+States.&rft.au=Frisch%2C+M%3BHjalgrim%2C+H%3BJaeger%2C+A+B%3BBiggar%2C+R+J&rft.aulast=Frisch&rft.aufirst=M&rft.date=2000-07-01&rft.volume=11&rft.issue=6&rft.spage=489&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-12 N1 - Date created - 2000-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of oxidative DNA damage in u937 cells by TNF or anti-Fas stimulation. AN - 71228489; 10880232 AB - TNF and Fas signaling pathways are reported to induce mitochondrial damage associated with production of oxygen radicals. We examined whether such radical production elicited detectable nuclear DNA damage in U937 cells following treatment with TNF or with anti-Fas antibodies. Using GC-mass spectroscopy for analysing base oxidation, several oxidized species increased significantly following TNF treatment, whereas anti-Fas resulted in less detectable oxidative damage using this assay. Cytogenetic analysis showed that, in the presence of aphidicolin, which blocks several types of DNA repair, TNF induced extensive chromosomal damage. Aphidicolin also synergized with TNF and anti-Fas in inducing cell death which was prevented by reducing atmospheric oxygen or addition of n -acetyl cysteine, a scavenger of oxygen radicals. Thus, several lines of evidence point to the TNF and Fas pathways inducing extensive oxidative DNA damage and repair, and suggest potential roles for these pathways in mutagenesis and aging. Copyright 2000 Academic Press. JF - Cytokine AU - Nathan, I AU - Dizdaroglu, M AU - Bernstein, L AU - Junker, U AU - Lee, C AU - Muegge, K AU - Durum, S K AD - Laboratory of Molecular Immunology, National Cancer Institute, Frederick, MD 21702-1201, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 881 EP - 887 VL - 12 IS - 7 SN - 1043-4666, 1043-4666 KW - Antigens, CD95 KW - 0 KW - Enzyme Inhibitors KW - Free Radicals KW - Tumor Necrosis Factor-alpha KW - Aphidicolin KW - 38966-21-1 KW - Guanine KW - 5Z93L87A1R KW - DNA KW - 9007-49-2 KW - Adenosine KW - K72T3FS567 KW - Index Medicus KW - Oxidation-Reduction KW - Aphidicolin -- pharmacology KW - Humans KW - Apoptosis -- drug effects KW - Enzyme Inhibitors -- pharmacology KW - Guanine -- metabolism KW - U937 Cells KW - DNA -- drug effects KW - Adenosine -- metabolism KW - Antigens, CD95 -- metabolism KW - DNA Damage KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Tumor Necrosis Factor-alpha -- metabolism KW - Antigens, CD95 -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71228489?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytokine&rft.atitle=Induction+of+oxidative+DNA+damage+in+u937+cells+by+TNF+or+anti-Fas+stimulation.&rft.au=Nathan%2C+I%3BDizdaroglu%2C+M%3BBernstein%2C+L%3BJunker%2C+U%3BLee%2C+C%3BMuegge%2C+K%3BDurum%2C+S+K&rft.aulast=Nathan&rft.aufirst=I&rft.date=2000-07-01&rft.volume=12&rft.issue=7&rft.spage=881&rft.isbn=&rft.btitle=&rft.title=Cytokine&rft.issn=10434666&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-08 N1 - Date created - 2000-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of an anti-CD3 single-chain immunotoxin with a truncated diphtheria toxin in a mutant CHO cell line. AN - 71227487; 10873546 AB - ADP-ribosylating immunotoxins are generally expressed in Escherichia coli and then refolded in vitro. Because the efficiency of the in vitro refolding process decreases with the number of protein domains and internal disulfide bonds, these immunotoxins have been generally limited to single-chain monovalent structures. We now show that using the hamster cell line CHO K1 RE1.22c (J. M. Moehring and T. J. Moehring, 1979, Somat. Cell Genet. 5, 453-468) that has been mutated to ADP-ribosylation insensitivity, a level of 4 microg/ml of a truncated anti-T cell immunotoxin, DT390-scFvUCHT1, can be secreted into the medium. This immunotoxin is glycosylated at the two potential N-linked glycosylation sites in the toxin moiety: positions 16-18 in the A chain and residues 235-237 in the B chain. The glycosylated immunotoxin is relatively nontoxic (IC(50) 4.8 x 10(-10) M). Removal of the N-linked oligosaccharides by N-glycosidase F treatment or mutations at the two N-linked glycosylation sites results in a highly active immunotoxin with an IC(50) of 4 x 10(-12) M toward CD3(+) Jurkat cells. This is a 12-fold increase in toxicity over the same immunotoxin harvested from E. coli periplasm without refolding. A single Asn(235) Ala mutation that removed the B chain glycosylation was nearly as toxic as the double mutant. This suggests that B chain glycosylation is the major cause for the loss of toxicity. Copyright 2000 Academic Press. JF - Protein expression and purification AU - Liu, Y Y AU - Gordienko, I AU - Mathias, A AU - Ma, S AU - Thompson, J AU - Woo, J H AU - Neville, D M AD - Section on Biophysical Chemistry, National Institute of Mental Health, Bethesda, Maryland, 28092-4034, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 304 EP - 311 VL - 19 IS - 2 SN - 1046-5928, 1046-5928 KW - Antigens, CD3 KW - 0 KW - Diphtheria Toxin KW - Immunoglobulin Variable Region KW - Immunotoxins KW - Index Medicus KW - Animals KW - Protein Biosynthesis KW - Electrophoresis, Polyacrylamide Gel KW - Models, Molecular KW - Humans KW - Jurkat Cells KW - Glycosylation KW - Mutagenesis, Site-Directed KW - Blotting, Western KW - Point Mutation KW - CHO Cells KW - Protein Conformation KW - Cricetinae KW - Immunotoxins -- chemistry KW - Antigens, CD3 -- immunology KW - Immunotoxins -- toxicity KW - Diphtheria Toxin -- chemistry KW - Immunoglobulin Variable Region -- metabolism KW - Diphtheria Toxin -- toxicity KW - Diphtheria Toxin -- metabolism KW - Immunotoxins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71227487?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+expression+and+purification&rft.atitle=Expression+of+an+anti-CD3+single-chain+immunotoxin+with+a+truncated+diphtheria+toxin+in+a+mutant+CHO+cell+line.&rft.au=Liu%2C+Y+Y%3BGordienko%2C+I%3BMathias%2C+A%3BMa%2C+S%3BThompson%2C+J%3BWoo%2C+J+H%3BNeville%2C+D+M&rft.aulast=Liu&rft.aufirst=Y&rft.date=2000-07-01&rft.volume=19&rft.issue=2&rft.spage=304&rft.isbn=&rft.btitle=&rft.title=Protein+expression+and+purification&rft.issn=10465928&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-02 N1 - Date created - 2000-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pathological gambling among cocaine-dependent outpatients. AN - 71223263; 10873922 AB - The authors investigated the occurrence of pathological gambling among cocaine-dependent outpatients, its influence on short-term outcome of treatment, and comparative characteristics of patients with and without pathological gambling. The subjects were 313 cocaine-dependent (200 also opiate-dependent) outpatients in clinical trials of medication for cocaine dependence. Pathological gambling (DSM-III-R criteria) was assessed with the Diagnostic Interview Schedule, and sociodemographic and socioeconomic characteristics were determined with the Addiction Severity Index. Outcome was defined as time in treatment (proportion of maximum scheduled time) and proportion of cocaine-positive urine samples during treatment. Pathological gambling had a lifetime occurrence rate of 8.0% and a current (past month) occurrence of 3.8%. Onset preceded the onset of cocaine dependence in 72.0% of the patients (and preceded onset of opiate dependence in 44.4%). Patients with pathological gambling (lifetime or current) did not differ significantly from other patients in length of treatment or proportion of cocaine-positive urine samples. Those with lifetime pathological gambling were significantly more likely to have tobacco dependence (84.0% versus 61.1%) and antisocial personality disorder (56.0% versus 19.8%), to be unemployed (84.0% versus 49.3%), to have recently engaged in illegal activity for profit (64.0% versus 38.5%), and to have been incarcerated (62.5% versus 33.9%). Pathological gambling is substantially more prevalent among cocaine-dependent outpatients than in the general population. Patients with pathological gambling differ from other cocaine-dependent outpatients in some sociodemographic characteristics but not in short-term outcome of treatment for cocaine dependence. JF - The American journal of psychiatry AU - Hall, G W AU - Carriero, N J AU - Takushi, R Y AU - Montoya, I D AU - Preston, K L AU - Gorelick, D A AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 1127 EP - 1133 VL - 157 IS - 7 SN - 0002-953X, 0002-953X KW - Bupropion KW - 01ZG3TPX31 KW - Carbamazepine KW - 33CM23913M KW - Bromocriptine KW - 3A64E3G5ZO KW - Abridged Index Medicus KW - Index Medicus KW - Age of Onset KW - Bupropion -- therapeutic use KW - Humans KW - Bromocriptine -- therapeutic use KW - Carbamazepine -- therapeutic use KW - Comorbidity KW - Ambulatory Care KW - Substance Abuse Treatment Centers KW - Length of Stay KW - Substance Abuse Detection KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Psychiatric Status Rating Scales -- statistics & numerical data KW - Adolescent KW - Female KW - Male KW - Prevalence KW - Disruptive, Impulse Control, and Conduct Disorders -- epidemiology KW - Disruptive, Impulse Control, and Conduct Disorders -- diagnosis KW - Gambling -- psychology KW - Cocaine-Related Disorders -- diagnosis KW - Disruptive, Impulse Control, and Conduct Disorders -- therapy KW - Cocaine-Related Disorders -- drug therapy KW - Cocaine-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71223263?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=Pathological+gambling+among+cocaine-dependent+outpatients.&rft.au=Hall%2C+G+W%3BCarriero%2C+N+J%3BTakushi%2C+R+Y%3BMontoya%2C+I+D%3BPreston%2C+K+L%3BGorelick%2C+D+A&rft.aulast=Hall&rft.aufirst=G&rft.date=2000-07-01&rft.volume=157&rft.issue=7&rft.spage=1127&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-19 N1 - Date created - 2000-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of proliferative lesions of the uterus, testes, and liver in swiss mice given repeated injections of sodium arsenate: possible estrogenic mode of action. AN - 71219893; 10873715 AB - Inorganic arsenic (As) is a human carcinogen but has not been unequivocally proven carcinogenic in rodents. For instance, one older study indicates that repeated iv injections of sodium arsenate might induce lymphomas in Swiss mice (58% incidence) (Osswald and Goerttler, Verh. Dtsch. Ges. Pathol. 55, 289-293, 1971), but it was considered inadequate for critical evaluation of carcinogenic potential largely because of issues in experimental design. Therefore, we studied repeated iv sodium arsenate injection and neoplastic response in male and female Swiss mice. Groups (n = 25) of mice received sodium arsenate (0.5 mg/kg, iv) or saline (control) once/week for 20 weeks and were observed for a total of 96 weeks when the study ended. Differences in survival and body weights were unremarkable. In females, arsenate induced marked increases in the incidence and severity of cystic hyperplasia of the uterus compared against controls. Arsenate also was associated with a rare adenocarcinoma of the uterus. Hyperplastic uterine epithelium from arsenate-exposed animals showed strong positive immunostaining for the proliferating cell nuclear antigen (PCNA). There was also an upregulation of estrogen receptor (ER) immunoreactive protein in the early lesions of uterine luminal and glandular hyperplasia, although a progressive decrease in its expression was seen in the severe hyperplastic or neoplastic epithelium. In common with the preneoplastic and neoplastic gynecological lesions in humans, the levels of immunoreactive inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine-containing proteins were greater in the uterine hyperplastic epidermis and their intensity was positively correlated with the severity of the lesions. Arsenate-induced uterine hyperplastic lesions also showed a strong upregulation of cyclin D1, an estrogen-associated gene product essential for progression through the G1 phase of the cell cycle. In other tissues, arsenate increased testicular interstitial cell hyperplasia incidence and severity over control but without affecting the incidence of tubular degeneration. Arsenate also induced increases in hepatic proliferative lesions (HPL; foci of alteration + neoplasia), but only in females. Significant skin changes (incidence of hyperkeratotic lesions) and renal lesions (severity of nephropathy) also occurred in arsenate-treated females. Thus, repeated arsenate exposure, though not outright tumorigenic in the present study, was associated with proliferative, preneoplastic lesions of the uterus, testes, and liver. Estrogen treatment has been associated with proliferative lesions and tumors of the uterus, female liver, and testes in other studies, supporting a hypothesis that arsenate might somehow act through an estrogenic mode of action. JF - Toxicology and applied pharmacology AU - Waalkes, M P AU - Keefer, L K AU - Diwan, B A AD - Inorganic Carcinogenesis Section, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. waalkes@niehs.nih.gov Y1 - 2000/07/01/ PY - 2000 DA - 2000 Jul 01 SP - 24 EP - 35 VL - 166 IS - 1 SN - 0041-008X, 0041-008X KW - Arsenates KW - 0 KW - Estrogens KW - sodium arsenate KW - 7631-89-2 KW - Index Medicus KW - Animals KW - Estrogens -- pharmacology KW - Humans KW - Mice KW - Male KW - Female KW - Liver -- pathology KW - Testis -- drug effects KW - Liver -- drug effects KW - Testis -- pathology KW - Arsenates -- administration & dosage KW - Arsenates -- toxicity KW - Uterus -- pathology KW - Uterus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71219893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Induction+of+proliferative+lesions+of+the+uterus%2C+testes%2C+and+liver+in+swiss+mice+given+repeated+injections+of+sodium+arsenate%3A+possible+estrogenic+mode+of+action.&rft.au=Waalkes%2C+M+P%3BKeefer%2C+L+K%3BDiwan%2C+B+A&rft.aulast=Waalkes&rft.aufirst=M&rft.date=2000-07-01&rft.volume=166&rft.issue=1&rft.spage=24&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-15 N1 - Date created - 2000-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Proliferative lesions and reproductive tract tumors in male descendants of mice exposed developmentally to diethylstilbestrol. AN - 71217677; 10874014 AB - Prenatal exposure to diethylstilbestrol (DES) is associated with reproductive tract abnormalities, subfertility and neoplasia in experimental animals and humans. Studies using experimental animals suggest that the carcinogenic effects of DES may be transmitted to succeeding generations. To further evaluate this possibility and to determine if there is a sensitive window of exposure, outbred CD-1 mice were treated with DES during three developmental stages: group 1 was treated on days 9-16 of gestation (2.5, 5 or 10 microg/kg maternal body weight) during major organogenesis; group II was treated once on day 18 of gestation (1000 microg/kg maternal body weight) just prior to birth; and group III was treated on days 1-5 of neonatal life (0.002 microg/pup/day). DES-exposed female mice (F(1)) were raised to maturity and bred to control males to generate DES-lineage (F(2)) descendants. The F(2) males obtained from these matings are the subjects of this report; results in F(2) females have been reported previously [Newbold et al. (1998) CARCINOGENESIS:, 19, 1655-1663]. Reproductive performance of F(2) males when bred to control females was not different from control males. However, in DES F(2) males killed at 17-24 months, an increased incidence of proliferative lesions of the rete testis and tumors of the reproductive tract was observed. Since these increases were seen in all DES treatment groups, all exposure periods were considered susceptible to perturbation by DES. These data suggest that, while fertility of the DES F(2) mice appeared unaltered, increased susceptibility for tumors is transmitted from the DES 'grandmothers' to subsequent generations. JF - Carcinogenesis AU - Newbold, R R AU - Hanson, R B AU - Jefferson, W N AU - Bullock, B C AU - Haseman, J AU - McLachlan, J A AD - Developmental Endocrinology Section, Reproductive Toxicology Group, Laboratory of Toxicology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. newbold1@niehs.nih.gov Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 1355 EP - 1363 VL - 21 IS - 7 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Estrogens KW - Estrogens, Non-Steroidal KW - Testosterone KW - 3XMK78S47O KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Animals KW - Mice, Inbred ICR KW - Rete Testis -- drug effects KW - Disease Susceptibility KW - Rete Testis -- pathology KW - Gestational Age KW - Mice KW - Estrogens -- blood KW - Pregnancy KW - Testis -- anatomy & histology KW - Testis -- drug effects KW - Testosterone -- blood KW - Female KW - Male KW - Fertility -- drug effects KW - Organ Size -- drug effects KW - Genital Neoplasms, Male -- pathology KW - Fetus -- drug effects KW - Diethylstilbestrol -- toxicity KW - Estrogens, Non-Steroidal -- toxicity KW - Carcinogens -- toxicity KW - Genital Neoplasms, Male -- chemically induced KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71217677?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Proliferative+lesions+and+reproductive+tract+tumors+in+male+descendants+of+mice+exposed+developmentally+to+diethylstilbestrol.&rft.au=Newbold%2C+R+R%3BHanson%2C+R+B%3BJefferson%2C+W+N%3BBullock%2C+B+C%3BHaseman%2C+J%3BMcLachlan%2C+J+A&rft.aulast=Newbold&rft.aufirst=R&rft.date=2000-07-01&rft.volume=21&rft.issue=7&rft.spage=1355&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-17 N1 - Date created - 2000-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retinoids in chemoprevention and differentiation therapy. AN - 71217601; 10874003 AB - Retinoids are essential for the maintenance of epithelial differentiation. As such, they play a fundamental role in chemoprevention of epithelial carcinogenesis and in differentiation therapy. Physiological retinoic acid is obtained through two oxidation steps from dietary retinol, i.e. retinol-->retinal-->retinoic acid. The latter retinal-->retinoic acid step is irreversible and eventually marks disposal of this essential nutrient, through cytochrome P450-dependent oxidative steps. Mutant mice deficient in aryl hydrocarbon receptor (AHR) accumulate retinyl palmitate, retinol and retinoic acid. This suggests a direct connection between the AHR and retinoid homeostasis. Retinoids control gene expression through the nuclear retinoic acid receptors (RARs) alpha, beta and gamma and 9-cis-retinoic acid receptors alpha, beta and gamma, which bind with high affinity the natural ligands all-trans-retinoic acid and 9-cis-retinoic acid, respectively. Retinoids are effective chemopreventive agents against skin, head and neck, breast, liver and other forms of cancer. Differentiation therapy of acute promyelocytic leukemia (APL) is based on the ability of retinoic acid to induce differentiation of leukemic promyelocytes. Patients with relapsed, retinoid-resistant APL are now being treated with arsenic oxide, which results in apoptosis of the leukemic cells. Interestingly, induction of differentiation in promyelocytes and consequent remission of APL following retinoid therapy depends on expression of a chimeric PML-RAR alpha fusion protein resulting from a t(15;17) chromosomal translocation. This protein functions as a dominant negative against the function of both PML and RARs and its overexpression is able to recreate the phenotypes of the disease in transgenic mice. The development of new, more effective and less toxic retinoids, alone or in combination with other drugs, may provide additional avenues for cancer chemoprevention and differentiation therapy. JF - Carcinogenesis AU - Hansen, L A AU - Sigman, C C AU - Andreola, F AU - Ross, S A AU - Kelloff, G J AU - De Luca, L M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 1271 EP - 1279 VL - 21 IS - 7 SN - 0143-3334, 0143-3334 KW - Anticarcinogenic Agents KW - 0 KW - Antineoplastic Agents KW - Retinoids KW - Index Medicus KW - Animals KW - Humans KW - Cell Differentiation -- drug effects KW - Neoplasms -- drug therapy KW - Neoplasms -- pathology KW - Anticarcinogenic Agents -- therapeutic use KW - Retinoids -- therapeutic use KW - Neoplasms -- prevention & control KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71217601?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Retinoids+in+chemoprevention+and+differentiation+therapy.&rft.au=Hansen%2C+L+A%3BSigman%2C+C+C%3BAndreola%2C+F%3BRoss%2C+S+A%3BKelloff%2C+G+J%3BDe+Luca%2C+L+M&rft.aulast=Hansen&rft.aufirst=L&rft.date=2000-07-01&rft.volume=21&rft.issue=7&rft.spage=1271&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-17 N1 - Date created - 2000-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bioavailability of the genotoxic components in coal tar contaminated soils in Fischer 344 rats. AN - 71214309; 10869452 AB - The effect of chemical aging on the bioavailability and subsequent genotoxicity of coal tar (CT)-contaminated soils was evaluated in a 17-day feeding study using Fischer 344 male rats. Rats consumed a control diet or diets amended with soil, 0.35% CT, or soil freshly prepared or aged for 9 months with 0.35% CT. Mild treatment-related microscopic lesions in liver tissue and elevated enzyme levels in serum were detected in all CT treatment groups. The (32)P-postlabeling assay was employed to determine DNA adduct formation in treated animals. All CT treatment groups induced DNA adducts in both the liver and lung. Adduct levels were 3-fold higher in lung DNA compared to hepatic DNA. After correcting adduct levels for total ingested polycyclic aromatic hydrocarbons (PAHs), a significant decrease (p < 0.05) in adduct levels was observed in both CT/soil treatment groups compared to CT control in liver and lung DNA. Adduct profiles of (32)P-postlabeled hepatic and lung DNA displayed several nonpolar DNA adducts that comigrated with PAH-adducted calf thymus DNA standards as determined through both thin-layer chromatography (TLC) and high-pressure liquid chromatography (HPLC). These results suggest that soil, but not aging of contaminants in soil, decreases the bioavailability of genotoxic components in CT, as evidenced by DNA adduct analysis. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Bordelon, N R AU - Donnelly, K C AU - King, L C AU - Wolf, D C AU - Reeves, W R AU - George, S E AD - Department of Veterinary Anatomy and Public Health, Texas A&M University, College Station, Texas, USA. bordelo1@niehs.nih.gov Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 37 EP - 48 VL - 56 IS - 1 SN - 1096-6080, 1096-6080 KW - DNA Adducts KW - 0 KW - Mutagens KW - Phosphorus Radioisotopes KW - Polycyclic Aromatic Hydrocarbons KW - Soil Pollutants KW - Coal Tar KW - 8007-45-2 KW - Index Medicus KW - Eating -- drug effects KW - Animals KW - Liver -- pathology KW - Tissue Distribution KW - Chromatography, High Pressure Liquid KW - DNA Adducts -- metabolism KW - Biological Availability KW - DNA Damage -- drug effects KW - Rats KW - Rats, Inbred F344 KW - Liver -- drug effects KW - Body Weight -- drug effects KW - Polycyclic Aromatic Hydrocarbons -- analysis KW - Chromatography, Thin Layer KW - Phosphorus Radioisotopes -- metabolism KW - Male KW - Coal Tar -- toxicity KW - Soil Pollutants -- pharmacokinetics KW - Mutagens -- toxicity KW - Mutagens -- pharmacokinetics KW - Coal Tar -- chemistry KW - Coal Tar -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71214309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Bioavailability+of+the+genotoxic+components+in+coal+tar+contaminated+soils+in+Fischer+344+rats.&rft.au=Bordelon%2C+N+R%3BDonnelly%2C+K+C%3BKing%2C+L+C%3BWolf%2C+D+C%3BReeves%2C+W+R%3BGeorge%2C+S+E&rft.aulast=Bordelon&rft.aufirst=N&rft.date=2000-07-01&rft.volume=56&rft.issue=1&rft.spage=37&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 - 2000-08-10 N1 - Date created - 2000-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta). AN - 71208822; 10866668 AB - To determine the physiological roles of peroxisome proliferator-activated receptor beta (PPARbeta), null mice were constructed by targeted disruption of the ligand binding domain of the murine PPARbeta gene. Homozygous PPARbeta-null term fetuses were smaller than controls, and this phenotype persisted postnatally. Gonadal adipose stores were smaller, and constitutive mRNA levels of CD36 were higher, in PPARbeta-null mice than in controls. In the brain, myelination of the corpus callosum was altered in PPARbeta-null mice. PPARbeta was not required for induction of mRNAs involved in epidermal differentiation induced by O-tetradecanoylphorbol-13-acetate (TPA). The hyperplastic response observed in the epidermis after TPA application was significantly greater in the PPARbeta-null mice than in controls. Inflammation induced by TPA in the skin was lower in wild-type mice fed sulindac than in similarly treated PPARbeta-null mice. These results are the first to provide in vivo evidence of significant roles for PPARbeta in development, myelination of the corpus callosum, lipid metabolism, and epidermal cell proliferation. JF - Molecular and cellular biology AU - Peters, J M AU - Lee, S S AU - Li, W AU - Ward, J M AU - Gavrilova, O AU - Everett, C AU - Reitman, M L AU - Hudson, L D AU - Gonzalez, F J AD - Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. jmp21@psu.edu Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 5119 EP - 5128 VL - 20 IS - 14 SN - 0270-7306, 0270-7306 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Antigens, CD36 KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - Sulindac KW - 184SNS8VUH KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Tetradecanoylphorbol Acetate -- toxicity KW - Animals KW - Antigens, CD36 -- metabolism KW - Antigens, CD36 -- genetics KW - Inflammation -- chemically induced KW - Inflammation -- drug therapy KW - Mice KW - Fasting KW - Body Temperature -- genetics KW - Mice, Mutant Strains KW - Hyperplasia KW - Embryonic and Fetal Development -- genetics KW - Sulindac -- pharmacology KW - Mice, Inbred C57BL KW - Myelin Sheath -- metabolism KW - Female KW - Male KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology KW - Brain -- abnormalities KW - Transcription Factors -- drug effects KW - Body Constitution -- genetics KW - Transcription Factors -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Brain -- pathology KW - Skin -- pathology KW - Receptors, Cytoplasmic and Nuclear -- drug effects KW - Adipose Tissue -- abnormalities KW - Receptors, Cytoplasmic and Nuclear -- genetics KW - Transcription Factors -- genetics KW - Brain -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71208822?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Growth%2C+adipose%2C+brain%2C+and+skin+alterations+resulting+from+targeted+disruption+of+the+mouse+peroxisome+proliferator-activated+receptor+beta%28delta%29.&rft.au=Peters%2C+J+M%3BLee%2C+S+S%3BLi%2C+W%3BWard%2C+J+M%3BGavrilova%2C+O%3BEverett%2C+C%3BReitman%2C+M+L%3BHudson%2C+L+D%3BGonzalez%2C+F+J&rft.aulast=Peters&rft.aufirst=J&rft.date=2000-07-01&rft.volume=20&rft.issue=14&rft.spage=5119&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 - 2000-07-24 N1 - Date created - 2000-07-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Biol Evol. 1993 Nov;10(6):1136-49 [8277848] J Biol Chem. 1993 Jun 5;268(16):11811-6 [7685021] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7355-9 [8041794] J Biol Chem. 1995 Feb 3;270(5):2367-71 [7836471] Mol Cell Biol. 1995 Jun;15(6):3012-22 [7539101] J Biol Chem. 1995 Jun 2;270(22):12953-6 [7768881] Endocrinology. 1996 Jan;137(1):354-66 [8536636] Cell. 1995 Dec 15;83(6):841-50 [8521508] Biochem Biophys Res Commun. 1995 Dec 26;217(3):1015-25 [8554552] J Invest Dermatol. 1996 Feb;106(2):294-304 [8601731] J Biol Chem. 1996 Jul 12;271(28):16748-52 [8663269] Cell. 1996 Nov 1;87(3):377-89 [8898192] Mol Endocrinol. 1997 Jun;11(6):779-91 [9171241] Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 [9254694] J Biol Chem. 1997 Oct 24;272(43):26827-32 [9341113] J Biol Chem. 1997 Oct 24;272(43):27307-12 [9341179] J Biol Chem. 1997 Nov 7;272(45):28210-7 [9353271] J Biol Chem. 1998 Mar 6;273(10):5678-84 [9488698] J Neurochem. 1998 Apr;70(4):1366-75 [9523552] Diabetes. 1998 Apr;47(4):507-14 [9568680] Endocrinology. 1998 Jun;139(6):2748-54 [9607781] J Biol Chem. 1998 Jul 3;273(27):16710-4 [9642225] Carcinogenesis. 1998 Nov;19(11):1989-94 [9855014] Genomics. 1999 Jan 1;55(1):28-42 [9888996] Biochim Biophys Acta. 1999 Jan 4;1436(3):331-42 [9989264] Mol Cell Endocrinol. 1999 Jan 25;147(1-2):85-92 [10195695] J Clin Invest. 1999 Jun;103(11):1489-98 [10359558] Genes Dev. 1999 Jun 15;13(12):1561-74 [10385625] J Biol Chem. 1999 Jul 30;274(31):21920-5 [10419513] Curr Opin Lipidol. 1999 Jun;10(3):245-57 [10431661] J Biol Chem. 1999 Aug 13;274(33):23368-77 [10438514] Curr Opin Clin Nutr Metab Care. 1999 Jul;2(4):307-12 [10453311] Mol Reprod Dev. 1992 Nov;33(3):259-69 [1280449] Mol Cell. 1999 Oct;4(4):585-95 [10549290] Mol Cell. 1999 Oct;4(4):597-609 [10549291] Mol Cell. 1999 Oct;4(4):611-7 [10549292] Cell. 1999 Oct 29;99(3):335-45 [10555149] J Biol Chem. 1999 Dec 10;274(50):35881-8 [10585473] Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14623-8 [10588755] Proc Natl Acad Sci U S A. 1985 Mar;82(6):1673-7 [3856848] Neurochem Res. 1985 Mar;10(3):377-86 [4000393] Proc Natl Acad Sci U S A. 1987 Mar;84(5):1454-8 [3469678] J Neurosci Res. 1987;17(1):65-70 [3106645] Glia. 1989;2(5):318-29 [2478465] Cell. 1990 Oct 19;63(2):313-24 [2208288] Nature. 1990 Oct 18;347(6294):645-50 [2129546] Proc Natl Acad Sci U S A. 1990 Dec;87(23):9333-7 [1979171] Nucleic Acids Res. 1991 Aug 11;19(15):4293 [1870982] J Biochem. 1992 Feb;111(2):197-203 [1569043] Cell. 1992 Oct 16;71(2):323-34 [1423597] J Biol Chem. 1994 Apr 22;269(16):11683-6 [8163464] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Replacement of the ectodomains of the hemagglutinin-neuraminidase and fusion glycoproteins of recombinant parainfluenza virus type 3 (PIV3) with their counterparts from PIV2 yields attenuated PIV2 vaccine candidates. AN - 71207102; 10864657 AB - We sought to develop a live attenuated parainfluenza virus type 2 (PIV2) vaccine strain for use in infants and young children, using reverse genetic techniques that previously were used to rapidly produce a live attenuated PIV1 vaccine candidate. The PIV1 vaccine candidate, designated rPIV3-1cp45, was generated by substituting the full-length HN and F proteins of PIV1 for those of PIV3 in the attenuated cp45 PIV3 vaccine candidate (T. Tao et al., J. Virol. 72:2955-2961, 1998; M. H. Skiadopoulos et al., Vaccine 18:503-510, 1999). However, using the same strategy, we failed to recover recombinant chimeric PIV3-PIV2 isolate carrying the full-length PIV2 glycoproteins in a wild-type PIV3 backbone. Viable PIV3-PIV2 chimeras were recovered when chimeric HN and F open reading frames (ORFs) rather than complete PIV2 F and HN ORFs were used to construct the full-length cDNA. The recovered viruses, designated rPIV3-2CT, in which the PIV2 ectodomain and transmembrane domain were fused to the PIV3 cytoplasmic domain, and rPIV3-2TM, in which the PIV2 ectodomain was fused to the PIV3 transmembrane and cytoplasmic tail domain, possessed similar in vitro and in vivo phenotypes. Thus, it appeared that only the cytoplasmic tail of the HN or F glycoprotein of PIV3 was required for successful recovery of PIV3-PIV2 chimeras. Although rPIV3-2CT and rPIV3-2TM replicated efficiently in vitro, they were moderately to highly attenuated for replication in the respiratory tracts of hamsters, African green monkeys (AGMs), and chimpanzees. This unexpected finding indicated that chimerization of the HN and F proteins of PIV2 and PIV3 itself specified an attenuation phenotype in vivo. Despite this attenuation, these viruses were highly immunogenic and protective against challenge with wild-type PIV2 in hamsters and AGMs, and they represent promising candidates for clinical evaluation as a vaccine against PIV2. These chimeric viruses were further attenuated by the addition of 12 mutations of PIV3cp45 which lie outside of the HN and F genes. The attenuating effects of these mutations were additive with that of the chimerization, and thus inclusion of all or some of the cp45 mutations provides a means to further attenuate the PIV3-PIV2 chimeric vaccine candidates if necessary. JF - Journal of virology AU - Tao, T AU - Skiadopoulos, M H AU - Davoodi, F AU - Riggs, J M AU - Collins, P L AU - Murphy, B R AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ttao@niaid.nih.gov Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 6448 EP - 6458 VL - 74 IS - 14 SN - 0022-538X, 0022-538X KW - HN Protein KW - 0 KW - Vaccines, Attenuated KW - Vaccines, Synthetic KW - Viral Fusion Proteins KW - Viral Vaccines KW - Index Medicus KW - Virus Replication KW - Vaccines, Attenuated -- pharmacology KW - Animals KW - Amino Acid Sequence KW - Vaccines, Attenuated -- metabolism KW - Vaccination KW - Pan troglodytes KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Respiratory System -- virology KW - Vaccines, Attenuated -- immunology KW - Cercopithecus aethiops KW - Recombination, Genetic KW - Vaccines, Attenuated -- genetics KW - Molecular Sequence Data KW - Mesocricetus KW - Vero Cells KW - Protein Structure, Tertiary KW - Cell Line KW - Respiratory System -- drug effects KW - Cricetinae KW - Viral Vaccines -- genetics KW - Viral Fusion Proteins -- metabolism KW - Viral Vaccines -- immunology KW - Viral Fusion Proteins -- genetics KW - Viral Vaccines -- pharmacology KW - Viral Fusion Proteins -- immunology KW - HN Protein -- immunology KW - Vaccines, Synthetic -- pharmacology KW - Vaccines, Synthetic -- metabolism KW - HN Protein -- genetics KW - Parainfluenza Virus 2, Human -- genetics KW - Viral Vaccines -- metabolism KW - HN Protein -- metabolism KW - Parainfluenza Virus 2, Human -- metabolism KW - Parainfluenza Virus 3, Human -- genetics KW - Parainfluenza Virus 3, Human -- metabolism KW - Vaccines, Synthetic -- immunology KW - Vaccines, Synthetic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71207102?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Replacement+of+the+ectodomains+of+the+hemagglutinin-neuraminidase+and+fusion+glycoproteins+of+recombinant+parainfluenza+virus+type+3+%28PIV3%29+with+their+counterparts+from+PIV2+yields+attenuated+PIV2+vaccine+candidates.&rft.au=Tao%2C+T%3BSkiadopoulos%2C+M+H%3BDavoodi%2C+F%3BRiggs%2C+J+M%3BCollins%2C+P+L%3BMurphy%2C+B+R&rft.aulast=Tao&rft.aufirst=T&rft.date=2000-07-01&rft.volume=74&rft.issue=14&rft.spage=6448&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 - 2000-08-22 N1 - Date created - 2000-08-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Virology. 1995 Jun 1;209(2):457-69 [7778280] J Virol. 1998 Feb;72(2):1224-34 [9445022] J Virol. 1999 Dec;73(12):9773-80 [10559287] Vaccine. 2000 Jan 31;18(14):1359-66 [10618533] Infect Immun. 1975 Jul;12(1):62-8 [166929] Infect Immun. 1982 Jul;37(1):160-5 [7107002] J Med Virol. 1982;10(4):235-42 [6298358] J Med Virol. 1984;13(3):243-9 [6327899] Virology. 1985 Jun;143(2):569-82 [2414910] Virus Res. 1988 Aug;11(1):1-15 [2845680] J Infect Dis. 1990 Sep;162(3):746-9 [2167342] J Gen Virol. 1991 Jul;72 ( Pt 7):1703-7 [1649904] J Virol Methods. 1991 Feb-Mar;31(2-3):161-70 [1650782] J Clin Microbiol. 1991 Jun;29(6):1175-82 [1650789] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10342-6 [1682924] Virus Res. 1992 Mar;22(3):173-84 [1320790] J Virol. 1993 Aug;67(8):4822-30 [8392616] Virology. 1994 Nov 1;204(2):506-14 [7941317] J Virol. 1995 Mar;69(3):1444-51 [7853476] J Infect Dis. 1995 May;171(5):1107-14 [7751684] J Virol. 1995 Nov;69(11):7045-53 [7474124] Virology. 1995 Oct 20;213(1):190-203 [7483263] J Infect Dis. 1995 Dec;172(6):1445-50 [7594701] J Virol. 1996 Jun;70(6):3930-7 [8648730] J Virol. 1996 Sep;70(9):6112-8 [8709235] Pediatr Infect Dis J. 1996 Aug;15(8):650-4 [8858666] J Virol. 1997 Jun;71(6):4272-7 [9151814] J Gen Virol. 1998 Feb;79 ( Pt 2):279-89 [9472612] Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1746-51 [9465088] J Virol. 1998 Mar;72(3):1762-8 [9499025] J Virol. 1998 Mar;72(3):2150-9 [9499071] J Virol. 1998 Apr;72(4):2955-61 [9525616] J Virol. 1998 May;72(5):4467-71 [9557743] J Gen Virol. 1998 Apr;79 ( Pt 4):683-7 [9568961] N Engl J Med. 1998 May 14;338(20):1405-12 [9580647] Dev Biol Stand. 1998;93:119-23 [9737386] J Virol. 1998 Dec;72(12):9747-54 [9811709] J Virol. 1999 Feb;73(2):1374-81 [9882342] Virology. 1999 Jan 5;253(1):43-54 [9887317] J Virol. 1999 Apr;73(4):3438-42 [10074199] Vaccine. 1999 Mar 5;17(9-10):1100-8 [10195620] Virology. 1999 May 10;257(2):363-72 [10329547] Virology. 1999 Jul 20;260(1):125-35 [10405364] Virology. 1999 Sep 1;261(2):319-30 [10497117] Vaccine. 1999 Oct 14;18(5-6):503-10 [10519940] Am J Hyg. 1963 Mar;77:150-9 [14022784] Virology. 1997 Jul 21;234(1):74-83 [9234948] Virology. 1997 Sep 1;235(2):323-32 [9281512] N Engl J Med. 1997 Oct 23;337(17):1181-7 [9337376] Arch Virol Suppl. 1997;13:115-30 [9413532] Virology. 1995 Jun 20;210(1):202-5 [7793072] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Apoptosis induced by immunotoxins used in the treatment of hematologic malignancies. AN - 71198169; 10861457 AB - The recombinant immunotoxins anti-Tac(Fv)-PE38 (LMB-2), targeting the interleukin-2 receptor alpha subunit (IL-2Ralpha, Tac or CD25), and RFB4(dsFv)-PE38 (BL22), targeting CD22, are being evaluated in clinical trials as treatment for hematologic malignancies. The toxin moiety Pseudomonas exotoxin A (PE) of these recombinant molecules leads to the arrest of protein synthesis due to inactivation of elongation factor 2. Here, we provide evidence that cell lines derived from patients with hematologic malignancies react to immunotoxins not only with inhibition of protein synthesis but also with characteristic hallmarks of apoptosis such as caspase activation, cleavage of the "death substrate poly(ADP)-ribose polymerase and DNA laddering. Anti-Tac(Fv)-PE38 leads to a 10-fold increase in the cleavage of the fluorescent substrate DEVD-AFC, suggesting that a caspase-3-like enzyme is involved. This was verified by cleavage of caspase-3 (CPP32). MT1 cells exhibited DNA laddering after treatment with immunotoxin, which was reversed by pre-treatment with the protease inhibitor zVAD-fmk. This caspase inhibitor led to an at least 5-fold improvement in cell viability without altering inhibition of protein synthesis. Interestingly, HUT-102 cells did not undergo programmed cell death after exposure to immunotoxins that kill these cells. We conclude that immunotoxins may be valuable in the treatment of cancers that are resistant toward apoptosis because their targeted killing is often facilitated by, but not completely dependent on, programmed cell death. Int. J. Cancer 87:86-94, 2000. Published 2000 Wiley-Liss, Inc. JF - International journal of cancer AU - Keppler-Hafkemeyer, A AU - Kreitman, R J AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/07/01/ PY - 2000 DA - 2000 Jul 01 SP - 86 EP - 94 VL - 87 IS - 1 SN - 0020-7136, 0020-7136 KW - 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium KW - 0 KW - Amino Acid Chloromethyl Ketones KW - Antibodies KW - Antigens, CD KW - Antigens, Differentiation, B-Lymphocyte KW - Cell Adhesion Molecules KW - Coumarins KW - Immunotoxins KW - Lectins KW - Oligopeptides KW - Protease Inhibitors KW - Recombinant Proteins KW - Sialic Acid Binding Ig-like Lectin 2 KW - Tetrazolium Salts KW - antitac(FV)-PE38 recombinant immunotoxin KW - aspartyl-glutamyl-valyl-aspartyl-7-amino-4-trifluoromethylcoumarin KW - benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone KW - Caspase 3 KW - EC 3.4.22.- KW - Caspases KW - Leucine KW - GMW67QNF9C KW - Index Medicus KW - Protease Inhibitors -- pharmacology KW - Immunoblotting KW - Leukemia -- therapy KW - Dose-Response Relationship, Drug KW - Tetrazolium Salts -- pharmacology KW - Leukemia -- enzymology KW - Caspases -- metabolism KW - Burkitt Lymphoma -- therapy KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Coumarins -- pharmacology KW - Recombinant Proteins -- metabolism KW - Antigens, Differentiation, B-Lymphocyte -- immunology KW - Burkitt Lymphoma -- enzymology KW - Leucine -- metabolism KW - DNA Fragmentation -- drug effects KW - Oligopeptides -- pharmacology KW - Amino Acid Chloromethyl Ketones -- pharmacology KW - Lymphoma, T-Cell -- enzymology KW - Antigens, CD -- immunology KW - Lymphoma, T-Cell -- therapy KW - Hematologic Neoplasms -- therapy KW - Immunotoxins -- adverse effects KW - Apoptosis -- drug effects KW - Immunotoxins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71198169?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Apoptosis+induced+by+immunotoxins+used+in+the+treatment+of+hematologic+malignancies.&rft.au=Keppler-Hafkemeyer%2C+A%3BKreitman%2C+R+J%3BPastan%2C+I&rft.aulast=Keppler-Hafkemeyer&rft.aufirst=A&rft.date=2000-07-01&rft.volume=87&rft.issue=1&rft.spage=86&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 - 2000-07-13 N1 - Date created - 2000-07-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An IFN-gamma-inducible transcription factor, IFN consensus sequence binding protein (ICSBP), stimulates IL-12 p40 expression in macrophages. AN - 71196453; 10861061 AB - IL-12 is a cytokine that links innate and adaptive immunity. Its subunit p40 is induced in macrophages following IFN-gamma/LPS stimulation. Here we studied the role for IFN consensus sequence binding protein (ICSBP), an IFN-gamma/LPS-inducible transcription factor of the IFN regulatory factor (IRF) family in IL-12 p40 transcription. Macrophage-like cells established from ICSBP-/- mice did not induce IL-12 p40 transcripts, nor stimulated IL-12 p40 promoter activity after IFN-gamma/LPS stimulation, although induction of other inducible genes was normal in these cells. Transfection of ICSBP led to a marked induction of both human and mouse IL-12 p40 promoter activities in ICSBP+/+ and ICSBP-/- cells, even in the absence of IFN-gamma/LPS stimulation. Whereas IRF-1 alone was without effect, synergistic enhancement of promoter activity was observed following cotransfection of ICSBP and IRF-1. Deletion analysis of the human promoter indicated that the Ets site, known to be important for activation by IFN-gamma/LPS, also plays a role in the ICSBP activation of IL-12 p40. A DNA affinity binding assay revealed that endogenous ICSBP is recruited to the Ets site through protein-protein interaction. Last, transfection of ISCBP alone led to induction of the endogenous IL-12 p40 mRNA in the absence of IFN-gamma and LPS. Taken together, our results show that ICSBP induced by IFN-gamma/LPS, acts as a principal activator of IL-12p40 transcription in macrophages. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Wang, I M AU - Contursi, C AU - Masumi, A AU - Ma, X AU - Trinchieri, G AU - Ozato, K AD - Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2000/07/01/ PY - 2000 DA - 2000 Jul 01 SP - 271 EP - 279 VL - 165 IS - 1 SN - 0022-1767, 0022-1767 KW - DNA-Binding Proteins KW - 0 KW - IRF1 protein, human KW - IRF2 protein, human KW - Interferon Regulatory Factor-1 KW - Interferon Regulatory Factor-2 KW - Interferon Regulatory Factors KW - Irf1 protein, mouse KW - Irf2 protein, mouse KW - Lipopolysaccharides KW - Macromolecular Substances KW - Phosphoproteins KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-ets KW - Repressor Proteins KW - Transcription Factors KW - interferon regulatory factor-8 KW - Interleukin-12 KW - 187348-17-0 KW - Interferon-gamma KW - 82115-62-6 KW - Abridged Index Medicus KW - Index Medicus KW - Transcription Factors -- physiology KW - Animals KW - Transfection -- immunology KW - Promoter Regions, Genetic -- immunology KW - Gene Expression Regulation -- immunology KW - Humans KW - Lipopolysaccharides -- pharmacology KW - Phosphoproteins -- physiology KW - Transcription, Genetic -- immunology KW - Mice KW - Proto-Oncogene Proteins -- physiology KW - Mice, Knockout KW - Transcriptional Activation -- immunology KW - Consensus Sequence -- immunology KW - DNA-Binding Proteins -- physiology KW - Drug Synergism KW - Cell Line KW - Repressor Proteins -- biosynthesis KW - Macrophages -- immunology KW - Interleukin-12 -- biosynthesis KW - Repressor Proteins -- physiology KW - Interferon-gamma -- pharmacology KW - Interleukin-12 -- genetics KW - Repressor Proteins -- genetics KW - Macrophages -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71196453?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=An+IFN-gamma-inducible+transcription+factor%2C+IFN+consensus+sequence+binding+protein+%28ICSBP%29%2C+stimulates+IL-12+p40+expression+in+macrophages.&rft.au=Wang%2C+I+M%3BContursi%2C+C%3BMasumi%2C+A%3BMa%2C+X%3BTrinchieri%2C+G%3BOzato%2C+K&rft.aulast=Wang&rft.aufirst=I&rft.date=2000-07-01&rft.volume=165&rft.issue=1&rft.spage=271&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 - 2000-07-31 N1 - Date created - 2000-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The catalytic subunit of telomerase protects neurons against amyloid beta-peptide-induced apoptosis. AN - 71188568; 10854254 AB - The catalytic subunit of telomerase (TERT) is a specialized reverse transcriptase that has been associated with cell immortalization and cancer. It was reported recently that TERT is expressed in neurons throughout the brain in embryonic and early postnatal development, but is absent from neurons in the adult brain. We now report that suppression of TERT levels and function in embryonic mouse hippocampal neurons in culture using antisense technology and the telomerase inhibitor 3' -azido-2' 3' -dideoxythymidine significantly increases their vulnerability to cell death induced by amyloid beta-peptide, a neurotoxic protein believed to promote neuronal degeneration in Alzheimer's disease. Neurons in which TERT levels were reduced exhibited increased levels of oxidative stress and mitochondrial dysfunction following exposure to amyloid beta-peptide. Overexpression of TERT in pheochromocytoma cells resulted in decreased vulnerability to amyloid beta-peptide-induced apoptosis. Our findings demonstrate a neuroprotective function of TERT in an experimental model relevant to Alzheimer's disease, and suggest the possibility that restoration of TERT expression in neurons in the adult brain may protect against age-related neurodegeneration. JF - Journal of neurochemistry AU - Zhu, H AU - Fu, W AU - Mattson, M P AD - Sanders-Brown Research Center on Aging, University of Kentucky, Lexington, Kentucky. Laboratory of Neurosciences, National Institute on Aging, Baltimore, Maryland, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 117 EP - 124 VL - 75 IS - 1 SN - 0022-3042, 0022-3042 KW - Amyloid beta-Peptides KW - 0 KW - DNA-Binding Proteins KW - Enzyme Inhibitors KW - Oligonucleotides, Antisense KW - telomerase RNA KW - RNA KW - 63231-63-0 KW - Telomerase KW - EC 2.7.7.49 KW - Tert protein, mouse KW - Index Medicus KW - Animals KW - Mitochondria -- physiology KW - Hippocampus KW - Alzheimer Disease KW - Catalytic Domain KW - Gene Expression KW - Oligonucleotides, Antisense -- pharmacology KW - Mice KW - Rats KW - Cells, Cultured KW - Oxidative Stress KW - Enzyme Inhibitors -- pharmacology KW - Embryo, Mammalian KW - Immunohistochemistry KW - PC12 Cells KW - Telomerase -- antagonists & inhibitors KW - Telomerase -- physiology KW - Telomerase -- chemistry KW - Neurons -- cytology KW - Apoptosis -- drug effects KW - Amyloid beta-Peptides -- pharmacology KW - Neurons -- enzymology KW - Telomerase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71188568?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+catalytic+subunit+of+telomerase+protects+neurons+against+amyloid+beta-peptide-induced+apoptosis.&rft.au=Zhu%2C+H%3BFu%2C+W%3BMattson%2C+M+P&rft.aulast=Zhu&rft.aufirst=H&rft.date=2000-07-01&rft.volume=75&rft.issue=1&rft.spage=117&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 - 2000-07-17 N1 - Date created - 2000-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuronal apoptosis induced by pharmacological concentrations of 3-hydroxykynurenine: characterization and protection by dantrolene and Bcl-2 overexpression. AN - 71187176; 10854250 AB - We have studied neurotoxicity induced by pharmacological concentrations of 3-hydroxykynurenine (3-HK), an endogenous toxin implicated in certain neurodegenerative diseases, in cerebellar granule cells, PC12 pheochromocytoma cells, and GT1-7 hypothalamic neurosecretory cells. In all three cell types, the toxicity was induced in a dose-dependent manner by 3-HK at high micromolar concentrations and had features characteristic of apoptosis, including chromatin condensation and internucleosomal DNA cleavage. In cerebellar granule cells, the 3-HK neurotoxicity was unaffected by xanthine oxidase inhibitors but markedly potentiated by superoxide dismutase and its hemelike mimetic, MnTBAP [manganese(III) tetrakis(benzoic acid)porphyrin chloride]. Catalase blocked 3-HK neurotoxicity in the absence and presence of superoxide dismutase or MnTBAP. The formation of H(2)O(2) was demonstrated in PC12 and GT1-7 cells treated with 3-HK, by measuring the increase in the fluorescent product, 2',7'-dichlorofluorescein. In both PC12 and cerebellar granule cells, inhibitors of the neutral amino acid transporter that mediates the uptake of 3-HK failed to block 3-HK toxicity. However, their toxicity was slightly potentiated by the iron chelator, deferoxamine. Taken together, our results suggest that neurotoxicity induced by pharmacological concentrations of 3-HK in these cell types is mediated primarily by H(2)O(2), which is formed most likely by auto-oxidation of 3-HK in extracellular compartments. 3-HK-induced death of PC12 and GT1-7 cells was protected by dantrolene, an inhibitor of calcium release from the endoplasmic reticulum. The protection by dantrolene was associated with a marked increase in the protein level of Bcl-2, a prominent antiapoptotic gene product. Moreover, overexpression of Bcl-2 in GT1-7 cells elicited by gene transfection suppressed 3-HK toxicity. Thus, dantrolene may elicit its neuroprotective effects by mechanisms involving up-regulation of the level and function of Bcl-2 protein. JF - Journal of neurochemistry AU - Wei, H AU - Leeds, P AU - Chen, R W AU - Wei, W AU - Leng, Y AU - Bredesen, D E AU - Chuang, D M AD - Section on Molecular Neurobiology, Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 81 EP - 90 VL - 75 IS - 1 SN - 0022-3042, 0022-3042 KW - Chromatin KW - 0 KW - Enzyme Inhibitors KW - Free Radical Scavengers KW - Iron Chelating Agents KW - Metalloporphyrins KW - Proto-Oncogene Proteins c-bcl-2 KW - manganese(III)-tetrakis(4-benzoic acid)porphyrin KW - Kynurenine KW - 343-65-7 KW - 3-hydroxykynurenine KW - 484-78-6 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Xanthine Oxidase KW - EC 1.17.3.2 KW - Dantrolene KW - F64QU97QCR KW - Index Medicus KW - Animals KW - Xanthine Oxidase -- antagonists & inhibitors KW - Metalloporphyrins -- pharmacology KW - Iron Chelating Agents -- pharmacology KW - Chromatin -- ultrastructure KW - Cerebellum -- metabolism KW - Rats KW - Rats, Sprague-Dawley KW - Cerebellum -- cytology KW - Superoxide Dismutase -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Drug Synergism KW - DNA Fragmentation KW - PC12 Cells KW - Kynurenine -- pharmacology KW - Dantrolene -- pharmacology KW - Apoptosis -- drug effects KW - Neurons -- physiology KW - Gene Expression KW - Proto-Oncogene Proteins c-bcl-2 -- genetics KW - Kynurenine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71187176?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neuronal+apoptosis+induced+by+pharmacological+concentrations+of+3-hydroxykynurenine%3A+characterization+and+protection+by+dantrolene+and+Bcl-2+overexpression.&rft.au=Wei%2C+H%3BLeeds%2C+P%3BChen%2C+R+W%3BWei%2C+W%3BLeng%2C+Y%3BBredesen%2C+D+E%3BChuang%2C+D+M&rft.aulast=Wei&rft.aufirst=H&rft.date=2000-07-01&rft.volume=75&rft.issue=1&rft.spage=81&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 - 2000-07-17 N1 - Date created - 2000-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Proteasome-mediated degradation of the papillomavirus E2-TA protein is regulated by phosphorylation and can modulate viral genome copy number. AN - 71171521; 10846085 AB - The bovine papillomavirus E2 proteins regulate viral transcription, replication, and episomal genome maintenance. We have previously mapped the major phosphorylation sites of the E2 proteins to serine residues 298 and 301 and shown that mutation of serine residue 301 to alanine leads to a dramatic (10- to 20-fold) increase in viral DNA copy number. In this study we analyzed how phosphorylation regulates E2 protein function. S301 is located in a PEST sequence; these sequences are often found in proteins with a short half-life and can be regulated by phosphorylation. We show here that the E2 protein is ubiquitinated and degraded by the proteasome. Mutation of serine 301 to alanine increases the half-life of E2 from approximately 50 min to 160 min. Furthermore, the A301 E2 protein shows greatly reduced ubiquitination and degradation by the proteasome. These results suggest that the E2 protein level is regulated by phosphorylation, which in turn determines viral episomal copy number. JF - Journal of virology AU - Penrose, K J AU - McBride, A A AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0455, USA. Y1 - 2000/07// PY - 2000 DA - July 2000 SP - 6031 EP - 6038 VL - 74 IS - 13 SN - 0022-538X, 0022-538X KW - Cysteine Proteinase Inhibitors KW - 0 KW - DNA, Viral KW - DNA-Binding Proteins KW - E2 protein, Bovine papillomavirus KW - Lactones KW - Leupeptins KW - Multienzyme Complexes KW - Viral Proteins KW - acetyl-leucinyl-leucinyl-methional KW - acetylleucyl-leucyl-norleucinal KW - 110044-82-1 KW - clasto-lactacystin beta-lactone KW - 155975-72-7 KW - Serine KW - 452VLY9402 KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Alanine KW - OF5P57N2ZX KW - benzyloxycarbonylleucyl-leucyl-leucine aldehyde KW - RF1P63GW3K KW - Index Medicus KW - Animals KW - Papilloma -- pathology KW - Warts -- virology KW - Papillomavirus Infections -- virology KW - Genome, Viral KW - Serine -- metabolism KW - Serine -- genetics KW - Lactones -- pharmacology KW - Papillomavirus Infections -- pathology KW - Cysteine Proteinase Inhibitors -- pharmacology KW - Mutagenesis, Site-Directed KW - Leupeptins -- pharmacology KW - Cattle KW - Phosphorylation KW - Alanine -- metabolism KW - Warts -- pathology KW - Papilloma -- virology KW - Cercopithecus aethiops KW - Alanine -- genetics KW - Gene Dosage KW - Cell Line KW - Viral Proteins -- genetics KW - Bovine papillomavirus 1 -- metabolism KW - Multienzyme Complexes -- metabolism KW - DNA, Viral -- analysis KW - Cysteine Endopeptidases -- metabolism KW - DNA-Binding Proteins -- genetics KW - Viral Proteins -- metabolism KW - DNA-Binding Proteins -- metabolism KW - Bovine papillomavirus 1 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71171521?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Proteasome-mediated+degradation+of+the+papillomavirus+E2-TA+protein+is+regulated+by+phosphorylation+and+can+modulate+viral+genome+copy+number.&rft.au=Penrose%2C+K+J%3BMcBride%2C+A+A&rft.aulast=Penrose&rft.aufirst=K&rft.date=2000-07-01&rft.volume=74&rft.issue=13&rft.spage=6031&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 - 2000-08-10 N1 - Date created - 2000-08-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1982 Dec;79(23):7147-51 [6296820] Science. 1986 Oct 17;234(4774):364-8 [2876518] Proc Natl Acad Sci U S A. 1988 Aug;85(16):5864-8 [2842752] J Virol. 1989 Dec;63(12):5076-85 [2555544] J Virol. 1990 Nov;64(11):5529-41 [2170685] J Virol. 1991 Feb;65(2):649-56 [1846189] Science. 1990 Dec 21;250(4988):1694-9 [2176744] J Biol Chem. 1991 Jun 15;266(17):11213-20 [2040628] J Virol. 1991 Dec;65(12):6528-34 [1658358] Cold Spring Harb Symp Quant Biol. 1991;56:335-46 [1668086] Cell. 1993 Jun 18;73(6):1207-21 [8390328] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7051-5 [8041744] Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11259-63 [7479976] EMBO J. 1996 Jan 2;15(1):1-11 [8598191] Mol Cell Biol. 1996 Apr;16(4):1295-304 [8657102] Trends Biochem Sci. 1996 Jul;21(7):267-71 [8755249] EMBO J. 1996 Aug 15;15(16):4182-93 [8861947] Mol Cell Biol. 1996 Nov;16(11):6037-45 [8887633] EMBO J. 1997 Jan 15;16(2):318-31 [9029152] J Virol. 1997 May;71(5):3652-65 [9094639] Genes Dev. 1997 Apr 15;11(8):957-72 [9136925] Mol Cell Biol. 1998 Jan;18(1):314-21 [9418878] J Virol. 1998 Mar;72(3):2079-88 [9499063] Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4338-43 [9539738] Annu Rev Biochem. 1998;67:425-79 [9759494] J Cell Biol. 1998 Dec 28;143(7):1883-98 [9864362] Electrophoresis. 1999 Feb;20(2):418-28 [10197449] J Virol. 1999 May;73(5):4404-12 [10196338] J Cell Biol. 1999 Jul 12;146(1):113-24 [10402464] EMBO J. 1999 Aug 2;18(15):4280-91 [10428966] Mol Biol Cell. 1999 Oct;10(10):3263-77 [10512865] J Biol Chem. 1999 Oct 22;274(43):30874-81 [10521480] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intracellular mechanisms mediating the neuronal death and astrogliosis induced by the prion protein fragment 106-126. AN - 71120007; 10817932 AB - Prion encephalopathies include fatal diseases of the central nervous system of men and animals characterized by nerve cell loss, glial proliferation and deposition of amyloid fibrils into the brain. During these diseases a cellular glycoprotein (the prion protein, PrP(C)) is converted, through a not yet completely clear mechanism, in an altered isoform (the prion scrapie, PrP(Sc)) that accumulates within the brain tissue by virtue of its resistance to the intracellular catabolism. PrP(Sc) is believed to be responsible for the neuronal loss that is observed in the prion disease. The PrP 106-126, a synthetic peptide that has been obtained from the amyloidogenic portion of the prion protein, represents a suitable model for studying the pathogenic role of the PrP(Sc), retaining, in vitro, some characteristics of the entire protein, such as the capability to aggregate in fibrils, and the neurotoxicity. In this work we present the results we have recently obtained regarding the action of the PrP 106-126 in different cellular models. We report that the PrP 106-126 induces proliferation of cortical astrocytes, as well as degeneration of primary cultures of cortical neurons or of neuroectodermal stable cell lines (GH(3) cells). In particular, these two opposite effects are mediated by the same attitude of the peptide to interact with the L-type calcium channels: in the astrocytes, the activity of these channels seems to be activated by PrP 106-126, while, in the cortical neurons and in the GH(3) cells, the same treatment causes a blockade of these channels causing a toxic effect. JF - International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience AU - Thellung, S AU - Florio, T AU - Corsaro, A AU - Arena, S AU - Merlino, M AU - Salmona, M AU - Tagliavini, F AU - Bugiani, O AU - Forloni, G AU - Schettini, G AD - Unit of Pharmacology and Neuroscience National Cancer Institute, Advanced Biotechnology Centre, Department of Oncology, Section of Pharmacology University of Genoa, Largo Rosanna Benzi 10, 16132, Genoa, Italy. PY - 2000 SP - 481 EP - 492 VL - 18 IS - 4-5 SN - 0736-5748, 0736-5748 KW - Calcium Channel Blockers KW - 0 KW - Calcium Channels, L-Type KW - Peptide Fragments KW - Prions KW - prion protein (106-126) KW - Tritium KW - 10028-17-8 KW - Potassium Chloride KW - 660YQ98I10 KW - DNA KW - 9007-49-2 KW - Nicardipine KW - CZ5312222S KW - Calcium KW - SY7Q814VUP KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - Animals KW - Cerebral Cortex -- cytology KW - Thymidine -- pharmacokinetics KW - Humans KW - Potassium Chloride -- pharmacology KW - Cell Division -- physiology KW - Amino Acid Sequence KW - DNA -- biosynthesis KW - Nicardipine -- pharmacology KW - Rats KW - Calcium -- metabolism KW - In Situ Nick-End Labeling KW - Calcium Channel Blockers -- pharmacology KW - Molecular Sequence Data KW - Calcium Channels, L-Type -- metabolism KW - Creutzfeldt-Jakob Syndrome -- metabolism KW - Cell Line KW - Gliosis -- pathology KW - Prions -- toxicity KW - Prions -- chemistry KW - Cell Death -- physiology KW - Peptide Fragments -- toxicity KW - Peptide Fragments -- chemistry KW - Neurons -- metabolism KW - Neurons -- chemistry KW - Cell Death -- drug effects KW - Astrocytes -- pathology KW - Neurons -- pathology KW - Astrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71120007?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+developmental+neuroscience+%3A+the+official+journal+of+the+International+Society+for+Developmental+Neuroscience&rft.atitle=Intracellular+mechanisms+mediating+the+neuronal+death+and+astrogliosis+induced+by+the+prion+protein+fragment+106-126.&rft.au=Thellung%2C+S%3BFlorio%2C+T%3BCorsaro%2C+A%3BArena%2C+S%3BMerlino%2C+M%3BSalmona%2C+M%3BTagliavini%2C+F%3BBugiani%2C+O%3BForloni%2C+G%3BSchettini%2C+G&rft.aulast=Thellung&rft.aufirst=S&rft.date=2000-07-01&rft.volume=18&rft.issue=4-5&rft.spage=481&rft.isbn=&rft.btitle=&rft.title=International+journal+of+developmental+neuroscience+%3A+the+official+journal+of+the+International+Society+for+Developmental+Neuroscience&rft.issn=07365748&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-17 N1 - Date created - 2000-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Relation of Child Care to Cognitive and Language Development AN - 54470108; 2000006665 JF - Child Development AU - National Institute of Child Health and Human Development Early Child Care Research Network AD - National Institute of Child Health and Human Development Early Child Care Research Network PY - 2000 SP - 960 EP - 980 VL - 71 IS - 4 SN - 0009-3920, 0009-3920 KW - language KW - psycholinguistics KW - development of language KW - cognitive development KW - childcare UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/54470108?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amlaib&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Development&rft.atitle=The+Relation+of+Child+Care+to+Cognitive+and+Language+Development&rft.au=National+Institute+of+Child+Health+and+Human+Development+Early+Child+Care+Research+Network&rft.aulast=National+Institute+of+Child+Health+and+Human+Development+Early+Child+Care+Research+Network&rft.aufirst=&rft.date=2000-07-01&rft.volume=71&rft.issue=4&rft.spage=960&rft.isbn=&rft.btitle=&rft.title=Child+Development&rft.issn=00093920&rft_id=info:doi/ L2 - http://links.jstor.org/sici?sici=0009-3920%28200007/08%2971%3A4%3C960%3ATROCCT%3E2.0.CO%3B2-2 L2 - http://links.jstor.org/sici?sici=0009-3920%28200007/08%2971%3A4%3C960%3ATROCCT%3E2.0.CO%3B2-2 LA - English DB - MLA International Bibliography N1 - Update - 200001 N1 - Last updated - 2017-01-04 ER - TY - JOUR T1 - Comprehensive genetic analysis of cancer cells. AN - 1859376998; 12167284 AB - Human cancer is viewed as a disorder of genes originating from the progeny of a single cell that has accumulated multiple genetic alterations. The genetic alterations include point mutation, chromosomal rearrangements and imbalances. Amplifications primarily involve oncogenes whose overexpression leads to growth deregulation, while deletions commonly target tumor suppressor genes that control cell cycle checkpoints and DNA repair mechanisms. With the advent of molecular cytogenetics procedures for global detection of genomic imbalances and for multicolor visualization of structural chromosome changes, as well as the completion of human genome mapping and the development of microarray technology for serial gene expression analysis of the entire genomes, a significant progress has been made in uncovering the molecular basis of cancer. The major challenge in cancer biology is to decipher the molecular anatomy of various cancers and to identify cancer-related genes that now comprise only a fraction of human genes. The complete genetic anatomy of specific cancers would allow a better understanding of the role of genetic alterations in carcinogenesis, provide diagnostic and prognostic markers and discriminate between cells at different stages of progression toward malignancy. This review highlights current technologies that are available to explore cancer cells and outlines their application to investigations in human hepatocellular carcinoma. JF - Journal of cellular and molecular medicine AU - Popescu, Nicholas C. AD - National Cancer Institute, 37/3C05, 37 Convent Drive MSC 4255, Bethesda, Md 20892-4255, USA. PY - 2000 SP - 151 EP - 163 VL - 4 IS - 3 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859376998?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comprehensive+genetic+analysis+of+cancer+cells.&rft.au=Popescu%2C+Nicholas+C.&rft.aulast=Popescu&rft.aufirst=Nicholas&rft.date=2000-07-01&rft.volume=4&rft.issue=3&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+and+molecular+medicine&rft.issn=1582-4934&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2002-08-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antibiotic Susceptibility Profiles for Group B Streptococci Isolated from Neonates, 1995-1998 AN - 18479552; 5444898 AB - Antibiotic susceptibility profiles were analyzed for 119 invasive and 227 colonizing strains of group B streptococci isolated from neonates at 6 US academic centers. All strains were susceptible to penicillin, vancomycin, chloramphenicol, and cefotaxime. The rate of resistance to erythromycin was 20.2% and to clindamycin was 6.9%. Resistance to erythromycin increased in 1997. Type V strains were more resistant to erythromycin than were type Ia (P = .003) and type Ib (P = .004) strains and were more resistant to clindamycin than were type Ia (P < .001), type Ib (P = .01), and type III (P = .001) strains. Resistance rates varied with geographic region: in California, there were high rates of resistance to erythromycin and clindamycin (32% and 12%, respectively), and low rates in Florida (8.5% and 2.1%, respectively). Penicillin continues to be the drug of choice for treatment of group B streptococcus infection. For women who are penicillin intolerant, however, the selection of an alternative antibiotic should be guided by contemporary resistance patterns observed in that region. JF - Clinical Infectious Diseases AU - Lin, F-YC AU - Azimi, PH AU - Weisman, LE AU - Philips, JB III AU - Regan, J AU - Clark, P AU - Rhoads, G G AU - Clemens, J AU - Troendle, J AU - Pratt, E AU - Brenner, R A AU - Gill, V AD - National Institute of Child Health and Human Development and the Microbiology Service, Department of Clinical Pathology, W. G. Magnuson Clinical Center, National Institutes of Health, Bethesda Y1 - 2000/07// PY - 2000 DA - Jul 2000 SP - 76 EP - 79 VL - 31 IS - 1 SN - 1058-4838, 1058-4838 KW - cefotaxime KW - chloramphenicol KW - man KW - penicillin KW - vancomycin KW - Microbiology Abstracts B: Bacteriology KW - J 02855:Human Bacteriology: Others KW - J 02783:Antibiotics: General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18479552?accountid=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+Infectious+Diseases&rft.atitle=Antibiotic+Susceptibility+Profiles+for+Group+B+Streptococci+Isolated+from+Neonates%2C+1995-1998&rft.au=Lin%2C+F-YC%3BAzimi%2C+PH%3BWeisman%2C+LE%3BPhilips%2C+JB+III%3BRegan%2C+J%3BClark%2C+P%3BRhoads%2C+G+G%3BClemens%2C+J%3BTroendle%2C+J%3BPratt%2C+E%3BBrenner%2C+R+A%3BGill%2C+V&rft.aulast=Lin&rft.aufirst=F-YC&rft.date=2000-07-01&rft.volume=31&rft.issue=1&rft.spage=76&rft.isbn=&rft.btitle=&rft.title=Clinical+Infectious+Diseases&rft.issn=10584838&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Early infant feeding and growth status of US-born infants and children aged 4-71 mo: analyses from the third National Health and Nutrition Examination Survey, 1988-1994 AN - 18277780; 5326367 AB - There is controversy over what growth references to use in evaluating breast-fed infants and concern about whether never-breast-fed infants are at risk of overweight in childhood. The objective of this study was to determine whether infants who are exclusively breast-fed for 4 mo differ in average size from infants who are fed in other ways and whether such differences persist through age 5 y. Data from the third National Health and Nutrition Examination Survey (NHANES III) were linked to birth certificates of US-born infants and children. Feeding groups were defined on the basis of feeding patterns over the first 4 mo of life: exclusively breast-fed for 4 mo, partially breast-fed, breast-fed for <4 mo, and never breast-fed. Growth status, indexed as internally derived z scores (SD units) for weight, length (height), weight-for-length (height), midupper arm circumference, and triceps skinfold thickness, was compared among feeding groups. The final sample consisted of 5594 non-Hispanic white, non-Hispanic black, and Mexican American infants and children aged 4-71 mo. Of these, 21% were exclusively breast-fed for 4 mo, 10% were partially breast-fed, 24% were breast-fed for <4 mo, and 45% were never breast-fed. At 8-11 mo, infants who were exclusively breast-fed for 4 mo had adjusted mean z scores for weight (-0.21; -0.2 kg), weight-for-length (-0.27), and midupper arm circumference (-0.15) that differed significantly from zero (P < 0.05). By 12-23 mo, the differences had dissipated; there were no significant differences subsequent to 5 y. Triceps skinfold thickness was not related to early infant feeding. Infants who were exclusively breast-fed for 4 mo weighed less at 8-11 mo than did infants who were fed in other ways, but there were few other significant differences in growth status through age 5 y associated with early infant feeding. JF - American Journal of Clinical Nutrition AU - Hediger, M L AU - Overpeck, MD AU - Ruan, W J AU - Troendle, J F AD - Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, Bethesda, MD, USA Y1 - 2000/07// PY - 2000 DA - Jul 2000 SP - 159 EP - 167 VL - 72 IS - 1 SN - 0002-9165, 0002-9165 KW - Physical Education Index KW - Growth and development KW - Preschool children KW - Diet KW - Nutrition KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18277780?accountid=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=American+Journal+of+Clinical+Nutrition&rft.atitle=Early+infant+feeding+and+growth+status+of+US-born+infants+and+children+aged+4-71+mo%3A+analyses+from+the+third+National+Health+and+Nutrition+Examination+Survey%2C+1988-1994&rft.au=Hediger%2C+M+L%3BOverpeck%2C+MD%3BRuan%2C+W+J%3BTroendle%2C+J+F&rft.aulast=Hediger&rft.aufirst=M&rft.date=2000-07-01&rft.volume=72&rft.issue=1&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Clinical+Nutrition&rft.issn=00029165&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Preschool children; Diet; Nutrition; Growth and development ER - TY - JOUR T1 - Vitamin C status and mortality in US adults AN - 18277078; 5326366 AB - Low vitamin C status may increase the risk of mortality from cancer and cardiovascular disease. The objective was to test whether an association existed between serum ascorbate concentrations and mortality and whether the association was modified by cigarette smoking status or sex. Serum ascorbate concentrations were measured in adults as part of the second National Health and Nutrition Examination Survey (1976-1980). Vital status was ascertained 12-16 y later. The relative risk (RR) of death, adjusted for potential confounders, was estimated by using Cox proportional hazards models. Men in the lowest (<28.4 mu mol/L) compared with the highest ( greater than or equal to 73.8 mu mol/L) serum ascorbate quartile had a 57% higher risk of dying from any cause (RR: 1.57; 95% CI: 1.21, 2.03) and a 62% higher risk of dying from cancer (RR: 1.62; 95% CI: 1.01, 2.59). In contrast, there was no increased risk among men in the middle 2 quartiles for these outcomes and no increased risk of cardiovascular disease mortality in any quartile. There was no association between serum ascorbate quartile and mortality among women. These findings were consistent when analyses were limited to nonsmokers or further to adults who never smoked, suggesting that the observed relations were not due to cigarette smoking. These data suggest that men with low serum ascorbate concentrations may have an increased risk of mortality, probably because of an increased risk of dying from cancer. In contrast, serum ascorbate concentrations were not related to mortality among women. JF - American Journal of Clinical Nutrition AU - Loria, C M AU - Klag, MJ AU - Caulfield, LE AU - Whelton, P K AD - Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, MD, USA Y1 - 2000/07// PY - 2000 DA - Jul 2000 SP - 139 EP - 145 VL - 72 IS - 1 SN - 0002-9165, 0002-9165 KW - Physical Education Index KW - Death KW - Risk factors KW - Vitamins KW - Gerontology KW - Nutrition KW - Cancer KW - Heart diseases KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18277078?accountid=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=American+Journal+of+Clinical+Nutrition&rft.atitle=Vitamin+C+status+and+mortality+in+US+adults&rft.au=Loria%2C+C+M%3BKlag%2C+MJ%3BCaulfield%2C+LE%3BWhelton%2C+P+K&rft.aulast=Loria&rft.aufirst=C&rft.date=2000-07-01&rft.volume=72&rft.issue=1&rft.spage=139&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Clinical+Nutrition&rft.issn=00029165&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Death; Vitamins; Gerontology; Nutrition; Risk factors; Cancer; Heart diseases ER - TY - JOUR T1 - Domain size distributions can predict domain boundaries AN - 17892003; 5143133 AB - The sizes of protein domains observed in the 3D-structure database follow a surprisingly narrow distribution. Structural domains are furthermore formed from a single-chain continuous segment in over 80% of instances. These observations imply that some choices of domain boundaries on an otherwise uncharacterized sequence are more likely than others, based solely on the size and segment number of predicted domains. This property might be used to guess the locations of protein domain boundaries. To test this possibility we enumerate putative domain boundaries and calculate their relative likelihood under a probability model that considers only the size and segment number of predicted domains. We ask, in a cross-validated test using sequences with known 3D structure, whether the most likely guesses agree with the observed domain structure. We find that domain boundary predictions are surprisingly successful for sequences up to 400 residues long and that guessing domain boundaries in this way can improve the sensitivity of threading analysis. The DGS algorithm, for `Domain Guess by Size', is available as a web service at http://www.ncbi.nlm.nih.gov/dgs. This site also provides the DGS source code. JF - Bioinformatics AU - Wheelan, S J AU - Marchler-Bauer, A AU - Bryant, SH AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA, bryant@ncbi.nlm.nih.gov Y1 - 2000/07// PY - 2000 DA - Jul 2000 SP - 613 EP - 618 VL - 16 IS - 7 SN - 1367-4803, 1367-4803 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Probability KW - Algorithms KW - Bioinformatics KW - Computer applications KW - W3 33080:Bioinformatics and computer applications KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17892003?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioinformatics&rft.atitle=Domain+size+distributions+can+predict+domain+boundaries&rft.au=Wheelan%2C+S+J%3BMarchler-Bauer%2C+A%3BBryant%2C+SH&rft.aulast=Wheelan&rft.aufirst=S&rft.date=2000-07-01&rft.volume=16&rft.issue=7&rft.spage=613&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bioinformatics; Computer applications; Algorithms; Probability ER - TY - JOUR T1 - Stochastic effects of environmental radiation exposure in populations living near the Mayak Industrial Association: Preliminary report on study of cancer morbidity AN - 17829126; 4855377 AB - The Mayak Industrial Association, located in the South Ural Mountains, began operation in 1948 and was the first Russian site for the production and separation of plutonium. During the early days of operation, technological failures resulted in the release of large amounts of radioactive waste into the Techa River. Residents who lived in villages on the banks of the Techa and Iset Rivers were exposed to varying levels of radioactivity. The objective of this study is to assess stochastic (carcinogenic) effects in populations exposed to offsite releases of radioactive materials from the Mayak nuclear facility in Russia. Subjects of the present study are those individuals who lived during the period January 1950 through December 1960 in any of the exposed villages along the Techa River in Chelyabinsk Oblast. Death certificates and cancer incidence data have been routinely collected in the past from a five-rayon catchment area of Chelyabinsk Oblast. The registry of exposed residents along the Techa River assembled and maintained by the Urals Research Center for Radiation Medicine for the past 40 y is the basis for identifying study subjects for this project. Specific study objectives are to evaluate the incidence of cancer among current and former residents of Chelyabinsk Oblast who are in the exposed Techa River cohort; integrate results from the dose-reconstruction study to estimate doses for risk assessment; and develop a structure for maintaining continued follow-up of the cohort for cancer incidence. In the earlier part of our collaborative effort, the focus has been to enhance the cancer morbidity registry by updating it with cancer cases diagnosed through 1997, to conduct a series of validation procedures to ensure completeness and accuracy of the registry, and to reduce the numbers of subjects lost to follow-up. A feasibility study to determine cancer morbidity in migrants from the catchment area has been proposed. Our preliminary analyses of cancer morbidity underscore the importance of examining both cancer mortality and cancer morbidity in conducting a comprehensive analysis of the occurrence of cancer in this important cohort. JF - Health Physics AU - Kossenko, M M AU - Hoffman, DA AU - Thomas, T L AD - Radiation Epidemiology Branch, National Cancer Institute, Room 7100 EPS, 6120 Executive Boulevard, Rockville, MD 20852-7238, USA, thomast@mail.nih.gov Y1 - 2000/07// PY - 2000 DA - Jul 2000 SP - 55 EP - 62 VL - 79 IS - 1 SN - 0017-9078, 0017-9078 KW - man KW - Russia, Urals KW - Russia, Urals, Techa R. KW - Health & Safety Science Abstracts; Pollution Abstracts; Toxicology Abstracts KW - Risk assessment KW - Environmental health KW - Morbidity KW - Radiation KW - Carcinogenicity KW - Rivers KW - Plutonium KW - Radioactive pollution KW - Water pollution KW - Cancer KW - Nuclear power plants KW - Environmental quality KW - Research programs KW - H 8000:Radiation Safety/Electrical Safety KW - X 24210:Radiation & radioactive materials KW - P 8000:RADIATION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17829126?accountid=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=Stochastic+effects+of+environmental+radiation+exposure+in+populations+living+near+the+Mayak+Industrial+Association%3A+Preliminary+report+on+study+of+cancer+morbidity&rft.au=Kossenko%2C+M+M%3BHoffman%2C+DA%3BThomas%2C+T+L&rft.aulast=Kossenko&rft.aufirst=M&rft.date=2000-07-01&rft.volume=79&rft.issue=1&rft.spage=55&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 N1 - SubjectsTermNotLitGenreText - Radiation; Nuclear power plants; Cancer; Morbidity; Environmental health; Rivers; Water pollution; Plutonium; Environmental quality; Radioactive pollution; Carcinogenicity; Research programs; Risk assessment ER - TY - JOUR T1 - Haligramides A and B, Two New Cytotoxic Hexapeptides from the Marine Sponge Haliclona nigra AN - 17762605; 4824018 AB - Bioassay-guided fractionation of a cytotoxic aqueous extract of the sponge Haliclona nigra provided two new cyclic hexapeptides, haligramides A (1) and B (2), in addition to the known peptide, waiakeamide (3). The structures of peptides 1 and 2 were elucidated by extensive NMR analyses and by comparison of their spectral data with those of waiakeamide (3). The identity of haligramide A (1) was confirmed by its oxidative conversion to waiakeamide (3). Further structural confirmation was provided by oxidation of peptides 1, 2, and 3 to the common bis-sulfone derivative 4. JF - Journal of Natural Products AU - Rashid, MA AU - Gustafson, K R AU - Boswell, J L AU - Boyd, M R AD - Laboratory of Drug Discovery Research and Development, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick Cancer Research and Development Center, Building 1052, Room 121, Frederick, MD 21702-1201, USA, boyd@dtpax2.neiferf.gov Y1 - 2000/07// PY - 2000 DA - Jul 2000 SP - 956 EP - 959 VL - 63 IS - 7 SN - 0163-3864, 0163-3864 KW - bioassays KW - haligramide A KW - haligramide B KW - ASFA 3: Aquatic Pollution & Environmental Quality; Toxicology Abstracts; ASFA Marine Biotechnology Abstracts KW - Protein structure KW - Haliclona nigra KW - Chemical composition KW - Biological poisons KW - N.M.R. KW - Peptides KW - Toxins KW - Q4 27390:Toxins KW - X 24173:Animals KW - Q5 08524:Public health, medicines, dangerous organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17762605?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Natural+Products&rft.atitle=Haligramides+A+and+B%2C+Two+New+Cytotoxic+Hexapeptides+from+the+Marine+Sponge+Haliclona+nigra&rft.au=Rashid%2C+MA%3BGustafson%2C+K+R%3BBoswell%2C+J+L%3BBoyd%2C+M+R&rft.aulast=Rashid&rft.aufirst=MA&rft.date=2000-07-01&rft.volume=63&rft.issue=7&rft.spage=956&rft.isbn=&rft.btitle=&rft.title=Journal+of+Natural+Products&rft.issn=01633864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - Chemical composition; Biological poisons; Peptides; Protein structure; N.M.R.; Toxins; Haliclona nigra ER - TY - JOUR T1 - Production, properties and application to nonaqueous enzymatic catalysis of lipase from a newly isolated Pseudomonas strain AN - 17726356; 4789678 AB - A potent bacterium for lipase production was isolated from soil and identified as Pseudomonas species. It produced lipase constitutively. A mutant of this strain with a lipase productivity 3.25-fold higher was obtained by treatment with ultraviolet (UV) and nitrosoguanidine (NTG). Its fermentation condition was optimized to a lipase yield of 87.5 U/ml. The lipase had maximum activity at pH 9.0 and 45 degree C. It was stable at pHs from 7.0 to 11.0 and below 60 degree C. The effects of metal ions, surfactants and bile salts were also studied. The lipase was 1,3-specific. In organic solvents, the thermal stability of the lipase was significantly enhanced. Its optimum temperature was also slightly increased. The optimum water activity was found between 0.5 and 0.6. The lipase was successfully applied in organic phase to catalyze the glycerolysis of palm oil for monoglyceride (MG) production, and the enantioselective esterification of (R,S)-2-octanol. The enantioselectivity of the lipase could be enhanced substantially by treatment with an amphipathic. JF - Enzyme and Microbial Technology AU - Gao, X-G AU - Cao, S-G AU - Zhang, K-C AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, 37 Convent Dr., Bldg. 37, Rm 1B23, Bethesda, MD 20892, USA, gaox@mail.nih.gov Y1 - 2000/07// PY - 2000 DA - Jul 2000 SP - 74 EP - 82 VL - 27 IS - 1-2 SN - 0141-0229, 0141-0229 KW - monoglyceride KW - (R,S)-2-octanol KW - Biotechnology and Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology KW - Temperature effects KW - Pseudomonas KW - Triacylglycerol lipase KW - pH effects KW - A 01006:Enzymes & cofactors KW - J 02728:Enzymes KW - W2 32310:Enzymes and cofactors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17726356?accountid=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=Enzyme+and+Microbial+Technology&rft.atitle=Production%2C+properties+and+application+to+nonaqueous+enzymatic+catalysis+of+lipase+from+a+newly+isolated+Pseudomonas+strain&rft.au=Gao%2C+X-G%3BCao%2C+S-G%3BZhang%2C+K-C&rft.aulast=Gao&rft.aufirst=X-G&rft.date=2000-07-01&rft.volume=27&rft.issue=1-2&rft.spage=74&rft.isbn=&rft.btitle=&rft.title=Enzyme+and+Microbial+Technology&rft.issn=01410229&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 - Pseudomonas; Triacylglycerol lipase; pH effects; Temperature effects ER - TY - JOUR T1 - Continuous production and recovery of recombinant Ca2+ binding receptor from HEK 293 cells using perfusion through a packed bed bioreactor AN - 17691713; 4769618 AB - The extracellular domain of human parathyroid Ca super(2+) receptor was needed in order to study its structure and clinical application. The Ca super(2+) receptor is a unique member of the G protein-coupled receptor super-family, expressed in parathyroid and kidney cells where it has been shown to play a critical role in extracellular calcium homeostasis. The desired protein was produced by immobilizing the transformed HEK 293 cells in a packed-bed configuration using a 1.6 l (working volume) bioreactor equipped with a vertical mixing impeller assembly and an internal basket. The process included a propagation phase followed by a production phase. In the propagation phase, lasting approximately 160 h, the bed was perfused with a serum-containing medium, allowing the cells to grow at a constant growth rate to approximately 3 x 10 super(10). At this point the production phase was begun, replacing the medium with serum-free medium and continuing the perfusion process for additional 350 h. During this phase, the medium was pumped through the packed bed at a rate of 4-6 l per day, keeping the residual glucose concentration around 1 g l super(-1) and collecting and processing approximately 80 l of spent medium. This continuous perfusion method of the packed-bed bioreactor was compared to a repeated batch method in which existing medium was replenished when the glucose concentration was down to 1 g l super(-1). Using this method, serum-free medium was replaced with serum containing medium a few times when a decline in the glucose consumption was observed. Though medium consumption and protein yield are similar in both methods (roughly 10 mg l super(-1)), there are differences related to the ease of operation and processing of the produced protein. The continuous perfusion operation was found to be preferable and was chosen as the production strategy. JF - Cytotechnology AU - Kaufman, J AU - Wang, G AU - Zhang, W AU - Valle, M AU - Shiloach, J AD - Biotechnology Unit, LCDB, NIDDK, NIH, Bldg 6 Rm B1-33 Bethesda, MD 20892, U.S.A. Y1 - 2000/07// PY - 2000 DA - Jul 2000 SP - 3 EP - 11 PB - Kluwer Academic Publishers VL - 33 IS - 1-3 SN - 0920-9069, 0920-9069 KW - Ca2+-binding receptor KW - HEK 293 cells KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Calcium homeostasis KW - Parathyroid KW - Continuous culture KW - Perfusion KW - Bioreactors KW - Transformed cells KW - W3 33340:Other proteins, peptides, amino acids KW - W3 33580:Process engineering KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17691713?accountid=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=Cytotechnology&rft.atitle=Continuous+production+and+recovery+of+recombinant+Ca2%2B+binding+receptor+from+HEK+293+cells+using+perfusion+through+a+packed+bed+bioreactor&rft.au=Kaufman%2C+J%3BWang%2C+G%3BZhang%2C+W%3BValle%2C+M%3BShiloach%2C+J&rft.aulast=Kaufman&rft.aufirst=J&rft.date=2000-07-01&rft.volume=33&rft.issue=1-3&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Cytotechnology&rft.issn=09209069&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 - Perfusion; Bioreactors; Parathyroid; Continuous culture; Transformed cells; Calcium homeostasis ER - TY - JOUR T1 - Serratia Type Pore Forming Toxins AN - 17667285; 4757662 AB - The Serratia marcescens hemolysin represents a new type of hemolysin and has been studied in great molecular detail with regard to structure, activation and secretion. It has nothing in common with the pore forming toxins of E. coli type (RTX toxins), the Staphylococcus aureus alpha -toxin or the thiol activated toxin of group A beta -hemolytic streptococci (Streptolysin O). Studies on erythrocytes, eukaryotic cells and artificial black lipid membranes, have shown that the mechanism of pore formation of ShlA is different from other pore forming toxins. The S. marcescens hemolysin proteins ShlB and ShlA exhibit protein sequence homologues in Proteus mirabilis, Haemophilus ducreyi, Edwardsiella tarda and Erwinia chrysantemi. Furthermore, sequence motifs present in ShlA and Shlb have been shown to be important for activity and secretion of the S. marcescens hemolysin. Thus, the S. marcescens hemolysin forms the prototype of a new class of hemolysins and of a new secretory mechanism. The uniqueness of this new mechanism is underlined by the fact that activation of ShlA by ShlB strictly requires phosphatidylethanolamine as a cofactor. New data implicate a conformational change in ShlA during activation. In addition, ShlA not only forms pores in erythrocytes but also in fibroblasts and epithelial cells. The cytotoxic action of ShlA is mainly determined by lysis of infected cells in vitro. In sublytic doses, as will normally be the situation in vivo, ShlA exerts additionally effects which are currently under investigation. The knowledge of the structure, activation, secretion and mode of action of S. marcescens hemolysin has implications for proteins, related in sequence or in mode of secretion and activation. JF - Current Protein & Peptide Science AU - Hertle, R AD - Laboratory of Molecular Biology NCI 37 Convent Drive, Bldg. 37 4B03 Bethesda, MD USA, ralf.hertle@mikrobio.uni-tuebingen.de Y1 - 2000/07// PY - 2000 DA - Jul 2000 SP - 75 EP - 89 VL - 1 IS - 1 SN - 1389-2037, 1389-2037 KW - pore-forming toxins KW - Edwardsiella tarda KW - Erwinia chrysanthemi KW - Escherichia coli KW - Haemophilus ducreyi KW - Proteus mirabilis KW - Serratia KW - Sh1B protein KW - ShlA protein KW - Staphylococcus aureus KW - alpha -toxin KW - phosphatidylethanolamine KW - streptolysin O KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Toxicology Abstracts; Microbiology Abstracts B: Bacteriology KW - ^a-toxin KW - Epithelial cells KW - Cytotoxins KW - Erythrocytes KW - Toxins KW - Fibroblasts KW - Pores KW - Cofactors KW - Reviews KW - Serratia marcescens KW - Hemolysins KW - Black lipid membranes KW - W3 33340:Other proteins, peptides, amino acids KW - X 24171:Microbial KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17667285?accountid=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=Current+Protein+%26+Peptide+Science&rft.atitle=Serratia+Type+Pore+Forming+Toxins&rft.au=Hertle%2C+R&rft.aulast=Hertle&rft.aufirst=R&rft.date=2000-07-01&rft.volume=1&rft.issue=1&rft.spage=75&rft.isbn=&rft.btitle=&rft.title=Current+Protein+%26+Peptide+Science&rft.issn=13892037&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 - Serratia marcescens; Pores; Toxins; Hemolysins; Cofactors; Erythrocytes; Fibroblasts; Epithelial cells; Cytotoxins; Reviews; Black lipid membranes ER - TY - JOUR T1 - Complex interactions between the replicating oncolytic effect and the enzyme/prodrug effect of vaccinia-mediated tumor regression AN - 17664036; 4743577 AB - Replicating viruses for cancer gene therapy have beneficial antitumor effects, however, in the setting of an enzyme/prodrug system, the interactions between these viruses and the activated agents are complex. A replicating vaccinia virus expressing the cytosine deaminase gene (VVCD), which converts the prodrug 5-FC into 5-FU, was characterized in vitro and in vivo for its antitumor effects and pathogenicity. Replicating VVCD ( plus or minus 5-FC) at various MOIs was used to infect MC38 murine colon adenocarcinoma cells. At high MOIs (>0.1) virus alone was able to kill the majority (65-90%) of cells by day 5 with no additional benefit from prodrug. At low MOIs only the effect of prodrug is seen. Cell lysates demonstrated 300-fold reduced viral recovery from cells treated with both VVCD and 5-FC compared with controls treated with virus alone. Nude mice bearing subcutaneous MC38 tumors were injected with VVCD (or control) and treated with 5FC or control. Mice injected with VVCD (with or without 5FC treatment) had smaller tumors than the controls, suggesting that replicating vaccinia alone is cytotoxic to tumors in vivo. The addition of 5-FC improved the antitumor response when a low dose of virus was injected into tumors. Also, compared with mice that received virus alone, those that received VVCD and 5FC had significantly prolonged survival from virus-mediated death. In conclusion, the addition of an enzyme/prodrug system to a replicating virus can improve the antitumor response and decrease viral pathogenicity. JF - Gene Therapy AU - McCart, JA AU - Puhlmann, M AU - Lee, J AU - Hu, Y AU - Libutti, S K AU - Alexander, H R AU - Bartlett, D L AD - Surgery Branch, NCI, NIH, Building 10, Rm 2B16, 9000 Rockville Pike, Bethesda, MD, 20892, USA Y1 - 2000/07// PY - 2000 DA - Jul 2000 SP - 1217 EP - 1223 VL - 7 IS - 14 SN - 0969-7128, 0969-7128 KW - mice KW - 5-fluorocytosine KW - 5-fluorouracil KW - vaccinia virus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Colon KW - Gene therapy KW - Cytosine deaminase KW - Tumors KW - Adenocarcinoma KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17664036?accountid=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=Gene+Therapy&rft.atitle=Complex+interactions+between+the+replicating+oncolytic+effect+and+the+enzyme%2Fprodrug+effect+of+vaccinia-mediated+tumor+regression&rft.au=McCart%2C+JA%3BPuhlmann%2C+M%3BLee%2C+J%3BHu%2C+Y%3BLibutti%2C+S+K%3BAlexander%2C+H+R%3BBartlett%2C+D+L&rft.aulast=McCart&rft.aufirst=JA&rft.date=2000-07-01&rft.volume=7&rft.issue=14&rft.spage=1217&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&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 - Tumors; Cytosine deaminase; Gene therapy; Colon; Adenocarcinoma ER - TY - JOUR T1 - Phasic inhibition of dopamine uptake in nucleus accumbens induced by intravenous cocaine in freely behaving rats AN - 17640432; 4777987 AB - A new approach combining fast-scan cyclic voltammetry with iontophoretic dopamine delivery was used in freely behaving rats to evaluate the time-course of dopamine uptake inhibition in nucleus accumbens induced by intravenous cocaine at a dose (1.0 mg/kg) known to maintain self-administration behavior. Cocaine significantly increased the decay time of the dopamine response without altering its magnitude or time to peak. An increase in decay time was evident at 2 min, peaked at 6 min ( + 87%), and decreased to baseline at 18 min after a single cocaine injection. The change in decay time was similar in all rats and remained essentially the same, albeit slightly larger, for subsequent cocaine injections both within a session and over repeated sessions. The change in dopamine decay time did not correlate with cocaine-induced motor activation, which was maximal during the first minute after injection and decreased slowly over the next 20 min. Our data provide direct evidence for a phasic change in dopamine uptake induced by intravenous cocaine under behaviorally relevant conditions. The relatively slow and gradual development of dopamine uptake inhibition, which peaks at times when behaving rats self-inject cocaine, is inconsistent with the suggested role of this mechanism in the acute rewarding (euphoric) effects of self-injected cocaine, but supports its role in the activational and motivational aspects of drug-seeking and drug-taking behavior. Because intravenous cocaine enters the brain rapidly and peaks in neural tissue (1-2 min) long before it effectively inhibits dopamine uptake (6 min), it appears that some of the acute psychoemotional ("rush"), behavioral, autonomic, and neuronal effects of this drug, which are apparently resistant to dopamine receptor blockade, are mediated via rapid central or peripheral mechanisms independent of monoamine uptake. JF - Neuroscience AU - Kiyatkin, E A AU - Kiyatkin, DE AU - Rebec, G V AD - Behavioral Neuroscience Branch, NIDA-IRP, NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, ekiyatki@intra.nida.nih.gov Y1 - 2000/07// PY - 2000 DA - Jul 2000 SP - 729 EP - 741 VL - 98 IS - 4 SN - 0306-4522, 0306-4522 KW - rats KW - phase variations KW - Toxicology Abstracts KW - Nucleus accumbens KW - Intravenous administration KW - Dopamine KW - Emotional behavior KW - Cocaine KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17640432?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Phasic+inhibition+of+dopamine+uptake+in+nucleus+accumbens+induced+by+intravenous+cocaine+in+freely+behaving+rats&rft.au=Kiyatkin%2C+E+A%3BKiyatkin%2C+DE%3BRebec%2C+G+V&rft.aulast=Kiyatkin&rft.aufirst=E&rft.date=2000-07-01&rft.volume=98&rft.issue=4&rft.spage=729&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Nucleus accumbens; Cocaine; Dopamine; Intravenous administration; Emotional behavior ER - TY - JOUR T1 - Alcohols inhibit N-methyl-D-aspartate receptors via a site exposed to the extracellular environment AN - 17631663; 4772488 AB - N-Methyl-D-aspartate (NMDA) receptors are important CNS target sites of alcohols, but the site and mechanism of action of alcohols on NMDA receptors remains unclear. In CHO-K1 cells transfected with NR1/NR2B NMDA receptor subunits, ethanol inhibited NMDA-activated current with an IC sub(50) of 138 mM. Truncation of the intracellular C-terminal domain of the NR1 subunit (NR1T) did not alter ethanol sensitivity when combined with the NR2B subunit, but a similar truncation of the NR2B subunit (NR2BT) slightly enhanced ethanol sensitivity of receptors formed from coexpression with either NR1 or NR1T subunits. 1-Pentanol applied externally inhibited NMDA receptors with an IC sub(50) of 9.9 mM, but intracellular application of 1-pentanol (25 mM) did not alter NMDA receptor inhibition by externally applied ethanol or 1-pentanol. In addition, the amplitude of NMDA-activated current did not decrease during the time required for 1-pentanol (25 mM) to diffuse throughout the cytoplasm. Ethanol did not inhibit NMDA receptors when bath-applied in cell-attached patches or when applied to the cytoplasmic face of inside-out membrane patches. These results appear to be best explained by an action of alcohols on the NMDA receptor-channel protein, at a site located in a domain exposed to, or only accessible from, the extracellular environment. JF - Neuropharmacology AU - Peoples, R W AU - Stewart, R R AD - Unit on Cellular Neuropharmacology, Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Park 5 Bldg. Rm. 158, 12420 Parklawn Dr. MSC 8115, Bethesda, MD 20892-8115, USA, bpeoples@helix.nih.gov Y1 - 2000/07// PY - 2000 DA - Jul 2000 SP - 1681 EP - 1691 VL - 39 IS - 10 SN - 0028-3908, 0028-3908 KW - receptor channels KW - 1-pentanol KW - alcohols KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - N-Methyl-D-aspartic acid receptors KW - CHO cells KW - Membrane currents KW - Ethanol KW - N3 11106:Neurobiology of drug abuse KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17631663?accountid=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=Neuropharmacology&rft.atitle=Alcohols+inhibit+N-methyl-D-aspartate+receptors+via+a+site+exposed+to+the+extracellular+environment&rft.au=Peoples%2C+R+W%3BStewart%2C+R+R&rft.aulast=Peoples&rft.aufirst=R&rft.date=2000-07-01&rft.volume=39&rft.issue=10&rft.spage=1681&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=00283908&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 - Ethanol; Membrane currents; N-Methyl-D-aspartic acid receptors; CHO cells ER - TY - JOUR T1 - The role of nonhuman primate models in AIDS vaccine development AN - 17608141; 4741554 AB - Although animal models have been useful in guiding vaccine development, HIV/AIDS models have not yielded a clear correlate of immunity nor given consistent results on the potential efficacy of various vaccine approaches. Further development and improved uniformity in the use of animal models would maximize their potential to meet the urgent worldwide need for a safe and effective HIV vaccine. JF - Molecular Medicine Today AU - Johnston, MI AD - National Institute of Allergy and Infectious Diseases, 6700-B Rockledge Drive, Room 4101, Bethesda, MD 20892-7628, USA, pj7p@nih.gov Y1 - 2000/07// PY - 2000 DA - Jul 2000 SP - 267 EP - 270 VL - 6 IS - 7 SN - 1357-4310, 1357-4310 KW - HIV KW - primates KW - Human immunodeficiency virus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Acquired immune deficiency syndrome KW - Reviews KW - Animal models KW - Vaccines KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews KW - W3 33000:General topics and reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17608141?accountid=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=Molecular+Medicine+Today&rft.atitle=The+role+of+nonhuman+primate+models+in+AIDS+vaccine+development&rft.au=Johnston%2C+MI&rft.aulast=Johnston&rft.aufirst=MI&rft.date=2000-07-01&rft.volume=6&rft.issue=7&rft.spage=267&rft.isbn=&rft.btitle=&rft.title=Molecular+Medicine+Today&rft.issn=13574310&rft_id=info:doi/10.1016%2FS1357-4310%2800%2901724-X LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; Reviews; Animal models; Acquired immune deficiency syndrome; Vaccines DO - http://dx.doi.org/10.1016/S1357-4310(00)01724-X ER - TY - JOUR T1 - Differential Gene Expression Detected by Suppression Subtractive Hybridization in the Ethylene Glycol Monomethyl Ether-Induced Testicular Lesion AN - 17562368; 4746324 AB - The solvent ethylene glycol monomethyl ether (EGME) produces the same testicular lesions in rodents and human testis cultures, whose onset is characterized by apoptosis of pachytene spermatocytes. To identify gene changes early in the lesion and determine the possible involvement of cells other than the spermatocytes, we employed a suppression subtractive hybridization technique using whole testes from mice treated 8 h previously with 500 mg/kg EGME to generate two subtracted mouse testis cDNA libraries enriched for gene populations either up-regulated or down-regulated by EGME. A total of 70 clones were screened, and 6 of them were shown by Northern blotting to be differentially expressed in the EGME lesion. The three clones with increased expression after EGME treatment were identical to t-complex testis expressed gene 1 (tctex1), a gene encoding ribosomal protein S25, and a heretofore uncharacterized mouse testis expressed sequence tag. Three other genes suppressed by EGME were tctex2, alpha-2,6-sialyltransferase gene, and another uncharacterized mouse testis expressed sequence tag. Predicted peptide sequences of these clones contain multiple motifs for phosphorylation, glycosylation, and myristoylation. In situ hybridization with the antisense RNA probes further supported the expression changes of these six clones and localized the changes in multiple germ cell stages as well as other cell types (Sertoli, interstitial and peritubular cells). These data at the gene expression level are the first to demonstrate the early involvement in this lesion of cell types other than the dying spermatocytes. JF - Toxicological Sciences AU - Wang, Wei AU - Chapin, R E AD - Laboratory of Toxicology, National Toxicology Program, National Institute of Environmental Health Sciences, Mail Drop B3-05, P. O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 2000/07// PY - 2000 DA - Jul 2000 SP - 165 EP - 174 VL - 56 IS - 1 SN - 1096-6080, 1096-6080 KW - mice KW - methyl cellosolve KW - Toxicology Abstracts KW - Gene expression KW - Testes KW - Northern blotting KW - Spermatocytes KW - Hybridization analysis KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17562368?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Differential+Gene+Expression+Detected+by+Suppression+Subtractive+Hybridization+in+the+Ethylene+Glycol+Monomethyl+Ether-Induced+Testicular+Lesion&rft.au=Wang%2C+Wei%3BChapin%2C+R+E&rft.aulast=Wang&rft.aufirst=Wei&rft.date=2000-07-01&rft.volume=56&rft.issue=1&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Testes; Gene expression; Northern blotting; Hybridization analysis; Spermatocytes ER - TY - JOUR T1 - A Plasmid Partition System of the P1-P7par Family from the pMT1 Virulence Plasmid of Yersinia pestis AN - 17549843; 4734419 AB - The complete sequence of the virulence plasmid pMT1 of Yersinia pestis KIM5 revealed a region homologous to the plasmid partition (par) region of the P7 plasmid prophage of Escherichia coli. The essential genes parA and parB and the downstream partition site gene parS, are highly conserved in sequence and organization. The pMT1parS site and the parA- parB operon were separately inserted into vectors that could be maintained in E. coli. A mini-P1 vector containing pMT1parS was stably maintained when the pMT1 ParA and ParB proteins were supplied in trans, showing that the pMT1par system is fully functional for plasmid partition in E. coli. The pMT1par system exerted a plasmid silencing activity similar to, but weaker than those of P7par and P1par. In spite of the high degree of similarity, especially to P7par, it showed unique specificities with respect to the interactions of key components. Neither the P7 nor P1 Par proteins could support partition via the pMT1parS site, and the pMT1 Par proteins failed to support partition with P1parS or P7parS. Typical of other partition sites, supernumerary copies of pMT1parS exerted incompatibility toward plasmids supported by pMT1par. However, no interspecies incompatibility effect was observed between pMT1par, P7par, and P1par. JF - Journal of Bacteriology AU - Youngren, B AU - Radnedge, L AU - Hu, P AU - Garcia, E AU - Austin, S AD - Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute, DBS, NCI-FCRDC, Frederick, MD 21702-1201, austin@ncifcrf.gov Y1 - 2000/07// PY - 2000 DA - Jul 2000 SP - 3924 EP - 3928 VL - 182 IS - 14 SN - 0021-9193, 0021-9193 KW - parA gene KW - parB gene KW - parS gene KW - plasmid pMT1 KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Virulence KW - Escherichia coli KW - Yersinia pestis KW - J 02760:Plasmids KW - G 07203:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17549843?accountid=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=A+Plasmid+Partition+System+of+the+P1-P7par+Family+from+the+pMT1+Virulence+Plasmid+of+Yersinia+pestis&rft.au=Youngren%2C+B%3BRadnedge%2C+L%3BHu%2C+P%3BGarcia%2C+E%3BAustin%2C+S&rft.aulast=Youngren&rft.aufirst=B&rft.date=2000-07-01&rft.volume=182&rft.issue=14&rft.spage=3924&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.182.14.3924-3928.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Yersinia pestis; Escherichia coli; Virulence DO - http://dx.doi.org/10.1128/JB.182.14.3924-3928.2000 ER - TY - JOUR T1 - Managing risks of arthropod vector research AN - 17548951; 4733856 AB - Vector-borne disease specialists, ethicists, and funding/regulatory agency officials should work in concert to reach consensus on the most appropriate risk-management recommendations for the complex scenarios that constitute vector field research. People who are affected by vector-borne diseases must be included in discussions of the appropriateness of research projects and their justifications. Open debate of the virtues and concerns of vector release experiments will cultivate new approaches and a more rigorous and reasonable system of accountability. Open forums will be an indispensable means of information exchange, consensus building, and, ultimately, policy development. JF - Science (Washington) AU - Aultman, K S AU - Walker, ED AU - Gifford, F AU - Severson, D W AU - Beard, C B AU - Scott, T W AD - Parasitol. and Int. Programs Branch, Natl. Inst. of Allergy and Infect. Dis., Bethesda, MD 20892-7630, USA, ka6z@nih.gov Y1 - 2000/06/30/ PY - 2000 DA - 2000 Jun 30 SP - 2321 EP - 2322 PB - American Association for the Advancement of Science VL - 288 IS - 5475 SN - 0036-8075, 0036-8075 KW - arthropods KW - vector-borne diseases KW - Risk Abstracts; Entomology Abstracts KW - Risk assessment KW - Hazards KW - Vector-borne diseases KW - Vectors KW - Research programs KW - Z 05100:General KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17548951?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28Washington%29&rft.atitle=Managing+risks+of+arthropod+vector+research&rft.au=Aultman%2C+K+S%3BWalker%2C+ED%3BGifford%2C+F%3BSeverson%2C+D+W%3BBeard%2C+C+B%3BScott%2C+T+W&rft.aulast=Aultman&rft.aufirst=K&rft.date=2000-06-30&rft.volume=288&rft.issue=5475&rft.spage=2321&rft.isbn=&rft.btitle=&rft.title=Science+%28Washington%29&rft.issn=00368075&rft_id=info:doi/10.1126%2Fscience.288.5475.2321 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Research programs; Hazards; Risk assessment; Vector-borne diseases; Vectors DO - http://dx.doi.org/10.1126/science.288.5475.2321 ER - TY - JOUR T1 - Distinct pattern of expression of differentiation and growth-related genes in squamous cell carcinomas of the head and neck revealed by the use of laser capture microdissection and cDNA arrays. AN - 71270728; 10918578 AB - Although risk factors for squamous cell carcinomas of the head and neck (HNSCC) are well recognized, very little is known about the molecular mechanisms responsible for this malignancy. Furthermore, the ability to investigate gene expression profiles at different stages of tumor progression is usually limited by the remarkable heterogeneity of these neoplastic lesions. Here, we show the successful use of laser capture microdissection (LCM) to procure specific cell populations. The 5000 cells from representative sets of HNSCC and their matching normal tissues are sufficient to extract RNA of high integrity for the synthesis of labeled amplified cDNA probes which can then be hybridized to these membranes arrayed with known human cancer-related cDNAs. Furthermore, when compared to normal tissues, we demonstrate a consistent decrease in expression of differentiation markers such as cytokeratins, and an increase in the expression of a number of signal transducing and cell cycle regulatory molecules, as well as growth and angiogenic factors and tissue degrading proteases. Unexpectedly, we also found that most HNSCC overexpress members of the wnt and notch growth and differentiation regulatory system, thus suggesting that the wnt and notch pathways may contribute in squamous cell carcinogenesis. This experimental approach may facilitate the identification candidate markers for the early detection of preneoplastic lesions, as well as novel targets for pharmacological intervention in this disease. JF - Oncogene AU - Leethanakul, C AU - Patel, V AU - Gillespie, J AU - Pallente, M AU - Ensley, J F AU - Koontongkaew, S AU - Liotta, L A AU - Emmert-Buck, M AU - Gutkind, J S AD - Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/06/29/ PY - 2000 DA - 2000 Jun 29 SP - 3220 EP - 3224 VL - 19 IS - 28 SN - 0950-9232, 0950-9232 KW - RNA, Neoplasm KW - 0 KW - Index Medicus KW - Epithelial Cells -- cytology KW - RNA, Neoplasm -- isolation & purification KW - Nucleic Acid Hybridization -- methods KW - Humans KW - Oligonucleotide Array Sequence Analysis -- methods KW - Cell Differentiation KW - Lasers KW - Microscopy, Confocal -- methods KW - Cell Division KW - Gene Expression Regulation, Neoplastic KW - Carcinoma, Squamous Cell -- genetics KW - Head and Neck Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71270728?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Distinct+pattern+of+expression+of+differentiation+and+growth-related+genes+in+squamous+cell+carcinomas+of+the+head+and+neck+revealed+by+the+use+of+laser+capture+microdissection+and+cDNA+arrays.&rft.au=Leethanakul%2C+C%3BPatel%2C+V%3BGillespie%2C+J%3BPallente%2C+M%3BEnsley%2C+J+F%3BKoontongkaew%2C+S%3BLiotta%2C+L+A%3BEmmert-Buck%2C+M%3BGutkind%2C+J+S&rft.aulast=Leethanakul&rft.aufirst=C&rft.date=2000-06-29&rft.volume=19&rft.issue=28&rft.spage=3220&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/10.1080%2F10643380802451946 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-17 N1 - Date created - 2000-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The indolocarbazole Gö6976 protects neurons from lipopolysaccharide/interferon-gamma-induced cytotoxicity in murine neuron/glia co-cultures. AN - 71269591; 10925141 AB - The expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) after exposure to endotoxins has been implicated in immune-mediated neurotoxicity. The indolocarbazole compound Gö6976, which has been described as a selective protein kinase C (PKC) inhibitor in vitro, rescued neurons from lipopolysaccharide/interferon-gamma (LPS/IFNgamma)- or interleukin-1alpha/tumor necrosis alpha/IFNgamma (IL-1alpha/TNFalpha/IFNgamma)-induced cytotoxicity in murine primary neuron-glia co-cultures. Other compounds known to inhibit PKC, Ro31-8220, GF109203X, Gö7874, H7, staurosporine and H89, failed to rescue neurons from the LPS/IFNgamma-induced cytotoxicity. These results suggest that the neuroprotection by Gö6976 from the LPS/IFNgamma-induced neuronal cell death is not mediated through its reputed effects on PKC activity. The neuroprotection paralleled the inhibition of iNOS gene expression and NO production. However, further analyses correlating NO production with the extent of neurotoxicity suggested that additional mechanism(s) besides the inhibition of the iNOS/NO system may be responsible for the neuroprotective effects of Gö6976. An understanding of the mechanism underlying the neuroprotective effect of Gö6976 may provide key insights into potential interventions for immune-mediated neurodegenerative diseases. JF - Brain research. Molecular brain research AU - Jeohn, G H AU - Wilson, B AU - Wetsel, W C AU - Hong, J S AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27709, USA. Y1 - 2000/06/23/ PY - 2000 DA - 2000 Jun 23 SP - 32 EP - 44 VL - 79 IS - 1-2 SN - 0169-328X, 0169-328X KW - Carbazoles KW - 0 KW - Indoles KW - Interleukin-1 KW - Lipopolysaccharides KW - Microtubule-Associated Proteins KW - Neural Cell Adhesion Molecules KW - Neuroprotective Agents KW - Recombinant Proteins KW - Tumor Necrosis Factor-alpha KW - Go 6976 KW - 136194-77-9 KW - Interferon-gamma KW - 82115-62-6 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Nitric Oxide Synthase Type II KW - Nos2 protein, mouse KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Coculture Techniques KW - Interleukin-1 -- pharmacology KW - Neural Cell Adhesion Molecules -- analysis KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Recombinant Proteins -- toxicity KW - Tumor Necrosis Factor-alpha -- toxicity KW - Animals, Newborn KW - Microtubule-Associated Proteins -- analysis KW - Protein Kinase C -- antagonists & inhibitors KW - Nitric Oxide Synthase -- genetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Gene Expression Regulation KW - Neuroglia -- cytology KW - Cell Survival -- drug effects KW - Interferon-gamma -- toxicity KW - Neurons -- drug effects KW - Neurons -- cytology KW - Neurons -- physiology KW - Carbazoles -- pharmacology KW - Lipopolysaccharides -- toxicity KW - Indoles -- pharmacology KW - Neuroglia -- drug effects KW - Neuroglia -- physiology KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71269591?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research.+Molecular+brain+research&rft.atitle=The+indolocarbazole+G%C3%B66976+protects+neurons+from+lipopolysaccharide%2Finterferon-gamma-induced+cytotoxicity+in+murine+neuron%2Fglia+co-cultures.&rft.au=Jeohn%2C+G+H%3BWilson%2C+B%3BWetsel%2C+W+C%3BHong%2C+J+S&rft.aulast=Jeohn&rft.aufirst=G&rft.date=2000-06-23&rft.volume=79&rft.issue=1-2&rft.spage=32&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Molecular+brain+research&rft.issn=0169328X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-04 N1 - Date created - 2000-10-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Post-transcriptional inhibition of lipopolysaccharide-induced expression of inducible nitric oxide synthase by Gö6976 in murine microglia. AN - 71264437; 10925140 AB - Glia in the brain respond to various toxins with an increased expression of inducible nitric oxide synthase (iNOS) and an increased production of nitric oxide (NO). Here, we report that lipopolysaccharide (LPS)-induced expression of iNOS was down-regulated post-transcriptionally through the destabilization of iNOS mRNA by the indolocarbazole compound, Gö6976, in murine microglia. This Gö6976 effect is specific for iNOS since tumor necrosis factor alpha was unaffected by the compound. Interestingly, the post-transcriptional effects ascribed to Gö6976 were not observed with other inhibitors of protein kinase A, C (PKC), G, or protein tyrosine kinases. Instead, these kinases appear to affect the iNOS/NO system at the transcriptional level. In the past, Gö6976 has been reported to be a rather specific inhibitor of PKC in vitro. Results from our experiments, through prolonged treatment with phorbol esters and with the various PKC inhibitors including phorbol ester-insensitive PKC isotype inhibitor, suggest that the Gö6976-mediated post-transcriptional regulation of iNOS gene expression and NO production in microglia is not mediated through its reputed effects on PKC activity. Since the effects of various neurotoxins and certain neurodegenerative diseases may be manifested through alterations in the iNOS/NO system, post-transcriptional control of this system may represent a novel strategy for therapeutic intervention. JF - Brain research. Molecular brain research AU - Jeohn, G H AU - Chang, R C AU - Kim, W G AU - Wilson, B AU - Mohney, R P AU - Wetsel, W C AU - Hong, J S AD - Neuropharmacology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. jeohn@niehs.nih.gov Y1 - 2000/06/23/ PY - 2000 DA - 2000 Jun 23 SP - 18 EP - 31 VL - 79 IS - 1-2 SN - 0169-328X, 0169-328X KW - Carbazoles KW - 0 KW - Enzyme Inhibitors KW - Indoles KW - Lipopolysaccharides KW - Protein Kinase Inhibitors KW - RNA, Messenger KW - Go 6976 KW - 136194-77-9 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Nitric Oxide Synthase Type II KW - Nos2 protein, mouse KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Transcription, Genetic -- drug effects KW - Brain -- cytology KW - Mice KW - RNA, Messenger -- genetics KW - Reverse Transcriptase Polymerase Chain Reaction KW - Protein Kinase C -- metabolism KW - Brain -- enzymology KW - Cells, Cultured KW - Kinetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Neuroglia -- cytology KW - Neuroglia -- enzymology KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Nitric Oxide Synthase -- genetics KW - Lipopolysaccharides -- pharmacology KW - Carbazoles -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Indoles -- pharmacology KW - RNA Processing, Post-Transcriptional -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71264437?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research.+Molecular+brain+research&rft.atitle=Post-transcriptional+inhibition+of+lipopolysaccharide-induced+expression+of+inducible+nitric+oxide+synthase+by+G%C3%B66976+in+murine+microglia.&rft.au=Jeohn%2C+G+H%3BChang%2C+R+C%3BKim%2C+W+G%3BWilson%2C+B%3BMohney%2C+R+P%3BWetsel%2C+W+C%3BHong%2C+J+S&rft.aulast=Jeohn&rft.aufirst=G&rft.date=2000-06-23&rft.volume=79&rft.issue=1-2&rft.spage=18&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Molecular+brain+research&rft.issn=0169328X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-04 N1 - Date created - 2000-10-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 3,4-Dihydroxyphenylacetaldehyde potentiates the toxic effects of metabolic stress in PC12 cells. AN - 71193411; 10854571 AB - 3,4-Dihydroxyphenylacetaldehyde (DOPAL) is a toxic metabolite formed by the oxidative deamination of dopamine. This aldehyde is mainly oxidized to 3,4-dihydroxyphenylacetic acid (DOPAC) by aldehyde dehydrogenase (ALDH), but is also partly reduced to 3, 4-dihydroxyphenylethanol (DOPET) by aldehyde or aldose reductase (ARs). In a previous study, we found that rotenone, a complex I inhibitor, induced a rapid accumulation of DOPAL and DOPET in the medium of cultured PC12 cells. Here, we examined the potential role of DOPAL in the toxicity induced by complex I inhibition in PC12 cells and compared the effects of rotenone on concentrations of DOPAL and DOPET to those of MPP(+). DOPAL and DOPET levels were increased by rotenone but decreased by MPP(+). Inhibition of ALDH by daidzein reduced the formation of DOPAC and increased the accumulation of DOPAL. Inhibition of ARs (with AL1576) diminished DOPET formation and elevated DOPAL concentrations. Combined inhibition of ALDH and ARs markedly elevated DOPAL concentrations while diminishing DOPET and DOPAC levels. The elevation of DOPAL levels induced by combined inhibition of ALDH and ARs had no effect on cell viability. However, combined inhibition of ALDH and ARs potentiated rotenone-induced toxicity. Both the potentiation of toxicity and the increase in DOPAL levels were blocked by inhibition of monoamine oxidase with clorgyline indicating that accumulation of DOPAL was responsible for the potentiated rotenone-induced toxicity following combined inhibition of ALDH and ARs. Since complex I dysfunction is reported to be involved in the pathogenesis of Parkinson's disease, DOPAL potentiation of the deleterious effects of complex I inhibition may contribute to the specific vulnerability of dopaminergic neurons to injury. JF - Brain research AU - Lamensdorf, I AU - Eisenhofer, G AU - Harvey-White, J AU - Nechustan, A AU - Kirk, K AU - Kopin, I J AD - Clinical Neuroscience Branch, NINDS, Building 10, Room 6N252, 10 Center Drive, MSC 1620, National Institutes of Health, Bethesda, MD 20892-1620, USA. lamensdo@helix.nih.gov Y1 - 2000/06/23/ PY - 2000 DA - 2000 Jun 23 SP - 191 EP - 201 VL - 868 IS - 2 SN - 0006-8993, 0006-8993 KW - Antioxidants KW - 0 KW - Enzyme Inhibitors KW - Estrogens, Non-Steroidal KW - Fluorenes KW - Hydantoins KW - Isoflavones KW - Rotenone KW - 03L9OT429T KW - 3,4-Dihydroxyphenylacetic Acid KW - 102-32-9 KW - 3,4-dihydroxyphenylethanol KW - 10597-60-1 KW - alconil KW - 4Z2DIE088U KW - 3,4-dihydroxyphenylacetaldehyde KW - 5707-55-1 KW - daidzein KW - 6287WC5J2L KW - Phenylethyl Alcohol KW - ML9LGA7468 KW - 1-Methyl-4-phenylpyridinium KW - R865A5OY8J KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Neurons -- metabolism KW - Oxidation-Reduction -- drug effects KW - Isoflavones -- pharmacology KW - Phenylethyl Alcohol -- analogs & derivatives KW - Neurons -- drug effects KW - Energy Metabolism -- physiology KW - Dopamine -- metabolism KW - Parkinson Disease -- physiopathology KW - Hydantoins -- pharmacology KW - Rotenone -- pharmacology KW - Rats KW - Fluorenes -- pharmacology KW - Antioxidants -- pharmacology KW - Phenylethyl Alcohol -- pharmacology KW - Energy Metabolism -- drug effects KW - Mitochondria -- drug effects KW - Mitochondria -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Estrogens, Non-Steroidal -- pharmacology KW - 1-Methyl-4-phenylpyridinium -- pharmacology KW - Oxidative Stress -- physiology KW - PC12 Cells -- metabolism KW - Oxidative Stress -- drug effects KW - PC12 Cells -- drug effects KW - 3,4-Dihydroxyphenylacetic Acid -- analogs & derivatives KW - 3,4-Dihydroxyphenylacetic Acid -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71193411?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=3%2C4-Dihydroxyphenylacetaldehyde+potentiates+the+toxic+effects+of+metabolic+stress+in+PC12+cells.&rft.au=Lamensdorf%2C+I%3BEisenhofer%2C+G%3BHarvey-White%2C+J%3BNechustan%2C+A%3BKirk%2C+K%3BKopin%2C+I+J&rft.aulast=Lamensdorf&rft.aufirst=I&rft.date=2000-06-23&rft.volume=868&rft.issue=2&rft.spage=191&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-18 N1 - Date created - 2000-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of xanthine derivatives on electroretinographic responsiveness. AN - 71192758; 10854570 AB - In view of the use of synthetic propentofylline (PPF) as a protective agent in brain ischemia, its possible side effects on vision capacities have been explored by electroretinography in comparative experiments with theophylline. We used eyecup preparations of small-spotted dogfish sharks and of European eels, particularly suitable for long-lasting experiments. The drug exerted profound but reversible modifications of ERG records: (1) a dose-dependent increase of the amplitude and duration of the chemically isolated late receptor potential (LRP), (2) a partial unmasking of LRP, (3) a strong potentiation of the LRP-unmasking effect of low temperature, (4) a potentiation of light adaptation effects, and (5) a strong potentiation of the post-illumination hyperexcitability. The effects were explicable as due to a strong phosphodiesterase (PDE) inhibiting, cyclic guanosine monophosphate (cGMP) promoting, action of the drug. The effects were considerably stronger, or even of opposite sign, in comparison to those of the chemically related theophylline. PPF did not seriously affect the ERG c-wave originating in the pigment epithelium. The results suggested that the effects of PPF on vision may not seriously hamper the therapeutic use of the drug. They indicated, on the other hand, that PPF was a retinoactive drug of potential usefulness in the exploration of the complex biochemical events underlying visual transduction. JF - Brain research AU - Andjus, R K AU - Konjević, D AU - Damjanović, I AU - Gacić, Z AD - Center for Multidisciplinary Studies, University of Belgrade, 29 Novembra 142, 11000, Belgrade, Yugoslavia. zgaga@helix.nih.gov Y1 - 2000/06/23/ PY - 2000 DA - 2000 Jun 23 SP - 176 EP - 190 VL - 868 IS - 2 SN - 0006-8993, 0006-8993 KW - Neuroprotective Agents KW - 0 KW - Xanthines KW - propentofylline KW - 5RTA398U4H KW - Theophylline KW - C137DTR5RG KW - Index Medicus KW - Theophylline -- adverse effects KW - Animals KW - Photic Stimulation KW - Photoreceptor Cells -- drug effects KW - Dogfish KW - Dose-Response Relationship, Drug KW - In Vitro Techniques KW - Anguilla KW - Body Temperature -- physiology KW - Photoreceptor Cells -- physiology KW - Adaptation, Ocular -- physiology KW - Electroretinography KW - Retina -- cytology KW - Xanthines -- adverse effects KW - Retina -- physiology KW - Retina -- drug effects KW - Neuroprotective Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71192758?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Effects+of+xanthine+derivatives+on+electroretinographic+responsiveness.&rft.au=Andjus%2C+R+K%3BKonjevi%C4%87%2C+D%3BDamjanovi%C4%87%2C+I%3BGaci%C4%87%2C+Z&rft.aulast=Andjus&rft.aufirst=R&rft.date=2000-06-23&rft.volume=868&rft.issue=2&rft.spage=176&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-18 N1 - Date created - 2000-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Probing the Escherichia coli Transcriptional Activator MarA using Alanine-scanning Mutagenesis: Residues Important for DNA Binding and Activation AN - 17555218; 4742897 AB - The MarA transcriptional activator binds to a 20 bp asymmetric degenerate sequence (marbox) located at different positions and orientations within the promoters of the genes of the Escherichia coli mar regulon. Solution of the MarA-marbox X-ray crystallographic structure suggested the presence of base-specific and non-specific interactions between the marbox and two helix-turn-helix (HTH) motifs on the monomeric MarA. Here, we use alanine-scanning mutagenesis and DNA retardation analysis to: (i) evaluate the contacts between MarA and the marboxes of five differently configured mar regulon promoters; (ii) assess the role of conserved hydrophobic amino acid residues for MarA activity; and (iii) identify residues required for RNA polymerase activation. These analyses revealed that the phosphate-backbone contacts and hydrogen bonds with the bases of the marbox are more significant for DNA binding than are the van der Waals interactions. While both N and C-terminal HTH motifs make essential contributions to binding site affinity, MarA is more sensitive to alterations in the N-terminal HTH. In a similar way, the activity of MarA is more sensitive to alterations in the hydrophobic core of this HTH. Solvent-exposed amino acid residues located at many positions on the MarA surface are important for activity. Some of these residues affect activity on all promoters and thus, are implicated in maintaining MarA structure whereas several solvent-exposed amino acids not involved in DNA binding were important for MarA activity on specific promoters. The pattern of activation defects defined a class II promoter-specific activating region. However, a localized class I activating region was not apparent. These results suggest that MarA activates transcription by at least two distinct mechanisms. Furthermore, the important role of phosphate contacts in marbox affinity suggests that indirect readout contributes to binding site recognition by MarA. JF - Journal of Molecular Biology AU - Gillette, W K 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, 20892-0560, MD, USA Y1 - 2000/06/23/ PY - 2000 DA - 2000 Jun 23 SP - 1245 EP - 1255 PB - Academic Press VL - 299 IS - 5 SN - 0022-2836, 0022-2836 KW - MarA protein KW - alanine scanning mutagenesis KW - mar genes KW - mar operon KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Transcription activators KW - Escherichia coli KW - J 02726:RNA and ribosomes KW - N 14930:Transcription factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17555218?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Probing+the+Escherichia+coli+Transcriptional+Activator+MarA+using+Alanine-scanning+Mutagenesis%3A+Residues+Important+for+DNA+Binding+and+Activation&rft.au=Gillette%2C+W+K%3BMartin%2C+R+G%3BRosner%2C+J+L&rft.aulast=Gillette&rft.aufirst=W&rft.date=2000-06-23&rft.volume=299&rft.issue=5&rft.spage=1245&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1006%2Fjmbi.2000.3827 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Transcription activators DO - http://dx.doi.org/10.1006/jmbi.2000.3827 ER - TY - JOUR T1 - Long nucleotide insertions between the HN and L protein coding regions of human parainfluenza virus type 3 yield viruses with temperature-sensitive and attenuation phenotypes. AN - 71220685; 10873765 AB - Recombinant parainfluenza virus 3 (rPIV3) is being developed as a vector to express foreign genes as a bivalent or multivalent live attenuated virus vaccine. In the present study, we examined the effect of inserted foreign sequence on virus replication in vitro and in vivo, focusing on the parameter of insert length. In one type of construct, foreign sequence of increasing length was flanked by PIV3 transcription signals and inserted as an additional gene unit (GU insert) between the HN and L genes, so that one additional mRNA would be made. In a second type of construct, foreign sequence was inserted into the downstream NCR (NCR insert) of the HN gene, so that the number of encoded mRNAs remained unchanged. In each case, the foreign sequence was designed to lack any significant open reading frame, which permitted an evaluation of the effect of insert length on replication independent of an effect of an expressed protein. The GU or NCR insert sizes ranged from 168 nucleotides (nt) to 3918 nt. rPIV3s containing GU insertions of up to 3918 nt in length, the largest size tested, were viable and replicated efficiently at permissive temperatures in vitro, but a reduction in plaque size was seen at 39 degrees C and 40 degrees C. The rPIV3 with a 3918-nt GU insertion was restricted in replication in the upper (fivefold) and lower (25-fold) respiratory tracts of hamsters. Although a 1908-nt GU insertion did not significantly modify replication of wild-type PIV3 in vitro or in vivo, its introduction significantly augmented the level of temperature sensitivity (ts) and attenuation (att) specified by three mutations in the L protein of a cold-passaged attenuated PIV3 vaccine virus. rPIV3s bearing a 3126- or 3894-nt NCR insertion exhibited in vitro and in vivo phenotypes like those of the rPIV3s bearing similar-sized GU insertions. These findings indicate that rPIV3s whose genome length has been increased by more than 3000 nt by either a GU or an NCR insertion exhibit an unexpected host-range phenotype, that is, efficient replication in vitro but restricted replication in hamsters, especially in the lower respiratory tract. Furthermore, these effects were greatly enhanced when the rPIV3 backbone contained other ts or att mutations. The implications of these findings for the use of single-stranded, negative-sense RNA viruses as vectors for vaccines are discussed. Copyright 2000 Academic Press. JF - Virology AU - Skiadopoulos, M H AU - Surman, S R AU - Durbin, A P AU - Collins, P L AU - Murphy, B R AD - Respiratory Viruses Section, Bethesda, Maryland 20892, USA. mskiadopoulos@niad.nih.gov Y1 - 2000/06/20/ PY - 2000 DA - 2000 Jun 20 SP - 225 EP - 234 VL - 272 IS - 1 SN - 0042-6822, 0042-6822 KW - HN Protein KW - 0 KW - Nucleotides KW - RNA, Viral KW - Viral Proteins KW - Viral Vaccines KW - parainfluenza 3 virus, L Protein KW - Index Medicus KW - Animals KW - Viral Plaque Assay KW - Viral Vaccines -- genetics KW - Temperature KW - Genome, Viral KW - Respirovirus Infections -- virology KW - Molecular Weight KW - Phenotype KW - Virus Replication -- genetics KW - Base Sequence KW - Respiratory System -- virology KW - Molecular Sequence Data KW - Mesocricetus KW - Genetic Vectors -- genetics KW - RNA, Viral -- genetics KW - Cell Line KW - Cricetinae KW - Viral Proteins -- genetics KW - Nucleotides -- genetics KW - HN Protein -- genetics KW - Parainfluenza Virus 3, Human -- genetics KW - Parainfluenza Virus 3, Human -- physiology KW - Mutagenesis, Insertional -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71220685?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virology&rft.atitle=Long+nucleotide+insertions+between+the+HN+and+L+protein+coding+regions+of+human+parainfluenza+virus+type+3+yield+viruses+with+temperature-sensitive+and+attenuation+phenotypes.&rft.au=Skiadopoulos%2C+M+H%3BSurman%2C+S+R%3BDurbin%2C+A+P%3BCollins%2C+P+L%3BMurphy%2C+B+R&rft.aulast=Skiadopoulos&rft.aufirst=M&rft.date=2000-06-20&rft.volume=272&rft.issue=1&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-19 N1 - Date created - 2000-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selenium-dependent metabolism of purines: A selenium-dependent purine hydroxylase and xanthine dehydrogenase were purified from Clostridium purinolyticum and characterized AN - 17615630; 4760391 AB - During purification of the selenium- dependent xanthine dehydrogenase (XDH) from Clostridium purinolyticum, another hydroxylase was uncovered that also contained selenium and exhibited similar spectral properties. This enzyme was purified to homogeneity. It uses purine, 2OH-purine, and hypoxanthine as substrates, and based on its substrate specificity, this selenoenzyme is termed purine hydroxylase (PH). The product of hydroxylation of purine by PH is xanthine. A concomitant release of selenium from the enzyme and loss of catalytic activity on treatment with cyanide indicates that selenium is essential for PH activity. Selenium-dependent XDH, also purified from C. purinolyticum, was found to be insensitive to oxygen during purification and to use both potassium ferricyanide and 2,6-dichloroindophenol as electron acceptors. Selenium is required for the xanthine-dependent reduction of 2,6- dichloroindophenol by XDH. Kinetic analyses of both enzymes revealed that xanthine is the preferred substrate for XDH and purine and hypoxanthine are preferred by PH. This characterization of these selenium-requiring hydroxylases involved in the interconversion of purines describes an extension of the pathway for purine fermentation in the purinolytic clostridia. JF - Proceedings of the National Academy of Sciences, USA AU - Self, W T AU - Stadtman, T C AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, tcstadtman@nhlbi.nih.gov Y1 - 2000/06/20/ PY - 2000 DA - 2000 Jun 20 SP - 7208 EP - 7213 VL - 97 IS - 13 SN - 0027-8424, 0027-8424 KW - 2,6-dichloroindophenol KW - purine hydroxylase KW - purines KW - xanthine KW - Microbiology Abstracts B: Bacteriology KW - Selenium KW - Fermentation KW - Xanthine dehydrogenase KW - Clostridium purinolyticum KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17615630?accountid=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=Selenium-dependent+metabolism+of+purines%3A+A+selenium-dependent+purine+hydroxylase+and+xanthine+dehydrogenase+were+purified+from+Clostridium+purinolyticum+and+characterized&rft.au=Self%2C+W+T%3BStadtman%2C+T+C&rft.aulast=Self&rft.aufirst=W&rft.date=2000-06-20&rft.volume=97&rft.issue=13&rft.spage=7208&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.97.13.7208 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Clostridium purinolyticum; Selenium; Xanthine dehydrogenase; Fermentation DO - http://dx.doi.org/10.1073/pnas.97.13.7208 ER - TY - JOUR T1 - 6-[18F]fluoro-A-85380, a novel radioligand for in vivo imaging of central nicotinic acetylcholine receptors. AN - 72285541; 11003056 AB - A novel positron emission tomography (PET) radiotracer, 6-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[18F]fluoro-A-85380, 6-[18F]FA) was synthesized by a no-carrier-added fluorination. In vitro 6-[18F]FA bound to nicotinic acetylcholine receptors (nAChRs), with very high affinity (Kd 28 pM). In PET studies, 6-[18F]FA specifically labeled central nAChRs in the brain of the Rhesus monkey and demonstrated highest levels of accumulation of radioactivity in brain regions enriched with the alpha4beta2 subtype of nAChR. 6-[18F]FA exhibited a target-to-non-target ratio (estimated as radioactivity in the thalamus to that in the cerebellum) of binding in primate brain similar to that previously determined for a labeled analog of epibatidine, [18F]FPH. In contrast to [18F]FPH, the novel tracer is expected to exhibit substantially less toxicity. Thus, the novel radioligand, 6-[18F]FA, appears to be a suitable candidate for imaging nAChRs in human brain. JF - Life sciences AU - Horti, A G AU - Chefer, S I AU - Mukhin, A G AU - Koren, A O AU - Gündisch, D AU - Links, J M AU - Kurian, V AU - Dannals, R F AU - London, E D AD - Brain Imaging Center, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 2000/06/16/ PY - 2000 DA - 2000 Jun 16 SP - 463 EP - 469 VL - 67 IS - 4 SN - 0024-3205, 0024-3205 KW - A 85380 KW - 0 KW - Azetidines KW - Fluorine Radioisotopes KW - Receptors, Nicotinic KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Macaca mulatta KW - Tissue Distribution KW - Male KW - Chromatography, High Pressure Liquid KW - Azetidines -- chemical synthesis KW - Receptors, Nicotinic -- analysis KW - Tomography, Emission-Computed KW - Brain -- metabolism KW - Brain -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72285541?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=6-%5B18F%5Dfluoro-A-85380%2C+a+novel+radioligand+for+in+vivo+imaging+of+central+nicotinic+acetylcholine+receptors.&rft.au=Horti%2C+A+G%3BChefer%2C+S+I%3BMukhin%2C+A+G%3BKoren%2C+A+O%3BG%C3%BCndisch%2C+D%3BLinks%2C+J+M%3BKurian%2C+V%3BDannals%2C+R+F%3BLondon%2C+E+D&rft.aulast=Horti&rft.aufirst=A&rft.date=2000-06-16&rft.volume=67&rft.issue=4&rft.spage=463&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 - 2000-10-05 N1 - Date created - 2000-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The HIV-1 cell entry inhibitor T-20 potently chemoattracts neutrophils by specifically activating the N-formylpeptide receptor. AN - 71195836; 10860818 AB - T-20, a synthetic peptide corresponding to the heptad repeat sequence of HIV-1 gp41, blocks HIV-1 entry by targeting gp41, and is currently in clinical trials as an anti-retroviral agent. We recently reported that in vitro T-20 also functions as a phagocyte chemoattractant and a chemotactic agonist at the phagocyte N-formylpeptide receptor (FPR). Here we show that T-20 is also a potent chemotactic agonist in vitro at a related human phagocyte receptor FPRL1R. To test the relative importance of FPR and FPRL1R in primary cells, we identified the corresponding mouse T-20 receptors, mFPR and FPR2, which are both expressed in neutrophils, and compared T-20 action on neutrophils from wild type and mFPR knockout mice. Surprisingly, although T-20 activates mFPR and FPR2 in transfected cells with equal potency and efficacy in both calcium flux and chemotaxis assays, neutrophils from mFPR knockout mice did not respond to T-20. These results provide genetic evidence that FPR is the major phagocyte T-20 receptor in vivo and point to the potential feasibility of studying T-20 effects on immunity in a mouse model. This may help define the cause of local inflammation after T-20 injection that has recently been reported in Phase I clinical trials. Copyright 2000 Academic Press. JF - Biochemical and biophysical research communications AU - Hartt, J K AU - Liang, T AU - Sahagun-Ruiz, A AU - Wang, J M AU - Gao, J L AU - Murphy, P M AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2000/06/16/ PY - 2000 DA - 2000 Jun 16 SP - 699 EP - 704 VL - 272 IS - 3 SN - 0006-291X, 0006-291X KW - Anti-HIV Agents KW - 0 KW - HIV Envelope Protein gp41 KW - Peptide Fragments KW - Receptors, Formyl Peptide KW - Receptors, Immunologic KW - Receptors, Peptide KW - enfuvirtide KW - 19OWO1T3ZE KW - N-Formylmethionine Leucyl-Phenylalanine KW - 59880-97-6 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Dose-Response Relationship, Drug KW - Humans KW - Inflammation -- chemically induced KW - Mice KW - Mice, Knockout KW - Calcium -- metabolism KW - N-Formylmethionine Leucyl-Phenylalanine -- pharmacology KW - Multigene Family -- genetics KW - Calcium Signaling -- drug effects KW - Transfection KW - Cell Line KW - Anti-HIV Agents -- chemistry KW - HIV Envelope Protein gp41 -- adverse effects KW - Receptors, Immunologic -- agonists KW - Neutrophil Activation -- drug effects KW - Neutrophils -- cytology KW - Receptors, Peptide -- metabolism KW - Chemotaxis, Leukocyte -- drug effects KW - Peptide Fragments -- adverse effects KW - Neutrophils -- immunology KW - Anti-HIV Agents -- adverse effects KW - Neutrophil Activation -- immunology KW - Receptors, Immunologic -- genetics KW - Neutrophils -- metabolism KW - Neutrophils -- drug effects KW - Peptide Fragments -- chemistry KW - Receptors, Immunologic -- metabolism KW - Anti-HIV Agents -- pharmacology KW - Peptide Fragments -- pharmacology KW - Chemotaxis, Leukocyte -- immunology KW - Receptors, Peptide -- deficiency KW - Receptors, Peptide -- genetics KW - Receptors, Peptide -- agonists KW - HIV Envelope Protein gp41 -- pharmacology KW - Receptors, Immunologic -- deficiency KW - HIV Envelope Protein gp41 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71195836?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+HIV-1+cell+entry+inhibitor+T-20+potently+chemoattracts+neutrophils+by+specifically+activating+the+N-formylpeptide+receptor.&rft.au=Hartt%2C+J+K%3BLiang%2C+T%3BSahagun-Ruiz%2C+A%3BWang%2C+J+M%3BGao%2C+J+L%3BMurphy%2C+P+M&rft.aulast=Hartt&rft.aufirst=J&rft.date=2000-06-16&rft.volume=272&rft.issue=3&rft.spage=699&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 - 2000-07-26 N1 - Date created - 2000-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estimating the Number of Protein Folds and Families from Complete Genome Data AN - 17540774; 4723499 AB - Using the data on proteins encoded in complete genomes, combined with a rigorous theory of the sampling process, we estimate the total number of protein folds and families, as well as the number of folds and families in each genome. The total number of folds in globular, water- soluble proteins is estimated at about 1000, with structural information currently available for about one-third of that number. The sequenced genomes of unicellular organisms encode from approximately 25 %, for the minimal genomes of the Mycoplasmas, to 70-80 % for larger genomes, such as Escherichia coli and yeast, of the total number of folds. The number of protein families with significant sequence conservation was estimated to be between 4000 and 7000, with structures available for about 20 % of these. JF - Journal of Molecular Biology AU - Wolf, YI AU - Grishin, N V AU - Koonin, E V AD - National Center for Biotechnology Information National Library of Medicine, National Institutes of Health, Bethesda, 20894, MD, USA Y1 - 2000/06/16/ PY - 2000 DA - 2000 Jun 16 SP - 897 EP - 905 PB - Academic Press VL - 299 IS - 4 SN - 0022-2836, 0022-2836 KW - protein folds KW - protein families KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Nucleotide sequence KW - Escherichia coli KW - Proteins KW - Mycoplasma KW - Amino acid sequence KW - G 07320:Bacterial genetics KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17540774?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Estimating+the+Number+of+Protein+Folds+and+Families+from+Complete+Genome+Data&rft.au=Wolf%2C+YI%3BGrishin%2C+N+V%3BKoonin%2C+E+V&rft.aulast=Wolf&rft.aufirst=YI&rft.date=2000-06-16&rft.volume=299&rft.issue=4&rft.spage=897&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1006%2Fjmbi.2000.3786 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Mycoplasma; Nucleotide sequence; Proteins; Amino acid sequence DO - http://dx.doi.org/10.1006/jmbi.2000.3786 ER - TY - JOUR T1 - Poor compensatory function for sleep loss as a pathogenic factor in patients with delayed sleep phase syndrome. AN - 71216729; 10875562 AB - Delayed sleep phase syndrome (DSPS) is a condition in which the patient is unable to reset or phase-advance his/her sleep timing properly after transient sleep delay and consequently shows persistent sleep phase delay. Prior studies suggested that DSPS is associated with a phase delay in the circadian pacemaker, but there was no evidence to explain the patient's inability to reset sleep phase. We used an ultra-short sleep-wake schedule together with simultaneous measurement of dim light melatonin rhythm after 24-hour sleep deprivation to allow the differential observation of diurnal sleep propensity fluctuation both from circadian and homeostatic aspects in 11 patients with DSPS (17-37 years; 8 men, 3 women) and 15 healthy controls (19-32 years; 8 men, 7 women). NA. NA. NA. DSPS patients showed less ability to compensate for previous sleep loss during their circadian day and first hours of their circadian nighttime determined by dim light melatonin onset compared with controls, while controls compensated for previous sleep loss at most circadian times. Though shapes of dim light melatonin rhythm did not differ between the groups, phase angle between melatonin and sleep propensity rhythms was wider in DSPS patients than in controls. These findings suggest that poor compensatory function for sleep loss predisposes DSPS patients to failure to reset their sleep phase. Our results provide implications for understanding not only the pathophysiology of DSPS but also the biological basis for why some people can change their sleep schedule easily according to personal or social demands while others cannot. JF - Sleep AU - Uchiyama, M AU - Okawa, M AU - Shibui, K AU - Liu, X AU - Hayakawa, T AU - Kamei, Y AU - Takahashi, K AD - Department of Psychophysiology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Ichikawa, Japan. macoto@ncnp-k.go.jp Y1 - 2000/06/15/ PY - 2000 DA - 2000 Jun 15 SP - 553 EP - 558 VL - 23 IS - 4 SN - 0161-8105, 0161-8105 KW - Melatonin KW - JL5DK93RCL KW - Index Medicus KW - Severity of Illness Index KW - Melatonin -- blood KW - Humans KW - Adult KW - Body Temperature -- physiology KW - Adolescent KW - Time Factors KW - Male KW - Female KW - Sleep Disorders, Circadian Rhythm -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71216729?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Sleep&rft.atitle=Poor+compensatory+function+for+sleep+loss+as+a+pathogenic+factor+in+patients+with+delayed+sleep+phase+syndrome.&rft.au=Uchiyama%2C+M%3BOkawa%2C+M%3BShibui%2C+K%3BLiu%2C+X%3BHayakawa%2C+T%3BKamei%2C+Y%3BTakahashi%2C+K&rft.aulast=Uchiyama&rft.aufirst=M&rft.date=2000-06-15&rft.volume=23&rft.issue=4&rft.spage=553&rft.isbn=&rft.btitle=&rft.title=Sleep&rft.issn=01618105&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-18 N1 - Date created - 2000-10-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The lyase activity of the DNA repair protein beta-polymerase protects from DNA-damage-induced cytotoxicity. AN - 71201182; 10866204 AB - Small DNA lesions such as oxidized or alkylated bases are repaired by the base excision repair (BER) pathway. BER includes removal of the damaged base by a lesion-specific DNA glycosylase, strand scission by apurinic/apyrimidinic endonuclease, DNA resynthesis and ligation. BER may be further subdivided into DNA beta-polymerase (beta-pol)-dependent single-nucleotide repair and beta-pol-dependent or -independent long patch repair subpathways. Two important enzymatic steps in mammalian single-nucleotide BER are contributed by beta-pol: DNA resynthesis of the repair patch and lyase removal of 5'-deoxyribose phosphate (dRP). Fibroblasts from beta-pol null mice are hypersensitive to mono-functional DNA-methylating agents, resulting in increases in chromosomal damage, apoptosis and necrotic cell death. Here we show that only the dRP lyase activity of beta-pol is required to reverse methylating agent hypersensitivity in beta-pol null cells. These results indicate that removal of the dRP group is a pivotal step in BER in vivo. Persistence of the dRP moiety in DNA results in the hypersensitivity phenotype of beta-pol null cells and may signal downstream events such as apoptosis and necrotic cell death. JF - Nature AU - Sobol, R W AU - Prasad, R AU - Evenski, A AU - Baker, A AU - Yang, X P AU - Horton, J K AU - Wilson, S H AD - Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709-2233, USA. Y1 - 2000/06/15/ PY - 2000 DA - 2000 Jun 15 SP - 807 EP - 810 VL - 405 IS - 6788 SN - 0028-0836, 0028-0836 KW - Mutagens KW - 0 KW - Deoxyribose KW - 533-67-5 KW - DNA KW - 9007-49-2 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - DNA Polymerase beta KW - EC 2.7.7.- KW - Lyases KW - EC 4.- KW - Index Medicus KW - DNA Methylation KW - Transfection KW - Deoxyribose -- metabolism KW - Cell Line, Transformed KW - Cell Line KW - Methyl Methanesulfonate -- toxicity KW - DNA Repair KW - DNA Damage KW - DNA -- metabolism KW - Mutagens -- toxicity KW - DNA -- biosynthesis KW - DNA Polymerase beta -- metabolism KW - Lyases -- metabolism KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71201182?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=The+lyase+activity+of+the+DNA+repair+protein+beta-polymerase+protects+from+DNA-damage-induced+cytotoxicity.&rft.au=Sobol%2C+R+W%3BPrasad%2C+R%3BEvenski%2C+A%3BBaker%2C+A%3BYang%2C+X+P%3BHorton%2C+J+K%3BWilson%2C+S+H&rft.aulast=Sobol&rft.aufirst=R&rft.date=2000-06-15&rft.volume=405&rft.issue=6788&rft.spage=807&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-07 N1 - Date created - 2000-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Distinct patterns of behavioural impairments resulting from fornix transection or neurotoxic lesions of the perirhinal and postrhinal cortices in the rat. AN - 71163511; 10840144 AB - The present study provides evidence that lesions of the fornix (FNX) and of the perirhinal/postrhinal cortex (PPRH), which both disconnect the hippocampus from other brain regions, can lead to distinct patterns of behavioural impairments on tests of spatial memory and spontaneous object recognition. For example, whereas FNX lesions impaired allocentric spatial delayed alternation in a T-maze but generally spared a test of spontaneous object recognition, PPRH lesions produced the opposite pattern of results. Indeed, on the T-maze task PPRH animals significantly outperformed controls when the retention delay was increased to 60 s. In addition, some evidence was found that contributions from both the fornix and perirhinal/postrhinal cortex may be required when object and spatial information must be integrated. In an object-in-place test, for example, PPRH animals failed according to two measures, and FNX animals failed according to one measure, to discriminate objects that had remained in fixed locations from those that had exchanged locations with other objects. Neither lesion, however, affected performance of a visuospatial conditional task, a Pavlovian autoshaping task, or a one-pair pattern discrimination task. It is suggested that the perirhinal/postrhinal cortex, rather than being specialised for a particular type of associative learning, is important for processing complex visual stimuli. JF - Behavioural brain research AU - Bussey, T J AU - Duck, J AU - Muir, J L AU - Aggleton, J P AD - School of Psychology, Cardiff University, CF1O 3YG, Cardiff, UK. bussey@in.nimh.nih.gov Y1 - 2000/06/15/ PY - 2000 DA - 2000 Jun 15 SP - 187 EP - 202 VL - 111 IS - 1-2 SN - 0166-4328, 0166-4328 KW - Index Medicus KW - Retention (Psychology) -- physiology KW - Rats, Inbred Strains KW - Rats KW - Animals KW - Discrimination Learning -- physiology KW - Brain Mapping KW - Hippocampus -- physiology KW - Maze Learning -- physiology KW - Motor Activity -- physiology KW - Male KW - Orientation -- physiology KW - Temporal Lobe -- physiology KW - Olfactory Pathways -- physiology KW - Mental Recall -- physiology KW - Fornix, Brain -- physiology KW - Pattern Recognition, Visual -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71163511?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Behavioural+brain+research&rft.atitle=Distinct+patterns+of+behavioural+impairments+resulting+from+fornix+transection+or+neurotoxic+lesions+of+the+perirhinal+and+postrhinal+cortices+in+the+rat.&rft.au=Bussey%2C+T+J%3BDuck%2C+J%3BMuir%2C+J+L%3BAggleton%2C+J+P&rft.aulast=Bussey&rft.aufirst=T&rft.date=2000-06-15&rft.volume=111&rft.issue=1-2&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Behavioural+brain+research&rft.issn=01664328&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-10 N1 - Date created - 2000-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 6S RNA Regulates E. coli RNA Polymerase Activity AN - 17621448; 4758844 AB - The E. coli 6S RNA was discovered more than three decades ago, yet its function has remained elusive. Here, we demonstrate that 6S RNA associates with RNA polymerase in a highly specific and efficient manner. UV crosslinking experiments revealed that 6S RNA directly contacts the sigma super(70) and beta / beta ' subunits of RNA polymerase. 6S RNA accumulates as cells reach the stationary phase of growth and mediates growth phase-specific changes in RNA polymerase. Stable association between sigma super(70) and core RNA polymerase in extracts is only observed in the presence of 6S RNA. We show 6S RNA represses expression from a sigma super(70)-dependent promoter during stationary phase. Our results suggest that the interaction of 6S RNA with RNA polymerase modulates sigma super(70)-holoenzyme activity. JF - Cell AU - Wassarman, K M AU - Storz, G AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA, kwass@box-k.nih.gov Y1 - 2000/06/09/ PY - 2000 DA - 2000 Jun 09 SP - 613 EP - 623 VL - 101 IS - 6 SN - 0092-8674, 0092-8674 KW - RNA 6S KW - sigma 70 factor KW - sigma super(70) factor KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - s70 factor KW - ^s@@u70@ factor KW - DNA-directed RNA polymerase KW - Escherichia coli KW - N 14721:RNA polymerases KW - J 02726:RNA and ribosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17621448?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell&rft.atitle=6S+RNA+Regulates+E.+coli+RNA+Polymerase+Activity&rft.au=Wassarman%2C+K+M%3BStorz%2C+G&rft.aulast=Wassarman&rft.aufirst=K&rft.date=2000-06-09&rft.volume=101&rft.issue=6&rft.spage=613&rft.isbn=&rft.btitle=&rft.title=Cell&rft.issn=00928674&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA-directed RNA polymerase ER - TY - JOUR T1 - Annexin V inhibits the 12-O-tetradecanoylphorbol-13-acetate-induced activation of Ras/extracellular signal-regulated kinase (ERK) signaling pathway upstream of Shc in MCF-7 cells. AN - 71222815; 10871841 AB - Annexin V is a Ca2+-dependent phospholipid binding protein. Although it has been shown to inhibit protein kinase C (PKC) in cell-free systems, its role in the intact cell is unclear. A stable MCF-7 human breast cancer cell overexpression system was established to investigate the function of annexin V. In these cells, 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced phosphorylation and kinase activity of ERK1/2 were suppressed. Morphological changes induced by TPA were reduced by annexin V overexpression as well as by the pan-PKC inhibitor, bisindolylmaleimide I, and by the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) inhibitor, PD98059. TPA-induced MEK1/2 and Raf-1 phosphorylation were reduced in these cells. The TPA-enhanced active Ras, and its association with Raf-1, were reduced. TPA treatment of MCF-7 cells caused an increased association of Shc with Grb2. However, this increased association was prevented in the annexin V-overexpressors. p21WAF/CIP1 is responsible for inhibition of cell cycle progression in MCF-7 cells. TPA induced the expression of p21WAF/CIP1 to a greater extent in MCF-7 parent and control plasmid cells than in annexin V overexpressors. PD98059 inhibited this increase, suggesting that TPA upregulation of p21WAF/CIP1 occurs via the MEK pathway, and that annexin V overexpression blunts it. This work shows that annexin V overexpression suppresses the TPA-induced Ras/ERK signaling by inhibiting at/or upstream of Shc, possibly through the inhibition of PKCs. Oncogene (2000). JF - Oncogene AU - Sato, H AU - Ogata, H AU - De Luca, L M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institute of Health, Bethesda, Maryland, MD 20892-4255, USA. Y1 - 2000/06/08/ PY - 2000 DA - 2000 Jun 08 SP - 2904 EP - 2912 VL - 19 IS - 25 SN - 0950-9232, 0950-9232 KW - Annexin A5 KW - 0 KW - CDKN1A protein, human KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Enzyme Inhibitors KW - Protein Kinase C KW - EC 2.7.11.13 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Protein Kinase C -- antagonists & inhibitors KW - Tumor Cells, Cultured KW - Phosphorylation KW - Humans KW - Enzyme Inhibitors -- pharmacology KW - Cyclins -- metabolism KW - Mitogen-Activated Protein Kinases -- metabolism KW - Signal Transduction -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Annexin A5 -- pharmacology KW - Tetradecanoylphorbol Acetate -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71222815?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Annexin+V+inhibits+the+12-O-tetradecanoylphorbol-13-acetate-induced+activation+of+Ras%2Fextracellular+signal-regulated+kinase+%28ERK%29+signaling+pathway+upstream+of+Shc+in+MCF-7+cells.&rft.au=Sato%2C+H%3BOgata%2C+H%3BDe+Luca%2C+L+M&rft.aulast=Sato&rft.aufirst=H&rft.date=2000-06-08&rft.volume=19&rft.issue=25&rft.spage=2904&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-12 N1 - Date created - 2000-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Delayed-type hypersensitivity to Phlebotomus papatasi sand fly bite: An adaptive response induced by the fly? AN - 71187259; 10841567 AB - The saliva of bloodsucking arthropods contains a large array of pharmacologically active compounds that assist hematophagy. Arthropod saliva is also responsible for causing uncomfortable allergic responses in its vertebrate hosts. In this article, we investigate whether the sand fly Phlebotomus papatasi, known to produce a strong delayed-type hypersensitivity (DTH) in humans, could benefit from, and possibly adaptively induce, this response in their vertebrate hosts. In this study, we show that flies fed on humans to completion nearly twice as fast in DTH sites as compared with normal skin sites. DTH sites had significantly larger blood flow as measured by the laser Doppler method. Sand flies feeding at sites in mouse ears that had a DTH response also fed faster than at normal sites. We conclude that in the case of P. papatasi, and possibly other arthropods such as fleas and bed bugs, the strong saliva-induced DTH response may reflect an adaptation of the fly to manipulate host immunity for the insect's own advantage. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Belkaid, Y AU - Valenzuela, J G AU - Kamhawi, S AU - Rowton, E AU - Sacks, D L AU - Ribeiro, J M AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Building 4, Room 126, 4 Center Drive, MSC-425, Bethesda, MD 20892-0425, USA. Y1 - 2000/06/06/ PY - 2000 DA - 2000 Jun 06 SP - 6704 EP - 6709 VL - 97 IS - 12 SN - 0027-8424, 0027-8424 KW - Index Medicus KW - Animals KW - Humans KW - Insect Vectors KW - Adult KW - Mice, Inbred C57BL KW - CD4-Positive T-Lymphocytes -- immunology KW - Mice KW - Mice, Inbred BALB C KW - Feeding Behavior KW - Skin -- blood supply KW - Regional Blood Flow KW - Female KW - Insect Bites and Stings -- immunology KW - Hypersensitivity, Delayed -- etiology KW - Phlebotomus -- physiology KW - Hypersensitivity, Delayed -- physiopathology KW - Adaptation, Physiological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71187259?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Delayed-type+hypersensitivity+to+Phlebotomus+papatasi+sand+fly+bite%3A+An+adaptive+response+induced+by+the+fly%3F&rft.au=Belkaid%2C+Y%3BValenzuela%2C+J+G%3BKamhawi%2C+S%3BRowton%2C+E%3BSacks%2C+D+L%3BRibeiro%2C+J+M&rft.aulast=Belkaid&rft.aufirst=Y&rft.date=2000-06-06&rft.volume=97&rft.issue=12&rft.spage=6704&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 - 2000-07-13 N1 - Date created - 2000-07-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc R Soc Lond B Biol Sci. 1967 Mar 28;167(1008):316-29 [4382782] Nature. 1946 Oct 19;158(4016):554 [21001941] Annu Rev Entomol. 1982;27:21-48 [6123290] J Med Entomol. 1983 Oct 5;20(5):568-9 [6644754] Annu Rev Entomol. 1987;32:463-78 [2880553] Infect Immun. 1991 May;59(5):1592-8 [2019430] Arch Dermatol. 1992 Feb;128(2):272-3 [1739312] Parasite Immunol. 1993 Aug;15(8):481-7 [8233563] Int J Parasitol. 1994 Feb;24(1):59-66 [8021108] J Immunol. 1995 Oct 1;155(7):3501-6 [7561045] Infect Agents Dis. 1995 Sep;4(3):143-52 [8548192] Annu Rev Entomol. 1996;41:1-22 [8546443] J Immunol. 1998 Feb 15;160(4):1811-6 [9469441] Infect Immun. 1998 Apr;66(4):1534-7 [9529078] J Exp Med. 1998 Nov 16;188(10):1941-53 [9815271] Perspect Biol Med. 1974 Winter;17(2):233-9 [4273175] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure and promoter analysis of the human unc-33-like phosphoprotein gene. E-box required for maximal expression in neuroblastoma and myoblasts. AN - 71141827; 10748015 AB - The human unc-33-like phosphoprotein (hUlip/CRMP-4) is a member of a family of developmentally regulated genes that are highly expressed in the nervous system. Mutations in the C. elegans unc-33 gene lead to worms with abnormal movements. The hUlip gene encodes a 570-amino acid protein with 98% homology to its murine (Ulip) (Byk, T., Dobransky, T., Cifuentes-Diaz, C., and Sobel, A. (1996) J. Neurosci. 16, 688-701) and rat (CRMP-4) (Wang, L. H., and Strittmatter, S. M. (1996) J. Neurosci. 16, 6197-6207) counterparts (Gaetano, C., Matsuo, T., and Thiele, C. J. (1997) J. Biol. Chem. 272, 12195-12201). The hUlip gene was isolated from a human genomic library. It contains 15 exons, including an exon defined by an anaplastic oligodendroglioma expressed sequence tag, and spans at least 61.7 kilobases. hUlip lacks sequences corresponding to the first six exons found in unc-33. unc-33 exons correspond to homologous hUlip exons as follows: VII to 1 and 2, VIII to 3-9, IX to 10-12, and X to 13 and 14. Using the hUlip clone 1 phage, fluorescence in situ hybridization analysis indicates that the hybridization signal localizes to human chromosome 5q32. Deletion analysis of 5'-flanking sequences delineated the sequences sufficient to express a reporter gene in both neuroblastoma cells and myoblasts. A consensus MyoD/myogenin binding site is located in a region of the downstream promoter that is nearly identical to its mouse homologue. Mutagenesis shows that this conserved MyoD/myogenin site is necessary for full promoter activity in both myoblasts and neuroblastoma cells. JF - The Journal of biological chemistry AU - Matsuo, T AU - Stauffer, J K AU - Walker, R L AU - Meltzer, P AU - Thiele, C J AD - Cell and Molecular Biology Section, Pediatric Oncology Branch, Division of Clinical Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/06/02/ PY - 2000 DA - 2000 Jun 02 SP - 16560 EP - 16568 VL - 275 IS - 22 SN - 0021-9258, 0021-9258 KW - Caenorhabditis elegans Proteins KW - 0 KW - DNA, Complementary KW - DPYSL3 protein, human KW - Helminth Proteins KW - Muscle Proteins KW - Nerve Growth Factors KW - Phosphoproteins KW - unc-33 protein, C elegans KW - Index Medicus KW - Neuroblastoma -- pathology KW - Animals KW - Biological Evolution KW - Exons KW - Humans KW - Mice KW - Chromosome Mapping KW - Rats KW - Base Sequence KW - Neuroblastoma -- genetics KW - Introns KW - Molecular Sequence Data KW - Promoter Regions, Genetic KW - Phosphoproteins -- genetics KW - Nerve Growth Factors -- genetics KW - Nerve Growth Factors -- chemistry KW - Muscles -- metabolism KW - Helminth Proteins -- genetics KW - Helminth Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71141827?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Structure+and+promoter+analysis+of+the+human+unc-33-like+phosphoprotein+gene.+E-box+required+for+maximal+expression+in+neuroblastoma+and+myoblasts.&rft.au=Matsuo%2C+T%3BStauffer%2C+J+K%3BWalker%2C+R+L%3BMeltzer%2C+P%3BThiele%2C+C+J&rft.aulast=Matsuo&rft.aufirst=T&rft.date=2000-06-02&rft.volume=275&rft.issue=22&rft.spage=16560&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 - 2000-07-11 N1 - Date created - 2000-07-11 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF246693; GENBANK; AF246692 N1 - SuppNotes - Erratum In: J Biol Chem 2000 Aug 11;275(32):25052-3 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of stress and the hypothalamic-pituitary-adrenal axis in the pathogenesis of the metabolic syndrome: neuro-endocrine and target tissue-related causes AN - 877591075; 13652699 AB - The stress system coordinates the adaptive response of the organism to real or perceived stressors. The main components of the stress system are the corticotropin-releasing hormone (CRH) and locus ceruleus-norepinephrine/autonomic (LC/NE) systems and their peripheral effectors, the hypothalamic-pituitary-adrenal (HPA) axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. Thus, CRH and the LC/NE system stimulate arousal and attention, as well as the mesocorticolimbic dopaminergic system, which is involved in anticipatory and reward phenomena, and the amygdala, which are responsible for the generation of fear. Hypothalamic CRH plays an important role in inhibiting gonadotropin-releasing hormone secretion during stress, while via somatostatin it also inhibits growth hormone, thyrotropin-releasing hormone and thyrotropin secretion, suppressing thus reproduction, growth and thyroid function. Glucocorticoids directly inhibit pituitary gonadotropin, growth hormone and thyrotropin secretion and make the target tissues of sex steroids and growth factors resistant to these substances. In addition, glucocorticoids stimulate hepatic gluconeogenesis, and inhibit or potentiate insulin actions on skeletal muscle and adipose tissue respectively, ultimately promoting visceral adiposity and the metabolic syndrome. Glucocorticoids also have direct effects on the bone, inhibiting osteoblastic activity and causing osteoporosis. Obese subjects with psychiatric manifestations ranging from those of melancholic depression to anxiety with perception of 'uncontrollable' stress, frequently have mild hypercortisolism, while carefully screened obese subjects with no such manifestations are eucortisolemic. The former may have stress-induced glucocorticoid-mediated visceral obesity and metabolic syndrome manifestations, which in the extreme may be called a pseudo-Cushing state that needs to be differentiated from frank Cushing syndrome. Stress-induced hypercortisolism and visceral obesity and their cardiovascular and other sequelae increase the all-cause mortality risk of affected subjects by 2-3-fold and curtail their life expectancy by several years. INTERNATIONAL JOURNAL OF OBESITY: (2000) 24, Suppl 2, S50-S55 JF - International Journal of Obesity AU - Chrousos, G P AD - Pediatric Endocrinology Section, PREB, NICHD, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - S50 EP - S55 PB - Nature Publishing Group, The Macmillan Building London N1 9XW UK VL - 24 IS - S2 SN - 0307-0565, 0307-0565 KW - CSA Neurosciences Abstracts; Risk Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/877591075?accountid=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+Obesity&rft.atitle=The+role+of+stress+and+the+hypothalamic-pituitary-adrenal+axis+in+the+pathogenesis+of+the+metabolic+syndrome%3A+neuro-endocrine+and+target+tissue-related+causes&rft.au=Chrousos%2C+G+P&rft.aulast=Chrousos&rft.aufirst=G&rft.date=2000-06-01&rft.volume=24&rft.issue=S2&rft.spage=S50&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Obesity&rft.issn=03070565&rft_id=info:doi/10.1038%2Fsj.ijo.0801278 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2011-12-14 DO - http://dx.doi.org/10.1038/sj.ijo.0801278 ER - TY - JOUR T1 - Aging effects on motor units in the human thyroarytenoid muscle. AN - 85362036; pmid-10852524 AB - OBJECTIVES: To determine whether age differences are present in the human laryngeal thyroarytenoid muscle that would indicate that different normative values would be needed for identifying motor unit abnormalities. STUDY DESIGN: Twenty-six consecutively recruited healthy subjects between the ages of 21 and 72 years participated in a laryngeal electromyography study. METHODS: Bipolar needle electrodes were used to record motor unit action potentials from several locations in the right and left thyroarytenoid muscles of each subject. The duration of a motor unit was measured when at least 10 firings of the same motor unit could be identified. On the average, four units were measured per muscle. RESULTS: In the subjects less than 60 years of age, motor unit duration did not increase significantly with age. However, motor units from subjects greater than 60 years of age had longer durations than those from subjects less than 60 years of age (P < .00005), and 25% of the units measured in subjects greater than 60 years of age had longer durations than any of the units measured in subjects less than 60 years of age. Further, the older subjects differed from each other in their mean unit durations (P < .0001). In subjects less than 60 years of age, significantly longer durations were found for units innervated by the longer, left-side recurrent laryngeal nerve in comparison with the right-side nerve (P = .005). CONCLUSIONS: Different mean and SD values should be used for patients less than and greater than 60 years of age and for the right and left sides, when evaluating motor units in the thyroarytenoid muscles. JF - The Laryngoscope AU - Takeda, N AU - Thomas, G R AU - Ludlow, C L AD - Laryngeal and Speech Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1416, USA. Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 1018 EP - 1025 VL - 110 IS - 6 SN - 0023-852X, 0023-852X KW - Index Medicus KW - National Library of Medicine KW - Electromyography -- methods KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Time Factors KW - Recurrent Laryngeal Nerve -- physiology KW - Male KW - Female KW - Aging -- physiology KW - Laryngeal Muscles -- physiology KW - Arytenoid Cartilage -- innervation KW - Thyroid Gland -- innervation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85362036?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Laryngoscope&rft.atitle=Aging+effects+on+motor+units+in+the+human+thyroarytenoid+muscle.&rft.au=Takeda%2C+N%3BThomas%2C+G+R%3BLudlow%2C+C+L&rft.aulast=Takeda&rft.aufirst=N&rft.date=2000-06-01&rft.volume=110&rft.issue=6&rft.spage=1018&rft.isbn=&rft.btitle=&rft.title=The+Laryngoscope&rft.issn=0023852X&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - Role of endoscopic ultrasonography in the staging of rectal cancer: a retrospective study of 63 patients. AN - 85340886; pmid-10875472 AB - We evaluated retrospectively the accuracy of endoscopic ultrasonography (EUS) in the preoperative staging of 63 patients with rectal cancer who were hospitalized and underwent surgery at our institution from January 1994 to December 1997. These patients, 39 men and 24 women with a mean age of 60 years, underwent preoperative EUS, which was performed in all cases using an echo-colonoscope Olympus CF UM 20, with a 7.5 MHz radial scanner. Ten patients did not undergo surgery and, therefore, were excluded from the analysis. EUS showed an overall accuracy of 81% for the T stage (including nontraversable stenotic tumors) and of 70% for the N stage. The accuracy of EUS for the T stage increased from 81 to 90% when we excluded those cases with nontraversable stenotic cancers from the analysis. Five tumors (9.4%) were understaged. while another five cases (9.4%) were overstaged. Finally, EUS was highly accurate (81%) in differentiating T1 from T24 tumors. In conclusion, our data shows that EUS is very accurate in the locoregional staging of rectal cancer and confirms the role of this imaging technique in the preoperative staging of patients with rectal cancer. JF - Journal of clinical gastroenterology AU - Marone, P AU - Petrulio, F AU - de Bellis, M AU - Battista Rossi, G AU - Tempesta, A AD - Endoscopy Unit, National Cancer Institute and G. Pascale Foundation, Naples, Italy. Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 420 EP - 424 VL - 30 IS - 4 SN - 0192-0790, 0192-0790 KW - Index Medicus KW - National Library of Medicine KW - Preoperative Care KW - Neoplasm Staging KW - Humans KW - Retrospective Studies KW - Rectal Neoplasms -- pathology KW - Adenocarcinoma -- pathology KW - Rectal Neoplasms -- ultrasonography KW - Rectum -- pathology KW - Rectum -- ultrasonography KW - Adenocarcinoma -- ultrasonography KW - Middle Aged KW - Female KW - Male KW - Endosonography UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85340886?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+gastroenterology&rft.atitle=Role+of+endoscopic+ultrasonography+in+the+staging+of+rectal+cancer%3A+a+retrospective+study+of+63+patients.&rft.au=Marone%2C+P%3BPetrulio%2C+F%3Bde+Bellis%2C+M%3BBattista+Rossi%2C+G%3BTempesta%2C+A&rft.aulast=Marone&rft.aufirst=P&rft.date=2000-06-01&rft.volume=30&rft.issue=4&rft.spage=420&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+gastroenterology&rft.issn=01920790&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - The role of chemotherapy in the management of gastric cancer. AN - 85340855; pmid-10875463 AB - Despite a marked decline in the incidence of gastric carcinoma in Western countries, the majority of patients presents with advanced inoperable tumors. In this setting, usually the aim of therapy is palliation, with the exception of chemotherapy administered in the attempt to downstage the tumor and to facilitate potentially curative surgery in patients with locally advanced nonmetastatic disease. This review will focus on the use of chemotherapy for advanced gastric cancer and after curative surgery, providing an overview of future directions for clinical research: preoperative (neoadjuvant) systemic chemotherapy, intraperitoneal treatment, and newer drugs. JF - Journal of clinical gastroenterology AU - De Vivo, R AU - Pignata, S AU - Palaia, R AU - Parisi, V AU - Daniele, B AD - Division of Med Oncol B, National Cancer Institute, Napoli, Italy. Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 364 EP - 371 VL - 30 IS - 4 SN - 0192-0790, 0192-0790 KW - Index Medicus KW - National Library of Medicine KW - Fluorouracil -- therapeutic use KW - Neoplasm Staging KW - Humans KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Chemotherapy, Adjuvant KW - Stomach Neoplasms -- drug therapy KW - Stomach Neoplasms -- surgery KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85340855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+gastroenterology&rft.atitle=The+role+of+chemotherapy+in+the+management+of+gastric+cancer.&rft.au=De+Vivo%2C+R%3BPignata%2C+S%3BPalaia%2C+R%3BParisi%2C+V%3BDaniele%2C+B&rft.aulast=De+Vivo&rft.aufirst=R&rft.date=2000-06-01&rft.volume=30&rft.issue=4&rft.spage=364&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+gastroenterology&rft.issn=01920790&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - A protocol for assessing subtraction errors of arterial spin-tagging perfusion techniques in human brain. AN - 85273826; pmid-10861886 AB - A protocol for assessing signal contributions from static tissue (subtraction errors) in perfusion images acquired with arterial spin-labeling (ASL) techniques in human brain is proposed. The method exploits the reduction of blood T(1) caused by the clinically available paramagnetic contrast agent, gadopentetate dimeglumine (Gd-DTPA). The protocol is demonstrated clinically with multislice FAIR images acquired before, during, and after Gd-DTPA administration using a range of selective inversion widths. Perfusion images acquired postcontrast for selective inversion widths large enough (threshold) to avoid interaction with the imaging slice had signal intensities reduced to noise level, as opposed to subtraction errors manifested on images acquired using inversion widths below the threshold. The need for these experiments to be performed in vivo is further illustrated by comparison with phantom results. The protocol allows a one-time calibration of relevant ASL parameters (e.g., selective inversion widths) in vivo, which may otherwise cause subtraction errors. Magn Reson Med 43:896-900, 2000. Published 2000 Wiley-Liss, Inc. JF - Magnetic Resonance in Medicine AU - Yongbi, M N AU - Tan, C X AU - Frank, J A AU - Duyn, J H AD - Laboratory of Diagnostic Radiology Research, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 2000 SP - 896 EP - 900 VL - 43 IS - 6 SN - 0740-3194, 0740-3194 KW - Magnetic Resonance Imaging KW - Sensitivity and Specificity KW - Comparative Study KW - Gadolinium DTPA KW - Perfusion KW - Human KW - Brain KW - Contrast Media KW - Cerebral Arteries KW - Spin Labels KW - Artifacts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85273826?accountid=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=A+protocol+for+assessing+subtraction+errors+of+arterial+spin-tagging+perfusion+techniques+in+human+brain.&rft.au=Yongbi%2C+M+N%3BTan%2C+C+X%3BFrank%2C+J+A%3BDuyn%2C+J+H&rft.aulast=Yongbi&rft.aufirst=M&rft.date=2000-06-01&rft.volume=43&rft.issue=6&rft.spage=896&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 - Human corticospinal excitability evaluated with transcranial magnetic stimulation during different reaction time paradigms. AN - 85228931; pmid-10825355 AB - The aim of this study was to evaluate corticospinal excitability of both hemispheres during the reaction time (RT) using transcranial magnetic stimulation (TMS). Nine right-handed subjects performed right and left thumb extensions in simple (SRT), choice (CRT) and go/no-go auditory RT paradigms. TMS, inducing motor-evoked potentials (MEPs) simultaneously in the extensor pollicis brevis muscles bilaterally, was applied at different latencies from the tone. For all paradigms, MEP amplitudes on the side of movement increased progressively in the 80-120 ms before EMG onset, while the resting side showed inhibition. The inhibition was significantly more pronounced for right than for left thumb movements. For the left SRT, significant facilitation occurred on the right after EMG onset. Initial bilateral facilitation occurred in SRT trials with slow RT. After no-go tones, bilateral inhibition occurred at a time corresponding to the mean RT to go tones. The timing of the corticospinal rise in excitability on the side of movement was independent of task difficulty and RT. This suggests that corticospinal activation is, to some extent, in series and not in parallel with stimulus processing and response selection. Corticospinal inhibition on the side not to be moved implies that suppression of movement is an active process. This inhibition is more efficient for right- than for left-side movements in right-handed subjects, possibly because of left hemispheric dominance for movement. JF - Brain AU - Leocani, L AU - Cohen, L G AU - Wassermann, E M AU - Ikoma, K AU - Hallett, M AD - Human Motor Control Section, NINDS, NIH, Bethesda, Maryland 20892-1428, USA. Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 1161 EP - 1173 VL - 123 ( Pt 6) SN - 0006-8950, 0006-8950 KW - Auditory Cortex KW - Human KW - Electromyography KW - Electric Stimulation KW - Movement KW - Motor Cortex KW - Choice Behavior KW - Volition KW - Adult KW - Middle Age KW - Acoustic Stimulation KW - Laterality KW - Male KW - Female KW - Pyramidal Tracts KW - Reaction Time KW - Magnetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85228931?accountid=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&rft.atitle=Human+corticospinal+excitability+evaluated+with+transcranial+magnetic+stimulation+during+different+reaction+time+paradigms.&rft.au=Leocani%2C+L%3BCohen%2C+L+G%3BWassermann%2C+E+M%3BIkoma%2C+K%3BHallett%2C+M&rft.aulast=Leocani&rft.aufirst=L&rft.date=2000-06-01&rft.volume=123+%28+Pt+6%29&rft.issue=&rft.spage=1161&rft.isbn=&rft.btitle=&rft.title=Brain&rft.issn=00068950&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Evaluation of synthetic schemes to prepare immunogenic conjugates of Vibrio cholerae O139 capsular polysaccharide with chicken serum albumin AN - 815538713; 13880008 AB - Vibrio cholerae serotype O139 is a new etiologic agent of epidemic cholera. There is no vaccine available against cholera caused by this serotype. V. cholerae O139 is an encapsulated bacterium, and its polysaccharide capsule is an essential virulent factor and likely protective antigen. This study evaluated several synthetic schemes for preparation of conjugates of V. cholerae O139 capsular polysaccharide (CPS) with chicken serum albumin as the carrier protein (CSA) using 1-ethyl-3(3-dimethylaminopropyl)carbodiimide (EDC) or 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) as activating agents. Four conjugates described here as representative of many experiments were synthesized in 2 steps: 1) preparation of adipic acid hydrazide derivative of CPS (CPS sub(AH)) or of CSA (CSA sub(AH)), and 2) binding of CPS sub(AH) to CSA or of CPS to CSA sub(AH). Although all conjugates induced CPS antibodies, the conjugate prepared by EDC-mediated binding of CPS and CSA sub(AH) (EDC:CPS-CSA sub(AH)) was statistically significantly less immunogenic than the other three conjugates. Representative sera from mice injected with these three conjugates contained antibodies that mediated the lysis of V. cholerae O139 inoculum. Evaluation of the different synthetic schemes and reaction conditions in relation to the immunogenicity of the resultant conjugates provided the basis for the preparation of a V. cholerae O139 conjugate vaccine with a medically useful carrier protein such as diphtheria toxin mutant. JF - Glycoconjugate Journal AU - Kossaczka, Zuzana AU - Szu, Shousun C AD - Laboratory of Developmental and Molecular Immunity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892 Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 425 EP - 433 PB - Springer-Verlag, P.O. Box 2485 Secaucus NJ 07096-2485 USA VL - 17 IS - 6 SN - 0282-0080, 0282-0080 KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Epidemics KW - Serotypes KW - protective antigen KW - Diphtheria toxin KW - Vibrio cholerae KW - glycoconjugates KW - Antibodies KW - Immunogenicity KW - adipic acid KW - Albumin KW - Inoculum KW - Cholera KW - Vaccines KW - Capsular polysaccharides KW - F 06905:Vaccines KW - J 02350:Immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/815538713?accountid=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=Glycoconjugate+Journal&rft.atitle=Evaluation+of+synthetic+schemes+to+prepare+immunogenic+conjugates+of+Vibrio+cholerae+O139+capsular+polysaccharide+with+chicken+serum+albumin&rft.au=Kossaczka%2C+Zuzana%3BSzu%2C+Shousun+C&rft.aulast=Kossaczka&rft.aufirst=Zuzana&rft.date=2000-06-01&rft.volume=17&rft.issue=6&rft.spage=425&rft.isbn=&rft.btitle=&rft.title=Glycoconjugate+Journal&rft.issn=02820080&rft_id=info:doi/10.1023%2FA%3A1007164216202 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Serotypes; Epidemics; protective antigen; Diphtheria toxin; Antibodies; glycoconjugates; Immunogenicity; Albumin; adipic acid; Inoculum; Cholera; Vaccines; Capsular polysaccharides; Vibrio cholerae DO - http://dx.doi.org/10.1023/A:1007164216202 ER - TY - JOUR T1 - Effects of reduced energy intake on the biology of aging: the primate model AN - 754894625; 13522209 AB - Dietary energy restriction is the only proven method for extending lifespan and slowing aging in mammals, while maintaining health and vitality. Although the first experiments in this area were conducted over 60y ago in rodents, possible applicability to primates has only been examined in controlled studies since 1987. Our project at the National Institute on Aging began with 3-0 male rhesus and 30 male squirrel monkeys of various ages over their respective life spans. Subsequently, it has been expanded to include female rhesus monkeys, and several other laboratories have initiated related studies. Experimental animals are generally fed 30% less than controls, and diets are supplemented with micronutrients to achieve undernutrition without malnutrition. These calorically restricted (CR) monkeys are lighter, with less fat and lean mass than controls. Bone mass is also slightly reduced, but in approximate proportion to the smaller body size. CR animals mature more slowly and achieve shorter stature than controls as well. Metabolically, CR monkeys have slightly lower body temperature and initial energy expenditure following onset of restriction, and better glucose tolerance and insulin sensitivity. The latter suggest a reduced predisposition towards diabetes as the animals age. Other potential anti-disease effects include biomarkers suggestive of lessened risk of cardiovascular disease and possibly cancer. Candidate biomarkers of aging, including the age-related decrease in plasma dehydroepiandrosterone sulfate (DHEAS), suggest that the CR animals may be aging more slowly than controls in some respects, although sufficient survival data will require more time to accumulate. In summary, nearly all CR effects detected in rodents, which have thus far been examined in primates, exhibit similar phenomenology. Potential applicability of these beneficial effects to humans is discussed. EUROPEAN JOURNAL OF CLINICAL NUTRITION: (2000) 54, Suppl 3, S15-S20 JF - European Journal of Clinical Nutrition AU - Roth, G S AU - Ingram, D K AU - Black, A AU - Lane, M A AD - National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - S15 EP - S20 PB - Nature Publishing Group VL - 54 IS - S3 SN - 0954-3007, 0954-3007 KW - Risk Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/754894625?accountid=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=European+Journal+of+Clinical+Nutrition&rft.atitle=Effects+of+reduced+energy+intake+on+the+biology+of+aging%3A+the+primate+model&rft.au=Roth%2C+G+S%3BIngram%2C+D+K%3BBlack%2C+A%3BLane%2C+M+A&rft.aulast=Roth&rft.aufirst=G&rft.date=2000-06-01&rft.volume=54&rft.issue=S3&rft.spage=S15&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Clinical+Nutrition&rft.issn=09543007&rft_id=info:doi/10.1038%2Fsj.ejcn.1601020 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-09-01 N1 - Last updated - 2011-12-14 DO - http://dx.doi.org/10.1038/sj.ejcn.1601020 ER - TY - JOUR T1 - TNP-470: an angiogenesis inhibitor in clinical development for cancer. AN - 72387927; 11060750 AB - TNP-470, an analogue of fumagillin, has been shown to inhibit angiogenesis in vitro and in vivo. In 1992, TNP-470 entered clinical development for cancer as an anti-angiogenic agent. It is currently in Phase I/II trials in Kaposi's sarcoma, renal cell carcinoma, brain cancer, breast cancer, cervical cancer and prostate cancer. In early clinical reports, TNP-470 is tolerated up to 177 mg/m(2) with neurotoxic effects (fatigue, vertigo, ataxia, and loss of concentration) being the principal dose limiting toxicity (DLT). Terminal half-life values are short and have shown intermittent and intrapatient variation (range: 0.05 - 1.07 h). Recently, mechanistic studies have identified cell cycle mediators and the protein methionine aminopeptidase-2 (MetAP-2) as molecular targets of TNP-470 and fumagillin. Animal studies confirm some toxic effects on normal angiogenic processes such as the female reproductive system and wound healing, which will require caution and close monitoring in the clinic. TNP-470 is one of the first anti-angiogenic compounds to enter clinical trials, making it a valuable prototype for future trials of angiogenesis inhibitors in oncology. JF - Expert opinion on investigational drugs AU - Kruger, E A AU - Figg, W D AD - National Cancer Institute/NIH, Medicine Branch, 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 1383 EP - 1396 VL - 9 IS - 6 SN - 1354-3784, 1354-3784 KW - Angiogenesis Inhibitors KW - 0 KW - Cyclohexanes KW - Sesquiterpenes KW - O-(chloroacetylcarbamoyl)fumagillol KW - X47GR46481 KW - Index Medicus KW - Animals KW - Humans KW - Angiogenesis Inhibitors -- therapeutic use KW - Neoplasms -- drug therapy KW - Angiogenesis Inhibitors -- pharmacology KW - Angiogenesis Inhibitors -- pharmacokinetics KW - Sesquiterpenes -- therapeutic use KW - Sesquiterpenes -- pharmacology KW - Sesquiterpenes -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72387927?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+opinion+on+investigational+drugs&rft.atitle=TNP-470%3A+an+angiogenesis+inhibitor+in+clinical+development+for+cancer.&rft.au=Kruger%2C+E+A%3BFigg%2C+W+D&rft.aulast=Kruger&rft.aufirst=E&rft.date=2000-06-01&rft.volume=9&rft.issue=6&rft.spage=1383&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+investigational+drugs&rft.issn=13543784&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-08 N1 - Date created - 2001-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A general survey of glutamine level in different tissues of murine solid tumor bearing mice before and after therapy with purified glutaminase. AN - 72211969; 10965812 AB - Distribution of glutamine level in different tissues of tumor bearing mice such as brain, liver, kidney, spleen, large and small intestine and the tumor itself were studied in three solid tumor models, viz, Ehrlich ascites carcinoma, Sarcoma-180 and methylcholanthrene induced carcinoma. Tumor bearing mice were subjected to therapy for 7 days with the glutaminase purified from malignant S-180 cell. The results exhibit a significant decrease in tumor burden after enzyme therapy. Host tissue glutamine levels were significantly elevated in tumor bearing untreated mice in comparison to the normal ones, while significant lower values were obtained after enzyme therapy. It therefore appears that elevated levels of glutamine in host tissue are associated with the tumor burden. JF - Journal of experimental & clinical cancer research : CR AU - Maity, P AU - Chakraborty, S AU - Bhattacharya, P AD - Dept. of Metabolic Regulation, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 161 EP - 164 VL - 19 IS - 2 SN - 0392-9078, 0392-9078 KW - Glutamine KW - 0RH81L854J KW - Methylcholanthrene KW - 56-49-5 KW - Glutaminase KW - EC 3.5.1.2 KW - Index Medicus KW - Animals KW - Kidney -- metabolism KW - Spleen -- metabolism KW - Methylcholanthrene -- toxicity KW - Liver -- metabolism KW - Mice KW - Brain -- metabolism KW - Tissue Distribution KW - Intestines -- metabolism KW - Male KW - Skin Neoplasms -- drug therapy KW - Carcinoma, Ehrlich Tumor -- metabolism KW - Sarcoma 180 -- metabolism KW - Glutamine -- metabolism KW - Skin Neoplasms -- chemically induced KW - Sarcoma 180 -- drug therapy KW - Carcinoma, Ehrlich Tumor -- drug therapy KW - Glutaminase -- therapeutic use KW - Sarcoma 180 -- blood KW - Skin Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72211969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.atitle=A+general+survey+of+glutamine+level+in+different+tissues+of+murine+solid+tumor+bearing+mice+before+and+after+therapy+with+purified+glutaminase.&rft.au=Maity%2C+P%3BChakraborty%2C+S%3BBhattacharya%2C+P&rft.aulast=Maity&rft.aufirst=P&rft.date=2000-06-01&rft.volume=19&rft.issue=2&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.issn=03929078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-22 N1 - Date created - 2000-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA repeat expansions and human disease. AN - 71792332; 10950307 AB - The repeat expansion diseases are genetic disorders caused by intergenerational expansions of a specific tandem DNA repeat. These disorders range from mildly to severely debilitating or fatal, and all have limited treatment options. How expansion occurs and causes disease is only now beginning to be understood. Efforts to model expansion in mice have so far met with only limited success, perhaps due to a requirement for specific cis- or trans-acting factors. In vitro studies and data from bacteria and yeast suggest that in addition to secondary structures formed by the repeats, components of the DNA replication and recombination machinery are important determinants of instability. The consequences of expansion differ depending on where in the gene the repeat tract is located, and range from reduction of transcription initiation to protein toxicity. Recent advances are beginning to make rational approaches to the development of therapies possible. JF - Cellular and molecular life sciences : CMLS AU - Usdin, K AU - Grabczyk, E AD - Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0830, USA. ku@helix.nih.gov Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 914 EP - 931 VL - 57 IS - 6 SN - 1420-682X, 1420-682X KW - Peptides KW - 0 KW - polyglutamine KW - 26700-71-0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Chromosome Fragility -- genetics KW - Recombination, Genetic -- genetics KW - Models, Genetic KW - Humans KW - Promoter Regions, Genetic -- genetics KW - Peptides -- genetics KW - Nucleic Acid Conformation KW - Trinucleotide Repeat Expansion -- genetics KW - DNA -- metabolism KW - Genetic Diseases, Inborn -- genetics KW - DNA -- genetics KW - DNA -- chemistry KW - Genetic Diseases, Inborn -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71792332?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+and+molecular+life+sciences+%3A+CMLS&rft.atitle=DNA+repeat+expansions+and+human+disease.&rft.au=Usdin%2C+K%3BGrabczyk%2C+E&rft.aulast=Usdin&rft.aufirst=K&rft.date=2000-06-01&rft.volume=57&rft.issue=6&rft.spage=914&rft.isbn=&rft.btitle=&rft.title=Cellular+and+molecular+life+sciences+%3A+CMLS&rft.issn=1420682X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-31 N1 - Date created - 2000-08-31 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Cell Mol Life Sci 2000 Oct;57(11):1667 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Restricted expression of an adenoviral vector encoding Fas ligand (CD95L) enhances safety for cancer gene therapy. AN - 71757769; 10933980 AB - Gene transfer of Fas ligand (CD95L) using adenoviral vectors has been shown to generate apoptotic responses and potent inflammatory reactions that can be used to induce the regression of malignancies in vivo, but these vectors also cause significant hepatotoxicity that may limit their clinical utility. Here we describe an adenoviral vector encoding CD95L with restricted gene expression that reduces its toxicity in vivo. Preclinical efficacy and gene expression studies of lineage-restricted CD95L adenoviral vectors were performed. To enhance its cytotoxicity and reduce potential systemic effects, a noncleavable CD95L was made by deleting a segment containing the cleavage site (CD95L deltaQP). Higher CD95L expression of this mutant was observed on the tumor cell surface, together with a reduction in the release of soluble CD95L. This CD95L cleavage mutant was then expressed under control of a smooth muscle-specific promoter, SM22apha, and analyzed for its ability to suppress the growth of tumors of smooth muscle origin in vivo. Growth of human leiomyosarcomas but not gliomas was inhibited after ADV gene transfer into tumor-bearing immunodeficient mice. In contrast to viral promoters, in which mortality was uniformly seen after injection of 10(12) particles, no significant hepatic injury or systemic toxicity was observed in mice, and the maximum tolerated dose was increased > or = 10- to 100-fold. These findings suggest that restricted specificity of adenoviral CD95L gene expression enhances the safety of this approach for cancer gene therapy. JF - Molecular therapy : the journal of the American Society of Gene Therapy AU - Aoki, K AU - Akyürek, L M AU - San, H AU - Leung, K AU - Parmacek, M S AU - Nabel, E G AU - Nabel, G J AD - Vaccine Research Center, National Institutes of Health, Bethesda, Maryland 20892-3005, USA. Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 555 EP - 565 VL - 1 IS - 6 SN - 1525-0016, 1525-0016 KW - FASLG protein, human KW - 0 KW - Fas Ligand Protein KW - Fasl protein, mouse KW - Membrane Glycoproteins KW - Index Medicus KW - Animals KW - Leiomyosarcoma -- immunology KW - Apoptosis KW - Glioma -- immunology KW - Muscle, Smooth -- immunology KW - Liver -- injuries KW - Humans KW - Safety KW - Gene Expression KW - Mice KW - Leiomyosarcoma -- therapy KW - Mice, Inbred BALB C KW - Promoter Regions, Genetic KW - Glioma -- pathology KW - Tumor Cells, Cultured KW - Glioma -- therapy KW - Leiomyosarcoma -- pathology KW - Mutation KW - Neoplasms -- pathology KW - Genetic Therapy -- adverse effects KW - Genetic Vectors KW - Genetic Therapy -- methods KW - Neoplasms -- therapy KW - Neoplasms -- immunology KW - Membrane Glycoproteins -- genetics KW - Adenoviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71757769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+therapy+%3A+the+journal+of+the+American+Society+of+Gene+Therapy&rft.atitle=Restricted+expression+of+an+adenoviral+vector+encoding+Fas+ligand+%28CD95L%29+enhances+safety+for+cancer+gene+therapy.&rft.au=Aoki%2C+K%3BAky%C3%BCrek%2C+L+M%3BSan%2C+H%3BLeung%2C+K%3BParmacek%2C+M+S%3BNabel%2C+E+G%3BNabel%2C+G+J&rft.aulast=Aoki&rft.aufirst=K&rft.date=2000-06-01&rft.volume=1&rft.issue=6&rft.spage=555&rft.isbn=&rft.btitle=&rft.title=Molecular+therapy+%3A+the+journal+of+the+American+Society+of+Gene+Therapy&rft.issn=15250016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-19 N1 - Date created - 2000-09-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genotoxic and functional consequences of transplacental zidovudine exposure in fetal monkey brain mitochondria. AN - 71729981; 10935684 AB - Mitochondrial toxicity was assessed in the brains of developing Erythrocebus patas monkey fetuses exposed in utero to the nucleoside analogue drug zidovudine (3'-azido-3'deoxythymidine or AZT). Pregnant E. patas monkeys were given 0 (n = 5), 10 (n = 3), and 40 (n = 3) mg of AZT/day, equivalent to 21 and 86% of the human daily dose, for the last half (about 10 weeks) of gestation. Mitochondria were isolated from fetal cerebrum and cerebellum at birth and mitochondrial morphology was examined in these tissues by transmission electron microscopy (TEM). Oxidative phosphorylation (OXPHOS) enzyme specific activities were measured spectrophotometrically. Mitochondrial DNA (mtDNA) integrity and quantity were determined by Southern blot and slot blot analysis. In the cerebral mitochondria, reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase (complex I) specific activity decreased by 25% in monkeys treated with 40 mg of AZT/day compared with unexposed monkeys (p > or = .05). At the same AZT dose in the cerebral mitochondria, succinate dehydrogenase (complex II) and cytochrome c reductase (complex IV)-specific activities showed dose-dependent increases (p > or = .05), compared with those in controls. In the cerebellum, no difference was seen in mitochondrial OXPHOS enzyme activities between unexposed and exposed fetuses. Furthermore, TEM demonstrated no difference in mitochondrial morphology in frontal cerebrum or cerebellum from unexposed and exposed fetuses, and all fetuses had similar amounts of mtDNA in both tissues. Cerebral mtDNA degradation was noted in the highest AZT dosage group, whereas mtDNA from cerebellum was uneffected. Thus, in fetal patas monkeys given a human equivalent daily dose of AZT during the last half of pregnancy, mitochondria in the fetal cerebrum appear to sustain moderate damage, while the fetal cerebellum mitochondria were not effected. JF - Journal of acquired immune deficiency syndromes (1999) AU - Ewings, E L AU - Gerschenson, M AU - St Claire, M C AU - Nagashima, K AU - Skopets, B AU - Harbaugh, S W AU - Harbaugh, J W AU - Poirier, M C AD - Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 2000/06/01/ PY - 2000 DA - 2000 Jun 01 SP - 100 EP - 105 VL - 24 IS - 2 SN - 1525-4135, 1525-4135 KW - DNA, Mitochondrial KW - 0 KW - Multienzyme Complexes KW - Mutagens KW - Zidovudine KW - 4B9XT59T7S KW - Oxidoreductases KW - EC 1.- KW - Electron Transport Complex II KW - EC 1.3.5.1 KW - Succinate Dehydrogenase KW - EC 1.3.99.1 KW - NADH Dehydrogenase KW - EC 1.6.99.3 KW - Index Medicus KW - AIDS/HIV KW - Succinate Dehydrogenase -- genetics KW - Multienzyme Complexes -- metabolism KW - Animals KW - NADH Dehydrogenase -- metabolism KW - Humans KW - Multienzyme Complexes -- genetics KW - Pregnancy KW - Cerebellum -- metabolism KW - NADH Dehydrogenase -- genetics KW - Animals, Newborn KW - Cerebellum -- embryology KW - DNA, Mitochondrial -- drug effects KW - Oxidoreductases -- genetics KW - Oxidoreductases -- metabolism KW - Oxidative Phosphorylation -- drug effects KW - Cerebellum -- drug effects KW - Erythrocebus patas KW - Succinate Dehydrogenase -- metabolism KW - Female KW - DNA, Mitochondrial -- genetics KW - Maternal-Fetal Exchange KW - Zidovudine -- toxicity KW - Mitochondria -- ultrastructure KW - Brain -- drug effects KW - Mitochondria -- drug effects KW - Brain -- embryology KW - Mitochondria -- metabolism KW - Brain -- metabolism KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71729981?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genotoxic+and+functional+consequences+of+transplacental+zidovudine+exposure+in+fetal+monkey+brain+mitochondria.&rft.au=Ewings%2C+E+L%3BGerschenson%2C+M%3BSt+Claire%2C+M+C%3BNagashima%2C+K%3BSkopets%2C+B%3BHarbaugh%2C+S+W%3BHarbaugh%2C+J+W%3BPoirier%2C+M+C&rft.aulast=Ewings&rft.aufirst=E&rft.date=2000-06-01&rft.volume=24&rft.issue=2&rft.spage=100&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 - 2000-08-17 N1 - Date created - 2000-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Decreased mu-opioid receptor binding in the globus pallidus of rats treated with chronic haloperidol. AN - 71283256; 10923753 AB - Chronic neuroleptic treatment produces a movement disorder in rats characterized by vacuous chewing movements (VCMs). Neuroleptics also produce a variety of changes in opioid neurotransmission in several regions of the basal ganglia. Rats with the VCM syndrome show elevated mRNA for enkephalin in striatopallidal neurons, suggesting a possible role for enkephalin in the pathophysiology of VCMs. This study investigated the role of mu-opioid receptor density in the basal ganglia on the expression of VCMs. Rats were treated with haloperidol for 24 weeks and withdrawn for 9 weeks. Mu (m) receptors were labeled with [3H]-DAMGO. Haloperidol treatment produced a significant reduction in mu-receptor binding in the globus pallidus (P<0.05). There was, however, no relationship between mu-opioid receptor density and VCMs in this or any other region of the basal ganglia. These results replicate prior findings of a neuroleptic-induced reduction in [3H]-DAMGO binding in the globus pallidus. The lack of association between VCMs and [3H]-DAMGO binding in the globus pallidus or any other region suggests that prior reports of enkephalinergic mRNA changes in the striatum are not accompanied by compensatory changes in postsynaptic neurons. JF - Psychopharmacology AU - Bower, C M AU - Hyde, T M AU - Zaka, M AU - Hamid, E H AU - Baca, S M AU - Egan, M F AD - Clinical Brain Disorders Branch, NIMH, Bethesda, MD 20814-9692, USA. Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 260 EP - 263 VL - 150 IS - 3 SN - 0033-3158, 0033-3158 KW - Antipsychotic Agents KW - 0 KW - Receptors, Opioid, mu KW - Enkephalin, Ala(2)-MePhe(4)-Gly(5)- KW - 100929-53-1 KW - Haloperidol KW - J6292F8L3D KW - Index Medicus KW - Rats KW - Behavior, Animal -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Dyskinesia, Drug-Induced -- psychology KW - Autoradiography KW - Time Factors KW - Male KW - Globus Pallidus -- metabolism KW - Antipsychotic Agents -- pharmacology KW - Haloperidol -- pharmacology KW - Globus Pallidus -- drug effects KW - Receptors, Opioid, mu -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71283256?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Decreased+mu-opioid+receptor+binding+in+the+globus+pallidus+of+rats+treated+with+chronic+haloperidol.&rft.au=Bower%2C+C+M%3BHyde%2C+T+M%3BZaka%2C+M%3BHamid%2C+E+H%3BBaca%2C+S+M%3BEgan%2C+M+F&rft.aulast=Bower&rft.aufirst=C&rft.date=2000-06-01&rft.volume=150&rft.issue=3&rft.spage=260&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-07 N1 - Date created - 2000-12-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased levothyroxine requirements presenting as "inappropriate" TSH secretion syndrome in a patient with nephrotic syndrome. AN - 71264984; 10908166 AB - Patients with primary thyroid failure on levothyroxine (LT4) replacement who develop nephrotic syndrome (NS) may rarely present with an increase in LT4 requirements. In this report, we describe a patient with thyroid failure following radioactive iodine ablation for Graves' disease who required an escalation of LT4 doses following the onset of NS. The case presented with disproportionately elevated TSH levels in the presence of normal (or slightly subnormal) thyroid hormone levels, thus, masquerading as a state of "inappropriate" TSH secretion. This pattern of extreme dysregulation in thyroid function indices due to urinary loss of thyroid hormones has not been previously described in NS, and, therefore, extends the spectrum of endocrine manifestations of NS. JF - Journal of endocrinological investigation AU - Collins, M T AU - Remaley, A T AU - Csako, G AU - Pucino, F AU - Skarulis, M C AU - Balow, J E AU - Sarlis, N J AD - National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 383 EP - 392 VL - 23 IS - 6 SN - 0391-4097, 0391-4097 KW - Thyrotropin KW - 9002-71-5 KW - Thyroxine KW - Q51BO43MG4 KW - Index Medicus KW - Graves Disease -- radiotherapy KW - Thyrotropin -- blood KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Thyroid Diseases -- etiology KW - Radiation Injuries -- complications KW - Male KW - Nephrotic Syndrome -- drug therapy KW - Nephrotic Syndrome -- blood KW - Hyperpituitarism -- etiology KW - Thyroxine -- administration & dosage KW - Thyroxine -- therapeutic use KW - Nephrotic Syndrome -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71264984?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+endocrinological+investigation&rft.atitle=Increased+levothyroxine+requirements+presenting+as+%22inappropriate%22+TSH+secretion+syndrome+in+a+patient+with+nephrotic+syndrome.&rft.au=Collins%2C+M+T%3BRemaley%2C+A+T%3BCsako%2C+G%3BPucino%2C+F%3BSkarulis%2C+M+C%3BBalow%2C+J+E%3BSarlis%2C+N+J&rft.aulast=Collins&rft.aufirst=M&rft.date=2000-06-01&rft.volume=23&rft.issue=6&rft.spage=383&rft.isbn=&rft.btitle=&rft.title=Journal+of+endocrinological+investigation&rft.issn=03914097&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-13 N1 - Date created - 2000-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Maternal occupation in agriculture and risk of limb defects in Washington State, 1980-1993. AN - 71261556; 10901110 AB - This study examined the association between maternal occupational exposure to agricultural chemicals and the risk of limb defects among offspring. A retrospective cohort study was conducted using Washington State birth records for the years 1980 through 1993. The exposed group, consisting of 4466 births to mothers employed in agriculture, was compared with 2 reference groups: (i) 23,512 births in which neither parent worked in agriculture ("nonagricultural" group) and (ii) 5994 births in which only the father worked in agriculture ("paternal agriculture" group). The outcome of interest was limb defects [syndactyly, polydactyly, adactyly, and "other limb reductions" (as listed in the birth record)]. An elevated risk of limb defects was observed for the exposed group in comparison with both the nonagricultural and paternal agriculture groups, with ethnicity-adjusted prevalence ratios of 2.6 [95% confidence interval (95% CI) 1.1-5.8] and 2.6 (95% CI 0.7-9.5), respectively. These results support the hypothesis that maternal occupational exposure to agricultural chemicals may increase the risk of giving birth to a child with limb defects. JF - Scandinavian journal of work, environment & health AU - Engel, L S AU - O'Meara, E S AU - Schwartz, S M AD - Department of Epidemiology, University of Washington, Seattle, USA. engell@mail.nih.gov Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 193 EP - 198 VL - 26 IS - 3 SN - 0355-3140, 0355-3140 KW - Pesticides KW - 0 KW - Index Medicus KW - Washington -- epidemiology KW - Reproductive History KW - Logistic Models KW - Maternal Age KW - Humans KW - Seasons KW - Cohort Studies KW - Adult KW - Retrospective Studies KW - Infant, Newborn KW - Female KW - Prevalence KW - Pregnancy KW - Maternal Exposure -- adverse effects KW - Limb Deformities, Congenital -- epidemiology KW - Agriculture -- statistics & numerical data KW - Limb Deformities, Congenital -- chemically induced KW - Pesticides -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71261556?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scandinavian+journal+of+work%2C+environment+%26+health&rft.atitle=Maternal+occupation+in+agriculture+and+risk+of+limb+defects+in+Washington+State%2C+1980-1993.&rft.au=Engel%2C+L+S%3BO%27Meara%2C+E+S%3BSchwartz%2C+S+M&rft.aulast=Engel&rft.aufirst=L&rft.date=2000-06-01&rft.volume=26&rft.issue=3&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=Scandinavian+journal+of+work%2C+environment+%26+health&rft.issn=03553140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-13 N1 - Date created - 2000-10-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An abundant proneurotensin polymorphism, 479A>G, and a test of its association with alcohol dependence in a Finnish population. AN - 71240753; 10888062 AB - Neurotensin is a 13-amino acid neuropeptide that endogenously modulates dopamine release in the central nervous system. In substance dependence, the mesolimbic dopamine system has been postulated to be a central structure that mediates rewarding and reinforcing effects. Neurotensin receptors in the neurons of the ventral tegmental area facilitate dopamine release, making the neurotensin gene an excellent candidate gene for alcohol dependence and for other behaviors that involve reinforcement. A total of 639 psychiatrically interviewed Finns were genotyped for proneurotensin 479A>G polymorphism. We used the polymorphism as a marker to study the association between proneurotensin gene and alcohol dependence by comparing 229 unrelated Finnish healthy controls to 134 unrelated alcohol-dependent (DSM-III-R criteria) subjects who were also criminal offenders. In addition, 276 relatives of the alcohol-dependent and control subjects were genotyped. The frequencies of the genotypes in the whole sample (n = 639) were 0.84 for 479A/A, 0.16 for 479A/G, and 0.003 for 479G/G. The frequency of the rarer 479G allele was 0.07 and 0.06 in controls and alcohol-dependent subjects, respectively, and this difference was not statistically significant (chi2 = 0.264, df = 1, p = 0.61, controls vs. alcohol-dependent subjects). The results of the comparison between psychiatrically interviewed controls and alcoholics from a relatively well defined population indicate that the proneurotensin 479A>G polymorphism is not strongly associated with alcohol dependence. The results do not rule out a role for this gene in the pathogenesis of alcoholism or in differential vulnerability. JF - Alcoholism, clinical and experimental research AU - Vanakoski, J AU - Mazzanti, C AU - Naukkarinen, H AU - Virkkunen, M AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20852, USA. jyrkiv@mail.nih.gov Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 762 EP - 765 VL - 24 IS - 6 SN - 0145-6008, 0145-6008 KW - Protein Precursors KW - 0 KW - proneurotensin KW - Neurotensin KW - 39379-15-2 KW - Index Medicus KW - Genotype KW - Humans KW - Gene Frequency -- genetics KW - Finland -- epidemiology KW - Polymorphism, Genetic -- genetics KW - Protein Precursors -- genetics KW - Alcoholism -- genetics KW - Neurotensin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71240753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=An+abundant+proneurotensin+polymorphism%2C+479A%26gt%3BG%2C+and+a+test+of+its+association+with+alcohol+dependence+in+a+Finnish+population.&rft.au=Vanakoski%2C+J%3BMazzanti%2C+C%3BNaukkarinen%2C+H%3BVirkkunen%2C+M%3BGoldman%2C+D&rft.aulast=Vanakoski&rft.aufirst=J&rft.date=2000-06-01&rft.volume=24&rft.issue=6&rft.spage=762&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-07 N1 - Date created - 2000-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Peripheral blood progenitor cells for HPC transplants involving unrelated donors. AN - 71230440; 10864997 JF - Transfusion AU - Stroncek, D F AU - Confer, D L AU - Leitman, S F AD - Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. dstroncek@dtm.cc.nih.gov Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 731 EP - 741 VL - 40 IS - 6 SN - 0041-1132, 0041-1132 KW - Anticoagulants KW - 0 KW - Antigens, CD34 KW - Recombinant Proteins KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Citric Acid KW - 2968PHW8QP KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Index Medicus KW - Recombinant Proteins -- pharmacology KW - Leukemia -- chemically induced KW - Humans KW - Safety KW - Bone Marrow Transplantation -- trends KW - Granulocyte Colony-Stimulating Factor -- adverse effects KW - Granulocyte Colony-Stimulating Factor -- pharmacology KW - Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology KW - Leukopenia -- etiology KW - Citric Acid -- adverse effects KW - Blood Component Removal -- methods KW - Bone Marrow Transplantation -- immunology KW - Leukemia -- epidemiology KW - Histocompatibility KW - Anticoagulants -- adverse effects KW - Recombinant Proteins -- adverse effects KW - Hematopoietic Stem Cell Mobilization -- adverse effects KW - Antigens, CD34 -- analysis KW - Granulocyte-Macrophage Colony-Stimulating Factor -- adverse effects KW - Blood Cell Count -- drug effects KW - Hematopoietic Stem Cell Transplantation -- trends KW - Transplantation, Homologous KW - Tissue Donors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71230440?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Peripheral+blood+progenitor+cells+for+HPC+transplants+involving+unrelated+donors.&rft.au=Stroncek%2C+D+F%3BConfer%2C+D+L%3BLeitman%2C+S+F&rft.aulast=Stroncek&rft.aufirst=D&rft.date=2000-06-01&rft.volume=40&rft.issue=6&rft.spage=731&rft.isbn=&rft.btitle=&rft.title=Transfusion&rft.issn=00411132&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-12 N1 - Date created - 2000-09-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional analyses of amino acid substitutions Arg883Ser and Asp905Tyr of protein phosphatase-1 G-subunit. AN - 71221270; 10873397 AB - The PPP1R3 gene encoding the G-subunit of protein phosphatase-1 has three polymorphisms in linkage disequilibrium in the Pima Indians: an mRNA-destabilizing element in the 3'-untranslated region (ARE1/ARE2 alleles), Arg883Ser, and Asp905Tyr substitutions. The ARE2 allele, Arg883, and Asp905 variants are associated with insulin resistance and higher prevalence of type 2 diabetes in the Pima Indians. The ARE2 allele is associated with lower PPP1R3 transcript and protein levels in muscle tissue. Here we determined the functional contribution of the amino acid substitutions independent of the ARE alleles to insulin-stimulated glycogen synthesis by adenoviral-mediated gene expression in L6 myotubes. Similar overexpression levels of the G-subunit variants increased glycogen synthase fractional activity in the presence ( approximately 1. 5-fold) of insulin compared to control myotubes transduced with adenovirus encoding beta-galactosidase. The glycogen synthesis rate of myotubes overexpressing the G-subunit variants also increased by approximately 1.7-fold over the control with and without insulin. However, these measures were not significantly different among the variants. This study does not support a role for Arg883 and Asp905 variants independent of the ARE2 allele in the impaired insulin-stimulated glycogen synthesis in the muscle of Pima Indians. Copyright 2000 Academic Press. JF - Molecular genetics and metabolism AU - Permana, P A AU - Kahn, B B AU - Huppertz, C AU - Mott, D M AD - Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, 85016, USA. ppermana@mail.nih.gov Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 151 EP - 158 VL - 70 IS - 2 SN - 1096-7192, 1096-7192 KW - DNA Primers KW - 0 KW - Insulin KW - Aspartic Acid KW - 30KYC7MIAI KW - Tyrosine KW - 42HK56048U KW - Serine KW - 452VLY9402 KW - Glycogen KW - 9005-79-2 KW - Arginine KW - 94ZLA3W45F KW - Glycogen Synthase KW - EC 2.4.1.11 KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Protein Phosphatase 1 KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Adenoviridae -- metabolism KW - Glucose -- metabolism KW - Humans KW - Gene Expression KW - Insulin -- pharmacology KW - Muscle, Skeletal -- drug effects KW - Adenoviridae -- genetics KW - Mutagenesis, Site-Directed KW - Blotting, Western KW - beta-Galactosidase -- metabolism KW - Muscle, Skeletal -- cytology KW - Glycogen Synthase -- metabolism KW - Transfection KW - Cells, Cultured KW - beta-Galactosidase -- genetics KW - Glycogen -- biosynthesis KW - Mutation, Missense -- physiology KW - Muscle, Skeletal -- metabolism KW - DNA Primers -- chemistry KW - Amino Acid Substitution -- physiology KW - Phosphoprotein Phosphatases -- physiology KW - Phosphoprotein Phosphatases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71221270?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+genetics+and+metabolism&rft.atitle=Functional+analyses+of+amino+acid+substitutions+Arg883Ser+and+Asp905Tyr+of+protein+phosphatase-1+G-subunit.&rft.au=Permana%2C+P+A%3BKahn%2C+B+B%3BHuppertz%2C+C%3BMott%2C+D+M&rft.aulast=Permana&rft.aufirst=P&rft.date=2000-06-01&rft.volume=70&rft.issue=2&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=Molecular+genetics+and+metabolism&rft.issn=10967192&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-22 N1 - Date created - 2000-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A transitional model for longitudinal binary data subject to nonignorable missing data. AN - 71218506; 10877323 AB - Binary longitudinal data are often collected in clinical trials when interest is on assessing the effect of a treatment over time. Our application is a recent study of opiate addiction that examined the effect of a new treatment on repeated urine tests to assess opiate use over an extended follow-up. Drug addiction is episodic, and a new treatment may affect various features of the opiate-use process such as the proportion of positive urine tests over follow-up and the time to the first occurrence of a positive test. Complications in this trial were the large amounts of dropout and intermittent missing data and the large number of observations on each subject. We develop a transitional model for longitudinal binary data subject to nonignorable missing data and propose an EM algorithm for parameter estimation. We use the transitional model to derive summary measures of the opiate-use process that can be compared across treatment groups to assess treatment effect. Through analyses and simulations, we show the importance of properly accounting for the missing data mechanism when assessing the treatment effect in our example. JF - Biometrics AU - Albert, P S AD - Biometric Research Branch, National Cancer Institute, Bethesda, Maryland 20892-7434, USA. albertp@ctep.nci.nih.gov Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 602 EP - 608 VL - 56 IS - 2 SN - 0006-341X, 0006-341X KW - Index Medicus KW - Probability KW - Biometry -- methods KW - Humans KW - Patient Dropouts KW - Algorithms KW - Opioid-Related Disorders -- rehabilitation KW - Data Interpretation, Statistical KW - Opioid-Related Disorders -- urine KW - Models, Statistical KW - Markov Chains KW - Follow-Up Studies KW - Time Factors KW - Clinical Trials as Topic -- methods KW - Longitudinal Studies UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71218506?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometrics&rft.atitle=A+transitional+model+for+longitudinal+binary+data+subject+to+nonignorable+missing+data.&rft.au=Albert%2C+P+S&rft.aulast=Albert&rft.aufirst=P&rft.date=2000-06-01&rft.volume=56&rft.issue=2&rft.spage=602&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-10 N1 - Date created - 2000-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serum ferritin concentration and recurrence of colorectal adenoma. AN - 71206880; 10868699 AB - Both body iron stores and dietary iron intake have been reported to increase risk of colorectal neoplasms. We assessed whether serum ferritin concentration was associated with recurrence of colorectal adenomas among 733 individuals with baseline determinations of ferritin as part of a multicenter clinical trial of antioxidant supplements for adenoma prevention. All study participants had at least one adenoma removed within 3 months before enrollment, and 269 of them developed one or more adenomas between follow-up colonoscopies conducted 1 and 4 years after enrollment. Baseline serum ferritin concentrations were analyzed both as a log-transformed continuous variable and as a categorical variable, defined as whether iron stores were nonreplete and low (ferritin 160 microg/liter). Analyses were based on multiple logistic regression models, including age, sex, study center, energy, alcohol, fiber, folate, and total fat intake, number of months between colonoscopic examinations, smoking status, and aspirin use. Overall, there was no statistically significant linear association between log ferritin concentration and adenoma recurrence (P = 0.33). Risk of adenoma recurrence was modestly increased among participants with ferritin concentrations >70 microg/liter relative to those with lower ferritin (odds ratio, 1.39; 95% confidence interval, 0.96-2.02). This result seemed more pronounced among women than men. Dietary intake of iron and red meat was inversely associated with adenoma recurrence among participants with replete iron stores but not consistently associated among those with nonreplete stores. Our findings suggest that any role of iron stores and dietary iron in influencing risk of colorectal adenoma recurrence is likely complex. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Tseng, M AU - Greenberg, E R AU - Sandler, R S AU - Baron, J A AU - Haile, R W AU - Blumberg, B S AU - McGlynn, K A AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 625 EP - 630 VL - 9 IS - 6 SN - 1055-9965, 1055-9965 KW - Iron, Dietary KW - 0 KW - Ferritins KW - 9007-73-2 KW - Index Medicus KW - Meat KW - Sex Factors KW - Logistic Models KW - Risk Factors KW - Humans KW - Adult KW - Surveys and Questionnaires KW - Aged KW - Middle Aged KW - Recurrence KW - Male KW - Female KW - Ferritins -- blood KW - Iron, Dietary -- adverse effects KW - Colorectal Neoplasms -- etiology KW - Colorectal Neoplasms -- blood KW - Adenoma -- etiology KW - Adenoma -- blood KW - Iron, Dietary -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71206880?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Serum+ferritin+concentration+and+recurrence+of+colorectal+adenoma.&rft.au=Tseng%2C+M%3BGreenberg%2C+E+R%3BSandler%2C+R+S%3BBaron%2C+J+A%3BHaile%2C+R+W%3BBlumberg%2C+B+S%3BMcGlynn%2C+K+A&rft.aulast=Tseng&rft.aufirst=M&rft.date=2000-06-01&rft.volume=9&rft.issue=6&rft.spage=625&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-13 N1 - Date created - 2000-12-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic and immunohistochemical analyses of p53 independently predict regional metastasis of gastric cancers. AN - 71206236; 10868700 AB - Either p53 gene mutation or immunohistochemical detection of p53 protein has not been consistently shown to have prognostic significance in human cancers, including gastric carcinomas. One hypothesis to explain this inconsistency is that some p53 mutations and p53 protein accumulation are not indicative of tumor progression. To test this hypothesis, we categorized p53 status in 105 gastric carcinomas according to types of mutations, numerical scores of immunohistochemical staining (IHC), or combinations thereof. The p53 status was then correlated with metastasis to liver or peritoneum. Gastric cancers with no p53 mutations were significantly less likely to metastasize than tumors with mutations. Intermediate IHC scores were inversely associated with metastasis. A substantial number of gastric cancers (31 of 105) showed positive p53 immunostaining without detectable mutations (p53-/IHC+), which suggested an accumulation of wild-type p53 protein, and also a significantly lower risk for metastasis. After adjusting for depth of invasion and lymph node involvement, the p53-/IHC+ combination predicted low metastatic risk better than either p53- or IHC+ with intermediate scores. These findings suggest that an accumulation of wild-type p53 protein occurs in gastric cancer cells and represents a stress-response mechanism that lowers metastatic potential. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Shiao, Y H AU - Palli, D AU - Caporaso, N E AU - Alvord, W G AU - Amorosi, A AU - Nesi, G AU - Saieva, C AU - Masala, G AU - Fraumeni, J F AU - Rice, J M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, NIH, Maryland 21702, USA. Shiao@mail.ncifcrf.gov Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 631 EP - 633 VL - 9 IS - 6 SN - 1055-9965, 1055-9965 KW - Biomarkers, Tumor KW - 0 KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Humans KW - Prognosis KW - Aged KW - Predictive Value of Tests KW - Multivariate Analysis KW - Biomarkers, Tumor -- metabolism KW - Risk Factors KW - Adult KW - Middle Aged KW - Immunohistochemistry KW - Mutation KW - Female KW - Male KW - Stomach Neoplasms -- pathology KW - Stomach Neoplasms -- metabolism KW - Neoplasm Metastasis -- genetics KW - Stomach Neoplasms -- genetics KW - Genes, p53 -- genetics KW - Tumor Suppressor Protein p53 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71206236?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Genetic+and+immunohistochemical+analyses+of+p53+independently+predict+regional+metastasis+of+gastric+cancers.&rft.au=Shiao%2C+Y+H%3BPalli%2C+D%3BCaporaso%2C+N+E%3BAlvord%2C+W+G%3BAmorosi%2C+A%3BNesi%2C+G%3BSaieva%2C+C%3BMasala%2C+G%3BFraumeni%2C+J+F%3BRice%2C+J+M&rft.aulast=Shiao&rft.aufirst=Y&rft.date=2000-06-01&rft.volume=9&rft.issue=6&rft.spage=631&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-13 N1 - Date created - 2000-12-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The von Hippel-Lindau tumor suppressor targets to mitochondria. AN - 71205196; 10850420 AB - Subcellular localization of von Hippel-Lindau (VHL) tumor suppressor may clarify its role in tumorigenesis. In rat kidney, we observed a granular cytoplasmic immunostaining of VHL, as seen in human tissues. The green fluorescent protein (GFP)-tagged VHL also appeared as cytoplasmic granules in vitro and was colocalized with a mitochondrion-selective dye. Immunogold electron microscopy localized VHL specifically to the mitochondrion. Mitochondria retaining GFP-VHL fusion protein, mimicking an insertional VHL mutant, displayed abnormal phenotypes. Among these, small mitochondria have been observed in clear cell renal carcinomas known to have frequent VHL alterations. Thus, VHL may contribute to tumorigenesis through mitochondria-based action. JF - Cancer research AU - Shiao, Y H AU - Resau, J H AU - Nagashima, K AU - Anderson, L M AU - Ramakrishna, G AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, NIH, Maryland 21702, USA. shiao@mail.ncifcrf.gov Y1 - 2000/06/01/ PY - 2000 DA - 2000 Jun 01 SP - 2816 EP - 2819 VL - 60 IS - 11 SN - 0008-5472, 0008-5472 KW - Luminescent Proteins KW - 0 KW - Tumor Suppressor Proteins KW - Green Fluorescent Proteins KW - 147336-22-9 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 - Microscopy, Confocal KW - Animals KW - Kidney -- metabolism KW - Luminescent Proteins -- metabolism KW - Plasmids KW - Epithelial Cells -- metabolism KW - Rats KW - Epithelial Cells -- cytology KW - Transfection KW - Cytoplasm -- metabolism KW - Immunohistochemistry KW - Cell Line KW - Protein Biosynthesis KW - Mitochondria -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71205196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=The+von+Hippel-Lindau+tumor+suppressor+targets+to+mitochondria.&rft.au=Shiao%2C+Y+H%3BResau%2C+J+H%3BNagashima%2C+K%3BAnderson%2C+L+M%3BRamakrishna%2C+G&rft.aulast=Shiao&rft.aufirst=Y&rft.date=2000-06-01&rft.volume=60&rft.issue=11&rft.spage=2816&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 - 2000-06-30 N1 - Date created - 2000-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Indoor coal combustion emissions, GSTM1 and GSTT1 genotypes, and lung cancer risk: a case-control study in Xuan Wei, China. AN - 71204161; 10868696 AB - The lung cancer mortality rate in Xuan Wei County, China is among the highest in the country and has been associated with exposure to indoor smoky coal emissions that contain high levels of polycyclic aromatic hydrocarbons. This risk may be modified by variation in metabolism genes, including GSTM1, which encodes an enzyme known to detoxify polycyclic aromatic hydrocarbons. To investigate the relationship between GST genotypes and lung cancer risk in Xuan Wei County, we analyzed GSTM1 and GSTT1 genotypes in a population-based case-control study. A total of 122 lung cancer patients and 122 controls, individually matched by age, sex, and home fuel type, were studied. Compared to subjects who used less than 130 tons of smoky coal during their lifetime, heavier users (> or =130 tons) had a 2.4-fold (95% confidence interval, 1.3-4.4) increased risk of lung cancer. The GSTM1-null genotype was associated with a 2.3-fold (95% confidence interval, 1.3-4.2) increased risk of lung cancer. Furthermore, there was some evidence that smoky coal use was more strongly associated with lung cancer risk among GSTM1-null versus GSTM1-positive individuals. In contrast, the GSTT1 genotype was not significantly associated with lung cancer risk. Our data suggest that the GSTM1-null genotype may enhance susceptibility to air pollution from indoor coal combustion emissions. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Lan, Q AU - He, X AU - Costa, D J AU - Tian, L AU - Rothman, N AU - Hu, G AU - Mumford, J L AD - Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill 27599-7315, USA. qingl@mail.nih.gov Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 605 EP - 608 VL - 9 IS - 6 SN - 1055-9965, 1055-9965 KW - Coal KW - 0 KW - glutathione S-transferase T1 KW - EC 2.5.1.- KW - Glutathione Transferase KW - EC 2.5.1.18 KW - glutathione S-transferase M1 KW - Index Medicus KW - Genotype KW - Air Pollution, Indoor -- adverse effects KW - Risk Factors KW - Humans KW - Case-Control Studies KW - Middle Aged KW - Male KW - Female KW - China KW - Lung Neoplasms -- enzymology KW - Lung Neoplasms -- etiology KW - Coal -- adverse effects KW - Polymorphism, Genetic KW - Lung Neoplasms -- genetics KW - Glutathione Transferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71204161?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Indoor+coal+combustion+emissions%2C+GSTM1+and+GSTT1+genotypes%2C+and+lung+cancer+risk%3A+a+case-control+study+in+Xuan+Wei%2C+China.&rft.au=Lan%2C+Q%3BHe%2C+X%3BCosta%2C+D+J%3BTian%2C+L%3BRothman%2C+N%3BHu%2C+G%3BMumford%2C+J+L&rft.aulast=Lan&rft.aufirst=Q&rft.date=2000-06-01&rft.volume=9&rft.issue=6&rft.spage=605&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-13 N1 - Date created - 2000-12-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quantitation of benzo[a]pyrene-DNA adducts by postlabeling with 14C-acetic anhydride and accelerator mass spectrometry. AN - 71202363; 10862816 AB - Quantitation of carcinogen-DNA adducts provides an estimate of the biologically effective dose of a chemical carcinogen reaching the target tissue. In order to improve exposure-assessment and cancer risk estimates, we are developing an ultrasensitive procedure for the detection of carcinogen-DNA adducts. The method is based upon postlabeling of carcinogen-DNA adducts by acetylation with 14C-acetic anhydride combined with quantitation of 14C by accelerator mass spectrometry (AMS). For this purpose, adducts of benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide (BPDE) with DNA and deoxyguanosine (dG) were synthesized. The most promutagenic adduct of BPDE, 7R,8S,9R-trihydroxy-10S-(N(2)-deoxyguanosyl)-7,8,9, 10-tetrahydrobenzo[a]pyrene (BPdG), was HPLC purified and structurally characterized. Postlabeling of the BPdG adduct with acetic anhydride yielded a major product with a greater than 60% yield. The postlabeled adduct was identified by liquid chromatography-mass spectrometry as pentakis(acetyl) BPdG (AcBPdG). Postlabeling of the BPdG adduct with 14C-acetic anhydride yielded a major product coeluting with an AcBPdG standard. Quantitation of the 14C-postlabeled adduct by AMS promises to allow detection of attomolar amounts of adducts. The method is now being optimized and validated for use in human samples. JF - Chemico-biological interactions AU - Goldman, R AU - Day, B W AU - Carver, T A AU - Mauthe, R J AU - Turteltaub, K W AU - Shields, P G AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. rg26@gunet.georgetown.edu Y1 - 2000/06/01/ PY - 2000 DA - 2000 Jun 01 SP - 171 EP - 183 VL - 126 IS - 3 SN - 0009-2797, 0009-2797 KW - Acetic Anhydrides KW - 0 KW - Carbon Radioisotopes KW - Carcinogens, Environmental KW - DNA Adducts KW - benzo(a)pyrene-DNA adduct KW - acetic anhydride KW - 2E48G1QI9Q KW - Benzo(a)pyrene KW - 3417WMA06D KW - Index Medicus KW - Animals KW - Acetylation KW - Cattle KW - Isotope Labeling -- methods KW - Spectrophotometry, Atomic KW - Chromatography, High Pressure Liquid KW - Acetic Anhydrides -- chemistry KW - DNA Adducts -- analysis KW - Benzo(a)pyrene -- analysis KW - Mass Spectrometry -- methods KW - Carcinogens, Environmental -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71202363?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemico-biological+interactions&rft.atitle=Quantitation+of+benzo%5Ba%5Dpyrene-DNA+adducts+by+postlabeling+with+14C-acetic+anhydride+and+accelerator+mass+spectrometry.&rft.au=Goldman%2C+R%3BDay%2C+B+W%3BCarver%2C+T+A%3BMauthe%2C+R+J%3BTurteltaub%2C+K+W%3BShields%2C+P+G&rft.aulast=Goldman&rft.aufirst=R&rft.date=2000-06-01&rft.volume=126&rft.issue=3&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=Chemico-biological+interactions&rft.issn=00092797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-20 N1 - Date created - 2000-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A four-nucleotide translation enhancer in the 3'-terminal consensus sequence of the nonpolyadenylated mRNAs of rotavirus. AN - 71200822; 10864041 AB - The 5' cap and poly(A) tail of eukaryotic mRNAs work synergistically to enhance translation through a process that requires interaction of the cap-associated eukaryotic initiation factor, eIF-4G, and the poly(A)-binding protein, PABP. Because the mRNAs of rotavirus, and other members of the Reoviridae, contain caps but lack poly(A) tails, their translation may be enhanced through a unique mechanism. To identify translation-enhancement elements in the viral mRNAs that stimulate translation in vivo, chimeric RNAs were prepared that contained an open reading frame for luciferase and the 5' and 3' untranslated regions (UTRs) of a rotavirus mRNA or of a nonviral mRNA. Transfection of the chimeric RNAs into rotavirus-infected cells showed that the viral 3' UTR contained a translation-enhancement element that promoted gene expression. The element did not enhance gene expression in uninfected cells and did not affect the stability of the RNAs. Mutagenesis showed that the conserved sequence GACC located at the 3' end of rotavirus mRNAs operated as an enhancement element. The 3'-GACC element stimulated protein expression independently of the sequence of the 5' UTR, although efficient expression required the RNA to contain a cap. The results indicate that the expression of viral proteins in rotavirus-infected cells is specifically up-regulated by the activity of a novel 4-nt 3' translation enhancer (TE) common to the 11 nonpolyadenylated mRNAs of the virus. The 4-nt sequence of the rotavirus 3' TE represents by far the shortest of any of the sequence enhancers known to stimulate translation. JF - RNA (New York, N.Y.) AU - Chizhikov, V AU - Patton, J T AD - Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 814 EP - 825 VL - 6 IS - 6 SN - 1355-8382, 1355-8382 KW - 3' Untranslated Regions KW - 0 KW - 5' Untranslated Regions KW - Nucleotides KW - RNA, Messenger KW - RNA, Viral KW - Poly A KW - 24937-83-5 KW - Index Medicus KW - Animals KW - 5' Untranslated Regions -- genetics KW - Consensus Sequence -- genetics KW - Gene Expression Regulation, Viral KW - Chimera -- genetics KW - Mutagenesis, Site-Directed -- genetics KW - Sequence Deletion -- genetics KW - RNA Stability -- genetics KW - Macaca mulatta KW - Templates, Genetic KW - Cell Line KW - Nucleotides -- genetics KW - 3' Untranslated Regions -- chemistry KW - Poly A -- genetics KW - Enhancer Elements, Genetic -- genetics KW - Poly A -- chemistry KW - Protein Biosynthesis -- genetics KW - Rotavirus -- genetics KW - RNA, Viral -- genetics KW - RNA, Messenger -- genetics KW - 3' Untranslated Regions -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71200822?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=RNA+%28New+York%2C+N.Y.%29&rft.atitle=A+four-nucleotide+translation+enhancer+in+the+3%27-terminal+consensus+sequence+of+the+nonpolyadenylated+mRNAs+of+rotavirus.&rft.au=Chizhikov%2C+V%3BPatton%2C+J+T&rft.aulast=Chizhikov&rft.aufirst=V&rft.date=2000-06-01&rft.volume=6&rft.issue=6&rft.spage=814&rft.isbn=&rft.btitle=&rft.title=RNA+%28New+York%2C+N.Y.%29&rft.issn=13558382&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-17 N1 - Date created - 2000-07-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1981 Sep;25(3):737-41 [7285116] Virology. 1992 Sep;190(1):68-83 [1326821] J Virol. 1983 Jul;47(1):125-36 [6306269] Virology. 1986 Dec;155(2):655-65 [3024405] Nucleic Acids Res. 1988 Jul 11;16(13):6244 [2840642] J Virol. 1988 Oct;62(10):3581-8 [3418781] J Virol. 1993 Jun;67(6):3159-65 [8388495] Mol Cell Biol. 1993 Sep;13(9):5331-47 [8355685] Mol Cell Biol. 1994 Mar;14(3):1709-20 [8114706] Curr Top Microbiol Immunol. 1994;185:31-66 [8050283] EMBO J. 1994 Sep 1;13(17):4165-73 [8076612] Virology. 1994 Oct;204(1):69-81 [8091686] J Virol. 1994 Nov;68(11):7030-9 [7933085] Nucleic Acids Res. 1995 Feb 25;23(4):654-62 [7899087] J Gen Virol. 1995 Nov;76 ( Pt 11):2633-44 [7595370] J Virol. 1996 Jun;70(6):3961-71 [8648733] J Virol. 1996 Nov;70(11):7833-41 [8892905] J Virol. 1996 Nov;70(11):7940-7 [8892917] EMBO J. 1996 Dec 16;15(24):7168-77 [9003792] Mol Cell Biol. 1997 Apr;17(4):2005-13 [9121448] J Biol Chem. 1997 Jun 27;272(26):16247-55 [9195926] Nature. 1998 Apr 2;392(6675):516-20 [9548259] J Virol. 1998 Sep;72(9):7387-96 [9696835] Gene. 1998 Aug 17;216(1):1-11 [9714706] EMBO J. 1998 Oct 1;17(19):5811-21 [9755181] Cell. 1998 Oct 2;95(1):135-46 [9778254] RNA. 1998 Nov;4(11):1347-56 [9814756] EMBO J. 1998 Dec 15;17(24):7480-9 [9857202] J Virol. 1999 Feb;73(2):1382-91 [9882343] J Mol Biol. 1999 May 21;288(5):911-40 [10329189] J Virol. 1999 Jul;73(7):5411-21 [10364288] RNA. 1999 Jun;5(6):728-38 [10376873] J Virol. 1989 May;63(5):2048-55 [2539501] Genes Dev. 1990 Jul;4(7):1149-57 [1976569] Genes Dev. 1991 Nov;5(11):2108-16 [1682219] Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5784-8 [1321421] Virology. 1983 Apr 15;126(1):204-12 [6302982] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - cDNA cloning and mapping of mouse pleckstrin (Plek), a gene upregulated in transformation-resistant cells. AN - 71197909; 10860665 AB - Changes that occur during tumor promotion, the rate-limiting phase of multistep carcinogenesis, may offer the best targets for prevention of cancer or reversal of early disease. The murine epidermal JB6 promotion-sensitive (P+) and -resistant (P-) cell lines provide a cell culture model for tumor promoter-induced neoplastic transformation ideally suited to the identification of molecular events that mediate or inhibit transformation. A differential display comparison of P+ and P- cell mRNAs yielded seven differentially expressed sequences. One of the sequences preferentially expressed in P- cells identified an approximately 3. 6-kb message that was induced to higher levels in P- cells following exposure to the tumor promoter 12-O-tetradecanoylphorbol acetate than in P+ cells. The message was detected in mRNA from heart, lung, and spleen. cDNA cloning of the P- preferential sequence revealed a high degree of identity to human pleckstrin (PLEK), the major PKC substrate in platelets (Tyers et al., 1988, Nature 333: 470). We report the complete mouse cDNA sequence of pleckstrin and the localization of the gene to chromosome 11, its expression in a nonhematopoetic cell line, and its potential role in blocking neoplastic transformation. JF - Genomics AU - Cmarik, J L AU - Hegamyer, G AU - Gerrard, B AU - Dean, M AU - Colburn, N H AD - Basic Research Laboratory, National Cancer Institute, Frederick, Maryland, 21702, USA. Y1 - 2000/06/01/ PY - 2000 DA - 2000 Jun 01 SP - 204 EP - 212 VL - 66 IS - 2 SN - 0888-7543, 0888-7543 KW - Blood Proteins KW - 0 KW - DNA, Complementary KW - Phosphoproteins KW - platelet protein P47 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Base Sequence KW - Sequence Homology, Nucleic Acid KW - Humans KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Cloning, Molecular KW - Phosphoproteins -- genetics KW - Up-Regulation KW - Cell Transformation, Neoplastic -- genetics KW - Blood Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71197909?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genomics&rft.atitle=cDNA+cloning+and+mapping+of+mouse+pleckstrin+%28Plek%29%2C+a+gene+upregulated+in+transformation-resistant+cells.&rft.au=Cmarik%2C+J+L%3BHegamyer%2C+G%3BGerrard%2C+B%3BDean%2C+M%3BColburn%2C+N+H&rft.aulast=Cmarik&rft.aufirst=J&rft.date=2000-06-01&rft.volume=66&rft.issue=2&rft.spage=204&rft.isbn=&rft.btitle=&rft.title=Genomics&rft.issn=08887543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-11 N1 - Date created - 2000-08-11 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF181829; GENBANK; AF181830 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Beta-catenin mutations and protein accumulation in all hepatoblastomas examined from B6C3F1 mice treated with anthraquinone or oxazepam. AN - 71176872; 10850429 AB - The molecular pathogenesis of hepatoblastomas in the B6C3F1 mouse is unclear but may involve alterations in the beta-catenin/Wnt signaling pathway as was recently described for chemically induced hepatocellular neoplasms and human liver cancers. The objective of this study was to characterize the mutation frequency and spectrum of beta-catenin mutations and the intracellular localization of beta-catenin protein accumulation in chemically induced hepatoblastomas. In this study, beta-catenin mutations were identified in all 19 anthraquinone-induced hepatoblastomas and all 8 oxazepam-induced hepatoblastomas examined. Although several hepatoblastomas had multiple deletion and/or point mutations, the pattern of mutations in the hepatoblastomas did not differ from that identified in hepatocellular neoplasms. In a majority of the hepatoblastomas (six of seven) examined by immunohistochemical methods, both nuclear and cytoplasmic localization of beta-catenin protein were detected, whereas in hepatocellular adenomas, carcinomas, and normal liver only membrane staining was observed. Our data suggest that beta-catenin mutations and the subsequent translocation of beta-catenin protein from the cell membrane to the cytoplasm and nucleus may be critical steps in providing hepatocellular proliferative lesions with the growth advantage to progress to hepatoblastoma. JF - Cancer research AU - Anna, C H AU - Sills, R C AU - Foley, J F AU - Stockton, P S AU - Ton, T V AU - Devereux, T R AD - Laboratories of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000/06/01/ PY - 2000 DA - 2000 Jun 01 SP - 2864 EP - 2868 VL - 60 IS - 11 SN - 0008-5472, 0008-5472 KW - Anthraquinones KW - 0 KW - CTNNB1 protein, mouse KW - Carcinogens KW - Codon KW - Cytoskeletal Proteins KW - Trans-Activators KW - beta Catenin KW - Oxazepam KW - 6GOW6DWN2A KW - Index Medicus KW - Animals KW - Blotting, Western KW - Liver -- metabolism KW - Mice KW - Immunohistochemistry KW - Polymorphism, Single-Stranded Conformational KW - Male KW - Liver Neoplasms -- metabolism KW - Liver Neoplasms -- chemically induced KW - Hepatoblastoma -- metabolism KW - Hepatoblastoma -- chemically induced KW - Cytoskeletal Proteins -- biosynthesis KW - Hepatoblastoma -- genetics KW - Mutation KW - Cytoskeletal Proteins -- genetics KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71176872?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Beta-catenin+mutations+and+protein+accumulation+in+all+hepatoblastomas+examined+from+B6C3F1+mice+treated+with+anthraquinone+or+oxazepam.&rft.au=Anna%2C+C+H%3BSills%2C+R+C%3BFoley%2C+J+F%3BStockton%2C+P+S%3BTon%2C+T+V%3BDevereux%2C+T+R&rft.aulast=Anna&rft.aufirst=C&rft.date=2000-06-01&rft.volume=60&rft.issue=11&rft.spage=2864&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 - 2000-06-30 N1 - Date created - 2000-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A review of tobacco smoking in adolescents: treatment implications. AN - 71174478; 10846302 AB - To review current data on the tobacco epidemic in adolescents that impact treatment decisions. Epidemiological and pharmacological data, risk factors, characteristics of nicotine use in adolescents, and treatment intervention reports from the literature are discussed. Of students in grades 9 to 12, 42.7% have used tobacco; 75% of teenage smokers will smoke as adults. Environmental and biological factors influence adolescent smoking, including sociodevelopmental aspects of adolescence, psychiatric history, genetic background, ethnic and gender characteristics, drug effects, and regulatory factors. Criteria for nicotine dependence are currently based on the experience with adult smokers. Overall, smoking cessation treatment for adolescents has been disappointing because of low participation, high attrition, and low quit rates. Characterization of nicotine dependence and further assessment of the safety and efficacy of pharmacological treatment interventions in adolescents are needed given the formidable challenge of the tobacco epidemic in adolescents. JF - Journal of the American Academy of Child and Adolescent Psychiatry AU - Moolchan, E T AU - Ernst, M AU - Henningfield, J E AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 682 EP - 693 VL - 39 IS - 6 SN - 0890-8567, 0890-8567 KW - Index Medicus KW - Humans KW - Behavior, Addictive -- psychology KW - Adolescent KW - Male KW - Female KW - Smoking Cessation -- psychology KW - Tobacco Use Disorder -- epidemiology KW - Adolescent Behavior -- psychology KW - Smoking Cessation -- methods KW - Tobacco Use Disorder -- prevention & control KW - Smoking -- psychology KW - Smoking -- prevention & control KW - Smoking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71174478?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.atitle=A+review+of+tobacco+smoking+in+adolescents%3A+treatment+implications.&rft.au=Moolchan%2C+E+T%3BErnst%2C+M%3BHenningfield%2C+J+E&rft.aulast=Moolchan&rft.aufirst=E&rft.date=2000-06-01&rft.volume=39&rft.issue=6&rft.spage=682&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.issn=08908567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-27 N1 - Date created - 2000-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Xenopus IRBP, a phylogenetically remote protein, is uveitogenic in Lewis rats. AN - 71173847; 10843777 AB - Mammalian interphotoreceptor retinoid-binding proteins (IRBPs) are highly uveitogenic in Lewis rats. Xenopus laevis IRBP resembles mammalian IRBP in its four-fold structure, and has approximately 70% amino acid sequence identity with the bovine protein. This study investigated the uveitogenicity of recombinant Xenopus IRBP and two of its derived peptides in Lewis rats. Rats immunized with Xenopus IRBP developed uveoretinitis as well as pineal inflammation. The Xenopus molecule was, however, less immunopathogenic than the bovine IRBP. Of the two Xenopus IRBP peptides tested, 1180-1191 was remarkably uveitogenic, whereas sequence 521-540 exhibited low activity. It is assumed, therefore, that as with bovine IRBP, peptide 1180-1191 is the major uveitogenic sequence in Xenopus IRBP. The role individual residues of these peptides play in the immunopathogenic process is discussed. Our data thus demonstrate that despite its being phylogenetically remote, Xenopus IRBP is uveitogenic in Lewis rats Copyright 2000 Academic Press. JF - Experimental eye research AU - Gelderman, M P AU - Gonzalez-Fernandez, F AU - Baer, C A AU - Wiggert, B AU - Chan, C C AU - Vistica, B P AU - Gery, I AD - National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1857, USA. Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 731 EP - 736 VL - 70 IS - 6 SN - 0014-4835, 0014-4835 KW - Eye Proteins KW - 0 KW - Recombinant Fusion Proteins KW - Retinol-Binding Proteins KW - interstitial retinol-binding protein KW - Index Medicus KW - Rats KW - Animals KW - Uvea -- pathology KW - Recombinant Fusion Proteins -- adverse effects KW - Rats, Inbred Lew KW - Cattle KW - Pineal Gland -- pathology KW - Humans KW - Xenopus KW - Retina -- pathology KW - Rats, Inbred BN KW - Male KW - Immunization KW - Uveitis -- pathology KW - Retinitis -- pathology KW - Retinol-Binding Proteins -- administration & dosage KW - Retinol-Binding Proteins -- adverse effects KW - Autoimmune Diseases -- chemically induced KW - Retinitis -- chemically induced KW - Uveitis -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71173847?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+eye+research&rft.atitle=Xenopus+IRBP%2C+a+phylogenetically+remote+protein%2C+is+uveitogenic+in+Lewis+rats.&rft.au=Gelderman%2C+M+P%3BGonzalez-Fernandez%2C+F%3BBaer%2C+C+A%3BWiggert%2C+B%3BChan%2C+C+C%3BVistica%2C+B+P%3BGery%2C+I&rft.aulast=Gelderman&rft.aufirst=M&rft.date=2000-06-01&rft.volume=70&rft.issue=6&rft.spage=731&rft.isbn=&rft.btitle=&rft.title=Experimental+eye+research&rft.issn=00144835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-17 N1 - Date created - 2000-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recurrent intraocular inflammation in endotoxin-induced uveitis. AN - 71173742; 10845604 AB - Endotoxin-induced uveitis (EIU) in rats and mice peaks 24 hours after endotoxin injection and is commonly assumed to be a monophasic disease. This study examined intraocular inflammation at later time points to determine whether endotoxin injection can induce recurrent intraocular inflammation in strains of mice with high or moderate levels of susceptibility to EIU. EIU was elicited in two mouse strains with high (C3H/HeN) and moderate (FVB/N) susceptibility, by means of intraperitoneal injections of Salmonella typhimurium endotoxin. Inflammatory cells in the anterior and posterior segments of the eye were counted by a masked observer on histologic sections of eyes from 1 to 17 days after endotoxin injection. A bimodal distribution of inflammatory cell infiltration was noted in eyes from C3H/HeN mice. As previously reported, inflammation peaked at 24 hours after endotoxin injection. However, a second, more pronounced peak of intraocular inflammation occurred approximately 5 days after endotoxin injection. FVB/N mice had a single peak of intraocular inflammation 4 days after injection. Endotoxin injection in C3H/HeN elicits recurrent intraocular inflammation. The previously unrecognized second peak of inflammation is more severe than the initial inflammatory disease. Studies on this second inflammatory peak may be useful in determining the pathogenesis of recurrent uveitis in humans. JF - Investigative ophthalmology & visual science AU - Kozhich, A T AU - Chan, C C AU - Gery, I AU - Whitcup, S M AD - National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 1823 EP - 1826 VL - 41 IS - 7 SN - 0146-0404, 0146-0404 KW - Lipopolysaccharides KW - 0 KW - Index Medicus KW - Injections, Intraperitoneal KW - Animals KW - Neutrophils -- pathology KW - Leukocytes, Mononuclear -- pathology KW - Cell Count KW - Mice, Inbred C3H KW - Mice KW - Anterior Eye Segment -- immunology KW - Time Factors KW - Anterior Eye Segment -- pathology KW - Recurrence KW - Female KW - Uveitis -- pathology KW - Lipopolysaccharides -- toxicity KW - Uveitis -- immunology KW - Salmonella typhimurium KW - Uveitis -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71173742?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Recurrent+intraocular+inflammation+in+endotoxin-induced+uveitis.&rft.au=Kozhich%2C+A+T%3BChan%2C+C+C%3BGery%2C+I%3BWhitcup%2C+S+M&rft.aulast=Kozhich&rft.aufirst=A&rft.date=2000-06-01&rft.volume=41&rft.issue=7&rft.spage=1823&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 - 2000-06-14 N1 - Date created - 2000-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hypoxia-inducible factor-1 (HIF-1) up-regulates adrenomedullin expression in human tumor cell lines during oxygen deprivation: a possible promotion mechanism of carcinogenesis. AN - 71169043; 10847587 AB - Little is known about the molecular mechanisms that control adrenomedullin (AM) production in human cancers. We demonstrate here that the expression of AM mRNA in a variety of human tumor cell lines is highly induced in a time-dependent manner by reduced oxygen tension (1% O2) or exposure to hypoxia mimetics such as desferrioxamine mesylate (DFX) or CoCl2. This AM expression seems to be under hypoxia-inducible factor-1 (HIF-1) transcriptional regulation, since HIF-1alpha and HIF-1beta knockout mouse cell lines had an ablated or greatly reduced hypoxia AM mRNA induction. Similarly, inhibition or enhancement of HIF-1 activity in human tumor cells showed an analogous modulation of AM mRNA. Under hypoxic conditions, immunohistochemical analysis of tumor cell lines revealed elevated levels of AM and HIF-1alpha as compared with normoxia, and we also found an increase of immunoreactive AM in the conditioned medium of tumor cells analyzed by RIA. AM mRNA stabilization was shown to be partially responsible for the hypoxic up-regulated expression of AM. In addition, we have identified several putative hypoxia response elements (HREs) in the human AM gene, and reporter studies with selected HREs were capable of enhancing luciferase expression after exposure to DFX. Furthermore, transient coexpression of HIF-1alpha resulted in an augmented transactivation of the reporter gene after DFX treatment. Given that most solid human tumors have focal hypoxic areas and that AM functions as a mitogen, angiogenic factor, and apoptosis-survival factor, our findings implicate the HIF-1/AM link as a possible promotion mechanism of carcinogenesis. JF - Molecular endocrinology (Baltimore, Md.) AU - Garayoa, M AU - Martínez, A AU - Lee, S AU - Pío, R AU - An, W G AU - Neckers, L AU - Trepel, J AU - Montuenga, L M AU - Ryan, H AU - Johnson, R AU - Gassmann, M AU - Cuttitta, F AD - Department of Cell and Cancer Biology, National Cancer Institute, National Institutes of Health Bethesda, Maryland 20892, USA. garayoam@bprb.nci.nih.gov Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 848 EP - 862 VL - 14 IS - 6 SN - 0888-8809, 0888-8809 KW - Culture Media, Conditioned KW - 0 KW - DNA-Binding Proteins KW - HIF1A protein, human KW - Hypoxia-Inducible Factor 1 KW - Hypoxia-Inducible Factor 1, alpha Subunit KW - Nuclear Proteins KW - Peptides KW - RNA, Messenger KW - Transcription Factors KW - Adrenomedullin KW - 148498-78-6 KW - DNA KW - 9007-49-2 KW - Luciferases KW - EC 1.13.12.- KW - Deferoxamine KW - J06Y7MXW4D KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - DNA -- metabolism KW - Humans KW - RNA, Messenger -- biosynthesis KW - Promoter Regions, Genetic KW - Deferoxamine -- pharmacology KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - DNA -- chemistry KW - Oxygen -- administration & dosage KW - Response Elements KW - Luciferases -- genetics KW - Immunohistochemistry KW - Nuclear Proteins -- analysis KW - Nuclear Proteins -- pharmacology KW - DNA-Binding Proteins -- analysis KW - DNA-Binding Proteins -- pharmacology KW - Peptides -- analysis KW - Peptides -- metabolism KW - Peptides -- genetics KW - Cell Hypoxia KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71169043?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+endocrinology+%28Baltimore%2C+Md.%29&rft.atitle=Hypoxia-inducible+factor-1+%28HIF-1%29+up-regulates+adrenomedullin+expression+in+human+tumor+cell+lines+during+oxygen+deprivation%3A+a+possible+promotion+mechanism+of+carcinogenesis.&rft.au=Garayoa%2C+M%3BMart%C3%ADnez%2C+A%3BLee%2C+S%3BP%C3%ADo%2C+R%3BAn%2C+W+G%3BNeckers%2C+L%3BTrepel%2C+J%3BMontuenga%2C+L+M%3BRyan%2C+H%3BJohnson%2C+R%3BGassmann%2C+M%3BCuttitta%2C+F&rft.aulast=Garayoa&rft.aufirst=M&rft.date=2000-06-01&rft.volume=14&rft.issue=6&rft.spage=848&rft.isbn=&rft.btitle=&rft.title=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.issn=08888809&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-03 N1 - Date created - 2000-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Triplet repeat expansion in neuromuscular disease. AN - 71167837; 10842259 AB - Expansions of unstable trinucleotide repeats cause at least 15 inherited neurologic diseases. Here we review what has been learned of three neuromuscular diseases caused by this type of mutation. X-linked spinal and bulbar muscular atrophy is a motor neuronopathy caused by a CAG repeat expansion in the androgen receptor gene. The mutated protein has an expanded polyglutamine tract, forms intranuclear aggregates, and mediates neurodegeneration through a toxic gain-of-function mechanism. Oculopharyngeal muscular dystrophy is a dominantly inherited myopathy caused by a GCG/polyalanine expansion in the gene encoding poly(A)-binding protein 2. Myotonic dystrophy is a clinically variable multisystem disease caused by a CTG expansion in the 3' untranslated region of the myotonin gene. For each of these disorders, we summarize the clinical and pathologic features and review current understanding of the molecular mechanisms underlying their pathogenesis. Copyright 2000 John Wiley & Sons, Inc. JF - Muscle & nerve AU - Lieberman, A P AU - Fischbeck, K H AD - Neurogenetics Branch, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. lieberma@ninds.nih.gov Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 843 EP - 850 VL - 23 IS - 6 SN - 0148-639X, 0148-639X KW - Index Medicus KW - Humans KW - Trinucleotide Repeats KW - Neuromuscular Diseases -- genetics KW - Neuromuscular Diseases -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71167837?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Muscle+%26+nerve&rft.atitle=Triplet+repeat+expansion+in+neuromuscular+disease.&rft.au=Lieberman%2C+A+P%3BFischbeck%2C+K+H&rft.aulast=Lieberman&rft.aufirst=A&rft.date=2000-06-01&rft.volume=23&rft.issue=6&rft.spage=843&rft.isbn=&rft.btitle=&rft.title=Muscle+%26+nerve&rft.issn=0148639X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-21 N1 - Date created - 2000-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vulnerability to calcium-induced neurotoxicity in cultured neurons expressing calretinin. AN - 71158499; 10833305 AB - Calretinin (CR) is a calcium-binding protein purported to have neuroprotective properties. This study was designed to characterize the types of neurons containing CR in two different primary cultures and to determine which, if any, CR-immunoreactive (CR-ir) neurons are resistant to excitotoxic insults. Calretinin-containing neurons in cortical primary cultures derived from E14 rat embryos were not resistant to either kainic acid or a brief calcium overload induced by the calcium ionophore A23187. Equal proportions of CR-ir and GABAergic cortical neurons were lost after a 24-h exposure to 100 or 500 microM kainic acid. A 3 microM, 3-h exposure to A23187 induced equivalent amounts of cell loss in both the total cell and CR-ir cortical neuron culture populations. Cortical cultures grown for 6-7 days were more vulnerable than 12- to 13-day-old cultures to short-term, low-concentration treatments of A23187. Older cultures, however, were more severely affected when examined 24 h after a 3-h exposure to A23187. Calretinin-immunoreactive neurons derived from the diencephalon were relatively more resistant than cortical neurons to kainic acid at 6-7 days in vitro. In cortical or diencephalic cultures, CR was rarely coexpressed with GABA or calbindin D-28k. No vasoactive intestinal peptide, substance P, or parvalbumin was detected in CR-ir neurons in either culture system. We suggest that the presence of CR alone is not sufficient to spare neurons from a toxic calcium overload. Calretinin may still buffer calcium at low concentrations or be a component in a calcium-based signal transduction system. Copyright 2000 Academic Press. JF - Experimental neurology AU - Isaacs, K R AU - Wolpoe, M E AU - Jacobowitz, D M AD - Laboratory of Clinical Science, National Institute of Mental Health, Bldg. 10, Rm. 3D48, Bethesda, Maryland 20892, USA. Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 311 EP - 323 VL - 163 IS - 2 SN - 0014-4886, 0014-4886 KW - Calb2 protein, rat KW - 0 KW - Calbindin 2 KW - Excitatory Amino Acid Agonists KW - Ionophores KW - Receptors, AMPA KW - S100 Calcium Binding Protein G KW - glutamate receptor ionotropic, AMPA 2 KW - glutamate receptor ionotropic, AMPA 3 KW - Calcimycin KW - 37H9VM9WZL KW - Kainic Acid KW - SIV03811UC KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Receptors, AMPA -- drug effects KW - Cerebral Cortex -- drug effects KW - Diencephalon -- metabolism KW - Kainic Acid -- pharmacology KW - Diencephalon -- drug effects KW - Cerebral Cortex -- metabolism KW - Receptors, AMPA -- metabolism KW - Calcimycin -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Ionophores -- pharmacology KW - Cells, Cultured KW - Excitatory Amino Acid Agonists -- pharmacology KW - Embryo, Mammalian KW - Calcium -- metabolism KW - Neurons -- metabolism KW - S100 Calcium Binding Protein G -- drug effects KW - Neurons -- drug effects KW - S100 Calcium Binding Protein G -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71158499?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Vulnerability+to+calcium-induced+neurotoxicity+in+cultured+neurons+expressing+calretinin.&rft.au=Isaacs%2C+K+R%3BWolpoe%2C+M+E%3BJacobowitz%2C+D+M&rft.aulast=Isaacs&rft.aufirst=K&rft.date=2000-06-01&rft.volume=163&rft.issue=2&rft.spage=311&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 - 2000-07-17 N1 - Date created - 2000-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of disease severity in mice with targeted disruption of the acid alpha-glucosidase gene. AN - 71156135; 10838256 AB - Glycogen storage disease type II (GSDII) is a recessively inherited disorder caused by defects in lysosomal acid alpha-glucosidase. In an attempt to reproduce the range of clinical manifestations of the human illness we have created null alleles at the acid alpha-glucosidase locus (GAA) with several gene targeting strategies. In each knockout strain, enzyme activity was completely abolished and glycogen accumulated at indistinguishable rates. The phenotypes, however, differed strikingly. Acid alpha-glucosidase deficiency on a 129xC57BL/6 background resulted in a severe phenotype with progressive cardiomyopathy and profound muscle wasting similar to that in patients with glycogen storage disease type II. On a 129/C57BL/6xFVB background, homozygous mutants developed a milder phenotype with a later age of onset. Females were more affected than males irrespective of genetic background. As in humans with glycogen storage disease type II, therefore, other genetic loci affect the phenotypic expression of a single gene mutation. JF - Neuromuscular disorders : NMD AU - Raben, N AU - Nagaraju, K AU - Lee, E AU - Plotz, P AD - Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 10/9N244, 9000 Rockville Pike, Bethesda, MD 20892, USA. rabenn@arb.niams.nih.gov Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 283 EP - 291 VL - 10 IS - 4-5 SN - 0960-8966, 0960-8966 KW - RNA, Messenger KW - 0 KW - alpha-Glucosidases KW - EC 3.2.1.20 KW - Index Medicus KW - Motor Activity -- genetics KW - Animals KW - Age Factors KW - Disease Progression KW - Disease Models, Animal KW - Mice KW - Motor Activity -- physiology KW - Mutagenesis -- genetics KW - Mice, Knockout KW - Phenotype KW - RNA, Messenger -- metabolism KW - Treatment Outcome KW - Mice, Inbred C57BL KW - Genetic Therapy -- methods KW - Gene Targeting KW - Glycogen Storage Disease Type II -- genetics KW - Glycogen Storage Disease Type II -- physiopathology KW - alpha-Glucosidases -- deficiency KW - Glycogen Storage Disease Type II -- pathology KW - alpha-Glucosidases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71156135?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuromuscular+disorders+%3A+NMD&rft.atitle=Modulation+of+disease+severity+in+mice+with+targeted+disruption+of+the+acid+alpha-glucosidase+gene.&rft.au=Raben%2C+N%3BNagaraju%2C+K%3BLee%2C+E%3BPlotz%2C+P&rft.aulast=Raben&rft.aufirst=N&rft.date=2000-06-01&rft.volume=10&rft.issue=4-5&rft.spage=283&rft.isbn=&rft.btitle=&rft.title=Neuromuscular+disorders+%3A+NMD&rft.issn=09608966&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-02 N1 - Date created - 2000-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Localization and molecular determinants of the Hanatoxin receptors on the voltage-sensing domains of a K(+) channel. AN - 71153515; 10828242 AB - Hanatoxin inhibits voltage-gated K(+) channels by modifying the energetics of activation. We studied the molecular determinants and physical location of the Hanatoxin receptors on the drk1 voltage-gated K(+) channel. First, we made multiple substitutions at three previously identified positions in the COOH terminus of S3 to examine whether these residues interact intimately with the toxin. We also examined a region encompassing S1-S3 using alanine-scanning mutagenesis to identify additional determinants of the toxin receptors. Finally, guided by the structure of the KcsA K(+) channel, we explored whether the toxin interacts with the peripheral extracellular surface of the pore domain in the drk1 K(+) channel. Our results argue for an intimate interaction between the toxin and the COOH terminus of S3 and suggest that the Hanatoxin receptors are confined within the voltage-sensing domains of the channel, at least 20-25 A away from the central pore axis. JF - The Journal of general physiology AU - Li-Smerin, Y AU - Swartz, K J AD - Molecular Physiology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 673 EP - 684 VL - 115 IS - 6 SN - 0022-1295, 0022-1295 KW - Delayed Rectifier Potassium Channels KW - 0 KW - Peptides KW - Potassium Channel Blockers KW - Potassium Channels KW - Potassium Channels, Voltage-Gated KW - hanatoxin KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Animals KW - Membrane Potentials -- physiology KW - Amino Acid Sequence KW - Oocytes -- physiology KW - Electric Stimulation KW - Binding Sites -- physiology KW - Protein Structure, Quaternary KW - Xenopus laevis KW - Patch-Clamp Techniques KW - Molecular Sequence Data KW - Mutagenesis, Site-Directed -- physiology KW - Membrane Potentials -- drug effects KW - Female KW - Ion Channel Gating -- physiology KW - Potassium Channels -- chemistry KW - Potassium Channels -- genetics KW - Peptides -- metabolism KW - Peptides -- pharmacology KW - Ion Channel Gating -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71153515?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+general+physiology&rft.atitle=Localization+and+molecular+determinants+of+the+Hanatoxin+receptors+on+the+voltage-sensing+domains+of+a+K%28%2B%29+channel.&rft.au=Li-Smerin%2C+Y%3BSwartz%2C+K+J&rft.aulast=Li-Smerin&rft.aufirst=Y&rft.date=2000-06-01&rft.volume=115&rft.issue=6&rft.spage=673&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+general+physiology&rft.issn=00221295&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-21 N1 - Date created - 2000-07-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Neuron. 1996 Jun;16(6):1159-67 [8663992] Neuron. 1996 Jan;16(1):131-9 [8562077] Cell. 1996 Jun 28;85(7):1067-76 [8674113] J Biol Chem. 1996 Jul 5;271(27):15950-62 [8663157] Pflugers Arch. 1996 Nov-Dec;433(1-2):91-7 [9019737] Biophys J. 1997 Apr;72(4):1489-500 [9083655] Biophys J. 1997 May;72(5):2117-28 [9129813] Neuron. 1997 Apr;18(4):665-73 [9136774] Neuron. 1997 Apr;18(4):675-82 [9136775] Biochemistry. 1997 Jun 10;36(23):6936-40 [9188688] Neuron. 1997 Nov;19(5):1127-40 [9390525] J Gen Physiol. 1998 Mar;111(3):399-420 [9482708] J Gen Physiol. 1998 Mar;111(3):421-39 [9482709] Science. 1998 Apr 3;280(5360):69-77 [9525859] Science. 1998 Apr 3;280(5360):106-9 [9525854] J Mol Biol. 1998 Apr 17;277(5):1111-28 [9571026] J Mol Biol. 1998 Jul 3;280(1):1-9 [9653027] Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8585-9 [9671721] Biochemistry. 1998 Sep 22;37(38):13291-9 [9748337] Biochemistry. 1998 Oct 20;37(42):14867-74 [9778362] J Mol Biol. 1999 Feb 5;285(5):2177-98 [9925793] J Gen Physiol. 1999 Mar;113(3):389-414 [10051516] J Gen Physiol. 1999 Mar;113(3):415-23 [10051517] Nat Neurosci. 1998 Dec;1(8):668-74 [10196582] J Gen Physiol. 1999 Oct;114(4):551-60 [10498673] Neuron. 1996 Feb;16(2):387-97 [8789953] J Gen Physiol. 2000 Jan;115(1):33-50 [10613917] J Gen Physiol. 2000 Jan;115(1):51-8 [10613918] Neuron. 2000 Feb;25(2):411-23 [10719895] J Mol Biol. 2000 Mar 31;297(3):771-80 [10731427] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] J Mol Biol. 1982 May 5;157(1):105-32 [7108955] J Gen Physiol. 1988 Mar;91(3):335-49 [2454283] Nature. 1989 Aug 24;340(6235):642-5 [2770868] Science. 1989 Sep 22;245(4924):1382-5 [2476850] Neuron. 1988 Dec;1(10):1003-6 [2483092] Nature. 1991 Jan 24;349(6307):305-10 [1846229] Mol Pharmacol. 1991 Oct;40(4):572-6 [1921987] Nature. 1991 Oct 24;353(6346):752-6 [1944534] Proc Biol Sci. 1991 Aug 22;245(1313):101-7 [1682932] Neuron. 1992 Aug;9(2):307-13 [1379820] Biochemistry. 1992 Sep 1;31(34):7749-55 [1380827] Biophys J. 1993 Oct;65(4):1613-9 [7506068] Biochemistry. 1994 Jan 18;33(2):443-50 [7506933] Biophys J. 1994 Feb;66(2 Pt 1):345-54 [8161688] Biochemistry. 1994 Jun 7;33(22):6834-9 [8204618] Neuron. 1994 Jun;12(6):1377-88 [7516689] Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9509-13 [7524078] Curr Biol. 1994 Feb 1;4(2):110-5 [7953509] Science. 1995 Jan 20;267(5196):383-6 [7529940] Science. 1995 Apr 14;268(5208):307-10 [7716527] J Mol Biol. 1995 Apr 28;248(2):478-86 [7739054] Neuron. 1995 Jun;14(6):1293-301 [7605638] Neuron. 1995 Jul;15(1):5-10 [7542463] Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9422-6 [7568145] Neuron. 1995 Oct;15(4):941-9 [7576642] Protein Sci. 1995 Aug;4(8):1478-89 [8520473] EMBO J. 1995 Nov 1;14(21):5170-8 [7489706] Science. 1996 Jan 12;271(5246):213-6 [8539623] Neuron. 1996 Jan;16(1):113-22 [8562074] Neuron. 1996 Jan;16(1):123-30 [8562075] Neuron. 1996 Jun;16(6):1169-77 [8663993] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cross-talk between epidermal growth factor receptor and protein kinase C during calcium-induced differentiation of keratinocytes. AN - 71149806; 10839717 AB - The induction of epidermal differentiation by extracellular Ca2+ involves activation of both tyrosine kinase and protein kinase C (PKC) signaling cascades. To determine if the differentiation-dependent activation of tyrosine kinase signaling can influence the PKC pathway, we examined the tyrosine phosphorylation status of PKC isoforms in primary mouse keratinocytes stimulated to terminally differentiate with Ca2+. Elevation of extracellular Ca2+ induced tyrosine phosphorylation of PKC-delta, but not the other keratinocyte PKC isoforms (alpha, epsilon, eta, zeta). We have previously demonstrated that activation of the epidermal growth factor receptor (EGFR) pathway induces PKC-delta tyrosine phosphorylation in basal keratinocytes (Denning M F, Dlugosz A A, Threadgill D W, Magnuson T, Yuspa S H (1996) J Biol Chem 271: 5325-5331). When basal keratinocytes were stimulated to differentiate by Ca2+, the level of cell-associated transforming growth factor-alpha (TGF-alpha) increased 30-fold, while no increase in secreted TGF-alpha was detected. Furthermore, Ca2+-induced tyrosine phosphorylation of PKC-delta and phosphotyrosine-association of the receptor adapter protein Shc was diminished in EGFR -/- keratinocytes, suggesting that EGFR activation may occur during keratinocyte differentiation. Tyrosine phosphorylated PKC-delta was also detected in mouse epidermis, suggesting that this differentiation-associated signaling pathway is physiological. These results establish a requirement for the EGFR in Ca2+-induced tyrosine phosphorylation of PKC-delta, and document the production of cell-associated TGF-alpha in differentiated keratinocytes which may function independent of its usual mitogenic effects. JF - Experimental dermatology AU - Denning, M F AU - Dlugosz, A A AU - Cheng, C AU - Dempsey, P J AU - Coffey, R J AU - Threadgill, D W AU - Magnuson, T AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD, USA. Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 192 EP - 199 VL - 9 IS - 3 SN - 0906-6705, 0906-6705 KW - Isoenzymes KW - 0 KW - Transforming Growth Factor alpha KW - Tyrosine KW - 42HK56048U KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-delta KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Epidermis -- cytology KW - Receptor Cross-Talk KW - Epidermis -- metabolism KW - Calcium -- pharmacology KW - Mice KW - Mice, Knockout KW - Phosphorylation KW - Cells, Cultured KW - Transforming Growth Factor alpha -- biosynthesis KW - Tyrosine -- metabolism KW - Cell Differentiation -- drug effects KW - Protein Kinase C -- metabolism KW - Receptor, Epidermal Growth Factor -- metabolism KW - Receptor, Epidermal Growth Factor -- genetics KW - Keratinocytes -- drug effects KW - Keratinocytes -- cytology KW - Keratinocytes -- metabolism KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71149806?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+dermatology&rft.atitle=Cross-talk+between+epidermal+growth+factor+receptor+and+protein+kinase+C+during+calcium-induced+differentiation+of+keratinocytes.&rft.au=Denning%2C+M+F%3BDlugosz%2C+A+A%3BCheng%2C+C%3BDempsey%2C+P+J%3BCoffey%2C+R+J%3BThreadgill%2C+D+W%3BMagnuson%2C+T%3BYuspa%2C+S+H&rft.aulast=Denning&rft.aufirst=M&rft.date=2000-06-01&rft.volume=9&rft.issue=3&rft.spage=192&rft.isbn=&rft.btitle=&rft.title=Experimental+dermatology&rft.issn=09066705&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-25 N1 - Date created - 2000-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of gonadal steroids in women with a history of postpartum depression. AN - 71147911; 10831472 AB - Endocrine factors are purported to play a role in the etiology of postpartum depression, but direct evidence for this role is lacking. The authors investigated the possible role of changes in gonadal steroid levels in postpartum depression by simulating two hormonal conditions related to pregnancy and parturition in euthymic women with and without a history of postpartum depression. The supraphysiologic gonadal steroid levels of pregnancy and withdrawal from these high levels to a hypogonadal state were simulated by inducing hypogonadism in euthymic women-eight with and eight without a history of postpartum depression-with the gonadotropin-releasing hormone agonist leuprolide acetate, adding back supraphysiologic doses of estradiol and progesterone for 8 weeks, and then withdrawing both steroids under double-blind conditions. Outcome measures were daily symptom self-ratings and standardized subjective and objective cross-sectional mood rating scales. Five of the eight women with a history of postpartum depression (62.5%) and none of the eight women in the comparison group developed significant mood symptoms during the withdrawal period. Analysis of variance with repeated measures of daily and cross-sectional ratings of mood showed significant phase-by-group effects. These effects reflected significant increases in depressive symptoms in women with a history of postpartum depression but not in the comparison group after hormone withdrawal (and during the end of the hormone replacement phase), compared with baseline. The data provide direct evidence in support of the involvement of the reproductive hormones estrogen and progesterone in the development of postpartum depression in a subgroup of women. Further, they suggest that women with a history of postpartum depression are differentially sensitive to mood-destabilizing effects of gonadal steroids. JF - The American journal of psychiatry AU - Bloch, M AU - Schmidt, P J AU - Danaceau, M AU - Murphy, J AU - Nieman, L AU - Rubinow, D R AD - Behavioral Endocrinology Branch, NIMH, NIH, Bethesda, MD 20892-1276, USA. Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 924 EP - 930 VL - 157 IS - 6 SN - 0002-953X, 0002-953X KW - Placebos KW - 0 KW - Progesterone KW - 4G7DS2Q64Y KW - Estradiol KW - 4TI98Z838E KW - Leuprolide KW - EFY6W0M8TG KW - Abridged Index Medicus KW - Index Medicus KW - Substance Withdrawal Syndrome -- physiopathology KW - Affect -- drug effects KW - Personality Inventory -- statistics & numerical data KW - Humans KW - Hypogonadism -- physiopathology KW - Mood Disorders -- etiology KW - Hypogonadism -- blood KW - Cross-Sectional Studies KW - Hypogonadism -- etiology KW - Leuprolide -- pharmacology KW - Substance Withdrawal Syndrome -- etiology KW - Adult KW - Middle Aged KW - Substance Withdrawal Syndrome -- blood KW - Psychiatric Status Rating Scales -- statistics & numerical data KW - Female KW - Depression, Postpartum -- diagnosis KW - Progesterone -- physiology KW - Estradiol -- blood KW - Estradiol -- administration & dosage KW - Estradiol -- physiology KW - Progesterone -- administration & dosage KW - Depression, Postpartum -- blood KW - Progesterone -- blood KW - Depression, Postpartum -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71147911?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=Effects+of+gonadal+steroids+in+women+with+a+history+of+postpartum+depression.&rft.au=Bloch%2C+M%3BSchmidt%2C+P+J%3BDanaceau%2C+M%3BMurphy%2C+J%3BNieman%2C+L%3BRubinow%2C+D+R&rft.aulast=Bloch&rft.aufirst=M&rft.date=2000-06-01&rft.volume=157&rft.issue=6&rft.spage=924&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-29 N1 - Date created - 2000-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exendin-4 decelerates food intake, weight gain, and fat deposition in Zucker rats. AN - 71144579; 10830274 AB - Exendin-4 is a 39 amino acid peptide produced in the salivary gland of the Gila monster lizard. It has a 53% amino acid homology to the incretin hormone glucagon-like peptide-1 (GLP-1). Exendin-4 induces insulin release through activation of the GLP- 1 receptor but is a much more potent insulinotropic agent than GLP-1. Of critical importance for its potential use as a treatment for diabetes is its much longer biological effect in vivo. Previous studies involving once daily administration of exendin-4 over 13 weeks to db/db mice demonstrated that it lowers hemoglobin A1c (HbA1c), a marker of mean blood glucose levels. Food consumption in the treated animals dropped over the first 4 days and then increased to a level comparable with that of the untreated animals. In this study, we initially examined the effect of once daily injections (over 14 days) on the food consumption of Zucker fatty rats. We observed an immediate reduction in food intake which then leveled off(after 5 days) to match that of the untreated animals. Subsequently we injected the same animals twice daily (treatment period of 56 days in total) and observed a sustained reduction in food intake and weight-gain. This was matched by a reduction in the critical parameters of HbA1c, fasting blood glucose and plasma insulin. MRI imaging of the abdominal regions of the animals showed that initially only the amount of fat deposited in the sc region was reduced after 4 weeks exendin-4 treatment. At the 8-week time point there was a corresponding decrease in the amount of visceral fat deposition. The combination of appetite reduction, decreased fat deposition and an improvement in the parameters associated with glucose intolerance makes a case for the use of exendin-4 as a treatment for diabetes. JF - Endocrinology AU - Szayna, M AU - Doyle, M E AU - Betkey, J A AU - Holloway, H W AU - Spencer, R G AU - Greig, N H AU - Egan, J M AD - NMR Unit, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 1936 EP - 1941 VL - 141 IS - 6 SN - 0013-7227, 0013-7227 KW - Hemoglobin A, Glycosylated KW - 0 KW - Peptides KW - Venoms KW - exenatide KW - 9P1872D4OL KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Magnetic Resonance Imaging KW - Glucose Tolerance Test KW - Animals KW - Hemoglobin A, Glycosylated -- analysis KW - Lizards KW - Rats, Zucker KW - Male KW - Obesity -- drug therapy KW - Eating -- drug effects KW - Weight Gain -- drug effects KW - Adipose Tissue -- drug effects KW - Peptides -- pharmacology KW - Obesity -- physiopathology KW - Body Composition -- drug effects KW - Peptides -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71144579?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology&rft.atitle=Exendin-4+decelerates+food+intake%2C+weight+gain%2C+and+fat+deposition+in+Zucker+rats.&rft.au=Szayna%2C+M%3BDoyle%2C+M+E%3BBetkey%2C+J+A%3BHolloway%2C+H+W%3BSpencer%2C+R+G%3BGreig%2C+N+H%3BEgan%2C+J+M&rft.aulast=Szayna&rft.aufirst=M&rft.date=2000-06-01&rft.volume=141&rft.issue=6&rft.spage=1936&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-15 N1 - Date created - 2000-06-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Filgrastim as an alternative to donor leukocyte infusion for relapse after allogeneic stem-cell transplantation. AN - 71143121; 10829047 AB - Donor leukocyte infusion (DLI) effectively treats relapse after allogeneic stem-cell transplantation (alloSCT), but the response may require several months and may be associated with significant toxicity. Filgrastim has also been observed to effectively treat leukemic relapse after alloSCT. A retrospective analysis was performed to determine the effectiveness of filgrastim in treating relapses after alloSCT. Fourteen patients with hematologic malignancies were treated with filgrastim at relapse after alloSCT. Filgrastim was given at 5 mcg/kg/d subcutaneously for 21 consecutive days. Response was evaluated at 7 days after completion of filgrastim. Immunosuppressants, if present, were rapidly tapered to complete discontinuation at the time of relapse. Three patients were not assessable for response because additional therapy was necessary before completion of filgrastim. Six patients (43%) achieved a complete response on an intent-to-treat basis. When response was evaluated based on relapse type, three of four cytogenetic relapses, two of three morphologic relapses, and one of four hematologic relapses achieved a complete remission. Two responses were observed in patients who were completely off of any immunosuppression at the time of relapse. Six patients developed chronic graft-versus-host disease. The event-free and overall survival rates for all 14 patients are 43% and 73%, respectively. The use of filgrastim with rapid discontinuation of immunosuppression results in response rates that are similar to results using DLI. Filgrastim could be considered as an alternative or an adjunct to DLI for relapses after alloSCT. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Bishop, M R AU - Tarantolo, S R AU - Pavletic, Z S AU - Lynch, J C AU - Morris, M E AU - Zacharias, D AU - Armitage, J O AU - Kessinger, A AD - Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE. mbishop@mail.NIH.gov Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 2269 EP - 2272 VL - 18 IS - 11 SN - 0732-183X, 0732-183X KW - Genetic Markers KW - 0 KW - Recombinant Proteins KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Filgrastim KW - PVI5M0M1GW KW - Index Medicus KW - Cytogenetic Analysis KW - Humans KW - Retrospective Studies KW - Transplantation, Homologous KW - Recurrence KW - Survival Rate KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Female KW - Male KW - Leukocyte Transfusion KW - Leukemia, Lymphocytic, Chronic, B-Cell -- genetics KW - Myelodysplastic Syndromes -- therapy KW - Leukemia, Myeloid, Acute -- therapy KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Leukemia, Myeloid, Acute -- genetics KW - Hematopoietic Stem Cell Transplantation KW - Myelodysplastic Syndromes -- genetics KW - Leukemia, Lymphocytic, Chronic, B-Cell -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71143121?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Filgrastim+as+an+alternative+to+donor+leukocyte+infusion+for+relapse+after+allogeneic+stem-cell+transplantation.&rft.au=Bishop%2C+M+R%3BTarantolo%2C+S+R%3BPavletic%2C+Z+S%3BLynch%2C+J+C%3BMorris%2C+M+E%3BZacharias%2C+D%3BArmitage%2C+J+O%3BKessinger%2C+A&rft.aulast=Bishop&rft.aufirst=M&rft.date=2000-06-01&rft.volume=18&rft.issue=11&rft.spage=2269&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 - 2000-07-06 N1 - Date created - 2000-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetics of ventral forebrain development and holoprosencephaly. AN - 71136915; 10826992 AB - The disease holoprosencephaly is the basis of the most common structural anomaly of the developing forebrain in humans. Numerous teratogens when administered during early gastrulation, have been associated with this condition. Recent studies have characterized molecules expressed in the prechordal plate which are critical for normal brain formation. Perturbation of signaling pathways involving these molecules have been shown to cause holoprosencephaly in humans and other organisms. JF - Current opinion in genetics & development AU - Muenke, M AU - Beachy, P A AD - Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-1852, USA. mmuenke@nhgri.nih.gov Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 262 EP - 269 VL - 10 IS - 3 SN - 0959-437X, 0959-437X KW - Teratogens KW - 0 KW - Index Medicus KW - Animals KW - Embryonic and Fetal Development KW - Humans KW - Morphogenesis KW - Signal Transduction KW - Holoprosencephaly -- genetics KW - Holoprosencephaly -- embryology KW - Holoprosencephaly -- chemically induced KW - Prosencephalon -- embryology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71136915?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+genetics+%26+development&rft.atitle=Genetics+of+ventral+forebrain+development+and+holoprosencephaly.&rft.au=Muenke%2C+M%3BBeachy%2C+P+A&rft.aulast=Muenke&rft.aufirst=M&rft.date=2000-06-01&rft.volume=10&rft.issue=3&rft.spage=262&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+genetics+%26+development&rft.issn=0959437X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-14 N1 - Date created - 2000-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality from multiple sclerosis and exposure to residential and occupational solar radiation: a case-control study based on death certificates. AN - 71123850; 10810132 AB - To explore whether mortality from multiple sclerosis is negatively associated with exposure to sunlight. Two case-control studies based on death certificates were conducted for mortality from multiple sclerosis and non-melanoma skin cancer (as a positive control) to examine associations with residential and occupational exposure to sunlight. Cases were all deaths from multiple sclerosis between 1984 and 1995 in 24 states of the United States. Controls, which were age frequency matched to a series of cases, excluded cancer and certain neurological deaths. The effects of occupational exposure to sunlight were assessed among subjects with usual occupations requiring substantial activity, so as to exclude those whose indoor jobs resulted from disabilities subsequent to the onset of the disease. Multiple logistic regression analyses were applied, with adjustment for age, sex, race, and socioeconomic status. Unlike mortality from skin cancer, mortality from multiple sclerosis was negatively associated with residential exposure to sunlight (odds ratio (OR)=0.53 (multiple sclerosis) and OR=1.24 (skin cancer)). Odds ratios for the highest occupational exposure to sunlight were 0.74 (95% confidence interval (95% CI) 0.61 to 0.89) for mortality from multiple sclerosis, compared with 1.21 (1.09 to 1.34) for mortality from non-melanoma skin cancer. The OR was 0.24 for the combined effect of the highest levels of residential and occupational exposure to sunlight on multiple sclerosis, compared with an OR of 1.38 for skin cancer. In this exploratory study, mortality from multiple sclerosis, unlike mortality from skin cancer, was negatively associated with both residential and occupational exposure to sunlight. JF - Occupational and environmental medicine AU - Freedman, D M AU - Dosemeci, M AU - Alavanja, M C AD - Radiation Epidemiology Branch, National Cancer Institute, 6120 Executive Boulevard, Bethesda, Maryland 20892, USA. mf101e@nih.gov Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 418 EP - 421 VL - 57 IS - 6 SN - 1351-0711, 1351-0711 KW - Index Medicus KW - Social Class KW - Humans KW - Death Certificates KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - United States -- epidemiology KW - Male KW - Female KW - Radiation Injuries -- mortality KW - Radiation Injuries -- etiology KW - Sunlight -- adverse effects KW - Skin Neoplasms -- etiology KW - Occupational Exposure -- adverse effects KW - Multiple Sclerosis -- mortality KW - Skin Neoplasms -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71123850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+environmental+medicine&rft.atitle=Mortality+from+multiple+sclerosis+and+exposure+to+residential+and+occupational+solar+radiation%3A+a+case-control+study+based+on+death+certificates.&rft.au=Freedman%2C+D+M%3BDosemeci%2C+M%3BAlavanja%2C+M+C&rft.aulast=Freedman&rft.aufirst=D&rft.date=2000-06-01&rft.volume=57&rft.issue=6&rft.spage=418&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 completed - 2000-07-25 N1 - Date created - 2000-07-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Neuroepidemiology. 1995;14(6):286-96 [8570000] Am J Ind Med. 1995 Jun;27(6):817-35 [7645576] Cancer Causes Control. 1994 Jul;5(4):367-92 [8080949] Neuroepidemiology. 1994;13(3):120-8 [8015665] J Clin Epidemiol. 1994 Jan;47(1):43-8 [8283194] J Neurol Neurosurg Psychiatry. 1990 Oct;53(10):903-5 [2266373] Curr Opin Immunol. 1989 Apr;1(4):733-9 [2679727] JAMA. 1989 Oct 20;262(15):2097-100 [2795783] J Chronic Dis. 1983;36(8):551-9 [6885956] Am J Epidemiol. 1981 Jul;114(1):144-8 [7246522] Int J Epidemiol. 1980 Sep;9(3):227-31 [7440046] Neurology. 1979 Sep;29(9 Pt 1):1228-35 [573402] Public Health Rep. 1970 Sep;85(9):815-27 [4989476] Neurology. 1967 Jan;17(1):1-17 [5333273] Med Hypotheses. 1996 Feb;46(2):67-74 [8692046] Acta Psychiatr Scand Suppl. 1960;35(147):132-47 [13681205] Epidemiology. 1997 Nov;8(6):642-5 [9345663] Proc Soc Exp Biol Med. 1997 Oct;216(1):21-7 [9316607] Neurology. 1997 Aug;49(2 Suppl 2):S18-26 [9270689] South Med J. 1997 Feb;90(2):191-8 [9042170] Neurology. 1997 Jan;48(1):204-13 [9008519] Neurol Clin. 1996 May;14(2):291-308 [8827172] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conservation of polar residues as hot spots at protein interfaces. AN - 71120459; 10813815 AB - A number of studies have addressed the question of which are the critical residues at protein-binding sites. These studies examined either a single or a few protein-protein interfaces. The most extensive study to date has been an analysis of alanine-scanning mutagenesis. However, although the total number of mutations was large, the number of protein interfaces was small, with some of the interfaces closely related. Here we show that although overall binding sites are hydrophobic, they are studded with specific, conserved polar residues at specific locations, possibly serving as energy "hot spots." Our results confirm and generalize the alanine-scanning data analysis, despite its limited size. Previously Trp, Arg, and Tyr were shown to constitute energetic hot spots. These were rationalized by their polar interactions and by their surrounding rings of hydrophobic residues. However, there was no compelling reason as to why specifically these residues were conserved. Here we show that other polar residues are similarly conserved. These conserved residues have been detected consistently in all interface families that we have examined. Our results are based on an extensive examination of residues which are in contact across protein interfaces. We utilize all clustered interface families with at least five members and with sequence similarity between the members in the range of 20-90%. There are 11 such clustered interface families, comprising a total of 97 crystal structures. Our three-dimensional superpositioning analysis of the occurrences of matched residues in each of the families identifies conserved residues at spatially similar environments. Additionally, in enzyme inhibitors, we observe that residues are more conserved at the interfaces than at other locations. On the other hand, antibody-protein interfaces have similar surface conservation as compared to their corresponding linear sequence alignment, consistent with the suggestion that evolution has optimized protein interfaces for function. JF - Proteins AU - Hu, Z AU - Ma, B AU - Wolfson, H AU - Nussinov, R AD - NCI-FCRDC, Laboratory of Experimental and Computational Biology, Frederick, Maryland, USA. Y1 - 2000/06/01/ PY - 2000 DA - 2000 Jun 01 SP - 331 EP - 342 VL - 39 IS - 4 SN - 0887-3585, 0887-3585 KW - Hemoglobins KW - 0 KW - Histocompatibility Antigens KW - Hormones KW - Immunoglobulins KW - Proteins KW - Serine Proteinase Inhibitors KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Endopeptidases KW - EC 3.4.- KW - Index Medicus KW - Animals KW - Histocompatibility Antigens -- physiology KW - Hormones -- metabolism KW - Endopeptidases -- physiology KW - Histocompatibility Antigens -- chemistry KW - Molecular Sequence Data KW - Picornaviridae KW - Rhinovirus KW - Hemoglobins -- chemistry KW - Endopeptidases -- chemistry KW - Hormones -- chemistry KW - Immunoglobulins -- physiology KW - Hemoglobins -- physiology KW - Glutathione Transferase -- metabolism KW - Glutathione Transferase -- chemistry KW - Amino Acid Sequence KW - Serine Proteinase Inhibitors -- chemistry KW - Binding Sites KW - Glutathione Transferase -- physiology KW - Immunoglobulins -- chemistry KW - Hemoglobins -- metabolism KW - Hormones -- physiology KW - Serine Proteinase Inhibitors -- physiology KW - Histocompatibility Antigens -- metabolism KW - Immunoglobulins -- metabolism KW - Endopeptidases -- metabolism KW - Serine Proteinase Inhibitors -- metabolism KW - Proteins -- chemistry KW - Conserved Sequence KW - Proteins -- metabolism KW - Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71120459?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proteins&rft.atitle=Conservation+of+polar+residues+as+hot+spots+at+protein+interfaces.&rft.au=Hu%2C+Z%3BMa%2C+B%3BWolfson%2C+H%3BNussinov%2C+R&rft.aulast=Hu&rft.aufirst=Z&rft.date=2000-06-01&rft.volume=39&rft.issue=4&rft.spage=331&rft.isbn=&rft.btitle=&rft.title=Proteins&rft.issn=08873585&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-02 N1 - Date created - 2000-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drinking as a risk factor for sustained smoking. AN - 71114111; 10812284 AB - Data from a nationally representative sample of US adults (n=42862) were used to explore the associations between drinking and smoking, on a lifetime and past-year basis, and between drinking and smoking cessation for a subsample of past-year smokers (n=12586). Smoking cessation was defined as current nonsmoking (as of the time of interview) that had lasted at least 3 months. The proportions of both lifetime and past-year smokers increased with volume of alcohol intake and frequency of heavy drinking and were greater for individuals with DSM-IV alcohol abuse or dependence than for individuals without these disorders. For example, the proportion of past-year smokers rose from 22.5% of lifetime abstainers to 53.0% of heavy drinkers, from 23.8% of those who never drank 5+ drinks on any drinking day to 61.8% of those who drank 5+ drinks weekly or more often and from 27.6% of individuals without past-year DSM-IV alcohol abuse or dependence to 55.5% of those with either of these disorders. The proportion of past-year smokers who had stopped smoking decreased from 7.8% of former drinkers to 4.6% of heavy drinkers, from 7.3% of those who never drank 5+ drinks to 3.4% of those who did so weekly or more often and from 6.7% among individuals without past-year abuse or dependence compared to 4.4% among those with either disorder. In a multivariate analysis that adjusted for background variables and smoking history, average daily ethanol intake was not significantly associated with the odds of smoking cessation, but drinking 5+ drinks at least once a month reduced the odds of cessation by 42%. Having an alcohol use disorder increased the odds of smoking cessation below the age of 30 (an effect that disappeared after adjusting for the interaction between age group and having children in the home), but had an increasingly negative effect on smoking cessation at older ages. JF - Drug and alcohol dependence AU - Dawson, D A AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA. ddawson@willco.niaaa.nih.gov Y1 - 2000/06/01/ PY - 2000 DA - 2000 Jun 01 SP - 235 EP - 249 VL - 59 IS - 3 SN - 0376-8716, 0376-8716 KW - Index Medicus KW - Risk Factors KW - Humans KW - Adult KW - Middle Aged KW - Longitudinal Studies KW - Male KW - Female KW - Multivariate Analysis KW - Smoking Cessation -- psychology KW - Alcoholism -- epidemiology KW - Alcohol Drinking -- psychology KW - Smoking -- psychology KW - Alcohol Drinking -- epidemiology KW - Alcoholism -- psychology KW - Smoking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71114111?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=Drinking+as+a+risk+factor+for+sustained+smoking.&rft.au=Dawson%2C+D+A&rft.aulast=Dawson&rft.aufirst=D&rft.date=2000-06-01&rft.volume=59&rft.issue=3&rft.spage=235&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=03768716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-01 N1 - Date created - 2000-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dietary exposure to nitrite and nitrosamines and risk of nasopharyngeal carcinoma in Taiwan. AN - 71100687; 10797279 AB - Previous studies of nasopharyngeal carcinoma (NPC) have found elevated risks with higher consumption of salted fish and preserved foods, particularly during childhood. These foods can contain high levels of nitrosamines; however, most studies have not estimated exposure to nitrosamines directly. We conducted a case-control study in Taiwan to evaluate dietary intakes and NPC risk. A total of 375 cases (99% response rate) and 327 controls (88% response rate) were interviewed about their diet as an adult and at age 10 using a food-frequency questionnaire. We interviewed mothers of participants about their child's diet at age 10, age 3 and during weaning and the mother's diet while she was breast-feeding. Mothers of 96 cases and 120 controls were interviewed. Nitrosamine and nitrite levels were assigned to 66 foods based on published values. Intake of nitrosamines and nitrite as an adult was not associated with risk of NPC. High intakes of nitrosamines and nitrite during childhood and weaning were associated with increased risks of NPC for foods other than soy products. Adjusted odds ratios for the highest quartile were 2.2 [95% confidence interval (CI) 0.8-5.6] for age 10, 2.6 (95% CI 1.0-7.0) for age 3 and 3.9 (95% CI 1.4-10.4) for weaning diet. Intakes of nitrite and nitrosamines from soybean products during childhood and weaning were inversely associated with risk. Soybeans contain known inhibitors of nitrosation, and thus may explain the inverse association we observed. Our results suggest that nitrosamine and nitrite intake during childhood may play a role in the development of NPC. JF - International journal of cancer AU - Ward, M H AU - Pan, W H AU - Cheng, Y J AU - Li, F H AU - Brinton, L A AU - Chen, C J AU - Hsu, M M AU - Chen, I H AU - Levine, P H AU - Yang, C S AU - Hildesheim, A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 2000/06/01/ PY - 2000 DA - 2000 Jun 01 SP - 603 EP - 609 VL - 86 IS - 5 SN - 0020-7136, 0020-7136 KW - Nitrites KW - 0 KW - Nitrosamines KW - Index Medicus KW - Breast Feeding -- adverse effects KW - Risk Factors KW - Humans KW - Taiwan -- epidemiology KW - Adult KW - Surveys and Questionnaires KW - Weaning KW - Child KW - Female KW - Child, Preschool KW - Nasopharyngeal Neoplasms -- chemically induced KW - Nitrites -- adverse effects KW - Nasopharyngeal Neoplasms -- epidemiology KW - Nitrosamines -- adverse effects KW - Diet -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71100687?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dietary+exposure+to+nitrite+and+nitrosamines+and+risk+of+nasopharyngeal+carcinoma+in+Taiwan.&rft.au=Ward%2C+M+H%3BPan%2C+W+H%3BCheng%2C+Y+J%3BLi%2C+F+H%3BBrinton%2C+L+A%3BChen%2C+C+J%3BHsu%2C+M+M%3BChen%2C+I+H%3BLevine%2C+P+H%3BYang%2C+C+S%3BHildesheim%2C+A&rft.aulast=Ward&rft.aufirst=M&rft.date=2000-06-01&rft.volume=86&rft.issue=5&rft.spage=603&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 - 2000-06-08 N1 - Date created - 2000-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A single amino acid change in the murine leukemia virus capsid gene responsible for the Fv1(nr) phenotype. AN - 71097563; 10799620 AB - The nr allele at the mouse Fv1 restriction locus governs resistance to B-tropic and some N-tropic murine leukemia viruses (MLVs). Sequence analysis and site-specific mutagenesis of N-tropic MLVs identified a single amino acid difference responsible for this restriction that is distinct from the site that governs N or B tropism. Viruses with other substitutions at this site were evaluated for altered replication patterns. JF - Journal of virology AU - Jung, Y T AU - Kozak, C A AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA. Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 5385 EP - 5387 VL - 74 IS - 11 SN - 0022-538X, 0022-538X KW - Index Medicus KW - Phenotype KW - Animals KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Cell Line KW - Amino Acid Substitution KW - Capsid -- genetics KW - Friend murine leukemia virus -- pathogenicity KW - Friend murine leukemia virus -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71097563?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=A+single+amino+acid+change+in+the+murine+leukemia+virus+capsid+gene+responsible+for+the+Fv1%28nr%29+phenotype.&rft.au=Jung%2C+Y+T%3BKozak%2C+C+A&rft.aulast=Jung&rft.aufirst=Y&rft.date=2000-06-01&rft.volume=74&rft.issue=11&rft.spage=5385&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 - 2000-06-27 N1 - Date created - 2000-06-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Mol Biol. 1967 Jun 14;26(2):365-9 [4291934] Virology. 1997 Nov 10;238(1):64-7 [9375009] Virology. 1970 Dec;42(4):1136-9 [4099080] J Exp Med. 1971 Jun 1;133(6):1219-33 [4325132] Virology. 1975 Jun;65(2):333-42 [165617] Virology. 1975 May;65(1):128-34 [167514] J Virol. 1977 Jan;21(1):309-18 [189069] Annu Rev Genet. 1977;11:277-96 [202189] Proc Natl Acad Sci U S A. 1978 Sep;75(9):4170-4 [212738] Proc Natl Acad Sci U S A. 1978 Sep;75(9):4553-7 [212760] Nature. 1981 Oct 15-21;293(5833):543-8 [6169994] J Virol. 1982 May;42(2):519-29 [6283170] J Virol. 1983 Dec;48(3):685-96 [6313967] J Virol. 1983 Dec;48(3):779-84 [6313971] J Virol. 1984 Nov;52(2):695-8 [6092693] J Virol. 1985 Aug;55(2):281-5 [2991555] J Virol. 1990 Jul;64(7):3376-81 [1693703] Nucleic Acids Res. 1991 Dec 25;19(24):6950 [1762923] Nature. 1996 Aug 29;382(6594):826-9 [8752279] Virology. 1996 Nov 15;225(2):300-5 [8918916] J Virol. 1970 Feb;5(2):221-5 [4317349] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure-function studies of the self-assembly domain of the human immunodeficiency virus type 1 transmembrane protein gp41. AN - 71094084; 10799616 AB - The coiled-coil region of the human immunodeficiency virus type 1 transmembrane protein (gp41) makes up the interior core of the six-helix bundle structure of the gp41 self-assembly domain. We extended our previous study of this domain (Y. Weng and C. D. Weiss, J. Virol. 72:9676-9682, 1998) by analyzing 23 additional mutants at positions that lie at the interface of the interior core and outer helices. We found nine new functional mutants. For most mutants, the activity could be explained by the ability of the modeled mutants to stabilize the six-helix bundle structure. The present study provides insights into the envelope glycoprotein fusion mechanism and information for rational drug and vaccine design. JF - Journal of virology AU - Weng, Y AU - Yang, Z AU - Weiss, C D AD - Center for Biologics Evaluation and Research, Food and Drug Administration, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 5368 EP - 5372 VL - 74 IS - 11 SN - 0022-538X, 0022-538X KW - HIV Envelope Protein gp41 KW - 0 KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Hydrogen Bonding KW - Structure-Activity Relationship KW - Binding Sites KW - HIV-1 -- genetics KW - HIV Envelope Protein gp41 -- metabolism KW - HIV Envelope Protein gp41 -- genetics KW - HIV Envelope Protein gp41 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71094084?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Structure-function+studies+of+the+self-assembly+domain+of+the+human+immunodeficiency+virus+type+1+transmembrane+protein+gp41.&rft.au=Weng%2C+Y%3BYang%2C+Z%3BWeiss%2C+C+D&rft.aulast=Weng&rft.aufirst=Y&rft.date=2000-06-01&rft.volume=74&rft.issue=11&rft.spage=5368&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 - 2000-06-27 N1 - Date created - 2000-06-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1993 May;67(5):2747-55 [8474172] J Virol. 1999 Mar;73(3):2469-80 [9971832] Nature. 1993 Sep 9;365(6442):113 [8371754] J Virol. 1994 Feb;68(2):654-60 [7507183] J Virol. 1994 Mar;68(3):2002-10 [7509005] Nat Struct Biol. 1995 Dec;2(12):1075-82 [8846219] Cell. 1997 Apr 18;89(2):263-73 [9108481] Nature. 1997 May 22;387(6631):426-30 [9163431] Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12303-8 [9356444] J Virol. 1998 Feb;72(2):986-93 [9444991] Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9134-9 [9689046] EMBO J. 1998 Aug 17;17(16):4572-84 [9707417] J Virol. 1998 Dec;72(12):9676-82 [9811701] J Virol. 1999 May;73(5):4433-8 [10196341] J Struct Biol. 1999 Jun 15;126(2):131-44 [10388624] J Virol. 1993 Jun;67(6):3615-9 [8497069] J Virol. 1992 Aug;66(8):4748-56 [1629954] Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15613-7 [9861018] Erratum In: J Virol 2000 Oct;74(20):9811 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relationship between human immunodeficiency virus type 1 Gag multimerization and membrane binding. AN - 71093809; 10799589 AB - The human immunodeficiency virus type 1 (HIV-1) Gag precursor, Pr55(Gag), is necessary and sufficient for the assembly and release of viruslike particles. Binding of Gag to membrane and Gag multimerization are both essential steps in virus assembly, yet the domains responsible for these events have not been fully defined. In addition, the relationship between membrane binding and Gag-Gag interaction remains to be elucidated. To investigate these issues, we analyzed, in vivo, the membrane-binding and assembly properties of a series of C-terminally truncated Gag mutants. Pr55(Gag) was truncated at the C terminus of matrix (MAstop), between the N- and C-terminal domains of capsid (CA146stop), at the C terminus of capsid (p41stop), at the C terminus of p2 (p43stop), and after the N-terminal 35 amino acids of nucleocapsid (NC35stop). The ability of these truncated Gag molecules to assemble and release viruslike particles and their capacity to copackage into particles when coexpressed with full-length Gag were determined. We demonstrate that the amount of truncated Gag incorporated into particles is incrementally increased by extension from CA146 to NC35, suggesting that multiple sites in this region are involved in Gag multimerization. Using membrane flotation centrifugation, we observe that MA shows significantly reduced membrane binding relative to full-length Gag but that CA146 displays steady-state membrane-binding properties comparable to those of Pr55(Gag). The finding that the CA146 mutant, which contains only matrix and the N-terminal domain of capsid, exhibits levels of steady-state membrane binding equivalent to those of full-length Gag indicates that strong Gag-Gag interaction domains are not required for the efficient binding of HIV-1 Gag to membrane. JF - Journal of virology AU - Ono, A AU - Demirov, D AU - Freed, E O AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0460, USA. Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 5142 EP - 5150 VL - 74 IS - 11 SN - 0022-538X, 0022-538X KW - Gene Products, gag KW - 0 KW - Peptide Fragments KW - Protein Precursors KW - gag Gene Products, Human Immunodeficiency Virus KW - p2 gag peptide, Human immunodeficiency virus 1 KW - p55 gag precursor protein, Human immunodeficiency virus 1 KW - Index Medicus KW - AIDS/HIV KW - Peptide Fragments -- metabolism KW - Peptide Fragments -- genetics KW - HeLa Cells KW - Virus Assembly -- physiology KW - Humans KW - Virion -- physiology KW - Cell Membrane -- metabolism KW - Mutagenesis KW - HIV-1 -- metabolism KW - HIV-1 -- genetics KW - Gene Products, gag -- genetics KW - Protein Precursors -- metabolism KW - Protein Precursors -- genetics KW - HIV-1 -- physiology KW - Gene Products, gag -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71093809?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Relationship+between+human+immunodeficiency+virus+type+1+Gag+multimerization+and+membrane+binding.&rft.au=Ono%2C+A%3BDemirov%2C+D%3BFreed%2C+E+O&rft.aulast=Ono&rft.aufirst=A&rft.date=2000-06-01&rft.volume=74&rft.issue=11&rft.spage=5142&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 - 2000-06-27 N1 - Date created - 2000-06-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1993 Jul;67(7):4264-73 [7685414] J Virol. 1998 May;72(5):4116-26 [9557701] Biochemistry. 1993 Oct 5;32(39):10436-43 [8399188] J Virol. 1993 Nov;67(11):6487-98 [8411352] J Virol. 1993 Dec;67(12):7067-76 [7693966] J Virol. 1994 Apr;68(4):2503-12 [8139032] J Virol. 1994 Apr;68(4):2556-69 [8139035] Virology. 1994 May 1;200(2):524-34 [8178440] Proc Natl Acad Sci U S A. 1994 May 10;91(10):4594-8 [8183954] J Virol. 1994 Aug;68(8):5311-20 [8035531] Nature. 1994 Aug 25;370(6491):666-8 [8065455] J Virol. 1994 Oct;68(10):6644-54 [7521919] J Mol Biol. 1994 Nov 25;244(2):198-223 [7966331] J Virol. 1994 Dec;68(12):8017-27 [7966591] J Virol. 1994 Dec;68(12):8180-7 [7966609] J Virol. 1995 Feb;69(2):642-50 [7815527] J Virol. 1995 Jun;69(6):3407-19 [7745687] Trends Biochem Sci. 1995 Jul;20(7):272-6 [7667880] J Virol. 1995 Nov;69(11):6810-8 [7474093] Nature. 1995 Dec 14;378(6558):743-7 [7501025] Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3099-104 [8610175] J Gen Virol. 1996 Apr;77 ( Pt 4):743-51 [8627263] J Virol. 1996 Dec;70(12):8540-8 [8970978] Cell. 1996 Dec 27;87(7):1285-94 [8980234] J Virol. 1997 Sep;71(9):6582-92 [9261380] J Virol. 1997 Sep;71(9):6765-76 [9261401] Nature. 1997 Sep 11;389(6647):198-202 [9296500] J Gen Virol. 1997 Oct;78 ( Pt 10):2489-96 [9349469] Science. 1997 Oct 31;278(5339):849-53 [9346481] Curr Biol. 1997 Oct 1;7(10):729-38 [9368755] J Virol. 1998 Mar;72(3):1782-9 [9499028] J Virol. 1998 Mar;72(3):2072-8 [9499062] EMBO J. 1998 Mar 16;17(6):1555-68 [9501077] J Virol. 1998 Apr;72(4):2723-32 [9525590] Virology. 1998 Mar 30;243(1):78-93 [9527917] EMBO J. 1998 May 1;17(9):2699-708 [9564051] J Virol. 1998 Jun;72(6):4798-810 [9573245] J Virol. 1998 Sep;72(9):7659-63 [9696871] Virology. 1998 Aug 15;248(1):108-16 [9705260] J Virol. 2000 Jan;74(1):16-23 [10590086] J Virol. 2000 Mar;74(6):2855-66 [10684302] J Virol. 1986 Aug;59(2):284-91 [3016298] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580-4 [2849111] Cell. 1989 Oct 6;59(1):103-12 [2676191] J Gen Virol. 1991 Oct;72 ( Pt 10):2509-17 [1919528] J Virol. 1992 Aug;66(8):4874-83 [1629958] J Virol. 1992 Nov;66(11):6304-13 [1383561] J Gen Virol. 1992 Dec;73 ( Pt 12):3079-86 [1469349] Virology. 1993 Apr;193(2):981-5 [8460500] Virology. 1993 Jun;194(2):548-56 [8503172] J Virol. 1998 Oct;72(10):7950-9 [9733833] J Virol. 1998 Nov;72(11):9034-44 [9765448] Virology. 1998 Nov 10;251(1):1-15 [9813197] Virology. 1998 Nov 10;251(1):141-57 [9813210] J Virol. 1999 Mar;73(3):1902-8 [9971769] J Virol. 1999 Apr;73(4):2604-12 [10074105] Acta Crystallogr D Biol Crystallogr. 1999 Jan;55(Pt 1):85-92 [10089398] J Virol. 1999 May;73(5):4136-44 [10196310] AIDS. 1999 Feb 4;13(2):281-3 [10202836] J Virol. 1999 Jul;73(7):5654-62 [10364315] J Virol. 1999 Oct;73(10):8527-40 [10482606] J Virol. 1993 Oct;67(10):6159-69 [8371356] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional correlation in amino acid residue mutations of yeast iso-2-cytochrome c that is consistent with the prediction of the concomitantly variable codon theory in cytochrome c evolution. AN - 70768854; 11091908 AB - Fitch and Markowitz' theory of concomitantly variable codons (covarions) in evolution predicted the existence of functional correlation in amino acid residue mutations among present-day cytochromes c. Mutational analysis was carried out on yeast iso-2-cytochrome c, where hydrophobic core residues I20, M64, L85, and M98 and surface residue L9 were mutated, in selected combinations, to those found in mammalian and bird cytochromes c. The functionality assay is based upon the ability of yeast cells to grow in YPGE medium. Furthermore, experiments on the single M64L and M98L mutations as well as the double M64L/M98L mutation using NMR showed that the effects of these mutations are to perturb the structural integrity of the protein. We identified functional correlation in two cases of a pair of residue mutations, the I20-->V and M98-->L pair and the L9-->I and L85-->I pair. In both cases, only one of the two alternative, putative evolutionary pathways leads to a functional protein and the corresponding pairs of residue mutations are among those found in present-day cytochromes c. Since valine is predicted to be at position 20 in the ancestral form of cytochrome c, the present data provide an explanation for the ancient requirement of leucine rather than methionine in position 98. The present data provide further evidence for the role of those specific atom-atom interactions in directing a pathway in the evolutionary changes of the amino acid sequence that have taken place in cytochrome c, in accordance with Fitch and Markowitz. JF - Biochemical genetics AU - Fisher, A AU - Shi, Y AU - Ritter, A AU - Ferretti, J A AU - Perez-Lamboy, G AU - Shah, M AU - Shiloach, J AU - Taniuchi, H AD - Laboratory of Chemical Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 181 EP - 200 VL - 38 IS - 5-6 SN - 0006-2928, 0006-2928 KW - Codon KW - 0 KW - Cytochrome c Group KW - iso-2-cytochrome C KW - Cytochromes c KW - 9007-43-6 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Models, Molecular KW - Enzyme Stability KW - Temperature KW - Protein Denaturation KW - Amino Acid Substitution KW - Protein Conformation KW - Magnetic Resonance Spectroscopy KW - Cytochrome c Group -- genetics KW - Cytochrome c Group -- chemistry KW - Codon -- genetics KW - Models, Genetic KW - Yeasts -- genetics KW - Yeasts -- enzymology KW - Cytochrome c Group -- metabolism KW - Evolution, Molecular UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70768854?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+genetics&rft.atitle=Functional+correlation+in+amino+acid+residue+mutations+of+yeast+iso-2-cytochrome+c+that+is+consistent+with+the+prediction+of+the+concomitantly+variable+codon+theory+in+cytochrome+c+evolution.&rft.au=Fisher%2C+A%3BShi%2C+Y%3BRitter%2C+A%3BFerretti%2C+J+A%3BPerez-Lamboy%2C+G%3BShah%2C+M%3BShiloach%2C+J%3BTaniuchi%2C+H&rft.aulast=Fisher&rft.aufirst=A&rft.date=2000-06-01&rft.volume=38&rft.issue=5-6&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=Biochemical+genetics&rft.issn=00062928&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-22 N1 - Date created - 2001-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nm23/nucleoside diphosphate kinase in human cancers. AN - 70522099; 11768314 AB - Tumor metastasis is the leading cause of death in cancer patients. From a series of tumor cohort studies, low expression of Nm23/NDP kinase has been correlated with poor patient prognosis and survival, lymph node infiltration, and histopathological indicators of high metastatic potential in a number of cancer types, including mammary and ovarian carcinomas and melanoma. In other tumor types, no correlation has been established. Transfection of Nm23/NDP kinase cDNA into highly metastatic breast, melanoma, prostrate and squamous cell carcinomas, and colon adenocarcinoma cells significantly reduced the metastatic competency of the cells in vivo. In culture, cell motility, invasion, and colonization were inhibited, whereas tumorigenicity and cellular proliferation were not affected, indicating that Nm23/NDP kinase acts as a metastasis suppressor. JF - Journal of bioenergetics and biomembranes AU - Hartsough, M T AU - Steeg, P S AD - Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. hartso@box-h.nih.gov Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 301 EP - 308 VL - 32 IS - 3 SN - 0145-479X, 0145-479X KW - NM23 Nucleoside Diphosphate Kinases KW - 0 KW - Transcription Factors KW - NME1 protein, human KW - EC 2.7.4.6 KW - Nucleoside-Diphosphate Kinase KW - Monomeric GTP-Binding Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - Gene Expression Profiling KW - Loss of Heterozygosity KW - Transfection KW - Humans KW - Neoplasm Metastasis KW - Mutagenesis KW - Transcription Factors -- physiology KW - Nucleoside-Diphosphate Kinase -- genetics KW - Neoplasms -- enzymology KW - Nucleoside-Diphosphate Kinase -- physiology KW - Neoplasms -- therapy KW - Transcription Factors -- genetics KW - Neoplasms -- genetics KW - Monomeric GTP-Binding Proteins -- physiology KW - Monomeric GTP-Binding Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70522099?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+bioenergetics+and+biomembranes&rft.atitle=Nm23%2Fnucleoside+diphosphate+kinase+in+human+cancers.&rft.au=Hartsough%2C+M+T%3BSteeg%2C+P+S&rft.aulast=Hartsough&rft.aufirst=M&rft.date=2000-06-01&rft.volume=32&rft.issue=3&rft.spage=301&rft.isbn=&rft.btitle=&rft.title=Journal+of+bioenergetics+and+biomembranes&rft.issn=0145479X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-12 N1 - Date created - 2001-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Factors associated with fathers' caregiving activities and sensitivity with young children AN - 57715103; 159846 AB - A multifactorial model was used to identify child, sociodemographic, paternal, and maternal characteristics associated with 2 aspects of fathers' parenting. Fathers were interviewed about their caregiving responsibilities at 6, 15, 24, and 36 months, and a subset was videotaped during father-child play at 6 and 36 months. Caregiving activities and sensitivity during play interactions were predicted by different factors. Fathers were more involved in caregiving when they worked fewer hours and mothers worked more hours, when fathers and mothers were younger, when fathers had more positive personalities, when mothers reported greater marital intimacy, and when children were boys. (Original abstract - amended) JF - Journal of Family Psychology AU - NICHD Early Child Care Research Network AD - NICHD Early Child Care Research Network Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 200 EP - 219 VL - 14 IS - 2 SN - 0893-3200, 0893-3200 KW - Influences KW - Sensitivity KW - Preschool children KW - Fathers KW - Care UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/57715103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Family+Psychology&rft.atitle=Factors+associated+with+fathers%27+caregiving+activities+and+sensitivity+with+young+children&rft.au=NICHD+Early+Child+Care+Research+Network&rft.aulast=NICHD+Early+Child+Care+Research+Network&rft.aufirst=&rft.date=2000-06-01&rft.volume=14&rft.issue=2&rft.spage=200&rft.isbn=&rft.btitle=&rft.title=Journal+of+Family+Psychology&rft.issn=08933200&rft_id=info:doi/ LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Date revised - 2001-08-07 N1 - Document feature - refs. tbls. N1 - Last updated - 2016-09-27 N1 - CODEN - JFPSEV N1 - SubjectsTermNotLitGenreText - Preschool children; Care; Fathers; Sensitivity; Influences ER - TY - JOUR T1 - Critical windows of exposure for children's health: cancer in human epidemiological studies and neoplasms in experimental animal models. AN - 21250853; 11702231 AB - In humans, cancer may be caused by genetics and environmental exposures; however, in the majority of instances the identification of the critical time window of exposure is problematic. The evidence for exposures occurring during the preconceptional period that have an association with childhood or adulthood cancers is equivocal. Agents definitely related to cancer in children, and adulthood if exposure occurs in utero, include: maternal exposure to ionizing radiation during pregnancy and childhood leukemia and certain other cancers, and maternal use of diethylstilbestrol during pregnancy and clear-cell adenocarcinoma of the vagina of their daughters. The list of environmental exposures that occur during the perinatal/postnatal period with potential to increase the risk of cancer is lengthening, but evidence available to date is inconsistent and inconclusive. In animal models, preconceptional carcinogenesis has been demonstrated for a variety of types of radiation and chemicals, with demonstrated sensitivity for all stages from fetal gonocytes to postmeiotic germ cells. Transplacental and neonatal carcinogenesis show marked ontogenetic stage specificity in some cases. Mechanistic factors include the number of cells at risk, the rate of cell division, the development of differentiated characteristics including the ability to activate and detoxify carcinogens, the presence of stem cells, and possibly others. Usefulness for human risk estimation would be strengthened by the study of these factors in more than one species, and by a focus on specific human risk issues. Images Figure 1 JF - Environmental Health Perspectives AU - Anderson, L M AU - Diwan, B A AU - Fear, N T AU - Roman, E AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, FCRDC, Frederick, Maryland, USA., andersol@mail.ncifcrf.gov Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 573 EP - 594 PB - US Government Printing Office, Superintendent of Documents, P.O. Box 371954 Pittsburgh PA 15250-7954 USA VL - 108 IS - Suppl 3 SN - 0091-6765, 0091-6765 KW - Risk Abstracts; Environment Abstracts KW - Chemicals KW - Sensitivity KW - Animal models KW - Carcinogens KW - Children KW - Cancer KW - Pregnancy KW - Leukemia KW - Genetics KW - stem cells KW - Ionizing radiation KW - Carcinogenesis KW - Neonates KW - R2 23060:Medical and environmental health KW - ENA 02:Toxicology & Environmental Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21250853?accountid=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=Critical+windows+of+exposure+for+children%27s+health%3A+cancer+in+human+epidemiological+studies+and+neoplasms+in+experimental+animal+models.&rft.au=Anderson%2C+L+M%3BDiwan%2C+B+A%3BFear%2C+N+T%3BRoman%2C+E&rft.aulast=Anderson&rft.aufirst=L&rft.date=2000-06-01&rft.volume=108&rft.issue=Suppl+3&rft.spage=573&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 - 2010-01-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Chemicals; Sensitivity; Animal models; Carcinogens; Children; Cancer; Pregnancy; Genetics; Leukemia; stem cells; Ionizing radiation; Carcinogenesis; Neonates ER - TY - JOUR T1 - Development of a Cyanovirin-N-HIV-1 gpl20 Binding Assay for High Throughput Screening of Natural Product Extracts by Time-Resolved Fluorescence AN - 21208352; 11617072 AB - The unique, high-affinity binding of cyanovirin-N (CV-N), a potent anti-human immunodeficiency virus (HIV) protein, to the HIV envelope glycoprotein gp120, was exploited to develop an HTS assay in an attempt to discover small-molecule mimetics of CV-N. A competition binding assay was developed using CV-N labeled with europium (Eu super(3)1). The labeling protocol did not significantly alter the gpl20 binding properties or the antiviral activity of CV-N. This report describes the assay development, validation, and results of screening a large library of aqueous and organic natural product extracts. The extracts were incubated with immobilized recombinant gpl20 in 96-well plates prior to the addition of Eu super(3+)-labeled CV-N. Following a wash step, bound CV-N was measured by dissociation-enhanced time-resolved fluorometry of Eu super(3+). The assay proved to be robust, rapid, and reproducible, and was used to screen over 50,000 natural product extracts, and has resulted in the identification of several aqueous natural product extracts that inhibited CV-N-gp120 binding and also had anti-HIV activity. JF - Journal of Biomolecular Screening AU - McMahon, James B AU - Beutler, John A AU - O'Keefe, Barry R AU - Goodrum, Colby BB AU - Myers, Marc A AU - Boyd, Michael R AD - Laboratory of Drug Discovery Research and Development, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 169 EP - 176 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 5 IS - 3 SN - 1087-0571, 1087-0571 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts; Biotechnology and Bioengineering Abstracts KW - Glycoprotein gp120 KW - cyanovirin-N KW - Envelopes KW - Fluorescence KW - Human immunodeficiency virus KW - Fluorometry KW - natural products KW - high-throughput screening KW - Antiviral activity 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/21208352?accountid=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=Development+of+a+Cyanovirin-N-HIV-1+gpl20+Binding+Assay+for+High+Throughput+Screening+of+Natural+Product+Extracts+by+Time-Resolved+Fluorescence&rft.au=McMahon%2C+James+B%3BBeutler%2C+John+A%3BO%27Keefe%2C+Barry+R%3BGoodrum%2C+Colby+BB%3BMyers%2C+Marc+A%3BBoyd%2C+Michael+R&rft.aulast=McMahon&rft.aufirst=James&rft.date=2000-06-01&rft.volume=5&rft.issue=3&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomolecular+Screening&rft.issn=10870571&rft_id=info:doi/10.1177%2F108705710000500309 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-01-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Glycoprotein gp120; cyanovirin-N; Fluorescence; Envelopes; Fluorometry; high-throughput screening; natural products; Antiviral activity; Human immunodeficiency virus DO - http://dx.doi.org/10.1177/108705710000500309 ER - TY - JOUR T1 - Improving vaccine performance with adjuvants AN - 18551077; 5513815 AB - New vaccines are presently under development and in testing for the control of infectious diseases, including human immunodeficiency virus (HIV) and tuberculosis. Several of these vaccines are composed of synthetic, recombinant, or highly purified subunit antigens. Subunit vaccines are designed to include only the antigens required for protective immunization and to be safer than whole-inactivated or live-attenuated vaccines. However, the purity of the subunit antigens and the absence of the self-adjuvanting immunomodulatory components associated with attenuated or killed vaccines often result in weaker immunogenicity. Immunologic adjuvants are agents that enhance specific immune responses to vaccines. Formulation of vaccines with potent adjuvants is an attractive approach for improving the performance of vaccines composed of subunit antigens. Adjuvants have diverse mechanisms of action and should be selected for use on the basis of the route of administration and the type of immune response (antibody, cell-mediated, or mucosal immunity) that is desired for a particular vaccine. JF - Clinical Infectious Diseases AU - Vogel AD - Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - S266 EP - S270 VL - 30 SN - 1058-4838, 1058-4838 KW - Microbiology Abstracts B: Bacteriology KW - J 02834:Vaccination and immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18551077?accountid=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+Infectious+Diseases&rft.atitle=Improving+vaccine+performance+with+adjuvants&rft.au=Vogel&rft.aulast=Vogel&rft.aufirst=&rft.date=2000-06-01&rft.volume=30&rft.issue=&rft.spage=S266&rft.isbn=&rft.btitle=&rft.title=Clinical+Infectious+Diseases&rft.issn=10584838&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Associations between uncoupling protein 2, body composition, and resting energy expenditure in lean and obese African American, white, and Asian children AN - 18281059; 5342172 AB - Little is known about genes that affect childhood body weight. The objective of this study was to examine the association between alleles of the mitochondrial uncoupling protein 2 (UCP2) gene and obesity because UCP2 may influence energy expenditure. We related UCP2 genotype to body composition and resting energy expenditure in 105 children aged 6-10 y. Overweight children and nonoverweight children of overweight parents were genotyped for a 45-base pair deletion/insertion (del/ins) in 3'-untranslated region of exon 8 and for an exon 4 C to T transition. Eighty-nine children were genotyped for the exon 8 allele: 50 children had del/del, 33 had del/ins, and 6 had ins/ins. Mean ( plus or minus SD) body mass index (BMI; in kg/m super(2)) was greater for children with del/ins (24.1 plus or minus 5.9) than for children with del/del (20.4 plus or minus 4.8; P < 0.001). BMI of ins/ins children (23.7 plus or minus 7.8) was not significantly different from that of del/ins children. A greater BMI in del/ins children was independent of race and sex. Body composition was also different according to UCP2 genotype. All body circumferences and skinfold thicknesses examined were significantly greater in del/ins than in del/del children. Body fat mass as determined by dual-energy X-ray absorptiometry was also greater in del/ins than in del/del children (P < 0.005). For 104 children genotyped at exon 4, no significant differences in BMI or body composition were found among the 3 exon 4 genotypes. Neither resting energy expenditure nor respiratory quotient were different according to UCP2 exon 4 or exon 8 genotype. The exon 8 ins/del polymorphism of UCP2 appears to be associated with childhood-onset obesity. The UCP2/UCP3 genetic locus may play a role in childhood body weight. JF - American Journal of Clinical Nutrition AU - Yanovski, JA AU - Diament, AL AU - Sovik, K N AU - Nguyen, T T AU - Li, Hongzhe AU - Sebring, NG AU - Warden, CH AD - Unit on Growth and Obesity, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, MD, USA Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 1405 EP - 1420 VL - 71 IS - 6 SN - 0002-9165, 0002-9165 KW - Physical Education Index KW - Energy cost KW - Obesity KW - Proteins KW - Genetics (molecular) KW - Children KW - Body composition KW - Ethnic groups KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18281059?accountid=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=American+Journal+of+Clinical+Nutrition&rft.atitle=Associations+between+uncoupling+protein+2%2C+body+composition%2C+and+resting+energy+expenditure+in+lean+and+obese+African+American%2C+white%2C+and+Asian+children&rft.au=Yanovski%2C+JA%3BDiament%2C+AL%3BSovik%2C+K+N%3BNguyen%2C+T+T%3BLi%2C+Hongzhe%3BSebring%2C+NG%3BWarden%2C+CH&rft.aulast=Yanovski&rft.aufirst=JA&rft.date=2000-06-01&rft.volume=71&rft.issue=6&rft.spage=1405&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Clinical+Nutrition&rft.issn=00029165&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Energy cost; Body composition; Obesity; Children; Ethnic groups; Proteins; Genetics (molecular) ER - TY - JOUR T1 - Susceptibility to drug-induced apoptosis correlates with differential modulation of Bad, Bcl-2 and Bcl-x sub(L) protein levels AN - 18104974; 5200516 AB - To define the responses of apoptotic regulatory proteins to different chemotherapeutic agents, we investigated the expression of Bcl-2 family gene products, the release of cytochrome c, and the activation of pro-caspase-3 during apoptosis induced by Taxol and Thiotepa, in the MCF-7 breast carcinoma and the HL-60 leukemia cell lines. The earliest event induced by drug exposure was increase in Bad protein levels, followed by Bcl-2 down-regulation, cytochrome c release, and Bcl-x sub(L) and Bax up-regulation. Bak accumulation was a late event. Activation of pro-caspase-3 and cleavage of Bcl-2 protein occurred in the HL-60 cells only, and followed the cytochrome c release. The overall responses were qualitatively similar in both cell types, but MCF-7 cells treated with Taxol showed a significant delay in apoptosis, correlating with early up-regulation of Bcl-2 and delayed release of cytochrome c. We conclude that Bad up-regulation is an early indicator of a cellular response that will lead to cell death, but may be modulated by survival mechanisms, which cumulatively govern the ultimate susceptibility to apoptosis. JF - Cell Death and Differentiation AU - Tudor, G AU - Aguilera, A AU - Halverson, DO AU - Laing, N D AU - Sausville, E A AD - Science Applications International Corporation, NCI - FCRDC, P.O. Box B, Frederick, Maryland, MD 21702, USA Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 574 EP - 586 VL - 7 IS - 6 SN - 1350-9047, 1350-9047 KW - man KW - tumor cell lines KW - thiotepa KW - MCF-7 cells KW - HL-60 cells KW - modulation KW - Bad protein KW - Bcl-2 protein KW - Bcl-xL protein KW - cytochrome c KW - triethylenethiophosphoramide KW - Oncogenes & Growth Factors Abstracts; Toxicology Abstracts KW - Apoptosis KW - Taxol KW - B 26245:Apoptosis/Bcl-2 KW - X 24111:Acute exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18104974?accountid=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=Cell+Death+and+Differentiation&rft.atitle=Susceptibility+to+drug-induced+apoptosis+correlates+with+differential+modulation+of+Bad%2C+Bcl-2+and+Bcl-x+sub%28L%29+protein+levels&rft.au=Tudor%2C+G%3BAguilera%2C+A%3BHalverson%2C+DO%3BLaing%2C+N+D%3BSausville%2C+E+A&rft.aulast=Tudor&rft.aufirst=G&rft.date=2000-06-01&rft.volume=7&rft.issue=6&rft.spage=574&rft.isbn=&rft.btitle=&rft.title=Cell+Death+and+Differentiation&rft.issn=13509047&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 - Apoptosis; Bcl-2 protein; Taxol ER - TY - JOUR T1 - Non-Malignant Respiratory Diseases and Lung Cancer Among Chinese Workers Exposed to Silica AN - 17815042; 4847404 AB - The objective of this study was to explore whether a medical history for nonmalignant respiratory disease contributes to an increased lung cancer risk among workers exposed to silica. We analyzed data from a nested case-control study in 29 dusty workplaces in China. The study population consisted of 316 lung cancer cases and 1356 controls matched to cases by facility type and decade of birth who were alive at the time of diagnosis of the index case and who were identified in a follow-up study of about 68,000 workers. Age at first exposure and cigarette smoking were accounted for in the analysis. Smoking was the main risk factor for both lung cancer and chronic bronchitis. Lung cancer risk showed a modest association with silicosis and with cumulative silica exposure, which did not vary by history of previous pulmonary tuberculosis. Among subjects without a medical history for chronic bronchitis or asthma, lung cancer risk was associated with silicosis (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1 to 2.2), and it was increased in each quartile of cumulative silica exposure. However, risk was not elevated in the highest quartile (OR, 1.3, 1.6, 1.8, 1.4). Among subjects with a medical history for chronic bronchitis or asthma, lung cancer risk was associated with neither silicosis (subjects with chronic bronchitis: OR; O. 6; subjects with asthma: OR, 0.4) nor with silica exposure. In this study population, we observed a modest association of both silicosis and cumulative exposure to silica with lung cancer among subjects who were not previously diagnosed with chronic bronchitis or asthma, but not among subjects who had a medical history for either disease. Risk of lung cancer associated with silicosis or cumulative exposure to silica did not vary by previous medical history of pulmonary tuberculosis. JF - Journal of Occupational and Environmental Medicine AU - Cocco, P AU - Rice, CH AU - Chen, J Q AU - McCawley, M AU - McLaughlin, J K AU - Dosemeci, M AD - Occupational Epidemiology Branch, National Cancer Institute, 6120 Executive Boulevard, EPS Room 8002, Bethesda, MD 20892-7240, USA, dosemecm@epndce.nci.nih.gov Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 639 EP - 644 VL - 42 IS - 6 SN - 1076-2752, 1076-2752 KW - man KW - silicon dioxide KW - China KW - lung cancer KW - respiratory tract diseases KW - silica KW - Toxicology Abstracts; Pollution Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Lung diseases KW - Population studies KW - Silica KW - Occupational exposure KW - Silicon dioxide KW - Lung cancer KW - H 1000:Occupational Safety and Health KW - X 24162:Chronic exposure KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17815042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Occupational+and+Environmental+Medicine&rft.atitle=Non-Malignant+Respiratory+Diseases+and+Lung+Cancer+Among+Chinese+Workers+Exposed+to+Silica&rft.au=Cocco%2C+P%3BRice%2C+CH%3BChen%2C+J+Q%3BMcCawley%2C+M%3BMcLaughlin%2C+J+K%3BDosemeci%2C+M&rft.aulast=Cocco&rft.aufirst=P&rft.date=2000-06-01&rft.volume=42&rft.issue=6&rft.spage=639&rft.isbn=&rft.btitle=&rft.title=Journal+of+Occupational+and+Environmental+Medicine&rft.issn=10762752&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Risk assessment; Lung cancer; Occupational exposure; Silica; Lung diseases; Silicon dioxide; Population studies ER - TY - JOUR T1 - An inhibitory monoclonal antibody to human cytochrome P450 that specifically binds and inhibits P4502C9II, an allelic variant of P4502C9 having a single amino acid change Arg144 Cys AN - 17725046; 4784370 AB - A monoclonal antibody (MAb 292-2-3) has been isolated that binds specifically to a single allele of three expressed human cytochrome P4502C9 alleles. The MAb binds to 2C9 sub(Cys144) (II), and does not bind to the wild-type 2C9 sub(Arg144) (I), or the third allele 2C9 sub(Ile arrow right Leu359) (III) and thus the MAb detects an allele with > 99% homology and differing from the wild-type 2C9 sub(Arg144) (I) by a single amino acid. The MAb 292-2-3 does not bind to the other 2C isoforms (2C8, 2C18, 2C19) or the other human cytochrome P450s, 1A1, 1A2, 2A6, 2B6, 2C8, 2D6, 2E1 or 3A4/5. MAb 292-2-3 inhibits the metabolism of tolbutamide, diclofenac and phenanthrene by the target 2C9 sub(Cys144) (II) allele by > 90% and does not inhibit the catalytic activity of the wild-type 2C9 sub(Arg144) (I), or 2C9 sub(Ile arrow right Leu359) (III) the other 2C isoforms 2C8, 2C18, 2C19, or the other non-2C human P450s listed above. The MAb 292-2-3 is thus a prototype of an ideal and extraordinarily specific reagent for the detection and measurement of the metabolic role of highly related isoforms and polymorphic alleles of human cytochrome P450s. MAbs of high specificity can also determine the amount of phenotypic expression of polymorphic alleles and their metabolic role in drug and non-drug xenobiotic metabolism in heterozygote individuals. The inhibitory MAb might also identify allele-specific substrates of polymorphic human cytochrome P450s. JF - Xenobiotica AU - Krausz, K W AU - Goldfarb, I AU - Yang, T J AU - Gonzalez, F J AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bldg 37, Rm 3E24 Bethesda, MD 20892 USA, gelboinh@intra.nci.nih.gov Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 619 EP - 625 VL - 30 IS - 6 SN - 0049-8254, 0049-8254 KW - amino acid substitution KW - cytochrome P450 KW - Toxicology Abstracts KW - Monoclonal antibodies KW - Drug metabolism KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17725046?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Xenobiotica&rft.atitle=An+inhibitory+monoclonal+antibody+to+human+cytochrome+P450+that+specifically+binds+and+inhibits+P4502C9II%2C+an+allelic+variant+of+P4502C9+having+a+single+amino+acid+change+Arg144+Cys&rft.au=Krausz%2C+K+W%3BGoldfarb%2C+I%3BYang%2C+T+J%3BGonzalez%2C+F+J%3BGelboin%2C+H+V&rft.aulast=Krausz&rft.aufirst=K&rft.date=2000-06-01&rft.volume=30&rft.issue=6&rft.spage=619&rft.isbn=&rft.btitle=&rft.title=Xenobiotica&rft.issn=00498254&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Monoclonal antibodies; Drug metabolism ER - TY - JOUR T1 - Assessment of risk from long term exposure to waterborne pathogens AN - 17715141; 4794321 AB - Disease due to waterborne pathogens, whether in outbreak or endemic form, continues to be a problem in both the developing and the developed world. Control of waterborne disease requires accurate assessment of the pathogen dose-response relation and of likely patterns of exposure. Heretofore, risk assessment of pathogen exposure has been done on the basis of several standard biologically plausible dose-response models. In this paper, the problem of estimating the long-term risk from waterborne pathogens is put into a rigorous mathematical and statistical framework. The implications of the biologic assumptions embedded in the dose-response models (e.g., heterogeneity in susceptibility) are fully considered, as are the likely patterns of long-term exposure (e.g., temporal correlations within individuals and heterogeneity of mean exposures). Two types of long-term risk are described, risk per person-time and risk per individual where the latter is the risk of infection at least once. The effects on these risks of heterogeneity in individuals' susceptibilities and mean exposures and of temporal correlations of exposures are described, both theoretically and empirically using a sample of experimental data sets. Because different models with equal plausibility may give very different results in the low-dose range but fit the experimental data equally well, we apply the model uncertainty algorithm of Buckland et al. (1997) on example data sets. Finally, the computational aspects of the general problem, which are often challenging, are discussed along with the conditions under which simplifying approximations may be utilized. JF - Environmental and Ecological Statistics AU - Pinsky, P F AD - National Cancer Institute, EPN 330, 6130 Executive Blvd. MSC 7354, Bethesda MD 20892-7354, USA Y1 - 2000/06// PY - 2000 DA - June 2000 SP - 155 EP - 175 VL - 7 IS - 2 SN - 1352-8505, 1352-8505 KW - disease control KW - water-borne diseases KW - Water Resources Abstracts; Risk Abstracts; Pollution Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Risk KW - Public Health KW - Drinking Water KW - Safety KW - Diseases KW - Toxicity KW - Pathogens KW - Water quality KW - Public health KW - H 11000:Diseases/Injuries/Trauma KW - SW 3030:Effects of pollution KW - R2 23060:Medical and environmental health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17715141?accountid=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+and+Ecological+Statistics&rft.atitle=Assessment+of+risk+from+long+term+exposure+to+waterborne+pathogens&rft.au=Pinsky%2C+P+F&rft.aulast=Pinsky&rft.aufirst=P&rft.date=2000-06-01&rft.volume=7&rft.issue=2&rft.spage=155&rft.isbn=&rft.btitle=&rft.title=Environmental+and+Ecological+Statistics&rft.issn=13528505&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2016-06-22 N1 - SubjectsTermNotLitGenreText - Risk assessment; Safety; Pathogens; Water quality; Public health; Risk; Drinking Water; Public Health; Toxicity; Diseases ER - TY - JOUR T1 - The Growth and Morphological Behavior of Salivary Epithelial Cells on Matrix Protein-Coated Biodegradable Substrata AN - 17675789; 4733444 AB - The purpose of this study was to examine the growth and morphology of a salivary epithelial cell line (HSG) in vitro on several biodegradable substrata as an important step toward developing an artificial salivary gland. The substrates examined were poly-(L)-lactic acid (PLLA), polyglycolic acid (PGA), and two co-polymers, 85% and 50% PLGA, respectively. The substrates were formed into 20- to 25-mm disks, and the cells were seeded directly onto the polymers or onto polymers coated with specific extracellular matrix proteins. The two copolymer substrates became friable over time in aqueous media and proved not useful for these experiments. The purified matrix proteins examined included fibronectin (FN), laminin (LN), collagen I, collagen IV, and gelatin. In the absence of preadsorbed proteins, HSG cells did not attach to the polymer disks. The cells, in general, behaved similarly on both PLLA and PGA, although optimal results were obtained consistently in PLLA. On FN-coated PLLA disks, HSG cells were able to form a uniform monolayer, which was dependent on time and FN concentration. Coating of disks with LN, collagen I, and gelatin also promoted monolayer growth. This study defines the conditions necessary for establishing a monolayer organization of salivary epithelial cells with rapid proliferation on a biodegradable substrate useful for tissue engineering. JF - Tissue Engineering AU - Aframian, D J AU - Cukierman, E AU - Nikolovski, J AU - Mooney, D J AU - Yamada, K M AU - Baum, B J AD - GTTB, NIDCR, NIH, Bldg. 10, Rm 1N113, MSC-1190, Bethesda, MD 20892, USA Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 209 EP - 216 VL - 6 IS - 3 SN - 1076-3279, 1076-3279 KW - growth KW - morphology KW - fibronectin KW - gelatin KW - laminins KW - matrix proteins KW - polyglycolic acid KW - polylactic acid KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Collagen (type IV) KW - Copolymers KW - Epithelium KW - Salivary gland KW - Collagen (type I) KW - Coatings KW - W 30965:Miscellaneous, Reviews KW - W3 33220:Cell culture UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17675789?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tissue+Engineering&rft.atitle=The+Growth+and+Morphological+Behavior+of+Salivary+Epithelial+Cells+on+Matrix+Protein-Coated+Biodegradable+Substrata&rft.au=Aframian%2C+D+J%3BCukierman%2C+E%3BNikolovski%2C+J%3BMooney%2C+D+J%3BYamada%2C+K+M%3BBaum%2C+B+J&rft.aulast=Aframian&rft.aufirst=D&rft.date=2000-06-01&rft.volume=6&rft.issue=3&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Tissue+Engineering&rft.issn=10763279&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Salivary gland; Epithelium; Collagen (type IV); Collagen (type I); Coatings; Copolymers ER - TY - JOUR T1 - Mammalian deconstruction for stem cell reconstruction AN - 17670762; 4742399 AB - A collection of recent studies have suggested that adult stem cells taken from brain, muscle and blood can be converted into multiple mammalian tissue types. Can we build entire animals from stem cells found in the adult body? JF - Nature Medicine AU - McKay, R AD - Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA, mckay@codon.nih.gov Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 747 EP - 748 VL - 6 IS - 7 SN - 1078-8956, 1078-8956 KW - reconstruction KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Blood KW - Stem cells KW - Mammalian cells KW - Reviews KW - Muscles KW - Brain KW - W 30965:Miscellaneous, Reviews KW - W3 33000:General topics and reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17670762?accountid=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+Medicine&rft.atitle=Mammalian+deconstruction+for+stem+cell+reconstruction&rft.au=McKay%2C+R&rft.aulast=McKay&rft.aufirst=R&rft.date=2000-06-01&rft.volume=6&rft.issue=7&rft.spage=747&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Stem cells; Mammalian cells; Reviews; Brain; Muscles; Blood ER - TY - JOUR T1 - Avidin- or Streptavidin-Biotin as a Highly Sensitive Method to Stain Total Protein on Membranes AN - 17670280; 4754908 AB - A sensitive method for staining proteins after transfer from polyacrylamide gels to nitrocellulose paper is described. Transferred proteins are first derivatized by reaction of the nitrocellulose replica with sulfosuccinimidobiotin and are then reacted sequentially with streptavidin, rabbit anti-streptavidin, and horseradish peroxidase-conjugated goat anti-rabbit IgG antibody. Incubation with the enzyme substrate alpha -chloronaphthol, produces dark protein bands against a white background. The binding of streptavidin to the proteins is dependent on biotin derivatization as demonstrated by competition with biotinylated bovine serum albumin or 10 nM biotin. The procedure detects less than 5ng of transferred protein in a single band and is thus 5-10 times more sensitive than horseradish peroxidase-conjugated avidin alone. For bovine serum albumin, the method is comparable in sensitivity to silver staining of protein in polyacrylamide gels. JF - Molecular Biotechnology AU - Santora, KE AU - Nelson, SA AU - Lewis, KA AU - LaRochelle, W J AD - National Cancer Institute Laboratory of Cellular and Molecular Biology Building 37 Room 1E24 National Institutes of Health Bethesda, MD 20892, USA, billr@helix.nih.gov Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 161 EP - 165 VL - 15 IS - 2 SN - 1073-6085, 1073-6085 KW - avidin KW - biotin KW - nitrocellulose KW - polyacrylamide KW - streptavidin KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gels KW - Membranes KW - Immunoglobulin G KW - Staining KW - Silver KW - W3 33240:Immunology KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17670280?accountid=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=Molecular+Biotechnology&rft.atitle=Avidin-+or+Streptavidin-Biotin+as+a+Highly+Sensitive+Method+to+Stain+Total+Protein+on+Membranes&rft.au=Santora%2C+KE%3BNelson%2C+SA%3BLewis%2C+KA%3BLaRochelle%2C+W+J&rft.aulast=Santora&rft.aufirst=KE&rft.date=2000-06-01&rft.volume=15&rft.issue=2&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Molecular+Biotechnology&rft.issn=10736085&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 - Immunoglobulin G; Membranes; Silver; Staining; Gels ER - TY - JOUR T1 - Who's your neighbor? New computational approaches for functional genomics AN - 17655526; 4742412 AB - Several recently developed computational approaches in comparative genomics go beyond sequence comparison. By analyzing phylogenetic profiles of protein families, domain fusions, gene adjacency in genomes, and expression patterns, these methods predict many functional interactions between proteins and help deduce specific functions for numerous proteins. Although some of the resultant predictions may not be highly specific, these developments herald a new era in genomics in which the benefits of comparative analysis of the rapidly growing collection of complete genomes will become increasingly obvious. JF - Nature Biotechnology AU - Galperin, MY 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 - 2000/06// PY - 2000 DA - Jun 2000 SP - 609 EP - 613 VL - 18 IS - 6 SN - 1087-0156, 1087-0156 KW - protein families KW - genomics KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Agricultural and Environmental Biotechnology Abstracts KW - Phylogeny KW - Reviews KW - G 07190:General structure KW - W2 32000:General topics and reviews KW - W 30965:Miscellaneous, Reviews KW - W3 33000:General topics and reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17655526?accountid=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=Who%27s+your+neighbor%3F+New+computational+approaches+for+functional+genomics&rft.au=Galperin%2C+MY%3BKoonin%2C+E+V&rft.aulast=Galperin&rft.aufirst=MY&rft.date=2000-06-01&rft.volume=18&rft.issue=6&rft.spage=609&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2F76443 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Phylogeny; Reviews DO - http://dx.doi.org/10.1038/76443 ER - TY - JOUR T1 - In vivo targeted repair of a point mutation in the canine dystrophin gene by a chimeric RNA/DNA oligonucleotide AN - 17655323; 4742413 AB - In the canine model of Duchenne muscular dystrophy in golden retrievers (GRMD), a point mutation within the splice acceptor site of intron 6 leads to deletion of exon 7 from the dystrophin mRNA, and the consequent frameshift causes early termination of translation. We have designed a DNA and RNA chimeric oligonucleotide to induce host cell mismatch repair mechanisms and correct the chromosomal mutation to wild type. Direct skeletal muscle injection of the chimeric oligonucleotide into the cranial tibialis compartment of a six-week-old affected male dog, and subsequent analysis of biopsy and necropsy samples, demonstrated in vivo repair of the GRMD mutation that was sustained for 48 weeks. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of exons 5-10 demonstrated increasing levels of exon 7 inclusion with time. An isolated exon 7-specific dystrophin antibody confirmed synthesis of normal-sized dystrophin product and positive localization to the sarcolemma. Chromosomal repair in muscle tissue was confirmed by restriction fragment length polymorphism (RFLP)-PCR and sequencing the PCR product. This work provides evidence for the long-term repair of a specific dystrophin point mutation in muscle of a live animal using a chimeric oligonucleotide. JF - Nature Biotechnology AU - Bartlett, R J AU - Stockinger, S AU - Denis, M M AU - Bartlett, W T AU - Inverardi, L AU - Le, T T AU - Thi Man, N AU - Morris, GE AU - Bogan, D J AU - Metcalf-Bogan, J AU - Kornegay, J N AD - Department of Veterinary Medicine and Surgery, Dalton Cardiovascular Research Center, College of Veterinary Medicine, Columbia, MO 65202, USA, richard_bartlett@nih.gov Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 615 EP - 622 VL - 18 IS - 6 SN - 1087-0156, 1087-0156 KW - dogs KW - animal models KW - oligonucleotides KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts KW - Point mutation KW - Dystrophin KW - Restriction fragment length polymorphism KW - Muscles KW - Duchenne's muscular dystrophy KW - Splicing KW - N 14250:Biological properties KW - W 30965:Miscellaneous, Reviews KW - W3 33380:Antisense UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17655323?accountid=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=In+vivo+targeted+repair+of+a+point+mutation+in+the+canine+dystrophin+gene+by+a+chimeric+RNA%2FDNA+oligonucleotide&rft.au=Bartlett%2C+R+J%3BStockinger%2C+S%3BDenis%2C+M+M%3BBartlett%2C+W+T%3BInverardi%2C+L%3BLe%2C+T+T%3BThi+Man%2C+N%3BMorris%2C+GE%3BBogan%2C+D+J%3BMetcalf-Bogan%2C+J%3BKornegay%2C+J+N&rft.aulast=Bartlett&rft.aufirst=R&rft.date=2000-06-01&rft.volume=18&rft.issue=6&rft.spage=615&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2F76448 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Muscles; Restriction fragment length polymorphism; Splicing; Point mutation; Dystrophin; Duchenne's muscular dystrophy DO - http://dx.doi.org/10.1038/76448 ER - TY - JOUR T1 - Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells AN - 17652396; 4742435 AB - Embryonic stem (ES) cells are clonal cell lines derived from the inner cell mass of the developing blastocyst that can proliferate extensively in vitro and are capable of adopting all the cell fates in a developing embryo. Clinical interest in the use of ES cells has been stimulated by studies showing that isolated human cells with ES properties from the inner cell mass or developing germ cells can provide a source of somatic precursors. Previous studies have defined in vitro conditions for promoting the development of specific somatic fates, specifically, hematopoietic, mesodermal, and neurectodermal. In this study, we present a method for obtaining dopaminergic (DA) and serotonergic neurons in high yield from mouse ES cells in vitro. Furthermore, we demonstrate that the ES cells can be obtained in unlimited numbers and that these neuron types are generated efficiently. We generated CNS progenitor populations from ES cells, expanded these cells and promoted their differentation into dopaminergic and serotonergic neurons in the presence of mitogen and specific signaling molecules. The differentation and maturation of neuronal cells was completed after mitogen withdrawal from the growth medium. This experimental system provides a powerful tool for analyzing the molecular mechanisms controlling the functions of these neurons in vitro and in vivo, and potentially for understanding and treating neurodegenerative and psychiatric diseases. JF - Nature Biotechnology AU - Lee, Sang-Hun AU - Lumelsky, N AU - Studer, L AU - Auerbach, J M AU - McKay, R D AD - Laboratory of Molecular Biology, NINDS, NIH, Bethesda, MD 20892, USA, mckay@codon.nih.gov Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 675 EP - 679 VL - 18 IS - 6 SN - 1087-0156, 1087-0156 KW - mice KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Hindbrain KW - Cell culture KW - Serotonin KW - Mesencephalon KW - Stem cells KW - Neurogenesis KW - Dopamine KW - Neurons KW - Cell fate KW - N3 11020:Neuroprotocols and apparatus KW - W 30965:Miscellaneous, Reviews KW - W3 33220:Cell culture UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17652396?accountid=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=Efficient+generation+of+midbrain+and+hindbrain+neurons+from+mouse+embryonic+stem+cells&rft.au=Lee%2C+Sang-Hun%3BLumelsky%2C+N%3BStuder%2C+L%3BAuerbach%2C+J+M%3BMcKay%2C+R+D&rft.aulast=Lee&rft.aufirst=Sang-Hun&rft.date=2000-06-01&rft.volume=18&rft.issue=6&rft.spage=675&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2F76536 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Dopamine; Serotonin; Cell fate; Neurogenesis; Stem cells; Cell culture; Hindbrain; Neurons; Mesencephalon DO - http://dx.doi.org/10.1038/76536 ER - TY - JOUR T1 - The structure of the transcriptional antiterminator NusB from Escherichia coli AN - 17635459; 4790244 AB - We have determined the solution structure of NusB, a transcription antitermination protein from Escherichia coli. The structure reveals a novel, all alpha -helical protein fold. NusB mutations that cause a loss of function (NusB5) or alter specificity for RNA targets (NusB101) are localized to surface residues and likely affect RNA-protein or protein-protein interactions. Residues that are highly conserved among homologs stabilize the protein core. The solution structure of E. coli NusB presented here resembles that of Mycobacterium tuberculosis NusB determined by X-ray diffraction, but differs substantially from a solution structure of E. coli NusB reported earlier. JF - Nature Structural Biology AU - Altieri, A S AU - Mazzulla, MJ AU - Horita, DA AU - Coats, R H AU - Wingfield, P T AU - Das, A AU - Court, D L AU - Byrd, R A AD - Structural Biophysics Laboratory, National Cancer Institute-FCRDC, P.O. Box B, Building 538, Frederick, Maryland 21702, USA, rabyrd@ncifcrf.gov Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 470 EP - 474 VL - 7 IS - 6 SN - 1072-8368, 1072-8368 KW - solution structure KW - NusB protein KW - transcription antitermination KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Escherichia coli KW - N.M.R. KW - J 02726:RNA and ribosomes KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17635459?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Structural+Biology&rft.atitle=The+structure+of+the+transcriptional+antiterminator+NusB+from+Escherichia+coli&rft.au=Altieri%2C+A+S%3BMazzulla%2C+MJ%3BHorita%2C+DA%3BCoats%2C+R+H%3BWingfield%2C+P+T%3BDas%2C+A%3BCourt%2C+D+L%3BByrd%2C+R+A&rft.aulast=Altieri&rft.aufirst=A&rft.date=2000-06-01&rft.volume=7&rft.issue=6&rft.spage=470&rft.isbn=&rft.btitle=&rft.title=Nature+Structural+Biology&rft.issn=10728368&rft_id=info:doi/10.1038%2F75869 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; N.M.R. DO - http://dx.doi.org/10.1038/75869 ER - TY - JOUR T1 - Increased AP-1 DNA-Binding Activity and Nuclear REF-1 Accumulation in Lead-Exposed Primary Cultures of Astrocytes AN - 17567271; 4747216 AB - Pb was shown to perturb neuronal and glial function either directly by interacting with protein thiol groups or indirectly by mimicking Ca super(2+) and increasing oxidative stress. In view of the potential action of Pb on cellular redox homeostasis we studied the regulation of activator protein-1 (AP-1) DNA binding. A 1h incubation of astrocyte primary cultures with 10 mu M Pb caused a 2.5 fold increase in AP-1 DNA binding. An assessment of how Pb elicited this increase revealed the involvement of 1. transcriptional and 2. posttranslational processes. The first one was documented by an increase of c-jun mRNA content after 15 to 30 min of 10 mu M Pb exposure. The second one was suggested by an enhanced nuclear accumulation of redox factor-1 after 30 to 60 min of 10 mu M Pb exposure. The Pb-elicited increase of the reduction/oxidation-sensitive AP-1 signal transduction may regulate target genes operative in cell survival or cell death. JF - Neurochemical Research AU - Scortegagna, M AU - Hanbauer, I AD - Laboratory of Biochemistry, NHLBI, Bldg. 10, Room 7N312, National Institutes of Health, Bethesda, MD 20892-1674, USA, hanbauei@fido.nhlbi.nih.gov Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 861 EP - 866 VL - 25 IS - 6 SN - 0364-3190, 0364-3190 KW - redox factor-1 KW - Calcium & Calcified Tissue Abstracts; CSA Neurosciences Abstracts; Toxicology Abstracts KW - Cell survival KW - Calcium KW - Astrocytes KW - AP-1 protein KW - Lead KW - Oxidative stress KW - c-Jun protein KW - ^AAP-1 protein KW - Cell death KW - Neurons KW - Neurotoxicity KW - Signal transduction KW - X 24165:Biochemistry KW - N3 11073:Glial cell biology and metabolism KW - T 20019:Cellular calcium, channels and currents UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17567271?accountid=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=Neurochemical+Research&rft.atitle=Increased+AP-1+DNA-Binding+Activity+and+Nuclear+REF-1+Accumulation+in+Lead-Exposed+Primary+Cultures+of+Astrocytes&rft.au=Scortegagna%2C+M%3BHanbauer%2C+I&rft.aulast=Scortegagna&rft.aufirst=M&rft.date=2000-06-01&rft.volume=25&rft.issue=6&rft.spage=861&rft.isbn=&rft.btitle=&rft.title=Neurochemical+Research&rft.issn=03643190&rft_id=info:doi/10.1023%2FA%3A1007577710066 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Neurotoxicity; Lead; Calcium; Cell survival; Cell death; Neurons; Astrocytes; AP-1 protein; c-Jun protein; Oxidative stress; Signal transduction; ^AAP-1 protein DO - http://dx.doi.org/10.1023/A:1007577710066 ER - TY - JOUR T1 - Statistical Analysis of Skin Tumor Data from Tg.AC Mouse Bioassays AN - 17559181; 4746351 AB - New strategies for identifying chemical carcinogens and assessing risk have been proposed based on the Tg.AC (zetaglobin promoted v-Ha-ras) transgenic mouse. Preliminary studies suggest that the Tg.AC mouse bioassay may be an effective means of quickly evaluating the carcinogenic potential of a test agent. The skin of the Tg.AC mouse is genetically initiated, and the induction of epidermal papillomas in response to dermal or oral exposure to a chemical agent acts as a reporter phenotype of the activity of the test chemical. In Tg.AC mouse bioassays, the test agent is typically applied topically for up to 26 weeks, and the number of papillomas in the treated area is counted weekly. Statistical analyses are complicated by within-animal and serial dependency in the papilloma counts, survival differences between animals, and missing data. In this paper, we describe a statistical model for the analysis of skin tumor data from a Tg.AC mouse bioassay. The model separates effects on papilloma latency and multiplicity and accommodates important features of the data, including variability in expression of the transgene and dependency in the tumor counts. Methods are described for carcinogenicity testing and risk assessment. We illustrate our approach using data from a study of the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on tumorigenesis. JF - Toxicological Sciences AU - Dunson, D B AU - Haseman, J K AU - Van Birgelen, APJM AU - Stasiewicz, S AU - Tennant, R W AD - Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 293 EP - 302 VL - 55 IS - 2 SN - 1096-6080, 1096-6080 KW - mice KW - statistical analysis KW - Toxicology Abstracts KW - Risk assessment KW - Skin KW - Tumors KW - Toxicity testing KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17559181?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Statistical+Analysis+of+Skin+Tumor+Data+from+Tg.AC+Mouse+Bioassays&rft.au=Dunson%2C+D+B%3BHaseman%2C+J+K%3BVan+Birgelen%2C+APJM%3BStasiewicz%2C+S%3BTennant%2C+R+W&rft.aulast=Dunson&rft.aufirst=D&rft.date=2000-06-01&rft.volume=55&rft.issue=2&rft.spage=293&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Risk assessment; Toxicity testing; Skin; Tumors ER - TY - JOUR T1 - Metallothionein-I/II Null Mice Are More Sensitive than Wild-Type Mice to the Hepatotoxic and Nephrotoxic Effects of Chronic Oral or Injected Inorganic Arsenicals AN - 17554388; 4746370 AB - Metallothionein (MT) is a low-molecular-weight, sulfhydryl-rich, metal-binding protein that can protect against the toxicity of cadmium, mercury, and copper. However, the role of MT in arsenic (As)-induced toxicity is less certain. To better define the ability of MT to modify As toxicity, MT-I/II knockout (MT-null) mice and the corresponding wild-type mice (WT) were exposed to arsenite [As (III)] or arsenate [As(V)] either through the drinking water for 48 weeks, or through repeated sc injections (5 days/week) for 15 weeks. Chronic As exposure increased tissue MT concentrations (2-5-fold) in the WT but not in MT-null mice. Arsenic by both routes produced damage to the liver (fatty infiltration, inflammation, and focal necrosis) and kidney (tubular cell vacuolization, inflammatory cell infiltration, and interstitial fibrosis) in both MT-null and WT mice. However, in MT-null mice, the pathological lesions were more frequent and severe when compared to WT mice. This was confirmed biochemically in that, at the higher oral doses of As, blood urea nitrogen (BUN) levels were increased more in MT-null mice (60%) than in WT mice (30%). Chronic As exposures produced 2-10 fold elevation of serum interleukin-1 beta , interleukin-6, and tumor necrosis factor- alpha levels, with greater increases seen by repeated injections than by oral exposure, and again, MT-null mice had higher serum cytokines than WT mice after As exposure. Repeated As injections also decreased hepatic glutathione (GSH) by 35%, but GSH-peroxidase and GSH-reductase were minimally affected. MT-null mice were more sensitive than WT mice to the effect of GSH depletion by As(V). Hepatic caspase-3 activity was increased (2-3-fold) in both WT and MT-null mice, indicative of apoptotic cell death. In summary, chronic inorganic As exposure produced injuries to multiple organs, and MT-null mice are generally more susceptible than WT mice to As-induced toxicity regardless of route of exposure, suggesting that MT could be a cellular factor in protecting against chronic As toxicity. JF - Toxicological Sciences AU - Liu, Jie AU - Liu, Yaping AU - Goyer, R A AU - Achanzar, W AU - Waalkes, M P AD - Laboratory of Comparative Carcinogenesis, NCI at NIEHS, Mail Drop F0-09, Research Triangle Park, NC 27709, USA Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 460 EP - 467 VL - 55 IS - 2 SN - 1096-6080, 1096-6080 KW - mice KW - Toxicology Abstracts KW - Arsenic KW - Metallothionein KW - Kidney KW - Liver KW - X 24162:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17554388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Metallothionein-I%2FII+Null+Mice+Are+More+Sensitive+than+Wild-Type+Mice+to+the+Hepatotoxic+and+Nephrotoxic+Effects+of+Chronic+Oral+or+Injected+Inorganic+Arsenicals&rft.au=Liu%2C+Jie%3BLiu%2C+Yaping%3BGoyer%2C+R+A%3BAchanzar%2C+W%3BWaalkes%2C+M+P&rft.aulast=Liu&rft.aufirst=Jie&rft.date=2000-06-01&rft.volume=55&rft.issue=2&rft.spage=460&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Arsenic; Metallothionein; Liver; Kidney ER - TY - JOUR T1 - A novel episomal shuttle vector for transformation of Cryptococcus neoformans with the ccdB gene as a positive selection marker in bacteria AN - 17552408; 4735300 AB - We report the engineering of a new shuttle vector featuring its episomal maintenance in Cryptococcus neoformans and the lethal Escherichia coli ccdB gene for positive selection in bacteria. Telomere-like sequences from C. neoformans and the STAB fragment confer episomal maintenance to the vector (pPM8) upon transformation in C. neoformans. The vector generated high transformation frequencies and each transformant was estimated to harbor thirty copies of the plasmid. The plasmids recovered in E. coli from the C. neoformans transformants showed no evidence of rearrangement. This construct will be very useful for cloning and studying the regulation of genes in C. neoformans. JF - FEMS Microbiology Letters AU - Mondon, P AU - Chang, Y C AU - Varma, A AU - Kwon-Chung, K J AD - Molecular Microbiology Section, LCI, National Institute of Allergy and Infectious Diseases, N.I.H., Bldg. 10, 11C304, 20892 Bethesda, MD USA Y1 - 2000/06/01/ PY - 2000 DA - 2000 Jun 01 SP - 41 EP - 45 PB - Elsevier VL - 187 IS - 1 SN - 0378-1097, 0378-1097 KW - ccdB gene KW - shuttle vectors KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Transformation KW - Bacteria KW - Cryptococcus neoformans KW - N 14682:Cloning vectors KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17552408?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEMS+Microbiology+Letters&rft.atitle=A+novel+episomal+shuttle+vector+for+transformation+of+Cryptococcus+neoformans+with+the+ccdB+gene+as+a+positive+selection+marker+in+bacteria&rft.au=Mondon%2C+P%3BChang%2C+Y+C%3BVarma%2C+A%3BKwon-Chung%2C+K+J&rft.aulast=Mondon&rft.aufirst=P&rft.date=2000-06-01&rft.volume=187&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=FEMS+Microbiology+Letters&rft.issn=03781097&rft_id=info:doi/10.1016%2FS0378-1097%2800%2900168-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cryptococcus neoformans; Bacteria; Transformation DO - http://dx.doi.org/10.1016/S0378-1097(00)00168-3 ER - TY - JOUR T1 - Streptococcal erythrogenic toxin B abrogates fibronectin-dependent internalization of Streptococcus pyogenes by cultured mammalian cells AN - 17550945; 4734036 AB - Streptococcus pyogenes secretes several proteins that influence host-pathogen interactions. A tissue-culture model was used to study the influence of the secreted cysteine protease streptococcal erythrogenic toxin B (SPE B) on the interaction between S. pyogenes strain NZ131 (serotype M49) and mammalian cells. Inactivation of the speB gene enhanced fibronectin-dependent uptake of the pathogen by Chinese hamster ovary (CHO-K1) cells compared to that in the isogenic wild-type strain. Preincubation of the NZ131 speB mutant with purified SPE B protease significantly inhibited fibronectin-dependent uptake by both CHO-K1 and CHO-pgs745 cells. The effect was attributed to an abrogation of fibronectin binding to the surface of the bacteria that did not involve either the M49 protein or the streptococcal fibronectin-binding protein SfbI. In contrast, pretreatment of the NZ131 speB mutant with SPE B did not influence sulfated polysaccharide-mediated uptake by CHO-pgs745 cells. The results indicate that the SPE B protease specifically alters bacterial cell surface proteins and thereby influences pathogen uptake. JF - Infection and Immunity AU - Chaussee AU - Cole, R L AU - Van Putten, JPM AD - Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South Fourth St., Hamilton, MT 59840, USA, mchaussee@nih.gov Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 3226 EP - 3232 VL - 68 IS - 6 SN - 0019-9567, 0019-9567 KW - CHO cells KW - uptake KW - inactivation KW - Chinese hamster ovary KW - Cysteine proteinase KW - Streptococcal erythrogenic toxin B KW - cysteine proteinase KW - fibronectin KW - Toxicology Abstracts; Microbiology Abstracts B: Bacteriology KW - Virulence KW - Animal cells KW - Mammalian cells KW - Gene regulation KW - Host-pathogen interactions KW - Fibronectin KW - Toxins KW - Streptococcus pyogenes KW - X 24171:Microbial KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17550945?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Streptococcal+erythrogenic+toxin+B+abrogates+fibronectin-dependent+internalization+of+Streptococcus+pyogenes+by+cultured+mammalian+cells&rft.au=Chaussee%3BCole%2C+R+L%3BVan+Putten%2C+JPM&rft.aulast=Chaussee&rft.aufirst=&rft.date=2000-06-01&rft.volume=68&rft.issue=6&rft.spage=3226&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.68.6.3226-3232.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus pyogenes; Toxins; Mammalian cells; Fibronectin; Animal cells; Host-pathogen interactions; Gene regulation; Virulence DO - http://dx.doi.org/10.1128/IAI.68.6.3226-3232.2000 ER - TY - JOUR T1 - Replacement of histidine 340 with alanine inactivates the group A Streptococcus extracellular cysteine protease virulence factor AN - 17549787; 4734099 AB - Streptococcus pyogenes expresses a highly conserved extracellular cysteine protease that is a virulence factor for invasive disease, including soft tissue infection. Site-directed mutagenesis was used to generate a His340Ala recombinant mutant protein that was made as a stable 40-kDa zymogen by Escherichia coli. Purified His340Ala protein was proteolytically inactive when bovine casein and human fibronectin were used as substrates. Wild-type 28-kDa streptococcal protease purified from S. pyogenes processed the 40-kDa mutant zymogen to a 28-kDa mature form, a result suggesting that the derivative protein retained structural integrity. The data are consistent with the hypothesis that His340 is an enzyme active site residue, an idea confirmed by recent solution of the zymogen crystal structure (T.F. Kagawa, J.C. Cooney, H.M. Baker, S. McSweeney, M. Liu, S. Gubba, J.M. Musser, and E.N. Baker, Proc. Natl. Acad. Sci. USA 97:2235-2240, 2000). The data provide additional insight into structure-function relationships in this S. pyogenes virulence factor. JF - Infection and Immunity AU - Gubba, S AU - Cipriano, V 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, USA, jmusser@niaid.nih.gov Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 3716 EP - 3719 VL - 68 IS - 6 SN - 0019-9567, 0019-9567 KW - Cysteine proteinase KW - Histidine 340 KW - Microbiology Abstracts B: Bacteriology KW - Site-directed mutagenesis KW - Virulence KW - Streptococcus KW - Zymogen granules KW - Enzymatic activity KW - Plasmids KW - Structure-activity relationships KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17549787?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Replacement+of+histidine+340+with+alanine+inactivates+the+group+A+Streptococcus+extracellular+cysteine+protease+virulence+factor&rft.au=Gubba%2C+S%3BCipriano%2C+V%3BMusser%2C+J+M&rft.aulast=Gubba&rft.aufirst=S&rft.date=2000-06-01&rft.volume=68&rft.issue=6&rft.spage=3716&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.68.6.3716-3719.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus; Virulence; Site-directed mutagenesis; Enzymatic activity; Plasmids; Structure-activity relationships; Zymogen granules DO - http://dx.doi.org/10.1128/IAI.68.6.3716-3719.2000 ER - TY - JOUR T1 - Hypersensitivity of Escherichia coli Delta (uvrB-bio) Mutants to 6-Hydroxylaminopurine and Other Base Analogs Is Due to a Defect in Molybdenum Cofactor Biosynthesis AN - 17549547; 4734344 AB - We have shown previously that Escherichia coli and Salmonella enterica serovar Typhimurium strains carrying a deletion of the uvrB-bio region are hypersensitive to the mutagenic and toxic action of 6- hydroxylaminopurine (HAP) and related base analogs. This sensitivity is not due to the uvrB excision repair defect associated with this deletion because a uvrB point mutation or a uvrA deficiency does not cause hypersensitivity. In the present work, we have investigated which gene(s) within the deleted region may be responsible for this effect. Using independent approaches, we isolated both a point mutation and a transposon insertion in the moeA gene, which is located in the region covered by the deletion, that conferred HAP sensitivity equal to that conferred by the uvrB-bio deletion. The moeAB operon provides one of a large number of genes responsible for biosynthesis of the molybdenum cofactor. Defects in other genes in the same pathway, such as moa or mod, also lead to the same HAP-hypersensitive phenotype. We propose that the molybdenum cofactor is required as a cofactor for an as yet unidentified enzyme (or enzymes) that acts to inactivate HAP and other related compounds. JF - Journal of Bacteriology AU - Kozmin, S G AU - Pavlov, YI AU - Dunn, R L AU - Schaaper, R M AD - Laboratory of Molecular Genetics, MD E3-01, National Institute of Environmental Health Sciences, 111 TW Alexander Dr., Research Triangle Park, NC 27709, schaaper@niehs.nih.gov Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 3361 EP - 3367 VL - 182 IS - 12 SN - 0021-9193, 0021-9193 KW - point mutation KW - excision repair KW - 6-hydroxylaminopurine KW - moeA gene KW - moeAB operon KW - molybdenum KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Escherichia coli KW - DNA repair KW - Mutants KW - N 14681:Mutagenesis techniques KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17549547?accountid=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=Hypersensitivity+of+Escherichia+coli+Delta+%28uvrB-bio%29+Mutants+to+6-Hydroxylaminopurine+and+Other+Base+Analogs+Is+Due+to+a+Defect+in+Molybdenum+Cofactor+Biosynthesis&rft.au=Kozmin%2C+S+G%3BPavlov%2C+YI%3BDunn%2C+R+L%3BSchaaper%2C+R+M&rft.aulast=Kozmin&rft.aufirst=S&rft.date=2000-06-01&rft.volume=182&rft.issue=12&rft.spage=3361&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.182.12.3361-3367.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Mutants; DNA repair DO - http://dx.doi.org/10.1128/JB.182.12.3361-3367.2000 ER - TY - JOUR T1 - Retinal degeneration in licensed pesticide applicators AN - 17536119; 4726225 AB - Retinal degeneration is the leading cause of visual impairment in older adults, but little is known about its relationship to neurotoxic exposures. The Agricultural Health Study is a cohort study of licensed pesticide applicators from Iowa and North Carolina. We used cross-sectional data from self-administered questionnaires given at enrollment in 1994-1996 to compare pesticide use in 154 applicators who reported retinal degeneration and 17.804 controls. Retinal degeneration was associated with fungicide use (odds ratio = 1.8, 95% confidence interval = 1.3-2.6). This relationship was seen in subgroups defined by state, demographic characteristics, or medical history, as well as in the entire group. Risk increased with cumulative days of fungicide use (P for trend = 0.011) and was greater when application methods involving greater personal exposure were used. Retinal degeneration was also related to use of organochlorine or carbamate insecticides, but these associations were less consistent. Since nearly all applicators used organophosphate insecticides and herbicides, these exposures could not be effectively evaluated. These results suggest that exposure to some fungicides and insecticides may increase risk of retinal degeneration. JF - American Journal of Industrial Medicine AU - Kamel, F AU - Boyes, W K AU - Gladen, B C AU - Rowland, A S AU - Alavanja, MCR AU - Blair, A AU - Sandler, D P AD - Epidemiology Branch, MD A3-05, National Institute of Environmental Health Sciences, Box 12233, Research Triangle Park, NC 27709, USA, kamel@niehs.nih.gov Y1 - 2000/06// PY - 2000 DA - Jun 2000 SP - 618 EP - 628 VL - 37 IS - 6 SN - 0271-3586, 0271-3586 KW - retinal degeneration KW - Risk Abstracts; Health & Safety Science Abstracts KW - Neurotoxicity KW - Pesticides KW - Occupational exposure KW - R2 23080:Industrial and labor KW - H 5000:Pesticides UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17536119?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Industrial+Medicine&rft.atitle=Retinal+degeneration+in+licensed+pesticide+applicators&rft.au=Kamel%2C+F%3BBoyes%2C+W+K%3BGladen%2C+B+C%3BRowland%2C+A+S%3BAlavanja%2C+MCR%3BBlair%2C+A%3BSandler%2C+D+P&rft.aulast=Kamel&rft.aufirst=F&rft.date=2000-06-01&rft.volume=37&rft.issue=6&rft.spage=618&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/10.1002%2F%28SICI%291097-0274%28200006%2937%3A63.0.CO%3B2-E LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pesticides; Neurotoxicity; Occupational exposure DO - http://dx.doi.org/10.1002/(SICI)1097-0274(200006)37:6<618::AID-AJIM6>3.0.CO;2-E ER - TY - JOUR T1 - Detection of disease related immune complexes in the serum of leprosy patients: A novel single step method AN - 17506952; 4687408 AB - Mycobacterium leprae antigen and antibody complexes could be detected in the serum of leprosy patients using monoclonal antibody ML34 and anti-BCG antibodies by enzyme-linked immunosorbent assay. This simplified system detects disease related complexes without the need for isolating and purifying them from the serum. Immune complexes captured using monoclonal antibody ML34 revealed positivity in seven out of eight neuritic, two out of nine tuberculoid (TT), five out of ten borderline tuberculoid (BT), four out of ten borderline lepromatous (BL) and four out of ten lepromatous (LL), leprosy cases. One of the controls also showed immune complex of an IgM type. Anti-BCG based IgG immune complexes assay revealed positivity in six out of eight neuritic, one out of nine TT, four out of ten BT, two out of ten BL, four out of ten LL leprosy cases, and two out of 24 healthy controls. IgM type of mycobacterial immune complexes were almost negligible. Capture of complexes using monoclonal antibody ML34 which is against lipoarabinomannan of M. leprae seems to work better than polyclonal anti-BCG antibody. The probable role of immune complexes in nerve damage needs to be evaluated, as very high levels of immune complexes are found in neuritic leprosy by both the assays. The above test would be useful in immunodiagnosis of neuritic leprosy and also in cases where antibody response is not detectable because of the formation of immune complexes. JF - Journal of Neuroimmunology AU - Patil, SA AU - Ramu, G AU - Prasad, R AD - Department of Microbiology, National Institute of Mental Health and Neurosciences Bangalore India Y1 - 2000/06/01/ PY - 2000 DA - 2000 Jun 01 SP - 64 EP - 68 PB - Elsevier VL - 105 IS - 1 SN - 0165-5728, 0165-5728 KW - man KW - neuritic leprosy KW - immunology KW - Mycobacterium leprae KW - CSA Neurosciences Abstracts; Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Immunodiagnosis KW - Antigen-antibody complexes KW - Axons KW - Leprosy KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms KW - N3 11150:General and miscellaneous topics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17506952?accountid=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+Neuroimmunology&rft.atitle=Detection+of+disease+related+immune+complexes+in+the+serum+of+leprosy+patients%3A+A+novel+single+step+method&rft.au=Patil%2C+SA%3BRamu%2C+G%3BPrasad%2C+R&rft.aulast=Patil&rft.aufirst=SA&rft.date=2000-06-01&rft.volume=105&rft.issue=1&rft.spage=64&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neuroimmunology&rft.issn=01655728&rft_id=info:doi/10.1016%2FS0165-5728%2800%2900190-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium leprae; Antigen-antibody complexes; Leprosy; Immunodiagnosis; Axons DO - http://dx.doi.org/10.1016/S0165-5728(00)00190-9 ER - TY - JOUR T1 - Mutational spectra for polycyclic aromatic hydrocarbons in the supF target gene. AN - 71158331; 10838135 AB - An SV40-based shuttle vector system was used to identify the types of mutational changes and the sites of mutation within the supF DNA sequence generated by the four stereoisomers of benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide (B[c]PhDE), by racemic mixtures of bay or fjord region dihydrodiol epoxides (DE) of 5-methylchrysene, of 5, 6-dimethylchrysene, of benzo[g]chrysene and of 7-methylbenz[a]anthracene and by two direct acting polycyclic aromatic hydrocarbon carcinogens, 7-bromomethylbenz[a]anthracene (7-BrMeBA) and 7-bromomethyl-12-methylbenz[a]anthracene (7-BrMe-12-MeBA). The results of these studies demonstrated that the predominant type of mutation induced by these compounds is the base substitution. The chemical preference for reaction at deoxyadenosine (dAdo) or deoxyguanosine (dGuo) residues in DNA, which is in general correlated with the spatial structure (planar or non-planar) of the reactive polycyclic aromatic hydrocarbon, is reflected in the preference for mutation at A&z.ccirf;T or G&z.ccirf;C pairs. In addition, if the ability to react with DNA in vivo is taken into account, the relative mutagenic potencies of the B[c]PhDE stereoisomers are consistent with the higher tumorigenic activity associated with non-planar polycyclic aromatic hydrocarbons and their extensive reaction with dAdo residues in DNA. Comparison of the types of mutations generated by polycyclic aromatic hydrocarbons and other bulky carcinogens in this shuttle vector system suggests that all bulky lesions may be processed by a similar mechanism related to that involved in replication past apurinic sites. However, inspection of the distribution of mutations over the target gene induced by the different compounds demonstrated that individual polycyclic aromatic hydrocarbons induce unique patterns of mutational hotspots within the target gene. A polymerase arrest assay was used to determine the sequence specificity of the interaction of reactive polycyclic aromatic hydrocarbons with the shuttle vector DNA. The results of these assays revealed a divergence between mutational hotspots and polymerase arrest sites for all compounds investigated, i.e., sites of mutational hotspots do not correspond to sites where high levels of adduct formation occur, and suggested that some association between specific adducts and sequence context may be required to constitute a premutagenic lesion. A site-specific mutagenesis system employing a single-stranded vector (M13mp7L2) was used to investigate the mutational events a single benzo[a]pyrene or benzo[c]phenanthrene dihydrodiol epoxide-DNA adduct elicits within specific sequence contexts. These studies showed that sequence context can cause striking differences in mutagenic frequencies for given adducts. In addition, these sequence context effects do not originate only from nucleotides immediately adjacent to the adduct, but are also modulated by more distal nucleotides. The implications of these results for mechanisms of polycyclic aromatic hydrocarbon-induced mutagenesis and carcinogenesis are discussed. JF - Mutation research AU - Bigger, C A AU - Pontén, I AU - Page, J E AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, Basic Research Program, Advanced BioScience Laboratories, Frederick Cancer Research and Development Center, National Cancer Institute, Frederick, MD 21702, USA. biggera@cder.fda.gov Y1 - 2000/05/30/ PY - 2000 DA - 2000 May 30 SP - 75 EP - 93 VL - 450 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Polycyclic Aromatic Hydrocarbons KW - 0 KW - supF tRNA KW - DNA KW - 9007-49-2 KW - RNA, Transfer KW - 9014-25-9 KW - Index Medicus KW - Animals KW - Base Sequence KW - Humans KW - Genetic Vectors KW - DNA -- genetics KW - Point Mutation KW - Molecular Sequence Data KW - Sequence Deletion KW - DNA -- drug effects KW - Polycyclic Aromatic Hydrocarbons -- toxicity KW - RNA, Transfer -- genetics KW - Polycyclic Aromatic Hydrocarbons -- chemistry KW - Mutation KW - Genes, Suppressor -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71158331?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Mutational+spectra+for+polycyclic+aromatic+hydrocarbons+in+the+supF+target+gene.&rft.au=Bigger%2C+C+A%3BPont%C3%A9n%2C+I%3BPage%2C+J+E%3BDipple%2C+A&rft.aulast=Bigger&rft.aufirst=C&rft.date=2000-05-30&rft.volume=450&rft.issue=1-2&rft.spage=75&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-27 N1 - Date created - 2000-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutation spectra in supF: approaches to elucidating sequence context effects. AN - 71156529; 10838134 AB - Shuttle vectors carrying the supF suppressor tRNA gene were originally developed for mutagenesis experiments in primate and human cells. Since then, the supF gene has been used as a mutation reporter in other mammalian cells, yeast, Escherichia coli, and transgenic mice. The widespread use of the vector for studies of many DNA reactive agents has produced a large database of mutation spectra. These provide primary information on the kinds and distribution of mutations provoked by many agents and, in many instances, allow comparisons between related agents or the same agent in different cell backgrounds. In this review we will discuss some of these data with a primary focus on the interpretation of UV mutation spectra. We will also describe our development and application of custom supF marker genes as an approach to studying the effect of sequence context on mutation hotspots and cold spots. Our studies suggest that C-C photoproducts are not mutagenic in certain sequence contexts in which T-C photoproducts are mutation hotspots. In addition, we have found several examples of sequence context effects acting as much as 80 bases away from the site of mutation. We will consider some of the problems raised by these studies and the possible resolution of some of them offered by the newly discovered family of damage bypass DNA polymerases. JF - Mutation research AU - Canella, K A AU - Seidman, M M AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Room 3D06, Building 37, Bethesda, MD 20892, USA. Y1 - 2000/05/30/ PY - 2000 DA - 2000 May 30 SP - 61 EP - 73 VL - 450 IS - 1-2 SN - 0027-5107, 0027-5107 KW - supF tRNA KW - 0 KW - DNA KW - 9007-49-2 KW - RNA, Transfer KW - 9014-25-9 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Animals KW - Genetic Variation KW - Ultraviolet Rays KW - Humans KW - Xeroderma Pigmentosum -- genetics KW - Xeroderma Pigmentosum -- metabolism KW - Mice KW - Nucleic Acid Conformation KW - Base Sequence KW - Genetic Vectors KW - DNA -- genetics KW - Molecular Sequence Data KW - DNA -- chemistry KW - DNA -- radiation effects KW - DNA-Directed DNA Polymerase -- metabolism KW - RNA, Transfer -- genetics KW - RNA, Transfer -- chemistry KW - Genes, Suppressor -- radiation effects KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71156529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Mutation+spectra+in+supF%3A+approaches+to+elucidating+sequence+context+effects.&rft.au=Canella%2C+K+A%3BSeidman%2C+M+M&rft.aulast=Canella&rft.aufirst=K&rft.date=2000-05-30&rft.volume=450&rft.issue=1-2&rft.spage=61&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-27 N1 - Date created - 2000-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human Ca2+ receptor cysteine-rich domain. Analysis of function of mutant and chimeric receptors. AN - 71136576; 10747888 AB - The 612-residue extracellular domain of the human Ca(2+) receptor (hCaR) has been speculated to consist of a Venus's-flytrap domain (VFT) and a cysteine-rich domain. We studied the function of the hCaR Cys-rich domain by using mutagenesis and chimera approaches. A chimeric hCaR with the sequence from residues 540-601 replaced by the corresponding sequence from the Fugu CaR remained fully functional. Another chimeric hCaR with the same region of sequence replaced by the corresponding sequence from metabotropic glutamate receptor subtype 1 (mGluR1) still was activated by extracellular Ca(2+) ([Ca(2+)](o)), but its function was severely compromised. Chimeric receptors with the hCaR VFT and mGluR1 seven-transmembrane domain plus C-tail domain retained good response to [Ca(2+)](o) whether the Cys-rich domain was from hCaR or from mGluR1. Mutant hCaR with the Cys-rich domain deleted failed to respond to [Ca(2+)](o), although it was expressed at the cell surface and capable of dimerization. Our results indicate that the hCaR Cys-rich domain plays a critical role in signal transmission from VFT to seven-transmembrane domain. This domain tolerates a significant degree of amino acid substitution and may not be directly involved in the binding of [Ca(2+)](o). JF - The Journal of biological chemistry AU - Hu, J AU - Hauache, O AU - Spiegel, A M AD - Metabolic Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. jianxinh@intra.niddk.nih.gov Y1 - 2000/05/26/ PY - 2000 DA - 2000 May 26 SP - 16382 EP - 16389 VL - 275 IS - 21 SN - 0021-9258, 0021-9258 KW - Membrane Proteins KW - 0 KW - Phosphatidylinositols KW - Receptors, Calcium-Sensing KW - Receptors, Cell Surface KW - Receptors, Metabotropic Glutamate KW - Recombinant Fusion Proteins KW - metabotropic glutamate receptor type 1 KW - Cysteine KW - K848JZ4886 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Immunoblotting KW - Phosphatidylinositols -- metabolism KW - Receptors, Metabotropic Glutamate -- genetics KW - Humans KW - Membrane Proteins -- metabolism KW - Amino Acid Sequence KW - Calcium -- pharmacology KW - Membrane Proteins -- genetics KW - Protein Binding KW - Mutagenesis, Site-Directed KW - Cysteine -- chemistry KW - Transfection KW - Molecular Sequence Data KW - Signal Transduction KW - Calcium Signaling KW - Cell Line KW - Recombinant Fusion Proteins -- metabolism KW - Recombinant Fusion Proteins -- genetics KW - Receptors, Cell Surface -- genetics KW - Receptors, Cell Surface -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71136576?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Human+Ca2%2B+receptor+cysteine-rich+domain.+Analysis+of+function+of+mutant+and+chimeric+receptors.&rft.au=Hu%2C+J%3BHauache%2C+O%3BSpiegel%2C+A+M&rft.aulast=Hu&rft.aufirst=J&rft.date=2000-05-26&rft.volume=275&rft.issue=21&rft.spage=16382&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 - 2000-06-30 N1 - Date created - 2000-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An efficient recombination system for chromosome engineering in Escherichia coli AN - 17598493; 4716289 AB - A recombination system has been developed for efficient chromosome engineering in Escherichia coli by using electroporated linear DNA. A defective lambda prophage supplies functions that protect and recombine an electroporated linear DNA substrate in the bacterial cell. The use of recombination eliminates the requirement for standard cloning as all novel joints are engineered by chemical synthesis in vitro and the linear DNA is efficiently recombined into place in vivo. The technology and manipulations required are simple and straightforward. A temperature-dependent repressor tightly controls prophage expression, and, thus, recombination functions can be transiently supplied by shifting cultures to 42 degree C for 15 min. The efficient prophage recombination system does not require host RecA function and depends primarily on Exo, Beta, and Gam functions expressed from the defective lambda prophage. The defective prophage can be moved to other strains and can be easily removed from any strain. Gene disruptions and modifications of both the bacterial chromosome and bacterial plasmids are possible. This system will be especially useful for the engineering of large bacterial plasmids such as those from bacterial artificial chromosome libraries. JF - Proceedings of the National Academy of Sciences, USA AU - Yu, D AU - Ellis, H M AU - Lee, E AU - Jenkins, NA AU - Copeland, NG AU - Court, D L AD - Gene Regulation and Chromosome Biology Laboratory and Mouse Cancer Genetics Program, National Cancer Institute, Division of Basic Science, National Cancer Institute/Frederick Cancer Research and Development Center, Frederick, MD 21702, court@ncifcrf.gov Y1 - 2000/05/23/ PY - 2000 DA - 2000 May 23 SP - 5978 EP - 5983 VL - 97 IS - 11 SN - 0027-8424, 0027-8424 KW - Biotechnology and Bioengineering Abstracts; Microbiology Abstracts B: Bacteriology; Agricultural and Environmental Biotechnology Abstracts; Genetics Abstracts KW - Phage ^l KW - Phage l KW - Recombination KW - Chromosomes KW - Escherichia coli KW - RecA protein KW - G 07320:Bacterial genetics KW - W2 32060:Microorganisms KW - W 30965:Miscellaneous, Reviews KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17598493?accountid=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=An+efficient+recombination+system+for+chromosome+engineering+in+Escherichia+coli&rft.au=Yu%2C+D%3BEllis%2C+H+M%3BLee%2C+E%3BJenkins%2C+NA%3BCopeland%2C+NG%3BCourt%2C+D+L&rft.aulast=Yu&rft.aufirst=D&rft.date=2000-05-23&rft.volume=97&rft.issue=11&rft.spage=5978&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.100127597 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Phage ^l; Phage l; Chromosomes; Recombination; RecA protein DO - http://dx.doi.org/10.1073/pnas.100127597 ER - TY - JOUR T1 - Highly reduced protection against Streptococcus pneumoniae after deletion of a single heavy chain gene in mouse AN - 17524903; 4716298 AB - Phosphocholine (PC) is the immunodominant epitope found on the surface of Streptococcus pneumoniae (SPn). T15-idiotype Abs, whose heavy (H) chain variable region is encoded by the V1 gene, are dominant in the anti-PC response in adult mice and protect mice from lethal pneumococcal infection. The ability of anti-PC Abs using H chains other than the V1 H chain to protect against pneumococcal infection remains controversial. We generated V1 super(-/-) knockout mice to determine whether protective anti-PC Abs could be produced in the absence of the V1 gene. No anti-PC Abs were produced in V1 super(-/-) mice immunized with avirulent SPn; however, PC-BSA binding Abs were induced after immunization with PC-keyhole limpet hemocyanin but at significantly lower levels than those in wild-type mice. These Abs provided poor protection against virulent SPn; thus, <25% of V1 super(-/-) mice survived challenge with 10 super(4) bacteria as compared with 100% survival of V1 super(+/+) mice. The anti-PC Abs in V1 super(-/-) mice were heteroclitic, binding to nitrophenyl-PC better than to PC. None of nine hybridomas produced from V1 super(-/-) mice provided passive protection. However, the V1 super(-/-) mice produced normal amounts of Ab to SPn proteins that can partially protect mice against SPn. These data indicate that the V1 gene is critical for the production of anti-PC Abs providing optimum protection against infection with SPn, and the V1 super(-/-) mice could be useful in unmasking epitopes other than the immunodominant PC epitope on SPn capable of providing cross protection. JF - Proceedings of the National Academy of Sciences, USA AU - Mi, Q AU - Zhou, L AU - Schulze, D H AU - Fischer, R T AU - Lustig, A AU - Rezanka, L J AU - Donovan, D M AU - Longo, D L AU - Kenny, J J AD - Laboratory of Immunology, B Cell Development Section, Transgenic and Knockout Facility Section, Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, kennyj@grc.nia.nih.gov Y1 - 2000/05/23/ PY - 2000 DA - 2000 May 23 SP - 6031 EP - 6036 VL - 97 IS - 11 SN - 0027-8424, 0027-8424 KW - infectivity KW - mice KW - heavy chains KW - epitopes KW - immunology KW - Phosphocholine KW - Streptococcus pneumoniae KW - V1 gene KW - double prime V1 gene KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - ^AV1 gene KW - Antibodies KW - Infectivity KW - Antigens KW - Disease resistance KW - Immunodominance KW - J 02832:Antigenic properties and virulence KW - G 07397:Rodentia (mice) KW - F 06008:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17524903?accountid=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=Highly+reduced+protection+against+Streptococcus+pneumoniae+after+deletion+of+a+single+heavy+chain+gene+in+mouse&rft.au=Mi%2C+Q%3BZhou%2C+L%3BSchulze%2C+D+H%3BFischer%2C+R+T%3BLustig%2C+A%3BRezanka%2C+L+J%3BDonovan%2C+D+M%3BLongo%2C+D+L%3BKenny%2C+J+J&rft.aulast=Mi&rft.aufirst=Q&rft.date=2000-05-23&rft.volume=97&rft.issue=11&rft.spage=6031&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.110039497 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus pneumoniae; Disease resistance; Infectivity; Antibodies; Immunodominance; Antigens DO - http://dx.doi.org/10.1073/pnas.110039497 ER - TY - JOUR T1 - Immunomodulation by cannabinoids is absent in mice deficient for the cannabinoid CB(2) receptor. AN - 71131799; 10822068 AB - Cannabinoids have immunomodulatory as well as psychoactive effects. Because the central cannabinoid receptor (cannabinoid CB(1) receptor) is highly expressed in many neuronal tissues and the peripheral cannabinoid receptor (cannabinoid CB(2) receptor) is highly expressed in immune cells, it has been suggested that the central nervous system effects of cannabinoids are mediated by cannabinoid CB(1) receptors and that the immune effects are mediated by cannabinoid CB(2) receptors. To test this hypothesis, we have generated the first mouse strain with a targeted mutation in the cannabinoid CB(2) receptor gene. Binding studies using the highly specific synthetic cannabinoid receptor agonist (-)-cis-3-¿2-Hydroxy-4-(1, 1-dimethylheptyl)phenyl-trans-4-(3-hydroxypropyl)cyclohexanol (¿3HCP 55,940) revealed no residual cannabinoid binding sites in the spleen of the cannabinoid CB(2) receptor knockout mice, while binding in the central nervous system was unchanged. Cannabinoid CB(2) receptor knockout mice, which appear healthy, are fertile and care for their offspring. Fluorescence activated cell sorting (FACS) analysis showed no differences in immune cell populations between cannabinoid CB(2) receptor knockout and wildtype mice. We investigated the immunomodulatory effects of cannabinoids in cannabinoid CB(2) receptor deficient mice using a T cell co-stimulation assay. Delta(9)Tetrahydrocannabinol inhibits helper T cell activation through macrophages derived from wild type, but not from knockout mice, thus indicating that this effect is mediated by the cannabinoid CB(2) receptor. In contrast, central nervous system effects of cannabinoids were not altered in these mice. Our results suggest that cannabinoid CB(2) receptor-specific ligands may be clinically useful in the modulation of macrophage immune function while exhibiting no central nervous system activity. Furthermore, we conclude that the cannabinoid CB(2) receptor knockout mouse is a useful animal model in which to study the role of the cannabinoid system in immunoregulation. JF - European journal of pharmacology AU - Buckley, N E AU - McCoy, K L AU - Mezey, E AU - Bonner, T AU - Zimmer, A AU - Felder, C C AU - Glass, M AD - Basic Neuroscience Program, NINDS, National Institutes of Health, Bethesda, MD 20892, USA. nebuckley@csupomona.edu Y1 - 2000/05/19/ PY - 2000 DA - 2000 May 19 SP - 141 EP - 149 VL - 396 IS - 2-3 SN - 0014-2999, 0014-2999 KW - Cyclohexanols KW - 0 KW - Receptors, Cannabinoid KW - Receptors, Drug KW - Dronabinol KW - 7J8897W37S KW - 3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol KW - 83003-12-7 KW - Index Medicus KW - Lymphocyte Activation -- drug effects KW - Animals KW - Catalepsy -- chemically induced KW - Body Temperature -- drug effects KW - Cyclohexanols -- metabolism KW - Mice, Inbred C57BL KW - Mice KW - T-Lymphocytes -- drug effects KW - Mice, Knockout KW - Receptors, Drug -- genetics KW - Dronabinol -- pharmacology KW - Receptors, Drug -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71131799?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+pharmacology&rft.atitle=Immunomodulation+by+cannabinoids+is+absent+in+mice+deficient+for+the+cannabinoid+CB%282%29+receptor.&rft.au=Buckley%2C+N+E%3BMcCoy%2C+K+L%3BMezey%2C+E%3BBonner%2C+T%3BZimmer%2C+A%3BFelder%2C+C+C%3BGlass%2C+M&rft.aulast=Buckley&rft.aufirst=N&rft.date=2000-05-19&rft.volume=396&rft.issue=2-3&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-06 N1 - Date created - 2000-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural and functional characterization of interaction between hepatitis B virus X protein and the proteasome complex. AN - 71108735; 10748218 AB - Hepatitis B virus (HBV) has a unique fourth open reading frame coding for a 16.5-kDa protein known as hepatitis B virus X protein (HBX). The importance of HBX in the life cycle of HBV has been well established, but the underlying molecular function of HBX remains controversial. We previously identified a proteasome subunit PSMA7 that interacts specifically with HBX in the Saccharomyces cerevisiae two-hybrid system. Here we demonstrate that PSMC1, an ATPase-like subunit of the 19 S proteasome component, also interacts with HBX and PSMA7. Analysis of the interacting domains among PSMA7, PSMC1, and HBX by deletion and site-directed mutagenesis suggested a mutually competitive structural relationship among these polypeptides. The competitive nature of these interactions is further demonstrated using a modified yeast two-hybrid dissociator system. The crucial HBX sequences involved in interaction with PSMA7 and PSMC1 are important for its function as a transcriptional coactivator. HBX, while functioning as a coactivator of AP-1 and acidic activator VP-16 in mammalian cells, had no effect on the transactivation function of their functional orthologs GCN4 and Gal4 in yeast. Overexpression of PSMC1 seemed to suppress the expression of various reporters in mammalian cells; this effect, however, was overcome by coexpression of HBX. In addition, HBX expression inhibited the cellular turnover of c-Jun and ubiquitin-Arg-beta-galactosidase, two well known substrates of the ubiquitin-proteasome pathway. Thus, interaction of HBX with the proteasome complex in metazoan cells may underlie the functional basis of proteasome as a cellular target of HBX. JF - The Journal of biological chemistry AU - Zhang, Z AU - Torii, N AU - Furusaka, A AU - Malayaman, N AU - Hu, Z AU - Liang, T J AD - Liver Diseases Section, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/05/19/ PY - 2000 DA - 2000 May 19 SP - 15157 EP - 15165 VL - 275 IS - 20 SN - 0021-9258, 0021-9258 KW - Hepatitis B Antigens KW - 0 KW - Macromolecular Substances KW - Multienzyme Complexes KW - Recombinant Proteins KW - Trans-Activators KW - hepatitis B virus X protein KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Index Medicus KW - Protein Biosynthesis KW - Animals KW - Models, Molecular KW - Open Reading Frames KW - Adenosine Triphosphatases -- metabolism KW - Rabbits KW - Hepatitis B virus -- genetics KW - Protein Binding KW - Hepatitis B Antigens -- metabolism KW - Protein Structure, Quaternary KW - Cloning, Molecular KW - Saccharomyces cerevisiae -- genetics KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Hepatitis B Antigens -- chemistry KW - Reticulocytes -- metabolism KW - Recombinant Proteins -- chemistry KW - Multienzyme Complexes -- chemistry KW - Trans-Activators -- metabolism KW - Multienzyme Complexes -- metabolism KW - Trans-Activators -- genetics KW - Cysteine Endopeptidases -- metabolism KW - Cysteine Endopeptidases -- chemistry KW - Trans-Activators -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71108735?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Structural+and+functional+characterization+of+interaction+between+hepatitis+B+virus+X+protein+and+the+proteasome+complex.&rft.au=Zhang%2C+Z%3BTorii%2C+N%3BFurusaka%2C+A%3BMalayaman%2C+N%3BHu%2C+Z%3BLiang%2C+T+J&rft.aulast=Zhang&rft.aufirst=Z&rft.date=2000-05-19&rft.volume=275&rft.issue=20&rft.spage=15157&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 - 2000-06-21 N1 - Date created - 2000-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Integrin-mediated RON growth factor receptor phosphorylation requires tyrosine kinase activity of both the receptor and c-Src. AN - 71107055; 10747844 AB - Cooperation between integrins and growth factor receptors plays an important role in the regulation of cell growth, differentiation, and survival. The function of growth factor receptor tyrosine kinases (RTKs) can be regulated by cell adhesion to extracellular matrix (ECM) even in the absence of ligand. We investigated the pathway involved in integrin-mediated RTK activation, using RON, the receptor for macrophage-stimulating protein. Adhesion of RON-expressing epithelial cells to ECM caused phosphorylation of RON, which depended on the kinase activity of both RON itself and c-Src. This conclusion is based on these observations: 1) ECM-induced RON phosphorylation was inhibited in cells expressing kinase-inactive c-Src; 2) active c-Src could phosphorylate immunoprecipitated RON from ECM-stimulated cells but not from unstimulated cells; and 3) ECM did not cause RON phosphorylation in cells expressing kinase-dead RON, nor could active c-Src phosphorylate RON immunoprecipitated from these cells. The data fit a pathway in which ECM-induced integrin aggregation causes both c-Src activation and RON oligomerization followed by RON kinase-dependent autophosphorylation; this results in RON becoming a target for activated c-Src, which phosphorylates additional tyrosines on RON. Integrin-induced epidermal growth factor receptor (EGFR) phosphorylation also depended on both EGFR and c-Src kinase activities. This sequence appears to be a general pathway for integrin-dependent growth factor RTK activation. JF - The Journal of biological chemistry AU - Danilkovitch-Miagkova, A AU - Angeloni, D AU - Skeel, A AU - Donley, S AU - Lerman, M AU - Leonard, E J AD - Laboratory of Immunobiology, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. danilkovitch@mail.ncifcrf.gov Y1 - 2000/05/19/ PY - 2000 DA - 2000 May 19 SP - 14783 EP - 14786 VL - 275 IS - 20 SN - 0021-9258, 0021-9258 KW - Integrins KW - 0 KW - Receptors, Cell Surface KW - Recombinant Proteins KW - Collagen KW - 9007-34-5 KW - RON protein KW - EC 2.7.10.1 KW - Receptor Protein-Tyrosine Kinases KW - Receptor, Epidermal Growth Factor KW - Proto-Oncogene Proteins pp60(c-src) KW - EC 2.7.10.2 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Epithelial Cells -- physiology KW - Receptor, Epidermal Growth Factor -- metabolism KW - Phosphorylation KW - Transfection KW - Recombinant Proteins -- metabolism KW - Humans KW - Collagen -- physiology KW - Cell Line KW - Cell Adhesion KW - Receptors, Cell Surface -- metabolism KW - Receptor Protein-Tyrosine Kinases -- genetics KW - Proto-Oncogene Proteins pp60(c-src) -- metabolism KW - Macrophages -- physiology KW - Receptors, Cell Surface -- genetics KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Integrins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71107055?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Integrin-mediated+RON+growth+factor+receptor+phosphorylation+requires+tyrosine+kinase+activity+of+both+the+receptor+and+c-Src.&rft.au=Danilkovitch-Miagkova%2C+A%3BAngeloni%2C+D%3BSkeel%2C+A%3BDonley%2C+S%3BLerman%2C+M%3BLeonard%2C+E+J&rft.aulast=Danilkovitch-Miagkova&rft.aufirst=A&rft.date=2000-05-19&rft.volume=275&rft.issue=20&rft.spage=14783&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 - 2000-06-21 N1 - Date created - 2000-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conformational modulation of human cytochrome P450 2E1 by ethanol and other substrates: a CO flash photolysis study. AN - 71101104; 10801323 AB - The alcohol-inducible cytochrome P450 2E1 is a major human hepatic P450 which metabolizes a broad array of endogenous and exogenous compounds, including ethanol, low-molecular weight toxins, and fatty acids. Several substrates are known to stabilize this P450 and inhibit its cellular degradation. Furthermore, ethanol is a known modulator of P450 2E1 substrate metabolism. We examined the CO binding kinetics of P450 2E1 after laser flash photolysis of the heme-CO bond, to probe the effects of ethanol and other substrates on protein conformation and dynamics. Ethanol had an effect on the two kinetic parameters that describe CO binding: it decreased the rate of CO binding, suggesting a decrease in the protein's conformational flexibility, and increased the photosensitivity, which indicates a local effect in the active site region such as strengthening of the heme-CO bond. Other substrates decreased the CO binding rate to varying degrees. Of particular interest is the effect of arachidonic acid, which abolished photodissociation in the absence of ethanol but had no effect in the presence of ethanol. These results are consistent with a model of P450 2E1 whereby arachidonic acid binds along a long hydrophobic binding pocket and blocks exit of CO from the heme region. JF - Biochemistry AU - Smith, S V AU - Koley, A P AU - Dai, R AU - Robinson, R C AU - Leong, H AU - Markowitz, A AU - Friedman, F K AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, and Bioengineering and Physical Science Program, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/05/16/ PY - 2000 DA - 2000 May 16 SP - 5731 EP - 5737 VL - 39 IS - 19 SN - 0006-2960, 0006-2960 KW - Ligands KW - 0 KW - Arachidonic Acid KW - 27YG812J1I KW - Ethanol KW - 3K9958V90M KW - Carbon Monoxide KW - 7U1EE4V452 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Halothane KW - UQT9G45D1P KW - Index Medicus KW - Substrate Specificity -- drug effects KW - Models, Molecular KW - Halothane -- chemistry KW - Kinetics KW - Humans KW - Binding Sites -- drug effects KW - Arachidonic Acid -- chemistry KW - Protein Conformation -- drug effects KW - Photolysis -- drug effects KW - Cytochrome P-450 CYP2E1 -- chemistry KW - Ethanol -- chemistry KW - Cytochrome P-450 CYP2E1 -- metabolism KW - Carbon Monoxide -- metabolism KW - Carbon Monoxide -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71101104?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Conformational+modulation+of+human+cytochrome+P450+2E1+by+ethanol+and+other+substrates%3A+a+CO+flash+photolysis+study.&rft.au=Smith%2C+S+V%3BKoley%2C+A+P%3BDai%2C+R%3BRobinson%2C+R+C%3BLeong%2C+H%3BMarkowitz%2C+A%3BFriedman%2C+F+K&rft.aulast=Smith&rft.aufirst=S&rft.date=2000-05-16&rft.volume=39&rft.issue=19&rft.spage=5731&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-27 N1 - Date created - 2000-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diazeniumdiolates: pro- and antioxidant applications of the "NONOates". AN - 71270729; 10927170 AB - Diazeniumdiolates are compounds containing the X-[N(O)NO](-) structural unit that as a class offer many advantages as tools for probing the roles of nitric oxide (NO) in biological redox processes. Available examples in which X is a secondary amine group spontaneously generate up to two molecules of NO per [N(O)NO](-) unit when dissolved in aqueous media; their half-lives range from 2 s (for X = L-prolyl) to 20 h [for X = (H(2)NCH(2)CH(2))(2)N] at pH 7. 4 and 37 degrees C, and are in general relatively little influenced by medium effects or metabolism. When X = O(-) (Angeli's salt), first-order dissociation produces NO(-) rather than NO, but the ion becomes an NO source on 1-electron oxidation; diazeniumdiolate-derived NO can also be used to generate reactive nitrogen/oxygen species with higher nitrogen oxidation states (+3 and +4) in the presence of selected oxidizing agents. The advantages of diazeniumdiolates in biomedical research are briefly illustrated with examples from the recent literature probing NO's role in inhibiting oxidative drug metabolism, radical-induced lipid oxidation, the cytotoxicity of reactive oxygen species, and ischemia-induced vascular reoxygenation injury. Future work with this compound class should provide further insight into the mechanisms of NO's involvement in pro- and antioxidant processes, and may well lead to important medicinal advances, including reversal of cerebral vasospasm and radiosensitization of hypoxic tumors. JF - Free radical biology & medicine AU - Fitzhugh, A L AU - Keefer, L K AD - Intramural Research Support Program, SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA. afitzhugh@mail.ncifcrf.gov Y1 - 2000/05/15/ PY - 2000 DA - 2000 May 15 SP - 1463 EP - 1469 VL - 28 IS - 10 SN - 0891-5849, 0891-5849 KW - Antioxidants KW - 0 KW - Cytochrome P-450 Enzyme Inhibitors KW - Lipoproteins, LDL KW - Nitric Oxide Donors KW - Nitroso Compounds KW - Oxidants KW - Reactive Oxygen Species KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Oxidants -- pharmacology KW - Humans KW - Cell Death -- drug effects KW - Oxidation-Reduction KW - Antioxidants -- pharmacology KW - In Vitro Techniques KW - Oxidants -- chemistry KW - Nitric Oxide -- pharmacology KW - Lipoproteins, LDL -- metabolism KW - Nitric Oxide -- chemistry KW - Antioxidants -- chemistry KW - Nitric Oxide Donors -- pharmacology KW - Nitroso Compounds -- chemistry KW - Nitroso Compounds -- pharmacology KW - Nitric Oxide Donors -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71270729?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Diazeniumdiolates%3A+pro-+and+antioxidant+applications+of+the+%22NONOates%22.&rft.au=Fitzhugh%2C+A+L%3BKeefer%2C+L+K&rft.aulast=Fitzhugh&rft.aufirst=A&rft.date=2000-05-15&rft.volume=28&rft.issue=10&rft.spage=1463&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 - 2000-09-25 N1 - Date created - 2000-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Investigation of design and bias issues in case-control studies of cancer screening using microsimulation. AN - 71184074; 10853638 AB - Using a microsimulation approach, the authors examined design and bias issues in case-control studies of cancer screening. Specifically, they looked at the impact on the odds ratio of the way in which exposure to screening is defined, the type of age matching, the time scale used, and the criteria used to determine control eligibility. The results showed that defining exposure as "ever/never" screened produced, as expected, a serious bias in favor of screening. Defining exposure as being screened no later than the time the case's cancer is diagnosed has a serious bias against screening. An alternative exposure definition--screening can occur no later than the time the case would have been clinically diagnosed--eliminates the bias against screening. Further, the results showed that the type of age matching and the time scale used can produce a bias against screening and that this bias can be quite strong when case-control studies are performed in populations with a periodic screening program that is the only source of screening. Finally, control eligibility criteria had little effect. JF - American journal of epidemiology AU - Connor, R J AU - Boer, R AU - Prorok, P C AU - Weed, D L AD - Biometry Branch, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892-7354, USA. Y1 - 2000/05/15/ PY - 2000 DA - 2000 May 15 SP - 991 EP - 998 VL - 151 IS - 10 SN - 0002-9262, 0002-9262 KW - Index Medicus KW - Odds Ratio KW - Reproducibility of Results KW - Humans KW - Environmental Exposure -- analysis KW - Data Interpretation, Statistical KW - Aged KW - Middle Aged KW - Environmental Exposure -- adverse effects KW - Time Factors KW - Female KW - Survival Analysis KW - Age Distribution KW - Breast Neoplasms -- mortality KW - Computer Simulation KW - Breast Neoplasms -- diagnosis KW - Case-Control Studies KW - Breast Neoplasms -- etiology KW - Models, Statistical KW - Mass Screening -- standards KW - Bias (Epidemiology) KW - Epidemiologic Research Design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71184074?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Investigation+of+design+and+bias+issues+in+case-control+studies+of+cancer+screening+using+microsimulation.&rft.au=Connor%2C+R+J%3BBoer%2C+R%3BProrok%2C+P+C%3BWeed%2C+D+L&rft.aulast=Connor&rft.aufirst=R&rft.date=2000-05-15&rft.volume=151&rft.issue=10&rft.spage=991&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 - 2000-06-23 N1 - Date created - 2000-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - H19 and Igf2 monoallelic expression is regulated in two distinct ways by a shared cis acting regulatory region upstream of H19. AN - 71123687; 10817754 AB - H19 and Igf2 are expressed in a monoallelic fashion from the maternal and paternal chromosomes, respectively. A region upstream of H19 has been shown to regulate such imprinted expression of both genes in cis. We have taken advantage of a loxP/cre recombinase-based strategy to delete this region in mice in a conditional manner to determine the temporal requirement of the upstream region in initiating and maintaining the imprinted expression of H19 and Igf2. Analysis of allele-specific expression of H19 and Igf2 and DNA methylation at the H19 promoter demonstrates that this region controls the monoallelic expression of the two genes in different ways, suggesting that it harbors two functionally distinct regulatory elements. Continued presence of the region is required to silence maternal Igf2 in accordance with its proposed role as an insulator. However, it does not have a direct role in keeping the paternal H19 promoter silenced. Instead, on the paternal chromosome, the upstream element mediates epigenetic modifications of the H19 promoter region during development, leading to transcriptional silencing of H19. Thereafter, its presence is redundant for preventing transcription. Presently, this temporal requirement of the silencing element appears to be a unique cis activity in the mammalian system. However, it is likely that other cis-acting elements, positive and negative, have the ability to effect stable changes in the chromatin structure and are not constantly required to give signals to the transcriptional machinery. JF - Genes & development AU - Srivastava, M AU - Hsieh, S AU - Grinberg, A AU - Williams-Simons, L AU - Huang, S P AU - Pfeifer, K AD - Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. Y1 - 2000/05/15/ PY - 2000 DA - 2000 May 15 SP - 1186 EP - 1195 VL - 14 IS - 10 SN - 0890-9369, 0890-9369 KW - H19 long non-coding RNA KW - 0 KW - Muscle Proteins KW - RNA, Long Noncoding KW - RNA, Messenger KW - RNA, Untranslated KW - Viral Proteins KW - Insulin-Like Growth Factor II KW - 67763-97-7 KW - Cre recombinase KW - EC 2.7.7.- KW - Integrases KW - Index Medicus KW - Animals KW - Gene Silencing KW - Integrases -- genetics KW - Gametogenesis -- genetics KW - Transcription, Genetic -- genetics KW - Mice KW - Attachment Sites, Microbiological -- genetics KW - RNA, Messenger -- genetics KW - Chromosomes -- genetics KW - Integrases -- metabolism KW - RNA, Messenger -- metabolism KW - DNA Methylation KW - Models, Genetic KW - Sequence Deletion -- genetics KW - CpG Islands -- genetics KW - Promoter Regions, Genetic -- genetics KW - Time Factors KW - Mutagenesis, Insertional -- genetics KW - Female KW - Male KW - Muscle Proteins -- genetics KW - Regulatory Sequences, Nucleic Acid -- genetics KW - Alleles KW - Gene Expression Regulation, Developmental -- genetics KW - Insulin-Like Growth Factor II -- genetics KW - Genomic Imprinting -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71123687?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+%26+development&rft.atitle=H19+and+Igf2+monoallelic+expression+is+regulated+in+two+distinct+ways+by+a+shared+cis+acting+regulatory+region+upstream+of+H19.&rft.au=Srivastava%2C+M%3BHsieh%2C+S%3BGrinberg%2C+A%3BWilliams-Simons%2C+L%3BHuang%2C+S+P%3BPfeifer%2C+K&rft.aulast=Srivastava&rft.aufirst=M&rft.date=2000-05-15&rft.volume=14&rft.issue=10&rft.spage=1186&rft.isbn=&rft.btitle=&rft.title=Genes+%26+development&rft.issn=08909369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-26 N1 - Date created - 2000-06-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1999 Oct 29;99(3):247-57 [10555141] Nature. 1995 May 4;375(6526):34-9 [7536897] Mol Cell Biol. 1988 Jul;8(7):2896-909 [3405222] Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1143-7 [1671714] Cell. 1991 Feb 22;64(4):849-59 [1997210] Nature. 1991 May 9;351(6322):153-5 [1709450] Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1827-31 [1542678] Mol Cell Biol. 1992 May;12(5):2424-31 [1569958] Development. 1991 Nov;113(3):1017-29 [1668275] Genes Dev. 1992 Oct;6(10):1843-56 [1383088] Nature. 1993 Apr 22;362(6422):751-5 [8469285] Nat Genet. 1995 Apr;9(4):407-13 [7795647] Genes Dev. 1995 Sep 1;9(17):2079-89 [7544754] Genes Dev. 1996 Apr 15;10(8):1021-32 [8608937] Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5860-5 [8650183] Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13876-83 [8943029] Mol Cell Biol. 1997 Jan;17(1):309-17 [8972211] Nucleic Acids Res. 1996 Dec 15;24(24):5064-6 [9016686] Curr Opin Genet Dev. 1997 Apr;7(2):242-8 [9115431] Nat Genet. 1997 Jun;16(2):171-3 [9171828] Mol Cell Biol. 1997 Aug;17(8):4322-9 [9234689] Annu Rev Genet. 1997;31:493-525 [9442905] Mol Cell Biol. 1998 Jun;18(6):3466-74 [9584186] Nature. 1998 May 28;393(6683):386-9 [9620804] Hum Mol Genet. 1998 Nov;7(12):1979-85 [9811943] Mol Cell. 1998 Nov;2(5):559-69 [9844629] Genes Dev. 1998 Dec 1;12(23):3693-702 [9851976] Mol Cell Biol. 1999 Apr;19(4):2556-66 [10082521] Curr Opin Genet Dev. 1999 Apr;9(2):164-70 [10322141] Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9242-7 [10430927] Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9733-8 [10449763] Nat Genet. 1999 Sep;23(1):58-61 [10471499] Nat Genet. 1999 Sep;23(1):62-6 [10471500] FEBS Lett. 1999 Sep 10;458(1):45-50 [10518931] Cell. 1993 Jun 18;73(6):1155-64 [8513499] Cell. 1993 Aug 13;74(3):505-14 [8348617] Genes Dev. 1993 Sep;7(9):1663-73 [7690336] Nature. 1993 Nov 25;366(6453):362-5 [8247133] EMBO J. 1993 Sep;12(9):3669-77 [7504628] Science. 1994 Jul 1;265(5168):103-6 [8016642] Curr Opin Genet Dev. 1994 Apr;4(2):265-80 [8032205] Proc Natl Acad Sci U S A. 1995 Jan 3;92(1):160-4 [7816809] Nat Genet. 2000 Jan;24(1):88-91 [10615135] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk factors for syncope in a community-based sample (the Framingham Heart Study). AN - 71100741; 10801999 AB - The epidemiology of syncope has not been well described. Prior studies have examined risk factors for syncope in hospital-based or other acute or long-term care settings. To determine risk factors for syncope in a community-based sample, we performed a nested case-control study. We examined reports of syncope in Framingham Heart Study participants who underwent routine clinic visits from 1971 to 1990. For each syncope case (n = 543) 2 controls were matched for age, sex, and examination period. Mean age of subjects was 67 years (range 25 to 95); 59% were women. History of stroke or transient ischemic attack, history of myocardial infarction, high blood pressure, use of antihypertensive medication, use of other cardiac medication, smoking, alcohol intake, body mass index, systolic blood pressure, diastolic blood pressure, heart rate, atrial fibrillation, PR interval prolongation, interventricular block, and diabetes or elevated glucose level were examined as potential predictors. Using conditional logistic regression analysis, the predictors of syncope included a history of stroke or transient ischemic attack (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.62 to 4.04), use of cardiac medication (OR 1.67, 95% CI 1.21 to 2. 30), and high blood pressure (OR 1.46, 95% CI 1.14 to 1.88). Lower body mass index was marginally associated with syncope (OR per 4 kg/m(2) decrement 1.10, 95% CI 0.99 to 1.22), as were increased alcohol intake (OR per 5 oz/week 1.11, 95% CI 0.99 to 1.26), and diabetes or an elevated glucose level (OR 1.29, 95% CI 0.96 to 1.75). To our knowledge, this study represents the first community-based study of risk factors for syncope. JF - The American journal of cardiology AU - Chen, L AU - Chen, M H AU - Larson, M G AU - Evans, J AU - Benjamin, E J AU - Levy, D AD - National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts 01702-6334, USA. Y1 - 2000/05/15/ PY - 2000 DA - 2000 May 15 SP - 1189 EP - 1193 VL - 85 IS - 10 SN - 0002-9149, 0002-9149 KW - Cardiotonic Agents KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Alcohol Drinking -- adverse effects KW - Aged KW - Massachusetts -- epidemiology KW - Aged, 80 and over KW - Logistic Models KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Databases, Factual KW - Middle Aged KW - Female KW - Male KW - Hypertension -- complications KW - Cardiotonic Agents -- adverse effects KW - Stroke -- complications KW - Syncope -- epidemiology KW - Syncope -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71100741?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+cardiology&rft.atitle=Risk+factors+for+syncope+in+a+community-based+sample+%28the+Framingham+Heart+Study%29.&rft.au=Chen%2C+L%3BChen%2C+M+H%3BLarson%2C+M+G%3BEvans%2C+J%3BBenjamin%2C+E+J%3BLevy%2C+D&rft.aulast=Chen&rft.aufirst=L&rft.date=2000-05-15&rft.volume=85&rft.issue=10&rft.spage=1189&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+cardiology&rft.issn=00029149&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-14 N1 - Date created - 2000-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolic stress in PC12 cells induces the formation of the endogenous dopaminergic neurotoxin, 3,4-dihydroxyphenylacetaldehyde. AN - 71094617; 10797558 AB - 3,4-Dihydroxyphenylacetaldehyde (DOPAL) has been reported to be a toxic metabolite formed by the oxidative-deamination of dopamine (DA) catalyzed by monoamine oxidase. This aldehyde is either oxidized to 3,4-dihydroxyphenylacetic acid (DOPAC) by aldehyde dehydrogenase, an NAD-dependent enzyme or reduced to 3, 4-dihydroxyphenylethanol (DOPET) by aldehyde or aldose reductase. In the present study we examined whether levels of DOPAL are elevated by inhibition of the mitochondrial respiratory chain. Using inhibitors of mitochondrial complexes I, II, III and IV we found that inhibition of complex I and III increased levels of DOPAL and DOPET. Nerve growth factor-induced differentiation of PC12 cells markedly potentiated DOPAL and DOPET accumulation in response to metabolic stress. DOPAL was toxic to differentiated PC12 as well as to SK-N-SH cell lines. Because complex I dysfunction has been implicated in the pathogenesis of Parkinson's disease, the accumulation of DOPAL may explain the vulnerability of the dopaminergic system to complex I inhibition. The rapid appearance of DOPAL and DOPET after inhibition of complex I may be a useful early index of oxidative stress in DA-forming neurons. Copyright 2000 Wiley-Liss, Inc. JF - Journal of neuroscience research AU - Lamensdorf, I AU - Eisenhofer, G AU - Harvey-White, J AU - Hayakawa, Y AU - Kirk, K AU - Kopin, I J AD - CNS, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. lamensdo@helix.nih.gov Y1 - 2000/05/15/ PY - 2000 DA - 2000 May 15 SP - 552 EP - 558 VL - 60 IS - 4 SN - 0360-4012, 0360-4012 KW - Neurotoxins KW - 0 KW - Uncoupling Agents KW - Rotenone KW - 03L9OT429T KW - 3,4-Dihydroxyphenylacetic Acid KW - 102-32-9 KW - 3,4-dihydroxyphenylethanol KW - 10597-60-1 KW - 3,4-dihydroxyphenylacetaldehyde KW - 5707-55-1 KW - Nerve Growth Factor KW - 9061-61-4 KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Glucose KW - IY9XDZ35W2 KW - Phenylethyl Alcohol KW - ML9LGA7468 KW - Dopamine KW - VTD58H1Z2X KW - Homovanillic Acid KW - X77S6GMS36 KW - Index Medicus KW - Animals KW - Oxidation-Reduction -- drug effects KW - Dose-Response Relationship, Drug KW - Phenylethyl Alcohol -- analogs & derivatives KW - Glucose -- metabolism KW - Humans KW - Dopamine -- metabolism KW - Homovanillic Acid -- metabolism KW - Phenylethyl Alcohol -- metabolism KW - Nerve Growth Factor -- pharmacology KW - Electron Transport -- drug effects KW - Rats KW - Rotenone -- toxicity KW - Uncoupling Agents -- toxicity KW - Cell Survival -- drug effects KW - Mitochondria -- drug effects KW - Mitochondria -- metabolism KW - Cell Differentiation -- drug effects KW - Cell Line KW - L-Lactate Dehydrogenase -- metabolism KW - PC12 Cells KW - Neurotoxins -- biosynthesis KW - Stress, Physiological -- metabolism KW - 3,4-Dihydroxyphenylacetic Acid -- metabolism KW - Neurons -- drug effects KW - Neurons -- cytology KW - Neurons -- enzymology KW - 3,4-Dihydroxyphenylacetic Acid -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71094617?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Metabolic+stress+in+PC12+cells+induces+the+formation+of+the+endogenous+dopaminergic+neurotoxin%2C+3%2C4-dihydroxyphenylacetaldehyde.&rft.au=Lamensdorf%2C+I%3BEisenhofer%2C+G%3BHarvey-White%2C+J%3BHayakawa%2C+Y%3BKirk%2C+K%3BKopin%2C+I+J&rft.aulast=Lamensdorf&rft.aufirst=I&rft.date=2000-05-15&rft.volume=60&rft.issue=4&rft.spage=552&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 - 2000-06-23 N1 - Date created - 2000-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An altered peptide ligand antagonizes antigen-specific T cells of patients with human T lymphotropic virus type I-associated neurological disease. AN - 71089503; 10799878 AB - Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurologic disease associated with HTLV-I infection, in which chronically activated, HTLV-I-specific CD8+ CTL have been suggested to be immunopathogenic. In HLA-A2 HAM/TSP patients, CD8+ HTLV-I-specific CTLs recognize an immunodominant peptide of the HTLV-I Tax protein, Tax11-19. We examined the functional outcome on activation of both cloned peripheral blood and cerebrospinal spinal fluid-derived CTL and bulk PBMC from HAM/TSP patients by altered peptide ligands (APL) derived from HTLV-I Tax11-19. In CTL clones generated from PBMC and CSF of HLA-A2 HAM/TSP patients, an APL substituted at position 5 significantly decreased CTL responses when compared with the native peptide. Moreover, these ligands were also shown to inhibit CTL responses to the native peptide in bulk PBMC of HLA-A2 HAM/TSP patients. These data suggest that a modification of an antigenic peptide at the central position can manipulate the T cell responses in bulk PBMC from different individuals with an inflammatory disease. Additionally, these results have implications for the potential use of APL-based immunotherapy in this T cell-mediated CNS disease. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Kubota, R AU - Soldan, S S AU - Martin, R AU - Jacobson, S AD - Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2000/05/15/ PY - 2000 DA - 2000 May 15 SP - 5192 EP - 5198 VL - 164 IS - 10 SN - 0022-1767, 0022-1767 KW - Epitopes, T-Lymphocyte KW - 0 KW - Gene Products, tax KW - Ligands KW - Peptide Fragments KW - Receptors, Antigen, T-Cell KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Clone Cells KW - Amino Acid Substitution -- immunology KW - Cytotoxicity Tests, Immunologic -- methods KW - Humans KW - T-Lymphocytes, Cytotoxic -- immunology KW - Leukocytes, Mononuclear -- immunology KW - Receptors, Antigen, T-Cell -- immunology KW - Cytotoxicity, Immunologic -- immunology KW - Lymphocyte Activation KW - Receptors, Antigen, T-Cell -- antagonists & inhibitors KW - Leukocytes, Mononuclear -- metabolism KW - Receptors, Antigen, T-Cell -- agonists KW - Peptide Fragments -- metabolism KW - Paraparesis, Tropical Spastic -- immunology KW - Gene Products, tax -- metabolism KW - Epitopes, T-Lymphocyte -- metabolism KW - Gene Products, tax -- agonists KW - Gene Products, tax -- antagonists & inhibitors KW - Peptide Fragments -- agonists KW - Human T-lymphotropic virus 1 -- immunology KW - Epitopes, T-Lymphocyte -- immunology KW - Gene Products, tax -- immunology KW - Peptide Fragments -- immunology KW - Peptide Fragments -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71089503?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=An+altered+peptide+ligand+antagonizes+antigen-specific+T+cells+of+patients+with+human+T+lymphotropic+virus+type+I-associated+neurological+disease.&rft.au=Kubota%2C+R%3BSoldan%2C+S+S%3BMartin%2C+R%3BJacobson%2C+S&rft.aulast=Kubota&rft.aufirst=R&rft.date=2000-05-15&rft.volume=164&rft.issue=10&rft.spage=5192&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 - 2000-06-07 N1 - Date created - 2000-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification and characterization of a putative active site for peptide methionine sulfoxide reductase (MsrA) and its substrate stereospecificity. AN - 71098261; 10799493 AB - Peptide methionine sulfoxide reductases (MsrA) from many different organisms share a consensus amino acid sequence (GCFWG) that could play an important role in their active site. Site-directed single substitution of each of these amino acids except glycines in the yeast MsrA resulted in total loss of enzyme activity. Nevertheless, all the recombinant MsrA mutants and native proteins had a very similar circular dichroism spectrum. The demonstration that either treatment with iodoacetamide or replacement of the motif cysteine with serine leads to inactivation of the enzyme underscores the singular importance of cysteine residues in the activity of MsrA. The recombinant yeast MsrA was used for general characterization of the enzyme. Its K(m) value was similar to the bovine MsrA and appreciably lower than the K(m) of the bacterial enzyme. Also, it was shown that the enzymatic activity increased dramatically with increasing ionic strength. The recombinant yeast MsrA activity and the reduction activity of free methionine sulfoxide(s) were stereoselective toward the L-methionine S-sulfoxide and S-methyl p-tolyl sulfoxide. It was established that a methionine auxotroph yeast strain could grow on either form of L-methionine sulfoxide. JF - The Journal of biological chemistry AU - Moskovitz, J AU - Poston, J M AU - Berlett, B S AU - Nosworthy, N J AU - Szczepanowski, R AU - Stadtman, E R AD - Laboratory of Biochemistry and Laboratory of Biochemical Genetics, NHLBI, National Institutes of Health, Bethesda, Maryland 20982-0320, USA. jmosko@nih.gov Y1 - 2000/05/12/ PY - 2000 DA - 2000 May 12 SP - 14167 EP - 14172 VL - 275 IS - 19 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Recombinant Proteins KW - Methionine KW - AE28F7PNPL KW - Oxidoreductases KW - EC 1.- KW - Methionine Sulfoxide Reductases KW - EC 1.8.4.- KW - methionine sulfoxide reductase KW - EC 1.8.4.11 KW - methionine sulfoxide KW - XN1XVI4B2C KW - Index Medicus KW - Animals KW - Stereoisomerism KW - Methionine -- metabolism KW - Recombinant Proteins -- genetics KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Cattle KW - Recombinant Proteins -- metabolism KW - Methionine -- analogs & derivatives KW - Substrate Specificity KW - Methionine -- chemistry KW - Catalysis KW - Oxidoreductases -- genetics KW - Oxidoreductases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71098261?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+and+characterization+of+a+putative+active+site+for+peptide+methionine+sulfoxide+reductase+%28MsrA%29+and+its+substrate+stereospecificity.&rft.au=Moskovitz%2C+J%3BPoston%2C+J+M%3BBerlett%2C+B+S%3BNosworthy%2C+N+J%3BSzczepanowski%2C+R%3BStadtman%2C+E+R&rft.aulast=Moskovitz&rft.aufirst=J&rft.date=2000-05-12&rft.volume=275&rft.issue=19&rft.spage=14167&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 - 2000-06-08 N1 - Date created - 2000-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fortification of foods with folic acid--how much is enough? AN - 71073185; 10805832 JF - The New England journal of medicine AU - Mills, J L AD - National Institute of Child Health and Human Development, Bethesda, MD 20892-7510, USA. Y1 - 2000/05/11/ PY - 2000 DA - 2000 May 11 SP - 1442 EP - 1445 VL - 342 IS - 19 SN - 0028-4793, 0028-4793 KW - Folic Acid KW - 935E97BOY8 KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Vitamin B 12 Deficiency -- diagnosis KW - United States Food and Drug Administration KW - Humans KW - Aged KW - Anemia, Pernicious -- diagnosis KW - Female KW - Pregnancy KW - Food, Fortified -- adverse effects KW - Food, Fortified -- standards KW - Neural Tube Defects -- prevention & control KW - Folic Acid -- adverse effects KW - Folic Acid -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71073185?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Fortification+of+foods+with+folic+acid--how+much+is+enough%3F&rft.au=Mills%2C+J+L&rft.aulast=Mills&rft.aufirst=J&rft.date=2000-05-11&rft.volume=342&rft.issue=19&rft.spage=1442&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-11 N1 - Date created - 2000-05-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 2000 Sep 28;343(13):970; author reply 972 [11012325] N Engl J Med. 2000 Sep 28;343(13):970-1; author reply 972 [11012326] N Engl J Med. 2000 Sep 28;343(13):971; author reply 972 [11012327] N Engl J Med. 2000 Sep 28;343(13):971-2 [11012328] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prophylaxis against opportunistic infections in patients with human immunodeficiency virus infection. AN - 71072337; 10805828 JF - The New England journal of medicine AU - Kovacs, J A AU - Masur, H AD - Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892-1662, USA. Y1 - 2000/05/11/ PY - 2000 DA - 2000 May 11 SP - 1416 EP - 1429 VL - 342 IS - 19 SN - 0028-4793, 0028-4793 KW - Antitubercular Agents KW - 0 KW - Trimethoprim, Sulfamethoxazole Drug Combination KW - 8064-90-2 KW - Ganciclovir KW - P9G3CKZ4P5 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Ganciclovir -- therapeutic use KW - Drug Interactions KW - Humans KW - Trimethoprim, Sulfamethoxazole Drug Combination -- therapeutic use KW - Practice Guidelines as Topic KW - Antibiotic Prophylaxis KW - CD4 Lymphocyte Count KW - Secondary Prevention KW - Antitubercular Agents -- therapeutic use KW - AIDS-Related Opportunistic Infections -- drug therapy KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy KW - AIDS-Related Opportunistic Infections -- prevention & control KW - Chemoprevention UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71072337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Prophylaxis+against+opportunistic+infections+in+patients+with+human+immunodeficiency+virus+infection.&rft.au=Kovacs%2C+J+A%3BMasur%2C+H&rft.aulast=Kovacs&rft.aufirst=J&rft.date=2000-05-11&rft.volume=342&rft.issue=19&rft.spage=1416&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-11 N1 - Date created - 2000-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Gcd10p/Gcd14p complex is the essential two-subunit tRNA(1-methyladenosine) methyltransferase of Saccharomyces cerevisiae. AN - 71134105; 10779558 AB - The modified nucleoside 1-methyladenosine (m(1)A) is found at position 58 in the TPsiC loop of many eukaryotic tRNAs. The absence of m(1)A from all tRNAs in Saccharomyces cerevisiae mutants lacking Gcd10p elicits severe defects in processing and stability of initiator methionine tRNA (tRNA(i)(Met)). Gcd10p is found in a complex with Gcd14p, which contains conserved motifs for binding S-adenosylmethionine (AdoMet). These facts, plus our demonstration that gcd14Delta cells lacked m(1)A, strongly suggested that Gcd10p/Gcd14p complex is the yeast tRNA(m(1)A)methyltransferase [(m(1)A)MTase]. Supporting this prediction, affinity-purified Gcd10p/Gcd14p complexes used AdoMet as a methyl donor to synthesize m(1)A in either total tRNA or purified tRNA(i)(Met) lacking only this modification. Kinetic analysis of the purified complex revealed K(M) values for AdoMet or tRNA(i)(Met) of 5.0 microM and 2.5 nM, respectively. Mutations in the predicted AdoMet-binding domain destroyed GCD14 function in vivo and (m(1)A)MTase activity in vitro. Purified Flag-tagged Gcd14p alone had no enzymatic activity and was severely impaired for tRNA-binding compared with the wild-type complex, suggesting that Gcd10p is required for tight binding of the tRNA substrate. Our results provide a demonstration of a two-component tRNA MTase and suggest that binding of AdoMet and tRNA substrates depends on different subunits of the complex. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Anderson, J AU - Phan, L AU - Hinnebusch, A G AD - Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. Y1 - 2000/05/09/ PY - 2000 DA - 2000 May 09 SP - 5173 EP - 5178 VL - 97 IS - 10 SN - 0027-8424, 0027-8424 KW - Eukaryotic Initiation Factor-3 KW - 0 KW - Fungal Proteins KW - Macromolecular Substances KW - RNA, Transfer, Met KW - RNA-Binding Proteins KW - Recombinant Proteins KW - Repressor Proteins KW - Saccharomyces cerevisiae Proteins KW - S-Adenosylmethionine KW - 7LP2MPO46S KW - Gcd10 protein, S cerevisiae KW - EC 2.1.1.- KW - tRNA Methyltransferases KW - GCD14 protein, S cerevisiae KW - EC 2.1.1.220 KW - tRNA (adenine(58)-N(1))-methyltransferase KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - RNA, Transfer, Met -- metabolism KW - Kinetics KW - S-Adenosylmethionine -- metabolism KW - Recombinant Proteins -- chemistry KW - Binding Sites KW - tRNA Methyltransferases -- chemistry KW - RNA-Binding Proteins -- genetics KW - RNA-Binding Proteins -- metabolism KW - Saccharomyces cerevisiae -- growth & development KW - Repressor Proteins -- metabolism KW - Fungal Proteins -- genetics KW - RNA-Binding Proteins -- chemistry KW - Saccharomyces cerevisiae -- enzymology KW - Repressor Proteins -- chemistry KW - Repressor Proteins -- genetics KW - Fungal Proteins -- chemistry KW - Saccharomyces cerevisiae -- genetics KW - tRNA Methyltransferases -- genetics KW - Fungal Proteins -- metabolism KW - tRNA Methyltransferases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71134105?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+Gcd10p%2FGcd14p+complex+is+the+essential+two-subunit+tRNA%281-methyladenosine%29+methyltransferase+of+Saccharomyces+cerevisiae.&rft.au=Anderson%2C+J%3BPhan%2C+L%3BHinnebusch%2C+A+G&rft.aulast=Anderson&rft.aufirst=J&rft.date=2000-05-09&rft.volume=97&rft.issue=10&rft.spage=5173&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 - 2000-06-13 N1 - Date created - 2000-06-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genes Dev. 1999 Jan 1;13(1):1-10 [9887094] J Biol Chem. 1999 Jan 8;274(2):814-24 [9873020] Biochemistry. 1999 Oct 12;38(41):13725-35 [10521280] J Biol Chem. 1977 Jul 25;252(14):4790-5 [17605] Annu Rev Biochem. 1979;48:601-48 [382994] J Bacteriol. 1983 Jan;153(1):163-8 [6336730] Eur J Biochem. 1982 Dec 15;129(2):429-36 [7151806] Mol Gen Genet. 1984;197(2):345-6 [6394957] J Mol Biol. 1987 Feb 20;193(4):661-71 [2441068] Annu Rev Biochem. 1987;56:263-87 [3304135] Gene. 1988 Dec 30;74(2):527-34 [3073106] Nucleic Acids Res. 1989 Jun 26;17(12):4895 [2748349] EMBO J. 1991 Oct;10(10):3105-11 [1915284] J Bacteriol. 1991 Nov;173(22):7213-8 [1657884] Arch Biochem Biophys. 1994 May 1;310(2):417-27 [8179327] Biosci Biotechnol Biochem. 1994 Jun;58(6):1128-33 [7765037] Cell. 1994 Nov 4;79(3):535-46 [7954819] Biochimie. 1995;77(1-2):45-53 [7599275] Genes Dev. 1995 Jul 15;9(14):1781-96 [7542616] Mol Cell Biol. 1996 Feb;16(2):475-80 [8552073] EMBO J. 1996 Oct 1;15(19):5437-48 [8895587] Nucleic Acids Res. 1998 Jan 1;26(1):148-53 [9399820] J Bacteriol. 1998 Apr;180(7):1808-13 [9537379] Mol Cell. 1998 Jan;1(2):235-42 [9659920] Mol Cell Biol. 1998 Aug;18(8):4935-46 [9671501] Genes Dev. 1998 Dec 1;12(23):3650-62 [9851972] Mol Cell Biol. 1999 Jun;19(6):4167-81 [10330157] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A conserved negatively charged amino acid modulates function in human nonmuscle myosin IIA. AN - 71124725; 10820029 AB - A myosin surface loop (amino acids 391-404) is postulated to be an important actin binding site. In human beta-cardiac myosin, mutation of arginine-403 to a glutamine or a tryptophan causes hypertrophic cardiomyopathy. There is a phosphorylatable serine or threonine residue present on this loop in some lower eukaryotic myosin class I and myosin class VI molecules. Phosphorylation of the myosin I molecules at this site regulates their enzymatic activity. In almost all other myosins, the homologous residue is either a glutamine or an aspartate, suggesting that a negative charge at this location is important for activity. To study the function of this loop, we have used site-directed mutagenesis and baculovirus expression of a heavy meromyosin- (HMM-) like fragment of human nonmuscle myosin IIA. An R393Q mutation (equivalent to the R403Q mutation in human beta-cardiac muscle myosin) has essentially no effect on the actin-activated MgATPase or in vitro motility of the expressed HMM-like fragment. Three mutations, D399K, D399A, and a deletion mutation that removes residues 393-402, all decrease both the V(max) of the actin-activated MgATPase by 8-10-fold and the rate of in vitro motility by a factor of 2-3. The K(ATPase) of the actin-activated MgATPase activity and the affinity constant for binding of HMM to actin in the presence of ADP are affected by less than a factor of 2. These data support an important role for the negative charge at this location but show that it is not critical to enzymatic activity. JF - Biochemistry AU - Wang, F AU - Harvey, E V AU - Conti, M A AU - Wei, D AU - Sellers, J R AD - Laboratory of Molecular Cardiology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1762, USA. Y1 - 2000/05/09/ PY - 2000 DA - 2000 May 09 SP - 5555 EP - 5560 VL - 39 IS - 18 SN - 0006-2960, 0006-2960 KW - Actins KW - 0 KW - Molecular Motor Proteins KW - Myosin Subfragments KW - Recombinant Proteins KW - Ca(2+) Mg(2+)-ATPase KW - EC 3.6.1.- KW - Myosins KW - EC 3.6.4.1 KW - Index Medicus KW - Models, Molecular KW - Humans KW - Cardiomyopathy, Hypertrophic -- genetics KW - Myosin Subfragments -- chemistry KW - Actins -- metabolism KW - Amino Acid Sequence KW - Recombinant Proteins -- genetics KW - Protein Binding KW - Static Electricity KW - Baculoviridae KW - Mutagenesis, Site-Directed KW - Sequence Alignment KW - Kinetics KW - Molecular Motor Proteins -- genetics KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Mutation KW - Ca(2+) Mg(2+)-ATPase -- metabolism KW - Myosin Subfragments -- genetics KW - Myosins -- chemistry KW - Myosins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71124725?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=A+conserved+negatively+charged+amino+acid+modulates+function+in+human+nonmuscle+myosin+IIA.&rft.au=Wang%2C+F%3BHarvey%2C+E+V%3BConti%2C+M+A%3BWei%2C+D%3BSellers%2C+J+R&rft.aulast=Wang&rft.aufirst=F&rft.date=2000-05-09&rft.volume=39&rft.issue=18&rft.spage=5555&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-06 N1 - Date created - 2000-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rabies vaccination: comparison of neutralizing antibody responses after priming and boosting with different combinations of DNA, inactivated virus, or recombinant vaccinia virus vaccines AN - 17600251; 4727345 AB - Long-term levels of neutralizing antibody were evaluated in mice after a single immunization with experimental DNA or recombinant vaccinia virus (RVV) vaccines encoding the rabies virus glycoprotein (G), or the commercially available inactivated virus human diploid cell vaccine (HDCV). Anamnestic antibody titers were also evaluated after two booster immunizations with vaccines that were identical to or different from the priming vaccine. Five hundred and forty days (1.5 year) after a single immunization with any of the three vaccines, neutralizing antibody titers remained greater than the minimal acceptable human level of antibody titer (0.5 International Units (IU)/ml). In addition, either an HDCV or DNA booster elicited early and elevated anamnestic antibody responses in mice that had been primed with any of the three vaccines. In contrast, RVV boosters failed to elevate titers in mice that had been previously primed with RVV, and elicited slowly rising titers in mice that had been primed with either DNA or HDCV. Thus, a single vaccination with any of the three different vaccines elicited long-term levels of neutralizing antibody that exceeded 0.5 IU/ml. In contrast, different prime-booster vaccine combinations elicited anamnestic neutralizing antibody responses that increased quickly, increased slowly or failed to increase. JF - Vaccine AU - Lodmell, D L AU - Ewalt, L C AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, 903 South Forth Street, Hamilton, MT 59840, USA, dlodmell@nih.gov Y1 - 2000/05/08/ PY - 2000 DA - 2000 May 08 SP - 2394 EP - 2398 VL - 18 IS - 22 SN - 0264-410X, 0264-410X KW - man KW - immunology KW - rabies virus KW - vaccinia virus KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Animal models KW - Antibody response KW - Recombinants KW - Vaccinia virus KW - DNA vaccines KW - Rabies KW - Rabies virus KW - Vaccines KW - F 06807:Active immunization KW - V 22097:Immunization: Vaccines & vaccination: Human KW - V 22150:Animal models & experimentally-induced viral infections KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17600251?accountid=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+vaccination%3A+comparison+of+neutralizing+antibody+responses+after+priming+and+boosting+with+different+combinations+of+DNA%2C+inactivated+virus%2C+or+recombinant+vaccinia+virus+vaccines&rft.au=Lodmell%2C+D+L%3BEwalt%2C+L+C&rft.aulast=Lodmell&rft.aufirst=D&rft.date=2000-05-08&rft.volume=18&rft.issue=22&rft.spage=2394&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vaccinia virus; Rabies virus; Vaccines; DNA vaccines; Rabies; Antibody response; Animal models; Recombinants ER - TY - JOUR T1 - Interlaboratory comparison of the CB6F1-Tg rasH2 rapid carcinogenicity testing model. AN - 71126421; 10814847 AB - Several genetically engineered mouse models are currently being examined for potential use in cancer hazard identification. We have undertaken an interlaboratory comparison of the performance of the CB6F1-Tg rasH2 transgenic mouse in cancer bioassays concurrently conducted in the United States and Japan. Chemicals selected for study included known human carcinogens (melphalan and cyclosporin A) and known rodent carcinogens (p-cresidine and vinyl carbamate) tested at carcinogenic doses, and non-carcinogens (p-anisidine and resorcinol) tested at appropriate high doses. Because of abdominal adhesions caused by the intraperitoneal dosing vehicle, melphalan was excluded from the study results. The remaining five studies showed similar results between the two laboratories conducting each study. Vinyl carbamate gave the strongest positive response inducing lung adenomas and carcinomas and splenic hemangiosarcomas. p-Cresidine was considered positive for urinary bladder transitional neoplasia. Cyclosporin A, p-anisidine, and resorcinol were negative in all studies. Although only five chemicals were successfully tested in this interlaboratory comparison, there was good concordance in outcome for the strong carcinogens and for the non-carcinogens. Successful testing of chemicals with less carcinogenic potential may require modifications in study design to include more animals and longer study duration. JF - Toxicology AU - Maronpot, R R AU - Mitsumori, K AU - Mann, P AU - Takaoka, M AU - Yamamoto, S AU - Usui, T AU - Okamiya, H AU - Nishikawa, S AU - Nomura, T AD - National Institute of Environmental Health Sciences, Laboratory of Experimental Pathology, P.O. Box 12233, 111 Alexander Drive, Research Triangle Park, NC, USA. maronpot@niehs.nih.gov Y1 - 2000/05/05/ PY - 2000 DA - 2000 May 05 SP - 149 EP - 159 VL - 146 IS - 2-3 SN - 0300-483X, 0300-483X KW - Carcinogens KW - 0 KW - Index Medicus KW - Animals KW - Splenic Neoplasms -- chemically induced KW - Splenic Neoplasms -- pathology KW - Laboratories KW - Carcinogens -- toxicity KW - Hemangiosarcoma -- chemically induced KW - Mice KW - Neoplasms, Experimental -- pathology KW - Carcinoma -- pathology KW - Neoplasms, Experimental -- chemically induced KW - Adenoma -- chemically induced KW - Hemangiosarcoma -- pathology KW - Lung Neoplasms -- chemically induced KW - Adenoma -- pathology KW - Carcinoma -- chemically induced KW - Lung Neoplasms -- pathology KW - Genes, ras -- genetics KW - Mice, Transgenic -- physiology KW - Carcinogenicity Tests UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71126421?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Interlaboratory+comparison+of+the+CB6F1-Tg+rasH2+rapid+carcinogenicity+testing+model.&rft.au=Maronpot%2C+R+R%3BMitsumori%2C+K%3BMann%2C+P%3BTakaoka%2C+M%3BYamamoto%2C+S%3BUsui%2C+T%3BOkamiya%2C+H%3BNishikawa%2C+S%3BNomura%2C+T&rft.aulast=Maronpot&rft.aufirst=R&rft.date=2000-05-05&rft.volume=146&rft.issue=2-3&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-17 N1 - Date created - 2000-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Scientific position paper of the Movement Disorder Society evaluation of surgery for Parkinson's disease. Task Force on Surgery for Parkinson's Disease of the American Academy of Neurology Therapeutic and Technology Assessment Committee. AN - 85349026; pmid-10830406 JF - Movement disorders : official journal of the Movement Disorder Society AU - Hallett, M AU - Litvan, I AD - Human Motor Control Section, NINDS, NIH, Bethesda, MD 20892-1428, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 436 EP - 438 VL - 15 IS - 3 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Thalamic Nuclei -- physiopathology KW - Mesencephalon -- transplantation KW - Dominance, Cerebral -- physiology KW - Humans KW - Mesencephalon -- physiopathology KW - Outcome and Process Assessment (Health Care) KW - Adrenal Medulla -- transplantation KW - Globus Pallidus -- physiopathology KW - Globus Pallidus -- surgery KW - Parkinson Disease -- physiopathology KW - Thalamic Nuclei -- surgery KW - Brain Tissue Transplantation KW - Fetal Tissue Transplantation KW - Parkinson Disease -- surgery KW - Stereotaxic Techniques UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85349026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Scientific+position+paper+of+the+Movement+Disorder+Society+evaluation+of+surgery+for+Parkinson%27s+disease.+Task+Force+on+Surgery+for+Parkinson%27s+Disease+of+the+American+Academy+of+Neurology+Therapeutic+and+Technology+Assessment+Committee.&rft.au=Hallett%2C+M%3BLitvan%2C+I&rft.aulast=Hallett&rft.aufirst=M&rft.date=2000-05-01&rft.volume=15&rft.issue=3&rft.spage=436&rft.isbn=&rft.btitle=&rft.title=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.issn=08853185&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - Lactate-induced rage and panic in a select group of subjects who perpetrate acts of domestic violence. AN - 85251968; pmid-10812039 AB - BACKGROUND: Perpetrators of domestic violence frequently report symptoms of autonomic arousal and a sense of fear and/or loss of control at the time of the violence. Since many of these symptoms are also associated with panic attacks, we hypothesized that perpetrators of domestic violence and patients with panic attacks may share similar exaggerated fear-related behaviors. To test this hypothesis, we employed the panicogenic agent sodium lactate to examine the response of perpetrators to anxiety fear induced by a chemical agent. METHODS: Using a double-blind, placebo-controlled design, we infused 0.5 mol/L sodium lactate or placebo over 20 min on separate days to a select group of subjects who perpetrate acts of domestic violence and two nonviolent comparison groups. We compared their behavioral, neuroendocrine, and physiologic responses. RESULTS: Lactate administration elicited intense emotional responses in the perpetrators of domestic violence. Perpetrators evidenced more lactate-induced rage and panic and showed greater changes in speech, breathing, and motor activity than did nonviolent control subjects. There were no significant differences between the groups for any neuroendocrine or physiologic measure. CONCLUSIONS: These results are consistent with our hypothesis that some perpetrators of domestic violence have exaggerated fear-related behavioral responses. JF - Biological Psychiatry AU - George, D T AU - Hibbeln, J R AU - Ragan, P W AU - Umhau, J C AU - Phillips, M J AU - Doty, L AU - Hommer, D AU - Rawlings, R R AD - Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-1610, USA. PY - 2000 SP - 804 EP - 812 VL - 47 IS - 9 SN - 0006-3223, 0006-3223 KW - Videotape Recording KW - Blood Pressure KW - Double-Blind Method KW - Infusions, Intravenous KW - Human KW - Lactic Acid KW - Rage KW - Domestic Violence KW - Socioeconomic Factors KW - Heart Rate KW - Psychiatric Status Rating Scales KW - Alcoholism KW - Adult KW - Case Report KW - Panic KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85251968?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+Psychiatry&rft.atitle=Lactate-induced+rage+and+panic+in+a+select+group+of+subjects+who+perpetrate+acts+of+domestic+violence.&rft.au=George%2C+D+T%3BHibbeln%2C+J+R%3BRagan%2C+P+W%3BUmhau%2C+J+C%3BPhillips%2C+M+J%3BDoty%2C+L%3BHommer%2C+D%3BRawlings%2C+R+R&rft.aulast=George&rft.aufirst=D&rft.date=2000-05-01&rft.volume=47&rft.issue=9&rft.spage=804&rft.isbn=&rft.btitle=&rft.title=Biological+Psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Premorbid speech and language impairments in childhood-onset schizophrenia: association with risk factors. AN - 85240823; pmid-10784474 AB - OBJECTIVE: As both premorbid neurodevelopmental impairments and familial risk factors for schizophrenia are prominent in childhood-onset cases (with onset of psychosis by age 12), their relationship was examined. METHOD: Premorbid language, motor, and social impairments were assessed in a cohort of 49 patients with childhood-onset schizophrenia. Familial loading for schizophrenia spectrum disorders, familial eye-tracking dysfunction, and obstetrical complications were assessed without knowledge of premorbid abnormalities and were compared in the patients with and without developmental impairments. RESULTS: Over one-half of the patients in this group had developmental dysfunction in each domain assessed. The patients with premorbid speech and language impairments had higher familial loading scores for schizophrenia spectrum disorders and more obstetrical complications, and their relatives had worse smooth-pursuit eye movements. The boys had more premorbid motor abnormalities, but early language and social impairments did not differ significantly between genders. There were no other significant relationships between premorbid social or motor abnormalities and the risk factors assessed here. CONCLUSIONS: Premorbid developmental impairments are common in childhood-onset schizophrenia. The rates of three risk factors for schizophrenia (familial loading for schizophrenia spectrum disorders, familial eye-tracking dysfunction, and obstetrical complications) were increased for the probands with premorbid speech and language impairments, suggesting that the pathophysiology of schizophrenia involves the abnormal development of language-related brain regions. JF - The American Journal of Psychiatry AU - Nicolson, R AU - Lenane, M AU - Singaracharlu, S AU - Malaspina, D AU - Giedd, J N AU - Hamburger, S D AU - Gochman, P AU - Bedwell, J AU - Thaker, G K AU - Fernandez, T AU - Wudarsky, M AU - Hommer, D W AU - Rapoport, J L AD - The Child Psychiatry Branch, NIMH, Bethesda, MD 20892-1600, USA. PY - 2000 SP - 794 EP - 800 VL - 157 IS - 5 SN - 0002-953X, 0002-953X KW - Developmental Disabilities KW - Speech Disorders KW - Pregnancy Complications KW - Age of Onset KW - Human KW - Brain KW - Language Development Disorders KW - Child KW - Pursuit, Smooth KW - Comorbidity KW - Pregnancy KW - Child, Preschool KW - Schizophrenia KW - Mental Disorders KW - Risk Factors KW - Family KW - Schizophrenic Psychology KW - Adolescent KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85240823?accountid=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+American+Journal+of+Psychiatry&rft.atitle=Premorbid+speech+and+language+impairments+in+childhood-onset+schizophrenia%3A+association+with+risk+factors.&rft.au=Nicolson%2C+R%3BLenane%2C+M%3BSingaracharlu%2C+S%3BMalaspina%2C+D%3BGiedd%2C+J+N%3BHamburger%2C+S+D%3BGochman%2C+P%3BBedwell%2C+J%3BThaker%2C+G+K%3BFernandez%2C+T%3BWudarsky%2C+M%3BHommer%2C+D+W%3BRapoport%2C+J+L&rft.aulast=Nicolson&rft.aufirst=R&rft.date=2000-05-01&rft.volume=157&rft.issue=5&rft.spage=794&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Proteasome inhibition suppresses cisplatin-dependent ERCC-1 mRNA expression in human ovarian tumor cells. AN - 72607133; 11589365 AB - One of the major problems with ovarian cancer treatment is the clinical development of resistance to cisplatin. Considerable efforts have been directed toward the identification of biological and pharmacological agents that would reverse drug resistance to cisplatin. ALLnL is an inhibitor of the proteasome that can inhibit the ubiquitin-proteasome pathway, which plays an essential role in many processes in cell life. We have recently shown that ALLnL, at concentrations that do not appear harmful, has significantly enhanced DNA platination and decreased DNA repair of cisplatin-DNA adducts in human A2780/CP70 ovarian carcinoma cells. These activities of proteasome inhibition were also associated with substantially increased cisplatin toxicity in these cells. In this communication, we demonstrate that treatment of A2780/CP70 cells with ALLnL blocks cisplatin-induced ERCC-1 mRNA expression in a concentration- and time-dependent manner, as measured by Northern blot analysis. In addition, we showed that the cisplatin-dependent increase in steady-state levels of ERCC-1 mRNA was prevented by pretreatment with lactacystin, a potent and specific inhibitor of proteasome. These results suggest that the effect of proteasome inhibition on cisplatin cytotoxicity, DNA platination, and DNA repair of cisplatin adducts in ovarian cancer cells may be through down-regulating ERCC-1 expression. JF - Research communications in molecular pathology and pharmacology AU - Li, Q Q AU - Ding, L AU - Reed, E AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. qli001@umaryland.edu PY - 2000 SP - 387 EP - 396 VL - 107 IS - 5-6 SN - 1078-0297, 1078-0297 KW - Anti-Bacterial Agents KW - 0 KW - DNA-Binding Proteins KW - Lactams KW - Multienzyme Complexes KW - Proteins KW - RNA, Messenger KW - lactacystin KW - 133343-34-7 KW - ERCC1 protein, human KW - EC 3.1.- KW - Endonucleases KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Cisplatin KW - Q20Q21Q62J KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Humans KW - RNA, Messenger -- drug effects KW - Drug Resistance, Neoplasm KW - Female KW - DNA Repair -- drug effects KW - Proteins -- drug effects KW - Acetylcysteine -- analogs & derivatives KW - Tumor Cells, Cultured -- drug effects KW - Multienzyme Complexes -- antagonists & inhibitors KW - Cisplatin -- pharmacology KW - Anti-Bacterial Agents -- pharmacology KW - Acetylcysteine -- pharmacology KW - Ovarian Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72607133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Research+communications+in+molecular+pathology+and+pharmacology&rft.atitle=Proteasome+inhibition+suppresses+cisplatin-dependent+ERCC-1+mRNA+expression+in+human+ovarian+tumor+cells.&rft.au=Li%2C+Q+Q%3BDing%2C+L%3BReed%2C+E&rft.aulast=Li&rft.aufirst=Q&rft.date=2000-05-01&rft.volume=107&rft.issue=5-6&rft.spage=387&rft.isbn=&rft.btitle=&rft.title=Research+communications+in+molecular+pathology+and+pharmacology&rft.issn=10780297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-03-28 N1 - Date created - 2001-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The disease of addiction. AN - 72558573; 11271123 AB - Drug use is a preventable behavior, and addiction is a treatable disease. More than two decades of scientific research have yielded tremendous understanding concerning the nature of addiction and what to do about it. Many tools that can be used by health care providers to aid in the recognition, referral, and treatment for drug abuse and addiction also have been developed. To assist in these efforts, the National Institute on Drug Abuse recently has published the first ever science-based guide to drug treatment: Principles of Drug Addiction Treatment. This guide articulates some essential characteristics of addiction and its treatment and lays out the principles derived from two decades of scientific research that characterize effective treatment programs. This article elaborates many of those points. JF - Lippincott's primary care practice AU - Leshner, A I AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland, USA. leshner@nih.gov PY - 2000 SP - 249 EP - 253 VL - 4 IS - 3 SN - 1088-5471, 1088-5471 KW - Nursing KW - Humans KW - Primary Health Care -- methods KW - Substance-Related Disorders -- physiopathology KW - Substance-Related Disorders -- therapy KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72558573?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lippincott%27s+primary+care+practice&rft.atitle=The+disease+of+addiction.&rft.au=Leshner%2C+A+I&rft.aulast=Leshner&rft.aufirst=A&rft.date=2000-05-01&rft.volume=4&rft.issue=3&rft.spage=249&rft.isbn=&rft.btitle=&rft.title=Lippincott%27s+primary+care+practice&rft.issn=10885471&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-29 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Declawing of neonatal rabbits destined for use in animal biosafety level 4 containment studies. AN - 72551786; 11178319 AB - To protect personnel and protective outerwear from damage by scratching, rabbits to be housed in an Animal Biosafety Level 4 (ABSL4) facility are declawed routinely. The objective of the study presented here was to establish a procedure for declawing all four feet of neonatal rabbits in preparation for use in ABSL4 studies. Combining procedures conducted in private veterinary practice to remove dewclaws of canine pups with those used to declaw cats, we declawed rabbit kits at 3 to 8 days of age. Declawing neonates was believed to be advantageous because they are non-ambulatory, have soft, cartilaginous digits, and do not have extensive hair growth. These features resulted in decreased surgical preparation and surgery time, minimal bleeding, and minimal aftercare. The optimal age for declawing a litter was 6 or 7 days. Declawing of neonatal rabbits is relatively simple and efficient to perform and offers advantages over declawing of older animals. By using the method described, rabbits can be introduced into ABSL4 facilities by 12 weeks of age with confidence that nail regrowth will not occur. JF - Contemporary topics in laboratory animal science AU - Perdue, K A AU - Shaw, R E AU - Mage, R G AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 13 EP - 18 VL - 39 IS - 3 SN - 1060-0558, 1060-0558 KW - Index Medicus KW - Occupational Health KW - Animals, Newborn KW - Animals KW - Protective Clothing KW - Humans KW - Occupational Diseases -- prevention & control KW - Medical Laboratory Personnel KW - Rabbits KW - Wounds and Injuries -- prevention & control KW - Containment of Biohazards -- methods KW - Hoof and Claw KW - Animals, Laboratory KW - Containment of Biohazards -- veterinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72551786?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Contemporary+topics+in+laboratory+animal+science&rft.atitle=Declawing+of+neonatal+rabbits+destined+for+use+in+animal+biosafety+level+4+containment+studies.&rft.au=Perdue%2C+K+A%3BShaw%2C+R+E%3BMage%2C+R+G&rft.aulast=Perdue&rft.aufirst=K&rft.date=2000-05-01&rft.volume=39&rft.issue=3&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Contemporary+topics+in+laboratory+animal+science&rft.issn=10600558&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-03 N1 - Date created - 2001-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Incisional wound healing in transforming growth factor-beta1 null mice. AN - 71269071; 10886809 AB - Expression of endogenous transforming growth factor-beta1 is reduced in many animal models of impaired wound healing, and addition of exogenous transforming growth factor-beta has been shown to improve healing. To test the hypothesis that endogenous transforming growth factor-beta1 is essential for normal wound repair, we have studied wound healing in mice in which the transforming growth factor-beta1 gene has been deleted by homologous recombination. No perceptible differences were observed in wounds made in 3-10-day-old neonatal transforming growth factor-beta1 null mice compared to wild-type littermates. To preclude interference from maternally transferred transforming growth factor-beta1, cutaneous wounds were also made on the backs of 30-day-old transforming growth factor-beta1 null and littermate control mice treated with rapamycin, which extends their lifetime and suppresses the inflammatory response characteristic of the transforming growth factor-beta1 null mice. Again, no impairment in healing was seen in transforming growth factor-beta1 null mice. Instead these wounds showed an overall reduction in the amount of granulation tissue and an increased rate of epithelialization compared to littermate controls. Our data suggest that release of transforming growth factor-beta1 from degranulating platelets or secretion by infiltrating macrophages and fibroblasts is not critical to initiation or progression of tissue repair and that endogenous transforming growth factor-beta1 may actually function to increase inflammation and retard wound closure. JF - Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society AU - Koch, R M AU - Roche, N S AU - Parks, W T AU - Ashcroft, G S AU - Letterio, J J AU - Roberts, A B AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-5055, USA. PY - 2000 SP - 179 EP - 191 VL - 8 IS - 3 SN - 1067-1927, 1067-1927 KW - Immunosuppressive Agents KW - 0 KW - Transforming Growth Factor beta KW - Sirolimus KW - W36ZG6FT64 KW - Index Medicus KW - Granulation Tissue -- pathology KW - Animals KW - Inflammation -- physiopathology KW - Age Factors KW - Wounds and Injuries -- pathology KW - Disease Models, Animal KW - Mice KW - Sirolimus -- therapeutic use KW - Immunosuppressive Agents -- therapeutic use KW - Transforming Growth Factor beta -- physiology KW - Wound Healing -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71269071?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Wound+repair+and+regeneration+%3A+official+publication+of+the+Wound+Healing+Society+%5Band%5D+the+European+Tissue+Repair+Society&rft.atitle=Incisional+wound+healing+in+transforming+growth+factor-beta1+null+mice.&rft.au=Koch%2C+R+M%3BRoche%2C+N+S%3BParks%2C+W+T%3BAshcroft%2C+G+S%3BLetterio%2C+J+J%3BRoberts%2C+A+B&rft.aulast=Koch&rft.aufirst=R&rft.date=2000-05-01&rft.volume=8&rft.issue=3&rft.spage=179&rft.isbn=&rft.btitle=&rft.title=Wound+repair+and+regeneration+%3A+official+publication+of+the+Wound+Healing+Society+%5Band%5D+the+European+Tissue+Repair+Society&rft.issn=10671927&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-21 N1 - Date created - 2000-08-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Wound Repair Regen. 2000 May-Jun;8(3):161 [10886805] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of cyclocreatine in rat hepatocarcinogenesis model. AN - 71260321; 10928082 AB - Cyclocreatine (CCr), a substrate analogue of creatine kinase (CK: EC 2.7.3.2.), exhibits anti-tumor activity in vitro and in vivo. We examined the effects of CCr on the hepatocarcinogenesis of F344 rats caused by treatment with diethylnitrosamine (DEN), partial hepatectomy (PH) or 2-acetylaminofluorene (2-AAF). The rats were given a single intraperitoneal injection of 200 mg of DEN per kg in 0.85% NaCl solution at four weeks of age. Two weeks later they were divided into two groups. One group was continuously fed a commercial powder diet containing 0.02% 2-AAF for 12 weeks and the other was continuously fed a commercial powder diet containing 1% CCr plus 0.02% 2-AAF for 12 weeks. A third group of rats as a control was given only a normal powder diet for 12 weeks. All the groups were subjected to a two-thirds partial hepatectomy (PH) at 3 weeks under avertin anesthesia. To elucidate the inhibitory effect of CCr on chemical induced hepatocarcinogenesis, we examined not only the distribution of glutathione-S-transferase placental form (GST-P) a marker used for tumorigenesis, but also the inhibition of the degree of apoptosis. The number (No./cm2) and area (mm2/cm2) of GST-P positive liver foci were significantly lower in the 2-AAF + CCr treated when compared to the group treated with 2-AAF only. Our data suggest that CCr inhibits the degrees of GST-P-positive cells and apoptosis and is active against hepatocarcinogenesis in rat models. This result points out the unique nature of an anticancer agent that inhibits progression of chemically induced hepatocarcinogenesis of rats. JF - Anticancer research AU - Jeong, K S AU - Park, S J AU - Lee, C S AU - Kim, T W AU - Kim, S H AU - Ryu, S Y AU - Williams, B H AU - Veech, R L AU - Lee, Y S AD - Laboratory of Membrane Biochemistry and Biophysics, NIAAA, National Institutes of Health, Bethesda, MD 20852-8115, USA. PY - 2000 SP - 1627 EP - 1633 VL - 20 IS - 3A SN - 0250-7005, 0250-7005 KW - Antineoplastic Agents KW - 0 KW - cyclocreatine KW - 6732XGX1RK KW - Creatinine KW - AYI8EX34EU KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Apoptosis KW - Hyperplasia -- etiology KW - Disease Models, Animal KW - Immunohistochemistry KW - Female KW - Creatinine -- toxicity KW - Liver Neoplasms, Experimental -- pathology KW - Liver Neoplasms, Experimental -- etiology KW - Creatinine -- analogs & derivatives KW - Cell Transformation, Neoplastic -- chemically induced KW - Antineoplastic Agents -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71260321?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Effects+of+cyclocreatine+in+rat+hepatocarcinogenesis+model.&rft.au=Jeong%2C+K+S%3BPark%2C+S+J%3BLee%2C+C+S%3BKim%2C+T+W%3BKim%2C+S+H%3BRyu%2C+S+Y%3BWilliams%2C+B+H%3BVeech%2C+R+L%3BLee%2C+Y+S&rft.aulast=Jeong&rft.aufirst=K&rft.date=2000-05-01&rft.volume=20&rft.issue=3A&rft.spage=1627&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-17 N1 - Date created - 2000-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic ulceration of the leg following extensive scarring due to a snake bite complicated by squamous cell carcinoma. AN - 71237321; 10883453 AB - Chronic ulcers of the leg are common in Brazil, perhaps more common than in the developed world. We report a case of a chronic ulcer of the leg following extensive scarring due to a bite by a venomous snake, which eventually led to a squamous cell carcinoma. JF - Skeletal radiology AU - Mello, L F AU - Barcelos, M G AU - Meohas, W AU - Pinto, L W AU - Melo, P A AU - Nogueira Neto, N C AU - Smith, J AD - Department of Radiology, National Cancer Institute-INCA, Rio de Janeiro, Brazil. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 298 EP - 301 VL - 29 IS - 5 SN - 0364-2348, 0364-2348 KW - Index Medicus KW - Amputation KW - Humans KW - Brazil KW - Middle Aged KW - Follow-Up Studies KW - Chronic Disease KW - Male KW - Leg -- surgery KW - Carcinoma, Squamous Cell -- surgery KW - Skin Neoplasms -- surgery KW - Carcinoma, Squamous Cell -- etiology KW - Carcinoma, Squamous Cell -- pathology KW - Skin Neoplasms -- etiology KW - Cicatrix -- etiology KW - Snake Bites -- complications KW - Skin Neoplasms -- pathology KW - Leg Ulcer -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71237321?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Skeletal+radiology&rft.atitle=Chronic+ulceration+of+the+leg+following+extensive+scarring+due+to+a+snake+bite+complicated+by+squamous+cell+carcinoma.&rft.au=Mello%2C+L+F%3BBarcelos%2C+M+G%3BMeohas%2C+W%3BPinto%2C+L+W%3BMelo%2C+P+A%3BNogueira+Neto%2C+N+C%3BSmith%2C+J&rft.aulast=Mello&rft.aufirst=L&rft.date=2000-05-01&rft.volume=29&rft.issue=5&rft.spage=298&rft.isbn=&rft.btitle=&rft.title=Skeletal+radiology&rft.issn=03642348&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-01 N1 - Date created - 2000-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Correlations among human plasma levels of dioxin-like compounds and polychlorinated biphenyls (PCBs) and implications for epidemiologic studies. AN - 71233070; 10908103 AB - In studies of the potential health effects of background-level exposure to organochlorine compounds (e.g., polychlorinated biphenyls, polychlorinated dibenzodioxins, and polychlorinated dibenzofurans), investigators have often measured either polychlorinated biphenyls or polychlorinated dibenzodioxins/polychlorinated dibenzofuransbut not both. We measured polychlorinated biphenyls (including specific non-, mono-, and di-ortho congeners) and specific polychlorinated dibenzodioxins/dibenzofurans among 63 Canadian blood donors. Levels of these compounds were, in general, fairly correlated. For example, Pearson's correlation coefficient between log total polychlorinated biphenyl and log total polychlorinated dibenzodioxins was .52. These results suggest that in epidemiologic studies of health effects of background-level exposures to these compounds, the quantitative dose-response relation observed for a given compound (or class of compounds acting through a similar mechanism) may easily be miscalibrated or confounded. JF - Archives of environmental health AU - Longnecker, M P AU - Ryan, J J AU - Gladen, B C AU - Schecter, A J AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 2000 SP - 195 EP - 200 VL - 55 IS - 3 SN - 0003-9896, 0003-9896 KW - Dioxins KW - 0 KW - Environmental Pollutants KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Abridged Index Medicus KW - Index Medicus KW - Environmental Monitoring KW - Chromatography, Gas KW - Canada KW - Epidemiologic Methods KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Epidemiological Monitoring KW - Adolescent KW - Male KW - Female KW - Dioxins -- blood KW - Polychlorinated Biphenyls -- blood KW - Blood Donors KW - Environmental Pollutants -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71233070?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Correlations+among+human+plasma+levels+of+dioxin-like+compounds+and+polychlorinated+biphenyls+%28PCBs%29+and+implications+for+epidemiologic+studies.&rft.au=Longnecker%2C+M+P%3BRyan%2C+J+J%3BGladen%2C+B+C%3BSchecter%2C+A+J&rft.aulast=Longnecker&rft.aufirst=M&rft.date=2000-05-01&rft.volume=55&rft.issue=3&rft.spage=195&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 - 2000-08-03 N1 - Date created - 2000-08-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Combination chemotherapy followed by an immunotoxin (anti-B4-blocked ricin) in patients with indolent lymphoma: results of a phase II study. AN - 71231832; 10882329 AB - The purpose of this article was to evaluate the antitumor effects of a combination chemotherapy program based on ProMACE (prednisone, methotrexate, doxorubicin [Adriamycin], cyclophosphamide, etoposide) followed by a B cell-specific immunotoxin in the treatment of patients with advanced-stage indolent histology non-Hodgkin's lymphomas. We performed a prospective phase II clinical trial in a referral-based patient population. After confirmation of diagnosis and staging evaluation, 44 patients (10 small lymphocytic lymphoma, 27 follicular lymphoma, 7 mantle cell lymphoma; 30 without prior therapy, 14 previously treated) received six cycles of ProMACE-CytaBOM (cytarabine, bleomycin, vincristine [Oncovin], mechlorethamine) combination chemotherapy (with etoposide given orally daily for five days) followed by a 7-day continuous infusion of anti-B4-blocked ricin immunotoxin at 30 microg/kg/day given every 14 days for up to six cycles. A complete response was achieved in 25 of 44 patients (57%), 21 from the chemotherapy alone, 3 converted from partial to complete response with the immunotoxin, and 1 patient became a complete responder after a surgical procedure to remove an enlarged spleen that was histologically negative for lymphoma. With a median follow-up of 5 years, 14 of 25 complete responders have relapsed (56%); median remission duration was 2 years, and overall survival was 61%. Forty-two percent of the complete responders have been in continuous remission for more than 4 years. The median number of courses of immunotoxin delivered was two usually because of the development of human anti-ricin antibodies. ProMACE-CytaBOM plus anti-B4-blocked ricin does not produce durable complete remissions in the majority of patients with indolent lymphoma. However, the remissions appear quite durable (> 4 years) in about 40% of the complete responders. JF - Cancer journal (Sudbury, Mass.) AU - Longo, D L AU - Duffey, P L AU - Gribben, J G AU - Jaffe, E S AU - Curti, B D AU - Gause, B L AU - Janik, J E AU - Braman, V M AU - Esseltine, D AU - Wilson, W H AU - Kaufman, D AU - Wittes, R E AU - Nadler, L M AU - Urba, W J AD - Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland, USA. PY - 2000 SP - 146 EP - 150 VL - 6 IS - 3 SN - 1528-9117, 1528-9117 KW - Antineoplastic Agents KW - 0 KW - Immunoconjugates KW - Immunotoxins KW - anti-B4 blocked ricin immunoconjugate KW - Cytarabine KW - 04079A1RDZ KW - Bleomycin KW - 11056-06-7 KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Ricin KW - 9009-86-3 KW - Prednisone KW - VB0R961HZT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Lymphoma, Follicular -- mortality KW - Disease-Free Survival KW - Prednisone -- therapeutic use KW - Humans KW - Etoposide -- therapeutic use KW - Lymphoma, Follicular -- drug therapy KW - Aged KW - Cytarabine -- therapeutic use KW - Cyclophosphamide -- therapeutic use KW - Leukemia, Lymphocytic, Chronic, B-Cell -- drug therapy KW - Vincristine -- therapeutic use KW - Lymphoma, Mantle-Cell -- drug therapy KW - Adult KW - Treatment Outcome KW - Methotrexate -- therapeutic use KW - Middle Aged KW - Doxorubicin -- therapeutic use KW - Time Factors KW - Bleomycin -- therapeutic use KW - Leukemia, Lymphocytic, Chronic, B-Cell -- mortality KW - Male KW - Lymphoma, Mantle-Cell -- mortality KW - Female KW - Lymphoma -- mortality KW - Ricin -- therapeutic use KW - Lymphoma -- drug therapy KW - Immunotoxins -- therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Immunoconjugates -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71231832?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Combination+chemotherapy+followed+by+an+immunotoxin+%28anti-B4-blocked+ricin%29+in+patients+with+indolent+lymphoma%3A+results+of+a+phase+II+study.&rft.au=Longo%2C+D+L%3BDuffey%2C+P+L%3BGribben%2C+J+G%3BJaffe%2C+E+S%3BCurti%2C+B+D%3BGause%2C+B+L%3BJanik%2C+J+E%3BBraman%2C+V+M%3BEsseltine%2C+D%3BWilson%2C+W+H%3BKaufman%2C+D%3BWittes%2C+R+E%3BNadler%2C+L+M%3BUrba%2C+W+J&rft.aulast=Longo&rft.aufirst=D&rft.date=2000-05-01&rft.volume=6&rft.issue=3&rft.spage=146&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 - 2000-10-26 N1 - Date created - 2000-10-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Cancer J. 2000 May-Jun;6(3):135-8 [10882327] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthesis and antimalarial activities of base-catalyzed adducts of 11-azaartemisinin. AN - 71230617; 10882021 AB - A series of N-substituted 11-azaartemisinins were prepared in high yield employing base-catalyzed additions to an amide nitrogen of olefins and terminal acetylenes conjugated with electron withdrawing groups (EWGs). When the terminal acetylene was conjugated with carbomethoxy, N,N-dimethyl amide or carbonyl groups, the E-adducts resulted. A mixture of E- and Z-adducts were obtained when the EWG was a nitrile. In vitro antimalarial activities of each compound were determined against two drug-resistant strains of Plasmodium falciparum. Many of the compounds prepared were several times more active than artemisinin. JF - Bioorganic & medicinal chemistry AU - Mekonnen, B AU - Weiss, E AU - Katz, E AU - Ma, J AU - Ziffer, H AU - Kyle, D E AD - NIMH, Laboratory of Neurotoxicology, Bethesda, MD 20892-5100, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 1111 EP - 1116 VL - 8 IS - 5 SN - 0968-0896, 0968-0896 KW - Antimalarials KW - 0 KW - Aza Compounds KW - Sesquiterpenes KW - Index Medicus KW - Animals KW - Magnetic Resonance Spectroscopy KW - Catalysis KW - Antimalarials -- pharmacology KW - Aza Compounds -- chemical synthesis KW - Aza Compounds -- pharmacology KW - Sesquiterpenes -- chemical synthesis KW - Sesquiterpenes -- pharmacology KW - Plasmodium falciparum -- drug effects KW - Antimalarials -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71230617?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioorganic+%26+medicinal+chemistry&rft.atitle=Synthesis+and+antimalarial+activities+of+base-catalyzed+adducts+of+11-azaartemisinin.&rft.au=Mekonnen%2C+B%3BWeiss%2C+E%3BKatz%2C+E%3BMa%2C+J%3BZiffer%2C+H%3BKyle%2C+D+E&rft.aulast=Mekonnen&rft.aufirst=B&rft.date=2000-05-01&rft.volume=8&rft.issue=5&rft.spage=1111&rft.isbn=&rft.btitle=&rft.title=Bioorganic+%26+medicinal+chemistry&rft.issn=09680896&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-03 N1 - Date created - 2000-11-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of immunotoxins in the treatment of lymphoma. AN - 71229952; 10882327 JF - Cancer journal (Sudbury, Mass.) AU - Sausville, E A AD - Developmental Therapeutics Program, National Cancer Institute, Rockville, Maryland, USA. PY - 2000 SP - 135 EP - 138 VL - 6 IS - 3 SN - 1528-9117, 1528-9117 KW - Immunotoxins KW - 0 KW - Protein Synthesis Inhibitors KW - Proto-Oncogene Proteins c-bcl-2 KW - Ricin KW - 9009-86-3 KW - Index Medicus KW - Proto-Oncogene Proteins c-bcl-2 -- therapeutic use KW - Animals KW - Dose-Response Relationship, Drug KW - Ricin -- therapeutic use KW - Humans KW - Clinical Trials as Topic KW - Mice KW - Models, Biological KW - Lymphoma -- drug therapy KW - Immunotoxins -- therapeutic use KW - Protein Synthesis Inhibitors -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71229952?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Use+of+immunotoxins+in+the+treatment+of+lymphoma.&rft.au=Sausville%2C+E+A&rft.aulast=Sausville&rft.aufirst=E&rft.date=2000-05-01&rft.volume=6&rft.issue=3&rft.spage=135&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 - 2000-10-26 N1 - Date created - 2000-10-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Cancer J. 2000 May-Jun;6(3):146-50 [10882329] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human dopamine transporter gene: coding region conservation among normal, Tourette's disorder, alcohol dependence and attention-deficit hyperactivity disorder populations. AN - 71223140; 10889531 AB - The dopamine transporter (DAT) provides major regulation of the synaptic levels of dopamine and is a principal target of psychostimulant drugs. Associations between DAT gene polymorphisms and human disorders with possible links to dopaminergic neurotransmission, including attention-deficit/hyperactivity disorder (ADHD) and consequences of cocaine and alcohol administration, have been reported. We now report approximately 60000 bp of genomic sequence containing the entire DAT gene. This sequence was used to amplify each of the 15 DAT gene exons and several introns and analyze these amplification products by single-stranded sequence conformation (SSCP) and/or direct sequencing. These results define silent allelic single nucleotide sequence variants in DAT gene exons 2, 6, 9 and 15. Rare conservative mutations are identified in amino acids encoded by DAT exons 2 and 8. Analyses of the common nucleotide variants and the previously reported VNTR in the non-coding region of exon 15 define the pattern of linkage disequilibrium across the DAT locus. These comprehensive analyses, however, fail to identify any common protein coding DAT sequence variant in more than 150 unrelated individuals free of neuropsychiatric disease, 109 individuals meeting City of Hope criteria for Tourette's syndrome, 64 individuals with DSM-IV diagnoses of ethanol dependence, or 15 individuals with ADHD. These data are consistent with substantial evolutionary conservation of the DAT protein sequence. They suggest that gene variants that alter levels of DAT expression provide the best current candidate mechanism for reported associations between DAT gene markers, ADHD and other more tentatively associated neuropsychiatric disorders. JF - Molecular psychiatry AU - Vandenbergh, D J AU - Thompson, M D AU - Cook, E H AU - Bendahhou, E AU - Nguyen, T AU - Krasowski, M D AU - Zarrabian, D AU - Comings, D AU - Sellers, E M AU - Tyndale, R F AU - George, S R AU - O'Dowd, B F AU - Uhl, G R AD - Molecular Neurobiology Branch, National Institute on Drug Abuse, NIH, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 283 EP - 292 VL - 5 IS - 3 SN - 1359-4184, 1359-4184 KW - Carrier Proteins KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - SLC6A3 protein, human KW - Index Medicus KW - Minisatellite Repeats KW - Genetic Variation KW - Base Sequence KW - Conserved Sequence KW - Exons KW - Humans KW - Introns KW - Child KW - Adolescent KW - Linkage Disequilibrium KW - Polymorphism, Single-Stranded Conformational KW - Attention Deficit Disorder with Hyperactivity -- genetics KW - Carrier Proteins -- genetics KW - Tourette Syndrome -- genetics KW - Alcoholism -- genetics KW - Substance-Related Disorders -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71223140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+psychiatry&rft.atitle=Human+dopamine+transporter+gene%3A+coding+region+conservation+among+normal%2C+Tourette%27s+disorder%2C+alcohol+dependence+and+attention-deficit+hyperactivity+disorder+populations.&rft.au=Vandenbergh%2C+D+J%3BThompson%2C+M+D%3BCook%2C+E+H%3BBendahhou%2C+E%3BNguyen%2C+T%3BKrasowski%2C+M+D%3BZarrabian%2C+D%3BComings%2C+D%3BSellers%2C+E+M%3BTyndale%2C+R+F%3BGeorge%2C+S+R%3BO%27Dowd%2C+B+F%3BUhl%2C+G+R&rft.aulast=Vandenbergh&rft.aufirst=D&rft.date=2000-05-01&rft.volume=5&rft.issue=3&rft.spage=283&rft.isbn=&rft.btitle=&rft.title=Molecular+psychiatry&rft.issn=13594184&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-12 N1 - Date created - 2000-09-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a naturally occurring Pro385-Ser385 substitution in the GABA(A) receptor alpha6 subunit gene in alcoholics and healthy volunteers. AN - 71222655; 10889535 AB - In the rat, variation in alcohol and benzodiazepine sensitivity has been correlated with an inherited variant of the GABA(A)alpha6 receptor. Our goal was to identify polymorphisms in the human GABA(A)alpha6 receptor gene and determine whether a variant of the receptor is associated with alcoholism. The GABA(A)alpha6 receptor gene coding region was screened in 80 unrelated patients with alcoholism using single strand conformational polymorphism analysis. For rapid genotyping, a Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay was developed. A relatively abundant amino acid substitution and three synonymous DNA substitutions were detected. The synonymous variants, 35A>G, 665A>G, and 1031G>C had rare-allele frequencies of 0.25, 0.02, and 0.47, respectively. The Pro385Ser substitution is located in the second intracellular domain of the receptor adjacent to a putative phosphorylation site. Pro385Ser has rarer allele frequencies of 3.3% and 4.8% in 196 Finnish alcoholic patients and 189 controls, respectively (P = NS). A naturally occurring non-conservative Pro385Ser was detected in the GABA(A)alpha6 receptor. The variant is not associated with alcoholism. JF - Molecular psychiatry AU - Iwata, N AU - Virkkunen, M AU - Goldman, D AD - Laboratory of Neurogenetics, DICBR, National Institute on Alcohol Abuse and Alcoholism, 12420 Parklawn Drive, Park5/451, MSC8110, Bethesda, MD 20892-8110, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 316 EP - 319 VL - 5 IS - 3 SN - 1359-4184, 1359-4184 KW - Receptors, GABA-A KW - 0 KW - Serine KW - 452VLY9402 KW - Proline KW - 9DLQ4CIU6V KW - Index Medicus KW - Rats KW - Polymerase Chain Reaction KW - Animals KW - Reference Values KW - Polymorphism, Restriction Fragment Length KW - Finland KW - Humans KW - Point Mutation KW - European Continental Ancestry Group -- genetics KW - Receptors, GABA-A -- genetics KW - Genetic Variation KW - Receptors, GABA-A -- chemistry KW - Alcoholism -- genetics KW - Amino Acid Substitution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71222655?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+psychiatry&rft.atitle=Identification+of+a+naturally+occurring+Pro385-Ser385+substitution+in+the+GABA%28A%29+receptor+alpha6+subunit+gene+in+alcoholics+and+healthy+volunteers.&rft.au=Iwata%2C+N%3BVirkkunen%2C+M%3BGoldman%2C+D&rft.aulast=Iwata&rft.aufirst=N&rft.date=2000-05-01&rft.volume=5&rft.issue=3&rft.spage=316&rft.isbn=&rft.btitle=&rft.title=Molecular+psychiatry&rft.issn=13594184&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-12 N1 - Date created - 2000-09-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Influence of JC virus coding region genotype on risk of multiple sclerosis and progressive multifocal leukoencephalopathy. AN - 71218779; 10871796 AB - Two features of the biology of JC virus make it a particularly suitable candidate for an agent in MS-like disease: its neurotropic capability targeting glial cells as evidenced in progressive multifocal leukoencephalopathy lesions, and its capacity for latency and persistence as illustrated by its behaviour in the kidney. JC virus is chronically or intermittently excreted in the urine by some 40% of the population. The existence of JC virus in multiple coding-region genotypes provides a unique approach to the study of JC virus-induced neurological disease. We have previously shown that a genotype originating in Asia but also present in Europe and the US, called Type 2B, is more frequently found in PML brain than expected based on its prevalence in urine samples from a control population. In contrast, we find that the excretion of JCV in MS patients is similar in both genotype and frequency to that of control individuals, and appears to be regulated by factors unrelated to those that control CNS disease activity. JF - Journal of neurovirology AU - Agostini, H T AU - Ryschkewitsch, C F AU - Baumhefner, R W AU - Tourtellotte, W W AU - Singer, E J AU - Komoly, S AU - Stoner, G L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, MD 20892, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - S101 EP - S108 VL - 6 Suppl 2 SN - 1355-0284, 1355-0284 KW - Adjuvants, Immunologic KW - 0 KW - Antigens, Viral KW - CCAAT-Enhancer-Binding Proteins KW - DNA-Binding Proteins KW - NFI Transcription Factors KW - Nuclear Proteins KW - Transcription Factors KW - Y-Box-Binding Protein 1 KW - YBX1 protein, human KW - Interferon beta-1b KW - 145155-23-3 KW - Interferon-beta KW - 77238-31-4 KW - Interferon beta-1a KW - XRO4566Q4R KW - Index Medicus KW - Antigens, Viral -- cerebrospinal fluid KW - Genes, Viral -- genetics KW - Antigens, Viral -- urine KW - Humans KW - DNA-Binding Proteins -- genetics KW - Demyelinating Diseases -- virology KW - Disease Progression KW - Genotype KW - Regulatory Sequences, Nucleic Acid KW - Interferon-beta -- administration & dosage KW - Adjuvants, Immunologic -- administration & dosage KW - Risk Factors KW - Cohort Studies KW - Neuroglia -- virology KW - Male KW - Female KW - Leukoencephalopathy, Progressive Multifocal -- virology KW - Multiple Sclerosis, Chronic Progressive -- ethnology KW - Multiple Sclerosis, Chronic Progressive -- drug therapy KW - JC Virus -- genetics KW - Leukoencephalopathy, Progressive Multifocal -- ethnology KW - Multiple Sclerosis, Relapsing-Remitting -- ethnology KW - Multiple Sclerosis, Chronic Progressive -- virology KW - Leukoencephalopathy, Progressive Multifocal -- drug therapy KW - Multiple Sclerosis, Relapsing-Remitting -- virology KW - Multiple Sclerosis, Relapsing-Remitting -- drug therapy KW - JC Virus -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71218779?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurovirology&rft.atitle=Influence+of+JC+virus+coding+region+genotype+on+risk+of+multiple+sclerosis+and+progressive+multifocal+leukoencephalopathy.&rft.au=Agostini%2C+H+T%3BRyschkewitsch%2C+C+F%3BBaumhefner%2C+R+W%3BTourtellotte%2C+W+W%3BSinger%2C+E+J%3BKomoly%2C+S%3BStoner%2C+G+L&rft.aulast=Agostini&rft.aufirst=H&rft.date=2000-05-01&rft.volume=6+Suppl+2&rft.issue=&rft.spage=S101&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurovirology&rft.issn=13550284&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-27 N1 - Date created - 2000-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Growth hormone as an immunomodulating therapeutic agent. AN - 71198704; 10877541 JF - Immunology today AU - Murphy, W J AU - Longo, D L Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 211 EP - 213 VL - 21 IS - 5 KW - Adjuvants, Immunologic KW - 0 KW - Antigens, CD44 KW - Hematopoietic Cell Growth Factors KW - Receptors, Interleukin-7 KW - Growth Hormone KW - 9002-72-6 KW - Index Medicus KW - Thymus Gland -- immunology KW - Animals KW - Antigens, CD44 -- immunology KW - Receptors, Interleukin-7 -- immunology KW - Humans KW - Pilot Projects KW - Mice KW - Arthralgia -- chemically induced KW - Thymus Gland -- drug effects KW - Signal Transduction KW - Growth Hormone -- adverse effects KW - Hematopoietic Cell Growth Factors -- adverse effects KW - Adjuvants, Immunologic -- physiology KW - Growth Hormone -- physiology KW - T-Lymphocytes -- drug effects KW - Adjuvants, Immunologic -- adverse effects KW - T-Lymphocytes -- immunology KW - Hematopoietic Cell Growth Factors -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71198704?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Immunology+today&rft.atitle=Growth+hormone+as+an+immunomodulating+therapeutic+agent.&rft.au=Murphy%2C+W+J%3BLongo%2C+D+L&rft.aulast=Murphy&rft.aufirst=W&rft.date=2000-05-01&rft.volume=21&rft.issue=5&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Immunology+today&rft.issn=01675699&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-22 N1 - Date created - 2000-06-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Trends Immunol. 2001 Jan;22(1):14-6 [11334029] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mesenchymal-epithelial transition in the developing metanephric kidney: gene expression study by differential display. AN - 71194984; 10862152 AB - The developing metanephric kidney is a convenient model to study molecular events associated with epithelial cell differentiation. To determine the genes involved in the defining event of this process, namely, the conversion of metanephric mesenchyme to the epithelium of the nephron, we applied differential display (DD) techniques. Explants of rat metanephric mesenchymes were induced to condense ex vivo with fibroblast growth factor 2 (FGF2) or to form tubules with FGF2 and conditioned medium (CM) from a cell line (RUB1) of ureteric bud, the renal inductive tissue. Three time points (6, 24, and 72 h) were chosen to track the dynamics of gene expression during morphogenesis. Seventy-two up- or down-regulated mRNAs were identified, including 36 novel sequences and those of cell cycle regulatory proteins (TGF-beta2, Cyclin D1, p57Kip2), transcription factors (beta-catenin, Sox11, DP1), signaling proteins (SH3-domain binding protein, G-protein-coupled receptor, Ser-Thr protein kinase), cell adhesion molecules (syndecan-4, integrin-beta1), and also gene33, H19, SM20, IGFBP5, MAMA receptor, lectin, keratin, beta-tubulin, calreticulin, GRP78, ERp72, MnSoD, thioredoxin, and others. Some have previously been associated with kidney development and serve as good controls for expected changes, while most have not been linked with kidney epithelial cell differentiation. Using thin sections of embryonic kidney and labeled antisense RNA probes, we applied RNA hybridization to confirm the results of DD and related the expression of these genes to specific cell lineages of the developing kidney. These results provide a window into the events that mediate this critical differentiation process and suggest that a limited number of interrelated events direct the epithelial conversion of metanephric mesenchyme. genesis 27:22-31, 2000. Published 2000 Wiley-Liss, Inc. JF - Genesis (New York, N.Y. : 2000) AU - Plisov, S Y AU - Ivanov, S V AU - Yoshino, K AU - Dove, L F AU - Plisova, T M AU - Higinbotham, K G AU - Karavanova, I AU - Lerman, M AU - Perantoni, A O AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, Maryland 21702-1201, USA. plisov@mail.ncifcrf.gov Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 22 EP - 31 VL - 27 IS - 1 SN - 1526-954X, 1526-954X KW - DNA, Complementary KW - 0 KW - RNA, Messenger KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Base Sequence KW - In Situ Hybridization -- methods KW - Molecular Sequence Data KW - Reverse Transcriptase Polymerase Chain Reaction -- methods KW - Epithelium -- embryology KW - Kidney -- metabolism KW - Kidney -- embryology KW - Mesoderm -- physiology KW - Gene Expression Profiling -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71194984?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genesis+%28New+York%2C+N.Y.+%3A+2000%29&rft.atitle=Mesenchymal-epithelial+transition+in+the+developing+metanephric+kidney%3A+gene+expression+study+by+differential+display.&rft.au=Plisov%2C+S+Y%3BIvanov%2C+S+V%3BYoshino%2C+K%3BDove%2C+L+F%3BPlisova%2C+T+M%3BHiginbotham%2C+K+G%3BKaravanova%2C+I%3BLerman%2C+M%3BPerantoni%2C+A+O&rft.aulast=Plisov&rft.aufirst=S&rft.date=2000-05-01&rft.volume=27&rft.issue=1&rft.spage=22&rft.isbn=&rft.btitle=&rft.title=Genesis+%28New+York%2C+N.Y.+%3A+2000%29&rft.issn=1526954X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-29 N1 - Date created - 2000-08-29 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AW672643; GENBANK; AW672644; AW672631; AW672641; AW672642; AW672633; AW672634; AW672635; AW672645; AW672636; AW672637; AW672626; AW672625; AW672650; AW672624; AW672651; AW672623; AW672640; AW672619; AW672608; AW672628; AW672627; AW672639; AW672638 N1 - SuppNotes - Erratum In: Genesis 2000 Jul;27(3):136 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The use of genetically modified animals in carcinogenicity bioassays. AN - 71194641; 10862565 JF - Toxicologic pathology AU - Maronpot, R R AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. maronpot@niehs.nih.gov PY - 2000 SP - 450 EP - 453 VL - 28 IS - 3 SN - 0192-6233, 0192-6233 KW - Carcinogens KW - 0 KW - Index Medicus KW - Animals KW - International Cooperation KW - Disease Models, Animal KW - Mice KW - Species Specificity KW - Carcinogens -- toxicity KW - Carcinogenicity Tests -- methods KW - Mice, Transgenic KW - Mice, Knockout UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71194641?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=The+use+of+genetically+modified+animals+in+carcinogenicity+bioassays.&rft.au=Maronpot%2C+R+R&rft.aulast=Maronpot&rft.aufirst=R&rft.date=2000-05-01&rft.volume=28&rft.issue=3&rft.spage=450&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-05 N1 - Date created - 2000-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The use of genetically altered animals in toxicology. AN - 71194089; 10862564 JF - Toxicologic pathology AU - Mahler, J F AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 2000 SP - 447 EP - 449 VL - 28 IS - 3 SN - 0192-6233, 0192-6233 KW - Carcinogens KW - 0 KW - Cytokines KW - Ligands KW - Receptors, Aryl Hydrocarbon KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - Xenobiotics KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Transcription Factors -- metabolism KW - DNA Damage KW - Xenobiotics -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Carcinogens -- toxicity KW - Cytokines -- physiology KW - Receptors, Aryl Hydrocarbon -- metabolism KW - Oxidative Stress -- genetics KW - Xenobiotics -- toxicity KW - Models, Biological KW - DNA -- drug effects KW - Toxicity Tests -- methods KW - Animals, Genetically Modified UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71194089?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=The+use+of+genetically+altered+animals+in+toxicology.&rft.au=Mahler%2C+J+F&rft.aulast=Mahler&rft.aufirst=J&rft.date=2000-05-01&rft.volume=28&rft.issue=3&rft.spage=447&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-05 N1 - Date created - 2000-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - UCN-01 enhances the in vitro toxicity of clinical agents in human tumor cell lines. AN - 71193173; 10857990 AB - UCN-01 is undergoing Phase I evaluation and is a candidate for combination strategies in the clinic. UCN-01 has been shown to have a variety of effects on cellular targets and the cell cycle. It has also been reported to sensitize cells to several clinical drugs in vitro, possibly in a manner related to p53 status. Thus, combinations of UCN-01 with a series of clinical agents in variety of cell lines have been investigated in vitro. Certain cell lines demonstrated synergistic interactions with combinations of UCN-01 (20-150 nM) and thiotepa, mitomycin C, cisplatin, melphalan, topotecan, gemcitabine, fludarabine or 5-fluorouracil. In contrast, UCN-01 combinations with the antimitotic agents, paclitaxel and vincristine, or topoisomerase II inhibitors, adriamycin and etoposide, did not result in synergy, only in additive toxicity. Cells with non-functional p53 were significantly more susceptible to the supra-additive effects of certain DNA-damaging agents and UCN-01 combinations, than cells expressing functional p53 activity. In contrast, there was no significant relationship between p53 status and susceptibility to synergy between antimetabolites and UCN-01. The mechanism behind the observed synergy appeared unrelated to effects on protein kinase C or abrogation of the cell cycle in G2. Moreover, increased apoptosis did not fully explain the supradditive response. These data indicate that UCN-01 sensitizes a variety of cell lines to certain DNA-damaging agents (frequently covalent DNA-binding drugs) and antimetabolites in vitro, but the mechanism underlying this interaction remains undefined. JF - Investigational new drugs AU - Monks, A AU - Harris, E D AU - Vaigro-Wolff, A AU - Hose, C D AU - Connelly, J W AU - Sausville, E A AD - SAIC-Frederick, NCI-FCRDC, MD 21702, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 95 EP - 107 VL - 18 IS - 2 SN - 0167-6997, 0167-6997 KW - Alkaloids KW - 0 KW - Antineoplastic Agents KW - Antineoplastic Agents, Alkylating KW - Tumor Suppressor Protein p53 KW - 7-hydroxystaurosporine KW - 7BU5H4V94A KW - Thiotepa KW - 905Z5W3GKH KW - Protein Kinase C KW - EC 2.7.11.13 KW - Staurosporine KW - H88EPA0A3N KW - Index Medicus KW - Thiotepa -- toxicity KW - Protein Kinase C -- antagonists & inhibitors KW - Tumor Cells, Cultured KW - Humans KW - Apoptosis -- drug effects KW - Mitotic Index KW - Tumor Suppressor Protein p53 -- genetics KW - Drug Synergism KW - Cell Death -- drug effects KW - Antineoplastic Agents, Alkylating -- toxicity KW - Staurosporine -- analogs & derivatives KW - Cell Cycle -- drug effects KW - Alkaloids -- toxicity KW - Antineoplastic Agents -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71193173?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigational+new+drugs&rft.atitle=UCN-01+enhances+the+in+vitro+toxicity+of+clinical+agents+in+human+tumor+cell+lines.&rft.au=Monks%2C+A%3BHarris%2C+E+D%3BVaigro-Wolff%2C+A%3BHose%2C+C+D%3BConnelly%2C+J+W%3BSausville%2C+E+A&rft.aulast=Monks&rft.aufirst=A&rft.date=2000-05-01&rft.volume=18&rft.issue=2&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Investigational+new+drugs&rft.issn=01676997&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-11 N1 - Date created - 2000-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of lupus nephritis. AN - 71187065; 10855936 AB - Patients with lupus nephritis pose a therapeutic challenge and stimulate investigation of innovative treatment strategies. Although patient survival and renal function outcomes have improved over the last 4 decades, contemporary immunosuppressive regimens are not consistently effective and often require extended courses associated with insidious toxicities. Several strategies are under investigation to induce remissions more rapidly and to reduce the risk of long courses of cytotoxic drug therapy. The combination of pulse methylprednisolone and pulse cyclophosphamide may be more effective than pulse cyclophosphamide alone for patients with relatively severe proliferative lupus nephritis. Ongoing clinical studies evaluate the risk/benefit of other intensive induction regimens (eg, combination fludarabine with relatively low-dose pulse cyclophosphamide). A particularly vigorous strategy employs immunoablative cyclophosphamide with or without stem cell rescue. Several studies of sequential immunosuppressive therapy are in progress. It is anticipated that long-term toxicities can be lessened by substituting various maintenance agents (eg, azathioprine or mycophenolate mofetil) after initial cyclophosphamide therapy has induced a renal response. Additional information is needed to determine the role of this strategy. Furthermore, a number of standard and experimental immunosuppressive regimens (that do not include cyclophosphamide) are under investigation as well. Innovative approaches (eg, costimulatory blockade) offer the hope of more effective treatments without the risks of contemporary regimens. JF - Seminars in nephrology AU - Austin, H A AU - Balow, J E AD - Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1268, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 265 EP - 276 VL - 20 IS - 3 SN - 0270-9295, 0270-9295 KW - Index Medicus KW - Humans KW - Clinical Trials as Topic KW - Lupus Nephritis -- drug therapy KW - Lupus Nephritis -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71187065?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nephrology&rft.atitle=Treatment+of+lupus+nephritis.&rft.au=Austin%2C+H+A%3BBalow%2C+J+E&rft.aulast=Austin&rft.aufirst=H&rft.date=2000-05-01&rft.volume=20&rft.issue=3&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=Seminars+in+nephrology&rft.issn=02709295&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-18 N1 - Date created - 2000-10-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of changes evoked by GABA (gamma-aminobutyric acid) and anoxia in [K+]o, [Cl-]o, and [Na+]o in stratum pyramidale and stratum radiatum of the guinea pig hippocampus. AN - 71164838; 10841433 AB - Ion-selective microelectrode recordings were made to assess a possible contribution of extracellular gamma-aminobutyric acid (GABA) accumulation to early responses evoked in the brain by anoxia and ischemia. Changes evoked by GABA or N2 in [K+]o, [Cl-]o, [Na+]o, and [TMA+]o were recorded in the cell body and dendritic regions of the stratum pyramidale (SP) and stratum radiatum (SR), respectively, of pyramidal neurons in CA1 of guinea pig hippocampal slices. Bath application of GABA (1-10 mM) for approximately 5 min evoked changes in [K+]o and [Cl-]o with respective EC50 levels of 3.8 and 4.1 mM in SP, and 4.7 and 5.6 mM in SR. In SP 5 mM GABA reversibly increased [K+]o and [Cl-]o and decreased [Na+]o; replacement of 95% O2 -5% CO2 by 95% N2 -5% CO2 for a similar period of time evoked changes which were for each ion in the same direction as those with GABA. In SR both GABA and N2 caused increases in [K+]o and decreases in [Cl-]o and [Na+]. The reduction of extracellular space, estimated from levels of [TMA+]o during exposures to GABA and N2, was 5-6% and insufficient to cause the observed changes in ion concentration. Ion changes induced by GABA and N2 were reversibly attenuated by the GABA(A) receptor antagonist bicuculline methiodide (BMI, 100 microM). GABA-evoked changes in [K+]o in SP and SR and [Cl-]o in SP were depressed by > or =90%, and of [Cl-]o in SR by 50%; N2-evoked changes in [K+]o in SP and SR were decreased by 70% and those of [Cl-]o by 50%. BMI blocked delta [Na+]o with both GABA and N2 by 20-30%. It is concluded that during early anoxia: (i) accumulation of GABA and activation of GABA(A) receptors may contribute to the ion changes and play a significant role, and (ii) responses in the dendritic (SR) regions are greater than and (or) differ from those in the somal (SP) layers. A large component of the [K+]o increase may involve a GABA-evoked Ca2+-activated gk, secondary to [Ca2+]i increase. A major part of [Cl-]o changes may arise from GABA-induced g(Cl) and glial efflux, with strong stimulation of active outward transport and anion exchange at SP, and inward Na+/K+/2Cl- co-transport at SR. Na+ influx is attributable mainly to Na+-dependent transmitter uptake, with only a small amount related to GABA(A) receptor activation. Although the release and (or) accumulation of GABA during anoxia might be viewed as potentially protectant, the ultimate role may more likely be an important contribution to toxicity and delayed neuronal death. JF - Canadian journal of physiology and pharmacology AU - Obrocea, G V AU - Morris, M E AD - Department of Health and Human Services, National Institutes of Health/National Institute of Mental Health, Bethesda, MD 20892-1272, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 378 EP - 391 VL - 78 IS - 5 SN - 0008-4212, 0008-4212 KW - Chlorides KW - 0 KW - GABA Antagonists KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Sodium KW - 9NEZ333N27 KW - Nitrogen KW - N762921K75 KW - Potassium KW - RWP5GA015D KW - Bicuculline KW - Y37615DVKC KW - Index Medicus KW - Bicuculline -- pharmacology KW - Animals KW - Guinea Pigs KW - Extracellular Space -- metabolism KW - In Vitro Techniques KW - Nitrogen -- pharmacology KW - Electrophysiology KW - GABA Antagonists -- pharmacology KW - Extracellular Space -- drug effects KW - Microelectrodes KW - Pyramidal Tracts -- metabolism KW - Pyramidal Tracts -- drug effects KW - gamma-Aminobutyric Acid -- pharmacology KW - Hypoxia -- metabolism KW - Hippocampus -- metabolism KW - Chlorides -- metabolism KW - Potassium -- metabolism KW - Sodium -- metabolism KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71164838?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Canadian+journal+of+physiology+and+pharmacology&rft.atitle=Comparison+of+changes+evoked+by+GABA+%28gamma-aminobutyric+acid%29+and+anoxia+in+%5BK%2B%5Do%2C+%5BCl-%5Do%2C+and+%5BNa%2B%5Do+in+stratum+pyramidale+and+stratum+radiatum+of+the+guinea+pig+hippocampus.&rft.au=Obrocea%2C+G+V%3BMorris%2C+M+E&rft.aulast=Obrocea&rft.aufirst=G&rft.date=2000-05-01&rft.volume=78&rft.issue=5&rft.spage=378&rft.isbn=&rft.btitle=&rft.title=Canadian+journal+of+physiology+and+pharmacology&rft.issn=00084212&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-15 N1 - Date created - 2000-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nonmuscle myosin II localizes to the Z-lines and intercalated discs of cardiac muscle and to the Z-lines of skeletal muscle. AN - 71155298; 10842333 AB - To understand the role of nonmuscle myosin II in cardiac and skeletal muscle, we used a number of polyclonal antibodies, three detecting nonmuscle myosin heavy chain II-B (NMHC II-B) and two detecting NMHC II-A, to examine the localization of these two proteins in fresh-frozen, acetone-fixed sections of normal human and mouse hearts and human skeletal muscles. Results were similar in both species and were confirmed by examination of fresh-frozen sections of human hearts subjected to no fixation or to treatment with either 4% p-formaldehyde or 50% glycerol. NMHC II-B was diffusely distributed in the cytoplasm of cardiac myocytes during development, but after birth it was localized to the Z-lines and intercalated discs. Dual labeling showed almost complete colocalization of NMHC II-B with alpha-actinin. Whereas endothelial cells, smooth muscle cells and fibroblasts showed strong immunoreactivity for NMHC II-A and NMHC II-B, cardiac myocytes only showed reactivity for the latter. The Z-lines of human skeletal muscle cells, in contrast to those of cardiac myocytes, gave positive reactions for both NMHC II-A and NMHC II-B. The presence of a motor protein in the Z-lines and intercalated discs raises the possibility that these structures may play a more dynamic role in the contraction/relaxation mechanism of cardiac and skeletal muscle than has been previously suspected. Copyright 2000 Wiley-Liss, Inc. JF - Cell motility and the cytoskeleton AU - Takeda, K AU - Yu, Z X AU - Qian, S AU - Chin, T K AU - Adelstein, R S AU - Ferrans, V J AD - Pathology Section, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 59 EP - 68 VL - 46 IS - 1 SN - 0886-1544, 0886-1544 KW - Desmin KW - 0 KW - Fluorescent Dyes KW - Rhodamines KW - Actinin KW - 11003-00-2 KW - Phalloidine KW - 17466-45-4 KW - Myosins KW - EC 3.6.4.1 KW - Index Medicus KW - Microscopy, Confocal KW - Sarcomeres -- chemistry KW - Animals KW - Muscle Fibers, Skeletal -- chemistry KW - Humans KW - Aged KW - Child KW - Desmin -- immunology KW - Infant KW - Antibody Specificity KW - Adult KW - Actinin -- analysis KW - Adolescent KW - Actinin -- immunology KW - Fluorescent Antibody Technique, Indirect KW - Fetus -- cytology KW - Infant, Newborn KW - Mice KW - Rabbits KW - Desmin -- analysis KW - Child, Preschool KW - Mice, Inbred C57BL KW - Middle Aged KW - Tissue Fixation KW - Myocardium -- cytology KW - Muscle, Skeletal -- embryology KW - Muscle, Skeletal -- cytology KW - Myocardium -- chemistry KW - Myosins -- immunology KW - Myosins -- analysis KW - Heart -- embryology KW - Muscle, Skeletal -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71155298?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+motility+and+the+cytoskeleton&rft.atitle=Nonmuscle+myosin+II+localizes+to+the+Z-lines+and+intercalated+discs+of+cardiac+muscle+and+to+the+Z-lines+of+skeletal+muscle.&rft.au=Takeda%2C+K%3BYu%2C+Z+X%3BQian%2C+S%3BChin%2C+T+K%3BAdelstein%2C+R+S%3BFerrans%2C+V+J&rft.aulast=Takeda&rft.aufirst=K&rft.date=2000-05-01&rft.volume=46&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Cell+motility+and+the+cytoskeleton&rft.issn=08861544&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-21 N1 - Date created - 2000-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Decreased tolerance to interleukin-2 with repeated courses of therapy in patients with metastatic melanoma or renal cell cancer. AN - 71152154; 10838668 AB - High-dose interleukin-2 (IL-2) therapy has a response rate of approximately 20% in patients with metastatic melanoma and renal cell cancer. Animal models have shown that the anti-tumor effects of IL-2 are dose and schedule dependent, and one report has shown that patients with melanoma who responded to IL-2 therapy received more doses of IL-2 than did those who did not respond. The current study evaluated patients' tolerance to IL-2 over multiple courses of therapy and the factors that affected the number of doses delivered. Patients with metastatic melanoma or renal cell cancer who received at least two consecutive courses of high-dose intravenous IL-2 alone from October 1, 1985 through December 31, 1996 were evaluated. Patients served as their own controls in paired analyses. The number of doses tolerated from one course to the next and the reasons for stopping therapy were analyzed. One hundred fifty-nine patients received two or more courses of therapy during the study. The median number of doses of high-dose IL-2 decreased from course 1 (15 doses) to course 2 (12 doses) (p2 = 0.0001). Pretreatment factors were not found to significantly influence the decrease in the number of doses delivered. Only 2 of 33 separate toxic effects resulting in discontinuation of IL-2 dosing were found to be significantly different between courses. After adjusting for multiple tests of statistical significance, serum aspartate aminotransferase elevations were more likely to stop course 1 (p2 = 0.0033) and creatinine elevations were more likely to stop course 2 (p2 = 0.00007). The influence of renal toxicity was further assessed by comparing the median creatinine value at the time IL-2 dosing was discontinued. This difference was found to be significant when cycle 1 of course 1 (1.5 mg/dL) was compared with cycle 1 of course 2 (1.8 mg/dL; p2 = 0.0001). When pretreatment factors were analyzed, male sex (p2 = 0.006), a diagnosis of renal cell cancer (p2 = 0.008), previous nephrectomy (p2 = 0.001), and older age (p2 = 0.0055) were significantly associated with the development of renal toxicity that resulted in discontinuation of IL-2 therapy. Furthermore, the same four patient subsets had higher baseline creatinine values in individual univariate analyses. This study identified subsets of patients who tolerated less IL-2 with repeated courses. The decreasing tolerance to IL-2 was associated primarily with elevations in creatinine. Finding ways to ameliorate the renal toxicity seen during IL-2 therapy in this patient population may allow an increase in the number of IL-2 doses administered and potentially an increase in clinical response. JF - Journal of immunotherapy (Hagerstown, Md. : 1997) AU - Marroquin, C E AU - White, D E AU - Steinberg, S M AU - Rosenberg, S A AU - Schwartzentruber, D J AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1502, USA. PY - 2000 SP - 387 EP - 392 VL - 23 IS - 3 SN - 1524-9557, 1524-9557 KW - Interleukin-2 KW - 0 KW - Creatinine KW - AYI8EX34EU KW - Aspartate Aminotransferases KW - EC 2.6.1.1 KW - Index Medicus KW - Age Factors KW - Drug Administration Schedule KW - Sex Factors KW - Renal Insufficiency -- chemically induced KW - Humans KW - Retrospective Studies KW - Aged KW - Creatinine -- blood KW - Aspartate Aminotransferases -- blood KW - Nephrectomy KW - Adult KW - Neoplasm Metastasis KW - Middle Aged KW - Female KW - Male KW - Carcinoma, Renal Cell -- pathology KW - Kidney Neoplasms -- therapy KW - Kidney Neoplasms -- pathology KW - Kidney Neoplasms -- blood KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - Melanoma -- pathology KW - Carcinoma, Renal Cell -- therapy KW - Melanoma -- blood KW - Melanoma -- therapy KW - Carcinoma, Renal Cell -- blood KW - Kidney Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71152154?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.atitle=Decreased+tolerance+to+interleukin-2+with+repeated+courses+of+therapy+in+patients+with+metastatic+melanoma+or+renal+cell+cancer.&rft.au=Marroquin%2C+C+E%3BWhite%2C+D+E%3BSteinberg%2C+S+M%3BRosenberg%2C+S+A%3BSchwartzentruber%2C+D+J&rft.aulast=Marroquin&rft.aufirst=C&rft.date=2000-05-01&rft.volume=23&rft.issue=3&rft.spage=387&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.issn=15249557&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-16 N1 - Date created - 2000-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduction of lipopolysaccharide-induced neurotoxicity in mouse mixed cortical neuron/glia cultures by ultralow concentrations of dynorphins. AN - 71137589; 10810243 AB - Previously we reported that ultralow concentrations of dynorphins (10(-16) to 10(-12) M) inhibited lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and proinflammatory cytokines in mouse glia without the participation of kappa-opioid receptors. In the current study using mouse cortical neuron-glia cocultures, we examined the possibility that inhibition of glia inflammatory response by dynorphins might be neuroprotective for neurons. LPS, in a concentration-dependent manner, markedly increased the release of lactate dehydrogenase (LDH), an indicator of cellular injury. Ultralow concentrations (10(-14) to 10(-12) M) of dynorphin (dyn) A-(1-8) significantly prevented the LPS-induced release of LDH, loss of neurons, and changes in cell morphology, in addition to inhibition of LPS-induced nitrite production. Meanwhile, ultralow concentrations (10(-15) to 10(-13) M) of des-[Tyr(1)]-dyn A-(2-17), a nonopioid peptide which does not bind to kappa-opioid receptors, exhibited the same inhibitory effect as dyn A-(1-17). These results suggest that dynorphins at ultralow concentrations are capable of reducing LPS-induced neuronal injury and these neuroprotective effects of dynorphins are not mediated by classical opioid receptors. JF - Journal of biomedical science AU - Kong, L Y AU - Jeohn, G AU - Hudson, P M AU - Du, L AU - Liu, B AU - Hong, J S AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. PY - 2000 SP - 241 EP - 247 VL - 7 IS - 3 SN - 1021-7770, 1021-7770 KW - Analgesics, Opioid KW - 0 KW - Biomarkers KW - Lipopolysaccharides KW - Peptide Fragments KW - Receptors, Opioid, kappa KW - Nitric Oxide KW - 31C4KY9ESH KW - Dynorphins KW - 74913-18-1 KW - dynorphin (2-17) KW - 83608-80-4 KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Index Medicus KW - Mice, Inbred Strains KW - Coculture Techniques KW - Animals KW - Dose-Response Relationship, Drug KW - Analgesics, Opioid -- pharmacology KW - L-Lactate Dehydrogenase -- drug effects KW - Receptors, Opioid, kappa -- antagonists & inhibitors KW - Peptide Fragments -- pharmacology KW - Nitric Oxide -- metabolism KW - Mice KW - Time Factors KW - L-Lactate Dehydrogenase -- metabolism KW - Neuroglia -- cytology KW - Cerebral Cortex -- cytology KW - Cerebral Cortex -- drug effects KW - Lipopolysaccharides -- pharmacology KW - Neuroglia -- drug effects KW - Neurons -- pathology KW - Dynorphins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71137589?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biomedical+science&rft.atitle=Reduction+of+lipopolysaccharide-induced+neurotoxicity+in+mouse+mixed+cortical+neuron%2Fglia+cultures+by+ultralow+concentrations+of+dynorphins.&rft.au=Kong%2C+L+Y%3BJeohn%2C+G%3BHudson%2C+P+M%3BDu%2C+L%3BLiu%2C+B%3BHong%2C+J+S&rft.aulast=Kong&rft.aufirst=L&rft.date=2000-05-01&rft.volume=7&rft.issue=3&rft.spage=241&rft.isbn=&rft.btitle=&rft.title=Journal+of+biomedical+science&rft.issn=10217770&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-11 N1 - Date created - 2000-07-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The immunobiology of low-dose total-body irradiation: more questions than answers. AN - 71130576; 10790282 AB - Low-dose total-body irradiation (TBI) is used in the treatment of chronic lymphocytic leukemia and low-grade non-Hodgkin's lymphoma. The usual practice is to give very low individual fractions (0.1 to 0.25 Gy) several times a week, to a total dose of 1.5 to 2 Gy. Despite this low dose, low-dose TBI can induce long-term remissions in the majority of patients. Immune enhancement, rather than direct radiation cell killing, is one of the suggested mechanisms by which low-dose TBI can exert its effect. Data from animal experiments have shown that low-dose TBI could enhance the immune response through (1) augmenting the proliferative reactive response of the T cells to mitogenic stimulation; (2) altering cytokine release, particularly the activation of interferon gamma and Il2 production; (3) increasing the expression of Il2 receptors on the T-cell surface; (4) facilitating signal transduction in T lymphocytes; (5) increasing splenic catecholamine content and lowering the serum corticosterone level; and (6) eliminating a particularly radiosensitive subset of the suppressor T cells. Data for humans, though scarce, suggest that at least some of these mechanisms occur in patients treated with low-dose TBI. Whether these immunomodulatory effects are responsible for the clinical outcome is not yet clear. Much is still unknown about the immunobiology of low-dose TBI, its clinical potential, and the possible synergism with chemotherapy, biological response modifiers, or immunotherapy. This lack of comprehensive knowledge hampers the optimal and widespread use of this intriguing and potentially useful treatment modality in clinical practice. JF - Radiation research AU - Safwat, A AD - Radiotherapy Department, National Cancer Institute, Fom El-khalig, Cairo, Egypt. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 599 EP - 604 VL - 153 IS - 5 Pt 1 SN - 0033-7587, 0033-7587 KW - Cytokines KW - 0 KW - Index Medicus KW - Space life sciences KW - Animals KW - Neoplasms -- radiotherapy KW - Lymphoma, Non-Hodgkin -- radiotherapy KW - Humans KW - Mice KW - Radiation Dosage KW - T-Lymphocytes -- cytology KW - Whole-Body Irradiation KW - Cytokines -- biosynthesis KW - Cytokines -- radiation effects KW - Cytokines -- immunology KW - T-Lymphocytes -- radiation effects KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71130576?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+immunobiology+of+low-dose+total-body+irradiation%3A+more+questions+than+answers.&rft.au=Safwat%2C+A&rft.aulast=Safwat&rft.aufirst=A&rft.date=2000-05-01&rft.volume=153&rft.issue=5+Pt+1&rft.spage=599&rft.isbn=&rft.btitle=&rft.title=Radiation+research&rft.issn=00337587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-08 N1 - Date created - 2000-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Imaging and phase I study of 111In- and 90Y-labeled anti-LewisY monoclonal antibody B3. AN - 71121577; 10815890 AB - B3 is a murine monoclonal antibody (mAb) that recognizes a LewisY carbohydrate antigen present on the surface of many carcinomas. An imaging and Phase I trial was performed to study the ability of 111In-mAb B3 to image known metastasis and determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), kinetics, and biodistribution of 90Y-mAb B3. Patients (n = 26) with advanced epithelial tumors that express the LewisY antigen were entered. All patients received 5 mCi of 111In-mAb B3 for imaging. 90Y-mAb B3 doses were escalated from 5 to 25 mCi in 5-mCi increments. 111In-mAb B3 and 90Y-mAb B3 were coadministered over a 1-h infusion. Definite tumor imaging was observed in 20 of 26 patients. Sites imaged included lung, liver, bone, and soft tissues. The MTD of 90Y-mAb B3 was determined to be 20 mCi. The DLTs were neutropenia and thrombocytopenia. Tumor doses ranged from 7.7 to 65.1 rad/mCi. 111In- and 90Y-mAb B3 serum pharmacokinetics (n = 23) were found to be similar. The amount of B3 administered (5, 10, and 50 mg) did not alter the pharmacokinetics. Bone marrow biopsies (n = 23) showed 0.0038+/-0.0016% of injected dose/gram for 111In-mAb B3 compared to 0.0046+/-0.0017% of injected dose/gram for 90Y-mAb B3 (P = 0.009). When given to patients with carcinomas that express the LewisY antigen, 111In-mAb B3 demonstrated good tumor localization. The MTD of 90Y-mAb B3 is 20 mCi, with myelosuppression as the DLT. Higher doses of radioactivity need to be delivered to achieve an antitumor effect. Humanized mAb B3 is being developed for evaluation in radioimmunotherapy. A clinical trial to explore the use of higher doses of 90Y-mAb B3 with autologous stem cell support is planned. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Pai-Scherf, L H AU - Carrasquillo, J A AU - Paik, C AU - Gansow, O AU - Whatley, M AU - Pearson, D AU - Webber, K AU - Hamilton, M AU - Allegra, C AU - Brechbiel, M AU - Willingham, M C AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 1720 EP - 1730 VL - 6 IS - 5 SN - 1078-0432, 1078-0432 KW - Antibodies, Monoclonal KW - 0 KW - Indium Radioisotopes KW - Lewis Blood-Group System KW - Lewis Y antigen KW - Yttrium Radioisotopes KW - Index Medicus KW - Animals KW - Area Under Curve KW - Humans KW - Aged KW - Metabolic Clearance Rate KW - Mice KW - Tissue Distribution KW - Radionuclide Imaging KW - Hematologic Diseases -- chemically induced KW - Adult KW - Treatment Outcome KW - Indium Radioisotopes -- pharmacokinetics KW - Middle Aged KW - Female KW - Male KW - Neoplasms -- drug therapy KW - Neoplasms -- pathology KW - Neoplasms -- diagnostic imaging KW - Antibodies, Monoclonal -- pharmacokinetics KW - Antibodies, Monoclonal -- adverse effects KW - Lewis Blood-Group System -- immunology KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71121577?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Imaging+and+phase+I+study+of+111In-+and+90Y-labeled+anti-LewisY+monoclonal+antibody+B3.&rft.au=Pai-Scherf%2C+L+H%3BCarrasquillo%2C+J+A%3BPaik%2C+C%3BGansow%2C+O%3BWhatley%2C+M%3BPearson%2C+D%3BWebber%2C+K%3BHamilton%2C+M%3BAllegra%2C+C%3BBrechbiel%2C+M%3BWillingham%2C+M+C%3BPastan%2C+I&rft.aulast=Pai-Scherf&rft.aufirst=L&rft.date=2000-05-01&rft.volume=6&rft.issue=5&rft.spage=1720&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 - 2000-08-29 N1 - Date created - 2000-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Developmental profiles of growth-associated protein (Gap43), Ngfb, Bndf and Ntf4 mRNA levels in the rat forebrain after exposure to 60 Hz magnetic fields. AN - 71115347; 10790287 AB - Fischer 344 rats were exposed to 60 Hz magnetic fields (EMFs) during gestation and lactation. Rats received continuous exposure to 2-, 200- or 1000-microT magnetic fields for 18.5 h per day, 7 days a week, or sham exposure (sham controls). During postnatal development, on postnatal days 1, 3, 6, 9, 15 and 20, forebrain tissue from male pups was examined for alterations in mRNA level for developmentally regulated central nervous system-specific proteins. Alterations in these factors during critical periods of development could result in alterations in the final neural network. Gap43 (growth-associated protein 43) mRNA was measured by Northern hybridization as a developmental indicator of axonal growth during the development of the neuron. Between postnatal days 1 and 9, detectable levels of Gap43 mRNA displayed a similar pattern across all sham control and exposure groups. In addition to Gap43, mRNA levels for the nervous system-specific growth factors ciliary neurotrophic factor (Cntf), brain-derived neurotrophic factor (Bdnf), beta nerve growth factor (Ngfb), neurotrophin-3 (Ntf3), and neurotrophin-4 (Ntf4) were examined by RNase protection assay. While there is public concern for developmental neurotoxicity associated with exposure to EMFs, these data, generated from animals exposed to 2-, 200- or 1000-microT magnetic fields during both gestational and lactational periods of development, suggest that under these conditions no significant alterations in these critical factors for brain development occur. JF - Radiation research AU - Harry, G J AU - Bartenbach, M AU - Haines, W AU - Bruccoleri, A AD - Neurotoxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 642 EP - 647 VL - 153 IS - 5 Pt 2 SN - 0033-7587, 0033-7587 KW - Brain-Derived Neurotrophic Factor KW - 0 KW - GAP-43 Protein KW - Gdnf protein, rat KW - Glial Cell Line-Derived Neurotrophic Factor KW - Nerve Growth Factors KW - Nerve Tissue Proteins KW - Neurotrophin 3 KW - RNA, Messenger KW - Nerve Growth Factor KW - 9061-61-4 KW - Ribonucleases KW - EC 3.1.- KW - neurotrophin 4 KW - P658DCA9XD KW - Index Medicus KW - Space life sciences KW - Animals, Suckling KW - Animals KW - Nerve Growth Factors -- metabolism KW - Neurotrophin 3 -- metabolism KW - Nerve Growth Factor -- metabolism KW - RNA, Messenger -- analysis KW - Dose-Response Relationship, Radiation KW - Nerve Tissue Proteins -- genetics KW - Ribonucleases -- metabolism KW - Brain-Derived Neurotrophic Factor -- genetics KW - Rats KW - Neurotrophin 3 -- genetics KW - Animals, Newborn KW - Rats, Sprague-Dawley KW - Rats, Inbred F344 KW - Brain-Derived Neurotrophic Factor -- metabolism KW - Nerve Growth Factors -- genetics KW - Nerve Tissue Proteins -- metabolism KW - Nerve Growth Factor -- genetics KW - Female KW - Male KW - Maternal Exposure -- adverse effects KW - GAP-43 Protein -- metabolism KW - Prosencephalon -- metabolism KW - Prosencephalon -- growth & development KW - Electromagnetic Fields -- adverse effects KW - Prosencephalon -- radiation effects KW - GAP-43 Protein -- genetics KW - Environmental Exposure -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71115347?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Developmental+profiles+of+growth-associated+protein+%28Gap43%29%2C+Ngfb%2C+Bndf+and+Ntf4+mRNA+levels+in+the+rat+forebrain+after+exposure+to+60+Hz+magnetic+fields.&rft.au=Harry%2C+G+J%3BBartenbach%2C+M%3BHaines%2C+W%3BBruccoleri%2C+A&rft.aulast=Harry&rft.aufirst=G&rft.date=2000-05-01&rft.volume=153&rft.issue=5+Pt+2&rft.spage=642&rft.isbn=&rft.btitle=&rft.title=Radiation+research&rft.issn=00337587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-09 N1 - Date created - 2000-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug-induced hemolysis: cefotetan-dependent hemolytic anemia mimicking an acute intravascular immune transfusion reaction. AN - 71112947; 10815791 AB - Numerous cases of drug-induced hemolytic anemia have been described in patients treated with penicillin or cephalosporin. Second and third generation cephalosporins are more commonly implicated in hemolytic reactions than first generation cephalosporins. We report a case of severe cefotetan-induced hemolytic anemia in a previously healthy 46-year-old woman undergoing an elective hysterectomy. The patient received 2 g of intravenous cefotetan intraoperatively and subsequently at 12 and 24 h post-operatively. She complained of diarrhea and fever on the third post-operative day and was seen in her gynecologist's office on the fifth post-operative day (hemoglobin = 10.5 g/dL). On the seventh post-operative day, she complained of fever and soreness around the suprapubic catheter site and was given a prescription for 500 mg oral cephalexin four times a day. The next day she was seen in the gynecologist's office and reported feeling better. Ten days after the operation her fatigue worsened and her hemoglobin was 4.8 g/dL. She was transfused with 3 units of packed red blood cells (PRBC) and was given 1 g of cefotetan intravenously. During the transfusion of the second unit of PRBC nursing staff observed gross hemoglobinuria and she subsequently developed acute renal failure. Laboratory chemistry parameters were consistent with severe acute hemolysis. The patient's direct antiglobulin test was reactive and her serum reacted with cefotetan-coated red blood cells (RBCs) and serum plus soluble cefotetan reacted with untreated RBCs. The titration endpoint of the serum against cefotetan-coated RBCs was 40,960, while the serum plus soluble cefotetan against uncoated RBCs was 2,560. This case of severe cefotetan-induced hemolysis was complicated by an acute hemolytic event that occurred during the transfusion of PRBC. Clinical and transfusion service staff must consider drug-induced hemolysis in the differential diagnosis of acute anemia. JF - American journal of hematology AU - Stroncek, D AU - Procter, J L AU - Johnson, J AD - Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1184, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 67 EP - 70 VL - 64 IS - 1 SN - 0361-8609, 0361-8609 KW - Cephamycins KW - 0 KW - Cefotetan KW - 48SPP0PA9Q KW - Index Medicus KW - Diagnosis, Differential KW - Blood Group Incompatibility -- complications KW - Humans KW - Postoperative Complications -- prevention & control KW - Middle Aged KW - Female KW - Disseminated Intravascular Coagulation -- etiology KW - Anemia, Hemolytic -- chemically induced KW - Disseminated Intravascular Coagulation -- immunology KW - Blood Transfusion -- adverse effects KW - Cephamycins -- administration & dosage KW - Anemia, Hemolytic -- diagnosis KW - Cefotetan -- adverse effects KW - Cefotetan -- administration & dosage KW - Cephamycins -- adverse effects KW - Disseminated Intravascular Coagulation -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71112947?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+hematology&rft.atitle=Drug-induced+hemolysis%3A+cefotetan-dependent+hemolytic+anemia+mimicking+an+acute+intravascular+immune+transfusion+reaction.&rft.au=Stroncek%2C+D%3BProcter%2C+J+L%3BJohnson%2C+J&rft.aulast=Stroncek&rft.aufirst=D&rft.date=2000-05-01&rft.volume=64&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=American+journal+of+hematology&rft.issn=03618609&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-31 N1 - Date created - 2000-05-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cigarette smoking, N-acetyltransferase 2 acetylation status, and bladder cancer risk: a case-series meta-analysis of a gene-environment interaction. AN - 71112907; 10815690 AB - Tobacco use is an established cause of bladder cancer. The ability to detoxify aromatic amines, which are present in tobacco and are potent bladder carcinogens, is compromised in persons with the N-acetyltransferase 2 slow acetylation polymorphism. The relationship of cigarette smoking with bladder cancer risk therefore has been hypothesized to be stronger among slow acetylators. The few studies to formally explore such a possibility have produced inconsistent results, however. To assess this potential gene-environment interaction in as many bladder cancer studies as possible and to summarize results, we conducted a meta-analysis using data from 16 bladder cancer studies conducted in the general population (n = 1999 cases), Most had been conducted in European countries. Because control subjects were unavailable for a number of these studies, we used a case-series design, which can be used to assess multiplicative gene-environment interaction without inclusion of control subjects. A case-series interaction odds ratio (OR) > 1.0 indicates that the relationship of cigarette smoking and bladder cancer risk is stronger among slow acetylators as compared with rapid acetylators. We observed an interaction between smoking and N-acetyltransferase 2 slow acetylation (OR, 1.3; 95% confidence interval, 1.0-1.6) that was somewhat stronger when analyses were restricted to studies conducted in Europe (OR, 1.5; confidence interval, 1.1-1.9), a pooling that included nearly 80% of the collected data. Using the predominantly male European study population and assuming a 2.5-fold elevation in bladder cancer risk from smoking, we estimated that the population attributable risk percent was 35% for slow acetylators who had ever smoked and 13% for rapid acetylators who had ever smoked. These results suggest that the relationship of smoking and bladder cancer is stronger among slow acetylators than among rapid acetylators. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Marcus, P M AU - Hayes, R B AU - Vineis, P AU - Garcia-Closas, M AU - Caporaso, N E AU - Autrup, H AU - Branch, R A AU - Brockmöller, J AU - Ishizaki, T AU - Karakaya, A E AU - Ladero, J M AU - Mommsen, S AU - Okkels, H AU - Romkes, M AU - Roots, I AU - Rothman, N AD - Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 461 EP - 467 VL - 9 IS - 5 SN - 1055-9965, 1055-9965 KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - Index Medicus KW - Phenotype KW - Genotype KW - Acetylation KW - Aged, 80 and over KW - Risk Factors KW - Humans KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Male KW - Female KW - Urinary Bladder Neoplasms -- epidemiology KW - Urinary Bladder Neoplasms -- genetics KW - Urinary Bladder Neoplasms -- enzymology KW - Smoking -- adverse effects KW - Arylamine N-Acetyltransferase -- metabolism KW - Arylamine N-Acetyltransferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71112907?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Cigarette+smoking%2C+N-acetyltransferase+2+acetylation+status%2C+and+bladder+cancer+risk%3A+a+case-series+meta-analysis+of+a+gene-environment+interaction.&rft.au=Marcus%2C+P+M%3BHayes%2C+R+B%3BVineis%2C+P%3BGarcia-Closas%2C+M%3BCaporaso%2C+N+E%3BAutrup%2C+H%3BBranch%2C+R+A%3BBrockm%C3%B6ller%2C+J%3BIshizaki%2C+T%3BKarakaya%2C+A+E%3BLadero%2C+J+M%3BMommsen%2C+S%3BOkkels%2C+H%3BRomkes%2C+M%3BRoots%2C+I%3BRothman%2C+N&rft.aulast=Marcus&rft.aufirst=P&rft.date=2000-05-01&rft.volume=9&rft.issue=5&rft.spage=461&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-24 N1 - Date created - 2000-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quantitative grading of rat esophageal carcinogenesis using computer-assisted image tile analysis. AN - 71109956; 10815694 AB - Our objective was to grade, by computer-assisted quantitative image tile analysis, the intraepithelial neoplasia (also called dysplasia) that develops in esophagi of rats given N-nitrosomethybenzylamine (NMBA) for 5 weeks. To perform image tile analysis, the computer divides the video image of the neoplastic epithelium into a row of contiguous small rectangular images, or "tiles," 84 x 292 microm in size, and quantitatively measures four selected tissue features within each image tile. The computer then calculates a tile grade for each image tile as the weighted sum of the four feature measurements, transformed into statistical Z-scores, the weights being determined by Fisher linear discriminant analysis of 300 tile grades of the neoplastic epithelium referenced to the mean tile grade (MTG) of 300 image tiles of normal epithelium. The two grading parameters, MTG and the percentage of tile grades exceeding the MTG of normal epithelium by >4 SD units (%TG>4SD), were validated as endpoints for screening chemopreventive agents in the rat NMBA-induced esophageal carcinogenesis model in two ways: (a) after NMBA treatment, %TG>4SD developed in parallel with tumor incidence and tumor multiplicity (number of papillomas/tumor-bearing rat); and (b) placing the chemopreventive phenethylisothiocyanate in the food of NMBA-treated rats produced parallel reductions in MTG, tumor incidence, and tumor multiplicity. Both MTG and %TG>4SD, measured by quantitative image tile analysis, are sensitive and objective continuous parametric response variables expressed to three significant figures, with wide dynamic range, that may be evaluated by t tests to compare tissue neoplastic changes before and after treatment with a chemopreventive agent. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Boone, C W AU - Stoner, G D AU - Bacus, J V AU - Kagan, V AU - Morse, M A AU - Kelloff, G J AU - Bacus, J W AD - Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland 20892-7322, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 495 EP - 500 VL - 9 IS - 5 SN - 1055-9965, 1055-9965 KW - Anticarcinogenic Agents KW - 0 KW - Carcinogens KW - Isothiocyanates KW - phenethyl isothiocyanate KW - 6U7TFK75KV KW - nitrosobenzylmethylamine KW - 937-40-6 KW - Dimethylnitrosamine KW - M43H21IO8R KW - Index Medicus KW - Administration, Oral KW - Neoplasms, Multiple Primary -- etiology KW - Animals KW - Neoplasms, Multiple Primary -- prevention & control KW - Anticarcinogenic Agents -- therapeutic use KW - Neoplasms, Multiple Primary -- pathology KW - Dimethylnitrosamine -- toxicity KW - Isothiocyanates -- therapeutic use KW - Carcinogens -- toxicity KW - Epithelium -- drug effects KW - Rats KW - Rats, Inbred F344 KW - Dimethylnitrosamine -- analogs & derivatives KW - Incidence KW - Epithelium -- pathology KW - Time Factors KW - Male KW - Esophageal Neoplasms -- prevention & control KW - Image Interpretation, Computer-Assisted -- methods KW - Esophageal Neoplasms -- etiology KW - Esophageal Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71109956?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Quantitative+grading+of+rat+esophageal+carcinogenesis+using+computer-assisted+image+tile+analysis.&rft.au=Boone%2C+C+W%3BStoner%2C+G+D%3BBacus%2C+J+V%3BKagan%2C+V%3BMorse%2C+M+A%3BKelloff%2C+G+J%3BBacus%2C+J+W&rft.aulast=Boone&rft.aufirst=C&rft.date=2000-05-01&rft.volume=9&rft.issue=5&rft.spage=495&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-24 N1 - Date created - 2000-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Altered stationary-phase response in a Borrelia burgdorferi rpoS mutant. AN - 71108183; 10781562 AB - The homolog of the chromosomally encoded stationary-phase sigma factor RpoS in Borrelia burgdorferi was inactivated using gyrB(r) as a selectable marker. Two-dimensional nonequilibrium pH gradient electrophoresis of stationary-phase cell lysates identified at least 11 differences between the protein profiles of the rpoS mutant and wild-type organisms. Wild-type B. burgdorferi had a growth phase-dependent resistance to 1 N NaCl, similar to the stationary-phase response reported for other bacteria. The B. burgdorferi rpoS mutant strain was less resistant to osmotic stress in stationary phase than the isogenic rpoS wild-type organism. The results indicate that the B. burgdorferi rpoS homolog influences protein composition and participates in stationary-phase-dependent osmotic resistance. This rpoS mutant will be useful for studying regulation of gene expression in response to changing environmental conditions. JF - Journal of bacteriology AU - Elias, A F AU - Bono, J L AU - Carroll, J A AU - Stewart, P AU - Tilly, K AU - Rosa, P AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA. aelias@niaid.nih.gov Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 2909 EP - 2918 VL - 182 IS - 10 SN - 0021-9193, 0021-9193 KW - Bacterial Proteins KW - 0 KW - Sigma Factor KW - sigma factor KatF protein, Bacteria KW - Sodium Chloride KW - 451W47IQ8X KW - Index Medicus KW - Genes, Bacterial KW - Transcription, Genetic KW - Osmosis KW - Mutagenesis KW - Sigma Factor -- genetics KW - Bacterial Proteins -- genetics KW - Borrelia burgdorferi Group -- growth & development KW - Borrelia burgdorferi Group -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71108183?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Altered+stationary-phase+response+in+a+Borrelia+burgdorferi+rpoS+mutant.&rft.au=Elias%2C+A+F%3BBono%2C+J+L%3BCarroll%2C+J+A%3BStewart%2C+P%3BTilly%2C+K%3BRosa%2C+P&rft.aulast=Elias&rft.aufirst=A&rft.date=2000-05-01&rft.volume=182&rft.issue=10&rft.spage=2909&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 - 2000-06-12 N1 - Date created - 2000-06-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Annu Rev Entomol. 1991;36:587-609 [2006870] Photochem Photobiol. 1970 Jul;12(1):1-8 [4926413] J Bacteriol. 1992 Jan;174(1):1-7 [1729202] Infect Immun. 1992 Nov;60(11):4662-72 [1398980] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11978-82 [1465428] J Infect Dis. 1993 Jan;167(1):165-72 [8418163] Cell. 1993 Jan 29;72(2):165-8 [8425216] Am J Pathol. 1993 Sep;143(3):959-71 [8362988] Infect Immun. 1993 Dec;61(12):5097-105 [8225587] Annu Rev Microbiol. 1993;47:855-74 [8257118] Infect Immun. 1994 Aug;62(8):3213-21 [8039891] J Bacteriol. 1994 Sep;176(17):5378-84 [8071215] J Bacteriol. 1994 Nov;176(22):6852-60 [7961444] Annu Rev Microbiol. 1994;48:53-80 [7826018] Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2909-13 [7708747] Infect Immun. 1995 May;63(5):1840-7 [7729893] Infect Immun. 1995 Nov;63(11):4535-9 [7591099] Methods Mol Biol. 1995;47:253-9 [7550741] Am J Trop Med Hyg. 1995 Oct;53(4):397-404 [7485694] J Exp Med. 1996 Jan 1;183(1):261-9 [8551229] Infect Immun. 1996 Feb;64(2):392-8 [8550182] J Bacteriol. 1996 Oct;178(20):5946-53 [8830691] J Bacteriol. 1997 Jan;179(1):217-27 [8982001] Infect Immun. 1997 Apr;65(4):1165-71 [9119447] MMWR Morb Mortal Wkly Rep. 1997 Jun 13;46(23):531-5 [9191035] Mol Microbiol. 1997 Jul;25(2):361-73 [9282748] Nature. 1997 Dec 11;390(6660):580-6 [9403685] J Bacteriol. 1998 Feb;180(4):773-84 [9473029] Microbiology. 1998 Apr;144 ( Pt 4):1033-44 [9579077] J Biol Chem. 1975 May 25;250(10):4007-21 [236308] Anal Biochem. 1978 Jun 15;87(1):206-10 [98070] Infect Immun. 1978 Aug;21(2):575-84 [211086] Photochem Photobiol. 1979 Dec;30(6):667-76 [394165] Science. 1982 Jun 18;216(4552):1317-9 [7043737] N Engl J Med. 1983 Mar 31;308(13):733-40 [6828118] Infect Immun. 1983 Aug;41(2):795-804 [6192088] Yale J Biol Med. 1984 Jul-Aug;57(4):521-5 [6393604] Science. 1985 Dec 20;230(4732):1350-4 [2999980] Cold Spring Harb Symp Quant Biol. 1986;51 Pt 1:263-73 [3472723] J Bacteriol. 1988 Sep;170(9):3910-4 [3045081] Ann N Y Acad Sci. 1988;539:4-15 [3056204] Science. 1989 Feb 17;243(4893):916-22 [2537530] Microbiol Rev. 1989 Jun;53(2):210-30 [2569162] N Engl J Med. 1989 Aug 31;321(9):586-96 [2668764] J Infect Dis. 1989 Dec;160(6):1018-29 [2584750] Infect Immun. 1990 Apr;58(4):1038-42 [2318529] Am J Trop Med Hyg. 1990 Apr;42(4):352-7 [2331043] J Bacteriol. 1990 May;172(5):2779-81 [2185233] Infect Immun. 1990 Jul;58(7):2186-91 [2194963] Infect Immun. 1991 Apr;59(4):1572-5 [2004832] Infect Immun. 1999 Jul;67(7):3181-7 [10377088] J Bacteriol. 1999 Aug;181(16):4879-89 [10438758] Mol Microbiol. 1998 Aug;29(4):1039-51 [9767572] Infect Immun. 1998 Nov;66(11):5119-24 [9784512] FEMS Microbiol Rev. 1998 Sep;22(3):127-50 [9818380] J Bacteriol. 1998 Dec;180(23):6203-6 [9829928] J Bacteriol. 1991 Jul;173(13):4188-94 [2061293] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exposure assessment in the occupational setting. AN - 71107675; 10808266 AB - Exposure assessment, the first step in risk assessment, has traditionally been performed for a variety of purposes. These include compliance determinations; management of specific programs that are implemented by comparison with an occupational exposure limit (such as medical surveillance, training, and respiratory protection programs); task/source investigations for determination of exposure control strategies; epidemiologic studies; worker compensation/toxic tort cases; health complaint or problem investigations; risk assessment and management; and evaluation of future changes in the workplace (e.g., introduction of a new chemical). Each purpose requires slightly different approaches, but there are also many similarities. The goal of this paper is to identify a general approach to assessing exposures that can be used for all purposes with only slight modifications. Five components of exposure assessments are identified: collection of data, identification of the hazard, selection of exposure metrics, definition of exposure groups and estimation of the exposures. The characteristics of these components for each type of assessment are discussed. From this review, it is clear that there is substantial overlap across the types of assessment. A single exposure assessment program is suggested that encompasses all the needs of these assessments and incorporates assessment of exposures for an entire workforce at a site at minimal cost by using prediction models and validation with measurements. JF - Applied occupational and environmental hygiene AU - Stewart, P AU - Stenzel, M AD - National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 435 EP - 444 VL - 15 IS - 5 SN - 1047-322X, 1047-322X KW - Hazardous Substances KW - 0 KW - Index Medicus KW - Humans KW - Occupational Health KW - Risk Assessment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71107675?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+occupational+and+environmental+hygiene&rft.atitle=Exposure+assessment+in+the+occupational+setting.&rft.au=Stewart%2C+P%3BStenzel%2C+M&rft.aulast=Stewart&rft.aufirst=P&rft.date=2000-05-01&rft.volume=15&rft.issue=5&rft.spage=435&rft.isbn=&rft.btitle=&rft.title=Applied+occupational+and+environmental+hygiene&rft.issn=1047322X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-16 N1 - Date created - 2000-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Shared features of transcription: mutational analysis of the eosinophil/basophil Charcot-Leyden crystal protein gene promoter. AN - 71105528; 10811010 AB - The lineage-specific Charcot-Leyden crystal (CLC) protein is found in human eosinophils and basophils where it comprises 7-10% of the cellular protein content. Previous work from our laboratory has identified the motif GGAGA[A/G] as a powerful enhancer of gene transcription ill two eosinophil ribonuclease genes. To evaluate a potentially larger role for this motif in the transcriptional regulation of eosinophil genes, we have isolated 1504 nucleotides 5' to the transcriptional start site of the gene encoding CLC protein and identified a functionally active promoter that includes three distinct copies of the GGAGAA motif. Destruction of only one of the three motifs by site-directed mutagenesis resulted in loss of promoter activity (73 +/- 6% reduction), suggesting that this core motif is necessary but not sufficient to support enhanced transcriptional activity. Sequence comparisons and site-specific mutagenesis has permitted further delineation of this enhancer element which, as a result of this work, is now defined as GGAGA[A/G]NNNA. Electromobility shift assays demonstrated specific binding of nuclear protein(s) from an eosinophilic clone-15 nuclear extract to this extended motif. Similar analysis of a GATA-1 binding site demonstrated enhancer activity, with mutagenesis resulting in a 94 +/- 1.4% reduction in activity, whereas the AML1 site functioned as a gene silencer. JF - Journal of leukocyte biology AU - Dyer, K D AU - Rosenberg, H F AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1886, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 691 EP - 698 VL - 67 IS - 5 SN - 0741-5400, 0741-5400 KW - Glycoproteins KW - 0 KW - Transcription Factors KW - Ribonucleases KW - EC 3.1.- KW - Lysophospholipase KW - EC 3.1.1.5 KW - lysolecithin acylhydrolase KW - Index Medicus KW - Ribonucleases -- blood KW - Base Sequence KW - Sequence Alignment KW - Transcription Factors -- metabolism KW - Humans KW - DNA Mutational Analysis KW - Ribonucleases -- genetics KW - Molecular Sequence Data KW - Consensus Sequence KW - Sequence Homology, Amino Acid KW - Binding Sites KW - Promoter Regions, Genetic KW - Glycoproteins -- blood KW - Eosinophils -- metabolism KW - Transcription, Genetic KW - Glycoproteins -- genetics KW - Basophils -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71105528?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+leukocyte+biology&rft.atitle=Shared+features+of+transcription%3A+mutational+analysis+of+the+eosinophil%2Fbasophil+Charcot-Leyden+crystal+protein+gene+promoter.&rft.au=Dyer%2C+K+D%3BRosenberg%2C+H+F&rft.aulast=Dyer&rft.aufirst=K&rft.date=2000-05-01&rft.volume=67&rft.issue=5&rft.spage=691&rft.isbn=&rft.btitle=&rft.title=Journal+of+leukocyte+biology&rft.issn=07415400&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-01 N1 - Date created - 2000-06-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estrogen replacement therapy and MRI-demonstrated cerebral infarcts, white matter changes, and brain atrophy in older women: the Cardiovascular Health Study. AN - 71105074; 10811537 AB - We studied the relationship between the use of estrogen replacement therapy (ERT) and cerebral magnetic resonance imaging (MRI) abnormalities among older women. A population-based prospective study (Cardiovascular Health Study). Four regions in the United States. A total of 2133 (62.9% of the eligible) women aged 65 to 95 years (mean age 74.8), on whom MRI was performed in 1992-1994. Presence of global brain atrophy, white matter changes, small infarct-like lesion (ILL) ( or =3 mm, mostly small and asymptomatic), and cognitive function as measured by Mini-Mental State Exam (MMSE), and by ERT use (current/past/never), adjusted for a number of socioeconomic, lifestyle, and reproductive covariates. Current use of ERT was reported by 15% and past use by another 23% of participants; 35% of all women had MRI infarcts. The prevalence of MRI infarcts did not differ in current or past users from those who had never used ERT (nonusers). Bifrontal distance, the largest distance between frontal horns, and the size of ventricles were larger among current ERT users compared to past users or nonusers (P (trend) = .01), adjusted for all other covariates, but no dose-response relationship to current or past ERT use was found. Duration of estrogen use was not associated with any atrophy measure. Cortical atrophy measure, sulcal widening, or white matter disease did not differ significantly by ERT use or duration of use. Central measures of atrophy, bifrontal distance, and ventricular size were significantly associated with cognition as measured by MMSE. Current ERT users had much more clinically significant central atrophy than nonusers, but the implications remained unclear. JF - Journal of the American Geriatrics Society AU - Luoto, R AU - Manolio, T AU - Meilahn, E AU - Bhadelia, R AU - Furberg, C AU - Cooper, L AU - Kraut, M AD - National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 467 EP - 472 VL - 48 IS - 5 SN - 0002-8614, 0002-8614 KW - Index Medicus KW - Magnetic Resonance Imaging KW - Humans KW - Aged KW - Atrophy -- chemically induced KW - Life Style KW - Prospective Studies KW - Aged, 80 and over KW - Social Class KW - United States -- epidemiology KW - Atrophy -- epidemiology KW - Female KW - Intelligence Tests KW - Prevalence KW - Brain Infarction -- epidemiology KW - Brain Infarction -- chemically induced KW - Estrogen Replacement Therapy -- adverse effects KW - Brain -- pathology KW - Brain -- drug effects KW - Population Surveillance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71105074?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Geriatrics+Society&rft.atitle=Estrogen+replacement+therapy+and+MRI-demonstrated+cerebral+infarcts%2C+white+matter+changes%2C+and+brain+atrophy+in+older+women%3A+the+Cardiovascular+Health+Study.&rft.au=Luoto%2C+R%3BManolio%2C+T%3BMeilahn%2C+E%3BBhadelia%2C+R%3BFurberg%2C+C%3BCooper%2C+L%3BKraut%2C+M&rft.aulast=Luoto&rft.aufirst=R&rft.date=2000-05-01&rft.volume=48&rft.issue=5&rft.spage=467&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Geriatrics+Society&rft.issn=00028614&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-25 N1 - Date created - 2000-05-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Am Geriatr Soc. 2000 May;48(5):588-9 [10811555] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of ritonavir on the pharmacokinetics of meperidine and normeperidine. AN - 71103028; 10809341 AB - To determine the effects of ritonavir on the pharmacokinetics of meperidine and normeperidine. Open-label, crossover, pharmacokinetic study. United States government research hospital. Eight healthy volunteers who tested negative for the human immunodeficiency virus. Subjects received oral meperidine 50 mg and had serial blood samples collected for 48 hours. They then received ritonavir 500 mg twice/day for 10 days, followed by administration of a second 50-mg meperidine dose and collection of serial samples. Plasma samples were assayed for meperidine, normeperidine, and ritonavir. Meperidine's area under the curve (AUC) decreased in all subjects by a mean of 67+/-4% in the presence of ritonavir (p<0.005). Mean +/- SD maximum concentration was decreased from 126+/-47 to 51+/-21 ng/ml. Normeperidine's mean AUC was increased 47%, suggesting induction of hepatic metabolism. Meperidine's AUC is significantly reduced, not increased, by concomitant ritonavir. Based on these findings, the risk of narcotic-related adverse effects from this combination appears to be minimal. However, increased concentrations of normeperidine suggest a potential for toxicity with increased dosages or long-term therapy. JF - Pharmacotherapy AU - Piscitelli, S C AU - Kress, D R AU - Bertz, R J AU - Pau, A AU - Davey, R AD - Pharmacy Department, Clinical Center and Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 549 EP - 553 VL - 20 IS - 5 SN - 0277-0008, 0277-0008 KW - Analgesics, Opioid KW - 0 KW - Cholinesterase Inhibitors KW - HIV Protease Inhibitors KW - Meperidine KW - 9E338QE28F KW - normeperidine KW - JG096PMW2N KW - Ritonavir KW - O3J8G9O825 KW - Index Medicus KW - AIDS/HIV KW - Drug Interactions KW - Area Under Curve KW - Humans KW - Adult KW - Cross-Over Studies KW - Confidence Intervals KW - Male KW - Female KW - Ritonavir -- blood KW - Analgesics, Opioid -- blood KW - Meperidine -- pharmacokinetics KW - Ritonavir -- pharmacokinetics KW - Meperidine -- blood KW - Meperidine -- analogs & derivatives KW - HIV Protease Inhibitors -- blood KW - HIV Protease Inhibitors -- pharmacokinetics KW - Analgesics, Opioid -- pharmacokinetics KW - Cholinesterase Inhibitors -- pharmacokinetics KW - Cholinesterase Inhibitors -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71103028?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+effect+of+ritonavir+on+the+pharmacokinetics+of+meperidine+and+normeperidine.&rft.au=Piscitelli%2C+S+C%3BKress%2C+D+R%3BBertz%2C+R+J%3BPau%2C+A%3BDavey%2C+R&rft.aulast=Piscitelli&rft.aufirst=S&rft.date=2000-05-01&rft.volume=20&rft.issue=5&rft.spage=549&rft.isbn=&rft.btitle=&rft.title=Pharmacotherapy&rft.issn=02770008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-10 N1 - Date created - 2000-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cadmium induces c-myc, p53, and c-jun expression in normal human prostate epithelial cells as a prelude to apoptosis. AN - 71098079; 10799339 AB - Cadmium is a suspected human prostatic carcinogen shown to induce prostatic tumors and proliferative lesions in rats. The carcinogenic mechanism of cadmium is unknown, but its poor mutagenicity points toward an epigenetic mechanism. Here we studied the effect of cadmium on genes involved in growth regulation of prostate epithelial cell using the human prostate epithelial cell line RWPE-1, which is immortalized but not transformed and is androgen-responsive. Treatment with 10 microM cadmium resulted in transient increases in c-myc and p53 mRNA levels that peaked at 2-fold and 1.4-fold, respectively, compared to control after 2 h. In contrast, c-jun mRNA levels were increased >3-fold after 2, 4, and 6 h and 20-fold after 24 h. DNA synthesis decreased after 24 h of cadmium exposure. Further study revealed a significant increase in apoptosis after 48 h of cadmium exposure. However, approximately 35% of the cells were still viable and appeared normal, indicating this subpopulation was more resistant to cadmium. Furthermore, these resistant cells had 2.5-fold more metallothionein than untreated control cells. This suggests that cadmium could act to select for apoptotic-defective cells in vivo, thereby increasing the likelihood of tumor formation. This work represents the first description of cadmium affecting oncogene expression in a human cell model of a potential in vivo target site of cadmium carcinogenesis. Copyright 2000 Academic Press. JF - Toxicology and applied pharmacology AU - Achanzar, W E AU - Achanzar, K B AU - Lewis, J G AU - Webber, M M AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, National Cancer Institute at National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA. Y1 - 2000/05/01/ PY - 2000 DA - 2000 May 01 SP - 291 EP - 300 VL - 164 IS - 3 SN - 0041-008X, 0041-008X KW - Proliferating Cell Nuclear Antigen KW - 0 KW - RNA, Messenger KW - Cadmium KW - 00BH33GNGH KW - Metallothionein KW - 9038-94-2 KW - Index Medicus KW - Epithelial Cells -- metabolism KW - Epithelial Cells -- cytology KW - RNA, Messenger -- metabolism KW - Cell Survival -- drug effects KW - Proliferating Cell Nuclear Antigen -- genetics KW - Humans KW - Cell Line, Transformed KW - Metallothionein -- metabolism KW - Male KW - Gene Expression -- drug effects KW - Cadmium -- pharmacology KW - Apoptosis KW - Genes, p53 -- genetics KW - Prostate -- metabolism KW - Prostate -- cytology KW - Genes, myc -- genetics KW - Genes, jun -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71098079?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Cadmium+induces+c-myc%2C+p53%2C+and+c-jun+expression+in+normal+human+prostate+epithelial+cells+as+a+prelude+to+apoptosis.&rft.au=Achanzar%2C+W+E%3BAchanzar%2C+K+B%3BLewis%2C+J+G%3BWebber%2C+M+M%3BWaalkes%2C+M+P&rft.aulast=Achanzar&rft.aufirst=W&rft.date=2000-05-01&rft.volume=164&rft.issue=3&rft.spage=291&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-07 N1 - Date created - 2000-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High-resolution FRET microscopy of cholera toxin B-subunit and GPI-anchored proteins in cell plasma membranes. AN - 71088409; 10793141 AB - "Lipid rafts" enriched in glycosphingolipids (GSL), GPI-anchored proteins, and cholesterol have been proposed as functional microdomains in cell membranes. However, evidence supporting their existence has been indirect and controversial. In the past year, two studies used fluorescence resonance energy transfer (FRET) microscopy to probe for the presence of lipid rafts; rafts here would be defined as membrane domains containing clustered GPI-anchored proteins at the cell surface. The results of these studies, each based on a single protein, gave conflicting views of rafts. To address the source of this discrepancy, we have now used FRET to study three different GPI-anchored proteins and a GSL endogenous to several different cell types. FRET was detected between molecules of the GSL GM1 labeled with cholera toxin B-subunit and between antibody-labeled GPI-anchored proteins, showing these raft markers are in submicrometer proximity in the plasma membrane. However, in most cases FRET correlated with the surface density of the lipid raft marker, a result inconsistent with significant clustering in microdomains. We conclude that in the plasma membrane, lipid rafts either exist only as transiently stabilized structures or, if stable, comprise at most a minor fraction of the cell surface. JF - Molecular biology of the cell AU - Kenworthy, A K AU - Petranova, N AU - Edidin, M AD - Department of Biology, The Johns Hopkins University, Baltimore, Maryland 21218, USA. kenworta@mail.nih.gov Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 1645 EP - 1655 VL - 11 IS - 5 SN - 1059-1524, 1059-1524 KW - Glycosphingolipids KW - 0 KW - Glycosylphosphatidylinositols KW - Membrane Proteins KW - G(M1) Ganglioside KW - 37758-47-7 KW - Cholera Toxin KW - 9012-63-9 KW - Index Medicus KW - Rats KW - G(M1) Ganglioside -- analysis KW - Animals KW - Energy Transfer KW - Humans KW - Glycosphingolipids -- analysis KW - Microscopy -- methods KW - Cholera Toxin -- analysis KW - Glycosylphosphatidylinositols -- analysis KW - Cell Membrane -- chemistry KW - Membrane Proteins -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71088409?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=High-resolution+FRET+microscopy+of+cholera+toxin+B-subunit+and+GPI-anchored+proteins+in+cell+plasma+membranes.&rft.au=Kenworthy%2C+A+K%3BPetranova%2C+N%3BEdidin%2C+M&rft.aulast=Kenworthy&rft.aufirst=A&rft.date=2000-05-01&rft.volume=11&rft.issue=5&rft.spage=1645&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 - 2000-08-03 N1 - Date created - 2000-08-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Curr Opin Struct Biol. 1997 Aug;7(4):528-32 [9266174] J Membr Biol. 1997 Sep 15;159(2):137-47 [9307440] Histochem Cell Biol. 1997 Sep;108(3):211-20 [9342615] Biochemistry. 1997 Oct 14;36(41):12449-58 [9376349] Biophys J. 1980 Dec;32(3):1023-35 [7260308] Biophys J. 1979 Nov;28(2):197-210 [262548] Curr Biol. 1998 Feb 12;8(4):R114-6 [9501972] J Cell Biol. 1998 Mar 23;140(6):1357-67 [9508769] J Cell Biol. 1998 Apr 6;141(1):85-99 [9531550] J Biochem. 1998 Apr;123(4):579-86 [9538246] J Cell Biol. 1998 May 18;141(4):905-15 [9585410] J Cell Biol. 1998 May 18;141(4):917-27 [9585411] J Cell Biol. 1998 May 18;141(4):929-42 [9585412] J Cell Biol. 1998 Jul 13;142(1):69-84 [9660864] Biophys J. 1998 Aug;75(2):1117-30 [9675213] Eur Biophys J. 1998;27(4):377-89 [9691467] Nature. 1998 Aug 20;394(6695):798-801 [9723621] Annu Rev Biochem. 1998;67:199-225 [9759488] Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12312-6 [9770483] Annu Rev Cell Dev Biol. 1998;14:111-36 [9891780] Trends Cell Biol. 1999 Feb;9(2):57-60 [10087619] Science. 1999 Mar 26;283(5410):2085-9 [10092232] Trends Cell Biol. 1999 Mar;9(3):87-91 [10201072] Biochim Biophys Acta. 1999 Jul 8;1450(3):177-90 [10395933] Methods Mol Biol. 1999;116:37-49 [10399144] Immunol Today. 1999 Aug;20(8):356-61 [10431155] FEBS Lett. 1981 Jun 1;128(1):103-7 [6268444] Nature. 1982 Apr 15;296(5858):651-3 [7070509] Biochim Biophys Acta. 1982 Apr 29;720(2):181-7 [7082684] J Cell Biol. 1984 Jul;99(1 Pt 1):166-73 [6330125] J Cell Biol. 1986 Oct;103(4):1221-34 [3771633] J Comp Neurol. 1987 Oct 15;264(3):291-302 [3500190] Eur J Cell Biol. 1987 Oct;44(2):318-27 [2826169] Mol Immunol. 1989 Feb;26(2):153-61 [2918859] J Cell Biol. 1989 Mar;108(3):821-32 [2522097] Methods Cell Biol. 1989;30:219-43 [2648111] J Cell Biol. 1990 Dec;111(6 Pt 2):2931-8 [2148564] J Cell Biol. 1991 May;113(4):743-56 [2026647] Cancer Res. 1991 Nov 15;51(22):6125-32 [1840502] Science. 1991 Nov 15;254(5034):1016-9 [1719635] Cell. 1992 Feb 7;68(3):533-44 [1531449] Blood. 1992 Jun 1;79(11):2807-20 [1586732] Biochem J. 1992 May 15;284 ( Pt 1):169-76 [1376109] Biochem J. 1992 Jul 15;285 ( Pt 2):345-65 [1637327] Tissue Antigens. 1992 Nov;40(5):213-20 [1282740] Biochemistry. 1993 Jun 29;32(25):6365-73 [8518282] J Cell Sci. 1997 Dec;110 ( Pt 24):3001-9 [9365270] J Cell Biol. 1997 Dec 15;139(6):1447-54 [9396750] Curr Opin Cell Biol. 1999 Aug;11(4):424-31 [10449327] Mol Biol Cell. 1999 Oct;10(10):3187-96 [10512859] J Cell Biol. 1993 Aug;122(4):789-807 [8349730] J Histochem Cytochem. 1994 Feb;42(2):155-66 [8288861] Science. 1994 Jun 24;264(5167):1948-51 [7516582] J Cell Biol. 1994 Dec;127(5):1199-215 [7962085] J Biol Chem. 1994 Dec 9;269(49):30745-8 [7982998] J Cell Biol. 1995 Sep;130(5):1105-15 [7657695] Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10104-8 [7479734] J Cell Biol. 1995 Nov;131(3):669-77 [7593188] Mol Biol Cell. 1995 Jul;6(7):929-44 [7579703] J Cell Biol. 1996 Jun;133(6):1265-76 [8682863] Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8407-12 [8710884] J Histochem Cytochem. 1996 Aug;44(8):929-41 [8756764] Curr Opin Cell Biol. 1996 Aug;8(4):542-8 [8791446] J Cell Biol. 1996 Sep;134(5):1169-77 [8794859] Science. 1996 Oct 11;274(5285):239-42 [8824187] J Clin Invest. 1997 Jun 1;99(11):2588-601 [9169488] Nature. 1997 Jun 5;387(6633):569-72 [9177342] Curr Opin Cell Biol. 1997 Aug;9(4):534-42 [9261060] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Caenorhabditis elegans twist plays an essential role in non-striated muscle development. AN - 71087559; 10769229 AB - The basic helix-loop-helix (bHLH) transcription factor Twist plays a role in mesodermal development in both invertebrates and vertebrates. In an effort to understand the role of the unique Caenorhabditis elegans Twist homolog, hlh-8, we analyzed mesodermal development in animals with a deletion in the hlh-8 locus. This deletion was predicted to represent a null allele because the HLH domain is missing and the reading frame for the protein is disrupted. Animals lacking CeTwist function were constipated and egg-laying defective. Both of these defects were rescued in transgenic mutant animals expressing wild-type hlh-8. Observing a series of mesoderm-specific markers allowed us to characterize the loss of hlh-8 function more thoroughly. Our results demonstrate that CeTwist performs an essential role in the proper development of a subset of mesodermal tissues in C. elegans. We found that CeTwist was required for the formation of three out of the four non-striated enteric muscles born in the embryo. In contrast, CeTwist was not required for the formation of the embryonically derived striated muscles. Most of the post-embryonic mesoderm develops from a single lineage. CeTwist was necessary for appropriate patterning in this lineage and was required for expression of two downstream target genes, but was not required for the expression of myosin, a marker of differentiation. Our results suggest that mesodermal patterning by Twist is an evolutionarily conserved function. JF - Development (Cambridge, England) AU - Corsi, A K AU - Kostas, S A AU - Fire, A AU - Krause, M AD - Laboratory of Molecular Biology, NIDDK, NIH, Bethesda, MD 20892-0510, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 2041 EP - 2051 VL - 127 IS - 10 SN - 0950-1991, 0950-1991 KW - Helminth Proteins KW - 0 KW - Transcription Factors KW - Index Medicus KW - Phenotype KW - Muscle, Skeletal -- embryology KW - Animals KW - Cell Lineage KW - Gene Silencing KW - Oviposition -- physiology KW - Female KW - Mutagenesis KW - Transcription Factors -- physiology KW - Caenorhabditis elegans -- embryology KW - Helix-Loop-Helix Motifs KW - Muscle, Smooth -- cytology KW - Helminth Proteins -- genetics KW - Transcription Factors -- genetics KW - Helminth Proteins -- physiology KW - Muscle, Smooth -- embryology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71087559?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Development+%28Cambridge%2C+England%29&rft.atitle=Caenorhabditis+elegans+twist+plays+an+essential+role+in+non-striated+muscle+development.&rft.au=Corsi%2C+A+K%3BKostas%2C+S+A%3BFire%2C+A%3BKrause%2C+M&rft.aulast=Corsi&rft.aufirst=A&rft.date=2000-05-01&rft.volume=127&rft.issue=10&rft.spage=2041&rft.isbn=&rft.btitle=&rft.title=Development+%28Cambridge%2C+England%29&rft.issn=09501991&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-14 N1 - Date created - 2000-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mitomycin C and diepoxybutane action mechanisms and FANCC protein functions: further insights into the role for oxidative stress in Fanconi's anaemia phenotype. AN - 71078904; 10783335 AB - Evidence for redox-dependent toxicities of mitomycin C (MMC) and diepoxybutane (DEB), through different mechanisms, has been related to the phenotypic defect(s) of Fanconi's anaemia (FA) cells, due to their excess sensitivity to these agents. Recent data have pointed to interactions of the FANCC protein (encoded by the FA complementation group C gene, FA-C) with NADPH cytochrome P450 reductase and glutathione S-transferase (GST), two activities involved in either triggering or detoxifying reactive intermediates, including xenobiotics and reactive oxygen species. A body of evidence points to: (i) oxygen hypersensitivity of FA cells; (ii) oxygen-dependent MMC and DEB toxicity; (iii) excess oxidative DNA damage in FA cells; and (iv) DEB-induced glutathione depletion and GST inhibition. The available evidence corroborates the previously suggested role for oxidative stress in FA phenotype and disease progression, shedding new light on the redox-dependent mechanisms in MMC and DEB toxicities, and suggesting a direct association of oxidative stress with the primary genetic defect in FA. JF - Carcinogenesis AU - Pagano, G AD - Italian National Cancer Institute, G.Pascale Foundation, via M. Semmola,I-80131 Naples, Italy. gbpagano@tin.it. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 1067 EP - 1068 VL - 21 IS - 5 SN - 0143-3334, 0143-3334 KW - Cell Cycle Proteins KW - 0 KW - DNA-Binding Proteins KW - Epoxy Compounds KW - FANCC protein, human KW - Fanconi Anemia Complementation Group C Protein KW - Fanconi Anemia Complementation Group Proteins KW - Nuclear Proteins KW - Proteins KW - Mitomycin KW - 50SG953SK6 KW - erythritol anhydride KW - 60OB65YNAB KW - Index Medicus KW - Phenotype KW - Humans KW - Oxidative Stress KW - Fanconi Anemia -- metabolism KW - Epoxy Compounds -- pharmacology KW - Mitomycin -- pharmacology KW - Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71078904?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mitomycin+C+and+diepoxybutane+action+mechanisms+and+FANCC+protein+functions%3A+further+insights+into+the+role+for+oxidative+stress+in+Fanconi%27s+anaemia+phenotype.&rft.au=Pagano%2C+G&rft.aulast=Pagano&rft.aufirst=G&rft.date=2000-05-01&rft.volume=21&rft.issue=5&rft.spage=1067&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-15 N1 - Date created - 2000-06-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Is the human carcinogen arsenic carcinogenic to laboratory animals? AN - 71076394; 10788555 JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Huff, J AU - Chan, P AU - Nyska, A AD - Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. huff1@niehs.nih.gov Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 17 EP - 23 VL - 55 IS - 1 SN - 1096-6080, 1096-6080 KW - Carcinogens KW - 0 KW - Arsenic KW - N712M78A8G KW - Index Medicus KW - Animals KW - Neoplasms -- pathology KW - Neoplasms, Experimental -- chemically induced KW - Humans KW - Neoplasms -- chemically induced KW - Neoplasms, Experimental -- pathology KW - Species Specificity KW - Arsenic Poisoning -- pathology KW - Arsenic -- toxicity KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71076394?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Is+the+human+carcinogen+arsenic+carcinogenic+to+laboratory+animals%3F&rft.au=Huff%2C+J%3BChan%2C+P%3BNyska%2C+A&rft.aulast=Huff&rft.aufirst=J&rft.date=2000-05-01&rft.volume=55&rft.issue=1&rft.spage=17&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 - 2000-06-09 N1 - Date created - 2000-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanism of extracellular signal-regulated kinase (ERK)-1 and ERK-2 activation by vanadium pentoxide in rat pulmonary myofibroblasts. AN - 71073807; 10783131 AB - Vanadium pentoxide (V(2)O(5)) is a cause of occupational asthma and chronic bronchitis, yet the molecular mechanisms through which V(2)O(5) exerts its effects on cell function are unclear. In this study we investigated the potential of V(2)O(5) to activate the extracellular signal-regulated kinases 1 and 2 (ERK-1/2) in rat pulmonary myofibroblasts. Treatment of myofibroblasts with V(2)O(5) resulted in the activation of ERK-1/2, yet the inert metal titanium dioxide had no effect on ERK-1/2 activation. V(2)O(5)-induced ERK-1/2 activation was abolished by pretreatment with forskolin or PD98059, indicating a dependence on Raf and mitogen-activated protein (MAP) kinase kinase, respectively. Depletion of conventional protein kinase C activity with phorbol 12-myristate 13-acetate did not inhibit V(2)O(5)-induced ERK-1/2 activation. ERK-1/2 activation by V(2)O(5) was inhibited > 70% with the epidermal growth factor receptor (EGF-R) tyrosine kinase inhibitor AG1478. Phosphorylation of the 170-kD EGF-R by V(2)O(5) was detected after immunoprecipitation with an anti-EGF-R antibody followed by phosphotyrosine Western blotting. V(2)O(5) strongly tyrosine-phosphorylated a 115-kD protein (p115) and activation of p115 was inhibited 60 to 70% by AG1478, indicating that this protein was an EGF-R substrate. Phosphorylation of p115 was also observed in EGF-stimulated cells. Immunoprecipitation of V(2)O(5)- or EGF-treated cell lysates with an antibody against Src homology 2 protein tyrosine phosphatase (SH-PTP2) identified p115 as a SH-PTP2-binding protein. Pretreatment of cells with the antioxidant N-acetyl-L-cysteine blocked V(2)O(5)-induced MAP kinase activation and p115 phosphorylation > 90%. These data suggest that V(2)O(5) activation of ERK-1/2 is oxidant-dependent and mediated through tyrosine phosphorylation of EGF-R and an EGF-R substrate which we identified as a 115-kD SH-PTP2-binding protein. JF - American journal of respiratory cell and molecular biology AU - Wang, Y Z AU - Bonner, J C AD - Airway Inflammation Section, Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 590 EP - 596 VL - 22 IS - 5 SN - 1044-1549, 1044-1549 KW - 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one KW - 0 KW - Coal Ash KW - Flavonoids KW - Intracellular Signaling Peptides and Proteins KW - Particulate Matter KW - Quinazolines KW - Tyrphostins KW - Vanadium Compounds KW - titanium dioxide KW - 15FIX9V2JP KW - tyrphostin AG 1478 KW - 170449-18-0 KW - Colforsin KW - 1F7A44V6OU KW - Phosphotyrosine KW - 21820-51-9 KW - Carbon KW - 7440-44-0 KW - vanadium pentoxide KW - BVG363OH7A KW - Titanium KW - D1JT611TNE KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - Mitogen-Activated Protein Kinases KW - Protein Tyrosine Phosphatase, Non-Receptor Type 11 KW - EC 3.1.3.48 KW - Protein Tyrosine Phosphatase, Non-Receptor Type 6 KW - Protein Tyrosine Phosphatases KW - Ptpn11 protein, rat KW - Ptpn6 protein, rat KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Animals KW - Asthma -- etiology KW - Receptor, Epidermal Growth Factor -- metabolism KW - Protein Tyrosine Phosphatases -- metabolism KW - Bronchitis -- etiology KW - Phosphotyrosine -- metabolism KW - Acetylcysteine -- pharmacology KW - Fibroblasts KW - Rats KW - Titanium -- pharmacology KW - Colforsin -- pharmacology KW - Phosphorylation KW - Carbon -- adverse effects KW - Enzyme Activation -- drug effects KW - Flavonoids -- pharmacology KW - Tyrphostins -- pharmacology KW - Vanadium Compounds -- pharmacology KW - Mitogen-Activated Protein Kinases -- metabolism KW - Mitogen-Activated Protein Kinase 1 -- metabolism KW - Lung -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71073807?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+respiratory+cell+and+molecular+biology&rft.atitle=Mechanism+of+extracellular+signal-regulated+kinase+%28ERK%29-1+and+ERK-2+activation+by+vanadium+pentoxide+in+rat+pulmonary+myofibroblasts.&rft.au=Wang%2C+Y+Z%3BBonner%2C+J+C&rft.aulast=Wang&rft.aufirst=Y&rft.date=2000-05-01&rft.volume=22&rft.issue=5&rft.spage=590&rft.isbn=&rft.btitle=&rft.title=American+journal+of+respiratory+cell+and+molecular+biology&rft.issn=10441549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-09 N1 - Date created - 2000-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential role of Fas/Fas ligand interactions in cytolysis of primary and metastatic colon carcinoma cell lines by human antigen-specific CD8+ CTL. AN - 71071677; 10779805 AB - We have previously identified mutated ras peptides reflecting the glycine to valine substitution at position 12 as HLA-A2-restricted, CD8+ CTL neo-epitopes. CTL lines produced against these peptide epitopes lysed the HLA-A2+ Ag-bearing SW480 primary colon adenocarcinoma cell line, although IFN-gamma treatment of the targets was necessary to achieve efficient cytotoxicity. Here, we compared the lytic phenotype of the SW480 cell line to its metastatic derivative, SW620, as an in vitro paradigm to further characterize the nature of a HLA class I-restricted, Ag-specific CTL response against neoplastic cell lines of primary and metastatic origin. Although both colon carcinoma cell lines were lysed by these Ag-specific CTL following IFN-gamma pretreatment, the mechanisms of lysis were distinct, which reflected differential levels of sensitivity to the Fas pathway. Whereas IFN-gamma pretreatment rendered SW480 cells sensitive to both Fas-dependent and -independent (perforin) pathways, SW620 cells displayed lytic susceptibility to Fas-independent mechanisms only. Moreover, pretreatment of SW480 cells with the anti-colon cancer agent, 5-fluorouracil (5-FU), led to enhanced Fas and ICAM-1 expression and triggered Ag-specific CTL-mediated lysis via Fas- and perforin-based pathways. In contrast, these phenotypic and functional responses were not observed with SW620 cells. Overall, these data suggested that 1) IFN-gamma and 5-FU may enhance the lytic sensitivity of responsive colon carcinoma cells to immune effector mechanisms, including Fas-induced lysis; 2) the malignant phenotype may associate with resistance to Fas-mediated lysis in response to Ag-specific T cell attack; and 3) if Ag-specific CTL possess diverse lytic capabilities, this may overcome, to some extent, the potential "escape" of Fas-resistant carcinoma cells. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Bergmann-Leitner, E S AU - Abrams, S I AD - Laboratory of Tumor Immunology and Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2000/05/01/ PY - 2000 DA - 2000 May 01 SP - 4941 EP - 4954 VL - 164 IS - 9 SN - 0022-1767, 0022-1767 KW - Antigens, CD95 KW - 0 KW - Epitopes, T-Lymphocyte KW - FASLG protein, human KW - Fas Ligand Protein KW - Fasl protein, mouse KW - Ligands KW - Membrane Glycoproteins KW - Fluorouracil KW - U3P01618RT KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Humans KW - Mice, Nude KW - Mice KW - Adenocarcinoma -- immunology KW - Immunity, Innate KW - Mice, Inbred BALB C KW - Adenocarcinoma -- pathology KW - Tumor Cells, Cultured KW - Adenocarcinoma -- secondary KW - Cytotoxicity Tests, Immunologic KW - Fluorouracil -- pharmacology KW - Adenocarcinoma -- drug therapy KW - Immunophenotyping KW - Female KW - Membrane Glycoproteins -- physiology KW - T-Lymphocytes, Cytotoxic -- immunology KW - Epitopes, T-Lymphocyte -- immunology KW - Colonic Neoplasms -- immunology KW - T-Lymphocytes, Cytotoxic -- metabolism KW - Antigens, CD95 -- metabolism KW - Colonic Neoplasms -- secondary KW - Antigens, CD95 -- biosynthesis KW - Antigens, CD95 -- physiology KW - Colonic Neoplasms -- drug therapy KW - Cytotoxicity, Immunologic -- drug effects KW - Colonic Neoplasms -- pathology KW - Membrane Glycoproteins -- metabolism KW - T-Lymphocytes, Cytotoxic -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71071677?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Differential+role+of+Fas%2FFas+ligand+interactions+in+cytolysis+of+primary+and+metastatic+colon+carcinoma+cell+lines+by+human+antigen-specific+CD8%2B+CTL.&rft.au=Bergmann-Leitner%2C+E+S%3BAbrams%2C+S+I&rft.aulast=Bergmann-Leitner&rft.aufirst=E&rft.date=2000-05-01&rft.volume=164&rft.issue=9&rft.spage=4941&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 - 2000-05-22 N1 - Date created - 2000-05-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polychlorinated biphenyl (PCB) exposure in relation to thyroid hormone levels in neonates. AN - 71066059; 10784239 AB - Polychlorinated biphenyls (PCBs) are industrially produced environmentally persistent compounds. In developed countries all humans have detectable levels in blood and other tissues. PCBs alter thyroid hormone metabolism in animal experiments, and human data suggest background-level exposure may have similar effects in neonates. We evaluated this possible effect among 160 North Carolina children whose in utero PCB exposure was estimated on the basis of the mother's PCB levels in milk and blood, in 1978-1982 (estimated median PCB level in milk at birth, 1.8 mg/kg lipid). Their umbilical cord sera were thawed in 1998 and assayed for total thyroxine, free thyroxine, and thyroid stimulating hormone. We found that PCB exposure was not strongly related to any of the thyroid measures. For example, for a one unit change in milk PCB concentration (mg/kg lipid), the associated multivariate-adjusted increase in thyroid stimulating hormone level was 7% (95% confidence limits (CL) = -6, 21). Despite the possibility of sample degradation, these data suggest that within the range of background-level exposure in the United States, in utero PCB exposure is only slightly related to serum concentration of total thyroxine, free thyroxine, and thyroid stimulating hormone at birth. JF - Epidemiology (Cambridge, Mass.) AU - Longnecker, M P AU - Gladen, B C AU - Patterson, D G AU - Rogan, W J AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 249 EP - 254 VL - 11 IS - 3 SN - 1044-3983, 1044-3983 KW - Environmental Pollutants KW - 0 KW - Thyrotropin KW - 9002-71-5 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Thyroxine KW - Q51BO43MG4 KW - Index Medicus KW - Milk, Human -- chemistry KW - Fetal Blood -- chemistry KW - Thyroxine -- analysis KW - Humans KW - Adult KW - Infant, Newborn KW - Male KW - Female KW - Thyrotropin -- analysis KW - Thyroid Gland -- physiology KW - Maternal Exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71066059?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Polychlorinated+biphenyl+%28PCB%29+exposure+in+relation+to+thyroid+hormone+levels+in+neonates.&rft.au=Longnecker%2C+M+P%3BGladen%2C+B+C%3BPatterson%2C+D+G%3BRogan%2C+W+J&rft.aulast=Longnecker&rft.aufirst=M&rft.date=2000-05-01&rft.volume=11&rft.issue=3&rft.spage=249&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 - 2000-06-08 N1 - Date created - 2000-06-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Epidemiology. 2000 May;11(3):239-41 [10784237] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Altered cell cycle control at the G(2)/M phases in aryl hydrocarbon receptor-null embryo fibroblast. AN - 71063833; 10779392 AB - The aryl hydrocarbon receptor (AHR) is known to mediate the toxic and carcinogenic effects of polycyclic aromatic hydrocarbons and dioxins. High-affinity AHR ligands, such as 2,3,7, 8-tetrachlorodibenzeno-p-dioxin, have been shown to modify cell proliferation and differentiation. However, the mechanisms by which AHR affects cell proliferation and differentiation are not fully understood. To investigate the role of AHR in cell proliferation, mouse embryonic fibroblasts (MEFs) derived from AHR-null mice were obtained and characterized. Compared with wild-type MEFs, AHR-null cells exhibited a lower proliferation rate with an accumulation of 4N DNA content and increased apoptosis. The expression levels of Cdc2 and Plk, two kinases important for G(2)/M phase of cell cycle, were down-regulated in AHR-null MEFs. In contrast, transforming growth factor-beta (TGF-beta), a proliferation inhibitor in several cell lines, was present at high levels in conditioned medium from AHR-null MEFs. Concomitant with G(2)/M cell accumulation, treatment of wild-type MEFs with TGF-beta3 also resulted in down-regulation of both Cdc2 and Plk. Thus, overproduction of TGF-beta in AHR-deficient cells appears to be the primary factor that causes low proliferation rates and increased apoptosis. Taken together, these results suggest that AHR influences TGF-beta production, leading to an alteration in cell cycle control. JF - Molecular pharmacology AU - Elizondo, G AU - Fernandez-Salguero, P AU - Sheikh, M S AU - Kim, G Y AU - Fornace, A J AU - Lee, K S AU - Gonzalez, F J AD - Laboratory of Metabolism, Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 1056 EP - 1063 VL - 57 IS - 5 SN - 0026-895X, 0026-895X KW - Cell Cycle Proteins KW - 0 KW - Proteoglycans KW - Proto-Oncogene Proteins KW - RNA, Messenger KW - Receptors, Aryl Hydrocarbon KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor beta KW - betaglycan KW - 145170-29-2 KW - Protein Kinases KW - EC 2.7.- KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - polo-like kinase 1 KW - CDC2 Protein Kinase KW - EC 2.7.11.22 KW - Index Medicus KW - Animals KW - Apoptosis KW - CDC2 Protein Kinase -- genetics KW - CDC2 Protein Kinase -- metabolism KW - Mice KW - Protein Kinases -- metabolism KW - RNA, Messenger -- metabolism KW - Proteoglycans -- pharmacology KW - Down-Regulation KW - Cells, Cultured KW - Embryo, Mammalian -- cytology KW - Protein Kinases -- genetics KW - Transforming Growth Factor beta -- metabolism KW - G2 Phase -- physiology KW - G2 Phase -- genetics KW - Mitosis -- genetics KW - Receptors, Aryl Hydrocarbon -- metabolism KW - Receptors, Aryl Hydrocarbon -- genetics KW - Fibroblasts -- cytology KW - Mitosis -- physiology KW - Fibroblasts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71063833?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Altered+cell+cycle+control+at+the+G%282%29%2FM+phases+in+aryl+hydrocarbon+receptor-null+embryo+fibroblast.&rft.au=Elizondo%2C+G%3BFernandez-Salguero%2C+P%3BSheikh%2C+M+S%3BKim%2C+G+Y%3BFornace%2C+A+J%3BLee%2C+K+S%3BGonzalez%2C+F+J&rft.aulast=Elizondo&rft.aufirst=G&rft.date=2000-05-01&rft.volume=57&rft.issue=5&rft.spage=1056&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 - 2000-05-25 N1 - Date created - 2000-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of a tyrosine 155 to phenylalanine mutation of protein kinase cdelta on the proliferative and tumorigenic properties of NIH 3T3 fibroblasts. AN - 71063575; 10783308 AB - Tyrosine phosphorylation has emerged as an important mechanism in the regulation of enzyme function. In this paper, we describe a mutant of PKCdelta altered at a single tyrosine residue which has the opposite effect compared with wild-type PKCdelta on the growth characteristics of NIH 3T3 cells. Overexpression of wild-type PKCdelta results in a decreased growth rate and a lower cell density at confluency. On the other hand, overexpression of PKCdelta with a mutation from tyrosine to phenylalanine at position 155 results in a significantly higher rate of growth and a higher density at confluency compared with vector controls. Moreover, these cells are able to grow in soft agar and to form tumors in nude mice. In contrast to kinase negative PKC constructs, this mutant maintains in vitro kinase activity and shows a subcellular localization and a translocation pattern that are similar to those of the wild-type PKCdelta. Whether the altered biological effect is due to the missing phosphorylation on tyrosine or the mutation from tyrosine to phenylalanine per se remains under investigation. JF - Carcinogenesis AU - Acs, P AU - Beheshti, M AU - Szállási, Z AU - Li, L AU - Yuspa, S H AU - Blumberg, P M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, NCI, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 887 EP - 891 VL - 21 IS - 5 SN - 0143-3334, 0143-3334 KW - Isoenzymes KW - 0 KW - Tyrosine KW - 42HK56048U KW - Phenylalanine KW - 47E5O17Y3R KW - DNA KW - 9007-49-2 KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - PRKCD protein, human KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-delta KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Fibroblasts -- drug effects KW - Fibroblasts -- enzymology KW - Humans KW - Biological Transport KW - Mice KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Subcellular Fractions -- enzymology KW - Cell Line KW - Cell Transformation, Neoplastic -- genetics KW - Protein Kinase C -- metabolism KW - Isoenzymes -- chemistry KW - Phenylalanine -- metabolism KW - Protein Kinase C -- genetics KW - Protein Kinase C -- chemistry KW - Tyrosine -- genetics KW - Phenylalanine -- genetics KW - Tyrosine -- metabolism KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71063575?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+a+tyrosine+155+to+phenylalanine+mutation+of+protein+kinase+cdelta+on+the+proliferative+and+tumorigenic+properties+of+NIH+3T3+fibroblasts.&rft.au=Acs%2C+P%3BBeheshti%2C+M%3BSz%C3%A1ll%C3%A1si%2C+Z%3BLi%2C+L%3BYuspa%2C+S+H%3BBlumberg%2C+P+M&rft.aulast=Acs&rft.aufirst=P&rft.date=2000-05-01&rft.volume=21&rft.issue=5&rft.spage=887&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-15 N1 - Date created - 2000-06-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Naloxone protects rat dopaminergic neurons against inflammatory damage through inhibition of microglia activation and superoxide generation. AN - 71052463; 10773035 AB - Degeneration of dopaminergicrgic neurons in the substantia nigra of the brain is a hallmark of Parkinson's disease and inflammation and oxidative stress are closely associated with the pathogenesis of degenerative neurological disorders. Treatment of rat mesencephalic mixed neuron-glia cultures with lipopolysaccharide (LPS)-activated microglia, resident immune cells of the brain, to release proinflammatory and neurotoxic factors tumor necrosis factor-alpha, interleukin-1beta, nitric oxide, and superoxide and subsequently caused damage to midbrain neurons, including dopaminergic neurons. The LPS-induced degeneration of the midbrain neurons was significantly reduced by cotreatment with naloxone, an opioid receptor antagonist. This study focused on understanding the mechanism of action for the protective effect of naloxone on dopaminergic neurons because of relevance to Parkinson's disease. Both naloxone and its opioid receptor inactive stereoisomer (+)-naloxone protected the dopaminergic neurons with equal potency. Naloxone inhibited LPS-induced activation of microglia and release of proinflammatory factors, and inhibition of microglia generation of superoxide free radical best correlated with the neuroprotective effect of naloxone isomers. To further delineate the site of action, naloxone was found to partially inhibit the binding of [(3)H]LPS to cell membranes, whereas it failed to prevent damage to dopaminergic neurons by peroxynitrite, a product of nitric oxide and superoxide. These results suggest that naloxone at least in part interferes with the binding of LPS to cell membranes to inhibit microglia activation and protect dopaminergic neurons as well as other neurons in the midbrain cultures from inflammatory damage. JF - The Journal of pharmacology and experimental therapeutics AU - Liu, B AU - Du, L AU - Hong, J S AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. liu@niehs.nih.gov Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 607 EP - 617 VL - 293 IS - 2 SN - 0022-3565, 0022-3565 KW - Interleukin-1 KW - 0 KW - Lipopolysaccharides KW - Narcotic Antagonists KW - Nitrates KW - Nitrites KW - Oxidants KW - Tumor Necrosis Factor-alpha KW - Superoxides KW - 11062-77-4 KW - peroxynitric acid KW - 26404-66-0 KW - Naloxone KW - 36B82AMQ7N KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Mitogen-Activated Protein Kinase 3 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Tyrosine 3-Monooxygenase -- metabolism KW - Stereoisomerism KW - Oxidants -- pharmacology KW - Mitogen-Activated Protein Kinases -- metabolism KW - Nitrites -- metabolism KW - Lipopolysaccharides -- pharmacology KW - Nitrates -- pharmacology KW - Mesencephalon -- cytology KW - Rats KW - Mesencephalon -- metabolism KW - Mesencephalon -- drug effects KW - Rats, Inbred F344 KW - Interleukin-1 -- metabolism KW - Cells, Cultured KW - Tumor Necrosis Factor-alpha -- metabolism KW - Immunohistochemistry KW - Naloxone -- pharmacology KW - Neurons -- drug effects KW - Dopamine -- physiology KW - Substantia Nigra -- drug effects KW - Substantia Nigra -- enzymology KW - Neurons -- pathology KW - Superoxides -- metabolism KW - Microglia -- enzymology KW - Neurons -- enzymology KW - Microglia -- drug effects KW - Narcotic Antagonists -- pharmacology KW - Substantia Nigra -- cytology KW - Inflammation -- pathology KW - Microglia -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71052463?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Naloxone+protects+rat+dopaminergic+neurons+against+inflammatory+damage+through+inhibition+of+microglia+activation+and+superoxide+generation.&rft.au=Liu%2C+B%3BDu%2C+L%3BHong%2C+J+S&rft.aulast=Liu&rft.aufirst=B&rft.date=2000-05-01&rft.volume=293&rft.issue=2&rft.spage=607&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 - 2000-06-21 N1 - Date created - 2000-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The guanine nucleotide exchange factor RasGRP is a high -affinity target for diacylglycerol and phorbol esters. AN - 71052039; 10779365 AB - RasGRP is a recently described guanine nucleotide exchange factor (GEF) that possesses a single C1 domain homologous to that of protein kinase C (PKC). The phorbol ester [(3)H]phorbol 12, 13-dibutyrate ([(3)H]PDBu) bound to this C1 domain (C1-RasGRP) with a dissociation constant of 0.58 +/- 0.08 nM, similar to that observed previously for PKC. Likewise, the potent PKC activator bryostatin 1, a compound currently in clinical trials, showed high affinity binding for C1-RasGRP. Structure activity analysis using several phorbol ester analogs showed both similarities and differences in ligand selectivity compared with PKC; the differences were comparable in magnitude to those between different PKC isoforms. Similarly, the potency of the PKC inhibitor calphostin C to inhibit [(3)H]PDBu binding to C1-RasGRP was similar to that observed for PKC. In contrast to the relative similarities in ligand recognition, the lipid cofactor requirements differed between RasGRP and PKC. The C1 domain plus the EF-hand motif of RasGRP (C1EF-RasGRP) was markedly less dependent on acidic phospholipids than was PKCalpha. The differences in lipid requirements were reflected in differential ligand selectivity under conditions of limiting lipid. Despite the presence of twin EF-hand like motifs, calcium did not affect the binding of [(3)H]PDBu to C1EF-RasGRP. We conclude that RasGRP is a high affinity receptor for phorbol esters and diacylglycerol. RasGRP thus provides a direct link between diacylglycerol generation or phorbol ester/bryostatin treatment and Ras activation. JF - Molecular pharmacology AU - Lorenzo, P S AU - Beheshti, M AU - Pettit, G R AU - Stone, J C AU - Blumberg, P M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 840 EP - 846 VL - 57 IS - 5 SN - 0026-895X, 0026-895X KW - DNA-Binding Proteins KW - 0 KW - Diglycerides KW - Guanine Nucleotide Exchange Factors KW - Phospholipids KW - Rasgrp1 protein, rat KW - Tritium KW - 10028-17-8 KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Protein Kinase C -- metabolism KW - Calcium -- metabolism KW - Animals KW - Phospholipids -- metabolism KW - Binding, Competitive KW - Protein Kinase C -- chemistry KW - Escherichia coli KW - Structure-Activity Relationship KW - Diglycerides -- pharmacology KW - Guanine Nucleotide Exchange Factors -- metabolism KW - Guanine Nucleotide Exchange Factors -- drug effects KW - DNA-Binding Proteins -- drug effects KW - Phorbol 12,13-Dibutyrate -- pharmacology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71052039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=The+guanine+nucleotide+exchange+factor+RasGRP+is+a+high+-affinity+target+for+diacylglycerol+and+phorbol+esters.&rft.au=Lorenzo%2C+P+S%3BBeheshti%2C+M%3BPettit%2C+G+R%3BStone%2C+J+C%3BBlumberg%2C+P+M&rft.aulast=Lorenzo&rft.aufirst=P&rft.date=2000-05-01&rft.volume=57&rft.issue=5&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 - 2000-05-25 N1 - Date created - 2000-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Etiologic evidence and primary prevention of cancer. AN - 71048569; 10774769 AB - For many decades, primary prevention of cancer was implemented on the basis of evidence for a causal relationship between exposure and human cancer that took into consideration biological plausibility, but did not depend on the degree of understanding of the underlying mechanisms. One of the credos of public health is that primary prevention can be implemented before reaching a complete understanding of mechanisms that could confirm/explain causality. Measures of primary prevention are taken on the basis of what is recognized as causative factors of human cancer. The most authoritative lists of recognized human carcinogens are those compiled from the evaluations of carcinogenic risk carried out by the International Agency for Research on Cancer (IARC) and the evaluations that the U.S. National Toxicology Program (NTP) publishes in its periodical Report on Carcinogens. Knowledge of mechanisms is accumulating at a fast pace, and although it has not yet led to the definition of an efficient strategy for primary prevention for the majority of cancer cases, it may drive the scientific establishment toward a high-risk approach to prevention. The most reasonable and socially acceptable development of primary prevention should be the blending of a population approach; that is, the shifting of the distribution of risk factors across an entire population in a favorable direction (e.g., a general decrease of the levels of exposure to environmental carcinogens) with the high-risk approach that will concern individuals with extreme values of genetically determined weaknesses in the interactions with the environment. JF - Drug metabolism reviews AU - Tomatis, L AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. tomati@tin.it Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 129 EP - 137 VL - 32 IS - 2 SN - 0360-2532, 0360-2532 KW - Carcinogens KW - 0 KW - Index Medicus KW - Primary Prevention KW - Humans KW - Genetic Predisposition to Disease KW - Neoplasms -- epidemiology KW - Carcinogens -- toxicity KW - Neoplasms -- prevention & control KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71048569?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+reviews&rft.atitle=Etiologic+evidence+and+primary+prevention+of+cancer.&rft.au=Tomatis%2C+L&rft.aulast=Tomatis&rft.aufirst=L&rft.date=2000-05-01&rft.volume=32&rft.issue=2&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+reviews&rft.issn=03602532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-11 N1 - Date created - 2000-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Update on cyclophosphamide for systemic lupus erythematosus. AN - 71044819; 10768217 AB - Over the past decade cyclophosphamide has come to assume an increasingly prominent role in the management of severe, life-threatening manifestations of SLE. Intermittent, intravenous pulse cyclophosphamide has become the standard of treatment of diffuse proliferative lupus nephritis (WHO Class IV), and there is now substantial clinical literature to suggest an indication for intermittent cyclophosphamide therapy in most other forms of serious lupus affecting major organ systems, in particular lupus vasculitis and acute central nervous system manifestations. This update reviews the use of cyclophosphamide in the management of lupus nephritis, expands on its role in other manifestations of SLE, and discusses potential complications of the drug. JF - Rheumatic diseases clinics of North America AU - Ortmann, R A AU - Klippel, J H AD - Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA. Robert_Ortmann@nih.gov Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 363 EP - 75, vii VL - 26 IS - 2 SN - 0889-857X, 0889-857X KW - Immunosuppressive Agents KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Drug Therapy, Combination KW - Humans KW - Prognosis KW - Lupus Erythematosus, Systemic -- complications KW - Cyclophosphamide -- therapeutic use KW - Lupus Erythematosus, Systemic -- drug therapy KW - Immunosuppressive Agents -- therapeutic use KW - Immunosuppressive Agents -- pharmacology KW - Immunosuppressive Agents -- adverse effects KW - Cyclophosphamide -- pharmacology KW - Cyclophosphamide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71044819?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Rheumatic+diseases+clinics+of+North+America&rft.atitle=Update+on+cyclophosphamide+for+systemic+lupus+erythematosus.&rft.au=Ortmann%2C+R+A%3BKlippel%2C+J+H&rft.aulast=Ortmann&rft.aufirst=R&rft.date=2000-05-01&rft.volume=26&rft.issue=2&rft.spage=363&rft.isbn=&rft.btitle=&rft.title=Rheumatic+diseases+clinics+of+North+America&rft.issn=0889857X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-21 N1 - Date created - 2000-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular and environmental causes of cancer. AN - 71044794; 10774770 AB - The multistep, clonal evolution model of cancer predicts fundamental mechanisms by which chemicals may influence the cancer process. These are illustrated by studies of the mechanisms of induction of carcinogenesis by estrogens and the inhibition of carcinogenesis by caloric restriction. JF - Drug metabolism reviews AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 139 EP - 142 VL - 32 IS - 2 SN - 0360-2532, 0360-2532 KW - Carcinogens, Environmental KW - 0 KW - Estrogens KW - Index Medicus KW - Risk Factors KW - Humans KW - Energy Intake -- physiology KW - Cell Transformation, Neoplastic KW - Carcinogens, Environmental -- adverse effects KW - Neoplasms -- chemically induced KW - Neoplasms -- diet therapy KW - Estrogens -- adverse effects KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71044794?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+reviews&rft.atitle=Molecular+and+environmental+causes+of+cancer.&rft.au=Barrett%2C+J+C&rft.aulast=Barrett&rft.aufirst=J&rft.date=2000-05-01&rft.volume=32&rft.issue=2&rft.spage=139&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+reviews&rft.issn=03602532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-11 N1 - Date created - 2000-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A conditioned medium from a human liposarcoma-derived cell line induces p53-dependent apoptosis in several tumor cell lines. AN - 71042000; 10767381 AB - A novel cell line, named LSA, has been obtained, stabilized, and characterized from a human liposarcoma. These cells have morphological and biochemical features strongly resembling the adipocytes and were able to grow in the Ham's F12 medium, in presence or absence of FCS. A conditioned medium (LSA-CM) was obtained by growing the LSA cells in the F12 medium in the absence of FCS. LSA-CM had cytostatic and cytotoxic effects (apoptosis and necrosis) associated with down-regulation of c-myc and upregulation of p53 in several human cell lines (breast, lung, glioblastoma, etc. ). The MCF-7 and glioblastoma cells were killed by LSA-CM in 5-6 days, whereas the same cells were killed by LSA-CM co-incubated with low doses of cisplatin in 30 h. LSA-CM peri-tumoral injections for 15 days in Balb-c-fc3H mice affected by mammary tumors, resulted in the rapid disruption of tumors and absence of metastases. In contrast, in the untreated animals the tumor masses were 4 times larger than initial lesions, and numerous metastases were found in the lungs. The toxicity analysis of LSA-CM, performed on three different animal species, showed that LSA-CM is absolutely free of acute, subacute, and subchronic toxicity. The possible use of LSA-CM/cisplatin for cancer treatment is discussed. JF - Oncology reports AU - Mancini, A AU - Borrelli, A AU - Masucci, M T AU - Schiattarella, A AU - Filice, S AU - Rashan, J AU - Maggino, T AD - National Cancer Institute, Fondazione Pascale, 80110 Naples, Italy. PY - 2000 SP - 629 EP - 637 VL - 7 IS - 3 SN - 1021-335X, 1021-335X KW - Culture Media, Conditioned KW - 0 KW - Tumor Suppressor Protein p53 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Animals KW - Glioblastoma KW - Guinea Pigs KW - Humans KW - Skin -- pathology KW - Cell Division -- drug effects KW - Breast Neoplasms KW - Salmonella typhimurium -- drug effects KW - Mice KW - Necrosis KW - Mutagenicity Tests KW - Skin -- drug effects KW - Tumor Cells, Cultured KW - Lung Neoplasms KW - Cisplatin -- toxicity KW - Mice, Inbred C3H KW - Neoplasm Metastasis -- prevention & control KW - Female KW - Culture Media, Conditioned -- pharmacology KW - Liposarcoma KW - Apoptosis -- drug effects KW - Mammary Neoplasms, Experimental -- drug therapy KW - Culture Media, Conditioned -- toxicity KW - Tumor Suppressor Protein p53 -- metabolism KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71042000?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+reports&rft.atitle=A+conditioned+medium+from+a+human+liposarcoma-derived+cell+line+induces+p53-dependent+apoptosis+in+several+tumor+cell+lines.&rft.au=Mancini%2C+A%3BBorrelli%2C+A%3BMasucci%2C+M+T%3BSchiattarella%2C+A%3BFilice%2C+S%3BRashan%2C+J%3BMaggino%2C+T&rft.aulast=Mancini&rft.aufirst=A&rft.date=2000-05-01&rft.volume=7&rft.issue=3&rft.spage=629&rft.isbn=&rft.btitle=&rft.title=Oncology+reports&rft.issn=1021335X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-16 N1 - Date created - 2000-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Why do neuroprotective drugs work in animals but not humans? AN - 71026735; 10757837 AB - Many neuroprotective agents that seemed promising in animal studies of ischemic brain injury prove to have no effect when tested in clinical trials, suggesting that fundamental elements of translational research require better definition. A number of modifications have led to improvements in preclinical and human studies since the earliest controlled trials failed to confirm hypotheses suggested by animal data. Continued re-evaluation and sharing of information derived from the laboratory bench or the patient's bedside should eventually lead to effective neuroprotection in acute stroke. Experimental data should be carefully studied to improve the quality of agents coming to clinical trials and to design trial phasing that effectively determines drug safety and efficacy. This article will examine preclinical modeling and its translation to prospective studies of acute stroke therapy and will focus on some potential solutions directed at clinical trial design. JF - Neurologic clinics AU - DeGraba, T J AU - Pettigrew, L C AD - Stroke Branch, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 475 EP - 493 VL - 18 IS - 2 SN - 0733-8619, 0733-8619 KW - Neuroprotective Agents KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Treatment Outcome KW - Clinical Trials as Topic KW - Disease Models, Animal KW - Brain Damage, Chronic -- prevention & control KW - Stroke -- drug therapy KW - Neuroprotective Agents -- adverse effects KW - Neuroprotective Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71026735?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurologic+clinics&rft.atitle=Why+do+neuroprotective+drugs+work+in+animals+but+not+humans%3F&rft.au=DeGraba%2C+T+J%3BPettigrew%2C+L+C&rft.aulast=DeGraba&rft.aufirst=T&rft.date=2000-05-01&rft.volume=18&rft.issue=2&rft.spage=475&rft.isbn=&rft.btitle=&rft.title=Neurologic+clinics&rft.issn=07338619&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-21 N1 - Date created - 2000-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Aged mice exhibit greater mortality concomitant to increased brain and plasma TNF-alpha levels following intracerebroventricular injection of lipopolysaccharide. AN - 71017539; 10754368 AB - Age-related defects in the development of peripheral inflammatory responses have been observed in rodents and humans. We examined the effects of age on a centrally injected endotoxin-induced cytokine production and cellular activation in mice. Male C57BL/6J (B6) mice, C3H/HeN mice, and C3H/HeJ mice received an intracerebroventricular injection of lipopolysaccharide (LPS) and were sacrificed at various times (2, 4, 8 h) thereafter. ELISA for IL-1beta, IL-6, IL-12, and TNF-alpha were conducted on forebrain tissue homogenates as well as plasma samples, and lectin staining to detect activated microglia was prepared for selected brain slices. Intracerebroventricular injection of LPS in B6 mice produced an age-associated increase in mortality which was paralleled with a significant increase in brain and plasma levels of TNF-alpha. AntiTNF-alpha- and IL-6-immunoreactive cells possessed macrophagelike morphologies and were observed along the LPS injection tract and scattered throughout the hilus of the dorsal hippocampus and cerebral cortices. This LPS-mediated response was found to be specific in that the LPS-hyporesponsive mouse strain (C3H/HeJ) failed to demonstrate significant brain or plasma levels of TNF-alpha after LPS administration compared to C3H/HeN mice. These results suggest that the age-related increases in TNF-alpha production and mortality following the intracerebroventricular administration of LPS may be due to an increased endotoxin hypersensitivity of brain microglia/macrophages within aged animals. Copyright 2000 S. Karger AG, Basel. JF - Gerontology AU - Kalehua, A N AU - Taub, D D AU - Baskar, P V AU - Hengemihle, J AU - Muñoz, J AU - Trambadia, M AU - Speer, D L AU - De Simoni, M G AU - Ingram, D K AD - Laboratory of Immunology, Clinical Immunology Section, and Laboratory of Cellular and Molecular Biology, Gerontology Research Center, National Institutes on Aging, National Institutes of Health, Baltimore, MD 21224, USA. PY - 2000 SP - 115 EP - 128 VL - 46 IS - 3 SN - 0304-324X, 0304-324X KW - Interleukin-6 KW - 0 KW - Lipopolysaccharides KW - Tumor Necrosis Factor-alpha KW - Index Medicus KW - Animals KW - Reference Values KW - Chi-Square Distribution KW - Interleukin-6 -- metabolism KW - Disease Models, Animal KW - Brain -- metabolism KW - Mice KW - Injections, Intraventricular KW - Culture Techniques KW - Neuroglia -- pathology KW - Mice, Inbred C57BL KW - Enzyme-Linked Immunosorbent Assay KW - Immunohistochemistry KW - Male KW - Survival Analysis KW - Aging -- metabolism KW - Brain Diseases -- chemically induced KW - Brain Diseases -- pathology KW - Tumor Necrosis Factor-alpha -- metabolism KW - Brain Diseases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71017539?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gerontology&rft.atitle=Aged+mice+exhibit+greater+mortality+concomitant+to+increased+brain+and+plasma+TNF-alpha+levels+following+intracerebroventricular+injection+of+lipopolysaccharide.&rft.au=Kalehua%2C+A+N%3BTaub%2C+D+D%3BBaskar%2C+P+V%3BHengemihle%2C+J%3BMu%C3%B1oz%2C+J%3BTrambadia%2C+M%3BSpeer%2C+D+L%3BDe+Simoni%2C+M+G%3BIngram%2C+D+K&rft.aulast=Kalehua&rft.aufirst=A&rft.date=2000-05-01&rft.volume=46&rft.issue=3&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Gerontology&rft.issn=0304324X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-14 N1 - Date created - 2000-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase 2 study of radio frequency interstitial tissue ablation of localized renal tumors. AN - 71006463; 10751849 AB - Small renal tumors are frequently detected during the screening of patients with a hereditary type of renal cancer. The development of nonsurgical treatment modalities would greatly improve quality of life in these patients. We present our experience with radio frequency interstitial tissue ablation, a heating device approved by the Food and Drug Administration for treating soft tissue tumors. Patients underwent radio frequency interstitial tissue ablation of small renal tumors just before surgical excision. Pathological examination of the renal tumors was done to evaluate the treatment effect. Computerized tomography and renal function testing were performed before and after therapy to evaluate toxicity. Four patients underwent treatment of a total of 14 tumors with the radio frequency interstitial tissue ablation device just before surgical removal of the tumors. All lesions were brown after ablation, in contrast to the normal pink appearance of untreated lesions that were resected. On color Doppler ultrasound blood flow to each tumor evident before was not visualized after treatment. The Wilcoxon rank sum test demonstrated no difference preoperatively and postoperatively in blood urea nitrogen, serum creatinine, creatinine clearance or differential renal function. We identified no toxicity associated with radio frequency interstitial tissue ablation. Of the excised tumors 11 were renal cell carcinoma and 3 fibrotic hemorrhagic cysts. For renal cell carcinoma the treatment effect involved the loss of nuclear detail and nonvisualization of nucleoli. These changes were not observed in any tumors resected without radio frequency interstitial tissue ablation. The treatment effect was noted in 10 of the 11 lesions, and in 1 case the treatment effect involved 35% of the tumor. No toxicity was associated with radio frequency interstitial tissue ablation. Percutaneous treatment of renal tumors is planned to evaluate the treatment effect better and further evaluate toxicity. JF - The Journal of urology AU - Walther, M C AU - Shawker, T H AU - Libutti, S K AU - Lubensky, I AU - Choyke, P L AU - Venzon, D AU - Linehan, W M AD - Urologic Oncology Branch, Department of Radiology, Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 1424 EP - 1427 VL - 163 IS - 5 SN - 0022-5347, 0022-5347 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Adult KW - Male KW - Female KW - Diathermy KW - Kidney Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71006463?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+urology&rft.atitle=A+phase+2+study+of+radio+frequency+interstitial+tissue+ablation+of+localized+renal+tumors.&rft.au=Walther%2C+M+C%3BShawker%2C+T+H%3BLibutti%2C+S+K%3BLubensky%2C+I%3BChoyke%2C+P+L%3BVenzon%2C+D%3BLinehan%2C+W+M&rft.aulast=Walther&rft.aufirst=M&rft.date=2000-05-01&rft.volume=163&rft.issue=5&rft.spage=1424&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+urology&rft.issn=00225347&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-02 N1 - Date created - 2000-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dissociation of primary and secondary reward-relevant limbic nuclei in an animal model of relapse. AN - 70985235; 10731622 AB - The neural substrates underlying relapse to drug-seeking behavior after chronic drug abuse may differ from those underlying immediate drug-taking behavior. In a model of relapse to drug-seeking behavior following chronic cocaine self-administration and prolonged extinction, we have previously shown that rats will significantly reinstate lever responding for either primary reward (cocaine) or secondary reward (tone + light stimulus previously paired with cocaine). In the present study, we utilized reversible inactivation of discrete brain nuclei with tetrodotoxin (TTX) in order to examine the neural substrates mediating primary and secondary cocaine reward in rats allowed two weeks of cocaine self-administration. After one week of daily extinction sessions, bilateral inactivation of the basolateral amygdala resulted in significant attenuation of lever pressing for a cocaine-conditioned reward (tone + light). Following three more days of extinction, bilateral TTX inactivation of the basolateral amygdala had no effect on the reinstatement of cocaine self-administration. In contrast, TTX inactivation of the nucleus accumbens produced the exact opposite effects, with significant blockade of primary reward (cocaine alone), but not secondary reward (tone + light). Thus, cocaine-conditioned reward is neuroanatomically dissociated from primary cocaine reward. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Grimm, J W AU - See, R E AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 473 EP - 479 VL - 22 IS - 5 SN - 0893-133X, 0893-133X KW - Dopamine Uptake Inhibitors KW - 0 KW - Sodium Channels KW - Tetrodotoxin KW - 4368-28-9 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Animals KW - Nucleus Accumbens -- drug effects KW - Infusion Pumps, Implantable KW - Disease Models, Animal KW - Nucleus Accumbens -- physiopathology KW - Recurrence KW - Rats KW - Rats, Sprague-Dawley KW - Amygdala -- physiopathology KW - Self Administration KW - Amygdala -- cytology KW - Amygdala -- drug effects KW - Nucleus Accumbens -- cytology KW - Tetrodotoxin -- pharmacology KW - Cocaine -- pharmacology KW - Sodium Channels -- drug effects KW - Male KW - Dopamine Uptake Inhibitors -- pharmacology KW - Limbic System -- physiopathology KW - Limbic System -- cytology KW - Limbic System -- drug effects KW - Reward KW - Cocaine-Related Disorders -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70985235?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=Dissociation+of+primary+and+secondary+reward-relevant+limbic+nuclei+in+an+animal+model+of+relapse.&rft.au=Grimm%2C+J+W%3BSee%2C+R+E&rft.aulast=Grimm&rft.aufirst=J&rft.date=2000-05-01&rft.volume=22&rft.issue=5&rft.spage=473&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-09 N1 - Date created - 2000-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lung cancer risk in relation to genetic polymorphisms of microsomal epoxide hydrolase among African-Americans and Caucasians in Los Angeles County. AN - 70971753; 10717332 AB - Microsomal epoxide hydrolase participates in the metabolism of benzo[a]pyrene, an important carcinogen in tobacco smoke. Two relatively common polymorphisms of the microsomal epoxide hydrolase gene that influence enzyme activity have been described. An association between genetic variation in microsomal epoxide hydrolase and lung cancer risk has been reported in one of two studies of Caucasians. We examined the relation between these two polymorphisms and lung cancer risk among 337 incident cases and 700 population controls of African-American and Caucasian ethnicity enrolled in a case-control study in Los Angeles County. African-Americans, homozygous for the exon 3 variant allele conferring reduced activity, were at decreased risk of lung cancer (odds ratio (OR)=0.08, 95% CI 0.01-0.62). When data from both the exon 3 and exon 4 polymorphisms were combined into indices of predicted microsomal epoxide hydrolase activity, a decreased risk was seen among African-American subjects with very low predicted activity OR=0.10 (95% CI 0.01-0.83). No comparable association was seen among Caucasians. Although the three published results for Caucasians are somewhat variable, the association among African-Americans in these data provides some support for the hypothesis that genetically reduced microsomal epoxide hydrolase activity may be protective against lung cancer. JF - Lung cancer (Amsterdam, Netherlands) AU - London, S J AU - Smart, J AU - Daly, A K AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. london2@niehs.nih.gov Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 147 EP - 155 VL - 28 IS - 2 SN - 0169-5002, 0169-5002 KW - Epoxide Hydrolases KW - EC 3.3.2.- KW - Index Medicus KW - Odds Ratio KW - Microsomes KW - Los Angeles -- ethnology KW - Humans KW - Aged KW - Middle Aged KW - Male KW - Female KW - Risk Assessment KW - Epoxide Hydrolases -- genetics KW - Epoxide Hydrolases -- metabolism KW - Lung Neoplasms -- etiology KW - African Continental Ancestry Group -- genetics KW - Polymorphism, Genetic KW - Lung Neoplasms -- genetics KW - Genetic Predisposition to Disease KW - European Continental Ancestry Group -- genetics KW - Lung Neoplasms -- ethnology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70971753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lung+cancer+%28Amsterdam%2C+Netherlands%29&rft.atitle=Lung+cancer+risk+in+relation+to+genetic+polymorphisms+of+microsomal+epoxide+hydrolase+among+African-Americans+and+Caucasians+in+Los+Angeles+County.&rft.au=London%2C+S+J%3BSmart%2C+J%3BDaly%2C+A+K&rft.aulast=London&rft.aufirst=S&rft.date=2000-05-01&rft.volume=28&rft.issue=2&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Lung+cancer+%28Amsterdam%2C+Netherlands%29&rft.issn=01695002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-23 N1 - Date created - 2000-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - How Does POSSLQ Measure Up? Historical Estimates of Cohabitation AN - 60094621; 200015759 AB - March Current Population Survey (CPS) data, 1977-1997, are used to produce a new historical series of indirect cohabitation prevalence estimates. After comparing the new estimates with those produced by the traditional method & evaluating the new estimates, the indirect estimates are compared with the new direct estimates to investigate whether biases exist in the indirect estimates. Findings indicate that the traditional indirect method of estimating cohabitation prevalence underestimates cohabitors in different subpopulations, especially among those with children. Also, the new indirect measure produces relatively unbiased estimates of cohabitors' characteristics. 4 Tables, 3 Figures, 23 References. Adapted from the source document. JF - Demography AU - Casper, Lynne M AU - Cohen, Philip N AD - National Instit Child Health & Human Development, Bethesda, MD casperl@mail.nih.gov Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 237 EP - 245 VL - 37 IS - 2 SN - 0070-3370, 0070-3370 KW - Cohabitation KW - Methodology (Data Analysis) KW - Estimation KW - Bias KW - Methodological Problems KW - article KW - 1837: demography and human biology; demography (population studies) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/60094621?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Demography&rft.atitle=How+Does+POSSLQ+Measure+Up%3F+Historical+Estimates+of+Cohabitation&rft.au=Casper%2C+Lynne+M%3BCohen%2C+Philip+N&rft.aulast=Casper&rft.aufirst=Lynne&rft.date=2000-05-01&rft.volume=37&rft.issue=2&rft.spage=237&rft.isbn=&rft.btitle=&rft.title=Demography&rft.issn=00703370&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-10-30 N1 - Last updated - 2016-09-28 N1 - SubjectsTermNotLitGenreText - Cohabitation; Estimation; Bias; Methodological Problems; Methodology (Data Analysis) ER - TY - JOUR T1 - Transplanted CNS stem cells form functional synapses in vivo AN - 19486711; 8528292 AB - An understanding of developmental mechanisms and new cell therapies can be achieved by transplantation into the nervous system. Multipotential stem cells have been isolated from the foetal and adult central nervous system (CNS). Immortalized and primary precursor cells integrate into the developing brain generating both neurons and glia as defined by immunological and morphological criteria. Here we show for the first time that in vitro-expanded CNS precursors, upon transplantation into the brains of rats, form electrically active and functionally connected neurons. These neurons exhibit spontaneous and evoked postsynaptic events and respond to focal glutamate application. Donor cells were grafted into the foetal hippocampus, and the amplitude and frequency of spontaneous synaptic events were monitored in the grafted cells in area CA1 for the first month of postnatal life. The formation of synapses onto grafted neurons indicates that grafted CNS stem cells can be used to study synaptic development in vivo and has important implications for clinical cell replacement therapies. JF - European Journal of Neuroscience AU - Auerbach, Jonathan M AU - Eiden, Maribeth V AU - McKay, Ron DG AD - Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, NIH, 36 Convent Drive,, mckay@codon.nih.gov Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 1696 EP - 1704 PB - Blackwell Publishing Ltd., 9600 Garsington Road VL - 12 IS - 5 SN - 0953-816X, 0953-816X KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts KW - CNS stem cells KW - electrophysiology KW - hippocampus KW - rat KW - synapse formation KW - transplantation KW - Central nervous system KW - Stem cells KW - Neurogenesis KW - Transplantation KW - Synaptogenesis KW - Hippocampus KW - Neurons KW - Brain KW - Glia KW - Glutamic acid KW - W 30965:Miscellaneous, Reviews KW - N3 11024:Neuroimmunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19486711?accountid=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=European+Journal+of+Neuroscience&rft.atitle=Transplanted+CNS+stem+cells+form+functional+synapses+in+vivo&rft.au=Auerbach%2C+Jonathan+M%3BEiden%2C+Maribeth+V%3BMcKay%2C+Ron+DG&rft.aulast=Auerbach&rft.aufirst=Jonathan&rft.date=2000-05-01&rft.volume=12&rft.issue=5&rft.spage=1696&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Neuroscience&rft.issn=0953816X&rft_id=info:doi/10.1046%2Fj.1460-9568.2000.00067.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-11-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Central nervous system; Neurogenesis; Stem cells; Transplantation; Hippocampus; Synaptogenesis; Neurons; Glia; Brain; Glutamic acid DO - http://dx.doi.org/10.1046/j.1460-9568.2000.00067.x ER - TY - JOUR T1 - X-ray evidence of increased asbestos exposure in the US population from NHANES I and NHANES II, 1973-1978 AN - 18210868; 5285296 AB - Objectives: Jobs involving heavy asbestos exposure increase risk for lung cancer and mesothelioma substantially, and low-level exposures may carry some risk. At least one indicator of asbestos exposure, mesothelioma, has been increasing in the US for decades. We investigated the prevalence of another indicator, pleural thickening on x-ray, in a defined sample of the US population. Methods: Certified physicians read 1060 x-rays from the second National Health and Nutrition Examination Survey (1976-1980) for pleural changes consistent with pneumoconiosis, which are a reasonably specific indicator of asbestos exposure. Results: Prevalence estimates, in NHANES II, in the age group 35-74 years, are 6.4% ( plus or minus 0.9%) among males, 1.7% ( plus or minus 0.6%) among females, and 3.9% ( plus or minus 0.6%) overall. These prevalences are approximately twice those estimated from NHANES I data (1971-1975). Conclusions: X-ray evidence of asbestos exposure was common in the late 1970s and increasing. The increase may be due to occupational asbestos exposure, but it is so large as to suggest some contribution from environmental, non-occupational asbestos exposure. JF - Cancer Causes & Control AU - Rogan, W J AU - Ragan, N B AU - Dinse, GE AD - Mail Drop A3-05, NIEHS, POB 12233, RTP, NC, 27709, USA, rogan@niehs.nih.gov Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 441 EP - 449 VL - 11 IS - 5 SN - 0957-5243, 0957-5243 KW - man KW - mesothelioma KW - Toxicology Abstracts KW - Asbestos KW - X radiation KW - Lung KW - Carcinogenesis KW - Pneumoconiosis KW - Population studies KW - Environmental factors KW - Occupational exposure KW - X 24156:Environmental impact UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18210868?accountid=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=X-ray+evidence+of+increased+asbestos+exposure+in+the+US+population+from+NHANES+I+and+NHANES+II%2C+1973-1978&rft.au=Rogan%2C+W+J%3BRagan%2C+N+B%3BDinse%2C+GE&rft.aulast=Rogan&rft.aufirst=W&rft.date=2000-05-01&rft.volume=11&rft.issue=5&rft.spage=441&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - X radiation; Asbestos; Occupational exposure; Environmental factors; Population studies; Pneumoconiosis; Lung; Carcinogenesis ER - TY - JOUR T1 - Leukemia and Lymphoma Incidence in Rodents Exposed to Low-Frequency Magnetic Fields AN - 17858593; 5973522 AB - A weak association between residential or occupational exposure to electric and magnetic fields (50/60 Hz fields) and an increased incidence of leukemia has been reported. Numerous animal studies have evaluated the potential association between magnetic-field exposure and leukemia. These include long-term (up to 2 one half years) bioassays, initiation/promotion studies, investigations in transgenic models, and tumor growth studies. Exposure to 60 Hz circularly polarized magnetic fields at 1,400 mu T for 28 months did not affect lymphoma incidence in mice. The study included over 2000 C57BL/6J mice. In another study, 1000 B6C3F1 mice exposed to 60 Hz magnetic fields up to 1000 mu T for 2 years showed no increase in lymphomas. Approximately 400 transgenic E mu -Pim1 mice exposed to 50 Hz fields up to 1000 mu T for up to 18 months had no increased incidence of leukemia. Similarly, Trp53+/- mice and Pim1transgenic mice exposed to 60 Hz magnetic fields for 23 weeks showed no increased incidence of lymphoma. Three studies in F344 rats exposed to 50 or 60 Hz magnetic fields up to 5 mT showed no increased incidence of leukemia. The combined animal bioassay results are nearly uniformly negative for magnetic-field exposures enhancing leukemia and weaken the possible epidemiological association between magnetic-field exposures and leukemia in humans as suggested by epidemiological data. JF - Radiation Research AU - Boorman, G A AU - Rafferty, C N AU - Ward, J M AU - Sills, R C AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 627 EP - 636 PB - Radiation Research Society VL - 153 IS - 5 SN - 0033-7587, 0033-7587 KW - Toxicology Abstracts KW - Leukemia KW - Magnetic fields KW - Transgenic mice KW - Lymphoma KW - Occupational exposure KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17858593?accountid=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=Leukemia+and+Lymphoma+Incidence+in+Rodents+Exposed+to+Low-Frequency+Magnetic+Fields&rft.au=Boorman%2C+G+A%3BRafferty%2C+C+N%3BWard%2C+J+M%3BSills%2C+R+C&rft.aulast=Boorman&rft.aufirst=G&rft.date=2000-05-01&rft.volume=153&rft.issue=5&rft.spage=627&rft.isbn=&rft.btitle=&rft.title=Radiation+Research&rft.issn=00337587&rft_id=info:doi/10.1043%2F0033-7587%282000%291532.0.CO%3B2 L2 - http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0033-7587&volume=153&page=627 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Magnetic fields; Leukemia; Transgenic mice; Lymphoma; Occupational exposure DO - http://dx.doi.org/10.1043/0033-7587(2000)153<0627:LALIIR>2.0.CO;2 ER - TY - JOUR T1 - Evaluation of In Vitro Effects of 50 and 60 Hz Magnetic Fields in Regional EMF Exposure Facilities AN - 17855209; 5973525 AB - A weak association between magnetic-field exposure and increased incidences of cancer has been reported. While alterations in cellular processes after in vitro magnetic-field exposures have also been reported to provide plausibility for this association, other laboratories have been unable to repeat the findings. As part of an accelerated electric- and magnetic-field (EMF) research program, the National Institute of Environmental Health Sciences with the Department of Energy identified the replication of the published positive effects as a priority. Regional EMF exposure facilities were established to investigate major in vitro effects from the literature. These included effects on gene expression, intracellular calcium, colony growth in soft agar, and ornithine decarboxylase activity. The laboratories that first reported these effects provided experimental protocols, cell lines, and other relevant experiment details. Regional facility studies included sham/sham exposures (no applied field in either chamber) and were done in a blinded fashion to minimize investigator bias. In nearly all experiments, no effects of magnetic-field exposure were found. The effort provided insight into dealing with the difficulty of replication of subtle effects in complex biological systems. Experimental techniques provided some clues for the differences in experimental results between the regional facility and the original investigator. Studies of subtle effects require extraordinary efforts to confirm that the effect can be attributed to the applied exposure. JF - Radiation Research AU - Boorman, G A AU - Owen, R D AU - Lotz, W G AU - Galvin, MJ Jr AD - National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709 Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 648 EP - 657 PB - Radiation Research Society VL - 153 IS - 5 SN - 0033-7587, 0033-7587 KW - Toxicology Abstracts KW - Gene expression KW - Magnetic fields KW - Agar KW - Colonies KW - Replication KW - Energy KW - Ornithine decarboxylase KW - Research programs KW - Cancer KW - Calcium (intracellular) KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17855209?accountid=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=Evaluation+of+In+Vitro+Effects+of+50+and+60+Hz+Magnetic+Fields+in+Regional+EMF+Exposure+Facilities&rft.au=Boorman%2C+G+A%3BOwen%2C+R+D%3BLotz%2C+W+G%3BGalvin%2C+MJ+Jr&rft.aulast=Boorman&rft.aufirst=G&rft.date=2000-05-01&rft.volume=153&rft.issue=5&rft.spage=648&rft.isbn=&rft.btitle=&rft.title=Radiation+Research&rft.issn=00337587&rft_id=info:doi/10.1043%2F0033-7587%282000%291532.0.CO%3B2 L2 - http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0033-7587&volume=153&page=648 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Gene expression; Agar; Magnetic fields; Colonies; Replication; Energy; Ornithine decarboxylase; Cancer; Research programs; Calcium (intracellular) DO - http://dx.doi.org/10.1043/0033-7587(2000)153<0648:EOIVEO>2.0.CO;2 ER - TY - JOUR T1 - Magnetic Fields and Mammary Cancer in Rodents: A Critical Review and Evaluation of Published Literature AN - 17855176; 5973521 AB - Epidemiological data suggesting a possible increase in breast cancer risk in male electricians have raised concerns about the relationship between exposure to power-frequency magnetic fields and breast cancer. In this paper, we review the results of animal studies that are relevant to identifying possible increases in breast cancer risk resulting from exposure to 50 or 60 Hz magnetic fields. Three large-scale chronic bioassays of carcinogenesis in rats or mice exposed to magnetic fields for 2 years demonstrated no increases in the incidence of mammary cancer; it is generally accepted that power-frequency magnetic fields have little or no activity as a complete carcinogen in the rodent mammary gland. Findings from one laboratory, though inconsistent, suggest that magnetic fields may stimulate mammary neoplasia in rats treated with a chemical carcinogen. However, studies conducted in two other laboratories failed to confirm these findings; rats exposed to magnetic fields demonstrated patterns of tumor incidence, multiplicity, size and latency that were generally similar to those in sham-exposed controls. Where differences were seen, the groups exposed to magnetic fields generally had fewer mammary tumors than did sham-exposed controls. On this basis, evaluations of the activity of 50 or 60 Hz magnetic fields in models of multistage mammary cancer in rodents have generally been negative; positive findings have been reported from only one laboratory. The totality of rodent data does not support the hypothesis that power-frequency magnetic-field exposure enhances mammary cancer in rodents, nor does it provide experimental support for possible epidemiological associations between magnetic-field exposure and increased breast cancer risk. JF - Radiation Research AU - Boorman, G A AU - McCormick, D L AU - Ward, J M AU - Haseman, J K AU - Sills, R C AD - National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709 Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 617 EP - 626 PB - Radiation Research Society VL - 153 IS - 5 SN - 0033-7587, 0033-7587 KW - Toxicology Abstracts KW - Magnetic fields KW - Mammary gland KW - Reviews KW - Carcinogenesis KW - Animal models KW - Breast cancer KW - Carcinogens KW - Tumors KW - Neoplasia KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17855176?accountid=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=Magnetic+Fields+and+Mammary+Cancer+in+Rodents%3A+A+Critical+Review+and+Evaluation+of+Published+Literature&rft.au=Boorman%2C+G+A%3BMcCormick%2C+D+L%3BWard%2C+J+M%3BHaseman%2C+J+K%3BSills%2C+R+C&rft.aulast=Boorman&rft.aufirst=G&rft.date=2000-05-01&rft.volume=153&rft.issue=5&rft.spage=617&rft.isbn=&rft.btitle=&rft.title=Radiation+Research&rft.issn=00337587&rft_id=info:doi/10.1043%2F0033-7587%282000%291532.0.CO%3B2 L2 - http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0033-7587&volume=153&page=617 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Magnetic fields; Mammary gland; Reviews; Carcinogenesis; Animal models; Breast cancer; Tumors; Carcinogens; Neoplasia DO - http://dx.doi.org/10.1043/0033-7587(2000)153<0617:MFAMCI>2.0.CO;2 ER - TY - JOUR T1 - Variable small protein (Vsp)-dependent and Vsp-independent pathways for glycosaminoglycan recognition by relapsing fever spirochaetes AN - 17829287; 4864970 AB - Tick-borne relapsing fever, caused by pathogenic Borrelia such as B. hermsii and B. turicatae, features recurrent episodes of bacteraemia, each of which is caused by a population of spirochaetes that expresses a different variable major protein. Relapsing fever is also associated with the infection of a variety of tissues, such as the central nervous system. In this study, we show that glycosaminoglycans (GAGs) mediate the attachment of relapsing fever spirochaetes to mammalian cells. B. hermsii strain DAH bound to immobilized heparin, and heparin and dermatan sulphate blocked bacterial binding to host cells. Bacterial binding was diminished by inhibition of host cell GAG synthesis or sulphation, or by the enzymatic removal of GAGs. GAGs mediated the attachment of relapsing fever spirochaetes to potentially relevant target cells, such as endothelial and glial cells. B. hermsii was able to attach to GAGs independently of variable major proteins, because strains expressing the variable major proteins Vsp33, Vlp7 or no variable major protein at all each recognized GAGs. Nevertheless, we found that a variable major protein of B. turicatae directly promoted GAG binding by this relapsing fever spirochaete. B. turicatae strain Oz1 serotype B, which expresses the variable major protein VspB, bound to GAGs more efficiently than did B. turicatae Oz1 serotype A, which expresses VspA. Recombinant VspB, but not VspA, bound to heparin and dermatan sulphate. Previous studies have shown that strain Oz1 serotype B grows to higher concentrations in the blood than does Oz1 serotype A. Thus, relapsing fever spirochaetes have the potential to express Vsp-dependent and Vsp-independent GAG-binding activities and, for one pair of highly related B. turicatae strains, differences in GAG binding correlate with differences in tissue tropism. JF - Molecular Microbiology AU - Magoun, L AU - Zueckert, R W AU - Robbins, D AU - Parveen, N AU - Alugupalli, R K AU - Schwan, G T AU - Barbour, G A AU - Leong, MJ AD - Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.Departments of Microbiology and Molecular Genetics and Medicine, University of California Irvine, Irvine, CA 92697, USA.Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, MT 59840, USA. Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 886 EP - 897 PB - Blackwell Science Ltd VL - 36 IS - 4 SN - 0950-382X, 0950-382X KW - pathways KW - recognition KW - Vsp protein KW - glycosaminoglycans KW - Microbiology Abstracts B: Bacteriology KW - Relapsing fever KW - Borrelia KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17829287?accountid=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=Variable+small+protein+%28Vsp%29-dependent+and+Vsp-independent+pathways+for+glycosaminoglycan+recognition+by+relapsing+fever+spirochaetes&rft.au=Magoun%2C+L%3BZueckert%2C+R+W%3BRobbins%2C+D%3BParveen%2C+N%3BAlugupalli%2C+R+K%3BSchwan%2C+G+T%3BBarbour%2C+G+A%3BLeong%2C+MJ&rft.aulast=Magoun&rft.aufirst=L&rft.date=2000-05-01&rft.volume=36&rft.issue=4&rft.spage=886&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&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 - Borrelia; Relapsing fever ER - TY - JOUR T1 - Limitations of Informed Consent for in Utero Gene Transfer Research: Implications for Investigators and Institutional Review Boards AN - 17661972; 4714306 AB - Only 10 years after the first human gene transfer protocols were approved for adults and children, researchers have begun to consider gene transfer on the fetus. While preliminary animal research is ongoing, the enthusiasm and pace of research in this area suggest that human protocols for in utero gene transfer research may be seriously considered in the foreseeable future. Federal guidelines for fetal research rely on minimizing risk and informed consent to protect the "rights and welfare" of both the fetus and pregnant woman. However, in utero gene transfer research poses special challenges to informed consent. This research represents an innovative approach for very ill subjects and takes place in the prenatal setting. These features may converge to undermine the expectant parents' comprehension of, and voluntariness for participation in, research. In this case, informed consent may not be able to bear the weight of adequately protecting the fetus from undue research risks. To compensate for this limitation, and using the regulations for pediatric research as a guide, a greater emphasis should be placed on the benefit/harm assessment rather than informed consent. Selecting diseases/patients where good alternative treatments exist may maximize informed consent, yet this may be a trade-off that exposes the fetus to greater relative risks. On the other hand, selecting diseases/patients without good alternative treatments to prolong life may convey an overestimation of the potential benefits of these interventions, and although care should be taken to strive to improve understanding of these limitations, misunderstanding may persist. However, selecting diseases/patients with no good alternatives might make serious risks more tolerable, and this should take precedence over informed consent. The limitations of informed consent brought into focus by the special features of in utero gene transfer research may be relevant to a broader range of innovative investigations. JF - Human Gene Therapy AU - Burger, I M AU - Wilfond, B S AD - National Human Genome Research Institute, Building 10, Room 1C118 (Department of Clinical Bioethics), 9000 Rockville Pike, Bethesda, MD 20892-1156, USA, wilfond@nih.gov Y1 - 2000/05/01/ PY - 2000 DA - 2000 May 01 SP - 1057 EP - 1063 VL - 11 IS - 7 SN - 1043-0342, 1043-0342 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene therapy KW - Pediatrics KW - Gene transfer KW - Reviews KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17661972?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Limitations+of+Informed+Consent+for+in+Utero+Gene+Transfer+Research%3A+Implications+for+Investigators+and+Institutional+Review+Boards&rft.au=Burger%2C+I+M%3BWilfond%2C+B+S&rft.aulast=Burger&rft.aufirst=I&rft.date=2000-05-01&rft.volume=11&rft.issue=7&rft.spage=1057&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene transfer; Reviews; Gene therapy; Pediatrics ER - TY - JOUR T1 - The genetics and biochemistry of isoniazid resistance in Mycobacterium tuberculosis AN - 17598930; 4732461 AB - Although the primary targets of activated isoniazid (INH) are proteins involved in the biosynthesis of cell wall mycolic acids, clinical resistance is dominated by specific point mutations in katG. Mutations associated with target mutations contribute to, but still cannot completely explain, resistance to INH. Despite the wealth of genetic information currently available, the molecular mechanism of cell death induced by INH remains elusive. JF - Microbes and Infection AU - Slayden, R A AU - Barry, CE AD - Tuberculosis Research Section, Laboratory of Host Defenses, NIAID, NIH, 12441 Parklawn Dr., Rockville, MD 20852, USA Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 659 EP - 669 VL - 2 IS - 6 SN - 1286-4579, 1286-4579 KW - isoniazid KW - katG gene KW - mycolic acids KW - Microbiology Abstracts B: Bacteriology KW - Cell death KW - Reviews KW - Drug resistance KW - Point mutation KW - Cell walls KW - Mycobacterium tuberculosis KW - J 02814:Drug resistance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17598930?accountid=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=Microbes+and+Infection&rft.atitle=The+genetics+and+biochemistry+of+isoniazid+resistance+in+Mycobacterium+tuberculosis&rft.au=Slayden%2C+R+A%3BBarry%2C+CE&rft.aulast=Slayden&rft.aufirst=R&rft.date=2000-05-01&rft.volume=2&rft.issue=6&rft.spage=659&rft.isbn=&rft.btitle=&rft.title=Microbes+and+Infection&rft.issn=12864579&rft_id=info:doi/10.1016%2FS1286-4579%2800%2900359-2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium tuberculosis; Drug resistance; Point mutation; Cell walls; Cell death; Reviews DO - http://dx.doi.org/10.1016/S1286-4579(00)00359-2 ER - TY - JOUR T1 - Alteration of the Behavioral Effects of Nicotine by Chronic Caffeine Exposure AN - 17554188; 4737933 AB - The prevalence of tobacco smoking and coffee drinking place nicotine and caffeine among the most used licit drugs in many societies and their consumption is often characterised by concurrent use. The pharmacological basis for any putative interaction between these drugs remains unclear. Some epidemiological reports support anecdotal evidence, which suggests that smokers consume caffeine to enhance the effects of nicotine. This paper reviews various aspects of the pharmacology of caffeine and nicotine, in humans and experimental animals, important for the understanding of the interactions between these drugs. In particular, recent experiments are reviewed in which chronic exposure to caffeine in the drinking water of rats facilitated acquisition of self-adminstration behavior, enhanced nicotine-induced increases in dopamine levels in the shell of the nucleus accumbens and altered the dopaminergic component of a nicotine discrimination. These studies provide evidence that the rewarding and subjective properties of nicotine can be changed by chronic caffeine exposure and indicate that caffeine exposure may be an important environmental factor in shaping and maintaining tobacco smoking. JF - Pharmacology Biochemistry and Behavior AU - Tanda, G AU - Goldberg AD - NIH, NIDA, IRP, Preclinical Pharmacology Section, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, sgoldber@intra.nida.nih.gov Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 47 EP - 64 VL - 66 IS - 1 SN - 0091-3057, 0091-3057 KW - chronic exposure KW - Toxicology Abstracts KW - Behavior KW - Nicotine KW - Reviews KW - Cigarette smoking KW - Caffeine KW - X 24120:Food, additives & contaminants KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17554188?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacology+Biochemistry+and+Behavior&rft.atitle=Alteration+of+the+Behavioral+Effects+of+Nicotine+by+Chronic+Caffeine+Exposure&rft.au=Tanda%2C+G%3BGoldberg&rft.aulast=Tanda&rft.aufirst=G&rft.date=2000-05-01&rft.volume=66&rft.issue=1&rft.spage=47&rft.isbn=&rft.btitle=&rft.title=Pharmacology+Biochemistry+and+Behavior&rft.issn=00913057&rft_id=info:doi/10.1016%2FS0091-3057%2800%2900234-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special issue: Drugs of desire. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Nicotine; Behavior; Cigarette smoking; Reviews; Caffeine DO - http://dx.doi.org/10.1016/S0091-3057(00)00234-3 ER - TY - JOUR T1 - Recent geographic patterns of lung cancer and mesothelioma mortality rates in 49 shipyard counties in the United States, 1970-94 AN - 17535634; 4720863 AB - Lung cancer mortality rates among white males in the United States were observed to be elevated during 1950-69 in counties with shipbuilding industries during World War II; risk was found to be associated with asbestos exposure. We evaluated the geographic patterns in more recent years, 1970-94, for whites and compared them with the 1950-69 patterns. We calculated age-adjusted rates and estimated rate ratios between comparison groups. Rates generally were higher in shipyard counties than in all nonshipyard counties and in coastal nonshipyard counties for both sexes and time periods. Rates increased markedly from 1950-69 to 1970-94 in all groups, with the changes more pronounced in females than males. Pleural mesothelioma mortality rates were also significantly higher in shipyard counties than coastal nonshipyard counties in all regions among males but not among females. The more pronounced changes in lung cancer mortality rates among females in shipyard counties may be attributed to the combined effects of low asbestos exposures and changes in smoking behavior. JF - American Journal of Industrial Medicine AU - Jemal, A AU - Grauman, D AU - Devesa, S AD - 6120 Executive Blvd, EPS 8049 Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7244, USA, jemala@exchange.nih.gov Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 512 EP - 521 VL - 37 IS - 5 SN - 0271-3586, 0271-3586 KW - USA KW - mesothelioma KW - shipbuilding KW - Health & Safety Science Abstracts KW - Mortality KW - Cigarette smoking KW - Occupational exposure KW - Lung cancer KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17535634?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Industrial+Medicine&rft.atitle=Recent+geographic+patterns+of+lung+cancer+and+mesothelioma+mortality+rates+in+49+shipyard+counties+in+the+United+States%2C+1970-94&rft.au=Jemal%2C+A%3BGrauman%2C+D%3BDevesa%2C+S&rft.aulast=Jemal&rft.aufirst=A&rft.date=2000-05-01&rft.volume=37&rft.issue=5&rft.spage=512&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Occupational exposure; Lung cancer; Mortality; Cigarette smoking ER - TY - JOUR T1 - Oxidative DNA damage in fetal tissues after transplacental exposure to 3'-azido-3'-deoxythymidine (AZT) AN - 17532823; 4717883 AB - The nucleoside analogue 3'-azido-3'-deoxythymidine (AZT) has been used successfully to reduce the incidence of transplacental and perinatal transmission of the HIV virus. However, prolonged treatment with high doses of AZT is utilized in this therapy, and AZT has been found to be a perinatal carcinogen in mice. Any possible perinatal carcinogenic side effects in the human can best be managed if the mechanism is understood. AZT targets mitochondria and might cause increased intracellular production of reactive oxygen species (ROS). We tested whether transplacental AZT may cause oxidative damage in nuclear DNA of fetal tissues. CD-1 Swiss pregnant mice were treated with the transplacental carcinogenesis regimen (25 mg/day AZT, for gestation days 12-18) and tissues collected on the day of birth. Significant increases in 8-oxo-2'-deoxyguano- sine (8-oxo-dG) were found in the livers, a target tissue for transplacental carcinogenesis, and in the kidneys. A non-significant increase occurred in brain, with no change in lung. Tissues were also obtained from fetal patas monkeys (Erythrocebus patas), whose mothers had received 10 mg AZT/day during the last half of gestation. Although limited numbers of samples were available, possible increases in 8-oxo-dG were noted, relative to controls, for placenta and for fetal lung and brain (P = 0.055 for treatment-related increases in these tissues). These results suggest that an increase in reactive oxygen species could contribute to the mechanism of transplacental carcinogenesis by AZT in mice, and that this may also occur in primates. JF - Carcinogenesis AU - Bialkowska, A AU - Bialkowski, K AU - Gerschenson, M AU - Diwan, BA AU - Jones, AB AU - Olivero, O A AU - Poirier, M C AU - Anderson, L M AU - Kasprzak, K S AU - Sipowicz, MA AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, FCRDC, Frederick, MD 21702, USA Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 1059 EP - 1062 VL - 21 IS - 5 SN - 0143-3334, 0143-3334 KW - mice KW - monkeys KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - DNA damage KW - Reactive oxygen species KW - Placental transfer KW - Carcinogenesis KW - Zidovudine KW - N 14630:Chemical reactions & interactions, including effects of radiation KW - X 24117:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17532823?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Oxidative+DNA+damage+in+fetal+tissues+after+transplacental+exposure+to+3%27-azido-3%27-deoxythymidine+%28AZT%29&rft.au=Bialkowska%2C+A%3BBialkowski%2C+K%3BGerschenson%2C+M%3BDiwan%2C+BA%3BJones%2C+AB%3BOlivero%2C+O+A%3BPoirier%2C+M+C%3BAnderson%2C+L+M%3BKasprzak%2C+K+S%3BSipowicz%2C+MA&rft.aulast=Bialkowska&rft.aufirst=A&rft.date=2000-05-01&rft.volume=21&rft.issue=5&rft.spage=1059&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Zidovudine; Carcinogenesis; Placental transfer; Reactive oxygen species; DNA damage ER - TY - JOUR T1 - Occupation and Prostate Cancer Risk in Sweden AN - 17531909; 4718498 AB - To provide new leads regarding occupational prostate cancer risk factors, we linked 36,269 prostate cancer cases reported to the Swedish National Cancer Registry during 1961 to 1979 with employment information from the 1960 National Census. Standardized incidence ratios for prostate cancer, within major (1-digit), general (2-digit), and specific (3-digit) industries and occupations, were calculated. Significant excess risks were seen for agriculture-related industries, soap and perfume manufacture, and leather processing industries. Significantly elevated standardized incidence ratios were also seen for the following occupations: farmers, leather workers, and white-collar occupations. Our results suggest that farmers; certain occupations and industries with exposures to cadmium, herbicides, and fertilizers; and men with low occupational physical activity levels have elevated prostate cancer risks. Further research is needed to confirm these findings and identify specific exposures related to excess risk in these occupations and industries. JF - Journal of Occupational and Environmental Medicine AU - Sharma-Wagner, S AU - Chokkalingam, A P AU - Malker, HSR AU - Stone, B J AU - McLaughlin, J K AU - Hsing, A W AD - Division of Cancer Epidemiology and Genetics, EPS 7058, MSC 7234, 6120 Executive Boulevard, Bethesda, MD 20892-7234, USA, hsinga@exchange.nih.gov Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 517 EP - 525 VL - 42 IS - 5 SN - 1076-2752, 1076-2752 KW - man KW - Sweden KW - prostate KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Agriculture KW - Fertilizers KW - Cadmium KW - Industrial pollution KW - Occupational exposure KW - Herbicides KW - Cancer KW - Tanning industry KW - Carcinogenesis KW - Prostate KW - R2 23080:Industrial and labor KW - X 24240:Miscellaneous KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17531909?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Occupational+and+Environmental+Medicine&rft.atitle=Occupation+and+Prostate+Cancer+Risk+in+Sweden&rft.au=Sharma-Wagner%2C+S%3BChokkalingam%2C+A+P%3BMalker%2C+HSR%3BStone%2C+B+J%3BMcLaughlin%2C+J+K%3BHsing%2C+A+W&rft.aulast=Sharma-Wagner&rft.aufirst=S&rft.date=2000-05-01&rft.volume=42&rft.issue=5&rft.spage=517&rft.isbn=&rft.btitle=&rft.title=Journal+of+Occupational+and+Environmental+Medicine&rft.issn=10762752&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cancer; Occupational exposure; Cadmium; Fertilizers; Herbicides; Tanning industry; Agriculture; Prostate; Carcinogenesis; Risk assessment; Industrial pollution ER - TY - JOUR T1 - Negligible genetic diversity of Mycobacterium tuberculosis host immune system protein targets: evidence of limited selective pressure AN - 17531014; 4715975 AB - A common theme in medical microbiology is that the amount of amino acid sequence variation in proteins that are targets of the host immune system greatly exceeds that found in metabolic enzymes or other housekeeping proteins. Twenty-four Mycobacterium tuberculosis genes coding for targets of the host immune system were sequenced in 16 strains representing the breadth of genomic diversity in the species. Of the 24 genes, 19 were invariant and only six polymorphic nucleotide sites were identified in the 5 genes that did have variation. The results document the highly unusual circumstance that prominent M. tuberculosis antigenic proteins have negligible structural variation worldwide. The data are best explained by a combination of three factors: (i) evolutionarily recent global dissemination in humans, (ii) lengthy intracellular quiescence, and (iii) active replication in relatively few fully immunocompetent hosts. The very low level of amino acid diversity in antigenic proteins may be cause for optimism in the difficult fight to control global tuberculosis. JF - Genetics AU - Musser, J M AU - Amin, A AU - Ramaswamy, S AD - 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 - 2000/05// PY - 2000 DA - May 2000 SP - 7 EP - 16 VL - 155 IS - 1 SN - 0016-6731, 0016-6731 KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Nucleotide sequence KW - Genetic diversity KW - Tuberculosis KW - Immune response KW - Mycobacterium tuberculosis KW - G 07320:Bacterial genetics KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17531014?accountid=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=Genetics&rft.atitle=Negligible+genetic+diversity+of+Mycobacterium+tuberculosis+host+immune+system+protein+targets%3A+evidence+of+limited+selective+pressure&rft.au=Musser%2C+J+M%3BAmin%2C+A%3BRamaswamy%2C+S&rft.aulast=Musser&rft.aufirst=J&rft.date=2000-05-01&rft.volume=155&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Corresponding author: James M. Musser N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium tuberculosis; Genetic diversity; Immune response; Nucleotide sequence; Tuberculosis ER - TY - JOUR T1 - DNA microarrays: translational tools for understanding the biology of Mycobacterium tuberculosis AN - 17529596; 4718015 AB - The determination of the complete genome sequence of Mycobacterium tuberculosis produced the first truly global information regarding the tubercle bacillus. We now know that M. tuberculosis has at least 3924 open reading frames (ORFs) that potentially encode proteins. The function of about one-third of these proteins can be predicted with precision and another third can be assigned to a functional class with some confidence or have other obvious bacterial homologs. The remaining third of the genome, however, encodes proteins that we know little or nothing about. Determining which of these proteins are actively expressed, and under what circumstances, represents the next great hurdle in understanding the biology of this important human pathogen. Such information will illuminate the biology of M. tuberculosis, unravel the dynamics of the host-pathogen interaction, and provide critical information regarding important new drug targets and reporters that will enable us to produce the next generation of anti-tubercular therapies. DNA microarrays will be a valuable tool in forging the link between genome and biology. This approach has recently matured from an idea with tremendous potential to an experimental technique that is now yielding useful data. The power of this technique has been demonstrated by two recent papers examining two different types of question. Behr et al. performed a comparative genomic analysis of the virulent M. tuberculosis strain H37Rv with various bacillus Calmette-Guerin (BCG) strains (the vaccine derived from Mycobacterium bovis, the causative agent of bovine tuberculosis) that had been passaged for several decades. Wilson and co-workers profiled the effects of the drug isoniazid on M. tuberculosis gene expression using differential gene expression analysis. These two different techniques rely on the same conceptually simple but technically daunting task: to create and array PCR products (corresponding to virtually all of the predicted ORFs) on a single glass microscope slide in an ultra-high-density grid, and to do so with pinpoint accuracy. Fluorescently labeled DNA or cDNA probes are then allowed to hybridize to the array and the intensity of each individual probe is quantitated by confocal fluorescence microscopy. JF - Trends in Microbiology AU - Barry, CE III AU - Schroeder, B G AD - Tuberculosis Research Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Disease, National Institutes of Health, Twinbrook II, Room 239, 12441 Parklawn Drive, Rockville, MD 20852, USA, clifton_barry@nih.gov Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 209 EP - 210 VL - 8 IS - 5 SN - 0966-842X, 0966-842X KW - DNA microarrays KW - Biotechnology and Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts; Microbiology Abstracts B: Bacteriology KW - Open reading frames KW - Mycobacterium tuberculosis KW - J 02704:Enumeration KW - W2 32385:DNA/RNA KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17529596?accountid=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=Trends+in+Microbiology&rft.atitle=DNA+microarrays%3A+translational+tools+for+understanding+the+biology+of+Mycobacterium+tuberculosis&rft.au=Barry%2C+CE+III%3BSchroeder%2C+B+G&rft.aulast=Barry&rft.aufirst=CE&rft.date=2000-05-01&rft.volume=8&rft.issue=5&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Trends+in+Microbiology&rft.issn=0966842X&rft_id=info:doi/10.1016%2FS0966-842X%2800%2901740-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium tuberculosis; Open reading frames DO - http://dx.doi.org/10.1016/S0966-842X(00)01740-6 ER - TY - JOUR T1 - Fetal Mitochondrial Heart and Skeletal Muscle Damage in Erythrocebus patas Monkeys Exposed in Utero to 3'-Azido-3'-Deoxythymidine AN - 17527244; 4713139 AB - 3'-Azido-3'-deoxythymidine (AZT) is given to pregnant women positive for the human immunodeficiency virus type 1 (HIV-1) to reduce maternal-fetal viral transmission. To explore fetal mitochondrial consequences of this exposure, pregnant Erythrocebus patas monkeys were given daily doses of 1.5 mg (21% of the human daily dose) and 6.0 mg (86% of the human daily dose) of AZT/kg body weight (bw), for the second half of gestation. At term, electron microscopy of fetal cardiac and skeletal muscle showed abnormal and disrupted sarcomeres with myofibrillar loss. Some abnormally shaped mitochondria with disrupted cristae were observed in skeletal muscle myocytes. Oxidative phosphorylation (OXPHOS) enzyme assays showed dose-dependent alterations. At the human-equivalent dose of AZT (6 mg of AZT/kg bw), there was an similar to 85% decrease in the specific activity of NADH dehydrogenase (complex I) and three- to sixfold increases in specific activities of succinate dehydrogenase (complex II) and cytochrome-c oxidase (complex IV). Furthermore, a dose-dependent depletion of mitochondrial DNA levels was observed in both tissues. The data demonstrate that transplacental AZT exposure causes cardiac and skeletal muscle mitochondrial myopathy in the patas monkey fetus. JF - AIDS Research and Human Retroviruses AU - Gerschenson, M AU - Erhart, S W AU - Paik, CY AU - St Claire, MC AU - Nagashima, Kunio AU - Skopets, B AU - Harbaugh, S W AU - Harbaugh, J W AU - Quan, Wing AU - Poirier, M C AD - Division of Basic Sciences, National Cancer Institute, NIH, 37 Convent Drive, Room 2A03, Bethesda, MD 20892-4255, USA, gerschem@exchange.nih.gov Y1 - 2000/05/01/ PY - 2000 DA - 2000 May 01 SP - 635 EP - 644 VL - 16 IS - 7 SN - 0889-2229, 0889-2229 KW - animal models KW - HIV KW - Virology & AIDS Abstracts; Toxicology Abstracts KW - Animal models KW - Zidovudine KW - Cytochrome-c oxidase KW - Antiviral agents KW - Succinate dehydrogenase KW - Skeletal muscle KW - Electron microscopy KW - Muscles KW - Cardiac muscle KW - NADH dehydrogenase KW - Human immunodeficiency virus KW - Erythrocebus patas KW - Side effects KW - X 24115:Pathology KW - V 22004:AIDS: Clinical aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17527244?accountid=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=AIDS+Research+and+Human+Retroviruses&rft.atitle=Fetal+Mitochondrial+Heart+and+Skeletal+Muscle+Damage+in+Erythrocebus+patas+Monkeys+Exposed+in+Utero+to+3%27-Azido-3%27-Deoxythymidine&rft.au=Gerschenson%2C+M%3BErhart%2C+S+W%3BPaik%2C+CY%3BSt+Claire%2C+MC%3BNagashima%2C+Kunio%3BSkopets%2C+B%3BHarbaugh%2C+S+W%3BHarbaugh%2C+J+W%3BQuan%2C+Wing%3BPoirier%2C+M+C&rft.aulast=Gerschenson&rft.aufirst=M&rft.date=2000-05-01&rft.volume=16&rft.issue=7&rft.spage=635&rft.isbn=&rft.btitle=&rft.title=AIDS+Research+and+Human+Retroviruses&rft.issn=08892229&rft_id=info:doi/10.1089%2F088922200308864 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; Erythrocebus patas; Zidovudine; Antiviral agents; Side effects; Electron microscopy; Cardiac muscle; Skeletal muscle; NADH dehydrogenase; Succinate dehydrogenase; Muscles; Cytochrome-c oxidase; Animal models DO - http://dx.doi.org/10.1089/088922200308864 ER - TY - JOUR T1 - The Stability Region of the Large Virulence Plasmid of Shigella flexneri Encodes an Efficient Postsegregational Killing System AN - 17524104; 4701971 AB - The large virulence plasmid pMYSH6000 of Shigella flexneri contains a determinant that is highly effective in stabilizing otherwise unstable plasmids in Escherichia coli. Expression of two small contiguous genes, mvpA and mvpT (formerly termed STBORF1 and STBORF2), was shown to be sufficient for stability. Mutations in mvpT abolished plasmid stability, and plasmids expressing only mvpT killed the cells unless mvpA was supplied from a separate plasmid or from the host chromosome. When replication of a plasmid carrying the minimal mvp region was blocked, growth of the culture stopped after a short lag and virtually all of the surviving cells retained the plasmid. Thus, the mvp system stabilizes by a highly efficient postsegregational killing (PSK) mechanism, with mvpT encoding a cell toxin and mvpA encoding an antidote. The regions that surround the mvp genes in their original context have an inhibitory effect that attenuates plasmid stabilization and PSK. The region encompassing the mvp genes also appears to contain an additional element that can aid propagation of a pSC101-based plasmid under conditions where replication initiation is marginal. However, this appears to be a relatively nonspecific effect of DNA insertion into the plasmid vector. JF - Journal of Bacteriology AU - Sayeed, S AU - Reaves, L AU - Radnedge, L AU - Austin, S AD - Gene Regulation and Chromosome Biology Laboratory, ABL Basic Research Program NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, austin@ncifcrf.gov Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 2416 EP - 2421 VL - 182 IS - 9 SN - 0021-9193, 0021-9193 KW - mvpA gene KW - mvpT gene KW - plasmid pMYSH6000 KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Virulence KW - Chromosomes KW - Shigella flexneri KW - Escherichia coli KW - J 02760:Plasmids KW - G 07203:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17524104?accountid=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=The+Stability+Region+of+the+Large+Virulence+Plasmid+of+Shigella+flexneri+Encodes+an+Efficient+Postsegregational+Killing+System&rft.au=Sayeed%2C+S%3BReaves%2C+L%3BRadnedge%2C+L%3BAustin%2C+S&rft.aulast=Sayeed&rft.aufirst=S&rft.date=2000-05-01&rft.volume=182&rft.issue=9&rft.spage=2416&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.182.9.2416-2421.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Shigella flexneri; Escherichia coli; Virulence; Chromosomes DO - http://dx.doi.org/10.1128/JB.182.9.2416-2421.2000 ER - TY - JOUR T1 - Efficient Targeted Mutagenesis in Borrelia burgdorferi AN - 17523729; 4701974 AB - Genetic studies in Borrelia burgdorferi have been hindered by the lack of a nonborrelial selectable marker. Currently the only selectable marker is gyrB super(r), a mutated form of the chromosomal gyrB gene that encodes the B subunit of DNA gyrase and confers resistance to the antibiotic coumermycin A sub(1). The utility of the coumermycin-resistant gyrB super(r) gene for targeted gene disruption is limited by a high frequency of recombination with the endogenous gyrB gene. A kanamycin resistance gene (kan) was introduced into B. burgdorferi, and its use as a selectable marker was explored in an effort to improve the genetic manipulation of this pathogen. B. burgdorferi transformants with the kan gene expressed from its native promoter were susceptible to kanamycin. In striking contrast, transformants with the kan gene expressed from either the B. burgdorferi flaB or flgB promoter were resistant to high levels of kanamycin. The kanamycin resistance marker allows efficient direct selection of mutants in B. burgdorferi and hence is a significant improvement in the ability to construct isogenic mutant strains in this pathogen. JF - Journal of Bacteriology AU - Bono, J L AU - Elias, A F AU - Kupko, JJ III AU - Stevenson, B AU - Tilly, K AU - Rosa, P AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, 903 South 4th St., Hamilton, MT 59840, jbono@niaid.nih.gov Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 2445 EP - 2452 VL - 182 IS - 9 SN - 0021-9193, 0021-9193 KW - mutagenesis KW - coumermycin KW - gyrB gene KW - kan gene KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Borrelia burgdorferi KW - DNA topoisomerase KW - Antibiotic resistance KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17523729?accountid=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=Efficient+Targeted+Mutagenesis+in+Borrelia+burgdorferi&rft.au=Bono%2C+J+L%3BElias%2C+A+F%3BKupko%2C+JJ+III%3BStevenson%2C+B%3BTilly%2C+K%3BRosa%2C+P&rft.aulast=Bono&rft.aufirst=J&rft.date=2000-05-01&rft.volume=182&rft.issue=9&rft.spage=2445&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.182.9.2445-2452.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Borrelia burgdorferi; DNA topoisomerase; Antibiotic resistance DO - http://dx.doi.org/10.1128/JB.182.9.2445-2452.2000 ER - TY - JOUR T1 - Effects of Glutaraldehyde in a 2-Year Inhalation Study in Rats and Mice AN - 17523077; 4710017 AB - Whole-body inhalation toxicology and carcinogenicity studies were performed with the widely used fixative and cold-sterilant glutaraldehyde. Groups of 50 male and female F344/N rats and B6C3F sub(1) mice were exposed to glutaraldehyde (rats: 0, 250, 500, or 750 ppb; mice: 0, 62.5, 125, or 250 ppb) 6 h/day, 5 days/week, for 104 weeks. Survival of 500- and 750-ppb female rats was less than that of controls. Mean body weights of all exposed groups of male rats, 500- and 750-ppb female rats, and 250-ppb female mice were generally less than those of controls. No exposure-related neoplastic lesions were observed in either rats or mice. Non-neoplastic lesions were limited primarily to the most anterior region of the nasal cavity. In rats, hyperplasia and inflammation of the squamous epithelium; hyperplasia, goblet cell hyperplasia, inflammation, and squamous metaplasia of the respiratory epithelium; and hyaline degeneration of the olfactory epithelium were observed. In mice, the nasal lesions were qualitatively similar to those in rats. Squamous metaplasia of the respiratory epithelium was observed in both sexes of mice while female mice also had inflammation and hyaline degeneration of the respiratory epithelium. In contrast to the nasal carcinogen formaldehyde, no neoplastic lesions were observed after inhalation exposure to glutaraldehyde. However, exposure to glutaraldehyde resulted in considerable non-neoplastic lesions in the noses of rats and mice. JF - Toxicological Sciences AU - van Birgelen, APJM AU - Chou, B J AU - Renne, R A AU - Grumbein, S L AU - Roycroft, J H AU - Hailey, J R AU - Bucher, J R AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 195 EP - 205 PB - Academic Press, Inc. VL - 55 IS - 1 SN - 1096-6080, 1096-6080 KW - sterilants KW - rats KW - mice KW - glutaraldehyde KW - Toxicology Abstracts KW - Body weight KW - Fixatives KW - Carcinogenicity KW - Lesions KW - Nose KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17523077?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Effects+of+Glutaraldehyde+in+a+2-Year+Inhalation+Study+in+Rats+and+Mice&rft.au=van+Birgelen%2C+APJM%3BChou%2C+B+J%3BRenne%2C+R+A%3BGrumbein%2C+S+L%3BRoycroft%2C+J+H%3BHailey%2C+J+R%3BBucher%2C+J+R&rft.aulast=van+Birgelen&rft.aufirst=APJM&rft.date=2000-05-01&rft.volume=55&rft.issue=1&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Carcinogenicity; Body weight; Lesions; Fixatives; Nose ER - TY - JOUR T1 - Possible Role of Caspase-3 Inhibition in Cadmium-Induced Blockage of Apoptosis AN - 17522865; 4710349 AB - Cadmium (Cd) and chromium (Cr) are human carcinogens. Cr(VI) is taken up into cells and reduced by cellular reductants to the potential DNA damaging species Cr(V), (IV), and (III). Reactive oxygen species and carbon-based radicals may also be produced during Cr reduction. We previously found that Cd blocks Cr-induced apoptosis, which could allow a larger proportion of genetically damaged cells to escape and become transformed. This study helped define the mechanisms of Cd-induced suppression of apoptosis. Chinese hamster ovary (CHO K1-BH4) cells were treated with either Cd (5-20 mu M), Cr(VI) (350 mu M), or Cd (5-20 mu M) plus Cr(VI) (350 mu M) for 3 h and then cultured in metal-free media for an additional 48 h at which time DNA was extracted or nuclei were examined to determine apoptosis. Cd markedly reduced Cr-induced DNA fragmentation and reduced the number of Cr-induced apoptotic cell nuclei to control levels. Additional study investigated the biokinetics and cellular metabolism of Cr. Cd did not alter the cellular Cr accumulation and there were no differences in the levels of reduced glutathione, a compound possibly important in Cr reduction and reflective of the cellular reducing environment. The antiapoptotic effect of Cd was not due to diminished cellular reduction of Cr(VI) as assessed by electron-spin resonance determination of the levels of Cr(V). Thus, Cd suppression of Cr-induced apoptosis is not based on altered Cr toxicokinetics or metabolism. In addition to Cr, Cd also inhibited apoptosis induced by hygromycin B and actinomycin D. Cd was a very effective inhibitor of caspase-3 activity, a central mediator of apoptosis, with nontoxic levels of Cd resulting in up to similar to 60% inhibition. These results indicate that Cd may have a generalized inhibitory effect on apoptosis, possibly by inhibiting caspase-3. Inhibition of apoptosis by Cd may allow a greater portion of genetically damaged cells to survive, or give selective growth advantages, and has implications as a potential nongenotoxic mechanism of Cd carcinogenesis. JF - Toxicology and Applied Pharmacology AU - Yuan, C AU - Kadiiska, M AU - Achanzar, W E AU - Mason, R P AU - Waalkes, M P AD - NCI at NIEHS, 111 Alexander Drive, P.O. Box 12233, MD F0-09, Research Triangle Park, NC 27709., waalkes@niehs.nih.gov Y1 - 2000/05/01/ PY - 2000 DA - 2000 May 01 SP - 321 EP - 329 PB - Academic Press VL - 164 IS - 3 SN - 0041-008X, 0041-008X KW - CHO cells KW - caspase-3 KW - Toxicology Abstracts KW - Apoptosis KW - Carcinogenesis KW - Cadmium KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17522865?accountid=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=Possible+Role+of+Caspase-3+Inhibition+in+Cadmium-Induced+Blockage+of+Apoptosis&rft.au=Yuan%2C+C%3BKadiiska%2C+M%3BAchanzar%2C+W+E%3BMason%2C+R+P%3BWaalkes%2C+M+P&rft.aulast=Yuan&rft.aufirst=C&rft.date=2000-05-01&rft.volume=164&rft.issue=3&rft.spage=321&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1006%2Ftaap.2000.8921 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cadmium; Apoptosis; Carcinogenesis DO - http://dx.doi.org/10.1006/taap.2000.8921 ER - TY - JOUR T1 - Multiple Antiviral Activities of Cyanovirin-N: Blocking of Human Immunodeficiency Virus Type 1 gp120 Interaction with CD4 and Coreceptor and Inhibition of Diverse Enveloped Viruses AN - 17513908; 4702389 AB - Cyanovirin-N (CV-N) is a cyanobacterial protein with potent neutralizing activity against human immunodeficiency virus (HIV). CV-N has been shown to bind HIV type 1 (HIV-1) gp120 with high affinity; moreover, it blocks the envelope glycoprotein-mediated membrane fusion reaction associated with HIV-1 entry. However, the inhibitory mechanism(s) remains unclear. In this study, we show that CV-N blocked binding of gp120 to cell-associated CD4. Consistent with this, pretreatment of gp120 with CV-N inhibited soluble CD4 (sCD4)-dependent binding of gp120 to cell-associated CCR5. To investigate possible effects of CV-N at post-CD4 binding steps we used an assay that measures sCD4 activation of the HIV-1 envelope glycoprotein for fusion with CCR5-expressing cells. CV-N displayed equivalently potent inhibitory effects when added before or after sCD4 activation, suggesting that CV-N also has blocking action at the level of gp120 interaction with coreceptor. This effect was shown not to be due to CV-N-induced coreceptor down-modulation after the CD4 binding step. The multiple activities against the HIV-1 envelope glycoprotein prompted us to examine other enveloped viruses. CV-N potently blocked infection by feline immunodeficiency virus, which utilizes the chemokine receptor CXCR4 as an entry receptor but is CD4 independent. CV-N also inhibited fusion and/or infection by human herpesvirus 6 and measles virus but not by vaccinia virus. Thus, CV-N has broad-spectrum antiviral activity, both for multiple steps in the HIV entry mechanism and for diverse enveloped viruses. This broad specificity has implications for potential clinical utility of CV-N. JF - Journal of Virology AU - Dey, B AU - Lerner, D L AU - Lusso, P AU - Boyd, M R AU - Elder, J H AU - Berger, E A AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Building 4, room 237, National Institutes of Health, Bethesda, MD 20892, edward_berger@nih.gov Y1 - 2000/05// PY - 2000 DA - May 2000 SP - 4562 EP - 4569 VL - 74 IS - 10 SN - 0022-538X, 0022-538X KW - HIV-1 KW - CCR5 antigen KW - CCR5 protein KW - CD4 antigen KW - cyanovirin-N KW - Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; ASFA Marine Biotechnology Abstracts KW - Feline immunodeficiency virus KW - Human herpesvirus 6 KW - Measles virus KW - Glycoprotein gp120 KW - Envelopes KW - Antiviral agents KW - Human immunodeficiency virus 1 KW - Receptors KW - Cyanophyta KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01068:Antiviral & viricidal KW - Q4 27380:Pharmaceuticals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17513908?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=Multiple+Antiviral+Activities+of+Cyanovirin-N%3A+Blocking+of+Human+Immunodeficiency+Virus+Type+1+gp120+Interaction+with+CD4+and+Coreceptor+and+Inhibition+of+Diverse+Enveloped+Viruses&rft.au=Dey%2C+B%3BLerner%2C+D+L%3BLusso%2C+P%3BBoyd%2C+M+R%3BElder%2C+J+H%3BBerger%2C+E+A&rft.aulast=Dey&rft.aufirst=B&rft.date=2000-05-01&rft.volume=74&rft.issue=10&rft.spage=4562&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/10.1128%2FJVI.74.10.4562-4569.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Measles virus; Feline immunodeficiency virus; Human herpesvirus 6; Cyanophyta; Human immunodeficiency virus 1; Receptors; Glycoprotein gp120; Antiviral agents; Envelopes DO - http://dx.doi.org/10.1128/JVI.74.10.4562-4569.2000 ER - TY - JOUR T1 - A model to estimate the probability of hepatitis B- and Haemophilus influenzae type b-vaccine uptake into national vaccination programs AN - 17541940; 4723853 AB - Most countries have been slow to adopt new vaccines into national vaccination schedules, despite recommendations from global multi-lateral agencies. Characteristics of countries that have adopted hepatitis B (HB) vaccine were analysed and used to formulate a logistic regression model. The model was applied to country-specific data to predict HB and Haemophilus influenzae type b (Hib) vaccine uptake. The greatest predictors of HB uptake were coverage rates of other vaccines, vaccine cost relative to the economy, and perceived disease burden. The logistic regression model's probability estimate of vaccine uptake agreed well with observed data for HB and Hib, (c-statistic 85 and 82%, respectively). Application of this model to other antigens may aid in predicting potential national markets to better plan new vaccine supply and demand. JF - Vaccine AU - Miller, MA AU - Flanders, W D AD - Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA, millermark@nih.gov Y1 - 2000/04/28/ PY - 2000 DA - 2000 Apr 28 SP - 2223 EP - 2230 VL - 18 IS - 21 SN - 0264-410X, 0264-410X KW - immunology KW - Haemophilus influenzae KW - Hepatitis B virus KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts; Immunology Abstracts KW - Control programs KW - Disease control KW - Government policy KW - Hepatitis B KW - Vaccines KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization KW - V 22097:Immunization: Vaccines & vaccination: Human UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17541940?accountid=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+model+to+estimate+the+probability+of+hepatitis+B-+and+Haemophilus+influenzae+type+b-vaccine+uptake+into+national+vaccination+programs&rft.au=Miller%2C+MA%3BFlanders%2C+W+D&rft.aulast=Miller&rft.aufirst=MA&rft.date=2000-04-28&rft.volume=18&rft.issue=21&rft.spage=2223&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Hepatitis B virus; Haemophilus influenzae; Hepatitis B; Vaccines; Control programs; Government policy; Disease control ER - TY - JOUR T1 - Low fidelity DNA synthesis by human DNA polymerase-eta. AN - 71087208; 10801132 AB - A superfamily of DNA polymerases that bypass lesions in DNA has been described. Some family members are described as error-prone because mutations that inactivate the polymerase reduce damage-induced mutagenesis. In contrast, mutations in the skin cancer susceptibility gene XPV, which encodes DNA polymerase (pol)-eta, lead to increased ultraviolet-induced mutagenesis. This, and the fact that pol-eta primarily inserts adenines during efficient bypass of thymine-thymine dimers in vitro, has led to the description of pol-eta as error-free. However, here we show that human pol-eta copies undamaged DNA with much lower fidelity than any other template-dependent DNA polymerase studied. Pol-eta lacks an intrinsic proofreading exonuclease activity and, depending on the mismatch, makes one base substitution error for every 18 to 380 nucleotides synthesized. This very low fidelity indicates a relaxed requirement for correct base pairing geometry and indicates that the function of pol-eta may be tightly controlled to prevent potentially mutagenic DNA synthesis. JF - Nature AU - Matsuda, T AU - Bebenek, K AU - Masutani, C AU - Hanaoka, F AU - Kunkel, T A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000/04/27/ PY - 2000 DA - 2000 Apr 27 SP - 1011 EP - 1013 VL - 404 IS - 6781 SN - 0028-0836, 0028-0836 KW - DNA KW - 9007-49-2 KW - DNA polymerase iota KW - EC 2.7.7.- KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Rad30 protein KW - Index Medicus KW - DNA Repair KW - DNA Damage KW - Humans KW - Mutagenesis KW - DNA -- biosynthesis KW - DNA-Directed DNA Polymerase -- genetics KW - DNA-Directed DNA Polymerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71087208?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Low+fidelity+DNA+synthesis+by+human+DNA+polymerase-eta.&rft.au=Matsuda%2C+T%3BBebenek%2C+K%3BMasutani%2C+C%3BHanaoka%2C+F%3BKunkel%2C+T+A&rft.aulast=Matsuda&rft.aufirst=T&rft.date=2000-04-27&rft.volume=404&rft.issue=6781&rft.spage=1011&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-25 N1 - Date created - 2000-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acute and chronic effects of the synthetic neuroactive steroid, ganaxolone, against the convulsive and lethal effects of pentylenetetrazol in seizure-kindled mice: comparison with diazepam and valproate. AN - 71029332; 10760361 AB - A high-affinity positive modulator of the GABA(A) receptor complex, ganaxolone, is a 3beta-methylated analog of the naturally occurring neuroactive steroid allopregnanolone. In the present study, ganaxolone was tested for its ability to (1) suppress seizures (clonic and tonic) and lethality induced by pentylenetetrazol (PTZ) in PTZ-kindled mice (anticonvulsive effect) and (2) to attenuate the development of sensitization to the convulsive and lethal effects of PTZ in kindled mice (anti-epileptogenic effect) when given as a pretreatment prior to each PTZ injection during kindling acquisition. Two classical antiepileptic drugs, diazepam and valproate, were tested for comparison. All three drugs dose-dependently suppressed tonic seizures and lethality induced by PTZ in kindled mice; only ganaxolone was effective against clonic seizures. Ganaxolone showed anti-epileptogenic properties as it reduced the sensitivity of kindled mice to the convulsive (clonic and tonic seizures) and lethal effects of PTZ. Diazepam showed anti-epileptogenic effects against tonic seizures and lethality, but not clonic seizures; valproate was ineffective in preventing development of any of these effects. Sensitivity to PTZ-induced seizures and lethality was not affected in mice with a history of repeated treatment with ganaxolone, diazepam, or valproate. The drugs had effects on ambulatory activity that ranged from no effect (ganaxolone) through moderate impairment (diazepam) to marked disruption (valproate). Taken together, the results of the present study add to accumulating evidence of the unique anticonvulsive/behavioral profile of neuroactive steroids. JF - Neuropharmacology AU - Gasior, M AU - Ungard, J T AU - Beekman, M AU - Carter, R B AU - Witkin, J M AD - Drug Development Group, Behavioral Neuroscience Research Branch, Addiction Research Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. mgasior@intra.nida.nih.gov Y1 - 2000/04/27/ PY - 2000 DA - 2000 Apr 27 SP - 1184 EP - 1196 VL - 39 IS - 7 SN - 0028-3908, 0028-3908 KW - Anticonvulsants KW - 0 KW - Convulsants KW - Valproic Acid KW - 614OI1Z5WI KW - ganaxolone KW - 98WI44OHIQ KW - Pregnanolone KW - BXO86P3XXW KW - Diazepam KW - Q3JTX2Q7TU KW - Pentylenetetrazole KW - WM5Z385K7T KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Motor Activity -- drug effects KW - Mice KW - Stereotypic Movement Disorder -- chemically induced KW - Male KW - Valproic Acid -- pharmacology KW - Anticonvulsants -- pharmacology KW - Kindling, Neurologic -- drug effects KW - Seizures -- mortality KW - Pentylenetetrazole -- toxicity KW - Diazepam -- pharmacology KW - Convulsants -- antagonists & inhibitors KW - Pregnanolone -- pharmacology KW - Seizures -- prevention & control KW - Pentylenetetrazole -- antagonists & inhibitors KW - Kindling, Neurologic -- physiology KW - Pregnanolone -- analogs & derivatives KW - Convulsants -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71029332?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Acute+and+chronic+effects+of+the+synthetic+neuroactive+steroid%2C+ganaxolone%2C+against+the+convulsive+and+lethal+effects+of+pentylenetetrazol+in+seizure-kindled+mice%3A+comparison+with+diazepam+and+valproate.&rft.au=Gasior%2C+M%3BUngard%2C+J+T%3BBeekman%2C+M%3BCarter%2C+R+B%3BWitkin%2C+J+M&rft.aulast=Gasior&rft.aufirst=M&rft.date=2000-04-27&rft.volume=39&rft.issue=7&rft.spage=1184&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=00283908&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-15 N1 - Date created - 2000-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - AMPA receptor blockade improves levodopa-induced dyskinesia in MPTP monkeys. AN - 71032019; 10762498 AB - To evaluate the contribution of amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) glutamate receptors to the pathogenesis of parkinsonian signs and levodopa-induced dyskinesias. Motor fluctuations and dyskinesias reflect, in part, altered function of glutamate receptors of the NMDA subtype. The possible role of AMPA receptors, however, has not yet been examined. The authors compared the ability of an AMPA agonist (CX516) and a noncompetitive AMPA antagonist (LY300164) to alter parkinsonian symptoms and levodopa-induced dyskinesia in MPTP-lesioned monkeys. Eight levodopa-treated parkinsonian monkeys received rising doses of each drug, first in monotherapy and then in combination with low-, medium-, and high-dose levodopa. CX516 alone, as well as when combined with low-dose levodopa, did not affect motor activity but induced dyskinesia. Moreover, following injection of the higher doses of levodopa, it increased levodopa-induced dyskinesia by up to 52% (p < 0.05). LY300164 potentiated the motor activating effects of low-dose levodopa, increasing motor activity by as much as 86% (p < 0.05), and that of medium-dose levodopa as much as 54% (p < 0.05). At the same time, LY300164 decreased levodopa-induced dyskinesia by up to 40% (p < 0.05). AMPA receptor upregulation may contribute to the expression of levodopa-induced dyskinesia. Conceivably, noncompetitive AMPA receptor antagonists could be useful, alone or in combination with NMDA antagonists, in the treatment of PD, by enhancing the antiparkinsonian effects of levodopa without increasing and possibly even decreasing levodopa-induced dyskinesia. JF - Neurology AU - Konitsiotis, S AU - Blanchet, P J AU - Verhagen, L AU - Lamers, E AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892-1406, USA. Y1 - 2000/04/25/ PY - 2000 DA - 2000 Apr 25 SP - 1589 EP - 1595 VL - 54 IS - 8 SN - 0028-3878, 0028-3878 KW - 1-(quinoxalin-6-ylcarbonyl)piperidine KW - 0 KW - Dioxoles KW - Excitatory Amino Acid Antagonists KW - Piperidines KW - Receptors, AMPA KW - Benzodiazepines KW - 12794-10-4 KW - GYKI 53405 KW - 143691-37-6 KW - Levodopa KW - 46627O600J KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Abridged Index Medicus KW - Index Medicus KW - Severity of Illness Index KW - Animals KW - Macaca fascicularis KW - Levodopa -- administration & dosage KW - Dose-Response Relationship, Drug KW - Excitatory Amino Acid Antagonists -- therapeutic use KW - Disease Models, Animal KW - Motor Activity -- drug effects KW - Drug Synergism KW - Male KW - Female KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Piperidines -- pharmacology KW - Parkinson Disease, Secondary -- chemically induced KW - Dyskinesia, Drug-Induced -- metabolism KW - Benzodiazepines -- therapeutic use KW - Receptors, AMPA -- antagonists & inhibitors KW - Dyskinesia, Drug-Induced -- drug therapy KW - Receptors, AMPA -- agonists KW - Benzodiazepines -- pharmacology KW - Dioxoles -- pharmacology KW - Parkinson Disease, Secondary -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71032019?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=AMPA+receptor+blockade+improves+levodopa-induced+dyskinesia+in+MPTP+monkeys.&rft.au=Konitsiotis%2C+S%3BBlanchet%2C+P+J%3BVerhagen%2C+L%3BLamers%2C+E%3BChase%2C+T+N&rft.aulast=Konitsiotis&rft.aufirst=S&rft.date=2000-04-25&rft.volume=54&rft.issue=8&rft.spage=1589&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-12 N1 - Date created - 2000-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functions of the N-terminal region of cyclic nucleotide phosphodiesterase 3 (PDE 3) isoforms. AN - 71073875; 10766874 AB - The N-terminal portion of phosphodiesterase (PDE) 3 was arbitrarily divided into region 1 (amino acids 1-300), which contains a large hydrophobic domain with six predicted transmembrane helices, and region 2 (amino acids 301-500), with a smaller hydrophobic domain ( approximately 50 residues). To analyze these regions, full-length human (H)PDE3A and mouse (M)PDE3B and a series of N-terminal truncated mutants were synthesized in Sf9 cells. Activities of HPDE3A, H3A-Delta189, MPDE3B, and M3B-Delta196, which retained all or part of the hydrophobic domain in region 1, were recovered almost entirely in particulate fractions. H3A-Delta321 and M3B-Delta302, containing region 2, were recovered essentially equally in particulate and cytosolic fractions. H3A-Delta397 and H3A-Delta457, lacking both hydrophobic domains, were predominantly cytosolic. H3A-Delta510 and M3B-Delta604, lacking both regions 1 and 2, were virtually completely cytosolic. M3B-Delta196 eluted as a large aggregated complex during gel filtration. With removal of greater amounts of N-terminal sequence, aggregation of PDE3 decreased, and H3A-Delta607, H3A-Delta721, and M3B-Delta604 eluted as dimers. Truncated HPDE3A proteins were more sensitive than full-length HPDE3A to inhibition by lixazinone. These results suggest that the hydrophobic domains in regions 1 and 2 contain structural determinants important for association of PDE3 with intracellular membranes, as well for self-association or aggregation during gel filtration and sensitivity to a specific inhibitor. JF - The Journal of biological chemistry AU - Kenan, Y AU - Murata, T AU - Shakur, Y AU - Degerman, E AU - Manganiello, V C AD - Pulmonary/Critical Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/04/21/ PY - 2000 DA - 2000 Apr 21 SP - 12331 EP - 12338 VL - 275 IS - 16 SN - 0021-9258, 0021-9258 KW - Isoenzymes KW - 0 KW - Quinazolines KW - lixazinone KW - 0FK7P66P1X KW - 3',5'-Cyclic-AMP Phosphodiesterases KW - EC 3.1.4.17 KW - Cyclic Nucleotide Phosphodiesterases, Type 3 KW - PDE3A protein, human KW - PDE3B protein, human KW - Pde3a protein, mouse KW - Pde3b protein, mouse KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Blotting, Western KW - Solubility KW - Kinetics KW - Humans KW - Mice KW - Quinazolines -- pharmacology KW - Structure-Activity Relationship KW - Sequence Deletion KW - Protein Conformation KW - Isoenzymes -- chemistry KW - Isoenzymes -- physiology KW - 3',5'-Cyclic-AMP Phosphodiesterases -- physiology KW - 3',5'-Cyclic-AMP Phosphodiesterases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71073875?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Functions+of+the+N-terminal+region+of+cyclic+nucleotide+phosphodiesterase+3+%28PDE+3%29+isoforms.&rft.au=Kenan%2C+Y%3BMurata%2C+T%3BShakur%2C+Y%3BDegerman%2C+E%3BManganiello%2C+V+C&rft.aulast=Kenan&rft.aufirst=Y&rft.date=2000-04-21&rft.volume=275&rft.issue=16&rft.spage=12331&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 - 2000-05-10 N1 - Date created - 2000-05-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Single nucleotide patch base excision repair is the major pathway for removal of thymine glycol from DNA in human cell extracts. AN - 71035725; 10766805 AB - The repair pathways involved in the removal of thymine glycol (TG) from DNA by human cell extracts have been examined. Closed circular DNA constructs containing a single TG at a defined site were used as substrates to determine the patch size generated after in vitro repair by cell extracts. Restriction analysis of the repair incorporation in the vicinity of the lesion indicated that the majority of TG was repaired through the base excision repair (BER) pathways. Repair incorporation 5' to the lesion, characteristic for the nucleotide excision repair pathway, was not found. More than 80% of the TG repair was accomplished by the single-nucleotide repair mechanism, and the remaining TGs were removed by the long patch BER pathway. We also analyzed the role of the xeroderma pigmentosum, complementation group G (XPG) protein in the excision step of BER. Cell extracts deficient in XPG protein had an average 25% reduction in TG incision. These data show that BER is the primary pathway for repair of TG in DNA and that XPG protein may be involved in repair of TG as an accessory factor. JF - The Journal of biological chemistry AU - Dianov, G L AU - Thybo, T AU - Dianova, I I AU - Lipinski, L J AU - Bohr, V A AD - Laboratory of Molecular Genetics, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA. dianovg@grc.nia.nih.gov Y1 - 2000/04/21/ PY - 2000 DA - 2000 Apr 21 SP - 11809 EP - 11813 VL - 275 IS - 16 SN - 0021-9258, 0021-9258 KW - thymine glycol KW - 2943-56-8 KW - DNA KW - 9007-49-2 KW - Thymine KW - QR26YLT7LT KW - Index Medicus KW - Base Sequence KW - Humans KW - Restriction Mapping KW - Molecular Sequence Data KW - Xeroderma Pigmentosum -- genetics KW - Xeroderma Pigmentosum -- metabolism KW - Fibroblasts -- metabolism KW - Cell Line KW - Mutagenesis KW - Thymine -- analogs & derivatives KW - DNA Repair KW - Thymine -- metabolism KW - DNA -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71035725?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Single+nucleotide+patch+base+excision+repair+is+the+major+pathway+for+removal+of+thymine+glycol+from+DNA+in+human+cell+extracts.&rft.au=Dianov%2C+G+L%3BThybo%2C+T%3BDianova%2C+I+I%3BLipinski%2C+L+J%3BBohr%2C+V+A&rft.aulast=Dianov&rft.aufirst=G&rft.date=2000-04-21&rft.volume=275&rft.issue=16&rft.spage=11809&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 - 2000-05-10 N1 - Date created - 2000-05-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assembly of Trp1 in a signaling complex associated with caveolin-scaffolding lipid raft domains. AN - 71031519; 10766822 AB - Trp1 has been proposed as a component of the store-operated Ca(2+) entry (SOC) channel. However, neither the molecular mechanism of SOC nor the role of Trp in this process is yet understood. We have examined possible molecular interactions involved in the regulation of SOC and Trp1 and report here for the first time that Trp1 is assembled in signaling complex associated with caveolin-scaffolding lipid raft domains. Endogenous hTrp1 and caveolin-1 were present in low density fractions of Triton X-100-extracted human submandibular gland cell membranes. Depletion of plasma membrane cholesterol increased Triton X-100 solubility of Trp1 and inhibited carbachol-stimulated Ca(2+) signaling. Importantly, thapsigargin stimulated Ca(2+) influx, but not internal Ca(2+) release, and inositol 1,4,5-triphosphate (IP(3))-stimulated I(soc) were also attenuated. Furthermore, both anti-Trp1 and anti-caveolin-1 antibodies co-immunoprecipitated hTrp1, caveolin-1, Galpha(q/11), and IP(3) receptor-type 3 (IP(3)R3). These results demonstrate that caveolar microdomains provide a scaffold for (i) assembly of key Ca(2+) signaling proteins into a complex and (ii) coordination of the molecular interactions leading to the activation of SOC. Importantly, we have shown that Trp1 is also localized in this microdomain where it interacts with one or more components of this complex, including IP(3)R3. This finding is potentially important in elucidating the physiological function of Trp. JF - The Journal of biological chemistry AU - Lockwich, T P AU - Liu, X AU - Singh, B B AU - Jadlowiec, J AU - Weiland, S AU - Ambudkar, I S AD - Secretory Physiology Section, Gene Therapy and Therapeutics Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/04/21/ PY - 2000 DA - 2000 Apr 21 SP - 11934 EP - 11942 VL - 275 IS - 16 SN - 0021-9258, 0021-9258 KW - CAV1 protein, human KW - 0 KW - Calcium Channels KW - Caveolin 1 KW - Caveolins KW - Cyclodextrins KW - Detergents KW - Membrane Lipids KW - Membrane Proteins KW - TRPC Cation Channels KW - beta-Cyclodextrins KW - transient receptor potential cation channel, subfamily C, member 1 KW - Carbachol KW - 8Y164V895Y KW - Octoxynol KW - 9002-93-1 KW - Cholesterol KW - 97C5T2UQ7J KW - betadex KW - JV039JZZ3A KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Octoxynol -- pharmacology KW - Solubility KW - Submandibular Gland -- metabolism KW - Humans KW - Submandibular Gland -- cytology KW - Detergents -- pharmacology KW - Structure-Activity Relationship KW - Calcium -- metabolism KW - Cyclodextrins -- pharmacology KW - Cells, Cultured KW - Cholesterol -- metabolism KW - Cell Membrane -- metabolism KW - Carbachol -- pharmacology KW - Protein Conformation KW - Calcium Channels -- metabolism KW - Membrane Proteins -- metabolism KW - Membrane Lipids -- metabolism KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71031519?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Assembly+of+Trp1+in+a+signaling+complex+associated+with+caveolin-scaffolding+lipid+raft+domains.&rft.au=Lockwich%2C+T+P%3BLiu%2C+X%3BSingh%2C+B+B%3BJadlowiec%2C+J%3BWeiland%2C+S%3BAmbudkar%2C+I+S&rft.aulast=Lockwich&rft.aufirst=T&rft.date=2000-04-21&rft.volume=275&rft.issue=16&rft.spage=11934&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 - 2000-05-10 N1 - Date created - 2000-05-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The lipophilicity of phorbol esters as a critical factor in determining the pattern of translocation of protein kinase C delta fused to green fluorescent protein. AN - 71030589; 10766849 AB - Our previous study showed differential subcellular localization of protein kinase C (PKC) delta by phorbol esters and related ligands, using a green fluorescent protein-tagged construct in living cells. Here we compared the abilities of a series of symmetrically substituted phorbol 12,13-diesters to translocate PKC delta. In vitro, the derivatives bound to PKC with similar potencies but differed in rate of equilibration. In vivo, the phorbol diesters with short, intermediate, and long chain fatty acids induced distinct patterns of translocation. Phorbol 12,13-dioctanoate and phorbol 12,13-nonanoate, the intermediate derivatives and most potent tumor promoters, showed patterns of translocation typical of phorbol 12-myristate 13-acetate, with plasma membrane and subsequent nuclear membrane translocation. The more hydrophilic compounds (phorbol 12,13-dibutyrate and phorbol 12,13-dihexanoate) induced a patchy distribution in the cytoplasm, more prominent nuclear membrane translocation, and little plasma membrane localization at all concentrations examined (100 nM to 10 microM). The highly lipophilic derivatives, phorbol 12,13-didecanoate and phorbol 12, 13-diundecanoate, at 1 microM caused either plasma membrane translocation only or no translocation at incubation times up to 60 min. Our results indicate that lipophilicity of phorbol esters is a critical factor contributing to differential PKC delta localization and thereby potentially to their different biological activities. JF - The Journal of biological chemistry AU - Wang, Q J AU - Fang, T W AU - Fenick, D AU - Garfield, S AU - Bienfait, B AU - Marquez, V E AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/04/21/ PY - 2000 DA - 2000 Apr 21 SP - 12136 EP - 12146 VL - 275 IS - 16 SN - 0021-9258, 0021-9258 KW - Isoenzymes KW - 0 KW - Luminescent Proteins KW - Phorbol Esters KW - Recombinant Fusion Proteins KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-delta KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Spectrometry, Fluorescence KW - Cell Membrane -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - CHO Cells KW - Cell Membrane -- metabolism KW - Luminescent Proteins -- genetics KW - Phorbol 12,13-Dibutyrate -- pharmacology KW - Cricetinae KW - Recombinant Fusion Proteins -- metabolism KW - Phorbol Esters -- metabolism KW - Protein Kinase C -- genetics KW - Recombinant Fusion Proteins -- genetics KW - Isoenzymes -- genetics KW - Lipid Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71030589?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+lipophilicity+of+phorbol+esters+as+a+critical+factor+in+determining+the+pattern+of+translocation+of+protein+kinase+C+delta+fused+to+green+fluorescent+protein.&rft.au=Wang%2C+Q+J%3BFang%2C+T+W%3BFenick%2C+D%3BGarfield%2C+S%3BBienfait%2C+B%3BMarquez%2C+V+E%3BBlumberg%2C+P+M&rft.aulast=Wang&rft.aufirst=Q&rft.date=2000-04-21&rft.volume=275&rft.issue=16&rft.spage=12136&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 - 2000-05-10 N1 - Date created - 2000-05-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nature of the inhibition of horseradish peroxidase and mitochondrial cytochrome c oxidase by cyanyl radical. AN - 71033459; 10757991 AB - Previous studies established that the cyanyl radical ((*)CN), detected as 5,5-dimethyl-1-pyrroline N-oxide (DMPO)/(*)CN by the electron spin resonance (ESR) spin-trapping technique, can be generated by horseradish peroxidase (HRP) in the presence of hydrogen peroxide (H(2)O(2)) and by mitochondrial cytochrome c oxidase (CcO) in the absence of H(2)O(2). To investigate the mechanism of inhibition by cyanyl radical, we isolated and characterized the iron protoporphyrin IX and heme a from the reactions of CN(-) with HRP and CcO, respectively. The purified heme from the reaction mixture of HRP/H(2)O(2)/KCN was unambiguously identified as cyanoheme by the observation of the protonated molecule, (M + H)(+), of m/z = 642.9 in the matrix-assisted laser desorption/ionization (MALDI) mass spectrum. The proton NMR spectrum of the bipyridyl ferrous cyanoheme complex revealed that one of the four meso protons was missing and had been replaced with a cyanyl group, indicating that the single, heme-derived product was meso-cyanoheme. The holoenzyme of HRP from the reconstitution of meso-cyanoheme with the apoenzyme of HRP (apoHRP) showed no detectable catalytic activity. The Soret peak of cyanoheme-reconstituted apoHRP was shifted to 411 nm from the 403 nm peak of native HRP. In contrast, the heme a isolated from partially or fully inhibited CcO did not show any change in the structure of the protoporphyrin IX as indicated by its MALDI mass spectrum, which showed an (M + H)(+) of m/z = 853.6, and by its pyridine hemochromogen spectrum. However, a protein-centered radical on the CcO can be detected in the reaction of CcO with cyanide and was identified as the thiyl radical(s) based on inhibition of its formation by N-ethylmaleimide pretreatment, suggesting that the protein matrix rather than protoporphyrin IX was attacked by the cyanyl radical. In addition to the difference in heme structures between HRP and CcO, the available crystallographic data also suggested that the distinct heme environments may contribute to the different inhibition mechanisms of HRP and CcO by cyanyl radical. JF - Biochemistry AU - Chen, Y R AU - Deterding, L J AU - Tomer, K B AU - Mason, R P AD - Laboratories of Pharmacology and Chemistry and of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. chen6@niehs.nih.gov Y1 - 2000/04/18/ PY - 2000 DA - 2000 Apr 18 SP - 4415 EP - 4422 VL - 39 IS - 15 SN - 0006-2960, 0006-2960 KW - Apoenzymes KW - 0 KW - Cyanides KW - Cyclic N-Oxides KW - Holoenzymes KW - Protons KW - Heme KW - 42VZT0U6YR KW - Guaiacol KW - 6JKA7MAH9C KW - 5,5-dimethyl-1-pyrroline-1-oxide KW - 7170JZ1QF3 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Horseradish Peroxidase KW - EC 1.11.1.- KW - Electron Transport Complex IV KW - EC 1.9.3.1 KW - Potassium Cyanide KW - MQD255M2ZO KW - Ethylmaleimide KW - O3C74ACM9V KW - Index Medicus KW - Holoenzymes -- metabolism KW - Hydrogen Peroxide -- metabolism KW - Hydrogen Peroxide -- pharmacology KW - Guaiacol -- metabolism KW - Heme -- analogs & derivatives KW - Molecular Weight KW - Chromatography, High Pressure Liquid KW - Magnetic Resonance Spectroscopy KW - Heme -- isolation & purification KW - Spin Trapping KW - Electron Spin Resonance Spectroscopy KW - Heme -- chemistry KW - Oxidative Stress KW - Catalysis -- drug effects KW - Cyclic N-Oxides -- metabolism KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization KW - Models, Chemical KW - Ethylmaleimide -- pharmacology KW - Heme -- metabolism KW - Apoenzymes -- metabolism KW - Potassium Cyanide -- metabolism KW - Cyanides -- metabolism KW - Mitochondria -- enzymology KW - Horseradish Peroxidase -- antagonists & inhibitors KW - Electron Transport Complex IV -- antagonists & inhibitors KW - Electron Transport Complex IV -- metabolism KW - Potassium Cyanide -- pharmacology KW - Horseradish Peroxidase -- metabolism KW - Cyanides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71033459?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Nature+of+the+inhibition+of+horseradish+peroxidase+and+mitochondrial+cytochrome+c+oxidase+by+cyanyl+radical.&rft.au=Chen%2C+Y+R%3BDeterding%2C+L+J%3BTomer%2C+K+B%3BMason%2C+R+P&rft.aulast=Chen&rft.aufirst=Y&rft.date=2000-04-18&rft.volume=39&rft.issue=15&rft.spage=4415&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-16 N1 - Date created - 2000-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term abecarnil administration produces tolerance and withdrawal signs in the rat. AN - 71050804; 10771289 AB - Abecarnil is a non-benzodiazepine that possesses anxiolytic and anticonvulsant properties. Conflicting reports of tolerance and withdrawal signs following chronic abecarnil administration have emerged from animal studies using different species and different models of tolerance and dependence. This study used a radiotelemetric method to examine any emergence of tolerance and abstinence signs in the rat following long-term abecarnil administration. Hooded Wistar rats, n=6 per group, were administered either abecarnil (8 mg/kg/bidaily, i.p.) or vehicle for 24 days. Locomotor activity, body temperature and electromyographic (EMG) activity were measured daily immediately following abecarnil administration. Tolerance to the abecarnil-induced muscle relaxant effects and decreased locomotor activity developed within 21 days. Administration of the benzodiazepine antagonist flumazenil (25 mg/kg), 18 h after abecarnil cessation, precipitated abstinence signs that included decreases in body temperature, and large increases in locomotor activity and muscle tone. Moreover, continuous recording of these measures over the 4 days after flumazenil administration indicated a prolonged increase in daytime locomotor activity, suggestive of spontaneous withdrawal. These data support earlier findings that reported signs of tolerance during administration of abecarnil and abstinence signs following abecarnil cessation. JF - European journal of pharmacology AU - Elliot, E E AU - White, J M AD - Department of Clinical and Experimental Pharmacology, University of Adelaide, South Australia, 5005, Australia. eelliot@intra.nida.nih.gov Y1 - 2000/04/14/ PY - 2000 DA - 2000 Apr 14 SP - 237 EP - 245 VL - 394 IS - 2-3 SN - 0014-2999, 0014-2999 KW - Anti-Anxiety Agents KW - 0 KW - Anticonvulsants KW - Carbolines KW - GABA Modulators KW - Flumazenil KW - 40P7XK9392 KW - abecarnil KW - IZM1PNJ3JL KW - Index Medicus KW - Rats KW - Drug Tolerance KW - Animals KW - Body Temperature -- drug effects KW - Telemetry KW - GABA Modulators -- pharmacology KW - Rats, Wistar KW - Electromyography -- drug effects KW - Motor Activity -- drug effects KW - Male KW - Flumazenil -- pharmacology KW - Carbolines -- adverse effects KW - Anticonvulsants -- adverse effects KW - Anti-Anxiety Agents -- adverse effects KW - Substance Withdrawal Syndrome -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71050804?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+pharmacology&rft.atitle=Long-term+abecarnil+administration+produces+tolerance+and+withdrawal+signs+in+the+rat.&rft.au=Elliot%2C+E+E%3BWhite%2C+J+M&rft.aulast=Elliot&rft.aufirst=E&rft.date=2000-04-14&rft.volume=394&rft.issue=2-3&rft.spage=237&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-11 N1 - Date created - 2000-07-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Arachidonic acid activates mitogen-activated protein (MAP) kinase-activated protein kinase 2 and mediates adhesion of a human breast carcinoma cell line to collagen type IV through a p38 MAP kinase-dependent pathway. AN - 71025426; 10753939 AB - Adhesion of metastatic human mammary carcinoma MDA-MB-435 cells to the basement membrane protein collagen type IV can be activated by treatment with arachidonic acid. We initially observed that this arachidonic acid-mediated adhesion was inhibited by the tyrosine kinase inhibitor genistein. Therefore, we examined the role of the mitogen-activated protein (MAP) kinase family tyrosine phosphorylation-regulated pathways in arachidonic acid-stimulated cell adhesion. Arachidonic acid stimulated the phosphorylation of p38, the activation of MAP kinase-activated protein kinase 2 (MAPKAPK2, a downstream substrate of p38), and the phosphorylation of heat shock protein 27 (a downstream substrate of MAP kinase-activated protein kinase 2). Treatment with the p38 inhibitor PD169316 completely and specifically inhibited arachidonic acid-mediated cell adhesion to collagen type IV. p38 activity was specifically associated with arachidonic acid-stimulated adhesion; this was demonstrated by the observation that 12-O-tetradecanoylphorbol 13-acetate-activated cell adhesion was not blocked by inhibiting p38 activity. Extracellular signal-regulated protein kinases (ERKs) 1 and 2 were also activated by arachidonic acid; however, cell adhesion to collagen type IV was not highly sensitive to PD98059, an inhibitor of MAP kinase kinase/ERK kinase 1 (MEK1) that blocks activation of the ERKs. c-Jun NH(2)-terminal kinase was not activated by arachidonic acid treatment of these cells. Together, these data suggest a novel role for p38 MAP kinase in regulating adhesion of breast cancer cells to collagen type IV. JF - The Journal of biological chemistry AU - Paine, E AU - Palmantier, R AU - Akiyama, S K AU - Olden, K AU - Roberts, J D AD - Laboratory of Molecular Carcinogenesis, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000/04/14/ PY - 2000 DA - 2000 Apr 14 SP - 11284 EP - 11290 VL - 275 IS - 15 SN - 0021-9258, 0021-9258 KW - HSP27 Heat-Shock Proteins KW - 0 KW - HSPB1 protein, human KW - Heat-Shock Proteins KW - Intracellular Signaling Peptides and Proteins KW - Neoplasm Proteins KW - Arachidonic Acid KW - 27YG812J1I KW - Collagen KW - 9007-34-5 KW - MAP-kinase-activated kinase 2 KW - EC 2.7.1.- KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - Mitogen-Activated Protein Kinases KW - p38 Mitogen-Activated Protein Kinases KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Humans KW - Mitogen-Activated Protein Kinases -- physiology KW - Mitogen-Activated Protein Kinase 1 -- physiology KW - Tumor Cells, Cultured KW - Phosphorylation KW - Breast Neoplasms -- pathology KW - Neoplasm Proteins -- physiology KW - Enzyme Activation -- drug effects KW - Cell Adhesion -- drug effects KW - Female KW - Arachidonic Acid -- pharmacology KW - Calcium-Calmodulin-Dependent Protein Kinases -- physiology KW - Protein-Serine-Threonine Kinases -- physiology KW - Collagen -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71025426?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Arachidonic+acid+activates+mitogen-activated+protein+%28MAP%29+kinase-activated+protein+kinase+2+and+mediates+adhesion+of+a+human+breast+carcinoma+cell+line+to+collagen+type+IV+through+a+p38+MAP+kinase-dependent+pathway.&rft.au=Paine%2C+E%3BPalmantier%2C+R%3BAkiyama%2C+S+K%3BOlden%2C+K%3BRoberts%2C+J+D&rft.aulast=Paine&rft.aufirst=E&rft.date=2000-04-14&rft.volume=275&rft.issue=15&rft.spage=11284&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 - 2000-05-05 N1 - Date created - 2000-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduction of human visual cortex excitability using 1-Hz transcranial magnetic stimulation. AN - 71010346; 10751273 AB - The effects of low-frequency (1-Hz) repetitive transcranial magnetic stimulation on visual cortex excitability were investigated by measuring phosphene thresholds (PTs) and stimulus-response curves. Stimulation over the visual cortex led to significantly decreased visual cortex excitability, expressed as an increase in PT. The motor threshold of the hand muscles did not change, indicating the topographic specificity of this effect. This intervention may be useful in situations associated with a hyperexcitable visual cortex. JF - Neurology AU - Boroojerdi, B AU - Prager, A AU - Muellbacher, W AU - Cohen, L G AD - Human Cortical Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD. 20892-1428, USA. Y1 - 2000/04/11/ PY - 2000 DA - 2000 Apr 11 SP - 1529 EP - 1531 VL - 54 IS - 7 SN - 0028-3878, 0028-3878 KW - Abridged Index Medicus KW - Index Medicus KW - Reference Values KW - Sensory Thresholds -- radiation effects KW - Motor Cortex -- physiology KW - Humans KW - Adult KW - Electromyography KW - Phosphenes -- radiation effects KW - Dose-Response Relationship, Radiation KW - Motor Cortex -- radiation effects KW - Electric Stimulation KW - Transcranial Magnetic Stimulation KW - Male KW - Female KW - Electromagnetic Fields KW - Visual Cortex -- radiation effects KW - Visual Cortex -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71010346?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Reduction+of+human+visual+cortex+excitability+using+1-Hz+transcranial+magnetic+stimulation.&rft.au=Boroojerdi%2C+B%3BPrager%2C+A%3BMuellbacher%2C+W%3BCohen%2C+L+G&rft.aulast=Boroojerdi&rft.aufirst=B&rft.date=2000-04-11&rft.volume=54&rft.issue=7&rft.spage=1529&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-04 N1 - Date created - 2000-05-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Factors determining mutagenic potential for individual cis and trans opened benzo[c]phenanthrene diol epoxide-deoxyadenosine adducts. AN - 71000004; 10747805 AB - Four adducts that would result from trans opening at C-1 of benzo[c]phenanthrene 3,4-diol 1,2-epoxide (B[c]PhDE) isomers (i.e., DE-1 enantiomers, where the epoxide oxygen and benzylic hydroxyl group are cis, and DE-2 enantiomers, where they are trans) by the N(6)-amino group of dAdo, together with the two cis opened N(6)-dAdo adducts of B[c]PhDE-1, were incorporated into two oligonucleotides at the underlined site in 5'-TTTAGAGTCTGCTCCC [context I(A)] and 5'-CAGATTTAGAGTCTGC [context II(A)]. After ligation of these, and the corresponding unsubstituted oligonucleotides, into single-stranded M13mp7L2 bacteriophage and transfection into SOS-induced Escherichia coli SMH77, base substitution mutations induced by the different B[c]PhDE-dAdo adducts were determined. These findings were compared with data [Pontén et al. (1999) Biochemistry 38, 1144-1152] for cis opened B[c]PhDE-2-dAdo adducts in the same sequence contexts. In most cases, adducts with S absolute configuration at the site of attachment of the nucleoside to the hydrocarbon had higher mutation frequencies (1.9-56.5%) than the corresponding adducts with R configuration (0.05-5.6%). For adducts derived from B[c]PhDE-1, the predominant mutations were A-->T transversions in context I(A) and A-->G transitions for most of these adducts in context II(A). For adducts derived from B[c]PhDE-2, A-->T base substitutions predominated for most of the trans adducts, but A-->G mutations were favored by the cis adduct with S configuration in either context. Thus, the structural feature that most dramatically affected mutagenic activity was the configuration of the carbon at the attachment point, with S configuration mostly being associated with greater mutagenicity than the R configuration. However, other structural variations and sequence context also affected mutagenicity, indicating that a combination of structure and context effects define mutagenicity. JF - Biochemistry AU - Pontén, I AU - Sayer, J M AU - Pilcher, A S AU - Yagi, H AU - Kumar, S AU - Jerina, D M AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. ponteni@ncifcrf.gov Y1 - 2000/04/11/ PY - 2000 DA - 2000 Apr 11 SP - 4136 EP - 4144 VL - 39 IS - 14 SN - 0006-2960, 0006-2960 KW - Carcinogens KW - 0 KW - DNA Adducts KW - Mutagens KW - Phenanthrenes KW - 1,2-epoxy-3,4-dihydroxy-1,2,3,4-tetrahydrobenzo(c)phenanthrene KW - 111001-48-0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Humans KW - Mutagens -- toxicity KW - Structure-Activity Relationship KW - Phenanthrenes -- toxicity KW - Carcinogens -- chemistry KW - DNA -- genetics KW - Carcinogens -- toxicity KW - Phenanthrenes -- chemistry KW - DNA Adducts -- drug effects KW - Mutation KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71000004?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Factors+determining+mutagenic+potential+for+individual+cis+and+trans+opened+benzo%5Bc%5Dphenanthrene+diol+epoxide-deoxyadenosine+adducts.&rft.au=Pont%C3%A9n%2C+I%3BSayer%2C+J+M%3BPilcher%2C+A+S%3BYagi%2C+H%3BKumar%2C+S%3BJerina%2C+D+M%3BDipple%2C+A&rft.aulast=Pont%C3%A9n&rft.aufirst=I&rft.date=2000-04-11&rft.volume=39&rft.issue=14&rft.spage=4136&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-02 N1 - Date created - 2000-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Absence of structural or functional alterations in male and female reproductive organs of F1 and F2 generations derived from female mice exposed to 3'-azido-3'-deoxythymidine during pregnancy. AN - 71118233; 10817626 AB - To investigate the effects of in utero exposure to 3'-azido-3'-deoxythymidine (AZT) on male and female reproductive system development, pregnant CD-1 mice were given daily intragastric doses of 25.0 mg AZT during days 12 through 18 of gestation. The offspring were examined at birth, as well as at pubertal, young adult and adult stages of development, for reproductive organ endpoints including anogenital distance, onset of testicular descent, latency to vaginal opening, and proportion of time for each of the stages of estrous cycle. These reproductive endpoints remained mostly unchanged in AZT-treated offspring as compared to the controls. Males and females exposed in utero to AZT (F1 generation) were fertile when mated to untreated females and males, respectively, and their liveborn F2 offspring showed no adverse effects for any of the reproductive parameters tested. Thus, no evidence of developmental reproductive toxicity was noted either in the F1 mice exposed to AZT during the critical period of male and female reproductive system development, or in the F2 mice born of matings between the AZT-exposed F1 mice and unexposed animals. JF - Toxicology letters AU - Diwan, B A AU - Olivero, O A AU - Poirier, M C AD - Intramural Research Support Program, SAIC Frederick, NCI-Frederick Cancer Research Development Center, MD 21702-1201, USA. bdiwan@mail.ncifcrf.gov Y1 - 2000/04/10/ PY - 2000 DA - 2000 Apr 10 SP - 9 EP - 15 VL - 115 IS - 1 SN - 0378-4274, 0378-4274 KW - Anti-HIV Agents KW - 0 KW - Reverse Transcriptase Inhibitors KW - Zidovudine KW - 4B9XT59T7S KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Mice KW - Reverse Transcriptase Inhibitors -- toxicity KW - Male KW - Female KW - Pregnancy Outcome KW - Pregnancy KW - Organ Size -- drug effects KW - Fertility -- drug effects KW - Genitalia -- drug effects KW - Anti-HIV Agents -- toxicity KW - Abnormalities, Drug-Induced KW - Zidovudine -- toxicity KW - Genitalia -- abnormalities KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71118233?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=Absence+of+structural+or+functional+alterations+in+male+and+female+reproductive+organs+of+F1+and+F2+generations+derived+from+female+mice+exposed+to+3%27-azido-3%27-deoxythymidine+during+pregnancy.&rft.au=Diwan%2C+B+A%3BOlivero%2C+O+A%3BPoirier%2C+M+C&rft.aulast=Diwan&rft.aufirst=B&rft.date=2000-04-10&rft.volume=115&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-28 N1 - Date created - 2000-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modified Human Immunodeficiency Virus-Based Lentiviral Vectors Display Decreased Sensitivity to Trans-Dominant Rev AN - 17595311; 4701263 AB - As a first step toward the development of HIV-based conditionally replicating defective interfering particles expressing trans-dominant Rev (TdRev), we studied whether mutation of the splicing signals and replacement of the RRE by the SRV-1 CTE would render these vectors less sensitive to TdRev. Vectors with mutations in the splicing signals (SD super(-)/RRE super(+)) yielded high titers (5 x 10 super(6) CFU/ml) and showed higher levels of cytoplasmic unspliced mRNA than the corresponding SD super(+)/RRE super(+) vectors either in the absence of Rev, in the presence of TdRev, or in the presence of both TdRev and Rev. Proviral copies of SD super(-)/RRE super(+) vectors were rescued more efficiently than SD super(+)/RRE super(+) vectors when TdRev was expressed. Vectors with the SRV-1 CTE (SD super(+)/CTE super(+) and SD super(-)/CTE super(+)) expressed high levels of cytoplasmic unspliced mRNA in the absence of Rev expression. Titers obtained with the SD super(-)/CTE super(+) vectors (10 super(6) CFU/ml) were higher than the titers obtained with SD super(+)/CTE super(+) vectors. We also tested the effect of other structural modifications such as the orientation of the expression cassette and the presence of the central polypurine tract (cPPT/CTS). We show that an expression cassette cloned in the reverse orientation with respect to the LTRs or elimination of the cPPT/CTS element severely affected vector titers. We also demonstrated that these vectors can be efficiently mobilized from their proviral state by HIV trans-complementing functions, and transduced into secondary target cells without suffering any genomic rearrangement. JF - Human Gene Therapy AU - Mautino, M R AU - Ramsey, W J AU - Reiser, J AU - Morgan, R A AD - Clinical Gene Therapy Branch, NHGRI, 10 Center Drive, MSC 1851, Building 10, Room 10C103, Bethesda, MD 20892-1851, USA, rmorgan@nhgri.nih.gov Y1 - 2000/04/10/ PY - 2000 DA - 2000 Apr 10 SP - 895 EP - 908 VL - 11 IS - 6 SN - 1043-0342, 1043-0342 KW - HIV KW - Human immunodeficiency virus KW - Rev protein KW - rev protein KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Splicing KW - Gene therapy KW - Lentivirus KW - Gene transfer KW - Gene manipulation KW - W3 33181:Gene therapy vectors KW - G 07313:Viruses KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17595311?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Modified+Human+Immunodeficiency+Virus-Based+Lentiviral+Vectors+Display+Decreased+Sensitivity+to+Trans-Dominant+Rev&rft.au=Mautino%2C+M+R%3BRamsey%2C+W+J%3BReiser%2C+J%3BMorgan%2C+R+A&rft.aulast=Mautino&rft.aufirst=M&rft.date=2000-04-10&rft.volume=11&rft.issue=6&rft.spage=895&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/10.1089%2F10430340050015509 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; Lentivirus; Gene transfer; Gene therapy; Splicing; Gene manipulation; Expression vectors DO - http://dx.doi.org/10.1089/10430340050015509 ER - TY - JOUR T1 - Treatment with delta opioid peptide enhances in vitro and in vivo survival of rat dopaminergic neurons. AN - 71085688; 10790856 AB - A major problem in neural transplantation therapy is poor survival of grafted cells, which may be due to low cell viability prior to transplantation or scarce trophic factors available to the cells following transplantation. Recently, the delta enkephalin analogue [D-Ala(2),D-Leu(5)]-enkephalin (DADLE) has been demonstrated to protect against, as well as to reverse methamphetamine-induced loss of dopamine transporters. Here, we show that pretreatment with DADLE (0.0025, 0.005, 0.01 g/ml) dose-dependently enhanced cell viability of cultured primary rat fetal mesencephalic cells. In addition, DADLE administration in adult rats (4 mg/kg every 2 h, 4 injections, i.p.) prior to 6-hydroxydopamine lesions of the medial forebrain bundle, significantly reduced the severity of loss of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra 1 month post-lesion. This is the first report suggesting that DADLE can be used as a supplement factor for improving the cell viability of fetal mesencephalic cells and as a protective agent against neurotoxicity in a Parkinson's disease model. JF - Neuroreport AU - Borlongan, C V AU - Su, T P AU - Wang, Y AD - Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 2000/04/07/ PY - 2000 DA - 2000 Apr 07 SP - 923 EP - 926 VL - 11 IS - 5 SN - 0959-4965, 0959-4965 KW - Adrenergic Agents KW - 0 KW - Neuroprotective Agents KW - Enkephalin, Leucine-2-Alanine KW - 63631-40-3 KW - Oxidopamine KW - 8HW4YBZ748 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Cell Death -- physiology KW - Age Factors KW - Substantia Nigra -- drug effects KW - Nerve Degeneration -- chemically induced KW - Parkinson Disease -- physiopathology KW - Cell Death -- drug effects KW - Parkinson Disease -- drug therapy KW - Neuroprotective Agents -- pharmacology KW - Oxidopamine -- pharmacology KW - Substantia Nigra -- metabolism KW - Rats KW - Adrenergic Agents -- pharmacology KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - Brain Tissue Transplantation -- methods KW - Time Factors KW - Substantia Nigra -- cytology KW - Male KW - Fetus -- drug effects KW - Neurons -- metabolism KW - Cell Survival -- drug effects KW - Neurons -- drug effects KW - Neurons -- cytology KW - Fetus -- cytology KW - Dopamine -- metabolism KW - Enkephalin, Leucine-2-Alanine -- pharmacology KW - Cell Survival -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71085688?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroreport&rft.atitle=Treatment+with+delta+opioid+peptide+enhances+in+vitro+and+in+vivo+survival+of+rat+dopaminergic+neurons.&rft.au=Borlongan%2C+C+V%3BSu%2C+T+P%3BWang%2C+Y&rft.aulast=Borlongan&rft.aufirst=C&rft.date=2000-04-07&rft.volume=11&rft.issue=5&rft.spage=923&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-10 N1 - Date created - 2000-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A positron emission tomographic study of auditory localization in the congenitally blind. AN - 85283565; pmid-10729347 AB - We have used positron emission tomography (PET) to measure regional cerebral blood flow (rCBF) in sighted and congenitally blind subjects performing auditory localization tasks. During scanning, the spectral and binaural cues of localized sound were reproduced by a sound system and delivered via headphones. During tasks that required auditory localization both the sighted and blind subjects strongly activated posterior parietal areas. In addition, the blind subjects activated association areas in the right occipital cortex, the foci of which were similar to areas previously identified in visual location and motion detection experiments in sighted subjects. The blind subjects, therefore, demonstrated visual to auditory cross-modal plasticity with auditory localization activating occipital association areas originally intended for dorsal-stream visual processing. To determine the functional connectivity of pre-selected brain regions in primary and non-primary auditory and posterior parietal cortex in the two cohorts, we performed an inter-regional correlation analysis on the rCBF data set. During auditory localization in the blind subjects, rCBF activity in the right posterior parietal cortex was positively correlated with that in the right occipital region, whereas in sighted subjects correlations were generally negative. There were no significant positive occipital correlations in either cohort when reference regions in temporal or left parietal cortex were chosen. This indicates that in congenitally blind subjects the right occipital cortex participates in a functional network for auditory localization and that occipital activity is more likely to arise from connections with posterior parietal cortex. JF - The Journal of Neuroscience AU - Weeks, R AU - Horwitz, B AU - Aziz-Sultan, A AU - Tian, B AU - Wessinger, C M AU - Cohen, L G AU - Hallett, M AU - Rauschecker, J P AD - Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 2000 SP - 2664 EP - 2672 VL - 20 IS - 7 SN - 0270-6474, 0270-6474 KW - Sound Localization KW - Support, U.S. Gov't, P.H.S. KW - Human KW - Adult KW - Support, U.S. Gov't, Non-P.H.S. KW - Tomography, Emission-Computed KW - Blindness KW - Cerebrovascular Circulation KW - Female KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85283565?accountid=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+Neuroscience&rft.atitle=A+positron+emission+tomographic+study+of+auditory+localization+in+the+congenitally+blind.&rft.au=Weeks%2C+R%3BHorwitz%2C+B%3BAziz-Sultan%2C+A%3BTian%2C+B%3BWessinger%2C+C+M%3BCohen%2C+L+G%3BHallett%2C+M%3BRauschecker%2C+J+P&rft.aulast=Weeks&rft.aufirst=R&rft.date=2000-04-01&rft.volume=20&rft.issue=7&rft.spage=2664&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Neuroscience&rft.issn=02706474&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Cerebral metabolic response to passive audiovisual stimulation in patients with Alzheimer's disease and healthy volunteers assessed by PET. AN - 85276430; pmid-10768555 AB - Alzheimer's disease is associated with reductions in resting-state brain metabolism, as measured by PET, progressing with dementia severity. The purpose of this study was to see to what extent brain regions with reduced resting-state metabolic rates in Alzheimer patients could be activated by a passive audiovisual stimulation test and to compare the result with activation in age-matched healthy volunteers. The extent of activation in Alzheimer's disease is considered to reflect the integrity of synaptic function, or inherent viability, and the potential responsiveness of the Alzheimer brain to drug therapy. METHODS: Regional cerebral metabolic rates for glucose (rCMRglc, in mg/ 100 g tissue/min) were measured in the resting state (eyes and ears covered) and during passive audiovisual stimulation (watching a movie) in 15 otherwise healthy Alzheimer patients of differing dementia severity (Mattis Dementia Rating Scale score, 23-128) and in 14 age-matched healthy volunteers (score, 141 +/- 3) using PET with 2 sequential injections of FDG. RESULTS: In the volunteers, audiovisual stimulation caused significant rCMRglc increases in visual and auditory cortical areas but significant decreases in frontal areas. In the mildly demented patients, rCMRglc responses were within 2 SDs of the mean in volunteers. However, the magnitude of the rCMRglc responses during stimulation declined significantly with dementia severity in the right occipitotemporal, right and left occipital association, and left calcarine cortical regions. CONCLUSION: Functional brain responsiveness, evaluated by a passive audiovisual stimulation paradigm with PET, is within normal limits in mildly demented Alzheimer patients but fails with worsening dementia severity. Declining responsiveness may account for the limited success of neurotransmitter replacement therapy in Alzheimer patients with moderate-to-severe dementia. JF - Journal of Nuclear Medicine AU - Pietrini, P AU - Alexander, G E AU - Furey, M L AU - Dani, A AU - Mentis, M J AU - Horwitz, B AU - Guazzelli, M AU - Shapiro, M B AU - Rapoport, S I AD - Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 2000 SP - 575 EP - 583 VL - 41 IS - 4 SN - 0161-5505, 0161-5505 KW - Support, U.S. Gov't, P.H.S. KW - Human KW - Alzheimer Disease KW - Brain KW - Glucose KW - Aged KW - Photic Stimulation KW - Fludeoxyglucose F 18 KW - Radiopharmaceuticals KW - Fluorine Radioisotopes KW - Case-Control Studies KW - Support, Non-U.S. Gov't KW - Acoustic Stimulation KW - Male KW - Female KW - Tomography, Emission-Computed UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85276430?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Nuclear+Medicine&rft.atitle=Cerebral+metabolic+response+to+passive+audiovisual+stimulation+in+patients+with+Alzheimer%27s+disease+and+healthy+volunteers+assessed+by+PET.&rft.au=Pietrini%2C+P%3BAlexander%2C+G+E%3BFurey%2C+M+L%3BDani%2C+A%3BMentis%2C+M+J%3BHorwitz%2C+B%3BGuazzelli%2C+M%3BShapiro%2C+M+B%3BRapoport%2C+S+I&rft.aulast=Pietrini&rft.aufirst=P&rft.date=2000-04-01&rft.volume=41&rft.issue=4&rft.spage=575&rft.isbn=&rft.btitle=&rft.title=Journal+of+Nuclear+Medicine&rft.issn=01615505&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - High-fidelity mRNA amplification for gene profiling AN - 762278958; 13744405 AB - The completion of the Human Genome Project has made possible the comprehensive analysis of gene expression, and cDNA microarrays are now being employed for expression analysis in cancer cell lines or excised surgical specimens. However, broader application of cDNA microarrays is limited by the amount of RNA required: 50-200 kg of total RNA (T-RNA) and 2-5 kg poly(A) RNA. To broaden the use of cDNA microarrays, some methods aiming at intensifying fluorescence signal have resulted in modest improvement. Methods devoted to amplifying starting poly(A) RNA or cDNA show promise, in that detection can be increased by orders of magnitude. However, despite the common use of these amplification procedures, no systematic assessment of their limits and biases has been documented. We devised a procedure that optimizes amplification of low-abundance RNA samples by combining antisense RNA (aRNA) amplification with a template-switching effect (Clonetech, Palo Alto, CA). The fidelity of aRNA amplified from 1:10,000 to 1:100,000 of commonly used input RNA was comparable to expression profiles observed with conventional poly(A) RNA- or T-RNA-based arrays. JF - Nature Biotechnology AU - Wang, Ena AU - Miller, Lance D AU - Ohnmacht, Galen A AU - Liu, Edison T AU - Marincola, Francesco M AD - [1] Surgery Branch, Division of Clinical Sciences, National Cancer Institute and the Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD [2] These two authors contributed equally to this project. Y1 - 2000/04// PY - 2000 DA - Apr 2000 SP - 457 EP - 459 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 18 IS - 4 SN - 1087-0156, 1087-0156 KW - Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Aqualine Abstracts; Biotechnology and Bioengineering Abstracts KW - Fluorescence KW - USA, California, Palo Alto KW - Human Genome Project KW - Antisense RNA KW - Systematics KW - DNA microarrays KW - Cancer KW - Gene expression KW - Fidelity KW - Tumor cell lines KW - Assessments KW - Profiles KW - Biotechnology KW - AQ 00001:Water Resources and Supplies KW - G 07730:Development & Cell Cycle KW - N 14810:Methods KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/762278958?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aaqualine&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=High-fidelity+mRNA+amplification+for+gene+profiling&rft.au=Wang%2C+Ena%3BMiller%2C+Lance+D%3BOhnmacht%2C+Galen+A%3BLiu%2C+Edison+T%3BMarincola%2C+Francesco+M&rft.aulast=Wang&rft.aufirst=Ena&rft.date=2000-04-01&rft.volume=18&rft.issue=4&rft.spage=457&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2F74546 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Gene expression; Tumor cell lines; Fidelity; Fluorescence; Human Genome Project; Antisense RNA; DNA microarrays; Cancer; Assessments; Profiles; Systematics; Biotechnology; USA, California, Palo Alto DO - http://dx.doi.org/10.1038/74546 ER - TY - JOUR T1 - Thyroid cancer following exposure to radioactive iodine. AN - 72618330; 11705004 AB - The thyroid gland is one of the most sensitive organs for radiation-induced oncogenesis and the magnitude of the risk from external radiation is well understood. This is not the case for internal radiation derived from the radioiodines, a matter of practical importance because of medical use and potential accidental exposure. This article reviews current knowledge derived from the follow-up of patients receiving diagnostic or therapeutic 131I and populations exposed to radioactive fallout. The latter includes the nuclear power station accident at Chernobyl and the results of atomic bomb development and testing at Hanford, the Nevada Test Site and the Marshall Islands. The most cogent information comes from Chernobyl where an epidemic of childhood thyroid cancer has followed exposure to radioiodine that was mainly 131I. Although much has been learned from this experience about the nature of radioiodine induced thyroid cancer in young children, the reconstruction of thyroid radiation doses is too preliminary to provide accurate knowledge of the risk in comparison to that from external radiation. In the Marshall Islands, much of the exposure was from short-lived radioiodines as well as external radiation, obviating the possibility to determine the risk from 131I. Exposure to 131I in the continental United States from atomic bomb testing is expected to have caused some thyroid cancers, but only in the immediate vicinity of the Nevada Test Site has any evidence of radiation-induced thyroid neoplasms been adduced. This evidence is minimally significant statistically, and not significant for thyroid cancer per se. Medical use of radioiodine has not been observed to cause thyroid cancer but very few of the patients studied were young children, the group most sensitive to thyroid radiation. Despite these limitations, this information is sufficient to make some suggestions concerning protective measures in the case of nuclear accidents and the follow up of individuals who have been exposed. JF - Reviews in endocrine & metabolic disorders AU - Robbins, J AU - Schneider, A B AD - National Institutes of Health, NIDDK, Genetics and Biochemistry Branch, Bldg 10, Rm 6C 201A, 10 Center Drive MSC 1587, Bethesda, MD 20892-1587, USA. jacobr@bdg10.niddk.nih.gov Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 197 EP - 203 VL - 1 IS - 3 SN - 1389-9155, 1389-9155 KW - Iodine Radioisotopes KW - 0 KW - Radioactive Fallout KW - Index Medicus KW - Radioactive Hazard Release KW - Nuclear Warfare KW - Humans KW - Iodine Radioisotopes -- therapeutic use KW - Iodine Radioisotopes -- adverse effects KW - Neoplasms, Radiation-Induced KW - Thyroid Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72618330?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reviews+in+endocrine+%26+metabolic+disorders&rft.atitle=Thyroid+cancer+following+exposure+to+radioactive+iodine.&rft.au=Robbins%2C+J%3BSchneider%2C+A+B&rft.aulast=Robbins&rft.aufirst=J&rft.date=2000-04-01&rft.volume=1&rft.issue=3&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=Reviews+in+endocrine+%26+metabolic+disorders&rft.issn=13899155&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-04 N1 - Date created - 2001-11-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Do glucocorticoids cause spinal epidural lipomatosis? When endocrinology and spinal surgery meet. AN - 72568947; 10707048 AB - Here, we report pathogenetic aspects of spinal epidural lipomatosis (SEL) based on a literature review. SEL is a rare entity but can cause significant morbidity. Its symptoms can be identical to those of more common disorders such as vertebral and disc disease, and cord lesions (for example, transverse myelitis, multiple sclerosis and syringomyelia). Therefore, it often goes undiagnosed. In addition, SEL occurs in patients on glucocorticoid therapy, which can lead to myopathy, thereby mimicking the motor symptoms of SEL. Glucocorticoids seem to play a major role in the development of SEL, although idiopathic SEL has also been reported. The latter occurs almost exclusively in obese individuals who may have concurrent hypercortisolism. Once clinically suspected, SEL is best diagnosed by magnetic resonance imaging (MRI). Treatment of SEL is directed at reducing body weight in patients with idiopathic SEL, and at decreasing glucocorticoid excess in patients with endogenous or exogenous hypercortisolism. In severe cases, decompressive laminectomy might become necessary to alleviate the neurological symptoms caused by spinal cord compression. JF - Trends in endocrinology and metabolism: TEM AU - Koch, C A AU - Doppman, J L AU - Patronas, N J AU - Nieman, L K AU - Chrousos, G P AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 86 EP - 90 VL - 11 IS - 3 SN - 1043-2760, 1043-2760 KW - Glucocorticoids KW - 0 KW - Index Medicus KW - Humans KW - Epidural Space KW - Spinal Cord Diseases -- chemically induced KW - Lipomatosis -- therapy KW - Lipomatosis -- chemically induced KW - Glucocorticoids -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72568947?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+endocrinology+and+metabolism%3A+TEM&rft.atitle=Do+glucocorticoids+cause+spinal+epidural+lipomatosis%3F+When+endocrinology+and+spinal+surgery+meet.&rft.au=Koch%2C+C+A%3BDoppman%2C+J+L%3BPatronas%2C+N+J%3BNieman%2C+L+K%3BChrousos%2C+G+P&rft.aulast=Koch&rft.aufirst=C&rft.date=2000-04-01&rft.volume=11&rft.issue=3&rft.spage=86&rft.isbn=&rft.btitle=&rft.title=Trends+in+endocrinology+and+metabolism%3A+TEM&rft.issn=10432760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-15 N1 - Date created - 2001-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ongoing trials in HIV protease inhibitors. AN - 72390122; 11060719 AB - The development of antiretrovirals has led to a revolution in the care of patients infected with HIV. What was once a uniformly fatal syndrome has become a more treatable, chronic, infectious disease. Central to this revolution have been the protease inhibitors, a class of drugs with potent antiretroviral activity. The first member of this class was approved for use in 1995 and there are now five protease inhibitors approved by the US Food and Drug Administration (FDA): amprenavir, indinavir, nelfinavir, ritonavir and saquinavir. As a result of the magnitude of the HIV pandemic coupled with the clinically proven efficacy of protease inhibitors, there are currently hundreds of ongoing clinical trials with these agents. Trial designs include comparisons between the various licensed protease inhibitors, comparisons of protease inhibitors to other classes of potent antiretroviral drugs, investigations with new protease inhibitors, investigations of protease inhibitor-related toxicities and attempts at simplifying current dosing regimens. JF - Expert opinion on investigational drugs AU - Tavel, J A AD - National Institute of Allergy and Infectious Diseases, 9000 Rockville Pike, Building 10, Room 11C-103, Bethesda, MD 20892-1880, USA. jtavel@nih.gov. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 917 EP - 928 VL - 9 IS - 4 SN - 1354-3784, 1354-3784 KW - Carbamates KW - 0 KW - HIV Protease Inhibitors KW - Sulfonamides KW - amprenavir KW - 5S0W860XNR KW - Indinavir KW - 5W6YA9PKKH KW - Nelfinavir KW - HO3OGH5D7I KW - Saquinavir KW - L3JE09KZ2F KW - Ritonavir KW - O3J8G9O825 KW - Index Medicus KW - United States KW - Ritonavir -- therapeutic use KW - United States Food and Drug Administration KW - Humans KW - Clinical Trials as Topic KW - Indinavir -- therapeutic use KW - Sulfonamides -- therapeutic use KW - Nelfinavir -- therapeutic use KW - Saquinavir -- therapeutic use KW - HIV Infections -- drug therapy KW - HIV Protease Inhibitors -- therapeutic use KW - HIV Infections -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72390122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+opinion+on+investigational+drugs&rft.atitle=Ongoing+trials+in+HIV+protease+inhibitors.&rft.au=Tavel%2C+J+A&rft.aulast=Tavel&rft.aufirst=J&rft.date=2000-04-01&rft.volume=9&rft.issue=4&rft.spage=917&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+investigational+drugs&rft.issn=13543784&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-14 N1 - Date created - 2000-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insulin-like growth factor I stimulates angiogenesis and the production of vascular endothelial growth factor. AN - 72251377; 10984289 JF - Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society AU - Dunn, S E AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, North Carolina, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - S41 EP - S42 VL - 10 Suppl A SN - 1096-6374, 1096-6374 KW - Endothelial Growth Factors KW - 0 KW - Lymphokines KW - Recombinant Proteins KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Factor VIII KW - 9001-27-8 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- pharmacology KW - Tumor Cells, Cultured KW - Factor VIII -- biosynthesis KW - Humans KW - Mice KW - Diet KW - Neovascularization, Pathologic -- etiology KW - Lymphokines -- biosynthesis KW - Insulin-Like Growth Factor I -- physiology KW - Endothelial Growth Factors -- biosynthesis KW - Insulin-Like Growth Factor I -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72251377?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Growth+hormone+%26+IGF+research+%3A+official+journal+of+the+Growth+Hormone+Research+Society+and+the+International+IGF+Research+Society&rft.atitle=Insulin-like+growth+factor+I+stimulates+angiogenesis+and+the+production+of+vascular+endothelial+growth+factor.&rft.au=Dunn%2C+S+E&rft.aulast=Dunn&rft.aufirst=S&rft.date=2000-04-01&rft.volume=10+Suppl+A&rft.issue=&rft.spage=S41&rft.isbn=&rft.btitle=&rft.title=Growth+hormone+%26+IGF+research+%3A+official+journal+of+the+Growth+Hormone+Research+Society+and+the+International+IGF+Research+Society&rft.issn=10966374&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-01 N1 - Date created - 2000-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exclusion of angiotensin I-converting enzyme as a candidate gene involved in exudative inflammatory resistance in F344/N rats. AN - 71750531; 10949912 AB - Inbred LEW/N and F344/N rats respectively, are susceptible and relatively resistant to a broad range of inflammatory/autoimmune diseases. We recently identified a quantitative trait locus (QTL) on chromosome 10 that protects the F344/N rat from carrageenan-induced exudation in a dominant fashion. Angiotensin I-converting enzyme (ACE) is one of the candidate genes located in this QTL region that plays an important role in inflammation. RNA was extracted from both LEW/N and F344/N rat strains and used to produce full length cDNA by reverse transcription polymerase chain reaction (RT-PCR). Both strands of the PCR products were entirely sequenced to determine nucleotide differences between strains. ACE activity was measured using the synthetic substrate 3H-hippuryl-glycylglycine. ACE protein levels were determined by Western blot using a specific ACE antibody. ACE kinetic and inhibition studies were performed using specific substrates (Hip-His-Leu and Acetyl-Seryl-Aspartyl-Acetyl-Lysyl-Proline) and inhibitors (lisinopril, captopril and quinaprilat) for each C- and N-terminal active site. Finally, the dose-effects of lisinopril treatment on carrageenen-induced exudate volume and ACE activity was studied. In this study, we report for the first time a missense mutation in the coding region of ACE cDNA at 5' 1021 from C to T, resulting in a Leu-341 to Phe substitution, close to the N-domain active site in the F344/N rats. Full characterization of soluble and tissue ACE in both LEW/N and F344/N rat strains showed that soluble ACE levels in serum and exudate were 1.5 fold higher in the F344/N rats than those in LEW/N rats. In addition, the soluble ACE level was inversely correlated with the exudate volume. However, the specific ACE activity and its catalytic properties were identical in both strains. Furthermore, the chronic inhibition of serum and exudate ACE levels by lisinopril treatment did not affect the exudate volume in F344/N rats, indicating that several factors besides ACE were involved in the control of carrageenan-induced exudation. This report describes a complete molecular, biochemical, enzymatic and pharmacologic study of a missense mutation in the ACE cDNA in F344/N rats, that taken together, excludes ACE as a candidate gene involved with resistance to carrageenan-induced exudation in F344/N rats. JF - Molecular medicine (Cambridge, Mass.) AU - Jafarian-Tehrani, M AU - Listwak, S AU - Barrientos, R M AU - Michaud, A AU - Corvol, P AU - Sternberg, E M AD - Section on Neuroendocrine Immunology and Behavior, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 319 EP - 331 VL - 6 IS - 4 SN - 1076-1551, 1076-1551 KW - Angiotensin-Converting Enzyme Inhibitors KW - 0 KW - Carrageenan KW - 9000-07-1 KW - Lisinopril KW - E7199S1YWR KW - Peptidyl-Dipeptidase A KW - EC 3.4.15.1 KW - Index Medicus KW - Animals KW - Rats, Inbred Lew KW - Solubility KW - DNA Mutational Analysis KW - Exudates and Transudates -- enzymology KW - Mutation, Missense -- genetics KW - Amino Acid Sequence KW - Reverse Transcriptase Polymerase Chain Reaction KW - Angiotensin-Converting Enzyme Inhibitors -- pharmacology KW - Binding Sites KW - Rats KW - Quantitative Trait, Heritable KW - Carrageenan -- pharmacology KW - Rats, Sprague-Dawley KW - Rats, Inbred F344 KW - Base Sequence KW - Blotting, Western KW - Amino Acid Substitution -- genetics KW - Kinetics KW - Molecular Sequence Data KW - Lung -- enzymology KW - Inhibitory Concentration 50 KW - Lisinopril -- pharmacology KW - Peptidyl-Dipeptidase A -- blood KW - Peptidyl-Dipeptidase A -- genetics KW - Peptidyl-Dipeptidase A -- chemistry KW - Inflammation -- chemically induced KW - Peptidyl-Dipeptidase A -- metabolism KW - Inflammation -- genetics KW - Inflammation -- metabolism KW - Inflammation -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71750531?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+medicine+%28Cambridge%2C+Mass.%29&rft.atitle=Exclusion+of+angiotensin+I-converting+enzyme+as+a+candidate+gene+involved+in+exudative+inflammatory+resistance+in+F344%2FN+rats.&rft.au=Jafarian-Tehrani%2C+M%3BListwak%2C+S%3BBarrientos%2C+R+M%3BMichaud%2C+A%3BCorvol%2C+P%3BSternberg%2C+E+M&rft.aulast=Jafarian-Tehrani&rft.aufirst=M&rft.date=2000-04-01&rft.volume=6&rft.issue=4&rft.spage=319&rft.isbn=&rft.btitle=&rft.title=Molecular+medicine+%28Cambridge%2C+Mass.%29&rft.issn=10761551&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-06 N1 - Date created - 2000-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk ranges for various endpoints following exposure to 2,3,7,8-TCDD. AN - 71260407; 10912247 AB - Conducting a dose-response analysis for an environmental contaminant requires a careful evaluation of most of the available data focusing on both the magnitude of the effect and the possible ranges of dose-response shapes which fit the data. This paper calculates potency values (1% response exposures) for human and animal data on cancer, non-cancer and biological effect endpoints for TCDD and finds that a reasonable estimate for 1% excess cancer would be between 1 and 50 pg/kg/day. The paper also evaluates the adequacy of linear and non-linear models for fitting these data and concludes that the assumption of a threshold dose-response is not fully supported by these data. JF - Food additives and contaminants AU - Portier, C AD - National Institute of Environmental Health Sciences, Laboratory of Computational Biology and Risk Analysis, Research Triangle Park, NC 27709, USA. portier@niehs.nih.gov Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 335 EP - 346 VL - 17 IS - 4 SN - 0265-203X, 0265-203X KW - Environmental Pollutants KW - 0 KW - Polychlorinated Dibenzodioxins KW - Index Medicus KW - Occupational Exposure KW - Animals KW - Dose-Response Relationship, Drug KW - Humans KW - Neoplasms -- chemically induced KW - Retrospective Studies KW - Environmental Exposure KW - Risk Assessment KW - Polychlorinated Dibenzodioxins -- adverse effects KW - Polychlorinated Dibenzodioxins -- administration & dosage KW - Environmental Pollutants -- administration & dosage KW - Environmental Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71260407?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+additives+and+contaminants&rft.atitle=Risk+ranges+for+various+endpoints+following+exposure+to+2%2C3%2C7%2C8-TCDD.&rft.au=Portier%2C+C&rft.aulast=Portier&rft.aufirst=C&rft.date=2000-04-01&rft.volume=17&rft.issue=4&rft.spage=335&rft.isbn=&rft.btitle=&rft.title=Food+additives+and+contaminants&rft.issn=0265203X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-22 N1 - Date created - 2000-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicokinetics. AN - 71254750; 10912241 AB - The toxicokinetic determinants of dioxin and related chemicals depend on three major properties: lipophilicity, metabolism, and binding to CYP1A2 in the liver. The induction of CYP1A2 is partially under the control of the aryl hydrocarbon receptor (AhR). Lipophilicity increases with more chlorination and controls absorption and tissue partitioning. Metabolism is the rate-limiting step for elimination. Induction of CYP1A2 leads to hepatic sequestration of TCDD. Binding to this inducible hepatic protein results in non-linear dose-dependent tissue distribution: with increasing doses, the relative concentration in extra-hepatic tissues decreases while that in liver increases. The induction of this protein occurs in both animals and humans and results in an increase in the liver to fat ratio of these compounds. Humans have similar sensitivities to rodents for dioxin-like compounds when using tissue concentration (from in vitro studies), body burden, average lifetime serum lipid concentration, or lifetime area-under-the-curve concentration based on both low dose (biochemical) and high dose (cancer) driven endpoints. To reach the same tissue concentration in humans as rodents however, humans need a lower daily intake than rodents based on differences in pharmacokinetic behaviour. This clearly indicates that physiologically based pharmacokinetic models should be explored for the estimation of the daily intake of dioxin-like compounds in humans based on tissue dose levels or derivatives of those. JF - Food additives and contaminants AU - van Birgelen, A P AU - van den Berg, M AD - National Institute of Environmental Health Sciences, Environmental Toxicology Program, Research Triangle Park, NC 27709, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 267 EP - 273 VL - 17 IS - 4 SN - 0265-203X, 0265-203X KW - Dioxins KW - 0 KW - Environmental Pollutants KW - Cytochrome P-450 CYP1A2 KW - EC 1.14.14.1 KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Body Burden KW - Liver -- metabolism KW - Mice KW - Tissue Distribution KW - Species Specificity KW - Cytochrome P-450 CYP1A2 -- biosynthesis KW - Dioxins -- adverse effects KW - Dioxins -- pharmacokinetics KW - Environmental Pollutants -- toxicity KW - Dioxins -- toxicity KW - Environmental Pollutants -- pharmacokinetics KW - Environmental Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71254750?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+additives+and+contaminants&rft.atitle=Toxicokinetics.&rft.au=van+Birgelen%2C+A+P%3Bvan+den+Berg%2C+M&rft.aulast=van+Birgelen&rft.aufirst=A&rft.date=2000-04-01&rft.volume=17&rft.issue=4&rft.spage=267&rft.isbn=&rft.btitle=&rft.title=Food+additives+and+contaminants&rft.issn=0265203X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-22 N1 - Date created - 2000-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acute methanol intoxication generates free radicals in rats: an ESR spin trapping investigation. AN - 71153358; 10832072 AB - Electron spin resonance (ESR) spectroscopy has been used to investigate free radical generation in rats with acute methanol poisoning. The spin trapping technique was used where a spin trapping agent, alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), reacted with the corresponding alcohol-derived or alcohol-dependent radical to form radical adducts. One radical adduct was detected in both bile and urine samples 2 h after acute methanol poisoning in male Sprague Dawley rats. The hyperfine coupling constants for the radical adduct from [(13)C]-labeled methanol detected in the bile were a(N) = 15.58, a(beta)(H) = 2.81 G, and a(beta)(13C) = 4.53 G, which unambiguously identified this species as POBN/*CH@OH. The same radical adduct was detected in urine. The identification of a methanol-derived radical adduct in samples from bile and urine provided strong direct evidence for the generation of the alcohol-derived radicals during acute intoxication by methanol. Simultaneous administration of the alcohol dehydrogenase inhibitor 4-methylpyrazole and methanol resulted in an increase in the generation of the free radical metabolite detected in the bile. This is the first ESR evidence of methanol-derived free radical generation in an animal model of acute methanol intoxication. JF - Free radical biology & medicine AU - Kadiiska, M B AU - Mason, R P AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. kadiiska@niehs.nih.gov Y1 - 2000/04/01/ PY - 2000 DA - 2000 Apr 01 SP - 1106 EP - 1114 VL - 28 IS - 7 SN - 0891-5849, 0891-5849 KW - Free Radicals KW - 0 KW - Nitrogen Oxides KW - Pyridines KW - Spin Labels KW - alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone KW - Hydroxyl Radical KW - 3352-57-6 KW - L-Iditol 2-Dehydrogenase KW - EC 1.1.1.14 KW - Aspartate Aminotransferases KW - EC 2.6.1.1 KW - Methanol KW - Y4S76JWI15 KW - Index Medicus KW - Bile -- chemistry KW - Injections, Intraperitoneal KW - Animals KW - Liver -- enzymology KW - Hydroxyl Radical -- metabolism KW - Intubation, Gastrointestinal KW - Free Radicals -- metabolism KW - Nitrogen Oxides -- urine KW - Rats KW - Aspartate Aminotransferases -- blood KW - Rats, Sprague-Dawley KW - Nitrogen Oxides -- pharmacokinetics KW - Nitrogen Oxides -- administration & dosage KW - L-Iditol 2-Dehydrogenase -- blood KW - Electron Spin Resonance Spectroscopy KW - Male KW - Methanol -- administration & dosage KW - Spin Trapping KW - Methanol -- metabolism KW - Methanol -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71153358?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Acute+methanol+intoxication+generates+free+radicals+in+rats%3A+an+ESR+spin+trapping+investigation.&rft.au=Kadiiska%2C+M+B%3BMason%2C+R+P&rft.aulast=Kadiiska&rft.aufirst=M&rft.date=2000-04-01&rft.volume=28&rft.issue=7&rft.spage=1106&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 - 2000-07-18 N1 - Date created - 2000-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cadmium carcinogenesis in review. AN - 71146698; 10830873 AB - Cadmium is an inorganic toxicant of great environmental and occupational concern which was classified as a human carcinogen in 1993. Occupational cadmium exposure is associated with lung cancer in humans. Cadmium exposure has also, on occasion, been linked to human prostate cancer. The epidemiological data linking cadmium and pulmonary cancer are much stronger than for prostatic cancer. Other target sites for cadmium carcinogenesis in humans (liver, kidney, stomach) are considered equivocal. In rodents, cadmium causes tumors at several sites and by various routes. Cadmium inhalation in rats results in pulmonary adenocarcinomas, supporting a role in human lung cancer. Prostate tumors and preneoplastic proliferative lesions can be induced in rats after cadmium ingestion or injection. Prostatic carcinogenesis in rats occurs only at cadmium doses below those that induce chronic degeneration and dysfunction of the testes, a well-known effect of cadmium, confirming the androgen dependency of prostate tumors. Other targets of cadmium in rodents include the testes, adrenals, injection sites, and hematopoietic system. Various treatments can modify cadmium carcinogenesis including supplemental zinc, which prevents cadmium-induced injection site and testicular tumors while facilitating prostatic tumors. Cadmium is poorly mutagenic and probably acts through indirect mechanisms, although the precise mechanisms remain unknown. JF - Journal of inorganic biochemistry AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, NC 27706, USA. waalkes@niehs.nih.gov Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 241 EP - 244 VL - 79 IS - 1-4 SN - 0162-0134, 0162-0134 KW - Carcinogens KW - 0 KW - Environmental Pollutants KW - Cadmium KW - 00BH33GNGH KW - Index Medicus KW - Rats KW - Occupational Exposure KW - Animals KW - Prostatic Neoplasms -- epidemiology KW - Environmental Pollutants -- toxicity KW - Humans KW - Neoplasms -- chemically induced KW - Prostatic Neoplasms -- chemically induced KW - Neoplasms -- epidemiology KW - Environmental Exposure KW - Male KW - Carcinogens -- toxicity KW - Cadmium -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71146698?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+inorganic+biochemistry&rft.atitle=Cadmium+carcinogenesis+in+review.&rft.au=Waalkes%2C+M+P&rft.aulast=Waalkes&rft.aufirst=M&rft.date=2000-04-01&rft.volume=79&rft.issue=1-4&rft.spage=241&rft.isbn=&rft.btitle=&rft.title=Journal+of+inorganic+biochemistry&rft.issn=01620134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-18 N1 - Date created - 2000-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of antimutagenic enzymes, 8-oxo-dGTPases, by carcinogenic metals. Recent developments. AN - 71146661; 10830871 AB - Nickel, cadmium, cobalt, and copper are carcinogenic to humans and/or animals, but the underlying mechanisms are poorly understood. Our studies have been focused on one such mechanism involving mediation by the metals of promutagenic oxidative damage to DNA bases. The damage may be inflicted directly in DNA or in the deoxynucleotide pool, from which the damaged bases are incorporated into DNA. Such incorporation is prevented in cells by 8-oxo-2'-deoxyguanosine 5'-triphosphate pyrophosphatases (8-oxo-dGTPases). Thus, inhibition of these enzymes should enhance carcinogenesis. We have studied effects of Cd(II), Cu(II), Co(II), and Ni(II) on the activity of isolated bacterial and human 8-oxo-dGTPases. Cd(II) and Cu(II) were strongly inhibitory, while Ni(II) and Co(II) were much less suppressive. After developing an assay for 8-oxo-dGTPase activity, we confirmed the inhibition by Cd(II) in cultured cells and in the rat testis, the target organ for cadmium carcinogenesis. 8-Oxo-dGTPase inhibition was accompanied by an increase in the 8-oxo-dG level in testicular DNA. JF - Journal of inorganic biochemistry AU - Kasprzak, K S AU - Bialkowski, K AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201, USA. kasprkaz@mail.ncifcrf.gov Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 231 EP - 236 VL - 79 IS - 1-4 SN - 0162-0134, 0162-0134 KW - Carcinogens KW - 0 KW - Enzyme Inhibitors KW - Metals, Heavy KW - Cadmium KW - 00BH33GNGH KW - Cobalt KW - 3G0H8C9362 KW - Copper KW - 789U1901C5 KW - Nickel KW - 7OV03QG267 KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - 8-oxodGTPase KW - EC 3.6.1.55 KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Rats KW - Cadmium -- pharmacology KW - Animals KW - Rats, Inbred F344 KW - Nickel -- pharmacology KW - Kinetics KW - Humans KW - Enzyme Inhibitors -- pharmacology KW - CHO Cells KW - Cobalt -- pharmacology KW - Copper -- pharmacology KW - Male KW - Cricetinae KW - Carcinogens -- pharmacology KW - Metals, Heavy -- pharmacology KW - Phosphoric Monoester Hydrolases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71146661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+inorganic+biochemistry&rft.atitle=Inhibition+of+antimutagenic+enzymes%2C+8-oxo-dGTPases%2C+by+carcinogenic+metals.+Recent+developments.&rft.au=Kasprzak%2C+K+S%3BBialkowski%2C+K&rft.aulast=Kasprzak&rft.aufirst=K&rft.date=2000-04-01&rft.volume=79&rft.issue=1-4&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=Journal+of+inorganic+biochemistry&rft.issn=01620134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-18 N1 - Date created - 2000-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A discussion of the chemistry of oxidative and nitrosative stress in cytotoxicity. AN - 71144848; 10830872 AB - Nitric oxide (NO) has been shown to be a key bioregulatory agent in a wide variety of biological processes, yet cytotoxic properties have been reported as well. This dichotomy has raised the question of how this potentially toxic species can be involved in so many fundamental physiological processes. We have investigated the effects of NO on a variety of toxic agents and correlated how its chemistry might pertain to the observed biology. The results generate a scheme termed the chemical biology of NO in which the pertinent reactions can be categorized into direct and indirect effects. The former involves the direct reaction of NO with its biological targets generally at low fluxes of NO. Indirect effects are reactions mediated by reactive nitrogen oxide species, such as those generated from the NO/O2 and NO/O2- reactions, which can lead to cellular damage via nitrosation or oxidation of biological components. This report discusses several examples of cytotoxicity involved with these stresses. JF - Journal of inorganic biochemistry AU - Miranda, K M AU - Espey, M G AU - Wink, D A AD - Radiation Biology Branch, National Cancer Institute, Bethesda, MD 20892, USA. kmiranda@box-k.nih.gov Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 237 EP - 240 VL - 79 IS - 1-4 SN - 0162-0134, 0162-0134 KW - Nitrates KW - 0 KW - Superoxides KW - 11062-77-4 KW - peroxynitric acid KW - 26404-66-0 KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Superoxides -- chemistry KW - Animals KW - Cell Survival -- drug effects KW - Nitrates -- toxicity KW - Oxidative Stress KW - Nitric Oxide -- pharmacology KW - Nitric Oxide -- physiology KW - Nitric Oxide -- chemistry KW - Cell Survival -- physiology KW - Nitrates -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71144848?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+inorganic+biochemistry&rft.atitle=A+discussion+of+the+chemistry+of+oxidative+and+nitrosative+stress+in+cytotoxicity.&rft.au=Miranda%2C+K+M%3BEspey%2C+M+G%3BWink%2C+D+A&rft.aulast=Miranda&rft.aufirst=K&rft.date=2000-04-01&rft.volume=79&rft.issue=1-4&rft.spage=237&rft.isbn=&rft.btitle=&rft.title=Journal+of+inorganic+biochemistry&rft.issn=01620134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-18 N1 - Date created - 2000-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Impact of alcohol on the ability of Kupffer cells to produce chemokines and its role in alcoholic liver disease. AN - 71139090; 10824877 AB - Chemokines are implicated in the pathogenesis of alcoholic liver disease in humans and in experimental models of alcohol intoxication. The major sources of these chemokines are Kupffer cells which represent more than 80% of tissue macrophages in the body. Kupffer cells are highly responsive to the effects of ethanol, endotoxin and human immunodeficiency virus (HIV)-1 glycoprotein120. These agents, either independently or in combination, may exacerbate the production of chemokines. Chemokines are agents that are highly chemotactic to mononuclear cells and granulocytes. The levels of these chemokines in sera and tissue are elevated in patients with alcoholic hepatitis, alcoholic cirrhosis, diseased livers, viral hepatitis, and in experimental models of chronic alcohol intoxication. Alcohol-induced influx of endotoxin from the gut into the portal circulation is suggested to play an important role in the activation of Kupffer cells which leads to enhanced chemokine release. The up-regulation of chemokines during alcohol consumption is selective. During the early phase of alcoholic liver disease, C-X-C or alpha-chemokines predominate. This is also associated with neutrophilic infiltration of the liver. In the later stage, up-regulation of C-C or beta-chemokine production and migration of mononuclear cells into the liver are observed, and this may lead to liver cirrhosis. Selective up-regulation of chemokine synthesis and release may involve differential modulation of the transcription factors required for chemokine gene expression. Increased cytokine release following alcohol consumption may also regulate chemokine secretion in Kupffer cells via paracrine and autocrine mechanisms and vice versa. In addition, infection with HIV-1 may further compromise the liver to more damage. During HIV-1 infection, a pre-existing liver disease superimposed on chronic alcohol consumption may also exacerbate HIV-1 replication and lymphocytic infiltration in the liver, because of the ability of HIV-1 gp120 to stimulate chemokine production by Kupffer cells and stimulate migration of inflammatory leucocytes in the liver. JF - Journal of gastroenterology and hepatology AU - Bautista, A P AD - Department of Physiology and National Institute on Alcohol Abuse and Alcoholism-Sponsored Alcohol Research Center, Louisiana State University Medical Center, New Orleans 70112, USA. abauti@lsumc.edu Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 349 EP - 356 VL - 15 IS - 4 SN - 0815-9319, 0815-9319 KW - Chemokines KW - 0 KW - Endotoxins KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - AIDS/HIV KW - Liver Cirrhosis, Experimental -- chemically induced KW - Animals KW - Neutrophils -- pathology KW - Macrophage Activation -- genetics KW - Humans KW - Alcohol Drinking -- adverse effects KW - Alcoholic Intoxication -- complications KW - Liver Cirrhosis, Experimental -- metabolism KW - Macrophage Activation -- drug effects KW - Neutrophils -- metabolism KW - Neutrophils -- drug effects KW - Endotoxins -- secretion KW - Up-Regulation -- drug effects KW - Signal Transduction -- drug effects KW - Cell Movement -- drug effects KW - Intestinal Mucosa -- drug effects KW - Intestinal Mucosa -- secretion KW - Liver Cirrhosis, Experimental -- pathology KW - Alcoholic Intoxication -- metabolism KW - Liver Diseases, Alcoholic -- metabolism KW - Ethanol -- adverse effects KW - Liver Diseases, Alcoholic -- pathology KW - Chemokines -- genetics KW - Kupffer Cells -- metabolism KW - Kupffer Cells -- drug effects KW - Ethanol -- toxicity KW - Chemokines -- biosynthesis KW - Liver Diseases, Alcoholic -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71139090?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+gastroenterology+and+hepatology&rft.atitle=Impact+of+alcohol+on+the+ability+of+Kupffer+cells+to+produce+chemokines+and+its+role+in+alcoholic+liver+disease.&rft.au=Bautista%2C+A+P&rft.aulast=Bautista&rft.aufirst=A&rft.date=2000-04-01&rft.volume=15&rft.issue=4&rft.spage=349&rft.isbn=&rft.btitle=&rft.title=Journal+of+gastroenterology+and+hepatology&rft.issn=08159319&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-27 N1 - Date created - 2000-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assessment of specificity of eight chemical inhibitors using cDNA-expressed cytochromes P450. AN - 71124702; 10821163 AB - 1. The selectivity of eight chemical inhibitors has been extensively evaluated with 10 cDNA-expressed human cytochrome P450 isoforms (CYP). The results indicate that sulphaphenazole, quinidine and alpha-naphthoflavone are selective inhibitors of CYP2C9 (IC50 = 0.5-0.7 microM), CYP2D6 (0.3-0.4 microM) and CYP1A (0.05-5 microM) respectively on the basis of the IC50, which are much lower than those of other P450 isoforms (> 10-fold). 2. Ketoconazole exhibited potent inhibition of both CYP3A4-catalysed metabolism of phenanthrene, testosterone, diazepam (IC50 = 0.03-0.5 microM) and CYP1A1-catalysed deethylation of 7-ethoxycoumarin (0.33 microM). The selectivity of ketoconazole for other P450s was highly related to the concentration used. 3. Diethyldithiocarbamate, orphenadrine and furafylline were shown separately to be less selective inhibitors of CYP2E1, CYP2B6 and CYP1A isoforms by a broad range of IC50 that overlap those observed with other P450 isoforms. 4. Furafylline, quinidine and alpha-naphthoflavone activated CYP3A4-catalysed phenanthrene metabolism by 1.7-, 2- and 15-fold respectively. 5. The selectivity of orphenadrine and ketoconazole was further examined by using inhibitory monoclonal antibodies (MAb). Inhibitory MAb specific for the individual P450 isoforms may be of greater value than chemical inhibitors. JF - Xenobiotica; the fate of foreign compounds in biological systems AU - Sai, Y AU - Dai, R AU - Yang, T J AU - Krausz, K W AU - Gonzalez, F J AU - Gelboin, H V AU - Shou, M AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 327 EP - 343 VL - 30 IS - 4 SN - 0049-8254, 0049-8254 KW - Cytochrome P-450 Enzyme Inhibitors KW - 0 KW - DNA, Complementary KW - Enzyme Inhibitors KW - Isoenzymes KW - Index Medicus KW - Isoenzymes -- antagonists & inhibitors KW - Humans KW - Substrate Specificity KW - DNA, Complementary -- genetics KW - Enzyme Inhibitors -- pharmacology KW - Enzyme Inhibitors -- analysis KW - DNA, Complementary -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71124702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Assessment+of+specificity+of+eight+chemical+inhibitors+using+cDNA-expressed+cytochromes+P450.&rft.au=Sai%2C+Y%3BDai%2C+R%3BYang%2C+T+J%3BKrausz%2C+K+W%3BGonzalez%2C+F+J%3BGelboin%2C+H+V%3BShou%2C+M&rft.aulast=Sai&rft.aufirst=Y&rft.date=2000-04-01&rft.volume=30&rft.issue=4&rft.spage=327&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 - 2000-08-08 N1 - Date created - 2000-08-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Addiction becomes a brain disease. AN - 71122919; 10798389 JF - Neuron AU - Wise, R A Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 27 EP - 33 VL - 26 IS - 1 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Humans KW - Mice KW - Mice, Knockout KW - Substance-Related Disorders -- physiopathology KW - Cerebral Cortex -- physiology KW - Reward KW - Brain Diseases -- genetics KW - Dopamine -- physiology KW - Behavior, Addictive -- psychology KW - Brain Diseases -- physiopathology KW - Behavior, Addictive -- physiopathology KW - Substance-Related Disorders -- psychology KW - Behavior, Addictive -- genetics KW - Substance-Related Disorders -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71122919?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Neuron&rft.atitle=Addiction+becomes+a+brain+disease.&rft.au=Wise%2C+R+A&rft.aulast=Wise&rft.aufirst=R&rft.date=2000-04-01&rft.volume=26&rft.issue=1&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Neuron&rft.issn=08966273&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-18 N1 - Date created - 2000-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retinal capillary dilation: early diabetic-like retinopathy in the galactose-fed rat model. AN - 71089302; 10803427 AB - The purpose of this study was to determine whether capillary dilation is one of the earliest structural changes in the diabetic-like retinopathy of the galactose-fed rat model and thus may represent a stage where intervention treatment might still be effective. Weanling female Sprague-Dawley rats were randomized into 3 groups and fed Purina laboratory chow plus one of the following for 4 months: 50% starch (CONTROL); 50% D-galactose (Galactose); or 50% D-galactose with ARI-509 (25 mg/kg body wt/day) (Inhibitor). One eye from each of 5 rats per treatment group was processed for retinal vasculature wholemounts using elastase digestion, stained with a standard periodic-acid-Schiff reaction and counterstained with hematoxylin. Average capillary width, overall capillary density and total capillary length were measured, using computerized image analysis, within an arc-shaped area (4.4 mm2) of each vasculature surrounding, but separated from, the optic disc margin by approximately 0.7 mm. Galactose rats exhibited significant (p < 0.001) increases in capillary width (Mean +/- SEM: 7.56 +/- 0.07 microm) and density (42.78 +/- 0.37%) compared with CONTROL rats (6.68 +/- 0.11 microm and 37.18 +/- 0.30%, respectively). These increases were prevented with inhibitor treatment (6.58 +/- 0.16 microm and 35.88 +/- 0.97%, respectively). Capillary length remained unchanged at 4 months ( 246.66 +/- 2.46 mm; Galactose: 250.75 +/- 1.26 mm; Inhibitor: 242.25 +/- 8.43 mm). Retinal capillary dilation, expressed as increased width and density, is one of the earliest detectable lesions in galactose-fed rats. In these rats, the lesion occurs as early as retinal capillary basement membrane thickening (RCBMT), one of the earliest reported changes in human diabetic retinopathy. Like RCBMT, capillary dilation can be prevented in rats with aldose reductase inhibitor treatment. Unlike RCBMT, capillary dilation could be clinically detectable and may be useful for the diagnosis of early retinopathy and for determining the timing of therapeutic intervention. JF - Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics AU - Glover, J P AU - Jacot, J L AU - Basso, M D AU - Hohman, T C AU - Robison, W G AD - National Eye Institute, NIH, Bethesda, Maryland 20892-2735, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 167 EP - 172 VL - 16 IS - 2 SN - 1080-7683, 1080-7683 KW - Enzyme Inhibitors KW - 0 KW - WAY 121-509 KW - Aldehyde Reductase KW - EC 1.1.1.21 KW - Galactose KW - X2RN3Q8DNE KW - Index Medicus KW - Rats KW - Basement Membrane -- pathology KW - Animals KW - Rats, Sprague-Dawley KW - Enzyme Inhibitors -- administration & dosage KW - Aldehyde Reductase -- administration & dosage KW - Dilatation, Pathologic KW - Capillaries -- pathology KW - Capillaries -- drug effects KW - Aldehyde Reductase -- antagonists & inhibitors KW - Female KW - Diabetic Retinopathy -- pathology KW - Diabetic Retinopathy -- chemically induced KW - Diabetes Mellitus, Experimental -- pathology KW - Diabetes Mellitus, Experimental -- prevention & control KW - Retinal Vessels -- drug effects KW - Diabetes Mellitus, Experimental -- chemically induced KW - Galactose -- adverse effects KW - Diabetic Retinopathy -- prevention & control KW - Retinal Vessels -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71089302?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+ocular+pharmacology+and+therapeutics+%3A+the+official+journal+of+the+Association+for+Ocular+Pharmacology+and+Therapeutics&rft.atitle=Retinal+capillary+dilation%3A+early+diabetic-like+retinopathy+in+the+galactose-fed+rat+model.&rft.au=Glover%2C+J+P%3BJacot%2C+J+L%3BBasso%2C+M+D%3BHohman%2C+T+C%3BRobison%2C+W+G&rft.aulast=Glover&rft.aufirst=J&rft.date=2000-04-01&rft.volume=16&rft.issue=2&rft.spage=167&rft.isbn=&rft.btitle=&rft.title=Journal+of+ocular+pharmacology+and+therapeutics+%3A+the+official+journal+of+the+Association+for+Ocular+Pharmacology+and+Therapeutics&rft.issn=10807683&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-16 N1 - Date created - 2000-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carbohydrate-deficient transferrin, gamma-glutamyltransferase, and macrocytic volume as biomarkers of alcohol problems in women. AN - 71086969; 10798585 AB - Early identification of alcohol problems in women is important. Differences in patterns of drinking and in biological function between genders, however, may present unique difficulties in biochemical screening. Published alcohol-screening studies with female samples and use as biomarkers of carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT), and macrocytic volume were reviewed. A wide range of sensitivities and specificities of GGT and CDT have been reported, although, in general, the two markers seem approximately equal in accuracy. As in the case of males, use of them in combination substantially enhances sensitivity and little reduces specificity. Use of macrocytic volume improves the sensitivity of both GGT and CDT as alcohol-screening markers. GGT and CDT have moderate sensitivity in screening for alcohol problems in women. Use of them in concert offers further advantage. JF - Alcoholism, clinical and experimental research AU - Allen, J P AU - Litten, R Z AU - Fertig, J B AU - Sillanaukee, P AD - Division of Clinical and Prevention Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-7003, USA. jallen@willco.niaaa.nih.gov Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 492 EP - 496 VL - 24 IS - 4 SN - 0145-6008, 0145-6008 KW - Biomarkers KW - 0 KW - Transferrin KW - carbohydrate-deficient transferrin KW - gamma-Glutamyltransferase KW - EC 2.3.2.2 KW - Index Medicus KW - Sex Factors KW - Humans KW - Biomarkers -- blood KW - Female KW - Erythrocyte Indices KW - Transferrin -- metabolism KW - Transferrin -- analogs & derivatives KW - Alcoholism -- diagnosis KW - gamma-Glutamyltransferase -- blood KW - Alcoholism -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71086969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Carbohydrate-deficient+transferrin%2C+gamma-glutamyltransferase%2C+and+macrocytic+volume+as+biomarkers+of+alcohol+problems+in+women.&rft.au=Allen%2C+J+P%3BLitten%2C+R+Z%3BFertig%2C+J+B%3BSillanaukee%2C+P&rft.aulast=Allen&rft.aufirst=J&rft.date=2000-04-01&rft.volume=24&rft.issue=4&rft.spage=492&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-24 N1 - Date created - 2000-07-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of food on the pharmacokinetics of alcohol absorption. AN - 71084522; 10798565 JF - Alcoholism, clinical and experimental research AU - Gentry, R T AD - Office of Collaborative Research, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, Maryland 20892-7003, USA. tgentry@niaaa.nih.gov Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 403 EP - 404 VL - 24 IS - 4 SN - 0145-6008, 0145-6008 KW - Central Nervous System Depressants KW - 0 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Humans KW - Biological Availability KW - Ethanol -- blood KW - Ethanol -- pharmacokinetics KW - Central Nervous System Depressants -- pharmacokinetics KW - Central Nervous System Depressants -- blood KW - Food-Drug Interactions KW - Intestinal Absorption -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71084522?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Effect+of+food+on+the+pharmacokinetics+of+alcohol+absorption.&rft.au=Gentry%2C+R+T&rft.aulast=Gentry&rft.aufirst=R&rft.date=2000-04-01&rft.volume=24&rft.issue=4&rft.spage=403&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-24 N1 - Date created - 2000-07-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intravascular lymphomatosis: contribution of cerebral MRI findings to diagnosis. AN - 71083234; 10800265 AB - Intravascular lymphomatosis (IL) is a rare variant of non-Hodgkin's lymphoma with an unusual predilection for the central nervous system (CNS). Most cases are not diagnosed until postmortem because of variable clinical presentation and nonspecific laboratory findings. Neuroimaging findings vary widely and range from diffuse involvement of the deep white matter to infarct-like lesions. Cerebral magnetic resonance imaging (MRI) may show parenchymal and meningeal gadolinium enhancement. The authors describe brain MRI findings of linear, punctate, and patchy enhancement suggestive of CNS IL in two patients confirmed by brain biopsy/histologic studies. High index of clinical suspicion and careful interpretation of MRI (including gadolinium contrast studies) may contribute to premortem diagnosis and early intervention of this often-missed disease. JF - Journal of neuroimaging : official journal of the American Society of Neuroimaging AU - Liow, K AU - Asmar, P AU - Liow, M AU - Spanaki, M AU - Townsend, J J AU - Buys, S AU - Baringer, J R AU - Osborn, A AD - National Institute of Neurological Disorders and Stroke, University of Utah School of Medicine, Salt Lake City, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 116 EP - 118 VL - 10 IS - 2 SN - 1051-2284, 1051-2284 KW - Vincristine KW - 5J49Q6B70F KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Cyclophosphamide -- therapeutic use KW - Vincristine -- therapeutic use KW - Prednisone -- therapeutic use KW - Humans KW - Aged KW - Doxorubicin -- therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Male KW - Female KW - Magnetic Resonance Imaging KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Lymphoma, Non-Hodgkin -- diagnosis KW - Brain -- pathology KW - Central Nervous System Neoplasms -- drug therapy KW - Central Nervous System Neoplasms -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71083234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neuroimaging+%3A+official+journal+of+the+American+Society+of+Neuroimaging&rft.atitle=Intravascular+lymphomatosis%3A+contribution+of+cerebral+MRI+findings+to+diagnosis.&rft.au=Liow%2C+K%3BAsmar%2C+P%3BLiow%2C+M%3BSpanaki%2C+M%3BTownsend%2C+J+J%3BBuys%2C+S%3BBaringer%2C+J+R%3BOsborn%2C+A&rft.aulast=Liow&rft.aufirst=K&rft.date=2000-04-01&rft.volume=10&rft.issue=2&rft.spage=116&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroimaging+%3A+official+journal+of+the+American+Society+of+Neuroimaging&rft.issn=10512284&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-06 N1 - Date created - 2000-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Eotaxin and RANTES expression by the dermal endothelium is associated with eosinophil infiltration after ivermectin treatment of onchocerciasis. AN - 71081702; 10794432 AB - The roles of eotaxin, RANTES, and MCP-3 expression in eosinophil recruitment to the site of parasite killing that occurs following ivermectin treatment of onchocerciasis were assessed in the skin of 13 Onchocerca volvulus-infected subjects and two noninfected controls before and after ivermectin treatment. Adverse reactions in infected subjects were associated with the appearance of eosinophils in the dermis as part of a perivascular inflammatory infiltrate. Although no expression of RANTES and eotaxin was seen in dermal vascular endothelial cells in biopsies taken before treatment (nor at any time in the skin of uninfected controls), endothelial expression of both eotaxin and RANTES was noted by 24 h following treatment. While RANTES expression was transient, eotaxin expression increased in parallel with increasing eosinophil recruitment up to 60 h posttreatment. These observations indicate that endothelial expression of eotaxin and RANTES may have an important role in eosinophil recruitment into the skin during helminth-killing reactions. JF - Clinical immunology (Orlando, Fla.) AU - Cooper, P J AU - Beck, L A AU - Espinel, I AU - Deyampert, N M AU - Hartnell, A AU - Jose, P J AU - Paredes, W AU - Guderian, R H AU - Nutman, T B AD - Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, Maryland 20892-0425, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 51 EP - 61 VL - 95 IS - 1 Pt 1 SN - 1521-6616, 1521-6616 KW - CCL11 protein, human KW - 0 KW - Chemokine CCL11 KW - Chemokine CCL5 KW - Chemokines KW - Chemokines, CC KW - Cytokines KW - Ivermectin KW - 70288-86-7 KW - Index Medicus KW - Chemokine CCL5 -- biosynthesis KW - Animals KW - Ecuador KW - Cytokines -- biosynthesis KW - Dermatologic Surgical Procedures KW - Humans KW - Biopsy KW - Chemotaxis, Leukocyte KW - Leukocyte Count KW - Adult KW - Middle Aged KW - Male KW - Female KW - Onchocerciasis -- drug therapy KW - Onchocerca volvulus -- immunology KW - Ivermectin -- therapeutic use KW - Ivermectin -- adverse effects KW - Dermis -- blood supply KW - Onchocerciasis -- immunology KW - Chemokines -- biosynthesis KW - Dermis -- immunology KW - Eosinophilia -- immunology KW - Endothelium, Vascular -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71081702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+immunology+%28Orlando%2C+Fla.%29&rft.atitle=Eotaxin+and+RANTES+expression+by+the+dermal+endothelium+is+associated+with+eosinophil+infiltration+after+ivermectin+treatment+of+onchocerciasis.&rft.au=Cooper%2C+P+J%3BBeck%2C+L+A%3BEspinel%2C+I%3BDeyampert%2C+N+M%3BHartnell%2C+A%3BJose%2C+P+J%3BParedes%2C+W%3BGuderian%2C+R+H%3BNutman%2C+T+B&rft.aulast=Cooper&rft.aufirst=P&rft.date=2000-04-01&rft.volume=95&rft.issue=1+Pt+1&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Clinical+immunology+%28Orlando%2C+Fla.%29&rft.issn=15216616&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-12 N1 - Date created - 2000-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The yeast p53 functional assay: a new tool for molecular epidemiology. Hopes and facts. AN - 71081492; 10767639 AB - The assumption of molecular epidemiology that carcinogens leave fingerprints has suggested that analysis of the frequency, type, and site of mutations in genes frequently altered in carcinogenesis may provide clues to the identification of the factors contributing to carcinogenesis. In this mini-review, we revise the development, and validation of the yeast-based p53 functional assay as a new tool for molecular epidemiology. We show that this assay has some very interesting virtues but also has some drawbacks. The yeast functional assay can be used to determine highly specific mutation fingerprints in the human p53 cDNA sequence. Discrimination is possible when comparing mutation spectra induced by sufficiently different mutagens. However, we also reported that the same carcinogen may induce distinguishable mutation spectra due to known influencing factors. JF - Mutation research AU - Fronza, G AU - Inga, A AU - Monti, P AU - Scott, G AU - Campomenosi, P AU - Menichini, P AU - Ottaggio, L AU - Viaggi, S AU - Burns, P A AU - Gold, B AU - Abbondandolo, A AD - Mutagenesis Laboratory, National Cancer Institute (IST), Largo Rossana Benzi 10, 16132, Genoa, Italy. fronzagi@hp380.ist.unige.it Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 293 EP - 301 VL - 462 IS - 2-3 SN - 0027-5107, 0027-5107 KW - Alkylating Agents KW - 0 KW - Mutagens KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Skin Neoplasms -- genetics KW - Ultraviolet Rays KW - Skin -- radiation effects KW - Mutagenicity Tests -- methods KW - Skin -- metabolism KW - Humans KW - Alkylating Agents -- pharmacology KW - Neoplasms -- chemically induced KW - Neoplasms -- epidemiology KW - Molecular Epidemiology -- methods KW - Mutagens -- pharmacology KW - Mutation KW - Neoplasms -- genetics KW - Saccharomyces cerevisiae -- genetics KW - Tumor Suppressor Protein p53 -- radiation effects KW - Tumor Suppressor Protein p53 -- drug effects KW - Tumor Suppressor Protein p53 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71081492?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=The+yeast+p53+functional+assay%3A+a+new+tool+for+molecular+epidemiology.+Hopes+and+facts.&rft.au=Fronza%2C+G%3BInga%2C+A%3BMonti%2C+P%3BScott%2C+G%3BCampomenosi%2C+P%3BMenichini%2C+P%3BOttaggio%2C+L%3BViaggi%2C+S%3BBurns%2C+P+A%3BGold%2C+B%3BAbbondandolo%2C+A&rft.aulast=Fronza&rft.aufirst=G&rft.date=2000-04-01&rft.volume=462&rft.issue=2-3&rft.spage=293&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-16 N1 - Date created - 2000-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Frequent human genomic DNA transduction driven by LINE-1 retrotransposition. AN - 71065596; 10779482 AB - Human L1 retrotransposons can produce DNA transduction events in which unique DNA segments downstream of L1 elements are mobilized as part of aberrant retrotransposition events. That L1s are capable of carrying out such a reaction in tissue culture cells was elegantly demonstrated. Using bioinformatic approaches to analyze the structures of L1 element target site duplications and flanking sequence features, we provide evidence suggesting that approximately 15% of full-length L1 elements bear evidence of flanking DNA segment transduction. Extrapolating these findings to the 600,000 copies of L1 in the genome, we predict that the amount of DNA transduced by L1 represents approximately 1% of the genome, a fraction comparable with that occupied by exons. JF - Genome research AU - Pickeral, O K AU - Makałowski, W AU - Boguski, M S AU - Boeke, J D AD - National Center for Biotechnology Information, National Institutes of Health, Bethesda, Maryland 20894, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 411 EP - 415 VL - 10 IS - 4 SN - 1088-9051, 1088-9051 KW - 3' Untranslated Regions KW - 0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Humans KW - Computational Biology -- methods KW - 3' Untranslated Regions -- genetics KW - Models, Biological KW - DNA -- metabolism KW - DNA -- genetics KW - Mutagenesis, Insertional -- genetics KW - Long Interspersed Nucleotide Elements -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71065596?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genome+research&rft.atitle=Frequent+human+genomic+DNA+transduction+driven+by+LINE-1+retrotransposition.&rft.au=Pickeral%2C+O+K%3BMaka%C5%82owski%2C+W%3BBoguski%2C+M+S%3BBoeke%2C+J+D&rft.aulast=Pickeral&rft.aufirst=O&rft.date=2000-04-01&rft.volume=10&rft.issue=4&rft.spage=411&rft.isbn=&rft.btitle=&rft.title=Genome+research&rft.issn=10889051&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-09 N1 - Date created - 2000-06-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: FEMS Microbiol Lett. 1999 May 15;174(2):247-50 [10339815] Gene. 1999 Apr 29;231(1-2):77-86 [10231571] Science. 1991 Dec 20;254(5039):1808-10 [1722352] Cancer Res. 1992 Feb 1;52(3):643-5 [1310068] Nat Genet. 1994 Jun;7(2):143-8 [7920631] EMBO J. 1995 Dec 15;14(24):6333-8 [8557053] Gene. 1995 Dec 29;167(1-2):GC1-10 [8566757] Cell. 1996 Nov 29;87(5):905-16 [8945517] Cell. 1996 Nov 29;87(5):917-27 [8945518] Curr Opin Genet Dev. 1996 Dec;6(6):743-8 [8994846] Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1872-7 [9050872] Genomics. 1997 Mar 1;40(2):294-304 [9119397] Nat Genet. 1997 May;16(1):6-7 [9140383] Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 [9254694] EMBO J. 1997 Nov 3;16(21):6590-602 [9351839] Science. 1999 Mar 5;283(5407):1530-4 [10066175] Nature. 1999 Mar 11;398(6723):108-9, 111 [10086353] Science. 1999 Mar 5;283(5407):1465;1467 [10206876] Nature. 1988 Mar 10;332(6160):164-6 [2831458] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I study of combination therapy with immunotoxins IgG-HD37-deglycosylated ricin A chain (dgA) and IgG-RFB4-dgA (Combotox) in patients with refractory CD19(+), CD22(+) B cell lymphoma. AN - 71063858; 10778955 AB - This study used an 8-day continuous infusion regimen of a 1:1 mixture of two immunotoxins (ITs) prepared from deglycosylated ricin A chain (dgA) conjugated to monoclonal antibodies directed against CD22 (RFB4-dgA) and CD19 (HD37-dgA; Combotox) in a Phase I trial involving 22 patients with refractory B cell lymphoma to determine the maximum tolerated dose, clinical pharmacology, and toxicity profile and to characterize any clinical responses. Adult patients received a continuous infusion of Combotox at 10, 20, or 30 mg/m2/192 h. No intrapatient dose escalation was permitted. Patients with > or =50 circulating tumor cells (CTCs)/mm3 in peripheral blood tolerated all doses without major toxicity. The maximum level of serum IT (Cmax) achieved in this group was 345 ng/ml of RFB4-dgA and 660 ng/ml of HD37-dgA (1005 ng/ml of Combotox). In contrast, patients without CTCs (<50/mm3) had unpredictable clinical courses that included two deaths probably related to the IT. Additionally, patients exhibited a significant potential for association between mortality and a history of either autologous bone marrow or peripheral blood stem cell transplants (P2 = 0.003) and between mortality and a history of radiation therapy (P2 = 0.036). In patients with CTCs, prior therapies appeared to have little impact on toxicity. Subsequent evaluation of the ITs revealed biochemical heterogeneity between two lots of HD37-dgA. In addition, HD37-dgA thawed at the study site tended to contain significant particulates, which were not apparent in matched controls stored at the originating site. This suggests that a tendency to aggregate may have resulted from shipping, storage, and handling of the IT that occurred prior to preparation for administration. It is not clear to what extent, if any, the aggregation of HD37-dgA IT was related to the encountered clinical toxicities; however, the potential to aggregate does suggest one possible basis for problems in our clinical experience with HD37-dgA and leads us to the conclusion that non-aggregate-forming formulations for these ITs should be pursued prior to future clinical trials. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Messmann, R A AU - Vitetta, E S AU - Headlee, D AU - Senderowicz, A M AU - Figg, W D AU - Schindler, J AU - Michiel, D F AU - Creekmore, S AU - Steinberg, S M AU - Kohler, D AU - Jaffe, E S AU - Stetler-Stevenson, M AU - Chen, H AU - Ghetie, V AU - Sausville, E A AD - Developmental Therapeutics Program, Clinical Trials Unit, Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892-1906, USA. messmann@pop.nci.nih.gov Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 1302 EP - 1313 VL - 6 IS - 4 SN - 1078-0432, 1078-0432 KW - Antibodies KW - 0 KW - Antibodies, Monoclonal KW - Antigens, CD KW - Antigens, CD19 KW - Antigens, Differentiation, B-Lymphocyte KW - CD22 protein, human KW - Cell Adhesion Molecules KW - Drug Combinations KW - Immunotoxins KW - Lectins KW - Sialic Acid Binding Ig-like Lectin 2 KW - combotox KW - Ricin KW - 9009-86-3 KW - Index Medicus KW - Humans KW - Ricin -- immunology KW - Neoplastic Cells, Circulating -- drug effects KW - Aged KW - Diarrhea -- chemically induced KW - Neoplastic Cells, Circulating -- pathology KW - Adult KW - Treatment Outcome KW - Chromatography, High Pressure Liquid -- methods KW - Antibodies -- drug effects KW - Male KW - Ricin -- adverse effects KW - Area Under Curve KW - Infusions, Intravenous KW - Dose-Response Relationship, Drug KW - Ricin -- therapeutic use KW - Fatigue -- chemically induced KW - Metabolic Clearance Rate KW - Capillary Permeability -- drug effects KW - Drug Therapy, Combination KW - Fever -- chemically induced KW - Antibodies -- blood KW - Middle Aged KW - Female KW - Immunotoxins -- pharmacokinetics KW - Antigens, CD19 -- immunology KW - Lymphoma, B-Cell -- therapy KW - Lymphoma, B-Cell -- immunology KW - Antibodies, Monoclonal -- pharmacokinetics KW - Antigens, Differentiation, B-Lymphocyte -- immunology KW - Immunotoxins -- adverse effects KW - Immunotoxins -- therapeutic use KW - Antibodies, Monoclonal -- adverse effects KW - Antigens, CD -- immunology KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71063858?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=A+phase+I+study+of+combination+therapy+with+immunotoxins+IgG-HD37-deglycosylated+ricin+A+chain+%28dgA%29+and+IgG-RFB4-dgA+%28Combotox%29+in+patients+with+refractory+CD19%28%2B%29%2C+CD22%28%2B%29+B+cell+lymphoma.&rft.au=Messmann%2C+R+A%3BVitetta%2C+E+S%3BHeadlee%2C+D%3BSenderowicz%2C+A+M%3BFigg%2C+W+D%3BSchindler%2C+J%3BMichiel%2C+D+F%3BCreekmore%2C+S%3BSteinberg%2C+S+M%3BKohler%2C+D%3BJaffe%2C+E+S%3BStetler-Stevenson%2C+M%3BChen%2C+H%3BGhetie%2C+V%3BSausville%2C+E+A&rft.aulast=Messmann&rft.aufirst=R&rft.date=2000-04-01&rft.volume=6&rft.issue=4&rft.spage=1302&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 - 2000-08-03 N1 - Date created - 2000-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytotoxic activity of disulfide-stabilized recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) toward fresh malignant cells from patients with B-cell leukemias. AN - 71055031; 10778980 AB - Chemical conjugates of anti-CD22 monoclonal antibodies and toxins have been used to treat CD22+ hematological malignancies. A new anti-CD22 recombinant immunotoxin RFB4(dsFv)-PE38, composed of the Fv portion of the monoclonal antibody RFB4 fused to a truncated form of Pseudomonas exotoxin A, is being developed to target CD22+ tumor cells. To explore the potential clinical utility of this recombinant toxin in treating patients with B-cell malignancies, the fresh cells of patients were incubated ex vivo with RFB4(dsFv)-PE38. Specific cytotoxicity was demonstrated in the malignant cells of 25 of 28 patients with a variety of B-cell malignancies, including acute and chronic lymphocytic leukemias and large cell, mantle cell, and follicular lymphomas. The IC50S, the concentrations necessary for 50% inhibition of protein synthesis, were 3-10 ng/ml in five patients and 10-50 ng/ml in seven patients. Cytotoxicity correlated with cell death upon direct examination of the malignant cells. Significant cytotoxicity was observed with cells containing as few as 350 CD22 sites/cell. A more active derivative of RFB4(dsFv)-PE38, RFB4(dsFv)-PE38KDEL, was produced and was slightly to more than 10-fold more cytotoxic toward patient cells and about twice as toxic to mice. Thus, RFB4(dsFv)-PE38 was specifically cytotoxic toward malignant cells from patients with B-cell leukemias. These data support the testing of RFB4(dsFv)-PE38 in patients with CD22+ leukemias and lymphomas, which is presently under way. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Kreitman, R J AU - Margulies, I AU - Stetler-Stevenson, M AU - Wang, Q C AU - FitzGerald, D J AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Cancer Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 1476 EP - 1487 VL - 6 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 - DNA, Recombinant KW - Disulfides 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 -- cytology KW - Tumor Cells, Cultured -- drug effects KW - Dose-Response Relationship, Drug KW - Immunoglobulin Fragments -- pharmacology KW - Humans KW - Immunoglobulin Fragments -- genetics KW - Plasmids KW - Cell Death -- drug effects KW - Binding Sites KW - Proteins -- drug effects KW - Antibody Specificity KW - Cytotoxicity, Immunologic KW - Disulfides -- chemistry KW - Cell Survival -- drug effects KW - DNA, Recombinant -- genetics KW - Inhibitory Concentration 50 KW - Leukocytes, Mononuclear -- drug effects KW - Time Factors KW - Mutation KW - Leukocytes, Mononuclear -- cytology KW - Leukemia, B-Cell -- pathology KW - Immunotoxins -- immunology KW - Antibodies, Monoclonal -- genetics KW - Antigens, Differentiation, B-Lymphocyte -- immunology KW - Immunotoxins -- genetics KW - Antibodies, Monoclonal -- pharmacology KW - Immunotoxins -- pharmacology KW - Leukemia, B-Cell -- drug therapy KW - Antigens, CD -- immunology KW - Leukemia, B-Cell -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71055031?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cytotoxic+activity+of+disulfide-stabilized+recombinant+immunotoxin+RFB4%28dsFv%29-PE38+%28BL22%29+toward+fresh+malignant+cells+from+patients+with+B-cell+leukemias.&rft.au=Kreitman%2C+R+J%3BMargulies%2C+I%3BStetler-Stevenson%2C+M%3BWang%2C+Q+C%3BFitzGerald%2C+D+J%3BPastan%2C+I&rft.aulast=Kreitman&rft.aufirst=R&rft.date=2000-04-01&rft.volume=6&rft.issue=4&rft.spage=1476&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 - 2000-08-03 N1 - Date created - 2000-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of TGF-beta signaling contributes to autoimmune pancreatitis. AN - 71052521; 10772650 AB - Recent observations suggest that immune response is involved in the development of pancreatitis. However, the exact pathogenesis underlying this immune-mediated response is still under debate. TGF-beta has been known to be an important regulating factor in maintaining immune homeostasis. To determine the role of TGF-beta in the initiation or progression of pancreatitis, TGF-beta signaling was inactivated in mouse pancreata by overexpressing a dominant-negative mutant form of TGF-beta type II receptor in the pancreas, under control of the pS2 mouse trefoil peptide promoter. Transgenic mice showed marked increases in MHC class II molecules and matrix metalloproteinase expression in pancreatic acinar cells. These mice also showed increased susceptibility to cerulein-induced pancreatitis. This pancreatitis was characterized by severe pancreatic edema, inflammatory cell infiltration, T- and B-cell hyperactivation, IgG-type autoantibodies against pancreatic acinar cells, and IgM-type autoantibodies against pancreatic ductal epithelial cells. Therefore, TGF-beta signaling seems to be essential either in maintaining the normal immune homeostasis and suppressing autoimmunity or in preserving the integrity of pancreatic acinar cells. JF - The Journal of clinical investigation AU - Hahm, K B AU - Im, Y H AU - Lee, C AU - Parks, W T AU - Bang, Y J AU - Green, J E AU - Kim, S J AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 1057 EP - 1065 VL - 105 IS - 8 SN - 0021-9738, 0021-9738 KW - Autoantibodies KW - 0 KW - Cytokines KW - Histocompatibility Antigens Class II KW - Immunoglobulin G KW - Immunoglobulin M KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor beta KW - Ceruletide KW - 888Y08971B 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 - Receptors, Transforming Growth Factor beta -- genetics KW - Animals KW - Cytokines -- genetics KW - Gene Expression KW - Immunoglobulin M -- immunology KW - Autoantibodies -- immunology KW - Mice KW - B-Lymphocytes -- immunology KW - Histocompatibility Antigens Class II -- immunology KW - Mice, Transgenic KW - Immunoglobulin G -- immunology KW - Mutagenesis KW - Promoter Regions, Genetic KW - Receptors, Transforming Growth Factor beta -- immunology KW - Autoimmune Diseases -- chemically induced KW - T-Lymphocytes -- immunology KW - Female KW - Male KW - Pancreatitis -- immunology KW - Pancreatitis -- metabolism KW - Transforming Growth Factor beta -- genetics KW - Pancreatitis -- etiology KW - Transforming Growth Factor beta -- metabolism KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71052521?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Loss+of+TGF-beta+signaling+contributes+to+autoimmune+pancreatitis.&rft.au=Hahm%2C+K+B%3BIm%2C+Y+H%3BLee%2C+C%3BParks%2C+W+T%3BBang%2C+Y+J%3BGreen%2C+J+E%3BKim%2C+S+J&rft.aulast=Hahm&rft.aufirst=K&rft.date=2000-04-01&rft.volume=105&rft.issue=8&rft.spage=1057&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 - 2000-05-19 N1 - Date created - 2000-05-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Pathol. 1975 Jun;79(3):465-80 [1094837] Ann N Y Acad Sci. 1999 Jun 30;880:5-16 [10415846] Nature. 1983 Jul 7-13;304(5921):73-6 [6346104] Gastroenterology. 1984 Dec;87(6):1344-50 [6092199] Pancreas. 1990 Jul;5(4):415-20 [1974351] Science. 1991 Nov 1;254(5032):707-10 [1948049] Neuron. 1991 Nov;7(5):703-16 [1742021] Ann Surg. 1992 Jan;215(1):44-56 [1731649] J Cell Biochem. 1992 Dec;50(4):400-10 [1469071] Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):770-4 [8421714] Crit Rev Oral Biol Med. 1993;4(2):197-250 [8435466] Gastroenterology. 1993 Mar;104(3):853-61 [7680018] Growth Factors. 1993;8(1):1-9 [8448037] Cell. 1993 Oct 22;75(2):263-74 [8402911] J Clin Immunol. 1993 Jul;13(4):265-71 [7693746] Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9944-8 [8234339] Gut. 1993 Oct;34(10):1452-7 [8244120] Pancreas. 1994 May;9(3):374-81 [8022761] Autoimmunity. 1994;19(1):23-9 [7749039] Dig Dis Sci. 1995 Jul;40(7):1561-8 [7628283] Gastroenterology. 1996 May;110(5):1579-86 [8613065] Surgery. 1996 Aug;120(2):284-8; discussion 289 [8751594] Science. 1996 Oct 11;274(5285):259-62 [8824193] Cytokine Growth Factor Rev. 1996 Jun;7(1):93-102 [8864357] J Clin Invest. 1996 Nov 1;98(9):2109-19 [8903331] Am J Gastroenterol. 1996 Dec;91(12):2607-9 [8946997] Cytokine. 1997 Mar;9(3):212-8 [9126710] EMBO J. 1997 May 15;16(10):2621-33 [9184209] Dig Dis Sci. 1997 Aug;42(8):1783-8 [9286248] Hum Immunol. 1997 May;54(2):159-69 [9297534] Am J Surg. 1998 Jan;175(1):76-83 [9445247] Pancreas. 1998 Apr;16(3):265-72 [9548665] Pancreas. 1998 May;16(4):539-44 [9598817] J Surg Res. 1998 Nov;80(1):110-4 [9790823] Gut. 1998 Sep;43(3):408-13 [9863488] Digestion. 1999;60 Suppl 1:27-33 [10026428] Digestion. 1999;60 Suppl 1:57-60 [10026433] Pancreas. 1999 May;18(4):371-7 [10231842] Gut. 1999 Jul;45(1):105-11 [10369712] Pancreas. 1999 Jul;19(1):33-8 [10416689] Virchows Arch A Pathol Anat Histol. 1977 Mar 11;373(2):97-117 [139754] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular epidemiology and carcinogenesis: endogenous and exogenous carcinogens. AN - 71051172; 10767641 AB - Mutations of the p53 tumor suppressor gene are found in about 50% of all human cancers. The p53 mutation spectra in these cancers are providing clues to the etiology and molecular pathogenesis of cancer. Recent studies indicate that the p53 protein is involved in several vital cellular functions, such as gene transcription, DNA synthesis and repair, cell cycle arrest, senescence and programmed cell death. Mutations in the p53 gene can abrogate these functions and may contribute to genomic instability and progression to cancer. Characteristic p53 mutation spectra have been associated with dietary aflatoxin B(1) (AFB(1)) exposure and hepatocellular carcinoma (HCC); sunlight exposure and skin cancer; and cigarette smoking and lung cancer. The mutation spectrum also reveals those p53 mutants that provide cells with a selective clonal expansion advantage during the multistep process of carcinogenesis. Although a number of different exogenous carcinogens have been shown to selectively target p53, pieces of evidence supporting the endogenous insult of p53 are accumulating. Furthermore, analysis of a characteristic p53 mutation load in nontumorous human tissue can indicate previous carcinogen exposure and may identify individuals at an increased cancer risk. JF - Mutation research AU - Hussain, S P AU - Harris, C C AD - Laboratory of Human Carcinogenesis, Building 37, Room 2C05, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 311 EP - 322 VL - 462 IS - 2-3 SN - 0027-5107, 0027-5107 KW - Carcinogens KW - 0 KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Carcinogens -- pharmacology KW - Molecular Epidemiology KW - Humans KW - Carcinoma, Hepatocellular -- genetics KW - Liver Neoplasms -- chemically induced KW - Mutation KW - Models, Biological KW - Carcinoma, Hepatocellular -- chemically induced KW - Liver Neoplasms -- genetics KW - Tumor Suppressor Protein p53 -- drug effects KW - Neoplasms -- chemically induced KW - Neoplasms -- epidemiology KW - Tumor Suppressor Protein p53 -- genetics KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71051172?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Molecular+epidemiology+and+carcinogenesis%3A+endogenous+and+exogenous+carcinogens.&rft.au=Hussain%2C+S+P%3BHarris%2C+C+C&rft.aulast=Hussain&rft.aufirst=S&rft.date=2000-04-01&rft.volume=462&rft.issue=2-3&rft.spage=311&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-16 N1 - Date created - 2000-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Discontinuation of antidepressant drugs during electroconvulsive therapy: a controlled study. AN - 71048061; 10760556 AB - The concurrent use of antidepressant drugs with ECT is recommended by a recent ECT guideline. The study aimed to examine differential therapeutic and side effect responses when antidepressants are discontinued or not during ECT. This study compared the effectiveness and side effect profile of unilateral ECT with antidepressant drugs (Group-1) or unilateral ECT with drug placebo (Group-2) in 30 major depressive disorder (DSM-IV) patients on antidepressants using a prospective randomised trial. Hamilton Rating Scale for Depression (HRSD), Montgomery Asberg Depression Rating Scale (MADRS), UKU scale, Columbia ECT side effect check list were used. The assessments were carried out before starting ECTs and at fixed intervals thereafter for four weeks. In addition, at six weeks a follow-up assessment was carried out using HRSD. ECTs were stopped after four weeks or earlier if patient obtained HRSD scores <8 and remained so for one week. Continuation of antidepressant drugs with ECT conferred no therapeutic advantage. Barring tricyclic antidepressant induced anticholinergic side effects, no differential side effect profile was noted. At follow-up none relapsed in Group-2 and the mean HRSD scores between the groups did not differ. The antidepressant treatment prior to ECT was uncontrolled. In addition, the design was not strictly double-blind. The study failed to support an advantage with antidepressant continuation during an ECT course in major depressive disorder. JF - Journal of affective disorders AU - Mayur, P M AU - Gangadhar, B N AU - Subbakrishna, D K AU - Janakiramaiah, N AD - Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 37 EP - 41 VL - 58 IS - 1 SN - 0165-0327, 0165-0327 KW - Antidepressive Agents KW - 0 KW - Index Medicus KW - Substance Withdrawal Syndrome -- etiology KW - Combined Modality Therapy KW - Humans KW - Adult KW - Treatment Outcome KW - Personality Inventory KW - Middle Aged KW - Male KW - Female KW - Depressive Disorder, Major -- diagnosis KW - Antidepressive Agents -- administration & dosage KW - Depressive Disorder, Major -- psychology KW - Electroconvulsive Therapy KW - Depressive Disorder, Major -- therapy KW - Antidepressive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71048061?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+affective+disorders&rft.atitle=Discontinuation+of+antidepressant+drugs+during+electroconvulsive+therapy%3A+a+controlled+study.&rft.au=Mayur%2C+P+M%3BGangadhar%2C+B+N%3BSubbakrishna%2C+D+K%3BJanakiramaiah%2C+N&rft.aulast=Mayur&rft.aufirst=P&rft.date=2000-04-01&rft.volume=58&rft.issue=1&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Journal+of+affective+disorders&rft.issn=01650327&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-21 N1 - Date created - 2000-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tolerance to the anticonvulsant effects of lamotrigine on amygdala kindled seizures: cross-tolerance to carbamazepine but not valproate or diazepam. AN - 71047641; 10739634 AB - Using an amygdala-kindled seizure paradigm, we evaluated the acute and chronic anticonvulsant effects of lamotrigine (LTG). Lamotrigine produced dose-dependent inhibitory effects on seizure stage, afterdischarge (AD), and seizure duration. Lamotrigine (15 mg/kg) also increased the afterdischarge and seizure thresholds. Following repeated LTG administration and stimulation at 48-h intervals, tolerance developed to LTG's (15 mg/kg) anticonvulsant effects, and cross-tolerance was observed to the anticonvulsant effects of carbamazepine (CBZ, 15 mg/kg). In a separate group of kindled rats, CBZ (15 mg/kg) was repeatedly administered to induce tolerance. This led to a partial cross-tolerance to LTG, manifesting as an increased rate of tolerance development to LTG, and seizures following the first injection in some animals, which were not observed in CBZ-nontolerant controls. When these rats were made fully tolerant to LTG and then exposed to higher doses of LTG (30 and 50 mg/kg), no anticonvulsant effects were observed. In contrast, higher doses of CBZ (30 mg/kg) did restore efficacy in CBZ-tolerant animals. Cross-tolerance from LTG to valproate and diazepam was not observed, although cross-tolerance from CBZ to valproate has been reported previously. These data suggest that LTG has both shared and distinct anticonvulsant mechanisms from those of CBZ on amygdala-kindled seizures. The implications of these results for clinical therapeutics remain to be evaluated. Copyright 2000 Academic Press. JF - Experimental neurology AU - Krupp, E AU - Heynen, T AU - Li, X L AU - Post, R M AU - Weiss, S R AD - Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 278 EP - 289 VL - 162 IS - 2 SN - 0014-4886, 0014-4886 KW - Anticonvulsants KW - 0 KW - Triazines KW - Carbamazepine KW - 33CM23913M KW - Valproic Acid KW - 614OI1Z5WI KW - Diazepam KW - Q3JTX2Q7TU KW - lamotrigine KW - U3H27498KS KW - Index Medicus KW - Diazepam -- administration & dosage KW - Animals KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Electrodes, Implanted KW - Diazepam -- pharmacology KW - Disease Models, Animal KW - Electric Stimulation KW - Valproic Acid -- administration & dosage KW - Valproic Acid -- pharmacology KW - Rats KW - Kindling, Neurologic -- drug effects KW - Rats, Sprague-Dawley KW - Male KW - Drug Tolerance KW - Anticonvulsants -- pharmacology KW - Amygdala -- physiopathology KW - Triazines -- pharmacology KW - Carbamazepine -- pharmacology KW - Carbamazepine -- administration & dosage KW - Seizures -- metabolism KW - Seizures -- drug therapy KW - Anticonvulsants -- administration & dosage KW - Amygdala -- drug effects KW - Triazines -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71047641?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tolerance+to+the+anticonvulsant+effects+of+lamotrigine+on+amygdala+kindled+seizures%3A+cross-tolerance+to+carbamazepine+but+not+valproate+or+diazepam.&rft.au=Krupp%2C+E%3BHeynen%2C+T%3BLi%2C+X+L%3BPost%2C+R+M%3BWeiss%2C+S+R&rft.aulast=Krupp&rft.aufirst=E&rft.date=2000-04-01&rft.volume=162&rft.issue=2&rft.spage=278&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 - 2000-05-23 N1 - Date created - 2000-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Instability of sleep patterns in children with attention-deficit/hyperactivity disorder. AN - 71047282; 10761352 AB - To compare the stability of the sleep-wake system of children with attention-deficit/hyperactivity disorder (ADHD) and controls by objective and subjective measures. Thirty-eight school-age boys with diagnosed ADHD and 64 control school-age boys were examined using actigraphic monitoring and sleep diaries, over 5 consecutive nights. Increased instability in sleep onset, sleep duration, and true sleep were found in the ADHD group compared with the control group. Discriminant analysis revealed that children's classification (ADHD versus control) could be significantly predicted on the basis of their sleep measures. The findings support the hypothesis that instability of the sleep-wake system is a characteristic of children with ADHD. Given the potential negative effects of disturbed or unstable sleep on daytime functioning, it is recommended that a thorough sleep assessment be conducted when a sleep disturbance is suspected or when symptoms associated with daytime sleepiness or decreased arousal level are present. JF - Journal of the American Academy of Child and Adolescent Psychiatry AU - Gruber, R AU - Sadeh, A AU - Raviv, A AD - Department of Psychology, Tel Aviv University, Israel. GruberR@intra.nimh.nih.gov Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 495 EP - 501 VL - 39 IS - 4 SN - 0890-8567, 0890-8567 KW - Biomarkers KW - 0 KW - Index Medicus KW - Polysomnography KW - Psychiatric Status Rating Scales KW - Humans KW - Case-Control Studies KW - Child KW - Adolescent KW - Male KW - Attention Deficit Disorder with Hyperactivity -- diagnosis KW - Attention Deficit Disorder with Hyperactivity -- complications KW - Sleep Disorders, Circadian Rhythm -- diagnosis KW - Sleep Disorders, Circadian Rhythm -- physiopathology KW - Sleep Disorders, Circadian Rhythm -- complications KW - Attention Deficit Disorder with Hyperactivity -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71047282?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.atitle=Instability+of+sleep+patterns+in+children+with+attention-deficit%2Fhyperactivity+disorder.&rft.au=Gruber%2C+R%3BSadeh%2C+A%3BRaviv%2C+A&rft.aulast=Gruber&rft.aufirst=R&rft.date=2000-04-01&rft.volume=39&rft.issue=4&rft.spage=495&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.issn=08908567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-03 N1 - Date created - 2000-05-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Olanzapine pharmacokinetics in pediatric and adolescent inpatients with childhood-onset schizophrenia. AN - 71042600; 10770461 AB - Well-designed studies investigating how pediatric or adolescent patients with mental disorders respond to and metabolize the newer antipsychotic drugs are practically nonexistent. Without such data, clinicians have difficulty designing appropriate dosage regimens for patients in these age groups. The results from a study of olanzapine pharmacokinetics in children and adolescents are described. Eight inpatients (ages 10-18 years) with treatment-resistant childhood-onset schizophrenia received olanzapine (2.5-20 mg/day) over 8 weeks. Blood samples, collected during dose titration and at a steady state provided pharmacokinetic data. The final evaluation (week 8) included extensive sampling for 36 hours after a 20-mg dose. Olanzapine concentrations in these eight pediatric patients were of the same magnitude as those for nonsmoking adult patients with schizophrenia but may be as much as twice the typical olanzapine concentrations in patients with schizophrenia who smoke. Olanzapine pharmacokinetic evaluation gave an apparent mean oral clearance of 9.6 +/- 2.4 L/hr and a mean elimination half-life of 37.2 +/- 5.1 hours in these young patients. The determination of the initial olanzapine dose for adolescent patients should take into consideration factors such as the patient's size. In general, however, the usual dose recommendation of 5 to 10 mg once daily with a target dose of 10 mg/day is likely a good clinical guideline for most adolescent patients on the basis of our pharmacokinetics results. JF - Journal of clinical psychopharmacology AU - Grothe, D R AU - Calis, K A AU - Jacobsen, L AU - Kumra, S AU - DeVane, C L AU - Rapoport, J L AU - Bergstrom, R F AU - Kurtz, D L AD - Clinical Center Pharmacy Department, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1196, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 220 EP - 225 VL - 20 IS - 2 SN - 0271-0749, 0271-0749 KW - Antipsychotic Agents KW - 0 KW - Benzodiazepines KW - 12794-10-4 KW - Pirenzepine KW - 3G0285N20N KW - olanzapine KW - N7U69T4SZR KW - Index Medicus KW - Drug Administration Schedule KW - Patient Admission KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Treatment Outcome KW - Metabolic Clearance Rate KW - Child KW - Adolescent KW - Male KW - Female KW - Antipsychotic Agents -- administration & dosage KW - Pirenzepine -- analogs & derivatives KW - Antipsychotic Agents -- pharmacokinetics KW - Pirenzepine -- pharmacokinetics KW - Antipsychotic Agents -- adverse effects KW - Pirenzepine -- administration & dosage KW - Pirenzepine -- adverse effects KW - Schizophrenia, Childhood -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71042600?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Olanzapine+pharmacokinetics+in+pediatric+and+adolescent+inpatients+with+childhood-onset+schizophrenia.&rft.au=Grothe%2C+D+R%3BCalis%2C+K+A%3BJacobsen%2C+L%3BKumra%2C+S%3BDeVane%2C+C+L%3BRapoport%2C+J+L%3BBergstrom%2C+R+F%3BKurtz%2C+D+L&rft.aulast=Grothe&rft.aufirst=D&rft.date=2000-04-01&rft.volume=20&rft.issue=2&rft.spage=220&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 - 2000-06-28 N1 - Date created - 2000-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical physiology of dopa dyskinesia. AN - 71042579; 10762142 AB - Levodopa-induced dyskinesias are clinically heterogeneous, both in appearance and timing with respect to dose. Electromyogram observations indicate that levodopa-induced dyskinesias are comprised of irregular bursts of either synchronous or asynchronous neuronal firing in antagonist muscles. Studies of the blink reflex and spontaneous blinking have provided useful neurophysiologic information on brainstem function that is sensitive to changes in brain dopamine concentrations. The blink rate is reduced in Parkinson's disease (PD) and increased with dopamine treatment. The blink rate in patients with levodopa-induced dyskinesias, however, has been shown to be faster than that in optimally treated PD patients and normal individuals. These results suggest that dyskinesias are associated with a relative hyperdopaminergic state. However, there appears to be no correlation of dopaminergic benefit to the parkinsonian symptoms, indicating perhaps that there are several dopaminergic systems, including one responsible for motor function and one for dyskinesia. Alternatively, it may be that the pattern of neural firing influences dyskinesias, while the average firing rate may be responsible for motor benefits. JF - Annals of neurology AU - Hallett, M AD - Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1428, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - S147 EP - 50; discussion S150-3 VL - 47 IS - 4 Suppl 1 SN - 0364-5134, 0364-5134 KW - Dopamine Agents KW - 0 KW - Levodopa KW - 46627O600J KW - Index Medicus KW - Humans KW - Electromyography KW - Dyskinesia, Drug-Induced -- diagnosis KW - Dopamine Agents -- adverse effects KW - Dyskinesia, Drug-Induced -- physiopathology KW - Levodopa -- adverse effects KW - Parkinson Disease -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71042579?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurology&rft.atitle=Clinical+physiology+of+dopa+dyskinesia.&rft.au=Hallett%2C+M&rft.aulast=Hallett&rft.aufirst=M&rft.date=2000-04-01&rft.volume=47&rft.issue=4+Suppl+1&rft.spage=S147&rft.isbn=&rft.btitle=&rft.title=Annals+of+neurology&rft.issn=03645134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-21 N1 - Date created - 2000-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Striatal mechanisms and pathogenesis of parkinsonian signs and motor complications. AN - 71042539; 10762139 AB - Recent studies suggest that motor dysfunction associated with the chronic nonphysiologic stimulation of dopaminergic receptors on striatal spiny neurons alters the sensitivity of nearby glutamatergic receptors, especially those of the N-methyl-D-aspartate (NMDA) subtype. Lesioning the nigrostriatal dopamine system of rats or nonhuman primates induces parkinsonian signs; subsequent once- or twice-daily treatment with levodopa produces many of the features of the human motor complication syndrome. Some drugs that block NMDA receptors palliate parkinsonian signs in these animal models, as well as in patients with Parkinson's disease. Certain NMDA receptor antagonists injected into the striatum or given systemically also have the ability to act palliatively or prophylactically to alleviate levodopa-induced response alterations. These observations support the view that sensitization of striatal NMDA receptors contributes to the pathogenesis of motor dysfunction in Parkinson's disease. Since protein phosphorylation serves as an important regulatory mechanism for NMDA receptors, differential increases in the phosphorylation state of tyrosine and serine residues, observed as a result of nigrostriatal system destruction as well as response alteration induction, could account for the apparent augmentation in synaptic efficacy. Current evidence thus suggests that the intermittent stimulation of dopaminergic receptors activates signal transduction pathways in striatal neurons, which augment phosphorylation of NMDA receptors and thus their sensitivity to cortical glutamatergic input. As a result, striatal output changes in ways that favor the appearance of parkinsonian signs and motor complications. JF - Annals of neurology AU - Chase, T N AU - Oh, J D AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - S122 EP - 9; discussion S129-30 VL - 47 IS - 4 Suppl 1 SN - 0364-5134, 0364-5134 KW - Dopamine Agents KW - 0 KW - Levodopa KW - 46627O600J KW - Index Medicus KW - Animals KW - Humans KW - Dopamine Agents -- adverse effects KW - Levodopa -- adverse effects KW - Parkinson Disease, Secondary -- physiopathology KW - Parkinson Disease -- etiology KW - Motor Neurons -- physiology KW - Corpus Striatum -- physiopathology KW - Parkinson Disease -- physiopathology KW - Parkinson Disease, Secondary -- etiology KW - Motor Neurons -- drug effects KW - Parkinson Disease, Secondary -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71042539?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurology&rft.atitle=Striatal+mechanisms+and+pathogenesis+of+parkinsonian+signs+and+motor+complications.&rft.au=Chase%2C+T+N%3BOh%2C+J+D&rft.aulast=Chase&rft.aufirst=T&rft.date=2000-04-01&rft.volume=47&rft.issue=4+Suppl+1&rft.spage=S122&rft.isbn=&rft.btitle=&rft.title=Annals+of+neurology&rft.issn=03645134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-21 N1 - Date created - 2000-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biphasic ocular inflammatory response to endotoxin-induced uveitis in the mouse. AN - 71042218; 10766138 AB - To examine the kinetics and mechanisms of endotoxin-induced uveitis in the mouse. C3H/HeN mice were injected subcutaneously with 0.3 mg of Salmonella typhimurium lipopolysaccharide (LPS) in 0.1 mL of phosphate-buffered saline solution or phosphate-buffered saline solution alone in 3 separate experiments; mice were killed after 1, 3, 5, and 7 days. In 2 other separate experiments, mice were killed 1, 3, 6, and 24 hours after LPS injection. All eyes were collected for histological examination, immunohistochemical analyses, aqueous protein level determination, and reverse transcriptase-polymerase chain reaction for ocular interleukin (IL)1alpha, IL-6, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor messenger RNA (mRNA). Enzyme-linked immunosorbent assay was used to measure tumor necrosis factor alpha and IL-6 levels in aqueous and serum samples. Results were consistent for all experiments. Numbers of ocular inflammatory cells and levels of aqueous protein peaked 1 and 5 days after LPS injection. Control mice did not develop inflammation. Serum and aqueous IL-6 and ocular IL-6 mRNA levels peaked at 1 day and subsided at 3 days. However, ocular IL-1alpha, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor mRNA appeared, peaked, and subsided at 3, 5, and 7 days, respectively. Predominant infiltrating cells were neutrophils at 1 day and macrophages at 5 days. Although no ocular inflammatory cells were detected before 24 hours after LPS injection, tumor necrosis factor alpha mRNA was noticed at 1 hour, peaked at 3 hours, and disappeared at 6 hours and granulocyte-macrophage colony-stimulating factor mRNA was spotted only at 3 hours after LPS injection. The ocular inflammatory response to C3H/ HeN mouse endotoxin-induced uveitis is biphasic for 7 days. The first wave appears at day 1 and subsides by day 3. A second, higher peak appears at day 5. The 2 inflammatory waves are related to the kinetics of the different cytokines released in the eye. This is in contrast to the rat monophasic endotoxin-induced uveitis model, which has only one peak of intense inflammation associated with cytokine release. A biphasic inflammatory response associated with cytokine release lasting several days is observed in C3H/HeN mice with endotoxin-induced uveitis. Because human anterior uveitis has a tendency to be recurrent in nature, this might be a better experimental model. JF - Archives of ophthalmology (Chicago, Ill. : 1960) AU - Shen, D F AU - Chang, M A AU - Matteson, D M AU - Buggage, R AU - Kozhich, A T AU - Chan, C C AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1857, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 521 EP - 527 VL - 118 IS - 4 SN - 0003-9950, 0003-9950 KW - Cytokines KW - 0 KW - Endotoxins KW - Eye Proteins KW - RNA, Messenger KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Aqueous Humor -- metabolism KW - Neutrophils -- pathology KW - Cytokines -- genetics KW - Macrophages -- immunology KW - Neutrophils -- immunology KW - Eye Proteins -- metabolism KW - Mice KW - Cytokines -- metabolism KW - Reverse Transcriptase Polymerase Chain Reaction KW - Neutrophil Infiltration -- immunology KW - Lymphocytes -- pathology KW - Lymphocytes -- immunology KW - Macrophages -- pathology KW - RNA, Messenger -- metabolism KW - Eye Proteins -- genetics KW - Mice, Inbred C3H KW - Enzyme-Linked Immunosorbent Assay KW - Immunophenotyping KW - Female KW - Uveitis, Anterior -- chemically induced KW - Uveitis, Anterior -- immunology KW - Uveitis, Anterior -- pathology KW - Salmonella typhimurium KW - Endotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71042218?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+ophthalmology+%28Chicago%2C+Ill.+%3A+1960%29&rft.atitle=Biphasic+ocular+inflammatory+response+to+endotoxin-induced+uveitis+in+the+mouse.&rft.au=Shen%2C+D+F%3BChang%2C+M+A%3BMatteson%2C+D+M%3BBuggage%2C+R%3BKozhich%2C+A+T%3BChan%2C+C+C&rft.aulast=Shen&rft.aufirst=D&rft.date=2000-04-01&rft.volume=118&rft.issue=4&rft.spage=521&rft.isbn=&rft.btitle=&rft.title=Archives+of+ophthalmology+%28Chicago%2C+Ill.+%3A+1960%29&rft.issn=00039950&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-17 N1 - Date created - 2000-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine-mediated gene regulation in models of Parkinson's disease. AN - 71040713; 10762131 AB - The normal functioning of the basal ganglia is dependent on dopamine maintaining a balance between the two major output pathways of the striatum, through the D1 and D2 dopamine receptors, which have opposing effects on these pathways. Lesions of the dopamine system, such as occur in Parkinson's disease (PD), disrupt this balance. Gene regulation studies provide a measure of the cellular and molecular effects of dopamine on striatal neurons in animal models of PD. Dopamine agonists, involving selective or mixed D1 and D2 agonists, such as levodopa, are able to reverse many of the homeostatic changes induced by striatal dopamine depletion. However, following dopamine depletion, a supersensitive responsiveness of D1 striatal neurons to dopamine agonists develops, indicated by the induction of immediate early genes. The molecular and cellular mechanisms underlying the irreversibility of this supersensitive response with long-term dopamine agonist treatments may provide insights into dyskinesias that develop with long-term levodopa therapy in the treatment of PD. JF - Annals of neurology AU - Gerfen, C R AD - Laboratory of Systems Neuroscience, NIMH, Bethesda, MD 20892-4075, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - S42 EP - 50; discussion S50-2 VL - 47 IS - 4 Suppl 1 SN - 0364-5134, 0364-5134 KW - Dopamine Agents KW - 0 KW - Levodopa KW - 46627O600J KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Humans KW - Dopamine Agents -- adverse effects KW - Gene Expression -- physiology KW - Levodopa -- adverse effects KW - Brain Chemistry -- physiology KW - Dopamine -- genetics KW - Corpus Striatum -- cytology KW - Corpus Striatum -- physiopathology KW - Neurons -- physiology KW - Parkinson Disease -- physiopathology KW - Parkinson Disease -- genetics KW - Parkinson Disease -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71040713?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurology&rft.atitle=Dopamine-mediated+gene+regulation+in+models+of+Parkinson%27s+disease.&rft.au=Gerfen%2C+C+R&rft.aulast=Gerfen&rft.aufirst=C&rft.date=2000-04-01&rft.volume=47&rft.issue=4+Suppl+1&rft.spage=S42&rft.isbn=&rft.btitle=&rft.title=Annals+of+neurology&rft.issn=03645134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-21 N1 - Date created - 2000-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics of 111In- and 125I-labeled antiTac single-chain Fv recombinant immunotoxin. AN - 71040154; 10768579 AB - The use of immunotoxins for cancer therapy is an attractive strategy that exploits the targeting specificity of monoclonal antibodies and their fragments as well as the exquisite toxicity of the toxins. However, few studies of immunotoxins have evaluated their biodistribution in vivo. Previous studies have used 125I for tracing immunotoxin biodistribution in mice. Because the immunotoxin works only when it is internalized and because of known problems with quick dehalogenation after internalization of antibodies, we decided to use 111In, which has greater intracellular retention than iodine. To trace the in vivo pharmacokinetics of the immunotoxin in mice, we labeled the antiTac(Fv)-PE38 with 111ln and compared it with 125I-labeled antiTac(Fv)-PE38. We successfully labeled antiTac(Fv)-PE38 with 111In at up to 2.96 GBq/mg. A 3- to 4-fold decrease in cytotoxicity was observed for both radiolabeled preparations. We evaluated the internalization of 111In- and 125I-labeled antiTac(Fv)PE38 into ATAC4 cells (Tac-positive) as well as their biodistribution and pharmacokinetics in vivo in mice. In addition, some mice receiving these reagents were co-infused with 30 mg L-lysine to inhibit renal accumulation. Significantly more 111In- than 125I-labeled antiTac(Fv)-PE38 accumulated in the ATAC4 cells (20% versus 5% of initial surface-bound radioactivity; P < 0.001). In vivo, significantly more 111In- than 125I-labeled antiTac(Fv)-PE38 accumulated in the kidney (119 versus 31 percentage injected dose per gram [%ID/g]; P < 0.001). The tumor accumulation of 111In-labeled antiTac(Fv)-PE38 at 96 h was 13-fold greater than that of 125I-labeled antiTac(Fv)-PE38 (1.4 versus 0.1 %ID/g; P < 0.001). No antiTac(Fv)-PE38 was excreted into the urine in its intact form unless lysine was co-infused. Co-injected lysine reduced the renal accumulation of 111In-labeled antiTac(Fv)-PE38 by 62%. We evaluated the biodistribution, pharmacokinetics, and catabolism of 111In-labeled antiTac(Fv)-PE38 and found that it differed from 125I-labeled antiTac(Fv)PE38. These studies suggest that 111In-labeled antiTac(Fv)-PE38 can be used to trace the fate of antiTac(Fv)-PE38 in humans. JF - Journal of nuclear medicine : official publication, Society of Nuclear Medicine AU - Kobayashi, H AU - Kao, C H AU - Kreitman, R J AU - Le, N AU - Kim, M K AU - Brechbiel, M W AU - Paik, C H AU - Pastan, I AU - Carrasquillo, J A AD - Department of Nuclear Medicine, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1180, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 755 EP - 762 VL - 41 IS - 4 SN - 0161-5505, 0161-5505 KW - Antibodies KW - 0 KW - Antibodies, Monoclonal KW - Immunotoxins KW - Indium Radioisotopes KW - Iodine Radioisotopes KW - Receptors, Interleukin-2 KW - Recombinant Proteins KW - antitac(FV)-PE38 recombinant immunotoxin KW - Index Medicus KW - Animals KW - Antibodies, Monoclonal -- pharmacokinetics KW - Recombinant Proteins -- pharmacokinetics KW - Mice, Nude KW - Mice KW - Tissue Distribution KW - Receptors, Interleukin-2 -- immunology KW - Female KW - Chromatography, High Pressure Liquid KW - Immunotoxins -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71040154?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nuclear+medicine+%3A+official+publication%2C+Society+of+Nuclear+Medicine&rft.atitle=Pharmacokinetics+of+111In-+and+125I-labeled+antiTac+single-chain+Fv+recombinant+immunotoxin.&rft.au=Kobayashi%2C+H%3BKao%2C+C+H%3BKreitman%2C+R+J%3BLe%2C+N%3BKim%2C+M+K%3BBrechbiel%2C+M+W%3BPaik%2C+C+H%3BPastan%2C+I%3BCarrasquillo%2C+J+A&rft.aulast=Kobayashi&rft.aufirst=H&rft.date=2000-04-01&rft.volume=41&rft.issue=4&rft.spage=755&rft.isbn=&rft.btitle=&rft.title=Journal+of+nuclear+medicine+%3A+official+publication%2C+Society+of+Nuclear+Medicine&rft.issn=01615505&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-09 N1 - Date created - 2000-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of p53 stability and activity in response to genotoxic stress. AN - 71038865; 10767629 AB - The p53 tumor suppressor is a universal sensor of genotoxic stress that regulates the transcription of genes required for cell-cycle arrest and apoptosis. In response to DNA damage, the p53 protein is phosphorylated at its amino-terminus and becomes stabilized upon disruption of an interaction with its negative regulator, MDM2. Subsequent phosphorylation and acetylation of p53 promote different interactions with other proteins and with target gene regulatory elements to facilitate cell-cycle arrest, apoptosis, or adaptation in response to DNA damage. Downstream of p53, p21 is responsible for growth arrest in G1, but other p53 target genes are responsible for G2 cell-cycle arrest. In response to genotoxic insult, p53-induced apoptosis results from overlapping downstream pathways that both suppress mitogenic and survival signaling and promote pro-apoptotic signaling. Adaptation to DNA damage is manifested by p53-mediated expression of its negative regulator, MDM2. The frequency of observed mutations in p53 predicts that its inactivation is a requisite step in tumorigenesis, as p53 is mutated in approximately 50% of human tumors. Thus, it is likely that in the remaining tumors, genetic aberrations will occur in pathways that regulate p53 or in pathways directly downstream of p53. The advances in the understanding of p53 signaling over the past few years point to many potential overlapping signaling pathways, where mutations may occur as alternative modes to p53 mutation. JF - Mutation research AU - Colman, M S AU - Afshari, C A AU - Barrett, J C AD - Cancer and Aging Group, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, MD C2-15, Research Triangle Park, NC, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 179 EP - 188 VL - 462 IS - 2-3 SN - 0027-5107, 0027-5107 KW - Mutagens KW - 0 KW - Nuclear Proteins KW - Proto-Oncogene Proteins KW - Tumor Suppressor Protein p53 KW - MDM2 protein, human KW - EC 2.3.2.27 KW - Proto-Oncogene Proteins c-mdm2 KW - Index Medicus KW - Phosphorylation KW - DNA Damage KW - Humans KW - Proto-Oncogene Proteins -- metabolism KW - Gene Expression Regulation KW - Tumor Suppressor Protein p53 -- drug effects KW - Tumor Suppressor Protein p53 -- genetics KW - Mutagens -- pharmacology KW - Tumor Suppressor Protein p53 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71038865?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Regulation+of+p53+stability+and+activity+in+response+to+genotoxic+stress.&rft.au=Colman%2C+M+S%3BAfshari%2C+C+A%3BBarrett%2C+J+C&rft.aulast=Colman&rft.aufirst=M&rft.date=2000-04-01&rft.volume=462&rft.issue=2-3&rft.spage=179&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-16 N1 - Date created - 2000-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methadone dose increase and abstinence reinforcement for treatment of continued heroin use during methadone maintenance. AN - 71037099; 10768702 AB - Although methadone maintenance is an effective therapy for heroin dependence, some patients continue to use heroin and may benefit from therapeutic modifications. This study evaluated a behavioral intervention, a pharmacological intervention, and a combination of both interventions. Throughout the study all patients received daily methadone hydrochloride maintenance (initially 50 mg/d orally) and weekly counseling. Following baseline treatment patients who continued to use heroin were randomly assigned to 1 of 4 interventions: (1) contingent vouchers for opiate-negative urine specimens (n = 29 patients); (2) methadone hydrochloride dose increase to 70 mg/d (n = 31 patients); (3) combined contingent vouchers and methadone dose increase (n = 32 patients); and (4) neither intervention (comparison standard; n = 28 patients). Methadone dose increases were double blind. Vouchers had monetary value and were exchangeable for goods and services. Groups not receiving contingent vouchers received matching vouchers independent of urine test results. Primary outcome measure was opiate-negative urine specimens (thrice weekly urinalysis). Contingent vouchers and a methadone dose increase each significantly increased the percentage of opiate-negative urine specimens during intervention. Contingent vouchers, with or without a methadone dose increase, increased the duration of sustained abstinence as assessed by urine screenings. Methadone dose increase, with or without contingent vouchers, reduced self-reported frequency of use and self-reported craving. In patients enrolled in a methadone-maintainence program who continued to use heroin, abstinence reinforcement and a methadone dose increase were each effective in reducing use. When combined, they did not dramatically enhance each other's effects on any 1 outcome measure, but they did seem to have complementary benefits. JF - Archives of general psychiatry AU - Preston, K L AU - Umbricht, A AU - Epstein, D H AD - National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 395 EP - 404 VL - 57 IS - 4 SN - 0003-990X, 0003-990X KW - Narcotics KW - 0 KW - Methadone KW - UC6VBE7V1Z KW - Abridged Index Medicus KW - Index Medicus KW - Drug Administration Schedule KW - Double-Blind Method KW - Combined Modality Therapy KW - Dose-Response Relationship, Drug KW - Humans KW - Cocaine-Related Disorders -- psychology KW - Narcotics -- urine KW - Behavior, Addictive -- psychology KW - Cocaine-Related Disorders -- rehabilitation KW - Behavior, Addictive -- rehabilitation KW - Life Style KW - Substance Abuse Treatment Centers KW - Substance Abuse Detection KW - Adult KW - Treatment Outcome KW - Crime -- statistics & numerical data KW - Male KW - Female KW - Methadone -- therapeutic use KW - Reward KW - Heroin Dependence -- rehabilitation KW - Heroin Dependence -- psychology KW - Behavior Therapy -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71037099?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+general+psychiatry&rft.atitle=Methadone+dose+increase+and+abstinence+reinforcement+for+treatment+of+continued+heroin+use+during+methadone+maintenance.&rft.au=Preston%2C+K+L%3BUmbricht%2C+A%3BEpstein%2C+D+H&rft.aulast=Preston&rft.aufirst=K&rft.date=2000-04-01&rft.volume=57&rft.issue=4&rft.spage=395&rft.isbn=&rft.btitle=&rft.title=Archives+of+general+psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-20 N1 - Date created - 2000-04-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I trial of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) in patients with hematologic malignancies. AN - 71035933; 10764422 AB - To evaluate the toxicity, pharmacokinetics, immunogenicity, and antitumor activity of anti-Tac(Fv)-PE38 (LMB-2), an anti-CD25 recombinant immunotoxin that contains an antibody Fv fragment fused to truncated Pseudomonas exotoxin. Patients with CD25(+) hematologic malignancies for whom standard and salvage therapies failed were treated with LMB-2 at dose levels that ranged from 2 to 63 microg/kg administered intravenously over 30 minutes on alternate days for three doses (QOD x 3). LMB-2 was administered to 35 patients for a total of 59 cycles. Dose-limiting toxicity at the 63 microg/kg level was reversible and included transaminase elevations in one patient and diarrhea and cardiomyopathy in another. LMB-2 was well tolerated in nine patients at the maximum-tolerated dose (40 microg/kg QOD x 3); toxicity was transient and most commonly included transaminase elevations (eight patients) and fever (seven patients). Only six of 35 patients developed significant neutralizing antibodies after the first cycle. The median half-life was 4 hours. One hairy cell leukemia (HCL) patient achieved a complete remission, which is ongoing at 20 months. Seven partial responses were observed in cutaneous T-cell lymphoma (one patient), HCL (three patients), chronic lymphocytic leukemia (one patient), Hodgkin's disease (one patient), and adult T-cell leukemia (one patient). Responding patients had 2 to 5 log reductions of circulating malignant cells, improvement in skin lesions, and regression of lymphomatous masses and splenomegaly. All four patients with HCL responded to treatment. LMB-2 has clinical activity in CD25(+) hematologic malignancies and is relatively nonimmunogenic. It is the first recombinant immunotoxin to induce major responses in cancer. LMB-2 and similar agents that target other cancer antigens merit further clinical development. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Kreitman, R J AU - Wilson, W H AU - White, J D AU - Stetler-Stevenson, M AU - Jaffe, E S AU - Giardina, S AU - Waldmann, T A AU - Pastan, I AD - Laboratory of Clinical Pathology, Metabolism Branch, Medicine Branch, and Biopharmaceutical Development Program, Science Applications International Corporation Frederick, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 1622 EP - 1636 VL - 18 IS - 8 SN - 0732-183X, 0732-183X KW - Antibodies KW - 0 KW - Antibodies, Monoclonal KW - B3(Fv)-PE38KDEL recombinant immunotoxin KW - Exotoxins KW - Immunotoxins KW - Receptors, Interleukin-2 KW - Index Medicus KW - Receptors, Interleukin-2 -- analysis KW - Humans KW - Adult KW - Enzyme-Linked Immunosorbent Assay KW - Aged KW - Middle Aged KW - Antibodies -- analysis KW - Male KW - Female KW - Immunotoxins -- pharmacokinetics KW - Leukemia -- drug therapy KW - Leukemia -- immunology KW - Immunotoxins -- immunology KW - Immunotoxins -- adverse effects KW - Lymphoma -- drug therapy KW - Immunotoxins -- therapeutic use KW - Lymphoma -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71035933?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+I+trial+of+recombinant+immunotoxin+anti-Tac%28Fv%29-PE38+%28LMB-2%29+in+patients+with+hematologic+malignancies.&rft.au=Kreitman%2C+R+J%3BWilson%2C+W+H%3BWhite%2C+J+D%3BStetler-Stevenson%2C+M%3BJaffe%2C+E+S%3BGiardina%2C+S%3BWaldmann%2C+T+A%3BPastan%2C+I&rft.aulast=Kreitman&rft.aufirst=R&rft.date=2000-04-01&rft.volume=18&rft.issue=8&rft.spage=1622&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 - 2000-05-18 N1 - Date created - 2000-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Developmental arrest of the human malaria parasite Plasmodium falciparum within the mosquito midgut via CTRP gene disruption. AN - 71027967; 10760158 AB - Apicomplexan protozoa possess a family of micronemal and cell surface-associated proteins, each comprised a combination of cell-adhesive vertebrate von Willebrand factor (vWF)-like A domains and thrombospondin (TSP) type 1-like domains. The human malaria parasite Plasmodium falciparum has in the extracellular portion of the CS protein TRAP-related protein (CTRP) six tandemly arrayed A domains followed by seven TSP type 1-like domains, whereas a second member of this family, thrombospondin-related anonymous protein (TRAP), contains a single vWF-like A domain and a single TSP type 1-like domain. Here we show that CTRP transcripts are present within the infected mosquito midgut and that CTRP protein is expressed with a punctate distribution and a predominance at the apical end of mosquito midgut-stage ookinetes. This expression pattern is analogous to micronemal expression of TRAP in Plasmodium sporozoites. Disruption of the CTRP gene by homologous recombination in cultures of the human malaria parasite P. falciparum demonstrates that CTRP is essential for mosquito midgut development. Oocyst formation was never observed following membrane feeds of CTRP disruptant lines to Anopheline mosquitoes, despite the development of mature ookinetes. We propose that CTRP is involved in essential recognition or motility processes at the ookinete cell surface within the mosquito midgut. JF - Molecular microbiology AU - Templeton, T J AU - Kaslow, D C AU - Fidock, D A AD - The Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0425, USA. ttempleton@niaid.nih.gov Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 1 EP - 9 VL - 36 IS - 1 SN - 0950-382X, 0950-382X KW - PbCTRP protein, Plasmodium KW - 0 KW - Protozoan Proteins KW - Receptors, Cell Surface KW - Index Medicus KW - Phenotype KW - Animals KW - Digestive System -- parasitology KW - Fluorescent Antibody Technique KW - Mutagenesis KW - Receptors, Cell Surface -- isolation & purification KW - Plasmodium falciparum -- growth & development KW - Plasmodium falciparum -- genetics KW - Genes, Protozoan KW - Receptors, Cell Surface -- genetics KW - Anopheles -- parasitology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71027967?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+microbiology&rft.atitle=Developmental+arrest+of+the+human+malaria+parasite+Plasmodium+falciparum+within+the+mosquito+midgut+via+CTRP+gene+disruption.&rft.au=Templeton%2C+T+J%3BKaslow%2C+D+C%3BFidock%2C+D+A&rft.aulast=Templeton&rft.aufirst=T&rft.date=2000-04-01&rft.volume=36&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Molecular+microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-23 N1 - Date created - 2000-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Base- and acid-catalyzed interconversions of O-acyl- and N-acyl-ethanolamines: a cautionary note for lipid analyses. AN - 71023092; 10744787 AB - The isolation and quantification of ethanolamine containing lipids from animal tissues may expose neutral lipid extracts to acidic or basic conditions during chromatographic separations or derivatization chemistry. While investigating the acid- and base-catalyzed production of anandamide in chromatographic fractions of rat brain extracts not containing anandamide, we observed that O,N-acyl migrations are facile. O,N-acyl migrations are well documented in synthetic organic chemistry literature, but are not well described or recognized with regard to methods in lipid isolation or lipid enzyme studies. We report here the synthesis and characterization of O- and N-acyl (palmitoyl- or arachidonoyl-)ethanolamines. Their rearrangements in base and acid are quantified by liquid chromatography;-electrospray ionization mass spectrometry. The rearrangements proceed through a cyclic intermediate that is also formed during chemical reactions commonly used for derivatization of acylethanolamines for gas chromatography-mass spectrometry. The isolation and characterization of N- or O-acylethanolamines and their enzymatic formation requires awareness and consideration of the proclivity of these compounds to chemically rearrange. JF - Journal of lipid research AU - Markey, S P AU - Dudding, T AU - Wang, T C AD - Laboratory of Neurotoxicology, National Institute of Mental Health, Bethesda, MD 20892-1262, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 657 EP - 662 VL - 41 IS - 4 SN - 0022-2275, 0022-2275 KW - Acids KW - 0 KW - Alkalies KW - Amides KW - Arachidonic Acids KW - Endocannabinoids KW - Esters KW - Ethanolamines KW - Palmitic Acids KW - Polyunsaturated Alkamides KW - anandamide KW - UR5G69TJKH KW - Index Medicus KW - Rats KW - Esters -- chemistry KW - Animals KW - Amides -- chemistry KW - Catalysis KW - Palmitic Acids -- chemistry KW - Ethanolamines -- chemistry KW - Arachidonic Acids -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71023092?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+lipid+research&rft.atitle=Base-+and+acid-catalyzed+interconversions+of+O-acyl-+and+N-acyl-ethanolamines%3A+a+cautionary+note+for+lipid+analyses.&rft.au=Markey%2C+S+P%3BDudding%2C+T%3BWang%2C+T+C&rft.aulast=Markey&rft.aufirst=S&rft.date=2000-04-01&rft.volume=41&rft.issue=4&rft.spage=657&rft.isbn=&rft.btitle=&rft.title=Journal+of+lipid+research&rft.issn=00222275&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-08 N1 - Date created - 2000-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - XPD polymorphisms: effects on DNA repair proficiency. AN - 71022546; 10753184 AB - XPD codes for a DNA helicase involved in transcription and nucleotide excision repair. Rare XPD mutations diminish nucleotide excision repair resulting in hypersensitivity to UV light and increased risk of skin cancer. Several polymorphisms in this gene have been identified but their impact on DNA repair is not known. We compared XPD genotypes at codons 312 and 751 with DNA repair proficiency in 31 women. XPD genotypes were measured by PCR-RFLP. DNA repair proficiency was assessed using a cytogenetic assay that detects X-ray induced chromatid aberrations (breaks and gaps). Chromatid aberrations were scored per 100 metaphase cells following incubation at 37 degrees C (1.5 h after irradiation) to allow for repair of DNA damage. Individuals with the Lys/Lys codon 751 XPD genotype had a higher number of chromatid aberrations (132/100 metaphase cells) than those having a 751Gln allele (34/100 metaphase cells). Individuals having greater than 60 chromatid breaks plus gaps were categorized as having sub-optimal repair. Possessing a Lys/Lys751 genotype increased the risk of sub-optimal DNA repair (odds ratio = 7.2, 95% confidence interval = 1.01-87.7). The Asp312Asn XPD polymorphism did not appear to affect DNA repair proficiency. These results suggest that the Lys751 (common) allele may alter the XPD protein product resulting in sub-optimal repair of X-ray-induced DNA damage. JF - Carcinogenesis AU - Lunn, R M AU - Helzlsouer, K J AU - Parshad, R AU - Umbach, D M AU - Harris, E L AU - Sanford, K K AU - Bell, D A AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, National Institutes of Health, MD C3-03, PO Box 12233, Research Triangle Park, NC 27709, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 551 EP - 555 VL - 21 IS - 4 SN - 0143-3334, 0143-3334 KW - DNA-Binding Proteins KW - 0 KW - Proteins KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - DNA Helicases KW - EC 3.6.4.- KW - Xeroderma Pigmentosum Group D Protein KW - EC 3.6.4.12 KW - ERCC2 protein, human KW - EC 5.99.- KW - Index Medicus KW - Genotype KW - Breast Neoplasms -- genetics KW - Humans KW - Chromosome Aberrations KW - Radiation Tolerance KW - DNA -- radiation effects KW - Female KW - DNA Repair KW - Polymorphism, Genetic KW - DNA Helicases -- genetics KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71022546?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=XPD+polymorphisms%3A+effects+on+DNA+repair+proficiency.&rft.au=Lunn%2C+R+M%3BHelzlsouer%2C+K+J%3BParshad%2C+R%3BUmbach%2C+D+M%3BHarris%2C+E+L%3BSanford%2C+K+K%3BBell%2C+D+A&rft.aulast=Lunn&rft.aufirst=R&rft.date=2000-04-01&rft.volume=21&rft.issue=4&rft.spage=551&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-22 N1 - Date created - 2000-05-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Axonal stratification patterns and glutamate-gated conductance mechanisms in zebrafish retinal bipolar cells. AN - 71018940; 10747188 AB - 1. Whole-cell patch recording and puff pipette techniques were used to identify glutamate receptor mechanisms on bipolar cell (BC) dendrites in the zebrafish retinal slice. Recorded neurons were stained with Lucifer Yellow, to correlate glutamate responses with BC morphology. 2. BC axon terminals (ATs) consisted of swellings or varicosities along the axon, as well as at its end. AT stratification patterns identified three regions in the inner plexiform layer (IPL): a thick sublamina a, with three bands of ATs, a narrow terminal-free zone in the mid-IPL, and a thin sublamina b, with two bands of ATs. BCs occurred with ATs restricted to sublamina a(Group a), sublamina b(Group b) or with ATs in both sublaminae (Group a/b). 3. OFF-BCs belonged to Group a or Group a/b. These cells responded to glutamate or kainate with a CNQX-sensitive conductance increase. Reversal potential (Erev) ranged from -0.6 to +18 mV. Bipolar cells stimulated sequentially with both kainate and glutamate revealed a population of glutamate-insensitive, kainate-sensitive cells in addition to cells sensitive to both agonists. 4. ON-BCs responded to glutamate via one of three mechanisms: (a) a conductance decrease with Erev approximately 0 mV, mimicked by L-(+)-2-amino-4-phosphonobutyric acid (APB) or trans-1-amino-1, 3-cyclopentanedicarboxylic acid (trans-ACPD), (b) a glutamate-gated chloride conductance increase (IGlu-like) characterized by Erev >= ECl (where ECl is the chloride equilibrium potential) and partial blockade by extracellular Li+/Na+ substitution or (c) the activation of both APB and chloride mechanisms simultaneously to produce a response with outward currents at all holding potentials. APB-like responses were found only among BCs in Group b, with a single AT ramifying deep within sublamina b; whereas, cells expressing IGlu-like currents had one or more ATs, and occurred within Groups b or a/b. 5. Multistratified cells (Group a/b) were common and occurred with either ON- or OFF-BC physiology. OFF-BCs typically had one or more ATs in sublamina a and only one AT in sublamina b. In contrast, multistratified ON-BCs had one or more ATs in sublamina b and a single AT ramifying deep in sublamina a. Multistratified ON-BCs expressed the IGlu-like mechanism only. 6. Visual processing in the zebrafish retina involves at least 13 BC types. Some of these BCs have ATs in both the ON- and OFF-sublaminae, suggesting a significant role for ON- and OFF-inputs throughout the IPL. JF - The Journal of physiology AU - Connaughton, V P AU - Nelson, R AD - Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 36 Convent Drive, Bethesda, MD 20892-4066, USA. vconn@american.edu Y1 - 2000/04/01/ PY - 2000 DA - 2000 Apr 01 SP - 135 EP - 146 VL - 524 Pt 1 SN - 0022-3751, 0022-3751 KW - Aminobutyrates KW - 0 KW - Chlorides KW - Excitatory Amino Acid Antagonists KW - Fluorescent Dyes KW - Isoquinolines KW - Cycloleucine KW - 0TQU7668EI KW - 1-amino-1,3-dicarboxycyclopentane KW - 111900-32-4 KW - Picrotoxin KW - 124-87-8 KW - Glutamic Acid KW - 3KX376GY7L KW - 2-amino-4-phosphonobutyric acid KW - 6323-99-5 KW - 6-Cyano-7-nitroquinoxaline-2,3-dione KW - 6OTE87SCCW KW - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid KW - 77521-29-0 KW - lucifer yellow KW - 9654F8OVKE KW - Strychnine KW - H9Y79VD43J KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Animals KW - Kainic Acid -- pharmacology KW - Cycloleucine -- pharmacology KW - 6-Cyano-7-nitroquinoxaline-2,3-dione -- pharmacology KW - Cycloleucine -- analogs & derivatives KW - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid -- pharmacology KW - Chlorides -- metabolism KW - Zebrafish KW - Axons -- physiology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Aminobutyrates -- pharmacology KW - Picrotoxin -- pharmacology KW - In Vitro Techniques KW - Strychnine -- pharmacology KW - Retina -- cytology KW - Retina -- physiology KW - Neurons -- drug effects KW - Neurons -- cytology KW - Neurons -- physiology KW - Dendrites -- physiology KW - Glutamic Acid -- physiology KW - Glutamic Acid -- pharmacology KW - Dendrites -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71018940?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+physiology&rft.atitle=Axonal+stratification+patterns+and+glutamate-gated+conductance+mechanisms+in+zebrafish+retinal+bipolar+cells.&rft.au=Connaughton%2C+V+P%3BNelson%2C+R&rft.aulast=Connaughton&rft.aufirst=V&rft.date=2000-04-01&rft.volume=524+Pt+1&rft.issue=&rft.spage=135&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+physiology&rft.issn=00223751&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-02 N1 - Date created - 2000-06-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1968 Oct 4;162(3849):132-4 [4175300] Vision Res. 1996 Mar;36(6):787-95 [8736215] Vision Res. 1975 Mar;15(3):456-8 [166508] Science. 1977 Dec 23;198(4323):1267-9 [73223] Science. 1977 Dec 23;198(4323):1269-71 [201028] J Physiol. 1978 Jul;280:449-70 [211229] J Gen Physiol. 1979 Jan;73(1):73-90 [438766] J Comp Neurol. 1980 Jun;191(3):315-35 [7410596] Science. 1981 Jan 9;211(4478):182-5 [6255566] Nature. 1981 Sep 17-23;293(5829):220-2 [7278979] J Comp Neurol. 1982 Feb 20;205(2):161-70 [7076890] Philos Trans R Soc Lond B Biol Sci. 1982 Sep 13;298(1092):355-93 [6127731] Am J Anat. 1967 Sep;121(2):401-23 [4862097] Vision Res. 1983;23(10):1183-95 [6649437] J Comp Neurol. 1985 Jun 8;236(2):141-60 [4056093] Nature. 1987 Jan 1-7;325(6099):56-8 [3025746] Nature. 1990 Jul 19;346(6281):269-71 [1695713] Vision Res. 1990;30(7):967-72 [1975465] Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):805-9 [1671534] J Neurosci. 1991 Aug;11(8):2372-82 [1714492] Brain Res. 1992 Apr 3;576(2):181-96 [1515915] Science. 1992 Oct 23;258(5082):597-603 [1329206] J Comp Neurol. 1993 Mar 8;329(2):188-200 [8454729] J Biol Chem. 1993 Jun 5;268(16):11868-73 [8389366] J Gen Physiol. 1994 Jun;103(6):1019-34 [7931135] J Neurophysiol. 1994 Jun;71(6):2258-68 [7931515] Cell. 1995 Mar 10;80(5):757-65 [7889569] J Neurosci. 1995 May;15(5 Pt 1):3571-82 [7538564] J Neurosci. 1995 May;15(5 Pt 2):3852-62 [7538566] J Neurophysiol. 1996 Jul;76(1):401-22 [8836233] J Neurophysiol. 1996 Dec;76(6):3842-9 [8985882] Vision Res. 1996 Dec;36(24):4015-23 [9068854] Eur J Neurosci. 1998 Apr;10(4):1350-62 [9749789] Nature. 1999 Jan 14;397(6715):157-60 [9923677] J Neurosci. 1999 Apr 15;19(8):2938-44 [10191311] Vis Neurosci. 1999 May-Jun;16(3):483-90 [10349969] Philos Trans R Soc Lond B Biol Sci. 1975 Feb 20;270(902):61-118 [234623] Neuropharmacology. 1995 Jan;34(1):1-26 [7623957] Vis Neurosci. 1995 Jul-Aug;12(4):755-65 [8527374] J Neurosci. 1996 May 1;16(9):2934-44 [8622124] Comment In: J Physiol. 2000 Apr 1;524 Pt 1:1 [10747178] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Peroxisome proliferator-activated receptor alpha is restricted to hepatic parenchymal cells, not Kupffer cells: implications for the mechanism of action of peroxisome proliferators in hepatocarcinogenesis. AN - 71018267; 10753222 AB - Peroxisome proliferators increase hepatocyte proliferation and cause liver tumors in rodents, yet the mechanism of action is not understood. Based on studies with null mice it is known that peroxisome proliferator-activated receptor-alpha (PPARalpha) is involved. There is also evidence that Kupffer cells play a central role in peroxisome proliferator-induced carcinogenesis, most likely via mechanisms involving increases in superoxide, activation of nuclear factor kappaB and production of tumor necrosis factor-alpha (TNFalpha). However, it is not known whether PPARalpha is constitutively expressed in Kupffer cells. Therefore, the expression of PPAR isoforms in rat Kupffer and parenchymal cells was examined. Kupffer cells and hepatocytes of >99% purity were isolated from rats fed either a control diet or one containing 0.1% WY-14,643 for 1 week. Protein and RNA were obtained and PPAR expression was analyzed using northern and western blots. PPARalpha, PPARbeta and PPARgamma mRNA was detected in purified hepatocytes. In Kupffer cells, mRNA encoding PPARgamma was present while transcripts for PPARalpha and PPARbeta were not detected. Immunoblots were consistent with the results found by northern analysis. Moreover, when Kupffer cells from wild-type or PPARalpha-null mice were treated with WY-14,643 in vitro, superoxide production was similar. Combined, these results show that PPARalpha is expressed in rat parenchymal cells but not in Kupffer cells. These data are consistent with the hypothesis that parenchymal cells respond to Kupffer cell-derived TNFalpha via mechanisms dependent on PPARalpha within the parenchymal cells. JF - Carcinogenesis AU - Peters, J M AU - Rusyn, I AU - Rose, M L AU - Gonzalez, F J AU - Thurman, R G AD - Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. jmp21@psu.edu Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 823 EP - 826 VL - 21 IS - 4 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Peroxisome Proliferators KW - RNA, Messenger KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - Tumor Necrosis Factor-alpha KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - RNA, Messenger -- analysis KW - Tumor Necrosis Factor-alpha -- physiology KW - Female KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Transcription Factors -- physiology KW - Liver Neoplasms, Experimental -- etiology KW - Peroxisome Proliferators -- toxicity KW - Carcinogens -- toxicity KW - Transcription Factors -- analysis KW - Receptors, Cytoplasmic and Nuclear -- genetics KW - Receptors, Cytoplasmic and Nuclear -- analysis KW - Transcription Factors -- genetics KW - Liver -- chemistry KW - Kupffer Cells -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71018267?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Peroxisome+proliferator-activated+receptor+alpha+is+restricted+to+hepatic+parenchymal+cells%2C+not+Kupffer+cells%3A+implications+for+the+mechanism+of+action+of+peroxisome+proliferators+in+hepatocarcinogenesis.&rft.au=Peters%2C+J+M%3BRusyn%2C+I%3BRose%2C+M+L%3BGonzalez%2C+F+J%3BThurman%2C+R+G&rft.aulast=Peters&rft.aufirst=J&rft.date=2000-04-01&rft.volume=21&rft.issue=4&rft.spage=823&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-22 N1 - Date created - 2000-05-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pubertal growth and development and prenatal and lactational exposure to polychlorinated biphenyls and dichlorodiphenyl dichloroethene. AN - 71016121; 10753247 AB - Polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) are ubiquitous toxic environmental contaminants. Prenatal and early life exposures affect pubertal events in experimental animals. We studied whether prenatal or lactational exposures to background levels of PCBs or DDE were associated with altered pubertal growth and development in humans. Follow-up of 594 children from an existing North Carolina cohort whose prenatal and lactational exposures had previously been measured. Height, weight, and stage of pubertal development were assessed through annual mail questionnaires. Height of boys at puberty increased with transplacental exposure to DDE, as did weight adjusted for height; adjusted means for those with the highest exposures (maternal concentration 4+ ppm fat) were 6.3 cm taller and 6.9 kg larger than those with the lowest (0 to 1 ppm). There was no effect on the ages at which pubertal stages were attained. Lactational exposures to DDE had no apparent effects; neither did transplacental or lactational exposure to PCBs. Girls with the highest transplacental PCB exposures were heavier for their heights than other girls by 5.4 kg, but differences were significant only if the analysis was restricted to white girls. Prenatal exposures at background levels may affect body size at puberty. JF - The Journal of pediatrics AU - Gladen, B C AU - Ragan, N B AU - Rogan, W J AD - Biostatistics Branch and the Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 490 EP - 496 VL - 136 IS - 4 SN - 0022-3476, 0022-3476 KW - Environmental Pollutants KW - 0 KW - Insecticides KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Dichlorodiphenyldichloroethane KW - V14159DF29 KW - Abridged Index Medicus KW - Index Medicus KW - Infant KW - Prospective Studies KW - Sex Characteristics KW - Humans KW - North Carolina KW - Infant, Newborn KW - Child KW - Longitudinal Studies KW - Adolescent KW - Male KW - Female KW - Pregnancy KW - Child, Preschool KW - Dichlorodiphenyldichloroethane -- adverse effects KW - Insecticides -- adverse effects KW - Puberty -- drug effects KW - Child Development -- drug effects KW - Growth -- drug effects KW - Environmental Pollutants -- adverse effects KW - Prenatal Exposure Delayed Effects KW - Polychlorinated Biphenyls -- adverse effects KW - Milk, Human -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71016121?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pediatrics&rft.atitle=Pubertal+growth+and+development+and+prenatal+and+lactational+exposure+to+polychlorinated+biphenyls+and+dichlorodiphenyl+dichloroethene.&rft.au=Gladen%2C+B+C%3BRagan%2C+N+B%3BRogan%2C+W+J&rft.aulast=Gladen&rft.aufirst=B&rft.date=2000-04-01&rft.volume=136&rft.issue=4&rft.spage=490&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pediatrics&rft.issn=00223476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-03 N1 - Date created - 2000-05-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A relationship between serotonin transporter genotype and in vivo protein expression and alcohol neurotoxicity. AN - 71013406; 10745057 AB - Genetic variation of the promoter for the serotonin transporter (5-HTT) gene has been associated with its functional capacity. In vitro, carriers of a short allele (s-carriers) of the 5-HTT promoter display significant reduction in 5-HTT capacity. Dysfunction of 5-HTT has been observed in alcoholic individuals. We assessed whether the allelic constitution of the 5-HTT gene is associated with reduced serotonin transporter availability among alcoholic individuals. We genotyped the 5-HTT promoter region and measured the availability of serotonin transporter protein with [I-123]beta-CIT SPECT in the raphe area in 14 abstinent male alcoholic subjects and 8 age-matched control subjects of European American descent. Among control subjects, the ratio of in vivo 5-HTT availability for ll-homozygous individuals relative to s-carriers was comparable to serotonin uptake ratios measured in vitro. There was a significant interaction of diagnosis and 5-HTT promoter genotype on 5-HTT availability (p <.01). Among controls, ll-homozygous individuals displayed a significant increase as compared with s-carriers. The availability of raphe 5-HTT was significantly reduced in ll-homozygous alcoholic individuals and was negatively correlated with their amount of alcohol consumption. Among s-carriers, 5-HTT availability did not differ significantly between control and alcoholic subjects. Our preliminary findings suggest an association between 5-HTT allelic constitution and in vivo measurements of human serotonin transporter availability, and a potentially selective susceptibility of ll-homozygous individuals to the neurotoxic effects of chronic excessive alcohol consumption. JF - Biological psychiatry AU - Heinz, A AU - Jones, D W AU - Mazzanti, C AU - Goldman, D AU - Ragan, P AU - Hommer, D AU - Linnoila, M AU - Weinberger, D R AD - Clinical Brain Disorders Branch, Intramural Research Program, NIMH, Bethesda, Maryland 20892-1379, USA. Y1 - 2000/04/01/ PY - 2000 DA - 2000 Apr 01 SP - 643 EP - 649 VL - 47 IS - 7 SN - 0006-3223, 0006-3223 KW - Carrier Proteins KW - 0 KW - Iodine Radioisotopes KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - SLC6A4 protein, human KW - Serotonin Plasma Membrane Transport Proteins KW - Serotonin KW - 333DO1RDJY KW - Ethanol KW - 3K9958V90M KW - 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane KW - 4H1Z7121WS KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Tomography, Emission-Computed, Single-Photon KW - Humans KW - Gene Expression KW - Genotype KW - Polymerase Chain Reaction KW - Alleles KW - Cocaine -- analogs & derivatives KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Temperance KW - Male KW - Carrier Proteins -- metabolism KW - Alcoholism -- diagnostic imaging KW - Carrier Proteins -- genetics KW - Alcoholism -- metabolism KW - Alcoholism -- genetics KW - Nerve Tissue Proteins -- genetics KW - Alcohol-Induced Disorders, Nervous System -- metabolism KW - Nerve Tissue Proteins -- metabolism KW - Ethanol -- toxicity KW - Serotonin -- metabolism KW - Alcohol-Induced Disorders, Nervous System -- genetics KW - Serotonin -- genetics KW - Membrane Glycoproteins -- genetics KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71013406?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=A+relationship+between+serotonin+transporter+genotype+and+in+vivo+protein+expression+and+alcohol+neurotoxicity.&rft.au=Heinz%2C+A%3BJones%2C+D+W%3BMazzanti%2C+C%3BGoldman%2C+D%3BRagan%2C+P%3BHommer%2C+D%3BLinnoila%2C+M%3BWeinberger%2C+D+R&rft.aulast=Heinz&rft.aufirst=A&rft.date=2000-04-01&rft.volume=47&rft.issue=7&rft.spage=643&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-09 N1 - Date created - 2000-05-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Biol Psychiatry. 2000 Aug 15;48(4):334-5 [11023299] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An open-label study of a functional opioid kappa antagonist in the treatment of opioid dependence. AN - 71010480; 10742642 AB - Several lines of evidence, including the well-established observation that kappa opiate agonists produce dysphoria and psychotomimetic effects in humans, suggest that dysfunction of the endogenous kappa opioid system may contribute to opioid and cocaine addiction. The objective of this open-label study was to determine the effectiveness of a functional kappa antagonist as a treatment for opioid dependence. This was accomplished by combining a partial mu agonist/kappa antagonist (buprenorphine, 4 mg, sublingual) with a mu antagonist (naltrexone, 50 mg by mouth), theoretically leaving kappa antagonism as the major medication effect. Subjects were treatment-seeking heroin-dependent (as per Diagnostic and Statistical Manual of Mental Disorders, 4th ed.) men (41 +/- 7 years old; 19 +/- 8 years heroin use) eligible for methadone maintenance. After inpatient detoxification and a naloxone-challenge test to verify that they were not physically dependent on opioids, subjects received naltrexone. Starting on the fourth day, patients also received liquid buprenorphine. All patients received medication at the clinic 6 days per week and a full program of psychosocial treatment. The major endpoints of the study were: pupil diameter to determine if the mu agonist effects of buprenorphine were blocked by naltrexone, urine toxicology, and retention in treatment. Five patients (33%) completed the 3-month study. Four were abstinent from opioids and cocaine for the entire study, and one was abstinent from opioids and cocaine for the last 9 weeks. Six subjects dropped out due to either minor side effects or disliking the sensation of sublingual buprenorphine. There were no significant changes in pupillary diameter. The positive response to treatment exceeds that expected from naltrexone alone (90% dropout). These promising results suggest that controlled studies of this medication combination should be conducted. JF - Journal of substance abuse treatment AU - Rothman, R B AU - Gorelick, D A AU - Heishman, S J AU - Eichmiller, P R AU - Hill, B H AU - Norbeck, J AU - Liberto, J G AD - National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. rrothman@intra.nida.nih.gov Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 277 EP - 281 VL - 18 IS - 3 SN - 0740-5472, 0740-5472 KW - Narcotic Antagonists KW - 0 KW - Receptors, Opioid, kappa KW - Buprenorphine KW - 40D3SCR4GZ KW - Naltrexone KW - 5S6W795CQM KW - Index Medicus KW - Drug Therapy, Combination KW - Psychiatric Status Rating Scales KW - Pupil -- drug effects KW - Substance Abuse Detection KW - Humans KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Affect KW - Administration, Sublingual KW - Recurrence KW - Male KW - Buprenorphine -- therapeutic use KW - Narcotic Antagonists -- therapeutic use KW - Heroin Dependence -- physiopathology KW - Heroin Dependence -- drug therapy KW - Buprenorphine -- pharmacology KW - Receptors, Opioid, kappa -- antagonists & inhibitors KW - Naltrexone -- pharmacology KW - Patient Dropouts -- psychology KW - Heroin Dependence -- psychology KW - Narcotic Antagonists -- pharmacology KW - Naltrexone -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71010480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+substance+abuse+treatment&rft.atitle=An+open-label+study+of+a+functional+opioid+kappa+antagonist+in+the+treatment+of+opioid+dependence.&rft.au=Rothman%2C+R+B%3BGorelick%2C+D+A%3BHeishman%2C+S+J%3BEichmiller%2C+P+R%3BHill%2C+B+H%3BNorbeck%2C+J%3BLiberto%2C+J+G&rft.aulast=Rothman&rft.aufirst=R&rft.date=2000-04-01&rft.volume=18&rft.issue=3&rft.spage=277&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse+treatment&rft.issn=07405472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-12 N1 - Date created - 2000-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine transporter proline mutations influence dopamine uptake, cocaine analog recognition, and expression. AN - 71008089; 10744628 AB - Analyses of mutation effects can aid in understanding how large proteins act. The dopamine transporter (DAT) mediates complex actions in recognizing cocaine and in recognizing and translocating dopamine, sodium, and chloride. DAT proline residues, especially those in transmembrane (TM) domains, are good candidates for involvement in these DAT actions. We now report production of mutants substituting alanine and/or glycine residues for 16 prolines located in or near putative DAT TM domains. We examine effects of these modifications on DAT expression, dopamine uptake, and cocaine analog binding. Mutants in prolines located in five DAT TM domains and four connecting loops alter apparent DAT membrane targeting. Five mutations decrease dopamine affinities more than threefold without significantly decreasing cocaine analog affinities. One decreases cocaine analog affinity without decreasing dopamine affinity. Two mutations decrease affinities for both dopamine and cocaine analog. P101 is especially implicated in dopamine uptake. Alanine substitution for this proline yields dopamine V(max) values of less than 3% of wild-type values despite dopamine affinities more than fourfold higher than wild-type and normal Na(+) and Cl(-) dependence. These DAT proline mutants identify DAT regions likely for dopamine translocation and for recognition of dopamine and cocaine. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Lin, Z AU - Itokawa, M AU - Uhl, G R AD - Molecular Neurobiology Branch, NIDA-IRP, National Institutes of Health, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 715 EP - 728 VL - 14 IS - 5 SN - 0892-6638, 0892-6638 KW - Carrier Proteins KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins 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 - Proline KW - 9DLQ4CIU6V KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - COS Cells KW - Models, Molecular KW - Gene Expression KW - Amino Acid Sequence KW - Proline -- genetics KW - Mutagenesis, Site-Directed KW - Biological Transport, Active -- drug effects KW - Cocaine -- analogs & derivatives KW - Transfection KW - Kinetics KW - Molecular Sequence Data KW - Cell Membrane -- metabolism KW - Cocaine -- metabolism KW - Protein Conformation KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry KW - Carrier Proteins -- genetics KW - Dopamine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71008089?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dopamine+transporter+proline+mutations+influence+dopamine+uptake%2C+cocaine+analog+recognition%2C+and+expression.&rft.au=Lin%2C+Z%3BItokawa%2C+M%3BUhl%2C+G+R&rft.aulast=Lin&rft.aufirst=Z&rft.date=2000-04-01&rft.volume=14&rft.issue=5&rft.spage=715&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=08926638&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-01 N1 - Date created - 2000-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of hormone replacement therapy and adenocarcinomas and squamous cell carcinomas of the uterine cervix. AN - 71007334; 10739704 AB - Exogenous hormones may influence the development of cervical adenocarcinomas. Incidence rates of adenocarcinomas and use of noncontraceptive hormones have increased since the 1970s, but few studies have investigated this potential relationship. We conducted a multicenter case-control study of 124 women with adenocarcinomas, 139 women with squamous cell carcinomas matched on age, diagnosis date, clinic, and stage of disease (in situ or invasive) to adenocarcinoma cases, and 307 healthy community controls who were also matched on age, ethnicity, and residence to adenocarcinoma cases. Participants completed in-person interviews regarding exogenous hormone use before diagnosis and other risk factors and volunteered cervical samples for human papillomavirus (HPV) testing via a PCR-based method. Odds ratios (ORs) with 95% confidence intervals (CIs) estimated relative risks. Only 13 adenocarcinoma cases (10.5%), 7 squamous carcinoma cases (5%), and 20 controls (6.5%) had used noncontraceptive hormones for menopausal symptoms, irregular periods, or disease prevention; most use was short-term, former use. Ever-use was associated with adenocarcinomas (OR = 2.1, 95% CI 0.95-4.6) but not squamous carcinomas (OR = 0.85, 95% CI 0.34-2.1). No trends were seen with duration of use or ages at first use, but unopposed estrogens were positively associated with adenocarcinomas (OR = 2.7). Unopposed estrogens remained associated with adenocarcinomas (OR = 2.0) when analyses were restricted to the HPV-positive controls. Menopausal status was not associated with adenocarcinomas or squamous carcinomas and did not modify the other associations. Although small numbers warrant tentative conclusions, exogenous estrogens, especially unopposed estrogens, were positively associated with adenocarcinomas. Noncontraceptive hormones were negatively but weakly associated with squamous carcinomas. Copyright 2000 Academic Press. JF - Gynecologic oncology AU - Lacey, J V AU - Brinton, L A AU - Barnes, W A AU - Gravitt, P E AU - Greenberg, M D AU - Hadjimichael, O C AU - McGowan, L AU - Mortel, R AU - Schwartz, P E AU - Kurman, R J AU - Hildesheim, A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 149 EP - 154 VL - 77 IS - 1 SN - 0090-8258, 0090-8258 KW - Estrogens KW - 0 KW - Index Medicus KW - Estrogens -- therapeutic use KW - Humans KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Estrogens -- adverse effects KW - Menopause KW - Female KW - Risk Assessment KW - Uterine Cervical Neoplasms -- etiology KW - Carcinoma, Squamous Cell -- etiology KW - Hormone Replacement Therapy -- adverse effects KW - Adenocarcinoma -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71007334?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gynecologic+oncology&rft.atitle=Use+of+hormone+replacement+therapy+and+adenocarcinomas+and+squamous+cell+carcinomas+of+the+uterine+cervix.&rft.au=Lacey%2C+J+V%3BBrinton%2C+L+A%3BBarnes%2C+W+A%3BGravitt%2C+P+E%3BGreenberg%2C+M+D%3BHadjimichael%2C+O+C%3BMcGowan%2C+L%3BMortel%2C+R%3BSchwartz%2C+P+E%3BKurman%2C+R+J%3BHildesheim%2C+A&rft.aulast=Lacey&rft.aufirst=J&rft.date=2000-04-01&rft.volume=77&rft.issue=1&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=Gynecologic+oncology&rft.issn=00908258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-25 N1 - Date created - 2000-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Establishment and characterization of a breast cell strain containing a BRCA1 185delAG mutation. AN - 71007290; 10739701 AB - The aim of this study was to examine whether cells containing the heterozygous form of a BRCA1 185delAG mutation would exhibit abnormal growth or an altered response to DNA damage. A primary culture of human mammary epithelial cells (90P) was obtained from the nontumor breast tissue of a 35-year-old patient who had undergone a mastectomy for removal of a breast tumor. These cells were immortalized (90PE6E7) following retroviral infection with HPV-16 viral E6/E7. genes. Both the 90P cell strain and the cell line were characterized for their ability to grow in culture, form colonies in soft agar, and produce tumors in athymic nude mice compared to normal breast epithelial cells containing wild-type BRCA1. 90P cells were also analyzed for cellular response to gamma radiation and H(2)O(2). These cells were confirmed to contain a frameshift mutation, 185delAG, of the BRCA1 gene. Despite being heterozygous for wild-type BRCA1, the 220-kDa full-size BRCA1 protein was abundantly expressed. 90P and 90PE6E7 cells grew at a similar rate and were anchorage dependent. 90PE6E7 also failed to form tumors in athymic nude mice. Finally, 90P cells exhibited a survival response similar to that of normal mammary epithelial cells to radiation damage and exposure to oxidative stress. To our knowledge the 90P cells and the 90PE6E7 cells are the first characterized, non-tumor-derived breast epithelial cells that are heterozygous for the BRCA1 germline mutation 185delAG. Our conclusion is that these BRCA1 mutant cells appear to have growth and stress response characteristics similar to those of normal human breast cells, which is consistent with the hypothesis that loss of heterozygosity must occur to impair putative BRCA1 function. Copyright 2000 Academic Press. JF - Gynecologic oncology AU - Annab, L A AU - Terry, L AU - Cable, P L AU - Brady, J AU - Stampfer, M R AU - Barrett, J C AU - Afshari, C A AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Annab@NIEHS.NIH.GOV Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 121 EP - 128 VL - 77 IS - 1 SN - 0090-8258, 0090-8258 KW - Culture Media KW - 0 KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - DNA Damage KW - Humans KW - Adult KW - Mice, Nude KW - Mice KW - Germ-Line Mutation KW - Female KW - Frameshift Mutation KW - Breast Neoplasms -- genetics KW - Loss of Heterozygosity KW - Breast Neoplasms -- pathology KW - Genes, BRCA1 -- genetics KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71007290?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gynecologic+oncology&rft.atitle=Establishment+and+characterization+of+a+breast+cell+strain+containing+a+BRCA1+185delAG+mutation.&rft.au=Annab%2C+L+A%3BTerry%2C+L%3BCable%2C+P+L%3BBrady%2C+J%3BStampfer%2C+M+R%3BBarrett%2C+J+C%3BAfshari%2C+C+A&rft.aulast=Annab&rft.aufirst=L&rft.date=2000-04-01&rft.volume=77&rft.issue=1&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Gynecologic+oncology&rft.issn=00908258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-25 N1 - Date created - 2000-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Negligible glucose-6-phosphatase activity in cultured astroglia. AN - 70999602; 10737595 AB - 2-Deoxy[14C]glucose-6-phosphate (2-[14C]DG-6-P) dephosphorylation and glucose-6-phosphatase (G-6-Pase) activity were examined in cultured rat astrocytes under conditions similar to those generally used in assays of glucose utilization. Astrocytes were loaded with 2-[14C]DG-6-P by preincubation for 15 min in medium containing 2 mM glucose and 50 microM 2-deoxy[14C]glucose (2-[14C]DG). The medium was then replaced with identical medium including 2 mM glucose but lacking 2-[14C]DG, and incubation was resumed for 5 min to diminish residual free 2-[14C]DG levels in the cells by either efflux or phosphorylation. The medium was again replaced with fresh 2-[14C]DG-free medium, and the incubation was continued for 5, 15, or 30 min. Intracellular and extracellular 14C contents were measured at each time point, and the distribution of 14C between 2-[14C]DG and 2-[14C]DG-6-P was characterized by paper chromatography. The results showed little if any hydrolysis of 2-[14C]DG-6-P or export of free 2-[14C]DG from cells to medium; there were slightly increasing losses of 2-[14C]DG and 2-[14C]DG-6-P into the medium with increasing incubation time, but they were in the same proportions found in the cells, suggesting they were derived from nonadherent or broken cells. Experiments carried out with medium lacking glucose during the assay for 2-deoxyglucose-6-phosphatase activity yielded similar results. Evidence for G-6-Pase activity was also sought by following the selective detritiation of glucose from the 2-C position when astrocytes were incubated with [2-3H]glucose and [U-14C]glucose in the medium. No change in the 3H/14C ratio was found in incubations for as long as 15 min. These results indicate negligible G-6-Pase activity in cultured astrocytes. JF - Journal of neurochemistry AU - Gotoh, J AU - Itoh, Y AU - Kuang, T Y AU - Cook, M AU - Law, M J AU - Sokoloff, L AD - Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, Maryland, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 1400 EP - 1408 VL - 74 IS - 4 SN - 0022-3042, 0022-3042 KW - Antimetabolites KW - 0 KW - Carbon Radioisotopes KW - Culture Media KW - Tritium KW - 10028-17-8 KW - Deoxyglucose KW - 9G2MP84A8W KW - Glucose-6-Phosphatase KW - EC 3.1.3.9 KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Animals KW - Glucose -- metabolism KW - Culture Media -- pharmacology KW - Pregnancy KW - Rats KW - Rats, Sprague-Dawley KW - Phosphorylation KW - Cells, Cultured KW - Antimetabolites -- pharmacokinetics KW - Deoxyglucose -- pharmacokinetics KW - Glucose -- pharmacokinetics KW - Biological Transport -- physiology KW - Female KW - Astrocytes -- cytology KW - Glucose-6-Phosphatase -- metabolism KW - Astrocytes -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70999602?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Negligible+glucose-6-phosphatase+activity+in+cultured+astroglia.&rft.au=Gotoh%2C+J%3BItoh%2C+Y%3BKuang%2C+T+Y%3BCook%2C+M%3BLaw%2C+M+J%3BSokoloff%2C+L&rft.aulast=Gotoh&rft.aufirst=J&rft.date=2000-04-01&rft.volume=74&rft.issue=4&rft.spage=1400&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 - 2000-04-11 N1 - Date created - 2000-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of the neurotoxic effects of methamphetamine by the selective kappa-opioid receptor agonist U69593. AN - 70997559; 10737612 AB - Kappa-opioid receptor agonists prevent alterations in dopamine neurotransmission that occur in response to repeated cocaine administration. The present microdialysis study examined whether administration of the selective kappa-opioid receptor agonist U69593 with methamphetamine prevents alterations in dopamine levels produced by neurotoxic doses of methamphetamine. Swiss Webster mice were injected intraperitoneally with methamphetamine (10.0 mg/kg) or saline, four times in 1 day, at 2-h intervals. Prior to the first and third injection, they received U69593 (0.32 mg/kg s.c.) or vehicle. Microdialysis was conducted 3, 7, or 21 days later. Basal and K+-evoked (60 and 100 mM) dopamine overflow were reduced 3 days after methamphetamine administration. These effects were long-lasting in that they were still apparent 7 and 21 days after methamphetamine treatment. Intrastriatal (5.0 and 50 microM) or systemic (1.0-10.0 mg/kg) administration of methamphetamine increased dopamine concentrations in control animals. In mice preexposed to methamphetamine, methamphetamine-evoked dopamine overflow was reduced. In animals that had received methamphetamine with U69593, basal dopamine levels did not differ from those of vehicle-treated controls. U69593 treatment attenuated the decrease in K+-evoked dopamine produced by prior methamphetamine exposure. The reduction in methamphetamine-evoked dopamine levels was also attenuated. The administration of U69593 alone did not modify basal or stimulus-evoked dopamine levels. These data demonstrate that repeated methamphetamine administration reduces presynaptic dopamine neuronal function in mouse striatum and that co-administration of a selective kappa-opioid receptor agonist with methamphetamine attenuates these effects. U69593 treatment did not modify the hyperthermic effects of methamphetamine, indicating that this kappa-opioid receptor agonist selectively attenuates methamphetamine-induced alterations in dopamine neurotransmission. JF - Journal of neurochemistry AU - El Daly, E AU - Chefer, V AU - Sandill, S AU - Shippenberg, T S AD - Integrative Neuroscience Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland 21224, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 1553 EP - 1562 VL - 74 IS - 4 SN - 0022-3042, 0022-3042 KW - Analgesics KW - 0 KW - Benzeneacetamides KW - Dopamine Agents KW - Pyrrolidines KW - Receptors, Opioid, kappa KW - Methamphetamine KW - 44RAL3456C KW - U 69593 KW - J5S4K6TKTG KW - Potassium KW - RWP5GA015D KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Microdialysis KW - Fever -- chemically induced KW - Animals KW - Drug Interactions KW - Body Temperature -- drug effects KW - Brain Chemistry -- drug effects KW - Potassium -- pharmacology KW - Dopamine -- metabolism KW - Mice KW - Male KW - Dopamine Agents -- toxicity KW - Receptors, Opioid, kappa -- agonists KW - Analgesics -- pharmacology KW - Pyrrolidines -- pharmacology KW - Methamphetamine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70997559?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Modulation+of+the+neurotoxic+effects+of+methamphetamine+by+the+selective+kappa-opioid+receptor+agonist+U69593.&rft.au=El+Daly%2C+E%3BChefer%2C+V%3BSandill%2C+S%3BShippenberg%2C+T+S&rft.aulast=El+Daly&rft.aufirst=E&rft.date=2000-04-01&rft.volume=74&rft.issue=4&rft.spage=1553&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 - 2000-04-11 N1 - Date created - 2000-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rasputin, the Drosophila homologue of the RasGAP SH3 binding protein, functions in ras- and Rho-mediated signaling. AN - 70992179; 10725247 AB - The small GTPase Ras plays an important role in many cellular signaling processes. Ras activity is negatively regulated by GTPase activating proteins (GAPs). It has been proposed that RasGAP may also function as an effector of Ras activity. We have identified and characterized the Drosophila homologue of the RasGAP-binding protein G3BP encoded by rasputin (rin). rin mutants are viable and display defects in photoreceptor recruitment and ommatidial polarity in the eye. Mutations in rin/G3BP genetically interact with components of the Ras signaling pathway that function at the level of Ras and above, but not with Raf/MAPK pathway components. These interactions suggest that Rin is required as an effector in Ras signaling during eye development, supporting an effector role for RasGAP. The ommatidial polarity phenotypes of rin are similar to those of RhoA and the polarity genes, e.g. fz and dsh. Although rin/G3BP interacts genetically with RhoA, affecting both photoreceptor differentiation and polarity, it does not interact with the gain-of-function genotypes of fz and dsh. These data suggest that Rin is not a general component of polarity generation, but serves a function specific to Ras and RhoA signaling pathways. JF - Development (Cambridge, England) AU - Pazman, C AU - Mayes, C A AU - Fanto, M AU - Haynes, S R AU - Mlodzik, M AD - LMG, NICHD, NIH, MSC 2785, Bethesda, MD 20892, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 1715 EP - 1725 VL - 127 IS - 8 SN - 0950-1991, 0950-1991 KW - Carrier Proteins KW - 0 KW - DNA-Binding Proteins KW - Drosophila Proteins KW - G3BP protein, human KW - Receptors, Steroid KW - Repressor Proteins KW - rasputin protein, Drosophila KW - seven-up protein, Drosophila KW - ras Proteins KW - EC 3.6.5.2 KW - rhoA GTP-Binding Protein KW - Index Medicus KW - rhoA GTP-Binding Protein -- metabolism KW - Animals KW - Cytosol -- metabolism KW - Humans KW - DNA-Binding Proteins -- genetics KW - Gene Expression KW - Amino Acid Sequence KW - Mutagenesis KW - Molecular Sequence Data KW - Drosophila -- physiology KW - Receptors, Steroid -- genetics KW - Drosophila -- genetics KW - Sequence Homology, Amino Acid KW - Signal Transduction KW - Photoreceptor Cells, Invertebrate -- embryology KW - Repressor Proteins -- physiology KW - Carrier Proteins -- genetics KW - Carrier Proteins -- physiology KW - ras Proteins -- metabolism KW - Photoreceptor Cells, Invertebrate -- physiology KW - Repressor Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70992179?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Development+%28Cambridge%2C+England%29&rft.atitle=Rasputin%2C+the+Drosophila+homologue+of+the+RasGAP+SH3+binding+protein%2C+functions+in+ras-+and+Rho-mediated+signaling.&rft.au=Pazman%2C+C%3BMayes%2C+C+A%3BFanto%2C+M%3BHaynes%2C+S+R%3BMlodzik%2C+M&rft.aulast=Pazman&rft.aufirst=C&rft.date=2000-04-01&rft.volume=127&rft.issue=8&rft.spage=1715&rft.isbn=&rft.btitle=&rft.title=Development+%28Cambridge%2C+England%29&rft.issn=09501991&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-30 N1 - Date created - 2000-06-30 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AA440649; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Golgi network targeting and plasma membrane internalization signals in vaccinia virus B5R envelope protein. AN - 70979776; 10729152 AB - The vaccinia virus B5R type I integral membrane protein accumulates in the Golgi network, from where it becomes incorporated into the envelope of extracellular virions. Our objective was to determine the domains of B5R responsible for Golgi membrane targeting in the absence of other viral components. Fusion of an enhanced green fluorescent protein to the C terminus of B5R allowed imaging of the chimeric protein without altering intracellular trafficking and Golgi network localization in transfected cells. Deletion or swapping of B5R domains with corresponding regions of the vesicular stomatitis virus G protein, which is targeted to the plasma membrane, indicated that (i) the N-terminal extracellular domain of B5R had no specific role in Golgi apparatus localization, (ii) the transmembrane domain of B5R was sufficient for exiting the endoplasmic reticulum, and (iii) removal of the cytoplasmic tail impaired Golgi network localization and increased the accumulation of B5R in the plasma membrane. Further experiments demonstrated that the cytoplasmic tail mediated internalization of B5R from the plasma membrane, suggesting a retrieval mechanism. Mutagenesis revealed residues required for Golgi membrane localization and efficient plasma membrane retrieval of the B5R protein: a tyrosine at residue 310 and two adjacent leucines at residues 315 and 316. JF - Journal of virology AU - Ward, B M AU - Moss, B AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0445, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 3771 EP - 3780 VL - 74 IS - 8 SN - 0022-538X, 0022-538X KW - Luminescent Proteins KW - 0 KW - Membrane Glycoproteins KW - Recombinant Fusion Proteins KW - Viral Envelope Proteins KW - 42kDa protein, Vaccinia virus KW - 134034-10-9 KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Index Medicus KW - Endoplasmic Reticulum -- metabolism KW - Vesicular stomatitis Indiana virus KW - Animals KW - COS Cells KW - HeLa Cells KW - Humans KW - Amino Acid Sequence KW - Luminescent Proteins -- metabolism KW - Recombinant Fusion Proteins -- metabolism KW - Microscopy, Fluorescence KW - Transfection KW - Molecular Sequence Data KW - Protein Structure, Tertiary KW - Luminescent Proteins -- genetics KW - Signal Transduction KW - Membrane Glycoproteins -- chemistry KW - Viral Envelope Proteins -- chemistry KW - Vaccinia virus -- metabolism KW - Viral Envelope Proteins -- metabolism KW - Cell Membrane -- metabolism KW - Golgi Apparatus -- metabolism KW - Viral Envelope Proteins -- genetics KW - Membrane Glycoproteins -- metabolism KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70979776?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Golgi+network+targeting+and+plasma+membrane+internalization+signals+in+vaccinia+virus+B5R+envelope+protein.&rft.au=Ward%2C+B+M%3BMoss%2C+B&rft.aulast=Ward&rft.aufirst=B&rft.date=2000-04-01&rft.volume=74&rft.issue=8&rft.spage=3771&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 - 2000-04-26 N1 - Date created - 2000-04-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Gen Virol. 1971 Oct;13(1):9-17 [4108676] J Cell Biol. 1998 Aug 24;142(4):923-36 [9722606] Prog Med Virol. 1973;16:86-108 [4356899] J Gen Virol. 1976 Jul;32(1):63-72 [986420] Virology. 1976 Aug;73(1):43-58 [960564] J Gen Virol. 1980 Sep;50(1):89-100 [7441216] Virology. 1982 Aug;121(1):157-67 [6180550] J Virol. 1985 Sep;55(3):651-9 [4020961] Virology. 1986 Apr 15;150(1):10-20 [3952982] Virology. 1986 Apr 30;150(2):451-62 [3008418] Annu Rev Biochem. 1998;67:509-44 [9759496] Virology. 1998 Dec 20;252(2):450-7 [9878625] J Biol Chem. 1999 Feb 12;274(7):4389-99 [9933643] J Biol Chem. 1999 May 28;274(22):15937-46 [10336500] J Cell Biol. 1999 Jul 26;146(2):345-59 [10465644] J Virol. 1986 Jun;58(3):757-64 [3701927] J Cell Biol. 1988 Jul;107(1):89-99 [2839523] J Biol Chem. 1989 Sep 25;264(27):16083-92 [2777777] J Cell Biol. 1990 Dec;111(6 Pt 1):2295-306 [2277061] J Virol. 1991 Nov;65(11):5910-20 [1920620] J Virol. 1992 Mar;66(3):1610-21 [1738204] Virology. 1992 Jun;188(2):801-10 [1585649] J Virol. 1992 Jul;66(7):4170-9 [1602540] J Virol. 1992 Dec;66(12):7217-24 [1433514] J Cell Biol. 1993 Mar;120(5):1123-35 [8436587] Eur J Cell Biol. 1993 Feb;60(1):163-78 [8385018] EMBO J. 1993 May;12(5):2219-28 [8491209] Virology. 1993 Jun;194(2):627-37 [8503178] J Virol. 1993 Aug;67(8):4732-41 [8331727] J Virol. 1994 Jan;68(1):130-47 [8254722] Virology. 1994 Oct;204(1):376-90 [8091668] EMBO J. 1995 Jun 1;14(11):2424-35 [7781597] J Virol. 1996 Jan;70(1):272-81 [8523536] J Virol. 1996 Jun;70(6):3753-62 [8648710] J Cell Biol. 1996 Oct;135(2):341-54 [8896593] J Virol. 1997 Apr;71(4):3178-87 [9060681] J Virol. 1997 May;71(5):3904-15 [9094667] EMBO J. 1997 May 1;16(9):2240-50 [9171339] Science. 1997 Jul 25;277(5325):556-8 [9228004] J Cell Biol. 1997 Jul 28;138(2):271-81 [9230070] Nature. 1997 Sep 4;389(6646):81-5 [9288971] J Biol Chem. 1997 Oct 3;272(40):24739-42 [9312065] J Biol Chem. 1997 Dec 12;272(50):31801-8 [9395526] J Virol. 1998 Jan;72(1):294-302 [9420227] J Virol. 1998 Mar;72(3):2429-38 [9499104] J Cell Biol. 1998 Feb 23;140(4):751-65 [9472029] J Virol. 1998 May;72(5):4192-204 [9557708] Virology. 1998 Apr 25;244(1):20-6 [9581774] J Gen Virol. 1998 Jun;79 ( Pt 6):1415-25 [9634084] Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7544-9 [9636186] J Biol Chem. 1998 Jul 3;273(27):17056-63 [9642270] Trends Cell Biol. 1998 Jan;8(1):11-5 [9695801] Virology. 1971 Dec;46(3):507-32 [4944855] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of fluconazole on the pharmacokinetics of doxorubicin in nonhuman primates. AN - 70978622; 10722523 AB - Antifungal prophylaxis in cancer patients who are undergoing chemotherapy is associated with prolonged neutropenia. We measured the effect of fluconazole on doxorubicin pharmacokinetics in nonhuman primates to determine if neutropenia is related to a pharmacokinetic interaction that delays the clearance of the chemotherapeutic agent. Fluconazole pretreatment had no effect on doxorubicin pharmacokinetics. JF - Antimicrobial agents and chemotherapy AU - Warren, K E AU - McCully, C M AU - Walsh, T J AU - Balis, F M AD - Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892-1928, USA. warrenk@exchange.nih.gov Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 1100 EP - 1101 VL - 44 IS - 4 SN - 0066-4804, 0066-4804 KW - Antibiotics, Antineoplastic KW - 0 KW - Antifungal Agents KW - Doxorubicin KW - 80168379AG KW - Fluconazole KW - 8VZV102JFY KW - Index Medicus KW - Animals KW - Drug Interactions KW - Spectrometry, Fluorescence KW - Injections, Intravenous KW - Half-Life KW - Area Under Curve KW - Macaca mulatta KW - Male KW - Chromatography, High Pressure Liquid KW - Doxorubicin -- pharmacokinetics KW - Antifungal Agents -- pharmacology KW - Fluconazole -- pharmacology KW - Antibiotics, Antineoplastic -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70978622?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Effect+of+fluconazole+on+the+pharmacokinetics+of+doxorubicin+in+nonhuman+primates.&rft.au=Warren%2C+K+E%3BMcCully%2C+C+M%3BWalsh%2C+T+J%3BBalis%2C+F+M&rft.aulast=Warren&rft.aufirst=K&rft.date=2000-04-01&rft.volume=44&rft.issue=4&rft.spage=1100&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-01 N1 - Date created - 2000-05-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1976 Oct;36(10):3803-6 [954004] Cancer Res. 1983 Jul;43(7):3417-21 [6850648] J Infect Dis. 1988 Jan;157(1):178-80 [2826606] Cancer Chemother Pharmacol. 1988;21(4):323-8 [3370741] Clin Pharmacokinet. 1988 Jul;15(1):15-31 [3042244] Lab Anim Sci. 1990 Sep;40(5):520-5 [2170754] Drug Saf. 1998 Feb;18(2):83-97 [9512916] J Intern Med. 1992 Apr;231(4):363-70 [1588260] Clin Pharmacokinet. 1993 Jan;24(1):10-27 [8448970] Clin Infect Dis. 1993 Nov;17 Suppl 2:S457-67 [8274612] Clin Infect Dis. 1993 Nov;17 Suppl 2:S468-80 [8274613] J Infect Dis. 1995 Oct;172(4):1035-41 [7561177] N Engl J Med. 1992 Mar 26;326(13):845-51 [1542320] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nucleotide excision repair/TFIIH helicases RAD3 and SSL2 inhibit short-sequence recombination and Ty1 retrotransposition by similar mechanisms. AN - 70969948; 10713167 AB - Eukaryotic genomes contain potentially unstable sequences whose rearrangement threatens genome structure and function. Here we show that certain mutant alleles of the nucleotide excision repair (NER)/TFIIH helicase genes RAD3 and SSL2 (RAD25) confer synthetic lethality and destabilize the Saccharomyces cerevisiae genome by increasing both short-sequence recombination and Ty1 retrotransposition. The rad3-G595R and ssl2-rtt mutations do not markedly alter Ty1 RNA or protein levels or target site specificity. However, these mutations cause an increase in the physical stability of broken DNA molecules and unincorporated Ty1 cDNA, which leads to higher levels of short-sequence recombination and Ty1 retrotransposition. Our results link components of the core NER/TFIIH complex with genome stability, homologous recombination, and host defense against Ty1 retrotransposition via a mechanism that involves DNA degradation. JF - Molecular and cellular biology AU - Lee, B S AU - Bi, L AU - Garfinkel, D J AU - Bailis, A M AD - Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute-Frederick Cancer Research and Development Center, National Institutes of Health, Frederick, Maryland 21702-1201, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 2436 EP - 2445 VL - 20 IS - 7 SN - 0270-7306, 0270-7306 KW - Fungal Proteins KW - 0 KW - Retroelements KW - SSL2 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - TAF6 protein, S cerevisiae KW - TATA-Binding Protein Associated Factors KW - Transcription Factor TFIID KW - Transcription Factors KW - Transcription Factors, TFII KW - Transcription Factor TFIIH KW - 148710-81-0 KW - DNA KW - 9007-49-2 KW - SCEI protein, S cerevisiae KW - EC 3.1.21.- KW - Deoxyribonucleases, Type II Site-Specific KW - EC 3.1.21.4 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Rad3 protein, S cerevisiae KW - DNA Helicases KW - EC 3.6.4.- KW - Index Medicus KW - Plasmids -- metabolism KW - Genes, Fungal KW - Plasmids -- genetics KW - DNA -- metabolism KW - Mutation KW - Mutagenesis, Insertional KW - Deoxyribonucleases, Type II Site-Specific -- metabolism KW - DNA Helicases -- metabolism KW - Adenosine Triphosphatases -- metabolism KW - Fungal Proteins -- genetics KW - Transcription Factors -- genetics KW - DNA Repair -- genetics KW - Saccharomyces cerevisiae -- genetics KW - Retroelements -- genetics KW - Fungal Proteins -- metabolism KW - Recombination, Genetic KW - DNA Helicases -- genetics KW - Adenosine Triphosphatases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70969948?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nucleotide+excision+repair%2FTFIIH+helicases+RAD3+and+SSL2+inhibit+short-sequence+recombination+and+Ty1+retrotransposition+by+similar+mechanisms.&rft.au=Lee%2C+B+S%3BBi%2C+L%3BGarfinkel%2C+D+J%3BBailis%2C+A+M&rft.aulast=Lee&rft.aufirst=B&rft.date=2000-04-01&rft.volume=20&rft.issue=7&rft.spage=2436&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 - 2000-04-03 N1 - Date created - 2000-04-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genetics. 1988 Jun;119(2):289-301 [2840336] EMBO J. 1988 Oct;7(10):3263-9 [2846277] Annu Rev Genet. 1988;22:147-68 [3071247] Genetics. 1989 May;122(1):19-27 [2659436] Mol Cell Biol. 1998 Feb;18(2):1115-24 [9448009] Mol Cell Biol. 1998 May;18(5):2502-13 [9566871] Genetics. 1998 Apr;148(4):1743-61 [9560391] J Acquir Immune Defic Syndr Hum Retrovirol. 1998 May 1;18(1):51-3 [9593458] Genetics. 1998 Nov;150(3):963-76 [9799251] Pathol Biol (Paris). 1998 Nov;46(9):679-80 [9885814] Curr Opin Genet Dev. 1999 Feb;9(1):89-96 [10072354] Trends Genet. 1999 Feb;15(2):43-5 [10098404] Genetics. 1999 Apr;151(4):1393-407 [10101165] Genes Dev. 1999 Apr 1;13(7):768-85 [10197977] Microbiol Mol Biol Rev. 1999 Jun;63(2):349-404 [10357855] Cell. 1998 Jun 26;93(7):1087-9 [9657139] Genetics. 2000 Feb;154(2):543-56 [10655210] Genetics. 1989 Dec;123(4):655-65 [2558956] Genetics. 1989 Dec;123(4):725-38 [2693208] Genes Dev. 1990 Mar;4(3):324-30 [2159935] J Bacteriol. 1990 Dec;172(12):6620-30 [2174856] Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):936-40 [1846969] Mol Cell Biol. 1992 Apr;12(4):1613-20 [1372387] Mol Cell Biol. 1992 Jun;12(6):2813-25 [1317008] Cell. 1992 Jun 12;69(6):1031-42 [1318786] Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11416-20 [1333609] Genetics. 1993 Mar;133(3):499-508 [8384143] Cell. 1993 Jun 4;73(5):1007-18 [8388781] Mol Cell Biol. 1993 Jul;13(7):3937-50 [8321201] Genes Dev. 1993 Nov;7(11):2161-71 [7693549] Genetics. 1993 Oct;135(2):309-20 [8243996] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3926-30 [8171014] Nature. 1994 Jun 16;369(6481):578-81 [8202161] Genetics. 1994 Apr;136(4):1245-59 [8013902] Mol Cell Biol. 1994 Oct;14(10):6540-51 [7523854] Cell. 1995 Jan 13;80(1):21-8 [7813015] J Biol Chem. 1995 May 5;270(18):10361-4 [7737964] Philos Trans R Soc Lond B Biol Sci. 1995 Jan 30;347(1319):63-8 [7746856] Mol Cell Biol. 1995 Aug;15(8):3998-4008 [7623796] Cell. 1995 Aug 11;82(3):453-61 [7634335] Nucleic Acids Res. 1995 Jul 25;23(14):2799-800 [7651842] Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10354-8 [7479783] Genes Dev. 1996 Mar 1;10(5):620-33 [8598291] J Bacteriol. 1996 Apr;178(7):2136-40 [8606195] J Biol Chem. 1996 May 3;271(18):10821-6 [8631896] J Biol Chem. 1996 Apr 12;271(15):8903-10 [8621533] Genetics. 1996 Jun;143(2):673-83 [8725218] Genetics. 1996 Mar;142(3):761-76 [8849886] Nature. 1996 Nov 28;384(6607):379-83 [8934527] Genes Dev. 1996 Nov 1;10(21):2657-83 [8946909] Mol Cell Biol. 1997 Jan;17(1):278-86 [8972208] Trends Genet. 1996 Nov;12(11):436-8 [8973141] J Biol Chem. 1997 Aug 1;272(31):19319-27 [9235928] Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8658-63 [9238033] Mol Cell Biol. 1997 Sep;17(9):5359-68 [9271413] Mol Cell Biol. 1998 Feb;18(2):1105-14 [9448008] Science. 1968 Aug 9;161(3841):529-40 [4874239] J Bacteriol. 1981 Aug;147(2):705-8 [7021538] J Bacteriol. 1981 Nov;148(2):618-23 [7028721] EMBO J. 1982;1(8):945-51 [6329717] Cell. 1984 Dec;39(3 Pt 2):675-82 [6096019] Cell. 1985 Mar;40(3):491-500 [2982495] Proc Natl Acad Sci U S A. 1986 Oct;83(20):7831-5 [3020559] Mol Cell Biol. 1986 Apr;6(4):1218-27 [3023877] Mol Cell Biol. 1986 Nov;6(11):3575-81 [3025601] Genetics. 1987 Aug;116(4):541-5 [3305158] Mol Cell Biol. 1988 Apr;8(4):1421-31 [2454391] Mol Cell Biol. 1988 Apr;8(4):1432-42 [2837641] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Local and downstream effects of excitotoxic lesions in the rat medial prefrontal cortex on In vivo 1H-MRS signals. AN - 70947862; 10700662 AB - The rat medial prefrontal cortex (mPFC) regulates subcortical dopamine transmission via projections to the striatum and ventral tegmental area. We used in vivo proton magnetic resonance spectroscopy (1H-MRS) at 4.7 T to determine whether excitotoxic lesions of the mPFC result in alterations of N-acetylaspartate (NAA), a marker of neuronal integrity, both locally and downstream in the striatum. Lesioned rats exhibited persistent reductions of NAA and other metabolites within the prefrontal cortex; selective reductions of NAA were seen in the striatum, but not in the parietal cortex. Consistent with earlier reports, lesioned rats exhibited a transient enhancement in amphetamine-induced hyperlocomotion. Prefrontal NAA losses correlated with lesion extent. In the striatum, while there was no change in tissue volume, expression of striatal glutamic acid decarboxylase-67 mRNA was significantly reduced. In vivo NAA levels thus appear sensitive to both local and downstream alterations in neuronal integrity, and may signal meaningful effects at cellular and behavioral levels. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Roffman, J L AU - Lipska, B K AU - Bertolino, A AU - Van Gelderen, P AU - Olson, A W AU - Khaing, Z Z AU - Weinberger, D R AD - Clinical Brain Disorders Branch, NIMH, National Institutes of Health, Bethesda, MD 20892-1379, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 430 EP - 439 VL - 22 IS - 4 SN - 0893-133X, 0893-133X KW - Dopamine Agents KW - 0 KW - Neurotoxins KW - RNA, Messenger KW - Aspartic Acid KW - 30KYC7MIAI KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - N-acetylaspartate KW - 997-55-7 KW - Amphetamine KW - CK833KGX7E KW - Glutamate Decarboxylase KW - EC 4.1.1.15 KW - Index Medicus KW - Aspartic Acid -- metabolism KW - Animals KW - Neurons -- metabolism KW - Corpus Striatum -- metabolism KW - Dopamine Agents -- pharmacology KW - RNA, Messenger -- analysis KW - Motor Activity -- physiology KW - Denervation KW - Glutamate Decarboxylase -- metabolism KW - Magnetic Resonance Spectroscopy KW - Rats KW - Rats, Sprague-Dawley KW - In Situ Hybridization KW - Aspartic Acid -- analogs & derivatives KW - Corpus Striatum -- physiology KW - Motor Activity -- drug effects KW - gamma-Aminobutyric Acid -- metabolism KW - Amphetamine -- pharmacology KW - Male KW - Efferent Pathways -- physiology KW - Efferent Pathways -- metabolism KW - Prefrontal Cortex -- metabolism KW - Prefrontal Cortex -- physiology KW - Neurotoxins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70947862?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=Local+and+downstream+effects+of+excitotoxic+lesions+in+the+rat+medial+prefrontal+cortex+on+In+vivo+1H-MRS+signals.&rft.au=Roffman%2C+J+L%3BLipska%2C+B+K%3BBertolino%2C+A%3BVan+Gelderen%2C+P%3BOlson%2C+A+W%3BKhaing%2C+Z+Z%3BWeinberger%2C+D+R&rft.aulast=Roffman&rft.aufirst=J&rft.date=2000-04-01&rft.volume=22&rft.issue=4&rft.spage=430&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-01 N1 - Date created - 2000-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An adeno-associated virus (AAV) initiator protein, Rep78, catalyzes the cleavage and ligation of single-stranded AAV ori DNA. AN - 70942324; 10708427 AB - The Rep78 protein of adeno-associated virus (AAV) contains amino acid sequence motifs common to rolling-circle replication (RCR) initiator proteins. In this report, we describe RCR initiator-like activities of Rep78. We demonstrate that a maltose-binding protein (MBP)-Rep78 fusion protein can catalyze the cleavage and ligation of single-stranded DNA substrates derived from the AAV origin of replication. Rep-mediated single-stranded DNA cleavage was strictly dependent on the presence of certain divalent cations (e.g., Mn(2+) or Mg(2+)) but did not require the presence of a nucleoside triphosphate cofactor. Electrophoretic mobility shift assays demonstrated that binding of single-stranded DNA by MBP-Rep78 was influenced by the length of the substrate as well as the presence of potential single-stranded cis-acting sequence elements. Site-directed mutagenesis was used to examine the role of specific tyrosine residues within a conserved RCR motif (motif 3) of Rep78. Replacement of Tyr-156 with phenylalanine abolished the ability of MBP-Rep78 to mediate the cleavage and ligation of single-stranded DNA substrates but not the ability to stably bind single-stranded DNA. The cleaving-joining activity of Rep78 is consistent with the mechanism of replicative intermediate dimer resolution proposed for the autonomous parvoviruses and may have implications for targeted integration of recombinant AAV vectors. JF - Journal of virology AU - Smith, R H AU - Kotin, R M AD - Laboratory of Molecular Hematology, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 3122 EP - 3129 VL - 74 IS - 7 SN - 0022-538X, 0022-538X KW - DNA, Single-Stranded KW - 0 KW - DNA, Viral KW - DNA-Binding Proteins KW - Viral Proteins KW - rep proteins, Adeno-associated virus 2 KW - 137750-19-7 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Molecular Sequence Data KW - Catalysis KW - Viral Proteins -- genetics KW - DNA, Single-Stranded -- metabolism KW - Dependovirus -- genetics KW - DNA-Binding Proteins -- genetics KW - Viral Proteins -- metabolism KW - Replication Origin -- genetics KW - DNA-Binding Proteins -- metabolism KW - DNA, Viral -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70942324?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=An+adeno-associated+virus+%28AAV%29+initiator+protein%2C+Rep78%2C+catalyzes+the+cleavage+and+ligation+of+single-stranded+AAV+ori+DNA.&rft.au=Smith%2C+R+H%3BKotin%2C+R+M&rft.aulast=Smith&rft.aufirst=R&rft.date=2000-04-01&rft.volume=74&rft.issue=7&rft.spage=3122&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 - 2000-04-07 N1 - Date created - 2000-04-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1990 Mar;87(6):2211-5 [2156265] Annu Rev Microbiol. 1989;43:537-65 [2679362] J Virol. 1990 Dec;64(12):6204-13 [2173787] Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8029-33 [1896448] EMBO J. 1991 Dec;10(12):3941-50 [1657596] J Virol. 1992 Feb;66(2):1119-28 [1309894] Proc Natl Acad Sci U S A. 1992 May 15;89(10):4673-7 [1316616] Nucleic Acids Res. 1992 Jul 11;20(13):3279-85 [1630899] J Gen Virol. 1992 Oct;73 ( Pt 10):2763-6 [1402808] J Virol. 1993 Feb;67(2):997-1005 [8380475] J Biol Chem. 1993 Nov 15;268(32):23830-6 [8226920] Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11538-42 [8265585] J Virol. 1994 Feb;68(2):1128-38 [8289342] Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5808-12 [8016070] J Virol. 1994 Aug;68(8):4998-5006 [8035499] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10039-43 [7937833] J Virol. 1995 Apr;69(4):2038-46 [7884849] J Virol. 1995 Jun;69(6):3542-8 [7538173] Virology. 1995 Jun 1;209(2):692-5 [7778304] FEMS Microbiol Lett. 1995 Aug 1;130(2-3):111-20 [7649431] J Virol. 1995 Nov;69(11):6917-24 [7474109] Prog Nucleic Acid Res Mol Biol. 1996;54:197-251 [8768076] Prog Nucleic Acid Res Mol Biol. 1996;55:245-85 [8787613] J Virol. 1997 Jun;71(6):4461-71 [9151837] J Virol. 1998 Jun;72(6):4874-81 [9573254] J Virol. 1999 Feb;73(2):1580-90 [9882364] J Virol. 1999 Apr;73(4):2682-93 [10074114] J Virol. 1999 Jul;73(7):5438-47 [10364291] Cold Spring Harb Symp Quant Biol. 1968;33:473-84 [4891987] Nature. 1976 Sep 9;263(5573):106-9 [967244] Virology. 1977 May 15;78(2):475-7 [194395] Proc Natl Acad Sci U S A. 1979 Nov;76(11):5567-71 [230481] J Virol. 1982 Feb;41(2):518-26 [6281463] J Virol. 1985 Apr;54(1):171-7 [3973977] Nucleic Acids Res. 1986 May 27;14(10):4229-38 [2940511] Adv Virus Res. 1987;32:243-306 [3039813] J Virol. 1989 Feb;63(2):1002-6 [2911112] J Virol. 1989 Feb;63(2):873-82 [2536109] Cell. 1990 May 4;61(3):447-57 [2159383] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Decreased accumulation of [14C]carboplatin in human cisplatin-resistant cells results from reduced energy-dependent uptake. AN - 70940905; 10699972 AB - We have isolated cisplatin-resistant human liver carcinoma (7404-CP20) cells with reduced accumulation of cisplatin and other drugs (methotrexate, arsenate, and arsenite) to which these cells are cross-resistant. To determine whether the reduction of drug accumulation in cisplatin-resistant cells results from impaired uptake or from active efflux, [(14)C]carboplatin was used for kinetic analysis of drug uptake and efflux. We demonstrate here that the uptake of [(14)C]carboplatin in 7404 parental cells is time, temperature, and energy dependent, and that the rate of uptake is reduced in 7404-CP20 cells. Efflux of [(14)C]carboplatin in cisplatin-resistant cells was comparable to efflux in the parental cisplatin-sensitive cells. There was little effect of temperature (between 37 degrees C and 4 degrees C) on efflux in cisplatin-resistant cells. Immunoblotting with specific antibodies directed to MRP1 and MRP2 (cMOAT) also showed that expression of these two ABC transporter genes was considerably reduced in 7404-CP20 cells and another cisplatin-resistant cell line KB-CP20, in contradistinction to previous studies suggesting that MRP might be responsible for cisplatin efflux. To rule out a generalized defect in uptake of small molecules, fluorescence-activated cell sorter (FACS) analysis of rhodamine 123 uptake showed that there was no difference between cisplatin-sensitive and -resistant cells. The presence of a pleiotropic defect in uptake of [(14)C]carboplatin, [(3)H]methotrexate, [(73)As]arsenate, and [(73)As]arsenite in cisplatin-resistant cells, in association with reduced expression of related cell surface proteins as demonstrated in our previous work, suggests a novel mechanism for acquisition of resistance to cisplatin associated with reduced activity of many different specific uptake systems. Copyright 2000 Wiley-Liss, Inc. JF - Journal of cellular physiology AU - Shen, D W AU - Goldenberg, S AU - Pastan, I AU - Gottesman, M M AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 108 EP - 116 VL - 183 IS - 1 SN - 0021-9541, 0021-9541 KW - Antineoplastic Agents KW - 0 KW - Carbon Radioisotopes KW - Uncoupling Agents KW - Rhodamine 123 KW - 1N3CZ14C5O KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Carboplatin KW - BG3F62OND5 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - KB Cells KW - Humans KW - Biological Transport KW - Temperature KW - Drug Resistance, Neoplasm KW - Uncoupling Agents -- pharmacology KW - Liver Neoplasms KW - Tumor Cells, Cultured KW - Kinetics KW - Adenosine Triphosphate -- metabolism KW - Mitochondria -- metabolism KW - Cell Membrane -- metabolism KW - Rhodamine 123 -- pharmacokinetics KW - Carboplatin -- toxicity KW - Cell Survival -- drug effects KW - Energy Metabolism -- physiology KW - Energy Metabolism -- drug effects KW - Cisplatin -- toxicity KW - Antineoplastic Agents -- pharmacokinetics KW - Antineoplastic Agents -- toxicity KW - Carboplatin -- pharmacokinetics KW - Drug Resistance, Multiple UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70940905?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+physiology&rft.atitle=Decreased+accumulation+of+%5B14C%5Dcarboplatin+in+human+cisplatin-resistant+cells+results+from+reduced+energy-dependent+uptake.&rft.au=Shen%2C+D+W%3BGoldenberg%2C+S%3BPastan%2C+I%3BGottesman%2C+M+M&rft.aulast=Shen&rft.aufirst=D&rft.date=2000-04-01&rft.volume=183&rft.issue=1&rft.spage=108&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+physiology&rft.issn=00219541&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-29 N1 - Date created - 2000-03-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality among Catholic nuns certified as radiologic technologists. AN - 70940833; 10706745 AB - Several studies have shown that Catholic nuns have a different mortality experience than women of similar age in the general population. We had a unique opportunity to evaluate mortality patterns of nuns identified in an occupational study of nearly 145,000 radiologic technologists (73% female). A total of 1,103 women were classified as nuns based on their titles of "Sister" or "SR". Their mortality experience was compared to other female radiologic technologists and to U.S. white females. Five hundred eighty-three nuns (53%) were deceased as of January 1, 1995. Compared to other technologists, nuns were at significantly increased risk of dying from all causes (Standardized mortality ratio (SMR)=1.1; 95% Confidence interval (CI)=1.0-1.2, stomach cancer (SMR=2.7; 95% CI=1.2-5.4), diabetes (SMR=2.2; 95% CI=1.0-4.1), ischemic heart disease (SMR=1.2; 95% CI=1.1-1.4), all digestive diseases (SMR=2.0; 95% CI=1.3-3.0), and gastric and duodenal ulcers (SMR=8.3; 95% CI=2.3-21.3). In contrast, we observed a significant deficit in lung cancer (SMR=0.5; 95% CI=0.2-0.9), no deaths from cervical cancer, and a breast cancer risk 10% lower than expected (SMR=0.9; 95% CI=0.6-1.3). When compared to U.S. females, nuns experienced significantly reduced mortality from all causes (SMR=0.8; 95% CI=0.7-0.9), cervical cancer (SMR=0.0; 95% CI=0.0-0.7), all endocrine, metabolic and nutritional diseases (SMR=0.5; 95% CI=0.3-0.9), all circulatory diseases (SMR=0.7; 95% CI=0.7-0.8) including ischemic heart disease and cerebrovascular disease, and all respiratory diseases (SMR=0.5; 95% CI=0.3-0.8), and a nearly significant deficit of diabetes (SMR=0.6; 95% CI=0.3-1.0). In contrast, nuns had an almost 3-fold greater risk of tuberculosis (SMR=2.9; 95% CI=1.4-5.3) and a 20% excess of breast cancer (SMR=1. 2; 95% CI=0.8-1.7). The breast cancer excess was concentrated among nuns first certified before 1940 (SMR=2.0; CI=1.3-3.0), when radiation doses were possibly the highest, but the risk did not increase with increasing length of certification. Compared with the general population, the mortality experience of nuns was favorable and reflected the "healthy worker effect" commonly seen in occupational studies. Patterns observed for breast and cervical cancer possibly indicate differences in reproductive and sexual activities associated with belonging to a religious order. The possibility of a radiation-related excess for breast cancer among nuns certified before 1940 cannot be completely discounted, although there was no dose-response relationship with a surrogate measure of exposure (number of years certified). When their mortality experience was compared with other radiologic technologists, the influence of lifestyle factors was not apparent. Am. J. Ind. Med. 37:339-348, 2000. Published 2000 Wiley-Liss, Inc. dagger JF - American journal of industrial medicine AU - Morin Doody, M AU - Mandel, J S AU - Linet, M S AU - Ron, E AU - Lubin, J H AU - Boice, J D AU - Fraumeni, J F AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 339 EP - 348 VL - 37 IS - 4 SN - 0271-3586, 0271-3586 KW - Index Medicus KW - United States KW - Healthy Worker Effect KW - Tuberculosis, Pulmonary -- mortality KW - Age Factors KW - Uterine Cervical Neoplasms -- mortality KW - Humans KW - Aged KW - Diabetes Mellitus -- mortality KW - Dose-Response Relationship, Radiation KW - Digestive System Diseases -- mortality KW - Cardiovascular Diseases -- mortality KW - Breast Neoplasms -- mortality KW - Stomach Neoplasms -- mortality KW - Risk Factors KW - Adult KW - Cohort Studies KW - Confidence Intervals KW - Myocardial Ischemia -- mortality KW - Middle Aged KW - Lung Neoplasms -- mortality KW - Respiratory Tract Diseases -- mortality KW - Female KW - Mortality KW - Catholicism KW - Certification KW - Technology, Radiologic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70940833?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Mortality+among+Catholic+nuns+certified+as+radiologic+technologists.&rft.au=Morin+Doody%2C+M%3BMandel%2C+J+S%3BLinet%2C+M+S%3BRon%2C+E%3BLubin%2C+J+H%3BBoice%2C+J+D%3BFraumeni%2C+J+F&rft.aulast=Morin+Doody&rft.aufirst=M&rft.date=2000-04-01&rft.volume=37&rft.issue=4&rft.spage=339&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-30 N1 - Date created - 2000-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Measuring Treatment Process Variables in Alcoholics Anonymous AN - 61619017; 200005200 AB - In a shift away from the traditional focus of efficacy in alcoholism intervention, studies have attempted to identify the variables that explain why there are varying effects of intervention treatments & if the varying effects are related to the treatment itself, or the patient. Several psychometric instruments have been developed to elucidate the processes involved in Alcoholic Anonymous (AA), a key adjunct of most formal alcoholism programs in the US. These instruments measure dimensions such as involvement in AA, completion of steps, & adoption of values encouraged by AA. Six such measures are summarized here, & several fruitful topics for future research on the measures are suggested. 1 Table, 18 References. Adapted from the source document. JF - Journal of Substance Abuse Treatment AU - Allen, John P AD - Division Clinical & Preventive Research, National Instit Alcohol Abuse & Alcoholism, Bethesda, MD jallen@wilco.niaaa.nih.gov Y1 - 2000/04// PY - 2000 DA - April 2000 SP - 227 EP - 230 VL - 18 IS - 3 SN - 0740-5472, 0740-5472 KW - Alcoholics Anonymous KW - Methodology (Data Collection) KW - Treatment Programs KW - Alcoholism KW - Self Help Groups KW - United States of America KW - Measures (Instruments) KW - article KW - 6129: addiction KW - 6123: self-help support groups/networks UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61619017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Substance+Abuse+Treatment&rft.atitle=Measuring+Treatment+Process+Variables+in+Alcoholics+Anonymous&rft.au=Allen%2C+John+P&rft.aulast=Allen&rft.aufirst=John&rft.date=2000-04-01&rft.volume=18&rft.issue=3&rft.spage=227&rft.isbn=&rft.btitle=&rft.title=Journal+of+Substance+Abuse+Treatment&rft.issn=07405472&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Last updated - 2016-09-28 N1 - SubjectsTermNotLitGenreText - Alcoholism; Treatment Programs; United States of America; Methodology (Data Collection); Self Help Groups; Measures (Instruments) ER - TY - JOUR T1 - Antifungal activity of splenic, liver and pulmonary macrophages against Candida albicans and effects of macrophage colony-stimulating factor AN - 19851863; 7386337 AB - Disseminated infections due to Candida albicans are frequently encountered in immunocompromised patients. We compared the antifungal activities of macrophages residing in spleen, liver and lungs of rabbits against blastoconidia and pseudohyphae of C. albicans. Splenic adherent cells (SAC), Kupffer cells (KC) and pulmonary alveolar macrophages (PAM) all ingested blastoconidia efficiently. SAC caused significantly more damage to unopsonized pseudohyphae compared with KC (P-0 super(.)01) or PAM (P-0 super(.)001). Incubation of SAC with 15 ng ml sub(-1) of recombinant human macrophage colony-stimulating factor (M-CSF) at 37 not equal to for 2 days significantly enhanced phagocytosis (P=0 super(.)02) and killing (P=0 super(.)05) of blastoconidia. In contrast, M-CSF had no effect on phagocytic activities of KC or PAM against blastoconidia or on damage caused by any of the macrophages to pseudohyphae of C. albicans. Thus, although all three resident macrophage types ingest blastoconidia efficiently, they differ in their capacity to cause damage to pseudohyphae and in their responsiveness to M-CSF for antifungal activation. M-CSF augments the capacity of SAC to ingest and kill blastoconidia and may therefore have a role in the treatment and prevention of hematogenously disseminated candidiasis. JF - Medical Mycology AU - Lyman, CA AU - Sein, T AU - Gonzalez, C AU - Walsh, T J AU - Roilides, E AD - Pediatric Oncology Branch, National Cancer Institute, Bethesda MD, USA Y1 - 2000/04// PY - 2000 DA - Apr 2000 SP - 161 EP - 168 PB - Taylor & Francis Ltd., 11 New Fetter Lane London EC4P 4EE UK, [mailto:info@tandf.co.uk], [URL:http://www.tandf.co.uk] VL - 38 IS - 2 SN - 1369-3786, 1369-3786 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - CANDIDA KW - M-CSF KW - TISSUE MACROPHAGES KW - Candidiasis KW - Disseminated infection KW - Spleen KW - Candida albicans KW - Macrophage colony-stimulating factor KW - Alveoli KW - Cell activation KW - Kupffer cells KW - Lung KW - Phagocytes KW - Immunocompromised hosts KW - Antifungal activity KW - Liver KW - Phagocytosis KW - Adherent cells KW - pseudohyphae KW - A 01340:Antibiotics & Antimicrobials KW - K 03350:Immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19851863?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medical+Mycology&rft.atitle=Antifungal+activity+of+splenic%2C+liver+and+pulmonary+macrophages+against+Candida+albicans+and+effects+of+macrophage+colony-stimulating+factor&rft.au=Lyman%2C+CA%3BSein%2C+T%3BGonzalez%2C+C%3BWalsh%2C+T+J%3BRoilides%2C+E&rft.aulast=Lyman&rft.aufirst=CA&rft.date=2000-04-01&rft.volume=38&rft.issue=2&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Medical+Mycology&rft.issn=13693786&rft_id=info:doi/10.1080%2F136937800100311007 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-06-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Candidiasis; Disseminated infection; Spleen; Macrophage colony-stimulating factor; Alveoli; Cell activation; Kupffer cells; Phagocytes; Lung; Immunocompromised hosts; Antifungal activity; Liver; Phagocytosis; pseudohyphae; Adherent cells; Candida albicans DO - http://dx.doi.org/10.1080/136937800100311007 ER - TY - JOUR T1 - Use of a herpes thymidine kinase/neomycin phosphotransferase chimeric gene for metabolic suicide gene transfer AN - 18183612; 5184631 AB - Metabolic suicide gene transfer is widely applied for gene therapy of cancer, and retroviral vectors expressing the herpes simplex virus thymidine kinase (HSV-tk) gene are commonly used in clinical trials. Most of these vectors contain positive selectable markers that undoubtedly facilitate the determination of viral titer and the identification of high-titer producer clones. However, the presence of additional transcriptional units may result in reduced expression of the gene of interest. The use of fusion genes expressing bifunctional proteins may help to overcome this problem. We have constructed a retroviral vector carrying the TNFUS69 chimeric gene, which originates from the fusion of the HSV-tk and neomycin phosphotransferase II genes, and evaluated the functional expression of the encoded fusion protein. In vitro, expression of the fusion gene conferred to target cells both resistance to neomycin and selective sensitivity to the antiherpetic drugs ganciclovir and (E)-5-(2-bromovinyl)-2'-deoxyuridine. Cells transduced with the fusion gene, however, showed reduced ability to phosphorylate ganciclovir compared with cells expressing the native HSV-tk. Therefore, although the fusion gene may be used as a constituent of retroviral cassettes for positive and negative selection in vitro, its usefulness for suicide gene transfer applications in vivo may depend upon the possibility of using (E)-5-(2-bromovinyl)-2'-deoxyuridine in a clinical context. JF - Cancer Gene Therapy AU - Candotti, F AU - Agbaria, R AU - Mullen, CA AU - Touraine, R AU - Balzarini, J AU - Johns, D G AU - Blaese, R M AD - Clinical Gene Therapy Branch, National Human Genome Research Institute, Building 10, Room 10C103, National Institutes of Health, 10 Center Drive MSC 1851, Bethesda, MD 20892-1851, USA Y1 - 2000/04// PY - 2000 DA - Apr 2000 SP - 574 EP - 580 VL - 7 IS - 4 SN - 0929-1903, 0929-1903 KW - HSV KW - (E)-5-(2-bromovinyl)-2'-deoxyuridine KW - TNFUS69 gene KW - ganciclovir KW - neomycin phosphotransferase KW - neomycin phosphotransferase II KW - tk gene KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene therapy KW - Gene transfer KW - Thymidine kinase KW - Herpes simplex virus KW - Cancer KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18183612?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Gene+Therapy&rft.atitle=Use+of+a+herpes+thymidine+kinase%2Fneomycin+phosphotransferase+chimeric+gene+for+metabolic+suicide+gene+transfer&rft.au=Candotti%2C+F%3BAgbaria%2C+R%3BMullen%2C+CA%3BTouraine%2C+R%3BBalzarini%2C+J%3BJohns%2C+D+G%3BBlaese%2C+R+M&rft.aulast=Candotti&rft.aufirst=F&rft.date=2000-04-01&rft.volume=7&rft.issue=4&rft.spage=574&rft.isbn=&rft.btitle=&rft.title=Cancer+Gene+Therapy&rft.issn=09291903&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Herpes simplex virus; Thymidine kinase; Gene therapy; Cancer; Gene transfer ER - TY - JOUR T1 - Compassion, communication and craniofacial orodental trauma: opportunities abound. AN - 18146708; 4867429 JF - Journal of the American Dental Association AU - Slavkin, H C AD - National Institute of Dental and Craniofacial Research, Bethesda, Md. 20892- 2290, USA. Y1 - 2000/04// PY - 2000 DA - Apr 2000 SP - 507 EP - 510 VL - 131 IS - 4 SN - 0002-8177, 0002-8177 KW - Physical Education Index KW - Teeth KW - Injuries KW - Dental care KW - Dental health KW - Sports medicine KW - Face KW - Trauma KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18146708?accountid=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+the+American+Dental+Association&rft.atitle=Compassion%2C+communication+and+craniofacial+orodental+trauma%3A+opportunities+abound.&rft.au=Slavkin%2C+H+C&rft.aulast=Slavkin&rft.aufirst=H&rft.date=2000-04-01&rft.volume=131&rft.issue=4&rft.spage=507&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Dental+Association&rft.issn=00028177&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Sports medicine; Face; Injuries; Trauma; Teeth; Dental care; Dental health ER - TY - JOUR T1 - Virus Load and Risk of Heterosexual Transmission of Human Immunodeficiency Virus and Hepatitis C Virus by Men with Hemophilia AN - 18085103; 5166922 AB - A high human immunodeficiency virus (HIV) load may increase the probability of HIV transmission by sexual contact, but the association of virus load of hepatitis C virus (HCV) with risk of HCV transmission is uncertain. HIV and HCV virus loads were examined in hemophilic men, as were risks of HIV and HCV transmission to their female partners in a hemophilia cohort in which most subjects are dually infected. A higher HIV load was associated with an increased risk of HIV transmission (odds ratio [OR], 1.31 per log sub(10) increase in virus load). A higher HCV load was associated, although not significantly, with an increased risk of HCV transmission (OR, 1.42 per log sub(10)). HCV load was higher among dually infected men than in those infected with HCV alone (P = .001). However, much larger studies are needed to clearly show whether HIV/HCV coinfection significantly increases the risk of HCV transmission to female partners. JF - Journal of Infectious Diseases AU - Hisada, M AU - O'Brien, T R AU - Rosenberg, P S AU - Goedert, J J AD - Viral Epidemiology Branch and Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA Y1 - 2000/04// PY - 2000 DA - Apr 2000 SP - 1475 EP - 1478 VL - 181 IS - 4 SN - 0022-1899, 0022-1899 KW - HIV KW - disease transmission KW - hemophilia KW - hepatitis C KW - viral load KW - Risk Abstracts; Virology & AIDS Abstracts KW - Risk assessment KW - Hepatitis C virus KW - Human immunodeficiency virus KW - Transmission (sexual) KW - Hemophilia KW - V 22006:AIDS: Other aspects KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18085103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Virus+Load+and+Risk+of+Heterosexual+Transmission+of+Human+Immunodeficiency+Virus+and+Hepatitis+C+Virus+by+Men+with+Hemophilia&rft.au=Hisada%2C+M%3BO%27Brien%2C+T+R%3BRosenberg%2C+P+S%3BGoedert%2C+J+J&rft.aulast=Hisada&rft.aufirst=M&rft.date=2000-04-01&rft.volume=181&rft.issue=4&rft.spage=1475&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; Hepatitis C virus; Transmission (sexual); Risk assessment; Hemophilia ER - TY - JOUR T1 - Seroprevalence and Ethnic Differences in Helicobacter pylori Infection among Adults in the United States AN - 17895081; 5166905 AB - The seroprevalence of Helicobacter pylori infection was examined in the adult US population and among different ethnic groups. Stored sera from 7465 adult participants in the first phase of the third National Health and Nutritional Examination Survey (1988-1991) were tested with a sensitive and specific IgG ELISA, to diagnose infection. Seroprevalence of H. pylori among all participants was 32.5%. This increased with age, from 16.7% for persons 20-29 years old to 56.9% for those greater than or equal to 70 years old. Age-adjusted prevalence was substantially higher among non-Hispanic blacks (52.7%) and Mexican Americans (61.6%) than among non-Hispanic whites (26.2%). After controlling for age and other associated factors, the odds ratios relative to non-Hispanic whites decreased for non-Hispanic blacks, from 3.9 (95% confidence interval [CI], 3.1-4.9) to 3.3 (95% CI, 2.6-4.2), and for Mexican Americans, from 6.3 (95% CI, 4.8-8.3) to 2.3 (95% CI, 1.6-3.5). The high prevalence of H. pylori infection among non-Hispanic blacks and Mexican Americans is partially explained by other factors associated with infection. JF - Journal of Infectious Diseases AU - Everhart, JE AU - Kruszon-Moran, D AU - Perez-Perez, GI AU - Tralka, T S AU - McQuillan, G AD - Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, USA Y1 - 2000/04// PY - 2000 DA - Apr 2000 SP - 1359 EP - 1363 VL - 181 IS - 4 SN - 0022-1899, 0022-1899 KW - USA KW - Microbiology Abstracts B: Bacteriology KW - Helicobacter pylori KW - Ethnic groups KW - J 02846:Gastrointestinal tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17895081?accountid=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=Seroprevalence+and+Ethnic+Differences+in+Helicobacter+pylori+Infection+among+Adults+in+the+United+States&rft.au=Everhart%2C+JE%3BKruszon-Moran%2C+D%3BPerez-Perez%2C+GI%3BTralka%2C+T+S%3BMcQuillan%2C+G&rft.aulast=Everhart&rft.aufirst=JE&rft.date=2000-04-01&rft.volume=181&rft.issue=4&rft.spage=1359&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Helicobacter pylori; Ethnic groups ER - TY - JOUR T1 - A mutant subtilisin E with enhanced thermostability AN - 17614848; 4750554 AB - A mutant subtilisin E with remarkably thermostability is reported. It is more active against the typical substrate s-AAPF-pna than the wild-type subtilisin E. The time required for getting 50% residual activity of Ser236Cys subtilisin E at 60 degree C in aqueous solution was approximately 80 min which is 4 times longer than that of wild-type subtilisin E. Similar to the wild-type subtilisin E, the amidase activity of Ser236Cys subtilisin E is dramatically reduced in the presence of dimethylformamide (DMF). JF - World Journal of Microbiology & Biotechnology AU - Yang, Y AU - Jiang, L AU - Yang, S AU - Zhu, L AU - Wu, Y AU - Li, Z AD - LPC, NIEHS/NH, P.O. Box 12233, Research Triangle Park, NC 27709, USA, yonghuayang@hotmail.com Y1 - 2000/04// PY - 2000 DA - Apr 2000 SP - 249 EP - 251 VL - 16 IS - 3 SN - 0959-3993, 0959-3993 KW - mutants KW - subtilisin E KW - Biotechnology and Bioengineering Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology; Agricultural and Environmental Biotechnology Abstracts KW - Temperature effects KW - Amidase KW - Heat resistance KW - Thermal stability KW - A 01006:Enzymes & cofactors KW - J 02728:Enzymes KW - W2 32310:Enzymes and cofactors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17614848?accountid=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=World+Journal+of+Microbiology+%26+Biotechnology&rft.atitle=A+mutant+subtilisin+E+with+enhanced+thermostability&rft.au=Yang%2C+Y%3BJiang%2C+L%3BYang%2C+S%3BZhu%2C+L%3BWu%2C+Y%3BLi%2C+Z&rft.aulast=Yang&rft.aufirst=Y&rft.date=2000-04-01&rft.volume=16&rft.issue=3&rft.spage=249&rft.isbn=&rft.btitle=&rft.title=World+Journal+of+Microbiology+%26+Biotechnology&rft.issn=09593993&rft_id=info:doi/10.1023%2FA%3A1008959825832 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Thermal stability; Heat resistance; Temperature effects; Amidase DO - http://dx.doi.org/10.1023/A:1008959825832 ER - TY - JOUR T1 - The Net Charge of the First 18 Residues of the Mature Sequence Affects Protein Translocation across the Cytoplasmic Membrane of Gram-Negative Bacteria AN - 17601021; 4701926 AB - This statistical study shows that in proteins of gram-negative bacteria exported by the Sec-dependent pathway, the first 14 to 18 residues of the mature sequences have the highest deviation between the observed and expected net charge distributions. Moreover, almost all sequences have either neutral or negative net charge in this region. This rule is restricted to gram-negative bacteria, since neither eukaryotic nor gram-positive bacterial exported proteins have this charge bias. Subsequent experiments performed with a series of Escherichia coli alkaline phosphatase mutants confirmed that this charge bias is associated with protein translocation across the cytoplasmic membrane. Two consecutive basic residues inhibit translocation effectively when placed within the first 14 residues of the mature protein but not when placed in positions 19 and 20. The sensitivity to arginine partially reappeared again 30 residues away from the signal sequence. These data provide new insight into the mechanism of protein export in gram-negative bacteria and lead to practical recommendations for successful secretion of hybrid proteins. JF - Journal of Bacteriology AU - Kajava, A V AU - Zolov, S N AU - Kalinen, A E AU - Nesmeyanova, MA AD - Center for Molecular Modeling CIT, NIH, Bldg. 12A Room 2011, Bethesda, MD 20892, kajava@helix.nih.gov Y1 - 2000/04// PY - 2000 DA - Apr 2000 SP - 2163 EP - 2169 VL - 182 IS - 8 SN - 0021-9193, 0021-9193 KW - Microbiology Abstracts B: Bacteriology KW - Protein transport KW - Alkaline phosphatase KW - Gram-negative bacteria KW - Escherichia coli KW - Surface charge KW - Translocation KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17601021?accountid=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=The+Net+Charge+of+the+First+18+Residues+of+the+Mature+Sequence+Affects+Protein+Translocation+across+the+Cytoplasmic+Membrane+of+Gram-Negative+Bacteria&rft.au=Kajava%2C+A+V%3BZolov%2C+S+N%3BKalinen%2C+A+E%3BNesmeyanova%2C+MA&rft.aulast=Kajava&rft.aufirst=A&rft.date=2000-04-01&rft.volume=182&rft.issue=8&rft.spage=2163&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.182.8.2163-2169.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Protein transport; Surface charge; Gram-negative bacteria; Alkaline phosphatase; Translocation DO - http://dx.doi.org/10.1128/JB.182.8.2163-2169.2000 ER - TY - JOUR T1 - The ATP-Cone: An Evolutionarily Mobile, ATP-Binding Regulatory Domain AN - 17591836; 4708143 AB - The crystal structure of the class I enzyme (NrdA) from E. coli revealed that this allosteric regulatory site maps to a distinct N-terminal region that is also conserved in the anaerobic class III enzyme (NrdD), but is lacking in the paralogous class IB enzyme (NrdE). In order to investigate the provenance of this N-terminal region, we undertook a systematic, iterative search of the non-redundant (NR) protein sequence database (National Center for Biotechnology Information, NIH, Bethesda) using the PSI-BLAST program with a profile-inclusion e-value cut-off of 0.01 and the conserved N-terminal domains from different ribonucleotide reductases as the queries. JF - Journal of Molecular Microbiology and Biotechnology AU - Aravind, L AU - Wolf, YI 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 - 2000/04// PY - 2000 DA - Apr 2000 SP - 191 EP - 194 VL - 2 IS - 2 SN - 1464-1801, 1464-1801 KW - amino acid sequence KW - NrdA protein KW - Microbiology Abstracts B: Bacteriology KW - Databases KW - Crystal structure KW - Escherichia coli KW - ATP KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17591836?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Microbiology+and+Biotechnology&rft.atitle=The+ATP-Cone%3A+An+Evolutionarily+Mobile%2C+ATP-Binding+Regulatory+Domain&rft.au=Aravind%2C+L%3BWolf%2C+YI%3BKoonin%2C+E+V&rft.aulast=Aravind&rft.aufirst=L&rft.date=2000-04-01&rft.volume=2&rft.issue=2&rft.spage=191&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Microbiology+and+Biotechnology&rft.issn=14641801&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; Crystal structure; Databases; ATP ER - TY - JOUR T1 - Hepatocarcinogenesis in Female Sprague-Dawley Rats following Discontinuous Treatment with 2,3,7,8-Tetrachlorodibenzo-p-dioxin AN - 17540325; 4716692 AB - In this study, we investigated the time course of promotion of tumors and putatively preneoplastic altered hepatic foci in the livers of diethylnitrosamine (DEN)-initiated female Sprague-Dawley rats. These rats had been treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) under different dosing regimens, but we used the same administered biweekly dose of 1.75 mu g/kg of body weight. Animals were treated continuously for up to 60 weeks, or continuously for 30 weeks, followed by cessation of treatment for up to 30 weeks. In addition, TCDD treatment in these groups was begun either 2 or 18 weeks after initiation with DEN. Liver tumors were only observed in animals after 60 weeks on the study and were increased by continuous TCDD treatment, relative to controls. The incidence of hepatocellular adenoma and carcinoma combined, in animals treated with TCDD for 30 weeks followed by no TCDD treatment for 30 weeks (17%), was lower than in animals receiving either TCDD (79%) or vehicle control (corn oil) alone (55%) for 60 weeks. The lower liver-tumor incidence after cessation of TCDD treatment paralleled time-dependent decreases in the volume fraction occupied by placental glutathione S-transferase-positive altered hepatic foci and the number of foci per unit volume, but not the mean focus volume that exhibited a time-dependent increase after cessation of TCDD treatment. Cessation of TCDD treatment led to reductions in liver TCDD levels, and these changes were reflected in a cessation of reduced body weight because of TCDD treatment. These data indicate that liver-tumor promotion by TCDD in female rats is dependent upon continuous exposure to TCDD, and that alterations in patterns of TCDD exposure can have significant effects on tumor incidence not reflected by standard measures of dioxin exposure. JF - Toxicological Sciences AU - Walker, N J AU - Tritscher, A M AU - Sills, R C AU - Lucier, G W AU - Portier, C J AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA Y1 - 2000/04// PY - 2000 DA - Apr 2000 SP - 330 EP - 337 VL - 54 IS - 2 SN - 1096-6080, 1096-6080 KW - rats KW - Toxicology Abstracts KW - Carcinogenesis KW - Liver KW - Diethylnitrosamine KW - TCDD KW - Tumors KW - Hepatocellular carcinoma KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17540325?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Hepatocarcinogenesis+in+Female+Sprague-Dawley+Rats+following+Discontinuous+Treatment+with+2%2C3%2C7%2C8-Tetrachlorodibenzo-p-dioxin&rft.au=Walker%2C+N+J%3BTritscher%2C+A+M%3BSills%2C+R+C%3BLucier%2C+G+W%3BPortier%2C+C+J&rft.aulast=Walker&rft.aufirst=N&rft.date=2000-04-01&rft.volume=54&rft.issue=2&rft.spage=330&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Liver; Carcinogenesis; Tumors; TCDD; Diethylnitrosamine; Hepatocellular carcinoma ER - TY - JOUR T1 - Studies on the Mechanisms of Arsenic-Induced Self Tolerance Developed in Liver Epithelial Cells through Continuous Low-Level Arsenite Exposure AN - 17540115; 4716710 AB - Arsenic (As) is a human carcinogen. Our prior work showed that chronic (>18 weeks) low level (500 nM) arsenite (As super(3+)) exposure induced malignant transformation in a rat liver epithelial cell line (TRL 1215). In these cells, metallothionein (MT) is hyper-expressible, a trait often linked to metal tolerance. Thus, this study examined whether the adverse effects of arsenicals and other metals were altered in these chronic arsenite-exposed (CAsE) cells. CAsE cells, which had been continuously exposed to 500 nM arsenite for 18 to 20 weeks, and control cells, were exposed to As super(3+), arsenate (As super(5+)), dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), antimony (Sb super(3+)), cadmium (Cd super(2+)), cisplatin (cis-Pt), and nickel (Ni super(2+)) for 24 h and cell viability was determined by metabolic integrity. The lethal concentration for 50% of exposed cells (LC sub(50)) for As super(3+) was 140 mu M in CAsE cells as compared to 26 mu M in control cells, a 5.4-fold increase in tolerance. CAsE cells were also very tolerant to the acute toxic effects of As super(5+) (LC sub(50) > 4000 mu M) compared to control (LC sub(50) = 180 mu M). The LC sub(50) for DMA was 4.4-fold higher in CAsE cells than in control cells, but the LC sub(50) for MMA was unchanged. There was a modest cross-tolerance to Sb super(3+), Cd super(2+), and cis-Pt in CAsE cells (LC sub(50) 1.5-2.0-fold higher) as compared to control. CAsE cells were very tolerant to Ni super(2+) (LC sub(50) > 8-fold higher). Culturing CAsE cells in As super(3+)-free medium for 5 weeks did not alter As super(3+) tolerance, implicating an irreversible phenotypic change. Cellular accumulation of As was 87% less in CAsE cells than control and the accumulated As was more readily eliminated. Although accumulating much less As, a greater portion was converted to DMA in CAsE cells. Altered glutathione (GSH) levels were not linked with As tolerance. A maximal induction of MT by Zn produced only a 2.5-fold increase in tolerance to As super(3+) in control cells. Cell lines derived from MT normal mice (MT+/+) were only slightly more resistant (1.6-fold) to As super(3+) than cells from MT null mice (MT-/-). These results show that CAsE cells acquire tolerance to As super(3+), As super(5+), and DMA. It appears that this self-tolerance is based primarily on reduced cellular disposition of the metalloid and is not accounted for by changes in GSH or MT. JF - Toxicological Sciences AU - Romach, E H AU - Zhao, C Q AU - Del Razo, LM AU - Cebrian, ME AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA Y1 - 2000/04// PY - 2000 DA - Apr 2000 SP - 500 EP - 508 VL - 54 IS - 2 SN - 1096-6080, 1096-6080 KW - tolerance mechanisms KW - arsenite KW - epithelial cells KW - Toxicology Abstracts KW - Arsenic KW - Liver KW - X 24162:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17540115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Studies+on+the+Mechanisms+of+Arsenic-Induced+Self+Tolerance+Developed+in+Liver+Epithelial+Cells+through+Continuous+Low-Level+Arsenite+Exposure&rft.au=Romach%2C+E+H%3BZhao%2C+C+Q%3BDel+Razo%2C+LM%3BCebrian%2C+ME%3BWaalkes%2C+M+P&rft.aulast=Romach&rft.aufirst=E&rft.date=2000-04-01&rft.volume=54&rft.issue=2&rft.spage=500&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Arsenic; Liver ER - TY - JOUR T1 - LacI mutation spectra following benzo[a]pyrene treatment of Big Blue super( registered ) mice AN - 17531907; 4718121 AB - The mutation spectrum of the lacI gene from the liver of C57B16 Big Blue super( registered ) transgenic mice treated with benzo[a]pyrene (B[a]P) has been compared with the spectrum of spontaneous mutations observed in the liver of untreated Big Blue super( registered ) mice. Mice were treated with B[a]P for 3 days followed by a partial hepatectomy one day after the last injection. Liver tissue was removed for analysis at hepatectomy and, again, 3 days later at the time of sacrifice. Earlier, we reported that the lacI mutant frequency in these B[a]P-treated mice was elevated in the liver both at the time of hepatectomy and at sacrifice; however, a statistically significant increase in the mutant frequency was observed only at sacrifice. In this study, the DNA sequence spectra of lacI mutations observed in the liver of B[a]P-treated Big Blue super( registered ) mice at hepatectomy and at time of sacrifice were compared with each other and with the spectrum of spontaneous liver mutations. No differences were observed between the two B [a]P-treatment spectra. However, mutation frequencies of both GC arrow right TA and GC arrow right CG at the time of hepatectomy and at sacrifice were significantly elevated compared with the spontaneous frequency of these same transversions. Also, the frequency of AT arrow right TA transversions was significantly higher than the spontaneous frequency at the time of hepatectomy but not at sacrifice. The frequency of all other classes of mutations scored was not significantly different from the frequency of these same events in the spontaneous spectra. These data support the view that B[a]P treatment results in the induction of GC arrow right TA and GC arrow right CG transversions within 1 day of the last injection and they provide insights regarding the relative roles of benzo[a]pyrene-7,8-diol-9,10-epoxide and radical cations of B[a]P in B [a]P-induced mutagenesis in vivo. Finally, these data provide evidence for B[a]P-induced mutagenesis under conditions where no statistical increase in mutant frequency could be shown. JF - Carcinogenesis AU - Shane, B S AU - de Boer, J AU - Watson, DE AU - Haseman, J K AU - Glickman, B W AU - Tindall, K R AD - Molecular Mutagenesis Group, Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA Y1 - 2000/04// PY - 2000 DA - Apr 2000 SP - 715 EP - 725 VL - 21 IS - 4 SN - 0143-3334, 0143-3334 KW - mice KW - mutation KW - LacI gene KW - lacI gene KW - Toxicology Abstracts; Genetics Abstracts KW - Mutagenicity KW - DNA KW - Liver KW - Benzo(a)pyrene KW - X 24190:Polycyclic hydrocarbons KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17531907?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=LacI+mutation+spectra+following+benzo%5Ba%5Dpyrene+treatment+of+Big+Blue+super%28+registered+%29+mice&rft.au=Shane%2C+B+S%3Bde+Boer%2C+J%3BWatson%2C+DE%3BHaseman%2C+J+K%3BGlickman%2C+B+W%3BTindall%2C+K+R&rft.aulast=Shane&rft.aufirst=B&rft.date=2000-04-01&rft.volume=21&rft.issue=4&rft.spage=715&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mutagenicity; Benzo(a)pyrene; Liver; DNA ER - TY - JOUR T1 - pTAR-Encoded Proteins in Plasmid Partitioning AN - 17526480; 4701909 AB - Partition cassettes, essential for the segregational stability of low-copy-number bacterial plasmids, typically encode two autoregulated proteins and an adjacent cis-acting centromere analog to which one or perhaps both proteins bind. The diminutive partition region of pTAR of Agrobacterium spp. was reported to be exceptional, encoding only a single protein, ParA (D. R. Gallie and C. I. Kado, J. Mol. Biol. 193:465-478, 1987). However resequencing of the region revealed two small downstream genes parB and orf-84, of which only parB was found to be essential for partitioning in A. tumefaciens. Purified ParA exhibited a weak ATPase activity that was modestly increased by nonspecific DNA. ParB bound in vitro to repeated sequences present in a region, parS, that possesses centromere and operator functions and within which we identified the primary transcription start site by primer extension. In certain respects the Par proteins behave normally in the foreign host Escherichia coli. In E. coli, as in A. tumefaciens, ParB repressed the partition operon; ParA, inactive alone, augmented this repression. Functional similarities between the partition system of pTAR and those of other plasmids and bacteria are prominent, despite differences in size, organization, and amino acid sequence. JF - Journal of Bacteriology AU - Kalnin, K AU - Stegalkin, S AU - Yarmolinsky, M AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, 37 Convent Dr., Bethesda, MD 20892-4255, myarmo@helix.nih.gov Y1 - 2000/04// PY - 2000 DA - Apr 2000 SP - 1889 EP - 1894 VL - 182 IS - 7 SN - 0021-9193, 0021-9193 KW - ParA protein KW - ParB protein KW - Partition cassettes KW - orf-84 gene KW - parB gene KW - parS gene KW - plasmid pTAR KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Agrobacterium KW - Adenosinetriphosphatase KW - J 02760:Plasmids KW - G 07203:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17526480?accountid=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=pTAR-Encoded+Proteins+in+Plasmid+Partitioning&rft.au=Kalnin%2C+K%3BStegalkin%2C+S%3BYarmolinsky%2C+M&rft.aulast=Kalnin&rft.aufirst=K&rft.date=2000-04-01&rft.volume=182&rft.issue=7&rft.spage=1889&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.182.7.1889-1894.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Agrobacterium; Adenosinetriphosphatase DO - http://dx.doi.org/10.1128/JB.182.7.1889-1894.2000 ER - TY - JOUR T1 - Creating molecular clues to uncover gene function AN - 17525980; 4705207 AB - Given a crime scene with scattered bodies and several suspects - but no smoking gun - the keen detective establishes a time line detailing who was where when. The indelible imprint each of the suspects makes on the environment through fingerprints, footprints, and the loss of hair, skin cells, and the like along the way can be important clues in such a reconstruction. The cell and molecular pathologist can have similar problems to tackle, though generally not related to homicide, but rather related to distinguishing cause and effect with respect to gene control in disease pathology. The "crime scene" involves genes that are activated or repressed, and numerous candidate regulatory factors that may be involved: the difficulty lies in determining responsibility. Now, van Steensel and Henikoff report a new approach to molecular forensics, whereby the history of the association of a particular regulatory factor with chromatin and chromosomes can be detected by linking a prokaryotic methyl-transferase to the regulatory factor of interest. The beauty of this method is that DNA is efficiently modified by methylation only at sites where the regulatory factor is (or has been) closely involved in chromatin or chromosome function. It can thus provide a "methylation fingerprint" from which the investigator can reconstruct molecular events. JF - Nature Biotechnology AU - Wolffe, A P AU - Leblanc, B P AD - Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-5431, USA, awlme@helix.nih.gov Y1 - 2000/04// PY - 2000 DA - Apr 2000 SP - 379 EP - 380 VL - 18 IS - 4 SN - 1087-0156, 1087-0156 KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts KW - DNA fingerprinting KW - Chromosomes KW - Chromatin KW - Reviews KW - DNA methylation KW - N 14100:Reviews KW - W3 33243:Molecular methods KW - W2 32000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17525980?accountid=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=Creating+molecular+clues+to+uncover+gene+function&rft.au=Wolffe%2C+A+P%3BLeblanc%2C+B+P&rft.aulast=Wolffe&rft.aufirst=A&rft.date=2000-04-01&rft.volume=18&rft.issue=4&rft.spage=379&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2F74426 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Chromatin; Chromosomes; DNA methylation; DNA fingerprinting DO - http://dx.doi.org/10.1038/74426 ER - TY - JOUR T1 - Frequent Codon 12 Ki-ras Mutations in Mouse Skin Tumors Initiated by N-methyl-N'-nitro-N-nitrosoguanidine and Promoted by Mezerein AN - 17518099; 4698723 AB - The skin tumor initiators N-methy-N'-nitrosoguanidine (MNNG) and 7,12-dimethylbenz[a]anthracene (DMBA) differ in effectiveness when tumor formation is promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA). Even at high doses, MNNG is less effective, producing fewer benign and malignant tumors with a longer latent period. In DMBA-initiated skin, 10 wk of TPA promotion produced a maximal tumor response. With MNNG, 20 wk of TPA promotion was required, producing nearly four times as many papillomas as 10 wk of promotion. Promotion of MNNG-initiated skin with mezerein induced the appearance of very rapidly-growing papillomas within 5 wk, 3 wk earlier than the first TPA-promoted papillomas. Thus, MNNG may induce a novel mutation resulting in a population of initiated cells that respond especially well to mezerein. Since ras mutations are common in experimental tumors in many tissues, we determined the frequency of activating mutations in the Ha-ras, Ki-ras, and N-ras oncogenes. Activating Ha-ras mutations were present in essentially all DMBA-initiated tumors and about 70% of MNNG-initiated tumors. No N-ras mutations were found in tumors lacking other ras mutations. Surprisingly, 41% of the papillomas arising in the first 11 wk in MNNG-initiated, mezerein-promoted mice bore mutations in codon 12 of the Ki-ras oncogene. Activating Ki-ras mutations were also found in more than 60% of squamous cell carcinomas and 40% of keratoacanthomas. Although mutations in Ha-ras are frequently detected in mouse skin tumors, mutations in Ki-ras are rare. This is the first report of mutated Ki-ras in skin tumors from mice initiated by MNNG. JF - Molecular Carcinogenesis AU - Rehman, I AU - Lowry, D T AU - Adams, C AU - Abdel-Fattah, R AU - Holly, A AU - Yuspa, SH AU - Hennings, H AD - National Institutes of Health, National Cancer Institute, Building 37, Room 3B12, 37 Convent Drive MSC4255, Bethesda, MD 20892-4255, USA Y1 - 2000/04// PY - 2000 DA - Apr 2000 SP - 298 EP - 307 VL - 27 IS - 4 SN - 0899-1987, 0899-1987 KW - mice KW - Ha-ras gene KW - K-ras gene KW - Ki-ras gene KW - N-Methyl-N'-nitro-N-nitrosoguanidine KW - mezerein KW - Toxicology Abstracts; Oncogenes & Growth Factors Abstracts KW - Ras protein KW - Oncogenes KW - Skin KW - Tumorigenesis KW - Tumors KW - Papilloma KW - X 24200:Nitrosamines & related compounds KW - B 26130:Ras and Ras related oncogenes (Rho/Rac/Ral) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17518099?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Carcinogenesis&rft.atitle=Frequent+Codon+12+Ki-ras+Mutations+in+Mouse+Skin+Tumors+Initiated+by+N-methyl-N%27-nitro-N-nitrosoguanidine+and+Promoted+by+Mezerein&rft.au=Rehman%2C+I%3BLowry%2C+D+T%3BAdams%2C+C%3BAbdel-Fattah%2C+R%3BHolly%2C+A%3BYuspa%2C+SH%3BHennings%2C+H&rft.aulast=Rehman&rft.aufirst=I&rft.date=2000-04-01&rft.volume=27&rft.issue=4&rft.spage=298&rft.isbn=&rft.btitle=&rft.title=Molecular+Carcinogenesis&rft.issn=08991987&rft_id=info:doi/10.1002%2F%28SICI%291098-2744%28200004%2927%3A43.0.CO%3B2-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Ras protein; Skin; Tumorigenesis; N-Methyl-N'-nitro-N-nitrosoguanidine; Oncogenes; Tumors; Papilloma DO - http://dx.doi.org/10.1002/(SICI)1098-2744(200004)27:4<298::AID-MC8>3.0.CO;2-4 ER - TY - JOUR T1 - Transcriptional silencing in bacteria AN - 17516503; 4703757 AB - Transcriptional silencing and repression are modes of negative control of gene expression that differ in specificity. Repressors, when present at promoter-specific binding sites, interfere locally with RNA polymerase function. Silencing proteins act by covering a continuous region of DNA, compete with a broader spectrum of proteins and are non-specific with respect to the promoters affected. Studies of transcriptional silencing promise an entree to relatively unexplored areas of prokaryotic biology. JF - Current Opinion in Microbiology AU - Yarmolinsky, M AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA, myarmo@helix.nih.gov Y1 - 2000/04// PY - 2000 DA - Apr 2000 SP - 138 EP - 143 VL - 3 IS - 2 SN - 1369-5274, 1369-5274 KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Bacteria KW - DNA-directed RNA polymerase KW - Reviews KW - Gene regulation KW - Gene silencing KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17516503?accountid=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=Current+Opinion+in+Microbiology&rft.atitle=Transcriptional+silencing+in+bacteria&rft.au=Yarmolinsky%2C+M&rft.aulast=Yarmolinsky&rft.aufirst=M&rft.date=2000-04-01&rft.volume=3&rft.issue=2&rft.spage=138&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Microbiology&rft.issn=13695274&rft_id=info:doi/10.1016%2FS1369-5274%2800%2900065-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene regulation; Gene silencing; DNA-directed RNA polymerase; Bacteria; Reviews DO - http://dx.doi.org/10.1016/S1369-5274(00)00065-5 ER - TY - JOUR T1 - Clostridium difficile recombinant toxin A repeating units as a carrier protein for conjugate vaccines: studies of pneumococcal type 14, Escherichia coli K1, and Shigella flexneri type 2a polysaccharides in mice AN - 17515281; 4704190 AB - Unlike the native protein, a nontoxic peptide (repeating unit of the native toxin designated rARU) from Clostridium difficile toxin A (CDTA) afforded an antigen that could be bound covalently to the surface polysaccharides of pneumococcus type 14, Shigella flexneri type 2a, and Escherichia coli K1. The yields of these polysaccharide-protein conjugates were significantly increased by prior treatment of rARU with succinic anhydride. Conjugates, prepared with rARU or succinylated (rARUsucc), were administered to mice by a clinically relevant dosage and immunization scheme. All conjugates elicited high levels of serum immunoglobulin G both to the polysaccharides and to CDTA. Conjugate-induced anti-CDTA had neutralizing activity in vitro and protected mice challenged with CDTA, similar to the rARU alone. Conjugates prepared with succinylated rARU, therefore, have potential for serving both as effective carrier proteins for polysaccharides and for preventing enteric disease caused by C. difficile. JF - Infection and Immunity AU - Pavliakova, D AU - Moncrief, J S AU - Lyerly, D M AU - Schiffman, G AU - Bryla, DA AU - Robbins, J B AU - Schneerson, R AD - National Institutes of Health, Building 6, Room 424, Bethesda, MD 20892, USA, schneerr@exchange.nih.gov Y1 - 2000/04// PY - 2000 DA - Apr 2000 SP - 2161 EP - 2166 VL - 68 IS - 4 SN - 0019-9567, 0019-9567 KW - conjugates KW - serum KW - recombinants KW - rARU protein KW - toxin A KW - Microbiology Abstracts B: Bacteriology KW - Antibodies KW - Streptococcus pneumoniae KW - Antigens KW - Shigella flexneri KW - Escherichia coli KW - Clostridium difficile KW - Vaccines KW - Polysaccharides KW - Immunization KW - Immunoglobulins KW - J 02834:Vaccination and immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17515281?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Clostridium+difficile+recombinant+toxin+A+repeating+units+as+a+carrier+protein+for+conjugate+vaccines%3A+studies+of+pneumococcal+type+14%2C+Escherichia+coli+K1%2C+and+Shigella+flexneri+type+2a+polysaccharides+in+mice&rft.au=Pavliakova%2C+D%3BMoncrief%2C+J+S%3BLyerly%2C+D+M%3BSchiffman%2C+G%3BBryla%2C+DA%3BRobbins%2C+J+B%3BSchneerson%2C+R&rft.aulast=Pavliakova&rft.aufirst=D&rft.date=2000-04-01&rft.volume=68&rft.issue=4&rft.spage=2161&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.68.4.2161-2166.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus pneumoniae; Clostridium difficile; Escherichia coli; Shigella flexneri; Vaccines; Antigens; Immunization; Immunoglobulins; Polysaccharides; Antibodies DO - http://dx.doi.org/10.1128/IAI.68.4.2161-2166.2000 ER - TY - JOUR T1 - The biogenesis and assembly of bacterial membrane proteins AN - 17514714; 4703768 AB - Bacterial proteins in the inner and outer membranes differ dramatically in their architecture. Although both types of proteins are transported across the inner membrane through a common pore, recent studies have identified distinct factors that target them to transport sites and catalyze proper folding. JF - Current Opinion in Microbiology AU - Bernstein, H D AD - Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 10, Room 9D-20, 10 Center Drive, Bethesda, MD 20892-1810, USA, harris_bernstein@nih.gov Y1 - 2000/04// PY - 2000 DA - Apr 2000 SP - 203 EP - 209 VL - 3 IS - 2 SN - 1369-5274, 1369-5274 KW - Microbiology Abstracts B: Bacteriology KW - Protein biosynthesis KW - Inner membranes KW - Outer membranes KW - Assembly KW - Membrane proteins KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17514714?accountid=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=Current+Opinion+in+Microbiology&rft.atitle=The+biogenesis+and+assembly+of+bacterial+membrane+proteins&rft.au=Bernstein%2C+H+D&rft.aulast=Bernstein&rft.aufirst=H&rft.date=2000-04-01&rft.volume=3&rft.issue=2&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Microbiology&rft.issn=13695274&rft_id=info:doi/10.1016%2FS1369-5274%2800%2900076-X LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Membrane proteins; Assembly; Protein biosynthesis; Inner membranes; Outer membranes DO - http://dx.doi.org/10.1016/S1369-5274(00)00076-X ER - TY - JOUR T1 - Ultrastructural analysis of developmental events in Chlamydia pneumoniae-infected cells AN - 17513102; 4704224 AB - Chlamydia pneumoniae is an obligate intracellular parasite with a developmental cycle believed to be common to all members of the genus Chlamydia. We present a detailed description based on transmission and scanning electron microscopy of temporal events and inclusion structures throughout the C. pneumoniae AR-39 developmental cycle. JF - Infection and Immunity AU - Wolf, K AU - Fischer, E AU - Hackstadt, T AD - Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT 59840, USA, ted_hackstadt@nih.gov Y1 - 2000/04// PY - 2000 DA - Apr 2000 SP - 2379 EP - 2385 VL - 68 IS - 4 SN - 0019-9567, 0019-9567 KW - growth stage KW - Microbiology Abstracts B: Bacteriology KW - Scanning electron microscopy KW - Respiratory tract diseases KW - HeLa cells KW - Transmission electron microscopy KW - Chlamydia pneumoniae KW - Intracellular levels KW - Life cycle KW - Reticulate bodies KW - Elementary bodies KW - J 02721:Cell cycle, morphology and motility UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17513102?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Ultrastructural+analysis+of+developmental+events+in+Chlamydia+pneumoniae-infected+cells&rft.au=Wolf%2C+K%3BFischer%2C+E%3BHackstadt%2C+T&rft.aulast=Wolf&rft.aufirst=K&rft.date=2000-04-01&rft.volume=68&rft.issue=4&rft.spage=2379&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.68.4.2379-2385.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia pneumoniae; Respiratory tract diseases; Life cycle; Reticulate bodies; Elementary bodies; HeLa cells; Intracellular levels; Transmission electron microscopy; Scanning electron microscopy DO - http://dx.doi.org/10.1128/IAI.68.4.2379-2385.2000 ER - TY - JOUR T1 - Identification of a MHC Class II-Restricted Human gp100 Epitope Using DR4-IE Transgenic Mice AN - 17511193; 4696917 AB - CD4 super(+) T cells play a central role in the induction and persistence of CD8 super(+) T cells in several models of autoimmune and infectious disease. To improve the efficacy of a synthetic peptide vaccine based on the self-Ag, gp100, we sought to provide Ag-specific T cell help. To identify a gp100 epitope restricted by the MHC class II allele with the highest prevalence in patients with malignant melanoma (HLA-DRB1*0401), we immunized mice transgenic for a chimeric human-mouse class II molecule (DR4-IE) with recombinant human gp100 protein. We then searched for the induction of CD4 super(+) T cell reactivity using candidate epitopes predicted to bind to DRB1*0401 by a computer-assisted algorithm. Of the 21 peptides forecasted to bind most avidly, murine CD4 super(+) T cells recognized the epitope (human gp100 sub(44-59), WNRQLYPEWTEAQRLD) that was predicted to bind best. Interestingly, the mouse helper T cells also recognized human melanoma cells expressing DRB1*0401. To evaluate whether human CD4 super(+) T cells could be generated from the peripheral blood of patients with melanoma, we used the synthetic peptide h-gp100 sub(44-59) to sensitize lymphocytes ex vivo. Resultant human CD4 super(+) T cells specifically recognized melanoma, as measured by tumor cytolysis and the specific release of cytokines and chemokines. HLA class II transgenic mice may be useful in the identification of helper epitopes derived from Ags of potentially great clinical utility. JF - Journal of Immunology AU - Touloukian, CE AU - Leitner, W W AU - Topalian, S L AU - Li, Y F AU - Robbins, P F AU - Rosenberg, SA AU - Restifo, N P AD - National Cancer Institute, Building 10, Room 2B42, Bethesda, MD 20892-1502, USA, restifo@nih.gov Y1 - 2000/04/01/ PY - 2000 DA - 2000 Apr 01 SP - 3535 EP - 3542 VL - 164 IS - 7 SN - 0022-1767, 0022-1767 KW - class II molecules KW - immunology KW - glycoprotein gp100 KW - synthetic peptides KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Major histocompatibility complex KW - Vaccines KW - Transgenic mice KW - Melanoma KW - W3 33056:Animal models of human disease KW - F 06756:Function KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17511193?accountid=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+Immunology&rft.atitle=Identification+of+a+MHC+Class+II-Restricted+Human+gp100+Epitope+Using+DR4-IE+Transgenic+Mice&rft.au=Touloukian%2C+CE%3BLeitner%2C+W+W%3BTopalian%2C+S+L%3BLi%2C+Y+F%3BRobbins%2C+P+F%3BRosenberg%2C+SA%3BRestifo%2C+N+P&rft.aulast=Touloukian&rft.aufirst=CE&rft.date=2000-04-01&rft.volume=164&rft.issue=7&rft.spage=3535&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&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 - Melanoma; Vaccines; Transgenic mice; Major histocompatibility complex ER - TY - JOUR T1 - Simulating the proposed reintroduction of the European beaver (Castor fiber) to Scotland AN - 17506708; 4696652 AB - We developed a spatially explicit model for investigating the proposed reintroduction of the European beaver to Scotland. The model simulates the births and deaths of individuals and their dispersal between habitat patches, using a habitat template created from an existing land cover map which was derived from aerial photography. Uncertainty in model parameter estimates was accounted for by using high, medium and low values for each, derived from the literature. We used the model to predict the result of different release protocols and compared the predictions to those generated by application of a population viability analysis package, Vortex. Predictions of the two approaches were similar. We showed that predictions were particularly sensitive to the levels of the demographic parameters and that, providing these were set to at least medium levels, reintroduction sizes of 20 animals led to high persistence and population increase. We describe the potential use of simulation modelling at all stages in the reintroduction process. JF - Biological Conservation AU - South, A AU - Rushton, S AU - Macdonald, D AD - Centre for Land Use and Water Resources Research, University of Newcastle, Porter Building, Newcastle upon Tyne NEI 7RU, UK, a.b.south@ncl.ac.uk Y1 - 2000/04// PY - 2000 DA - Apr 2000 SP - 103 EP - 116 VL - 93 IS - 1 SN - 0006-3207, 0006-3207 KW - European Beaver KW - British Isles, Scotland KW - Ecology Abstracts KW - Birth KW - Reintroduction KW - Death KW - Castor fiber KW - Dispersal KW - Models KW - D 04001:Methodology - general UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17506708?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+Conservation&rft.atitle=Simulating+the+proposed+reintroduction+of+the+European+beaver+%28Castor+fiber%29+to+Scotland&rft.au=South%2C+A%3BRushton%2C+S%3BMacdonald%2C+D&rft.aulast=South&rft.aufirst=A&rft.date=2000-04-01&rft.volume=93&rft.issue=1&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Biological+Conservation&rft.issn=00063207&rft_id=info:doi/10.1016%2FS0006-3207%2899%2900072-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Castor fiber; Reintroduction; Models; Birth; Death; Dispersal DO - http://dx.doi.org/10.1016/S0006-3207(99)00072-5 ER - TY - JOUR T1 - beta-amyloid peptide-induced death of PC 12 cells and cerebellar granule cell neurons is inhibited by long-term lithium treatment. AN - 71027851; 10762662 AB - Treatment of rat pheochromocytoma cells (PC 12) cells with beta-amyloid peptide-(1-42) for 24 h induced a concentration-dependent decrease in cellular redox activity in the dose range of 1 to 20 microM. These effects were markedly attenuated by pretreatment with 2 mM LiCl for 7 days, whereas 1-day pretreatment was ineffective. Measurements of live and dead cells by double-staining with fluorescein diacetate and propidium iodide, respectively revealed that protracted lithium pretreatment attenuated PC 12 cell death induced by beta-amyloid-(1-42) and cerebellar granule cell death induced by beta-amyloid-(25-35). Preceding PC 12 cell death, beta-amyloid peptide elicited a slight decrease in protein levels of Bcl-2. Conversely, 7-day pretreatment with lithium resulted in an approximate doubling of Bcl-2 protein levels in cells treated with or without beta-amyloid peptide-(1-42). Lithium-induced Bcl-2 upregulation was temporally associated with the cytoprotective effects of this drug. Thus, lithium protection against beta-amyloid peptide neurotoxicity might involve Bcl-2 overexpression, and lithium treatment for Alzheimer's disease should be reexamined. JF - European journal of pharmacology AU - Wei, H AU - Leeds, P R AU - Qian, Y AU - Wei, W AU - Chen, R AU - Chuang, D AD - Section on Molecular Neurobiology, Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1272, USA. Y1 - 2000/03/31/ PY - 2000 DA - 2000 Mar 31 SP - 117 EP - 123 VL - 392 IS - 3 SN - 0014-2999, 0014-2999 KW - Amyloid beta-Peptides KW - 0 KW - Peptide Fragments KW - Proto-Oncogene Proteins c-bcl-2 KW - Tetrazolium Salts KW - Thiazoles KW - amyloid beta-protein (1-42) KW - amyloid beta-protein (25-35) KW - thiazolyl blue KW - EUY85H477I KW - Lithium Chloride KW - G4962QA067 KW - Index Medicus KW - Animals KW - Oxidation-Reduction -- drug effects KW - Dose-Response Relationship, Drug KW - Tetrazolium Salts -- metabolism KW - Rats KW - Cerebellum -- cytology KW - Rats, Sprague-Dawley KW - Cell Survival -- drug effects KW - Thiazoles -- metabolism KW - Cells, Cultured KW - Proto-Oncogene Proteins c-bcl-2 -- drug effects KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - Time Factors KW - PC12 Cells KW - Neurons -- drug effects KW - Peptide Fragments -- pharmacology KW - Neurons -- cytology KW - Amyloid beta-Peptides -- pharmacology KW - Lithium Chloride -- pharmacology KW - Cell Death -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71027851?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+pharmacology&rft.atitle=beta-amyloid+peptide-induced+death+of+PC+12+cells+and+cerebellar+granule+cell+neurons+is+inhibited+by+long-term+lithium+treatment.&rft.au=Wei%2C+H%3BLeeds%2C+P+R%3BQian%2C+Y%3BWei%2C+W%3BChen%2C+R%3BChuang%2C+D&rft.aulast=Wei&rft.aufirst=H&rft.date=2000-03-31&rft.volume=392&rft.issue=3&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-17 N1 - Date created - 2000-05-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Visualization of two binding sites for the Escherichia coli UmuD'(2)C complex (DNA pol V) on RecA-ssDNA filaments. AN - 71001431; 10731413 AB - The heterotrimeric UmuD'(2)C complex of Escherichia coli has recently been shown to possess intrinsic DNA polymerase activity (DNA pol V) that facilitates error-prone translesion DNA synthesis (SOS mutagenesis). When overexpressed in vivo, UmuD'(2)C also inhibits homologous recombination. In both activities, UmuD'(2)C interacts with RecA nucleoprotein filaments. To examine the biochemical and structural basis of these reactions, we have analyzed the ability of the UmuD'(2)C complex to bind to RecA-ssDNA filaments in vitro. As estimated by a gel retardation assay, binding saturates at a stoichiometry of approximately one complex per two RecA monomers. Visualized by cryo-electron microscopy under these conditions, UmuD'(2)C is seen to bind uniformly along the filaments, such that the complexes are completely submerged in the deep helical groove. This mode of binding would impede access to DNA in a RecA filament, thus explaining the ability of UmuD'(2)C to inhibit homologous recombination. At sub-saturating binding, the distribution of UmuD'(2)C complexes along RecA-ssDNA filaments was characterized by immuno-gold labelling with anti-UmuC antibodies. These data revealed preferential binding at filament ends (most likely, at one end). End-specific binding is consistent with genetic models whereby such binding positions the UmuD'(2)C complex (pol V) appropriately for its role in SOS mutagenesis. JF - Journal of molecular biology AU - Frank, E G AU - Cheng, N AU - Do, C C AU - Cerritelli, M E AU - Bruck, I AU - Goodman, M F AU - Egelman, E H AU - Woodgate, R AU - Steven, A C AD - Section on DNA Replication Repair, National Institute of Child Health and Human Development, Bethesda, MD, 20892-2725, USA. Y1 - 2000/03/31/ PY - 2000 DA - 2000 Mar 31 SP - 585 EP - 597 VL - 297 IS - 3 SN - 0022-2836, 0022-2836 KW - Biopolymers KW - 0 KW - DNA, Single-Stranded KW - DNA-Binding Proteins KW - Escherichia coli Proteins KW - Rec A Recombinases KW - EC 2.7.7.- KW - DNA polymerase V, E coli KW - EC 2.7.7.7 KW - DNA-Directed DNA Polymerase KW - Index Medicus KW - Biopolymers -- chemistry KW - Biopolymers -- metabolism KW - DNA-Binding Proteins -- ultrastructure KW - Models, Molecular KW - Models, Biological KW - Protein Binding KW - Binding Sites KW - DNA Repair -- genetics KW - SOS Response (Genetics) -- genetics KW - Recombination, Genetic -- genetics KW - Cryoelectron Microscopy KW - Microscopy, Immunoelectron KW - DNA-Binding Proteins -- metabolism KW - DNA, Single-Stranded -- metabolism KW - Rec A Recombinases -- ultrastructure KW - DNA, Single-Stranded -- genetics KW - DNA, Single-Stranded -- ultrastructure KW - DNA-Directed DNA Polymerase -- ultrastructure KW - Escherichia coli -- genetics KW - Rec A Recombinases -- metabolism KW - Escherichia coli -- enzymology KW - DNA-Directed DNA Polymerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71001431?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aabiglobal&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Review+of+International+Studies&rft.atitle=The+politics+of+numbers%3A+the+normative+agendas+of+global+benchmarking&rft.au=BROOME%2C+ANDR%C3%89%3BQUIRK%2C+JOEL&rft.aulast=BROOME&rft.aufirst=ANDR%C3%89&rft.date=2015-12-01&rft.volume=41&rft.issue=5&rft.spage=813&rft.isbn=&rft.btitle=&rft.title=Review+of+International+Studies&rft.issn=02602105&rft_id=info:doi/10.1017%2FS0260210515000339 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-01 N1 - Date created - 2000-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Visualization of Two Binding Sites for the Escherichia coli UmuD'C Complex (DNA pol V) on RecA-ssDNA Filaments AN - 17525067; 4709448 AB - The heterotrimeric UmuD' sub(2)C complex of Escherichia coli has recently been shown to possess intrinsic DNA polymerase activity (DNA pol V) that facilitates error-prone translesion DNA synthesis (SOS mutagenesis). When overexpressed in vivo, UmuD' sub(2)C also inhibits homologous recombination. In both activities, UmuD' sub(2)C interacts with RecA nucleoprotein filaments. To examine the biochemical and structural basis of these reactions, we have analyzed the ability of the UmuD' sub(2)C complex to bind to RecA-ssDNA filaments in vitro. As estimated by a gel retardation assay, binding saturates at a stoichiometry of approximately one complex per two RecA monomers. Visualized by cryo-electron microscopy under these conditions, UmuD' sub(2)C is seen to bind uniformly along the filaments, such that the complexes are completely submerged in the deep helical groove. This mode of binding would impede access to DNA in a RecA filament, thus explaining the ability of UmuD' sub(2)C to inhibit homologous recombination. At sub-saturating binding, the distribution of UmuD' sub(2)C complexes along RecA-ssDNA filaments was characterized by immuno-gold labelling with anti-UmuC antibodies. These data revealed preferential binding at filament ends (most likely, at one end). End-specific binding is consistent with genetic models whereby such binding positions the UmuD' sub(2)C complex (pol V) appropriately for its role in SOS mutagenesis. JF - Journal of Molecular Biology AU - Frank, E G AU - Cheng, N AU - Do, C C AU - Cerritelli, ME AU - Bruck, I AU - Goodman, M F AU - Egelman, E H AU - Woodgate, R AU - Steven, A C AD - Section on DNA Replication Repair, and Mutagenesis, National Institute of Child Health and Human Development, Bethesda, 20892-2725, MD, USA Y1 - 2000/03/31/ PY - 2000 DA - 2000 Mar 31 SP - 585 EP - 597 PB - Academic Press VL - 297 IS - 3 SN - 0022-2836, 0022-2836 KW - SOS mutagenesis KW - SOS response KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Recombination KW - DNA-directed DNA polymerase KW - Escherichia coli KW - RecA protein KW - J 02728:Enzymes KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17525067?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Visualization+of+Two+Binding+Sites+for+the+Escherichia+coli+UmuD%27C+Complex+%28DNA+pol+V%29+on+RecA-ssDNA+Filaments&rft.au=Frank%2C+E+G%3BCheng%2C+N%3BDo%2C+C+C%3BCerritelli%2C+ME%3BBruck%2C+I%3BGoodman%2C+M+F%3BEgelman%2C+E+H%3BWoodgate%2C+R%3BSteven%2C+A+C&rft.aulast=Frank&rft.aufirst=E&rft.date=2000-03-31&rft.volume=297&rft.issue=3&rft.spage=585&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1006%2Fjmbi.2000.3591 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; RecA protein; DNA-directed DNA polymerase; Recombination DO - http://dx.doi.org/10.1006/jmbi.2000.3591 ER - TY - JOUR T1 - DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation. AN - 71039713; 10761921 AB - Cancer susceptibility genes have been classified into two groups: gatekeepers and caretakers. Gatekeepers are genes that control cell proliferation and death, whereas caretakers are DNA repair genes whose inactivation leads to genetic instability. Abrogation of both caretaker and gatekeeper function markedly increases cancer susceptibility. Although the importance of Ku80 in DNA double-strand break repair is well established, neither Ku80 nor other components of the non-homologous end-joining pathway are known to have a caretaker role in maintaining genomic stability. Here we show that mouse cells deficient for Ku80 display a marked increase in chromosomal aberrations, including breakage, translocations and aneuploidy. Despite the observed chromosome instabilities, Ku80-/- mice have only a slightly earlier onset of cancer. Loss of p53 synergizes with Ku80 to promote tumorigenesis such that all Ku80-/- p53-/- mice succumb to disseminated pro-B-cell lymphoma before three months of age. Tumours result from a specific set of chromosomal translocations and gene amplifications involving IgH and c-Myc, reminiscent of Burkitt's lymphoma. We conclude that Ku80 is a caretaker gene that maintains the integrity of the genome by a mechanism involving the suppression of chromosomal rearrangements. JF - Nature AU - Difilippantonio, M J AU - Zhu, J AU - Chen, H T AU - Meffre, E AU - Nussenzweig, M C AU - Max, E E AU - Ried, T AU - Nussenzweig, A AD - Genetics Department, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/03/30/ PY - 2000 DA - 2000 Mar 30 SP - 510 EP - 514 VL - 404 IS - 6777 SN - 0028-0836, 0028-0836 KW - Antigens, Nuclear KW - 0 KW - DNA-Binding Proteins KW - Nuclear Proteins KW - DNA KW - 9007-49-2 KW - DNA Helicases KW - EC 3.6.4.- KW - XRCC5 protein, human KW - EC 3.6.4.12 KW - Xrcc6 protein, human KW - Xrcc6 protein, mouse KW - Ku Autoantigen KW - EC 4.2.99.- KW - Index Medicus KW - Karyotyping KW - Animals KW - Gamma Rays KW - DNA Damage KW - Mice KW - Translocation, Genetic KW - Mutagenesis KW - Cloning, Molecular KW - Genes, p53 KW - Lymphoma -- genetics KW - DNA -- radiation effects KW - Cell Line KW - Female KW - Male KW - Nuclear Proteins -- deficiency KW - Nuclear Proteins -- genetics KW - DNA Repair KW - DNA-Binding Proteins -- deficiency KW - DNA-Binding Proteins -- genetics KW - Chromosome Aberrations KW - DNA-Binding Proteins -- physiology KW - Nuclear Proteins -- physiology KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71039713?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=DNA+repair+protein+Ku80+suppresses+chromosomal+aberrations+and+malignant+transformation.&rft.au=Difilippantonio%2C+M+J%3BZhu%2C+J%3BChen%2C+H+T%3BMeffre%2C+E%3BNussenzweig%2C+M+C%3BMax%2C+E+E%3BRied%2C+T%3BNussenzweig%2C+A&rft.aulast=Difilippantonio&rft.aufirst=M&rft.date=2000-03-30&rft.volume=404&rft.issue=6777&rft.spage=510&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-21 N1 - Date created - 2000-04-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Nature. 2000 Apr 20;404(6780):823-5 [10786775] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Infectious cDNA clones of Langat tick-borne flavivirus that differ from their parent in peripheral neurovirulence. AN - 70963905; 10725214 AB - Tick-borne flavivirus strain Langat TP21 (LGT TP21) recovered from ticks, is naturally attenuated for humans but retains demonstrable neurovirulence and peripheral virulence ("neuroinvasiveness") for mice. Previously a mutant, strain E5, less virulent for mice was derived from LGT TP21. Multiple attempts to prepare a full-length infectious TP21 cDNA from cDNA fragments cloned in E. coli were uniformly unsuccessful. A more informative sequence than that obtained from these cloned cDNA fragments and similar E5 cDNA fragments was derived from RT-PCR fragments that had not been cloned in E. coli. Comparison of the RT-PCR consensus sequence of TP21 and E5 identified only seven amino acid differences that might be responsible for the observed difference in virulence of these strains for mice. Eleven independent infectious cDNA clones of TP21 were recovered using two overlapping long RT-PCR fragments. Importantly, low-titered virus used to prepare cDNA as template for PCR was harvested early in the growth cycle to minimize the frequency of deletion mutants that accumulated late in infection. The four analyzed rescued clones exhibited clone-specific minimal divergence from the consensus sequence but this limited variation was associated with diminished peripheral virulence for immunocompetent mice. Manipulation of these clones should facilitate elucidation of LGT virulence. Copyright 2000 Academic Press. JF - Virology AU - Campbell, M S AU - Pletnev, A G AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. Y1 - 2000/03/30/ PY - 2000 DA - 2000 Mar 30 SP - 225 EP - 237 VL - 269 IS - 1 SN - 0042-6822, 0042-6822 KW - DNA, Complementary KW - 0 KW - Index Medicus KW - Animals KW - DNA, Complementary -- genetics KW - DNA Mutational Analysis KW - Genome, Viral KW - Mice KW - Virus Replication -- physiology KW - Reverse Transcriptase Polymerase Chain Reaction KW - Consensus Sequence -- genetics KW - Transfection KW - Amino Acid Substitution -- genetics KW - Virulence -- genetics KW - Lethal Dose 50 KW - Mutation -- genetics KW - Genetic Variation -- genetics KW - Mice, SCID KW - Cell Line KW - Encephalitis Viruses, Tick-Borne -- pathogenicity KW - Encephalitis Viruses, Tick-Borne -- genetics KW - Encephalitis Viruses, Tick-Borne -- isolation & purification KW - Encephalitis Viruses, Tick-Borne -- physiology KW - Encephalitis, Tick-Borne -- mortality KW - Neurons -- virology KW - Encephalitis, Tick-Borne -- virology KW - Encephalitis, Tick-Borne -- pathology KW - Neurons -- pathology KW - Cloning, Molecular UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70963905?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virology&rft.atitle=Infectious+cDNA+clones+of+Langat+tick-borne+flavivirus+that+differ+from+their+parent+in+peripheral+neurovirulence.&rft.au=Campbell%2C+M+S%3BPletnev%2C+A+G&rft.aulast=Campbell&rft.aufirst=M&rft.date=2000-03-30&rft.volume=269&rft.issue=1&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-18 N1 - Date created - 2000-04-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Defects in TGF-beta signaling overcome senescence of mouse keratinocytes expressing v-Ha-ras. AN - 71033689; 10763827 AB - Previous studies have shown that TGFbeta1 expression is upregulated in mouse keratinocytes infected with a v-rasHa retrovirus, although the functional significance of this has not been clear. Here we show that v-rasHa retrovirus transduced primary mouse keratinocytes undergo hyperproliferation followed by a TGFbeta1 dependent G1 growth arrest and senescence. The growth arrest is accompanied by a 15-fold increase in total TGFbeta1 secreted and a fourfold increase in secreted active TGFbeta1. When cultured in the presence of a neutralizing antibody to TGFbeta1, the senescence response is suppressed. Levels of the TGFbeta1 target p15ink4b increase during senescence as does association of this kinase inhibitor with cyclinD/cdk4 complexes. However, p16ink4a, p53 and p19ARF expression also increase during senescence. Genetic analysis shows that TGFbeta1 null and dominant negative TbetaBRII expressing v-rasHa keratinocytes resist the G1 growth arrest and do not senescence. This resistance is associated with low expression of p15ink4b and p16ink4a, constitutive Rb phosphorylation and high levels of cdk4 and cdk2 kinase activity. In contrast, inactivation of TGFbetabeta1 secretion or response does not block the induction of p53 and p19ARF, but the level of p21waf1, a p53 target gene, is reduced in cyclin D/cdk4 and cyclin E/cdk2 complexes. Thus, although multiple senescence pathways are activated in response to a ras oncogene, inactivation of TGFbeta1 secretion or response is sufficient to block the senescence program. Since v-rasHa transduced TGFbeta1-/- keratinocytes form squamous cell carcinomas following skin grafting, these results suggest that in mouse keratinocytes, defects in TGFbeta1 signaling accelerate malignant progression by overcoming oncogene induced replicative senescence. JF - Oncogene AU - Tremain, R AU - Marko, M AU - Kinnimulki, V AU - Ueno, H AU - Bottinger, E AU - Glick, A AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2000/03/23/ PY - 2000 DA - 2000 Mar 23 SP - 1698 EP - 1709 VL - 19 IS - 13 SN - 0950-9232, 0950-9232 KW - Antibodies, Monoclonal KW - 0 KW - Carrier Proteins KW - Cdkn2b protein, mouse KW - Cell Cycle Proteins KW - Culture Media, Conditioned KW - Culture Media, Serum-Free KW - Cyclin D KW - Cyclin-Dependent Kinase Inhibitor p15 KW - Cyclin-Dependent Kinase Inhibitor p16 KW - Cyclins KW - Macromolecular Substances KW - Proteins KW - Proto-Oncogene Proteins KW - Transforming Growth Factor beta KW - Tumor Suppressor Protein p14ARF KW - Tumor Suppressor Protein p53 KW - Tumor Suppressor Proteins KW - Cdk4 protein, mouse KW - EC 2.7.11.22 KW - Cyclin-Dependent Kinase 4 KW - Cyclin-Dependent Kinases KW - Oncogene Protein p21(ras) KW - EC 3.6.5.2 KW - Index Medicus KW - Culture Media, Conditioned -- pharmacology KW - Animals KW - Carrier Proteins -- genetics KW - Antibodies, Monoclonal -- pharmacology KW - Mice, Inbred BALB C KW - Antibodies, Monoclonal -- immunology KW - Mice, Knockout KW - Genes, p53 KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Cyclins -- metabolism KW - G1 Phase KW - Gene Expression Regulation KW - Cell Line, Transformed KW - Signal Transduction KW - Cell Division KW - Cyclin-Dependent Kinases -- metabolism KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Protein Biosynthesis KW - Carrier Proteins -- metabolism KW - Mice KW - Proteins -- genetics KW - Culture Media, Serum-Free -- pharmacology KW - Cell Transformation, Viral KW - Keratinocytes -- secretion KW - Cell Aging -- physiology KW - Oncogene Protein p21(ras) -- deficiency KW - Transforming Growth Factor beta -- immunology KW - Transforming Growth Factor beta -- deficiency KW - Transforming Growth Factor beta -- antagonists & inhibitors KW - Genes, ras KW - Transforming Growth Factor beta -- physiology KW - Keratinocytes -- cytology KW - Keratinocytes -- metabolism KW - Transforming Growth Factor beta -- genetics KW - Oncogene Protein p21(ras) -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71033689?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Defects+in+TGF-beta+signaling+overcome+senescence+of+mouse+keratinocytes+expressing+v-Ha-ras.&rft.au=Tremain%2C+R%3BMarko%2C+M%3BKinnimulki%2C+V%3BUeno%2C+H%3BBottinger%2C+E%3BGlick%2C+A&rft.aulast=Tremain&rft.aufirst=R&rft.date=2000-03-23&rft.volume=19&rft.issue=13&rft.spage=1698&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-04 N1 - Date created - 2000-05-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular modeling of the aldose reductase-inhibitor complex based on the X-ray crystal structure and studies with single-site-directed mutants. AN - 71005358; 10737739 AB - Aldose reductase (AR) has been implicated in the etiology of the secondary complications of diabetes. This enzyme catalyzes the reduction of glucose to sorbitol using nicotinamide adenine dinucleotide phosphate as an essential cofactor. AR has been localized at the sites of tissue damage, and inhibitors of this enzyme prevent the development of neuropathy, nephropathy, retinopathy, and cataract formation in animal models of diabetes. The crystal structure of AR complexed with zopolrestat, a potent inhibitor of AR, has been described.(1) We have generated a model of the AR-inhibitor complex based on the reported Calpha coordinates of the protein and results of a structure-activity relationship study using four structurally distinct classes of inhibitors, recombinant human AR, and four single-site-directed mutants of this enzyme. The effects of the site-directed mutations on residues within the active site of the enzyme were evaluated by average interaction energy calculations and by calculations of carbon atom surface area changes. These values correlated well with the IC(50) values for zopolrestat with the wild-type and mutant enzymes, validating the model. On the basis of the zopolrestat-binding model, we have proposed binding models for 10 other AR inhibitors. Our models have enabled us to gain a qualitative understanding of the binding domains of the enzyme and how different inhibitors impact the size and shape of the binding site. JF - Journal of medicinal chemistry AU - Singh, S B AU - Malamas, M S AU - Hohman, T C AU - Nilakantan, R AU - Carper, D A AU - Kitchen, D AD - Wyeth Ayerst Research, CN 8000, Princeton, New Jersey 08543-8000, National Eye Institute, NIH, Bethesda, Maryland 20892, USA. suresh_singh@merck.com Y1 - 2000/03/23/ PY - 2000 DA - 2000 Mar 23 SP - 1062 EP - 1070 VL - 43 IS - 6 SN - 0022-2623, 0022-2623 KW - Benzothiazoles KW - 0 KW - Enzyme Inhibitors KW - Phthalazines KW - Recombinant Proteins KW - Thiazoles KW - zopolrestat KW - 1PV3S9WP3D KW - Aldehyde Reductase KW - EC 1.1.1.21 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Thiazoles -- chemistry KW - Models, Molecular KW - Humans KW - Phthalazines -- chemistry KW - Crystallography, X-Ray KW - Recombinant Proteins -- chemistry KW - Structure-Activity Relationship KW - Binding Sites KW - Enzyme Inhibitors -- chemistry KW - Aldehyde Reductase -- chemistry KW - Aldehyde Reductase -- antagonists & inhibitors KW - Aldehyde Reductase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71005358?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Molecular+modeling+of+the+aldose+reductase-inhibitor+complex+based+on+the+X-ray+crystal+structure+and+studies+with+single-site-directed+mutants.&rft.au=Singh%2C+S+B%3BMalamas%2C+M+S%3BHohman%2C+T+C%3BNilakantan%2C+R%3BCarper%2C+D+A%3BKitchen%2C+D&rft.aulast=Singh&rft.aufirst=S&rft.date=2000-03-23&rft.volume=43&rft.issue=6&rft.spage=1062&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=00222623&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-13 N1 - Date created - 2000-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin-1 polymorphisms associated with increased risk of gastric cancer AN - 17496138; 4689698 AB - Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy, which are presumptive precursors of gastric cancer. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine and a powerful inhibitor of gastric acid secretion. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do not. JF - Nature AU - El-Omar, E M AU - Carrington, M AU - Chow, Wong-Ho AU - McColl, KEL AU - Bream, J H AU - Young, HA AU - Herrera, J AU - Lissowska, J AU - Yuan, Chiu-Chin AU - Rothman, N AU - Lanyon, G AU - Martin, M AU - Fraumeni, JF Jr AU - Rabkin, C S AD - Div. Cancer Epidemiol. and Genet., Natl. Cancer Inst., Bethesda, MD, USA, elomare@mail.nih.gov Y1 - 2000/03/23/ PY - 2000 DA - 2000 Mar 23 SP - 398 EP - 402 PB - Macmillan Journals Ltd. VL - 404 IS - 6776 SN - 0028-0836, 0028-0836 KW - polymorphism KW - gastric cancer KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Linkage disequilibrium KW - Helicobacter pylori KW - Genetic factors KW - Interleukin 1 KW - G 07240:Immunogenetics KW - J 02846:Gastrointestinal tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17496138?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Interleukin-1+polymorphisms+associated+with+increased+risk+of+gastric+cancer&rft.au=El-Omar%2C+E+M%3BCarrington%2C+M%3BChow%2C+Wong-Ho%3BMcColl%2C+KEL%3BBream%2C+J+H%3BYoung%2C+HA%3BHerrera%2C+J%3BLissowska%2C+J%3BYuan%2C+Chiu-Chin%3BRothman%2C+N%3BLanyon%2C+G%3BMartin%2C+M%3BFraumeni%2C+JF+Jr%3BRabkin%2C+C+S&rft.aulast=El-Omar&rft.aufirst=E&rft.date=2000-03-23&rft.volume=404&rft.issue=6776&rft.spage=398&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&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 - Helicobacter pylori; Linkage disequilibrium; Genetic factors; Interleukin 1 ER - TY - JOUR T1 - Recombinant toxins that bind to the urokinase receptor are cytotoxic without requiring binding to the alpha(2)-macroglobulin receptor. AN - 70948051; 10713063 AB - The alpha(2-)macroglobulin receptor (alpha(2)MR) has been reported to mediate the internalization of the urokinase plasminogen activator receptor (uPAR) via ligand binding to both receptors. To target malignant uPAR-expressing cells and to determine whether uPAR can internalize without ligand binding to alpha(2)MR, we engineered two recombinant toxins, ATF-PE38 and ATF-PE38KDEL. Each consists of the amino-terminal fragment (ATF) of human urokinase and a truncated form of Pseudomonas exotoxin (PE) devoid of domain Ia, which binds alpha(2)MR. ATF-PE38 and ATF-PE38KDEL were cytotoxic toward malignant uPAR-bearing cells, with IC(50) values as low as 0.02 ng/ml (0.3 pM). Cytotoxicity could be blocked using either recombinant urokinase or free ATF, indicating that the cytotoxicity of the recombinant toxins was specific. Radiolabeled ATF-PE38 had high affinity for uPAR (K(d) = 0.4-8 nM) on a variety of different malignant cell types and internalized at a rate similar to that of ATF. The cytotoxicity was not diminished by receptor-associated protein, which binds and shields the alpha(2)MR from other proteins, or by incubation with phorbol myristate acetate, which is known to decrease the number of alpha(2)MRs in U937 cells or by antibodies to alpha(2)MR. Therefore, these recombinant toxins appear to internalize via uPAR without association with the alpha(2)MR. JF - The Journal of biological chemistry AU - Rajagopal, V AU - Kreitman, R J AD - Laboratory of Molecular Biology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/03/17/ PY - 2000 DA - 2000 Mar 17 SP - 7566 EP - 7573 VL - 275 IS - 11 SN - 0021-9258, 0021-9258 KW - Antineoplastic Agents KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Immunotoxins KW - Low Density Lipoprotein Receptor-Related Protein-1 KW - PLAUR protein, human KW - Peptide Fragments KW - Receptors, Cell Surface KW - Receptors, Immunologic KW - Receptors, Urokinase Plasminogen Activator KW - Recombinant Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Urokinase-Type Plasminogen Activator KW - EC 3.4.21.73 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Peptide Fragments -- metabolism KW - Drug Stability KW - Peptide Fragments -- genetics KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Antineoplastic Agents -- metabolism KW - Biological Transport KW - Bacterial Toxins -- pharmacology KW - Protein Binding KW - Structure-Activity Relationship KW - Binding Sites KW - Bacterial Toxins -- genetics KW - Lymphocyte Activation KW - Bacterial Toxins -- metabolism KW - Recombinant Proteins -- metabolism KW - Peptide Fragments -- pharmacology KW - Binding, Competitive KW - Toxicity Tests KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Pseudomonas aeruginosa KW - Antineoplastic Agents -- pharmacology KW - U937 Cells KW - Urokinase-Type Plasminogen Activator -- pharmacology KW - Exotoxins -- genetics KW - Exotoxins -- pharmacology KW - Urokinase-Type Plasminogen Activator -- genetics KW - Immunotoxins -- metabolism KW - Urokinase-Type Plasminogen Activator -- metabolism KW - Receptors, Cell Surface -- metabolism KW - Receptors, Immunologic -- metabolism KW - Exotoxins -- metabolism KW - Immunotoxins -- genetics KW - Immunotoxins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70948051?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Recombinant+toxins+that+bind+to+the+urokinase+receptor+are+cytotoxic+without+requiring+binding+to+the+alpha%282%29-macroglobulin+receptor.&rft.au=Rajagopal%2C+V%3BKreitman%2C+R+J&rft.aulast=Rajagopal&rft.aufirst=V&rft.date=2000-03-17&rft.volume=275&rft.issue=11&rft.spage=7566&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 - 2000-04-12 N1 - Date created - 2000-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biomarkers of oxidative stress study: are plasma antioxidants markers of CCl(4) poisoning? AN - 71091271; 10802213 AB - Antioxidants in the blood plasma of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative stress. For this initial study an animal model of CCl(4) poisoning was studied. The time (2, 7, and 16 h) and dose (120 and 1200 mg/kg, intraperitoneally)-dependent effects of CCl(4) on plasma levels of alpha-tocopherol, coenzyme Q (CoQ), ascorbic acid, glutathione (GSH and GSSG), uric acid, and total antioxidant capacity were investigated to determine whether the oxidative effects of CCl(4) would result in losses of antioxidants from plasma. Concentrations of alpha-tocopherol and CoQ were decreased in CCl(4)-treated rats. Because of concomitant decreases in cholesterol and triglycerides, it was impossible to dissociate oxidation of alpha-tocopherol and the loss of CoQ from generalized lipid changes, due to liver damage. Ascorbic acid levels were higher with treatment at the earliest time point; the ratio of GSH to GSSG generally declined, and uric acid remained unchanged. Total antioxidant capacity showed no significant change except for 16 h after the high dose, when it was increased. These results suggest that plasma changes caused by liver malfunction and rupture of liver cells together with a decrease in plasma lipids do not permit an unambiguous interpretation of the results and impede detection of any potential changes in the antioxidant status of the plasma. JF - Free radical biology & medicine AU - Kadiiska, M B AU - Gladen, B C AU - Baird, D D AU - Dikalova, A E AU - Sohal, R S AU - Hatch, G E AU - Jones, D P AU - Mason, R P AU - Barrett, J C AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. kadiiska@niehs.nih.gov Y1 - 2000/03/15/ PY - 2000 DA - 2000 Mar 15 SP - 838 EP - 845 VL - 28 IS - 6 SN - 0891-5849, 0891-5849 KW - Antioxidants KW - 0 KW - Biomarkers KW - Free Radicals KW - Ubiquinone KW - 1339-63-5 KW - Vitamin E KW - 1406-18-4 KW - Uric Acid KW - 268B43MJ25 KW - Glutathione KW - GAN16C9B8O KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Ubiquinone -- blood KW - Electron Spin Resonance Spectroscopy KW - Disease Models, Animal KW - Glutathione -- blood KW - Ascorbic Acid -- blood KW - Free Radicals -- metabolism KW - Biomarkers -- blood KW - Vitamin E -- blood KW - Uric Acid -- blood KW - Antioxidants -- analysis KW - Carbon Tetrachloride Poisoning -- physiopathology KW - Liver -- physiopathology KW - Liver -- enzymology KW - Carbon Tetrachloride Poisoning -- blood KW - Oxidative Stress KW - Liver -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71091271?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Biomarkers+of+oxidative+stress+study%3A+are+plasma+antioxidants+markers+of+CCl%284%29+poisoning%3F&rft.au=Kadiiska%2C+M+B%3BGladen%2C+B+C%3BBaird%2C+D+D%3BDikalova%2C+A+E%3BSohal%2C+R+S%3BHatch%2C+G+E%3BJones%2C+D+P%3BMason%2C+R+P%3BBarrett%2C+J+C&rft.aulast=Kadiiska&rft.aufirst=M&rft.date=2000-03-15&rft.volume=28&rft.issue=6&rft.spage=838&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 - 2000-08-02 N1 - Date created - 2000-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - EWS-FLI1, EWS-ERG, and EWS-ETV1 oncoproteins of Ewing tumor family all suppress transcription of transforming growth factor beta type II receptor gene. AN - 71010004; 10749119 AB - Ewing sarcoma-specific chromosomal translocations fuse the EWS gene to a subset of ets transcription factor family members, most commonly the FLI1 gene and less frequently ERG, ETV1, E1A-F, or FEV. These fusion proteins are thought to act as aberrant transcription factors that bind DNA through their ets DNA binding domain. Recently, we have shown (K-B. Hahm et al., Nat. Genet., 23: 222-227, 1999) that the transforming growth factor beta (TGF-beta) type II receptor (TGF-beta RII), a putative tumor suppressor gene, is a target of the EWS-FLI1 fusion protein. Here, we also examined effects of EWS-ETV1 and EWS-ERG on expression of the TGF-beta RII gene. We show that relative to the control, NIH-3T3 cell lines stably transfected with the EWS-FLI1, EWS-ERG, or EWS-ETV1 gene fusion express reduced levels of TGF-beta RII mRNA and protein, and that these cell lines have reduced TGF-beta sensitivity. Cotransfection of these fusion genes and the TGF-beta RII promoter suppresses TGF-beta RII promoter activity and also FLI1-, ERG-, or ETV1-induced promoter activity. These results indicate that transcriptional repression of TGF-beta RII is an important target of the EWS-FLI1, EWS-ERG, or EWS-ETV1 oncogene, and that EWS-ets fusion proteins may function as dominant negative forms of ets transcription factors. JF - Cancer research AU - Im, Y H AU - Kim, H T AU - Lee, C AU - Poulin, D AU - Welford, S AU - Sorensen, P H AU - Denny, C T AU - Kim, S J AD - Laboratory of Cell Regulation and Carcinogenesis, DBS, National Cancer Institute, Bethesda, Maryland 20892-5055, USA. Y1 - 2000/03/15/ PY - 2000 DA - 2000 Mar 15 SP - 1536 EP - 1540 VL - 60 IS - 6 SN - 0008-5472, 0008-5472 KW - DNA-Binding Proteins KW - 0 KW - ERG protein, human KW - EWS-ETV1 fusion protein, human KW - EWS-FLI fusion protein KW - Oncogene Proteins KW - Oncogene Proteins, Fusion KW - Proto-Oncogene Protein c-fli-1 KW - RNA, Messenger KW - RNA-Binding Protein EWS KW - Receptors, Transforming Growth Factor beta KW - Recombinant Fusion Proteins KW - Trans-Activators KW - Transcription Factors KW - Transcriptional Regulator ERG KW - Transforming Growth Factor beta KW - Luciferases KW - EC 1.13.12.- 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 - 3T3 Cells KW - Animals KW - Humans KW - Luciferases -- metabolism KW - Oncogene Proteins -- genetics KW - Transcription, Genetic KW - Mice KW - Radioligand Assay KW - RNA, Messenger -- genetics KW - Transcription Factors -- genetics KW - Recombinant Fusion Proteins -- metabolism KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Recombinant Fusion Proteins -- genetics KW - Gene Expression Regulation KW - Promoter Regions, Genetic -- genetics KW - Luciferases -- genetics KW - Transforming Growth Factor beta -- metabolism KW - Receptors, Transforming Growth Factor beta -- genetics KW - Oncogene Proteins, Fusion -- genetics KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Bone Neoplasms -- genetics KW - Sarcoma, Ewing -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71010004?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=EWS-FLI1%2C+EWS-ERG%2C+and+EWS-ETV1+oncoproteins+of+Ewing+tumor+family+all+suppress+transcription+of+transforming+growth+factor+beta+type+II+receptor+gene.&rft.au=Im%2C+Y+H%3BKim%2C+H+T%3BLee%2C+C%3BPoulin%2C+D%3BWelford%2C+S%3BSorensen%2C+P+H%3BDenny%2C+C+T%3BKim%2C+S+J&rft.aulast=Im&rft.aufirst=Y&rft.date=2000-03-15&rft.volume=60&rft.issue=6&rft.spage=1536&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 - 2000-05-04 N1 - Date created - 2000-05-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Respiratory cancer in a cohort of copper smelter workers: results from more than 50 years of follow-up. AN - 70991609; 10733037 AB - Several studies have linked inhalation of airborne arsenic with increased risk of respiratory cancer, but few have analyzed the shape of the exposure-response curve. In addition, since inhaled airborne arsenic affects systemic levels of inhaled arsenic, there is concern that inhaled arsenic may be associated with cancers of the skin, bladder, kidney, and liver, which have been linked to ingested arsenic. The authors followed 8,014 white male workers who were employed for 12 months or more prior to 1957 at a Montana copper smelter from January 1, 1938 through December 31, 1989. A total of 4,930 (62%) were deceased, including 446 from respiratory cancer. Significantly increased standardized mortality ratios (SMRs) were found for all causes (SMR = 1.14), all cancers (SMR = 1.13), respiratory cancer (SMR = 1.55), diseases of the nervous system and sense organs (SMR = 1.31), nonmalignant respiratory diseases (SMR = 1.56), emphysema (SMR = 1.73), ill-defined conditions (SMR = 2.26), and external causes (SMR = 1.35). Internal analyses revealed a significant, linear increase in the excess relative risk of respiratory cancer with increasing exposure to inhaled airborne arsenic. The estimate of the excess relative risk per mg/m3-year was 0.21/(mg/m3-year) (95% confidence interval: 0.10, 0.46). No other cause of death was related to inhaled arsenic exposure. JF - American journal of epidemiology AU - Lubin, J H AU - Pottern, L M AU - Stone, B J AU - Fraumeni, J F AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. Y1 - 2000/03/15/ PY - 2000 DA - 2000 Mar 15 SP - 554 EP - 565 VL - 151 IS - 6 SN - 0002-9262, 0002-9262 KW - Air Pollutants, Occupational KW - 0 KW - Sulfur Dioxide KW - 0UZA3422Q4 KW - Copper KW - 789U1901C5 KW - Arsenic KW - N712M78A8G KW - Index Medicus KW - Risk KW - Regression Analysis KW - Aged, 80 and over KW - Humans KW - Montana -- epidemiology KW - Adult KW - Sulfur Dioxide -- adverse effects KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - Male KW - Arsenic -- adverse effects KW - Respiratory Tract Neoplasms -- mortality KW - Air Pollutants, Occupational -- adverse effects KW - Metallurgy KW - Occupational Diseases -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70991609?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Respiratory+cancer+in+a+cohort+of+copper+smelter+workers%3A+results+from+more+than+50+years+of+follow-up.&rft.au=Lubin%2C+J+H%3BPottern%2C+L+M%3BStone%2C+B+J%3BFraumeni%2C+J+F&rft.aulast=Lubin&rft.aufirst=J&rft.date=2000-03-15&rft.volume=151&rft.issue=6&rft.spage=554&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 - 2000-04-05 N1 - Date created - 2000-04-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Agonist peptide from a cytotoxic t-lymphocyte epitope of human carcinoembryonic antigen stimulates production of tc1-type cytokines and increases tyrosine phosphorylation more efficiently than cognate peptide. AN - 70948421; 10709104 AB - The identification of an agonist peptide (YLSGADLNL, designated CAP1-6D) to an immunodominant cytotoxic T-lymphocyte (CTL) epitope (designated CAP1) of human carcinoembryonic antigen (CEA) has previously been reported. The agonist peptide harbors a single amino acid substitution at a non-MHC anchor residue and is proposed to exert its effects at the level of the T-cell receptor (TCR). The type and magnitude of cytokines produced by CAP1-reactive CTL upon stimulation with the agonist peptide, CAP1-6D, were compared to those obtained upon stimulation with the cognate CAP1 peptide. In addition, early events in the TCR signaling pathway were examined for differences in tyrosine phosphorylation. Upon stimulation with the agonist peptide CAP1-6D, several different CEA-specific CTL lines exhibited a marked shift in the peptide dose response, which resulted in as much as a 1,000-fold increase in the levels of GM-CSF and gamma-IFN produced as compared with the use of the CAP1 peptide. However, levels of IL-4 and IL-10, which are associated with anti-inflammatory effects, were very low or non-existent. The cytokine profile of CAP1- and CAP1-6D-specific CTL is consistent with a Tc1-type CTL. Consistent with these findings, CEA-specific CTL showed increased tyrosine phosphorylation of TCR signaling proteins ZAP-70 and TCR zeta chains in response to both peptides. However, when CAP1-6D was compared with the wild-type peptide, the increase in ZAP-70 phosphorylation was greater than the increase in zeta phosphorylation. CTL generated with the CAP1-6D agonist were shown capable of lysis of human carcinoma cells expressing native CEA. The ability to upregulate the production of GM-CSF, gamma-IFN, TNFalpha and IL-2 with the agonist peptide, as compared with CAP1, may help in initiating or sustaining anti-tumor immune responses and thus potentially prove to be useful in the treatment of CEA-positive tumors. Copyright 2000 Wiley-Liss, Inc. JF - International journal of cancer AU - Salazar, E AU - Zaremba, S AU - Arlen, P M AU - Tsang, K Y AU - Schlom, J AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1750, USA. Y1 - 2000/03/15/ PY - 2000 DA - 2000 Mar 15 SP - 829 EP - 838 VL - 85 IS - 6 SN - 0020-7136, 0020-7136 KW - CAP1-6D KW - 0 KW - Carcinoembryonic Antigen KW - Cytokines KW - Immunodominant Epitopes KW - Oligopeptides KW - Peptides KW - Receptors, Antigen, T-Cell KW - Interleukin-10 KW - 130068-27-8 KW - Interleukin-4 KW - 207137-56-2 KW - Tyrosine KW - 42HK56048U KW - Interferon-gamma KW - 82115-62-6 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Index Medicus KW - Cytotoxicity, Immunologic KW - Granulocyte-Macrophage Colony-Stimulating Factor -- biosynthesis KW - Phosphorylation KW - Humans KW - Interleukin-4 -- biosynthesis KW - Interferon-gamma -- biosynthesis KW - Cytotoxicity Tests, Immunologic KW - Interleukin-10 -- biosynthesis KW - Tyrosine -- metabolism KW - Signal Transduction KW - Cell Line KW - Immunodominant Epitopes -- immunology KW - Carcinoembryonic Antigen -- metabolism KW - Carcinoembryonic Antigen -- immunology KW - Cytokines -- biosynthesis KW - Receptors, Antigen, T-Cell -- metabolism KW - Oligopeptides -- immunology KW - Peptides -- metabolism KW - Oligopeptides -- metabolism KW - T-Lymphocytes, Cytotoxic -- immunology KW - Receptors, Antigen, T-Cell -- immunology KW - T-Lymphocytes, Cytotoxic -- metabolism KW - Immunodominant Epitopes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70948421?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Agonist+peptide+from+a+cytotoxic+t-lymphocyte+epitope+of+human+carcinoembryonic+antigen+stimulates+production+of+tc1-type+cytokines+and+increases+tyrosine+phosphorylation+more+efficiently+than+cognate+peptide.&rft.au=Salazar%2C+E%3BZaremba%2C+S%3BArlen%2C+P+M%3BTsang%2C+K+Y%3BSchlom%2C+J&rft.aulast=Salazar&rft.aufirst=E&rft.date=2000-03-15&rft.volume=85&rft.issue=6&rft.spage=829&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 - 2000-03-23 N1 - Date created - 2000-03-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antiangiogenic Gene Therapy of Cancer Utilizing a Recombinant Adenovirus to Elevate Systemic Endostatin Levels in Mice AN - 17672755; 4730489 AB - Gene therapy represents a possible alternative to the chronic delivery of recombinant antiangiogenic proteins to cancer patients. Inducing normal host tissues to produce high circulating levels of these proteins may be more effective than targeting antiangiogenic genes to tumor tissue specifically. Previously reported gene therapy approaches in mice have achieved peak circulating endostatin levels of 8-33 ng/ml. Here we report plasma endostatin levels of 1770 ng/ml after administration of a recombinant adenovirus. Growth of MC38 adenocarcinoma, which is relatively resistant to adenoviral infection, was inhibited by 40%. These findings encourage gene delivery approaches that use the host as a "factory" to produce high circulating levels of antiangiogenic agents. JF - Cancer Research AU - Feldman, AL AU - Restifo, N P AU - Alexander, H R AU - Bartlett, D L AU - Hwu, P AU - Seth, P AU - Libutti, S K AD - Surgery Branch, National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 2000/03/15/ PY - 2000 DA - 2000 Mar 15 SP - 1503 EP - 1506 VL - 60 IS - 6 SN - 0008-5472, 0008-5472 KW - mice KW - Adenovirus KW - antiangiogenic agents KW - endostatin KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Gene therapy KW - Angiogenesis KW - Adenocarcinoma KW - Cancer KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17672755?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Antiangiogenic+Gene+Therapy+of+Cancer+Utilizing+a+Recombinant+Adenovirus+to+Elevate+Systemic+Endostatin+Levels+in+Mice&rft.au=Feldman%2C+AL%3BRestifo%2C+N+P%3BAlexander%2C+H+R%3BBartlett%2C+D+L%3BHwu%2C+P%3BSeth%2C+P%3BLibutti%2C+S+K&rft.aulast=Feldman&rft.aufirst=AL&rft.date=2000-03-15&rft.volume=60&rft.issue=6&rft.spage=1503&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene therapy; Cancer; Angiogenesis; Adenocarcinoma; Expression vectors ER - TY - CONF T1 - Transgenic mouse models in carcinogenesis research and testing AN - 17516803; 4703939 AB - Double transgenic mice bearing fusion genes consisting of mouse albumin enhancer/promoter-mouse c-myc cDNA and mouse metallothionein 1 promoter-human TGF- alpha cDNA were generated to investigate the interaction of these genes in hepatic oncogenesis and to provide a general paradigm for characterizing both the interaction of nuclear oncogenes and growth factors in tumorigenesis. In addition, these mice provide an experimental model to test how environmental chemicals might interact with the c-myc and TGF- alpha transgenes during the neoplastic process. We show experimental evidence that co-expression of TGF- alpha and c-myc transgenes in mouse liver promotes overproduction of ROS and thus creates an oxidative stress environment. This phenomenon may account for the massive DNA damage and acceleration of hepatocarcinogenesis observed in the TGF- alpha /c-myc mouse model. Also, the role of mutagenesis in hepatocarcinogenesis induced by 2-amino-3,8-dimethylimidazo(4,5-f)-quinoxaline (MeIQx) was demonstrated in C57BL/lacZ (Muta Mice) and double transgenic c-myc/lacZ mice that carry the lacZ mutation reporter gene. The MeLQx hepatocarcinogenicity was associated with an increase in in vivo mutagenicity as scored by mutations in the lacZ reporter gene. These results suggest that transgenic mouse models may provide important tools for testing both the carcinogenic potential of environmental chemicals and the interaction/cooperation of these compounds with specific genes during the neoplastic process. JF - Toxicology Letters AU - Thorgeirsson, S S AU - Factor, V M AU - Snyderwine, E G Y1 - 2000/03/15/ PY - 2000 DA - 2000 Mar 15 SP - 553 EP - 555 PB - Elsevier Science Ireland Ltd., P.O. Box 85 Limerick Ireland VL - 112-113 IS - 1-3 KW - Toxicology Abstracts KW - Carcinogenesis KW - Animal models KW - Transgenic mice KW - Toxicity testing KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17516803?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+Letters&rft.atitle=Transgenic+mouse+models+in+carcinogenesis+research+and+testing&rft.au=Thorgeirsson%2C+S+S%3BFactor%2C+V+M%3BSnyderwine%2C+E+G&rft.aulast=Thorgeirsson&rft.aufirst=S&rft.date=2000-03-15&rft.volume=112-113&rft.issue=1-3&rft.spage=553&rft.isbn=&rft.btitle=&rft.title=Toxicology+Letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - CONF T1 - Mutator phenotype due to loss of heterozygosity in diploid yeast strains with mutations in MSH2 and MLH1 AN - 17516218; 4703897 AB - Mutations in mismatch repair (MMR) genes predispose humans to cancer. Particularly prevalent are frameshift and point mutations in MSH2 and MLH1, two genes whose products are required for the early steps in MMR. In normal tissues of persons predisposed to hereditary non-polyposis colon cancer (HNPCC), these mutations are usually present in only one allele. In tumor cells of these patients, the second, wild type allele is typically found to be deleted or inactivated by point mutation. This suggests that loss of heterozygosity (LOH) results in a strong mutator phenotype that could eventually lead to the onset of disease. Here we demonstrate that diploid yeast strains that are heterozygous for MSH2 and MLH1 alleles have an elevated mutation rate. We further show that this effect results not from saturation of the MMR capacity of all cells in the population, but rather from loss of the wild type allele in a subpopulation of heterozygous cells. These results have implications for understanding the mechanisms of carcinogenesis in humans. JF - Toxicology Letters AU - Drotschmann, K AU - Shcherbakova, P V AU - Kunkel, T A Y1 - 2000/03/15/ PY - 2000 DA - 2000 Mar 15 SP - 239 EP - 244 PB - Elsevier Science Ireland Ltd., P.O. Box 85 Limerick Ireland VL - 112-113 IS - 1-3 KW - mutators KW - budding yeast KW - MLH1 gene KW - MSH2 gene KW - Toxicology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - DNA repair KW - Mutation KW - Saccharomyces cerevisiae KW - X 24240:Miscellaneous KW - K 03079:Fungi UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17516218?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+Letters&rft.atitle=Mutator+phenotype+due+to+loss+of+heterozygosity+in+diploid+yeast+strains+with+mutations+in+MSH2+and+MLH1&rft.au=Drotschmann%2C+K%3BShcherbakova%2C+P+V%3BKunkel%2C+T+A&rft.aulast=Drotschmann&rft.aufirst=K&rft.date=2000-03-15&rft.volume=112-113&rft.issue=1-3&rft.spage=239&rft.isbn=&rft.btitle=&rft.title=Toxicology+Letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Mammalian thioredoxin reductase: oxidation of the C-terminal cysteine/selenocysteine active site forms a thioselenide, and replacement of selenium with sulfur markedly reduces catalytic activity. AN - 70971383; 10688911 AB - Mammalian cytosolic thioredoxin reductase (TrxR) has a redox center, consisting of Cys(59)/Cys(64) adjacent to the flavin ring of FAD and another center consisting of Cys(497)/selenocysteine (SeCys)(498) near the C terminus. We now show that the C-terminal Cys(497)-SH/SeCys(498)-Se(-) of NADPH-reduced enzyme, after anaerobic dialysis, was converted to a thioselenide on incubation with excess oxidized Trx (TrxS(2)) or H(2)O(2). The Cys(59)-SH/Cys(64)-SH pair also was oxidized to a disulfide. At lower concentrations of TrxS(2), the Cys(59)-SH/Cys(64)-SH center was still converted to a disulfide, presumably by reduction of the thioselenide to Cys(497)-SH/SeCys(498)-Se(-). Specific alkylation of SeCys(498) completely blocked the TrxS(2)-induced oxidation of Cys(59)-SH/Cys(64)-SH, and the alkylated enzyme had negligible NADPH-disulfide oxidoreductase activity. The effect of replacing SeCys(498) with Cys was determined by using a mutant form of human placental TrxR1 expressed in Escherichia coli. The NADPH-disulfide oxidoreductase activity of the purified Cys(497)/Cys(498) mutant enzyme was 6% or 11% of that of wild-type rat liver TrxR1 with 5, 5'-dithiobis(2-nitrobenzoic acid) or TrxS(2), respectively, as substrate. Disulfide formation induced by excess TrxS(2) in the mutant form was 12% of that of the wild type. Thus, SeCys has a critical redox function during the catalytic cycle, which is performed poorly by Cys. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Lee, S R AU - Bar-Noy, S AU - Kwon, J AU - Levine, R L AU - Stadtman, T C AU - Rhee, S G AD - Laboratories of Cell Signaling and Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2000/03/14/ PY - 2000 DA - 2000 Mar 14 SP - 2521 EP - 2526 VL - 97 IS - 6 SN - 0027-8424, 0027-8424 KW - Selenocysteine KW - 0CH9049VIS KW - Sulfur KW - 70FD1KFU70 KW - Thioredoxin-Disulfide Reductase KW - EC 1.8.1.9 KW - Selenium KW - H6241UJ22B KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - Escherichia coli -- metabolism KW - Liver -- enzymology KW - Placenta -- enzymology KW - Dose-Response Relationship, Drug KW - Humans KW - Protein Binding KW - Chromatography, High Pressure Liquid KW - Binding Sites KW - Mutagenesis KW - Rats KW - Oxidation-Reduction KW - Spectrophotometry KW - Models, Chemical KW - Time Factors KW - Selenium -- chemistry KW - Cysteine -- chemistry KW - Selenocysteine -- chemistry KW - Thioredoxin-Disulfide Reductase -- metabolism KW - Thioredoxin-Disulfide Reductase -- chemistry KW - Sulfur -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70971383?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mammalian+thioredoxin+reductase%3A+oxidation+of+the+C-terminal+cysteine%2Fselenocysteine+active+site+forms+a+thioselenide%2C+and+replacement+of+selenium+with+sulfur+markedly+reduces+catalytic+activity.&rft.au=Lee%2C+S+R%3BBar-Noy%2C+S%3BKwon%2C+J%3BLevine%2C+R+L%3BStadtman%2C+T+C%3BRhee%2C+S+G&rft.aulast=Lee&rft.aufirst=S&rft.date=2000-03-14&rft.volume=97&rft.issue=6&rft.spage=2521&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 - 2000-04-25 N1 - Date created - 2000-04-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochemistry. 1999 Mar 9;38(10):3187-96 [10074374] J Biol Chem. 1999 Feb 19;274(8):4722-34 [9988709] J Biol Chem. 1999 Aug 27;274(35):24522-30 [10455115] Arch Biochem Biophys. 1999 Sep 1;369(1):133-42 [10462449] J Biol Chem. 1999 Sep 3;274(36):25379-85 [10464265] Biochemistry. 1982 Dec 21;21(26):6628-33 [7159551] J Biol Chem. 1988 Jun 25;263(18):9015-9 [3288628] Biochemistry. 1989 Feb 7;28(3):1194-205 [2653437] J Biol Chem. 1994 Nov 4;269(44):27670-8 [7961686] FEBS Lett. 1995 Oct 2;373(1):5-9 [7589432] J Chromatogr A. 1995 Sep 29;712(1):177-90 [8556150] Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1006-11 [8577704] Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):6146-51 [8650234] Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3621-6 [9108027] J Biol Chem. 1998 Apr 10;273(15):8581-91 [9535831] Biochem J. 1998 Jun 1;332 ( Pt 2):591-2 [9679027] Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8520-5 [9671710] J Biol Chem. 1999 Jul 30;274(31):21598-602 [10419466] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A common pharmacophore for epothilone and taxanes: molecular basis for drug resistance conferred by tubulin mutations in human cancer cells. AN - 70960657; 10688884 AB - The epothilones are naturally occurring antimitotic drugs that share with the taxanes a similar mechanism of action without apparent structural similarity. Although photoaffinity labeling and electron crystallographic studies have identified the taxane-binding site on beta-tubulin, similar data are not available for epothilones. To identify tubulin residues important for epothilone binding, we have isolated two epothilone-resistant human ovarian carcinoma sublines derived in a single-step selection with epothilone A or B. These epothilone-resistant sublines exhibit impaired epothilone- and taxane-driven tubulin polymerization caused by acquired beta-tubulin mutations (beta274(Thr-->Ile) and beta282(Arg-->Gln)) located in the atomic model of alphabeta-tubulin near the taxane-binding site. Using molecular modeling, we investigated the conformational behavior of epothilone, which led to the identification of a common pharmacophore shared by taxanes and epothilones. Although two binding modes for the epothilones were predicted, one mode was identified as the preferred epothilone conformation as indicated by the activity of a potent pyridine-epothilone analogue. In addition, the structure-activity relationships of multiple taxanes and epothilones in the tubulin mutant cells can be fully explained by the model presented here, verifying its predictive value. Finally, these pharmacophore and activity data from mutant cells were used to model the tubulin binding of sarcodictyins, a distinct class of microtubule stabilizers, which in contrast to taxanes and the epothilones interact preferentially with the mutant tubulins. The unification of taxane, epothilone, and sarcodictyin chemistries in a single pharmacophore provides a framework to study drug-tubulin interactions that should assist in the rational design of agents targeting tubulin. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Giannakakou, P AU - Gussio, R AU - Nogales, E AU - Downing, K H AU - Zaharevitz, D AU - Bollbuck, B AU - Poy, G AU - Sackett, D AU - Nicolaou, K C AU - Fojo, T AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. evigi@box-e.nih.gov Y1 - 2000/03/14/ PY - 2000 DA - 2000 Mar 14 SP - 2904 EP - 2909 VL - 97 IS - 6 SN - 0027-8424, 0027-8424 KW - Alkaloids KW - 0 KW - Antineoplastic Agents KW - Bridged-Ring Compounds KW - Diterpenes KW - Epothilones KW - Epoxy Compounds KW - Taxoids KW - Thiazoles KW - Tubulin KW - epothilone A KW - sarcodictyin A KW - docetaxel KW - 15H5577CQD KW - taxane KW - 1605-68-1 KW - Paclitaxel KW - P88XT4IS4D KW - epothilone B KW - UEC0H0URSE KW - Index Medicus KW - Paclitaxel -- chemistry KW - Tumor Cells, Cultured KW - Models, Molecular KW - Humans KW - Paclitaxel -- analogs & derivatives KW - Models, Chemical KW - Inhibitory Concentration 50 KW - Structure-Activity Relationship KW - Protein Conformation KW - Bridged-Ring Compounds -- chemistry KW - Thiazoles -- chemistry KW - Alkaloids -- chemistry KW - Tubulin -- genetics KW - Epoxy Compounds -- chemistry KW - Tubulin -- metabolism KW - Drug Resistance, Neoplasm KW - Antineoplastic Agents -- chemistry KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70960657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+common+pharmacophore+for+epothilone+and+taxanes%3A+molecular+basis+for+drug+resistance+conferred+by+tubulin+mutations+in+human+cancer+cells.&rft.au=Giannakakou%2C+P%3BGussio%2C+R%3BNogales%2C+E%3BDowning%2C+K+H%3BZaharevitz%2C+D%3BBollbuck%2C+B%3BPoy%2C+G%3BSackett%2C+D%3BNicolaou%2C+K+C%3BFojo%2C+T&rft.aulast=Giannakakou&rft.aufirst=P&rft.date=2000-03-14&rft.volume=97&rft.issue=6&rft.spage=2904&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 - 2000-04-25 N1 - Date created - 2000-04-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Chem Biol. 1998 Jul;5(7):365-72 [9662505] Cancer Res. 1998 Mar 15;58(6):1111-5 [9515790] Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4256-61 [10200249] Biochemistry. 1999 Apr 27;38(17):5490-8 [10220336] J Clin Oncol. 1999 Jun;17(6):1786-93 [10561216] Proc Natl Acad Sci U S A. 1986 Jun;83(12):4327-31 [3459176] J Biol Chem. 1994 Feb 4;269(5):3132-4 [7906266] Trends Biotechnol. 1994 Jun;12(6):222-7 [7765351] Cancer Res. 1995 Jun 1;55(11):2325-33 [7757983] J Biol Chem. 1995 Sep 1;270(35):20235-8 [7657589] Biochemistry. 1996 Jan 9;35(1):243-50 [8555181] Bioorg Med Chem. 1995 Apr;3(4):411-28 [8581425] Science. 1996 Dec 20;274(5295):2009 [8984658] J Biol Chem. 1997 Jan 24;272(4):2534-41 [8999970] Nature. 1997 May 15;387(6630):238-9 [9153384] Nature. 1997 May 15;387(6630):268-72 [9153390] J Biol Chem. 1997 Jul 4;272(27):17118-25 [9202030] Mol Pharmacol. 1997 Oct;52(4):613-22 [9380024] Nature. 1998 Jan 8;391(6663):199-203 [9428769] Curr Opin Cell Biol. 1998 Feb;10(1):123-30 [9484604] Cell. 1999 Jan 8;96(1):79-88 [9989499] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: cleavage of proteins with aspartate vs. glutamate at position 298. AN - 70952505; 10717002 AB - An endothelial nitric oxide synthase (eNOS) polymorphism in exon 7 (894 G/T) resulting in glutamate or aspartate, respectively, at position 298 on the protein is correlated with severity of cardiopulmonary diseases. Because glutamate and aspartate are considered to be conservative replacements, the polymorphism was thought to be a marker for a functional locus elsewhere in the gene. We now show in transfected cells, primary human endothelial cells, and human hearts, that eNOS with aspartate, but not glutamate, at position 298 is cleaved, resulting in the generation of 100-kDa and 35-kDa products. Recombinant or native eNOS was examined by immunoblotting either in lysates (COS7) or after partial purification over 2',5'-ADP-Sepharose and calmodulin-Sepharose. Immunoblotting after SDS/PAGE with a carboxyl-terminal antibody showed a single major protein band in the predicted position for eNOS at 135 kDa. An additional band at approximately 100 kDa was present only in the recombinant 298Asp eNOS and in the eNOS synthesized by primary cells and heart tissue with a G/T genotype. Using an eNOS amino-terminal-specific antibody, an immunoreactive band at approximately 35 kDa, corresponding to the residual N-terminal cleavage fragment, was observed in those cells with a T genotype. Thus, eNOS with aspartate but not glutamate at position 298 is cleaved, resulting in the generation of N-terminal 35-kDa and C-terminal 100-kDa fragments. Thus, the eNOS gene with polymorphisms at nucleotide 894 generates protein products with differing susceptibility to cleavage, suggesting that, in contrast to prior predictions, this polymorphism has a functional effect on the eNOS protein. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Tesauro, M AU - Thompson, W C AU - Rogliani, P AU - Qi, L AU - Chaudhary, P P AU - Moss, J AD - Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1590, USA. tesaurm@gwgate.nhlbi.nih.gov Y1 - 2000/03/14/ PY - 2000 DA - 2000 Mar 14 SP - 2832 EP - 2835 VL - 97 IS - 6 SN - 0027-8424, 0027-8424 KW - Isoenzymes KW - 0 KW - Aspartic Acid KW - 30KYC7MIAI KW - Glutamic Acid KW - 3KX376GY7L KW - NOS3 protein, human KW - EC 1.14.13.39 KW - Nitric Oxide Synthase KW - Nitric Oxide Synthase Type III KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Genotype KW - Immunoblotting KW - Animals KW - COS Cells KW - Transfection KW - Polymorphism, Genetic KW - Cells, Cultured KW - Humans KW - Aorta -- enzymology KW - Plasmids KW - Lung Diseases -- genetics KW - Cardiovascular Diseases -- enzymology KW - Nitric Oxide Synthase -- genetics KW - Glutamic Acid -- chemistry KW - Lung Diseases -- enzymology KW - Nitric Oxide Synthase -- metabolism KW - Cardiovascular Diseases -- genetics KW - Aspartic Acid -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70952505?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Intracellular+processing+of+endothelial+nitric+oxide+synthase+isoforms+associated+with+differences+in+severity+of+cardiopulmonary+diseases%3A+cleavage+of+proteins+with+aspartate+vs.+glutamate+at+position+298.&rft.au=Tesauro%2C+M%3BThompson%2C+W+C%3BRogliani%2C+P%3BQi%2C+L%3BChaudhary%2C+P+P%3BMoss%2C+J&rft.aulast=Tesauro&rft.aufirst=M&rft.date=2000-03-14&rft.volume=97&rft.issue=6&rft.spage=2832&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 - 2000-04-25 N1 - Date created - 2000-04-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1990 Jan;87(2):682-5 [1689048] Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10480-4 [1720542] J Biol Chem. 1993 Aug 15;268(23):17478-88 [7688726] Nat Med. 1996 Jan;2(1):41-5 [8564837] Pharmacol Rev. 1997 Jun;49(2):137-42 [9228663] J Clin Invest. 1997 Nov 1;100(9):2146-52 [9410890] Circulation. 1999 Oct 5;100(14):1515-20 [10510054] Hypertension. 1998 Jul;32(1):3-8 [9674630] Hum Genet. 1998 Jul;103(1):65-9 [9737779] Hypertension. 1998 Sep;32(3):521-6 [9740620] Cell. 1998 Dec 23;95(7):939-50 [9875848] Am J Respir Cell Mol Biol. 1999 Mar;20(3):441-7 [10030842] Circulation. 1999 Jun 8;99(22):2864-70 [10359729] J Am Coll Cardiol. 1998 Jun;31(7):1506-10 [9626827] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conformationally constrained analogues of diacylglycerol (DAG). 16. How much structural complexity is necessary for recognition and high binding affinity to protein kinase C? AN - 70981857; 10715158 AB - The design of potent protein kinase C (PK-C) ligands with low nanomolar binding affinities was accomplished by the combined use of pharmacophore- and receptor-guided approaches based on the structure of the physiological enzyme activator, diacylglycerol (DAG). Earlier use of the former approach, which was based on the structural equivalence of DAG and phorbol ester pharmacophores, identified a fixed template for the construction of a semirigid "recognition domain" that contained the three principal pharmacophores of DAG constrained into a lactone ring (DAG-lactones). In the present work, the pharmacophore-guided approach was refined to a higher level based on the X-ray structure of the C1b domain of PK-Cdelta complexed with phorbol-13-O-acetate. A systematic search that involved modifying the DAG-lactone template with a combination of linear or branched acyl and alpha-alkylidene chains, which functioned as variable hydrophobic "affinity domains", helped identify compounds that optimized hydrophobic contacts with a group of conserved hydrophobic amino acids located on the top half of the C1 domain where the phorbol binds. The hydrophilic/hydrophobic balance of the molecules was estimated by the octanol/water partition coefficients (log P) calculated according to a fragment-based approach. The presence of branched alpha-alkylidene or acyl chains was of critical importance to reach low nanomolar binding affinities for PK-C. These branched chains appear to facilitate important van der Waals contacts with hydrophobic segments of the protein and help promote the activation of PK-C through critical membrane interactions. Molecular modeling of these DAG-lactones into an empty C1b domain using the program AutoDock 2.4 suggests the existence of competing binding modes (sn-1 and sn-2) depending on which carbonyl is directly involved in binding to the protein. Inhibition of epidermal growth factor (EGF) binding, an indirect PK-C mediated response, was realized with some DAG-lactones at a dose 10-fold higher than with the standard phorbol-12, 13-dibutyrate (PDBU). Through the National Cancer Institute (NCI) 60-cell line in vitro screen, DAG-lactone 31 was identified as a very selective and potent antitumor agent. The NCI's computerized, pattern-recognition program COMPARE, which analyzes the degree of similarity of mean-graph profiles produced by the screen, corroborated our principles of drug design by matching the profile of compound 31 with that of the non-tumor-promoting antitumor phorbol ester, prostratin. The structural simplicity and the degree of potency achieved with some of the DAG-lactones described here should dispel the myth that chemical complexity and pharmacological activity go hand in hand. Even as a racemate, DAG-lactone 31 showed low namomolar binding affinity for PK-C and displayed selective antitumor activity at equivalent nanomolar levels. Our present approach should facilitate the generation of multiple libraries of structurally similar DAG-lactones to help exploit molecular diversity for PK-C and other high-affinity receptors for DAG and the phorbol esters. The success of this work suggests that substantially simpler, high-affinity structures could be identified to function as surrogates of other complex natural products. JF - Journal of medicinal chemistry AU - Nacro, K AU - Bienfait, B AU - Lee, J AU - Han, K C AU - Kang, J H AU - Benzaria, S AU - Lewin, N E AU - Bhattacharyya, D K AU - Blumberg, P M AU - Marquez, V E AD - Laboratories of Medicinal Chemistry and of Cellular Carcinogenesis and Tumor Promotion, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/03/09/ PY - 2000 DA - 2000 Mar 09 SP - 921 EP - 944 VL - 43 IS - 5 SN - 0022-2623, 0022-2623 KW - (1-(hydroxymethyl)-4-(4-methyl-3-(methylethyl)pentylidene)-3-oxo-2-oxolanyl)methyl 4-methyl-3-(methylethyl)pentanoate KW - 0 KW - Antineoplastic Agents KW - Isoenzymes KW - Ligands KW - Valerates KW - Epidermal Growth Factor KW - 62229-50-9 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-alpha KW - 4-Butyrolactone KW - OL659KIY4X KW - Index Medicus KW - Epidermal Growth Factor -- antagonists & inhibitors KW - Drug Screening Assays, Antitumor KW - Stereoisomerism KW - Tumor Cells, Cultured KW - Models, Molecular KW - Enzyme Activation KW - Binding, Competitive KW - Crystallography, X-Ray KW - Epidermal Growth Factor -- metabolism KW - Drug Design KW - Structure-Activity Relationship KW - Isoenzymes -- chemistry KW - Valerates -- chemistry KW - Valerates -- pharmacology KW - Antineoplastic Agents -- metabolism KW - 4-Butyrolactone -- metabolism KW - Isoenzymes -- metabolism KW - Protein Kinase C -- metabolism KW - Valerates -- metabolism KW - Protein Kinase C -- chemistry KW - Antineoplastic Agents -- chemical synthesis KW - 4-Butyrolactone -- pharmacology KW - 4-Butyrolactone -- chemical synthesis KW - Antineoplastic Agents -- chemistry KW - Antineoplastic Agents -- pharmacology KW - Valerates -- chemical synthesis KW - 4-Butyrolactone -- chemistry KW - 4-Butyrolactone -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70981857?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Conformationally+constrained+analogues+of+diacylglycerol+%28DAG%29.+16.+How+much+structural+complexity+is+necessary+for+recognition+and+high+binding+affinity+to+protein+kinase+C%3F&rft.au=Nacro%2C+K%3BBienfait%2C+B%3BLee%2C+J%3BHan%2C+K+C%3BKang%2C+J+H%3BBenzaria%2C+S%3BLewin%2C+N+E%3BBhattacharyya%2C+D+K%3BBlumberg%2C+P+M%3BMarquez%2C+V+E&rft.aulast=Nacro&rft.aufirst=K&rft.date=2000-03-09&rft.volume=43&rft.issue=5&rft.spage=921&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=00222623&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-13 N1 - Date created - 2000-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Provision of methadone treatment in primary care medical practices: review of the Scottish experience and implications for US policy. AN - 70963908; 10714738 AB - Under new proposed regulations, US physicians outside of traditional methadone clinics could prescribe methadone to patients with opioid dependence. No large-scale evaluations of US programs in which methadone maintenance is provided by primary care physicians are available, but primary care physicians in Scotland have participated in such programs on a large scale. To review the history, operation, and outcome data on the efficacy and safety of 2 Scottish primary care-based opioid agonist treatment programs to derive lessons for the US context. Naturalistic study of programs in Edinburgh and Glasgow, Scotland, with data obtained through site visits and interviews conducted in 1996 and 1998, as well as from published reports and retrospective analysis of electronic databases. Proportions of injection drug users who were enrolled in the methadone maintenance programs, average methadone doses in the programs, and methadone-related deaths. A total of 60% to 80% of injection drug users in Edinburgh and 41% to 73% of those in Glasgow were enrolled in methadone maintenance in 1998-1999. Dose levels are consistent with US recommendations (for Edinburgh in 1998, 61 mg; for Glasgow in 1994-1996, 54 mg). The Glasgow program required supervised consumption of methadone in community pharmacies for the first year and experienced significantly fewer methadone-related deaths than Edinburgh in 1997 (17 vs 30 deaths; P<.0001). Programs in both Edinburgh and Glasgow provided support to primary care physicians and achieved levels of general practitioner participation of 59% (1998) and 30% (1999), respectively. The Scottish experience indicates that prescription of methadone in office-based settings can expand access to an important treatment modality. Primary care physicians safely prescribed methadone for maintenance treatment when provided with adequate support. Diversion of methadone was minimized by requiring supervised consumption in community pharmacies. JF - JAMA AU - Weinrich, M AU - Stuart, M AD - Department of Neurology, University of Maryland, Baltimore, USA. mw287k@nih.gov Y1 - 2000/03/08/ PY - 2000 DA - 2000 Mar 08 SP - 1343 EP - 1348 VL - 283 IS - 10 SN - 0098-7484, 0098-7484 KW - Narcotics KW - 0 KW - Methadone KW - UC6VBE7V1Z KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Scotland KW - Policy Making KW - Substance Abuse Treatment Centers KW - Humans KW - Outcome Assessment (Health Care) KW - Family Practice KW - Methadone -- therapeutic use KW - Narcotics -- therapeutic use KW - Opioid-Related Disorders -- rehabilitation KW - Delivery of Health Care UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70963908?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Provision+of+methadone+treatment+in+primary+care+medical+practices%3A+review+of+the+Scottish+experience+and+implications+for+US+policy.&rft.au=Weinrich%2C+M%3BStuart%2C+M&rft.aulast=Weinrich&rft.aufirst=M&rft.date=2000-03-08&rft.volume=283&rft.issue=10&rft.spage=1343&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-16 N1 - Date created - 2000-03-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 2000 Mar 8;283(10):1337-9 [10714736] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Death and antimutagenicity. AN - 71084967; 10798932 JF - Mutation research AU - Zeiger, E AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2000/03/03/ PY - 2000 DA - 2000 Mar 03 SP - 125 EP - 127 VL - 466 IS - 1 SN - 0027-5107, 0027-5107 KW - Antimutagenic Agents KW - 0 KW - Antioxidants KW - Index Medicus KW - Antioxidants -- pharmacology KW - Mutagenicity Tests -- methods KW - Humans KW - Antimutagenic Agents -- pharmacology KW - Cell Death -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71084967?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Death+and+antimutagenicity.&rft.au=Zeiger%2C+E&rft.aulast=Zeiger&rft.aufirst=E&rft.date=2000-03-03&rft.volume=466&rft.issue=1&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-03 N1 - Date created - 2000-05-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo bypass of hemophilia A coagulation defect by Factor XIIa implant AN - 864952743; 13744329 AB - Hemophilia A and B coagulation defects, which are caused by deficiencies of Factor VIII and Factor IX, respectively, can be bypassed by administration of recombinant Factor VIIa. However, the short half-life of recombinant Factor VIIa in vivo negates its routine clinical use. We report here an in vivo method for the continuous generation of Factor VIIa. The method depends on the implantation of a porous chamber that contains Factor Xa or XIIa, and continuously generates Factor VIIa bypass activity from the subject's own Factor VII, which enters the chamber by diffusion. Once inside, the Factor VII is cleaved to Factor VIIa by the immobilized Factor Xa or XIIa. The newly created Factor VIIa diffuses out of the chamber and back into the circulation, where it can bypass the deficient Factors VIII or IX, and enable coagulation to occur. In vitro, this method generates sufficient Factor VIIa to substantially correct Factor VIII-deficient plasma when assessed by the classical aPTT coagulation assay. In vivo, a Factor XIIa peritoneal implant generates bypass activity for up to one month when tested in rhesus monkeys. Implantation of such a chamber in a patient with hemophilia A or B could eventually provide a viable alternative to replacement therapies using exogenous coagulation factors. JF - Nature Biotechnology AU - Ton-That, Tung T AU - Doron, David AU - Pollard, Bette S AU - Bacher, John AU - Pollard, Harvey B AD - [1] Department of Anatomy and Cell Biology, Uniformed Services University School of Medicine, USUHS, Bethesda, MD 10814. [2] Laboratory of Cell Biology and Genetics, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 289 EP - 295 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 18 IS - 3 SN - 1087-0156, 1087-0156 KW - Biotechnology and Bioengineering Abstracts KW - Coagulation KW - Peritoneum KW - Coagulation factors KW - Macaca mulatta KW - Diffusion KW - Coagulation factor VIIa KW - Hemophilia KW - W 30925:Genetic Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/864952743?accountid=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=In+vivo+bypass+of+hemophilia+A+coagulation+defect+by+Factor+XIIa+implant&rft.au=Ton-That%2C+Tung+T%3BDoron%2C+David%3BPollard%2C+Bette+S%3BBacher%2C+John%3BPollard%2C+Harvey+B&rft.aulast=Ton-That&rft.aufirst=Tung&rft.date=2000-03-01&rft.volume=18&rft.issue=3&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2F73727 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-05-01 N1 - Last updated - 2013-10-04 N1 - SubjectsTermNotLitGenreText - Coagulation; Peritoneum; Coagulation factors; Diffusion; Coagulation factor VIIa; Hemophilia; Macaca mulatta DO - http://dx.doi.org/10.1038/73727 ER - TY - JOUR T1 - Granular cell tumors of the colon: report of a case and review of the literature. AN - 85335485; pmid-10730927 AB - Granular cell tumors are uncommon, usually benign tumors that can be located anywhere in the body. They commonly occur in the oral cavity and in subcutaneous tissue. In the gastrointestinal tract, granular cell tumors are uncommon and are quite rare in the colon. To date, 55 patients diagnosed with granular cell tumors of the colon have been reported in the literature, only 15 had multiple tumors. We describe the case of a 38-year-old man with a family history of colon cancer who was diagnosed with multiple colonic granular cell tumors after a screening colonoscopy. This seems to be the first report of this type. However, in our patient, the diagnosis of colonic granular cell tumors was incidental and there is no data that correlates adenomas or colorectal cancer with granular cell tumors of the colon. Finally, since granular cell tumors are usually benign, we suggest a conservative approach to patients with multiple granular cell tumors of the colon by means of endoscopic resection and a strict endoscopic follow-up. JF - Journal of clinical gastroenterology AU - Rossi, G B AU - de Bellis, M AU - Marone, P AU - De Chiara, A AU - Losito, S AU - Tempesta, A AD - Endoscopy Unit, National Cancer Institute and G. Pascale Foundation, Naples, Italy. Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 197 EP - 199 VL - 30 IS - 2 SN - 0192-0790, 0192-0790 KW - Index Medicus KW - National Library of Medicine KW - Colonoscopy KW - Humans KW - Adult KW - Colorectal Neoplasms -- genetics KW - Male KW - Colonic Neoplasms -- epidemiology KW - Granular Cell Tumor -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85335485?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+gastroenterology&rft.atitle=Granular+cell+tumors+of+the+colon%3A+report+of+a+case+and+review+of+the+literature.&rft.au=Rossi%2C+G+B%3Bde+Bellis%2C+M%3BMarone%2C+P%3BDe+Chiara%2C+A%3BLosito%2C+S%3BTempesta%2C+A&rft.aulast=Rossi&rft.aufirst=G&rft.date=2000-03-01&rft.volume=30&rft.issue=2&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+gastroenterology&rft.issn=01920790&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - Measurement of dopamine release with continuous infusion of [11C]raclopride: optimization and signal-to-noise considerations. AN - 85277561; pmid-10716328 AB - PET studies with [11C]raclopride provide an indirect measure of changes in synaptic dopamine. Previously, we used the bolus-plus-infusion (B/I) method to assess dopamine response from the percentage change in binding potential (deltaBP) before and after administration of amphetamine. The goal of this work is to optimize the measurement of changes in neurotransmitter with the B/I method by choosing the optimal timing for pre- and poststimulus scanning. METHODS: Two sources of variability in deltaBP were considered: within-subject and between-subject noise. A noise model based on a phantom study and human data was used to evaluate the within-subject noise. For between-subject noise, simulated time--activity curves were generated from measured [11C]raclopride input functions. Optimal timing to measure deltaBP was determined and applied to human data. RESULTS: According to the simulation study, the optimal scan times for pre-and poststimulus scans were 39-50 and 58-100 min, respectively. The optimal timing resulted in a 28% noise reduction compared with the original timing. By applying the optimal timing to human studies, the statistical significance of the difference in deltaBP between patients with schizophrenia and healthy volunteers increased from P = 0.038 to 0.012. CONCLUSION: Careful assessment of the sources of noise in receptor imaging studies can increase the sensitivity of the B/I method for the detection of biologic signals. JF - Journal of Nuclear Medicine AU - Watabe, H AU - Endres, C J AU - Breier, A AU - Schmall, B AU - Eckelman, W C AU - Carson, R E AD - PET Department, Clinical Center, and Experimental Therapeutics Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1180, USA. PY - 2000 SP - 522 EP - 530 VL - 41 IS - 3 SN - 0161-5505, 0161-5505 KW - Phantoms, Imaging KW - Sensitivity and Specificity KW - Signal Processing, Computer-Assisted KW - Infusions, Intravenous KW - Human KW - Brain KW - Dopamine Antagonists KW - Schizophrenia KW - Dopamine KW - Adult KW - Raclopride KW - Time Factors KW - Image Processing, Computer-Assisted KW - Tomography, Emission-Computed UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85277561?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Nuclear+Medicine&rft.atitle=Measurement+of+dopamine+release+with+continuous+infusion+of+%5B11C%5Draclopride%3A+optimization+and+signal-to-noise+considerations.&rft.au=Watabe%2C+H%3BEndres%2C+C+J%3BBreier%2C+A%3BSchmall%2C+B%3BEckelman%2C+W+C%3BCarson%2C+R+E&rft.aulast=Watabe&rft.aufirst=H&rft.date=2000-03-01&rft.volume=41&rft.issue=3&rft.spage=522&rft.isbn=&rft.btitle=&rft.title=Journal+of+Nuclear+Medicine&rft.issn=01615505&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Modulation of laryngeal responses to superior laryngeal nerve stimulation by volitional swallowing in awake humans. AN - 85242527; pmid-10712454 AB - Laryngeal sensori-motor closure reflexes are important for the protection of the airway and prevent the entry of foreign substances into the trachea and lungs. The purpose of this study was to determine how such reflexes might be modulated during volitional swallowing in awake humans, when persons are at risk of entry of food or liquids into the airway. The frequency and the amplitude of laryngeal adductor responses evoked by electrical stimulation of the internal branch of the superior laryngeal nerve (ISLN) were studied during different phases of volitional swallowing. Subjects swallowed water on command while electrical stimuli were presented to the ISLN at various intervals from 500 ms to 5 s following the command. Laryngeal adductor responses to unilateral ISLN stimulation were recorded bilaterally in the thyroarytenoid muscles using hooked wire electrodes. Early ipsilateral R1 responses occurred at 17 ms, and later bilateral R2 began around 65 ms. The muscle responses to stimuli occurring during expiration without swallowing were quantified as control trials. Responses to stimulation presented before swallowing, during the swallow, within 3 s after swallowing, and between 3 and 5 s after a swallow were measured. The frequency and amplitude of three responses (ipsilateral R1 and bilateral R2) relative to the control responses were compared across the different phases relative to the occurrence of swallowing. Results demonstrated that a reduction occurred in both the frequency and amplitude of the later bilateral R2 laryngeal responses to electrical stimulation for up to 3 s after swallowing (P = 0.005). The amplitude and frequency of ipsilateral R1 laryngeal responses, however, did not show a significant main effect following the swallow (P = 0.28), although there was a significant time by measure interaction (P = 0.006) related to reduced R1 response amplitude up to 3 s after swallowing (P = 0.021). Therefore, the more rapid and shorter unilateral R1 responses continued to provide some, albeit reduced, laryngeal protective functions after swallowing, whereas the later bilateral R2 responses were suppressed both in occurrence and amplitude for up to 3 s after swallowing. The results suggest that R2 laryngeal adductor responses are suppressed following swallowing when residues may remain in the laryngeal vestibule putting persons at increased risk for the entry of foreign substances into the airway. JF - Journal of Neurophysiology AU - Barkmeier, Julie Marie AU - Bielamowicz, S AU - Takeda, N AU - Ludlow, Christy L AD - Department of Speech, Language, and Hearing Sciences, College of Science, University of Arizona; Laryngeal and Speech Section, National Institute of Neurological Disorders and Stroke PY - 2000 SP - 1264 EP - 1272 VL - 83 IS - 3 SN - 0022-3077, 0022-3077 KW - Laryngeal Nerves KW - Laryngeal Muscles KW - Human KW - Electromyography KW - Electric Stimulation KW - Deglutition KW - Mechanoreceptors KW - Adult KW - Electrodes KW - Larynx KW - Middle Age KW - Male KW - Female KW - Wakefulness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85242527?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Neurophysiology&rft.atitle=Modulation+of+laryngeal+responses+to+superior+laryngeal+nerve+stimulation+by+volitional+swallowing+in+awake+humans.&rft.au=Barkmeier%2C+Julie+Marie%3BBielamowicz%2C+S%3BTakeda%2C+N%3BLudlow%2C+Christy+L&rft.aulast=Barkmeier&rft.aufirst=Julie&rft.date=2000-03-01&rft.volume=83&rft.issue=3&rft.spage=1264&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Use of corncob for endoxylanase production by thermophilic fungus Thermomyces lanuginosus IOC-4145 AN - 815536177; 13858870 AB - The production of cellulase-free end oxylanase by the thermophilic fungus Thermomyces lanuginosus was investigated insemisolid fermentation and liquid fermentation. Different process variables were investigated in semisolid fermentation, employing corncobas the carbon source. The best results were with the following conditions: grain size=4.5 mm, solid:liquid ratio=1:2, and inoculum size=20% (v/v). Corncob, xylan, and xylose were the best inducers for endoxylanase production. Additionally, organic nitrogen sources were necessary for the production of high endoxylanase activities. The crude enzyme had optimum activity at pH 6.0 and 75C, displaying a high thermostability. The apparent K sub(25) and V sub(max) were 1.77 mg of xylan/mL and 21.5 U/mg of protein, respectively. JF - Applied Biochemistry and Biotechnology AU - Damaso, Monica CT AU - Andrade, Carolina MMC AU - Pereira, Nei AD - Escola de Quimica da Universidade Federal do Rio de Janeiro, PO Box 68542, CEP 21945-970, Rio de Janeiro, RJ, Brazil, nei@eq.ufrj.br Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 821 EP - 834 PB - Humana Press Inc., 999 Riverview Dr., Ste. 208 Totowa NJ 07512 USA VL - 84-86 IS - 1-9 SN - 0273-2289, 0273-2289 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; ASFA 1: Biological Sciences & Living Resources; Biotechnology and Bioengineering Abstracts KW - Xylose KW - Nitrogen sources KW - Organic nitrogen KW - Fermentation KW - Enzymes KW - Carbon sources KW - Xylan KW - Inoculum KW - Grain KW - Thermomyces lanuginosus KW - Thermal stability KW - pH effects KW - Biotechnology KW - Q1 08626:Food technology KW - W 30945:Fermentation & Cell Culture KW - K 03320:Cell Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/815536177?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+Biochemistry+and+Biotechnology&rft.atitle=Use+of+corncob+for+endoxylanase+production+by+thermophilic+fungus+Thermomyces+lanuginosus+IOC-4145&rft.au=Damaso%2C+Monica+CT%3BAndrade%2C+Carolina+MMC%3BPereira%2C+Nei&rft.aulast=Damaso&rft.aufirst=Monica&rft.date=2000-03-01&rft.volume=84-86&rft.issue=1-9&rft.spage=821&rft.isbn=&rft.btitle=&rft.title=Applied+Biochemistry+and+Biotechnology&rft.issn=02732289&rft_id=info:doi/10.1385%2FABAB%3A84-86%3A1-9%3A821 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-11-01 N1 - Last updated - 2014-05-02 N1 - SubjectsTermNotLitGenreText - Xylose; Organic nitrogen; Fermentation; Biotechnology; Nitrogen sources; Xylan; Grain; Inoculum; Enzymes; Carbon sources; Thermal stability; pH effects; Thermomyces lanuginosus DO - http://dx.doi.org/10.1385/ABAB:84-86:1-9:821 ER - TY - JOUR T1 - Effects of elevated cytoplasmic calcium and protein kinase C on endoplasmic reticulum structure and function in HEK293 cells. AN - 72296667; 11007130 AB - In human embryonic kidney (HEK) cells stably transfected with green fluorescent protein targeted to the endoplasmic reticulum (ER), elevation of intracellular Ca2+ ([Ca2+]i) altered ER morphology, making it appear punctate. Electron microscopy revealed that these punctate structures represented circular and branched rearrangements of the endoplasmic reticulum, but did not involve obvious swelling or pathological fragmentation. Activation of protein kinase C with phorbol 12-myristate 13-acetate (PMA), prevented the effects of ionomycin on ER structure without affecting the elevation of [Ca2+]i. These results suggest that protein kinase C activation alters cytoplasmic or ER components underlying the effects of high [Ca2+]i on ER structure. Treatment of HEK cells with PMA also reduced the size of the thapsigargin-sensitive Ca2+ pool and inhibited Ca2+ entry in response to thapsigargin. Thus, protein kinase C activation has multiple actions on the calcium storage and signalling function of the endoplasmic reticulum in HEK cells: (1) reduced intracellular Ca2+ storage capacity, (2) inhibition of capacitative Ca2+ entry, and (3) protection of the endoplasmic reticulum against the effects of high [Ca2+]i. JF - Cell calcium AU - Ribeiro, C M AU - McKay, R R AU - Hosoki, E AU - Bird, G S AU - Putney, J W AD - National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 175 EP - 185 VL - 27 IS - 3 SN - 0143-4160, 0143-4160 KW - Enzyme Inhibitors KW - 0 KW - Fluorescent Dyes KW - Ionophores KW - Muscarinic Agonists KW - Recombinant Fusion Proteins KW - Methacholine Chloride KW - 0W5ETF9M2K KW - Ionomycin KW - 56092-81-0 KW - Thapsigargin KW - 67526-95-8 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Fura-2 KW - TSN3DL106G KW - Index Medicus KW - Microscopy, Confocal KW - Methacholine Chloride -- pharmacology KW - Humans KW - Cytophotometry KW - Ionomycin -- pharmacology KW - Thapsigargin -- pharmacology KW - Recombinant Fusion Proteins -- metabolism KW - Ionophores -- pharmacology KW - Transfection KW - Muscarinic Agonists -- pharmacology KW - Recombinant Fusion Proteins -- genetics KW - Kidney KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Microscopy, Electron KW - Cell Line KW - Fura-2 -- metabolism KW - Protein Kinase C -- metabolism KW - Endoplasmic Reticulum -- metabolism KW - Calcium -- metabolism KW - Endoplasmic Reticulum -- ultrastructure KW - Calcium Signaling KW - Endoplasmic Reticulum -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72296667?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+calcium&rft.atitle=Effects+of+elevated+cytoplasmic+calcium+and+protein+kinase+C+on+endoplasmic+reticulum+structure+and+function+in+HEK293+cells.&rft.au=Ribeiro%2C+C+M%3BMcKay%2C+R+R%3BHosoki%2C+E%3BBird%2C+G+S%3BPutney%2C+J+W&rft.aulast=Ribeiro&rft.aufirst=C&rft.date=2000-03-01&rft.volume=27&rft.issue=3&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Cell+calcium&rft.issn=01434160&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-04 N1 - Date created - 2000-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular modeling of mammalian cytochrome P450s. AN - 71126015; 10823248 AB - The cytochrome P450s are a superfamily of hemoprotein enzymes responsible for the metabolism of a wide variety of xenobiotic and endogenous compounds. The individual P450s exhibit unique substrate specificity and stereoselectivity profiles which reflect corresponding differences in primary sequence and tertiary structure. In the absence of an experimental structure models for mammalian P450s have been generated by their homology with bacterial P450s of known structure. The rather low sequence identity between target and template proteins renders P450 modeling a challenging task. However, the substrate recognition properties of several P450s are consistent with recently developed working models. This review summarizes the major concepts and current approaches of molecular modeling of P450s. JF - Cellular and molecular life sciences : CMLS AU - Dai, R AU - Pincus, M R AU - Friedman, F K AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 487 EP - 499 VL - 57 IS - 3 SN - 1420-682X, 1420-682X KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Animals KW - Mammals KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Models, Molecular KW - Cytochrome P-450 Enzyme System -- chemistry KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71126015?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+and+molecular+life+sciences+%3A+CMLS&rft.atitle=Molecular+modeling+of+mammalian+cytochrome+P450s.&rft.au=Dai%2C+R%3BPincus%2C+M+R%3BFriedman%2C+F+K&rft.aulast=Dai&rft.aufirst=R&rft.date=2000-03-01&rft.volume=57&rft.issue=3&rft.spage=487&rft.isbn=&rft.btitle=&rft.title=Cellular+and+molecular+life+sciences+%3A+CMLS&rft.issn=1420682X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-06 N1 - Date created - 2000-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I clinical trial of liposomal daunorubicin in hepatocellular carcinoma complicating liver cirrhosis. AN - 71110871; 10810429 AB - Chemotherapy has been proposed for patients with hepatocellular carcinoma (HCC) associated with well-compensated cirrhosis who are unsuitable for locoregional treatments. Anthracyclines are the most active agents against HCC, although their toxicity is often unpredictable; thus, there is a need for new active drugs with a safe toxicity profile. The liposomal formulation of the anthracycline daunorubicin has low systemic toxicity and is taken up strongly by the liver. We started a phase I study with liposomal daunorubicin (starting dose 80 mg/m2 every 21 days) in patients with hepatocellular carcinoma and Child-Pugh stage A or B liver cirrhosis. At the starting dose, we recorded dose-limiting toxicities (1 hyperbilirubinemia, 1 prolonged prothrombin time, 1 persisting grade 3 neutropenia) in 3 out of 4 patients. Thus, according to protocol, we went down to the dose level of 60 mg/m2 but still 2 out of 3 patients had unacceptable toxicity (1 hypertransaminasemia, 1 hyperbilirubinemia with encephalopathia). Finally, we treated 4 more patients at the dose level of 40 mg/m2 and again we recorded liver toxicity in three of them. Overall haematological toxicity was mild and significant non-haematologic toxicities, other than hepatic, were not recorded. The toxicity profile observed warns against further assessment of liposomal daunorubicin in patients with hepatocellular carcinoma and liver cirrhosis. JF - Anticancer research AU - Daniele, B AU - De Vivo, R AU - Perrone, F AU - Lastoria, S AU - Tambaro, R AU - Izzo, F AU - Fiore, F AU - Vallone, P AU - Pignata, S AD - Division of Medical Oncology B, National Cancer Institute, Napoli, Italy. PY - 2000 SP - 1249 EP - 1251 VL - 20 IS - 2B SN - 0250-7005, 0250-7005 KW - Antibiotics, Antineoplastic KW - 0 KW - Drug Carriers KW - Liposomes KW - Daunorubicin KW - ZS7284E0ZP KW - Index Medicus KW - Drug Administration Schedule KW - Hyperbilirubinemia -- chemically induced KW - Neoplasm Staging KW - Dose-Response Relationship, Drug KW - Humans KW - Aged KW - Middle Aged KW - Prothrombin Time KW - Male KW - Female KW - Daunorubicin -- administration & dosage KW - Liver Neoplasms -- pathology KW - Antibiotics, Antineoplastic -- administration & dosage KW - Liver Neoplasms -- complications KW - Carcinoma, Hepatocellular -- complications KW - Carcinoma, Hepatocellular -- drug therapy KW - Liver Neoplasms -- drug therapy KW - Daunorubicin -- adverse effects KW - Carcinoma, Hepatocellular -- pathology KW - Liver Cirrhosis -- complications KW - Antibiotics, Antineoplastic -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71110871?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Phase+I+clinical+trial+of+liposomal+daunorubicin+in+hepatocellular+carcinoma+complicating+liver+cirrhosis.&rft.au=Daniele%2C+B%3BDe+Vivo%2C+R%3BPerrone%2C+F%3BLastoria%2C+S%3BTambaro%2C+R%3BIzzo%2C+F%3BFiore%2C+F%3BVallone%2C+P%3BPignata%2C+S&rft.aulast=Daniele&rft.aufirst=B&rft.date=2000-03-01&rft.volume=20&rft.issue=2B&rft.spage=1249&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-31 N1 - Date created - 2000-05-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A comparison of recent and long-term average measurements of nitrate in drinking water. AN - 71108037; 10791601 AB - We evaluated the usefulness of a recent measure of drinking water nitrate as a predictor of long-term average nitrate exposure calculated from historic data. Exposure estimates were calculated for 214 study participants who used public water supplies between 1947 and 1980 in Minnesota. Long-term average nitrate was calculated by linking residential histories to historical nitrate data. For recent exposures, we averaged nitrate measurements in 1980, or the next closest year with measurements. The Spearman correlation coefficient for the relationship between the two measures was 0.54 (95% confidence interval [CI]=0.44-0.63). Agreement was highest among those residing 34 or more years in their town as of 1980 (r(s)=0.70; 95% CI=0.55-0.80). These findings suggest that taking into account the study participants' duration of residence may enhance the validity of using a recent measure as an indicator of past exposures. JF - Journal of exposure analysis and environmental epidemiology AU - Freedman, D M AU - Cantor, K P AU - Ward, M H AU - Helzlsouer, K J AD - Radiation Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20892-7238, USA. mf101e@nih.gov PY - 2000 SP - 206 EP - 209 VL - 10 IS - 2 SN - 1053-4245, 1053-4245 KW - Nitrates KW - 0 KW - Index Medicus KW - Environmental Monitoring KW - Aged, 80 and over KW - Humans KW - Adult KW - Retrospective Studies KW - Aged KW - Middle Aged KW - Time Factors KW - Male KW - Female KW - Risk Assessment KW - Models, Theoretical KW - Water Supply -- analysis KW - Environmental Exposure -- analysis KW - Nitrates -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71108037?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+exposure+analysis+and+environmental+epidemiology&rft.atitle=A+comparison+of+recent+and+long-term+average+measurements+of+nitrate+in+drinking+water.&rft.au=Freedman%2C+D+M%3BCantor%2C+K+P%3BWard%2C+M+H%3BHelzlsouer%2C+K+J&rft.aulast=Freedman&rft.aufirst=D&rft.date=2000-03-01&rft.volume=10&rft.issue=2&rft.spage=206&rft.isbn=&rft.btitle=&rft.title=Journal+of+exposure+analysis+and+environmental+epidemiology&rft.issn=10534245&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-20 N1 - Date created - 2000-06-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association between the level of ERCC-1 expression and the repair of cisplatin-induced DNA damage in human ovarian cancer cells. AN - 71107179; 10810335 AB - Nucleotide excision repair (NER) is responsible for the repair of platinum-DNA lesions. ERCC-1 is a critical gene within the NER pathway, and cells without a functional ERCC-1 do not repair cisplatin-caused DNA damage. The present study was therefore designed to evaluate the relationship between the expression of ERCC-1 and the repair of cisplatin-induced DNA adducts in human ovarian cancer cells in vitro. One hour exposure of MCAS cells to cisplatin yielded an approximately two-fold increment in the levels of ERCC-1 mRNA and ERCC-1 protein, as determined, respectively, by Northern and Western blottings. In addition, nuclear run-on assay showed that ERCC-1 gene transcription rate was increased to about the same extent as steady-state ERCC-1 mRNA and protein, in response to cisplatin treatment. However, the levels of ERCC-1 mRNA, ERCC-1 protein, and ERCC-1 transcript in MCAS cells are two-fold lower than those in A2780/CP70 cells, as previously reported. Furthermore, the repair of cisplatin-DNA adducts in MCAS cells, as measured by atomic absorption spectrometry, is also nearly two-fold less than that in A2780/CP70 cells, indicating a strong association between the level of ERCC-1 expression and the activity of excision repair in these two human ovarian tumor cell lines. These results suggest that ERCC-1 may be a useful marker to monitor the repair of platinum-DNA damage in tumor cells, and further highlight that potential pharmacological approaches which specifically inhibit ERCC-1 expression may increase cellular sensitivity to cisplatin. JF - Anticancer research AU - Li, Q AU - Yu, J J AU - Mu, C AU - Yunmbam, M K AU - Slavsky, D AU - Cross, C L AU - Bostick-Bruton, F AU - Reed, E AD - Developmental Therapeutics Department, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 2000 SP - 645 EP - 652 VL - 20 IS - 2A SN - 0250-7005, 0250-7005 KW - DNA Adducts KW - 0 KW - DNA-Binding Proteins KW - Proteins KW - RNA, Messenger KW - cisplatin-DNA adduct KW - ERCC1 protein, human KW - EC 3.1.- KW - Endonucleases KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Ovarian Neoplasms KW - Tumor Cells, Cultured KW - Cell Nucleus -- metabolism KW - Kinetics KW - Humans KW - Transcription, Genetic KW - RNA, Messenger -- genetics KW - Female KW - DNA Repair KW - DNA Adducts -- analysis KW - DNA Damage KW - Cisplatin -- toxicity KW - Cisplatin -- analysis KW - Proteins -- genetics KW - Gene Expression Regulation, Neoplastic -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71107179?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Association+between+the+level+of+ERCC-1+expression+and+the+repair+of+cisplatin-induced+DNA+damage+in+human+ovarian+cancer+cells.&rft.au=Li%2C+Q%3BYu%2C+J+J%3BMu%2C+C%3BYunmbam%2C+M+K%3BSlavsky%2C+D%3BCross%2C+C+L%3BBostick-Bruton%2C+F%3BReed%2C+E&rft.aulast=Li&rft.aufirst=Q&rft.date=2000-03-01&rft.volume=20&rft.issue=2A&rft.spage=645&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-01 N1 - Date created - 2000-06-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Abnormal cell differentiation and p21 expression of endometrial epithelial cells following developmental exposure to diethylstilbestrol (DES). AN - 71100585; 10805141 AB - Gene expression relevant to abnormal cell differentiation and altered cell cycle in endometrial epithelial cells was investigated immunohistochemically in developing mouse uteri exposed neonatally to diethylstilbestrol (DES). Female CD-1 mice were given daily s.c. injections of 2 microg of DES in corn oil or were given corn oil alone (control) at 1-5 days of age and euthanatized at 5, 6, 7, 8, 15, and 22 days of age. The endometrial epithelial cells of DES-treated mice at 5-8 days of age showed enhanced staining intensity for the estrogen receptor alpha (ER alpha), whereas the stromal cells showed decreased staining reaction; the epithelial cells showed that the protein encoded by the c-fos proto-oncogene, which plays a key role in regulating diverse estrogen-related cellular differentiation patterns, was enhanced. These cells also showed increased expression of lactoferrin, a sensitive protein marker of estrogen exposure, although the staining intensity decreased after exposure ended. The stain for p21 protein, a mitotic inhibitor which suppresses cyclin-dependent kinase activity, showed frequent positively stained cells in DES-treated mice at 5-15 days of age, whereas no accumulation of p53 protein of either wild or mutant type was detected immunohistochemically in these cells. These results indicate that suppressed cell cycle activity of endometrial epithelial cells and abnormal estrogen-related differentiation at the developmental stage following neonatal DES exposure may be caused, in part, by transient altered expression of ER alpha and expression of the p21 gene, which appears to be induced by a p53-independent mechanism. JF - Toxicologic pathology AU - Yoshida, A AU - Newbold, R R AU - Dixon, D AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 2000 SP - 237 EP - 245 VL - 28 IS - 2 SN - 0192-6233, 0192-6233 KW - Estrogen Receptor alpha KW - 0 KW - Estrogens, Non-Steroidal KW - Proto-Oncogene Proteins c-fos KW - Receptors, Estrogen KW - Diethylstilbestrol KW - 731DCA35BT KW - Lactoferrin KW - EC 3.4.21.- KW - Oncogene Protein p21(ras) KW - EC 3.6.5.2 KW - Index Medicus KW - Animals KW - Proto-Oncogene Proteins c-fos -- metabolism KW - Mice KW - Receptors, Estrogen -- metabolism KW - Pregnancy KW - Epithelial Cells -- metabolism KW - Animals, Newborn KW - Epithelial Cells -- drug effects KW - Epithelial Cells -- pathology KW - Injections, Subcutaneous KW - Cell Differentiation -- drug effects KW - Immunohistochemistry KW - Female KW - Endometrium -- drug effects KW - Oncogene Protein p21(ras) -- metabolism KW - Diethylstilbestrol -- toxicity KW - Estrogens, Non-Steroidal -- toxicity KW - Endometrium -- pathology KW - Endometrium -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71100585?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Abnormal+cell+differentiation+and+p21+expression+of+endometrial+epithelial+cells+following+developmental+exposure+to+diethylstilbestrol+%28DES%29.&rft.au=Yoshida%2C+A%3BNewbold%2C+R+R%3BDixon%2C+D&rft.aulast=Yoshida&rft.aufirst=A&rft.date=2000-03-01&rft.volume=28&rft.issue=2&rft.spage=237&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-26 N1 - Date created - 2000-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of compounding drug-related stimuli: escalation of heroin self-administration. AN - 71077165; 10784010 AB - Previous experiments have demonstrated that presenting independently established discriminative stimuli in compound can substantially increase operant responding maintained by food reinforcement or shock avoidance. Recently, this phenomenon was also shown to occur with cocaine self-administration. The present study further assessed the generality of these stimulus-compounding effects by systematically replicating them with heroin self-administration. Rats' nose-poke responses produced intravenous heroin (0.025 mg/kg per infusion) on a variable-ratio schedule when either a tone or a light was present. In the absence of these stimuli, responding was not reinforced. Once discriminative control by the tone and light had been established, the stimuli were presented in compound under extinction (with heroin discontinued) or maintenance conditions (with heroin available during test-stimulus presentations). In extinction, the tone-light compound increased responding approximately threefold compared to tone or light alone. Under maintenance conditions, compounding increased heroin intake approximately twofold. These effects closely matched those obtained earlier with cocaine. This consistency across pharmacological classes and across drug and nondrug reinforcers further confirms that (a) self-administered drugs support conditioning and learning in a manner similar to that supported by other reinforcers; and (b) multiple drug-related cues interact in lawful and predictable ways to affect drug seeking and consumption. JF - Journal of the experimental analysis of behavior AU - Panlilio, L V AU - Weiss, S J AU - Schindler, C W AD - Preclinical Pharmacology Section, Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. lpanlili@intra.nida.nih.gov Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 211 EP - 224 VL - 73 IS - 2 SN - 0022-5002, 0022-5002 KW - Heroin KW - 70D95007SX KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Self Administration KW - Motivation KW - Reinforcement (Psychology) KW - Disease Models, Animal KW - Behavior, Animal -- physiology KW - Male KW - Heroin Dependence -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71077165?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+experimental+analysis+of+behavior&rft.atitle=Effects+of+compounding+drug-related+stimuli%3A+escalation+of+heroin+self-administration.&rft.au=Panlilio%2C+L+V%3BWeiss%2C+S+J%3BSchindler%2C+C+W&rft.aulast=Panlilio&rft.aufirst=L&rft.date=2000-03-01&rft.volume=73&rft.issue=2&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+experimental+analysis+of+behavior&rft.issn=00225002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-11 N1 - Date created - 2000-07-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: NIDA Res Monogr. 1988;84:180-95 [3147382] NIDA Res Monogr. 1988;84:122-40 [3147379] J Exp Anal Behav. 1988 Sep;50(2):237-47 [3193056] Psychol Rev. 1984 Apr;91(2):251-68 [6571424] NIDA Res Monogr. 1986;71:146-64 [3025733] JAMA. 1985 Jul 5;254(1):81-3 [4039767] Life Sci. 1983 Oct 3;33(14):1341-51 [6684721] Psychopharmacol Bull. 1982 Oct;18(4):210-4 [6130562] Pharmacol Biochem Behav. 2000 Jan 1;65(1):83-9 [10638640] Pharmacol Biochem Behav. 1989 Apr;32(4):1009-15 [2798525] J Exp Psychol. 1964 Aug;68:151-5 [14194401] J Neural Transm Gen Sect. 1989;78(3):231-47 [2803700] Ann N Y Acad Sci. 1992 Jun 28;654:171-91 [1632582] Pharmacol Biochem Behav. 1993 Jan;44(1):191-8 [8430122] Brain Res Brain Res Rev. 1993 Sep-Dec;18(3):247-91 [8401595] Psychopharmacology (Berl). 1993;112(2-3):163-82 [7871016] Synapse. 1995 Oct;21(2):140-8 [8584975] NIDA Res Monogr. 1994;145:163-90 [8742813] Curr Opin Neurobiol. 1996 Apr;6(2):243-51 [8725967] Psychopharmacology (Berl). 1996 Jun;125(3):202-8 [8815954] Q J Exp Psychol B. 1996 Nov;49(4):357-81 [8962540] Pharmacol Biochem Behav. 1997 May-Jun;57(1-2):145-50 [9164565] J Neurosci. 1998 Apr 15;18(8):3098-115 [9526026] Psychopharmacology (Berl). 1998 Mar;136(1):70-4 [9537684] Eur J Pharmacol. 1998 Mar 12;345(1):13-26 [9593589] Behav Pharmacol. 1997 Dec;8(8):691-8 [9832954] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of a two-stage case-control study with cluster sampling of controls: application to nonmelanoma skin cancer. AN - 71076838; 10783795 AB - We present a pseudolikelihood approach for analyzing a two-stage population-based case-control study with cluster sampling of controls. These methods were developed to analyze data from a study of nonmelanoma skin cancer (NMSC). This study was designed to evaluate the role of ultraviolet radiation (UVB) on NMSC risk while adjusting for age group, which is known for all subjects, and for other individual-level factors, such as susceptibility to sunburn, which are known only for participants in the case-control study. The methods presented yield estimates of relative and absolute risk, with standard errors, while accounting naturally for the two-stage sampling of the cohort and cluster sampling of controls. JF - Biometrics AU - Fears, T R AU - Gail, M H AD - Biostatistics Branch, National Cancer Institute, Rockville, Maryland 20892-7244, USA. fearst@exchange.nih.gov Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 190 EP - 198 VL - 56 IS - 1 SN - 0006-341X, 0006-341X KW - Index Medicus KW - Biometry KW - Humans KW - Aged KW - Models, Statistical KW - Likelihood Functions KW - Risk Factors KW - Adult KW - Cohort Studies KW - Ultraviolet Rays -- adverse effects KW - Case-Control Studies KW - Data Interpretation, Statistical KW - Middle Aged KW - Cluster Analysis KW - Neoplasms, Radiation-Induced -- etiology KW - Skin Neoplasms -- etiology KW - Neoplasms, Radiation-Induced -- epidemiology KW - Skin Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71076838?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometrics&rft.atitle=Analysis+of+a+two-stage+case-control+study+with+cluster+sampling+of+controls%3A+application+to+nonmelanoma+skin+cancer.&rft.au=Fears%2C+T+R%3BGail%2C+M+H&rft.aulast=Fears&rft.aufirst=T&rft.date=2000-03-01&rft.volume=56&rft.issue=1&rft.spage=190&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-19 N1 - Date created - 2000-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Addiction, dopamine, and the molecular mechanisms of memory. AN - 71058208; 10774721 JF - Neuron AU - Berke, J D AU - Hyman, S E AD - Secton on Molecular Plasticity, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 515 EP - 532 VL - 25 IS - 3 SN - 0896-6273, 0896-6273 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Humans KW - Substance-Related Disorders -- physiopathology KW - Dopamine -- genetics KW - Memory -- drug effects KW - Brain Chemistry -- genetics KW - Brain Chemistry -- drug effects KW - Memory -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71058208?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuron&rft.atitle=Addiction%2C+dopamine%2C+and+the+molecular+mechanisms+of+memory.&rft.au=Berke%2C+J+D%3BHyman%2C+S+E&rft.aulast=Berke&rft.aufirst=J&rft.date=2000-03-01&rft.volume=25&rft.issue=3&rft.spage=515&rft.isbn=&rft.btitle=&rft.title=Neuron&rft.issn=08966273&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-02 N1 - Date created - 2000-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NAT2 slow acetylation and bladder cancer risk: a meta-analysis of 22 case-control studies conducted in the general population. AN - 71029363; 10761999 AB - The NAT2 gene is involved in phase II detoxification of aromatic monoamines, a class of known bladder carcinogens. Certain allelic combinations result in the slow acetylation phenotype, which is thought to increase bladder cancer risk. We conducted a meta-analysis of all identifiable published case-control studies conducted in the general population that had examined the relationship of acetylation status and bladder cancer risk (22 studies, 2496 cases, 3340 controls). Using meta-analysis techniques that employed weighting based on individual-study variation, slow acetylators had an approximately 40% increase in risk compared with rapid acetylators [odds ratio (OR) 1.4, 95% confidence interval (CI) 1.2-1.6]. Statistical tests indicated, however, that pooling of all studies, or of studies conducted in Caucasian populations, hid potentially important heterogeneity in the individual study results, and suggested that the relationship of NAT2 slow acetylation and bladder cancer risk might differ by geographical region. Studies conducted in Asia generated a summary OR of 2.1 (CI 1.2-3.8), in Europe, a summary OR of 1.4 (CI 1.2-1.6), and in the USA, a summary OR of 0.9 (CI 0.7-1.3). Among European studies, the relationship between NAT2 slow acetylation and bladder cancer risk did not differ by method used to assess acetylation status (older drug-based phenotyping methods: 10 studies, OR 1.5, CI 1.2-1.8; more recent NAT2 genotyping methods: four studies, OR 1.4, CI 1.1-1.7). Our results suggest that in most populations studied to date, NAT2 slow acetylation status is associated with a modest increase in bladder cancer risk. JF - Pharmacogenetics AU - Marcus, P M AU - Vineis, P AU - Rothman, N AD - Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland 20892-7354, USA. pm145q@nih.gov Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 115 EP - 122 VL - 10 IS - 2 SN - 0960-314X, 0960-314X KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - NAT2 protein, human KW - Index Medicus KW - Phenotype KW - Genotype KW - Acetylation KW - Risk Factors KW - Humans KW - Case-Control Studies KW - Urinary Bladder Neoplasms -- epidemiology KW - Urinary Bladder Neoplasms -- genetics KW - Population Surveillance KW - Arylamine N-Acetyltransferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71029363?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenetics&rft.atitle=NAT2+slow+acetylation+and+bladder+cancer+risk%3A+a+meta-analysis+of+22+case-control+studies+conducted+in+the+general+population.&rft.au=Marcus%2C+P+M%3BVineis%2C+P%3BRothman%2C+N&rft.aulast=Marcus&rft.aufirst=P&rft.date=2000-03-01&rft.volume=10&rft.issue=2&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-08 N1 - Date created - 2000-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Progress in the treatment of proliferative lupus nephritis. AN - 71023158; 10757214 AB - Lupus nephritis is often well developed at the time of diagnosis. High-dose corticosteroids are universally accepted as the initial approach to the control of severe inflammation in the kidney. Long-term disease control and the minimization of iatrogenic risk usually require adjunctive therapies that target the more fundamental immunoregulatory disturbances of lymphoid cells. Of the available cytotoxic drugs, cyclophosphamide is currently among the most effective, although it cannot be considered ideal in terms of efficacy or toxicity. New prospects for the treatment of proliferative lupus nephritis include novel immunosuppressive agents (e.g. mycophenolate, cyclosporine, fludarabine), combination chemotherapy (e.g. cyclophosphamide plus fludarabine), and sequential chemotherapy (e.g. cyclophosphamide-azathioprine), immunological reconstitution using intensive cytoreductive chemotherapy (with or without stem cell rescue), co-stimulatory molecule inhibition (e.g. humanized anti-CD154 monoclonal antibody, CTLA4-Ig). Gene therapy remains an attractive prospect, but its feasibility clearly depends on the further definition of lupus-promoting genes and the availability of methods to establish stable expression of disease-corrective genes in the appropriate lymphoid cells. JF - Current opinion in nephrology and hypertension AU - Balow, J E AU - Austin, H A AD - Kidney Disease Section, NIDDK, National Institutes of Health, Bethesda, MD 20892-1818, USA. james_e_balow@nih.gov Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 107 EP - 115 VL - 9 IS - 2 SN - 1062-4821, 1062-4821 KW - Immunologic Factors KW - 0 KW - Immunosuppressive Agents KW - Index Medicus KW - Immunologic Factors -- therapeutic use KW - Humans KW - Immunosuppressive Agents -- therapeutic use KW - Lupus Nephritis -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71023158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nephrology+and+hypertension&rft.atitle=Progress+in+the+treatment+of+proliferative+lupus+nephritis.&rft.au=Balow%2C+J+E%3BAustin%2C+H+A&rft.aulast=Balow&rft.aufirst=J&rft.date=2000-03-01&rft.volume=9&rft.issue=2&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+nephrology+and+hypertension&rft.issn=10624821&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-25 N1 - Date created - 2000-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acute myocardial ischemia after administration of ondansetron hydrochloride. AN - 71003597; 10719974 JF - Anesthesiology AU - Bosek, V AU - Hu, P AU - Robinson, L A AD - Department of Anesthesiology, H. Lee Moffitt Cancer Center and Research Institute NCI, University of South Florida College of Medicine, Tampa 33612-9497, USA. bosekv@moffitt.usf.edu Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 885 EP - 887 VL - 92 IS - 3 SN - 0003-3022, 0003-3022 KW - Antiemetics KW - 0 KW - Vasodilator Agents KW - Ondansetron KW - 4AF302ESOS KW - Nitroglycerin KW - G59M7S0WS3 KW - Abridged Index Medicus KW - Index Medicus KW - Acute Disease KW - Injections, Intravenous KW - Humans KW - Electrocardiography KW - Vasodilator Agents -- therapeutic use KW - Middle Aged KW - Nitroglycerin -- therapeutic use KW - Female KW - Antiemetics -- administration & dosage KW - Postoperative Complications -- chemically induced KW - Ondansetron -- administration & dosage KW - Myocardial Ischemia -- drug therapy KW - Myocardial Ischemia -- chemically induced KW - Ondansetron -- adverse effects KW - Antiemetics -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71003597?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Acute+myocardial+ischemia+after+administration+of+ondansetron+hydrochloride.&rft.au=Bosek%2C+V%3BHu%2C+P%3BRobinson%2C+L+A&rft.aulast=Bosek&rft.aufirst=V&rft.date=2000-03-01&rft.volume=92&rft.issue=3&rft.spage=885&rft.isbn=&rft.btitle=&rft.title=Anesthesiology&rft.issn=00033022&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-28 N1 - Date created - 2000-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adrenal cancer. AN - 71002153; 10732261 AB - Adrenal cancer is a rare neoplasm. Up to 1 in 1500 adrenal incidentalomas, however, may hide a carcinoma, which, if diagnosed late or left untreated, is associated with significant morbidity and mortality. Despite extensive investigation of the molecular mechanisms involved in adrenal carcinogenesis and significant improvements in diagnostic imaging, efforts to cure advanced adrenal cancer remain largely unsuccessful. This article reviews the recent advances in molecular understanding, clinical diagnosis, and treatment of adrenal cancer. JF - Endocrinology and metabolism clinics of North America AU - Stratakis, C A AU - Chrousos, G P AD - Department of Pediatrics, Georgetown University School of Medicine, Washington, DC, USA. stratakc@ccl.nichd.nih.gov Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 15 EP - 25, vii-viii VL - 29 IS - 1 SN - 0889-8529, 0889-8529 KW - Index Medicus KW - Chromosomes, Human, Pair 17 KW - Humans KW - Prognosis KW - Chromosomes, Human, Pair 11 KW - Adrenal Cortex Neoplasms -- epidemiology KW - Adrenal Cortex Neoplasms -- surgery KW - Adrenal Cortex Neoplasms -- genetics KW - Adrenal Cortex Neoplasms -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71002153?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology+and+metabolism+clinics+of+North+America&rft.atitle=Adrenal+cancer.&rft.au=Stratakis%2C+C+A%3BChrousos%2C+G+P&rft.aulast=Stratakis&rft.aufirst=C&rft.date=2000-03-01&rft.volume=29&rft.issue=1&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=Endocrinology+and+metabolism+clinics+of+North+America&rft.issn=08898529&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-14 N1 - Date created - 2000-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Orbitofrontal cortex and human drug abuse: functional imaging. AN - 70991098; 10731228 AB - The orbitofrontal cortex (OFC) plays a central role in human behavior. Anatomically connected with association areas of all sensory modalities, limbic structures, prefrontal cortical regions that mediate executive function and subcortical nuclei, this brain region can serve to integrate the physical and emotional attributes of a stimulusobject and establish a motivational value based on estimation of potential reward. To the extent that addictive disorders reflect a dysregulation of the ability to evaluate potential reward against harm from drug self-administration, it would be anticipated that substance abuse disorder might reflect dysfunction of the OFC. With the application of brain imaging techniques to the study of human substance abuse, evidence has been obtained that activity in the OFC and its connections plays a role in several components of the maladaptive behavior of substance abuse, including expectancy, craving and impaired decision making. JF - Cerebral cortex (New York, N.Y. : 1991) AU - London, E D AU - Ernst, M AU - Grant, S AU - Bonson, K AU - Weinstein, A AD - Brain Imaging Center, National Institute on Drug Abuse, Baltimore, MD 21224, USA. elondon@tracer.org Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 334 EP - 342 VL - 10 IS - 3 SN - 1047-3211, 1047-3211 KW - Index Medicus KW - Personality -- drug effects KW - Humans KW - Substance-Related Disorders -- physiopathology KW - Magnetic Resonance Imaging KW - Frontal Lobe -- physiopathology KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70991098?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cerebral+cortex+%28New+York%2C+N.Y.+%3A+1991%29&rft.atitle=Orbitofrontal+cortex+and+human+drug+abuse%3A+functional+imaging.&rft.au=London%2C+E+D%3BErnst%2C+M%3BGrant%2C+S%3BBonson%2C+K%3BWeinstein%2C+A&rft.aulast=London&rft.aufirst=E&rft.date=2000-03-01&rft.volume=10&rft.issue=3&rft.spage=334&rft.isbn=&rft.btitle=&rft.title=Cerebral+cortex+%28New+York%2C+N.Y.+%3A+1991%29&rft.issn=10473211&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-27 N1 - Date created - 2000-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Are children living near high-voltage power lines at increased risk of acute lymphoblastic leukemia? AN - 70987771; 10707920 AB - In the National Cancer Institute/Children's Cancer Group case-control study of childhood acute lymphoblastic leukemia (1989-1993), living in a home with a high-voltage wire code was not associated with disease risk. To further investigate risk near power lines, the authors analyzed distance to transmission and three-phase primary distribution lines within 40 m of homes and created an exposure index of distance and strength of multiple power lines (408 case-control pairs). Neither distance nor exposure index was related to risk of childhood acute lymphoblastic leukemia, although both were associated with in-home magnetic field measurements. Residence near high-voltage lines did not increase risk. JF - American journal of epidemiology AU - Kleinerman, R A AU - Kaune, W T AU - Hatch, E E AU - Wacholder, S AU - Linet, M S AU - Robison, L L AU - Niwa, S AU - Tarone, R E AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20892, USA. Y1 - 2000/03/01/ PY - 2000 DA - 2000 Mar 01 SP - 512 EP - 515 VL - 151 IS - 5 SN - 0002-9262, 0002-9262 KW - Index Medicus KW - Risk Factors KW - Humans KW - Retrospective Studies KW - Incidence KW - Child KW - Adolescent KW - United States -- epidemiology KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- epidemiology KW - Electric Power Supplies -- adverse effects KW - Electromagnetic Fields -- adverse effects KW - Environmental Exposure -- adverse effects KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70987771?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Are+children+living+near+high-voltage+power+lines+at+increased+risk+of+acute+lymphoblastic+leukemia%3F&rft.au=Kleinerman%2C+R+A%3BKaune%2C+W+T%3BHatch%2C+E+E%3BWacholder%2C+S%3BLinet%2C+M+S%3BRobison%2C+L+L%3BNiwa%2C+S%3BTarone%2C+R+E&rft.aulast=Kleinerman&rft.aufirst=R&rft.date=2000-03-01&rft.volume=151&rft.issue=5&rft.spage=512&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 - 2000-03-17 N1 - Date created - 2000-03-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Epidemiol. 2001 Mar 15;153(6):615-7 [11257071] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence of hepatitis G virus in patients with hemophilia and their steady female sexual partners. AN - 70980849; 10726654 AB - Hepatitis G virus (HGV), also known as GB virus C, is a newly discovered Flavivirus that is transmissible by blood transfusion and other possible routes. To study the risk of sexual transmission of HGV in female sexual partners of men with hemophilia (n = 161 couples). Blood samples obtained from 11 medical centers were analyzed for (1) HGV RNA by polymerase chain reaction; (2) antibodies to HGV by enzyme immunoassay; and (3) other viruses and T-cell counts by routine laboratory tests. Subjects completed a questionnaire that assessed sexual intercourse frequency, number of sexual partners, condom usage, sexually transmitted diseases, illicit drug usage, and needlestick or broken-glass injuries. The HGV infection (RNA +/- antibody positive) prevalence was 48% among men and 21% among women. Prevalence of hepatitis C virus, hepatitis B virus, and HIV among men was 99%, 94%, and 86%, compared with 3%, 11%, and 12% among women, respectively. The odds ratio for HGV infection for women with an HGV-positive male sexual partner was 2.14 (P = 0.06) without adjustment, and 2.77 (P = 0.03) with adjustment for other variables, none of which were independently significant. These results suggest a low level of HGV sexual transmission. JF - Sexually transmitted diseases AU - Yeo, A E AU - Matsumoto, A AU - Shih, J W AU - Alter, H J AU - Goedert, J J AD - Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 178 EP - 182 VL - 27 IS - 3 SN - 0148-5717, 0148-5717 KW - Antibodies, Viral KW - 0 KW - RNA, Viral KW - Index Medicus KW - AIDS/HIV KW - United States KW - Greece KW - Humans KW - Seroepidemiologic Studies KW - Austria KW - Antibodies, Viral -- analysis KW - Sexual Behavior KW - Polymerase Chain Reaction KW - Logistic Models KW - Risk Factors KW - Surveys and Questionnaires KW - Substance Abuse, Intravenous -- complications KW - Female KW - Immunoenzyme Techniques KW - Male KW - RNA, Viral -- analysis KW - Flaviviridae -- genetics KW - Sexually Transmitted Diseases -- immunology KW - Hepatitis, Viral, Human -- blood KW - Flaviviridae -- immunology KW - Sexually Transmitted Diseases -- etiology KW - Hepatitis, Viral, Human -- etiology KW - Hepatitis, Viral, Human -- transmission KW - Hemophilia A -- complications KW - Sexually Transmitted Diseases -- blood KW - Hepatitis, Viral, Human -- immunology KW - Sexually Transmitted Diseases -- transmission KW - Sexual Partners UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70980849?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Sexually+transmitted+diseases&rft.atitle=Prevalence+of+hepatitis+G+virus+in+patients+with+hemophilia+and+their+steady+female+sexual+partners.&rft.au=Yeo%2C+A+E%3BMatsumoto%2C+A%3BShih%2C+J+W%3BAlter%2C+H+J%3BGoedert%2C+J+J&rft.aulast=Yeo&rft.aufirst=A&rft.date=2000-03-01&rft.volume=27&rft.issue=3&rft.spage=178&rft.isbn=&rft.btitle=&rft.title=Sexually+transmitted+diseases&rft.issn=01485717&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-12 N1 - Date created - 2000-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 mutations experimentally induced by 8-methoxypsoralen plus UVA (PUVA) differ from those found in human skin cancers in PUVA-treated patients. AN - 70972377; 10719037 AB - 8-Methoxypsoralen (8-MOP) plus UVA irradiation (PUVA therapy) has been used for the treatment of psoriasis. PUVA therapy has been associated with an increased risk of developing skin squamous cell carcinoma (SCC). In order to determine the PUVA-induced p53 mutation spectrum, a yeast expression vector harbouring a human wild-type p53 cDNA was incubated with 8-MOP, and UVA irradiated in vitro. PUVA-damaged and undamaged DNA was transfected into a yeast strain containing the ADE2 gene regulated by a p53-responsive promoter. An 8-MOP concentration-dependent decrease in survival and increase in mutant frequency were observed. At a fixed 8-MOP concentration, survival decreased and mutant frequency increased as UVA irradiation increased. Eleven mutant clones contained 11 mutations: 10 were single base pair substitutions, the remaining one being a complex mutation. All eight T:A-targeted mutations were at 5'-TpA sites, hallmark mutations of PUVA mutagenesis. Through a rigorous statistical test, the PUVA-induced p53 mutation spectrum appears to differ significantly (P < 0.0002) from that observed in SCC in PUVA-treated patients. The present work demonstrates that a specific PUVA-induced mutational fingerprint could be obtained and recognized on human p53 cDNA. This result may suggest that PUVA therapy can be a risk factor for the development of SCC in psoriasis patients through a mechanism not involving the induction of p53 mutations. JF - Mutagenesis AU - Monti, P AU - Inga, A AU - Aprile, A AU - Campomenosi, P AU - Menichini, P AU - Ottaggio, L AU - Viaggi, S AU - Ghigliotti, G AU - Abbondandolo, A AU - Fronza, G AD - Mutagenesis Laboratory, National Cancer Institute (IST), Largo Rosanna Benzi, 10, 16132-Genova. Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 127 EP - 132 VL - 15 IS - 2 SN - 0267-8357, 0267-8357 KW - Methoxsalen KW - U4VJ29L7BQ KW - Index Medicus KW - Transfection KW - Humans KW - DNA Mutational Analysis KW - Plasmids KW - Skin Neoplasms -- genetics KW - Ultraviolet Rays KW - Genes, p53 KW - PUVA Therapy KW - Mutation KW - Methoxsalen -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70972377?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutagenesis&rft.atitle=p53+mutations+experimentally+induced+by+8-methoxypsoralen+plus+UVA+%28PUVA%29+differ+from+those+found+in+human+skin+cancers+in+PUVA-treated+patients.&rft.au=Monti%2C+P%3BInga%2C+A%3BAprile%2C+A%3BCampomenosi%2C+P%3BMenichini%2C+P%3BOttaggio%2C+L%3BViaggi%2C+S%3BGhigliotti%2C+G%3BAbbondandolo%2C+A%3BFronza%2C+G&rft.aulast=Monti&rft.aufirst=P&rft.date=2000-03-01&rft.volume=15&rft.issue=2&rft.spage=127&rft.isbn=&rft.btitle=&rft.title=Mutagenesis&rft.issn=02678357&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-12 N1 - Date created - 2000-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemoprotection of hematopoietic cells by a mutant P-glycoprotein resistant to a potent chemosensitizer of multidrug-resistant cancers. AN - 70968267; 10724034 AB - Cancers are frequently chemoresistant because of overexpression of P-glycoprotein. Two different approaches to improve cancer treatment are currently being investigated in clinical trials: inhibition of P-glycoprotein function by reversing agents, and alleviation of leukocytopenia by MDR1 gene transfer to normal bone marrow of patients. We report here that retroviral vectors encoding a mutant P-glycoprotein (MDR1-F983A) protect hematopoietic cells from anticancer drugs even in the presence of trans-(E)-flupentixol, an inhibitor of P-glycoprotein. Transfer of either mutant or wild-type MDR1 to K562 erythroleukemia cells or primary murine bone marrow resulted in reduced accumulation of daunomycin and vinblastine because of increased drug efflux.trans-(E)-Flupentixol at concentrations up to 10 microM failed to reverse drug efflux mediated by the product of the mutant MDR1 while wild-type P-glycoprotein was inhibited. In the presence of 2 microM trans-(E)-flupentixol chemoresistance to daunomycin was circumvented only in K562 cells transduced with wild-type, but not with mutant, MDR1. Moreover, drug resistance of KB-8-5 epidermoid cancer cells, which express the wild-type MDR1 gene at levels comparable to clinical specimens from multidrug-resistant cancers, was fully overcome in the presence of trans-(E)-flupentixol. Vectors expressing mutant P-glycoprotein may help improve chemotherapy by allowing safe dose intensification under conditions in which multidrug-resistant cancers are rendered drug sensitive by reversing agents. JF - Human gene therapy AU - Hafkemeyer, P AU - Licht, T AU - Pastan, I AU - Gottesman, M M AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2000/03/01/ PY - 2000 DA - 2000 Mar 01 SP - 555 EP - 565 VL - 11 IS - 4 SN - 1043-0342, 1043-0342 KW - Antineoplastic Agents KW - 0 KW - P-Glycoprotein KW - Vincristine KW - 5J49Q6B70F KW - Flupenthixol KW - FA0UYH6QUO KW - Daunorubicin KW - ZS7284E0ZP KW - Index Medicus KW - Animals KW - Vincristine -- adverse effects KW - Gene Transfer Techniques KW - Humans KW - Genetic Vectors KW - Daunorubicin -- adverse effects KW - Mice KW - Retroviridae -- genetics KW - K562 Cells KW - Bone Marrow Cells -- drug effects KW - P-Glycoprotein -- genetics KW - Flupenthixol -- pharmacology KW - Drug Resistance, Neoplasm KW - Mutation KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70968267?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+gene+therapy&rft.atitle=Chemoprotection+of+hematopoietic+cells+by+a+mutant+P-glycoprotein+resistant+to+a+potent+chemosensitizer+of+multidrug-resistant+cancers.&rft.au=Hafkemeyer%2C+P%3BLicht%2C+T%3BPastan%2C+I%3BGottesman%2C+M+M&rft.aulast=Hafkemeyer&rft.aufirst=P&rft.date=2000-03-01&rft.volume=11&rft.issue=4&rft.spage=555&rft.isbn=&rft.btitle=&rft.title=Human+gene+therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-13 N1 - Date created - 2000-04-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Hum Gene Ther 2000 May 1;11(7):1112 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular mechanisms of inactivation of TGF-beta receptors during carcinogenesis. AN - 70962400; 10708963 AB - Signals from the TGF-betas are mediated by the TGF-beta receptors and their substrates, the Smad proteins. Inactivation of either of the two transmembrane serine/threonine kinases called the TGF-beta type I and type II receptors is now known to underlie a wide variety of human pathologies including, especially carcinogenesis. Numerous studies have now demonstrated that the TGF-beta receptor complex and its downstream signaling intermediates constitute a tumor suppressor pathway. We review here a specific pathway of mutational inactivation of the TGF-beta type II receptor resulting from microsatellite instability and demonstrate that, by contrast, the most common mechanism of loss of expression of the TGF-beta type II receptor involves transcriptional repression. This provides a new target for therapeutic intervention. JF - Cytokine & growth factor reviews AU - Kim, S J AU - Im, Y H AU - Markowitz, S D AU - Bang, Y J AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-5055, USA. kims@dce41.nci.nih.gov PY - 2000 SP - 159 EP - 168 VL - 11 IS - 1-2 SN - 1359-6101, 1359-6101 KW - Receptors, Transforming Growth Factor beta KW - 0 KW - TGF-beta type I receptor KW - EC 2.7.1.11 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Activin Receptors, Type I KW - EC 2.7.11.30 KW - transforming growth factor-beta type II receptor KW - Index Medicus KW - Animals KW - Protein-Serine-Threonine Kinases -- metabolism KW - Gene Silencing KW - Humans KW - Transcription, Genetic KW - Protein-Serine-Threonine Kinases -- genetics KW - Mutation KW - Receptors, Transforming Growth Factor beta -- genetics KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Neoplasms -- genetics KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70962400?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytokine+%26+growth+factor+reviews&rft.atitle=Molecular+mechanisms+of+inactivation+of+TGF-beta+receptors+during+carcinogenesis.&rft.au=Kim%2C+S+J%3BIm%2C+Y+H%3BMarkowitz%2C+S+D%3BBang%2C+Y+J&rft.aulast=Kim&rft.aufirst=S&rft.date=2000-03-01&rft.volume=11&rft.issue=1-2&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=Cytokine+%26+growth+factor+reviews&rft.issn=13596101&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-11 N1 - Date created - 2000-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Murine models define the role of TGF-beta as a master regulator of immune cell function. AN - 70962364; 10708955 AB - Many members of transforming growth factor-beta (TGF-beta) superfamily, including not only TGF-beta, but also the activins, and bone morphogenetic proteins (BMPs), have been demonstrated to affect the development and function of immune cells. From the proliferation and differentiation of pluripotent stem cells, to the activation and migration of mature lymphoid and myeloid lineages, the TGF-betas have been recognized for their ability to modulate the manner in which such cells respond to stimuli in their environment. Recent studies involving disruption of this pathway in genetically engineered mice now emphasize the importance of this activity and validate functional models predicted by in vitro studies. Phenotypic differences between mice harboring mutations in the TGF-beta1 ligand and the TGF-beta receptor-activated signaling intermediate Smad3 are presented and serve to highlight the valuable role of these in vivo genetic tests of function. JF - Cytokine & growth factor reviews AU - Letterio, J J AD - Laboratory of Cell Regulation and Carcinogenesis, The National Cancer Institute, NIH, Bethesda, MD 20892-5055, USA. letterij@mail.nih.gov PY - 2000 SP - 81 EP - 87 VL - 11 IS - 1-2 SN - 1359-6101, 1359-6101 KW - DNA-Binding Proteins KW - 0 KW - Smad3 Protein KW - Smad3 protein, mouse KW - Trans-Activators KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - Mice, Mutant Strains KW - Mice KW - Mice, Transgenic KW - Signal Transduction KW - Trans-Activators -- metabolism KW - Trans-Activators -- genetics KW - DNA-Binding Proteins -- genetics KW - Trans-Activators -- immunology KW - Transforming Growth Factor beta -- genetics KW - Immune System -- physiology KW - Transforming Growth Factor beta -- metabolism KW - Transforming Growth Factor beta -- immunology KW - DNA-Binding Proteins -- immunology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70962364?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytokine+%26+growth+factor+reviews&rft.atitle=Murine+models+define+the+role+of+TGF-beta+as+a+master+regulator+of+immune+cell+function.&rft.au=Letterio%2C+J+J&rft.aulast=Letterio&rft.aufirst=J&rft.date=2000-03-01&rft.volume=11&rft.issue=1-2&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Cytokine+%26+growth+factor+reviews&rft.issn=13596101&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-11 N1 - Date created - 2000-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Resolution of two [(35)S]GTP-gamma-S binding sites and their response to chronic morphine treatment: a binding surface analysis. AN - 70961063; 10704787 AB - The mechanisms by which prolonged exposure to morphine leads to tolerance are not fully understood. We investigated the effects of etorphine (ET) on [(35)S]guanosine 5'-(-thio)-triphosphate ([(35)S]GTP-gamma-S) binding in brains of rats made tolerant to morphine via the implantation of morphine (or placebo) pellets. Binding surface analysis was used to characterize the interactions of ET, Gpp(Np)H and GTP-gamma-S with sites labeled by [(35)S]GTP-gamma-S. Data sets were fitted to one- and two-site binding models using the nonlinear least squares curve fitting program MLAB-PC (Civilized Software, Bethesda, MD, USA). Two binding sites were readily resolved. Chronic morphine significantly increased the B(max) and K(d) of the high affinity binding site. ET stimulated [(35)S]GTP-gamma-S binding in placebo membranes via an increase in the B(max) of the high affinity binding site. In contrast, ET stimulated [(35)S]GTP-gamma-S in chronic morphine membranes via a large decrease in the K(d) of the high affinity site. These results suggest that chronic morphine treatment alters the mechanism by which ET stimulates [(35)S]GTP-gamma-S binding to G-proteins. Since proper G-protein/receptor coupling increases [(35)S]GTP-gamma-S binding via an increase in B(max) values, these results suggest that opioid receptors in chronic morphine membranes are not normally coupled to G-proteins. These findings corroborate earlier studies that reported changes in G-protein function in morphine tolerant animals. JF - Brain research bulletin AU - Heyliger, S O AU - Ni, Q AU - Rothman, R B AD - Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 2000/03/01/ PY - 2000 DA - 2000 Mar 01 SP - 357 EP - 362 VL - 51 IS - 4 SN - 0361-9230, 0361-9230 KW - Narcotic Antagonists KW - 0 KW - Narcotics KW - Receptors, Opioid KW - Guanosine Diphosphate KW - 146-91-8 KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Etorphine KW - 42M2Y6NU9O KW - Index Medicus KW - Receptors, Opioid -- agonists KW - Animals KW - Etorphine -- pharmacology KW - Brain -- metabolism KW - Radioligand Assay KW - Guanosine Diphosphate -- pharmacology KW - Narcotics -- pharmacology KW - Binding Sites KW - Rats KW - Rats, Sprague-Dawley KW - Binding, Competitive KW - In Vitro Techniques KW - Narcotic Antagonists -- pharmacology KW - Male KW - Morphine Dependence -- metabolism KW - Guanosine 5'-O-(3-Thiotriphosphate) -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70961063?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research+bulletin&rft.atitle=Resolution+of+two+%5B%2835%29S%5DGTP-gamma-S+binding+sites+and+their+response+to+chronic+morphine+treatment%3A+a+binding+surface+analysis.&rft.au=Heyliger%2C+S+O%3BNi%2C+Q%3BRothman%2C+R+B&rft.aulast=Heyliger&rft.aufirst=S&rft.date=2000-03-01&rft.volume=51&rft.issue=4&rft.spage=357&rft.isbn=&rft.btitle=&rft.title=Brain+research+bulletin&rft.issn=03619230&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-24 N1 - Date created - 2000-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Flutamide, testolactone, and reduced hydrocortisone dose maintain normal growth velocity and bone maturation despite elevated androgen levels in children with congenital adrenal hyperplasia. AN - 70957554; 10720048 AB - Treatment outcome in congenital adrenal hyperplasia is often sub-optimal due to hyperandrogenism, treatment-induced hypercortisolism, or both. We previously reported better control of linear growth, weight gain, and bone maturation in a short term cross-over study of a new four-drug treatment regimen containing an antiandrogen (flutamide), an inhibitor of androgen to estrogen conversion (testolactone), reduced hydrocortisone dose, and fludrocortisone, compared to the effects of a control regimen of hydrocortisone and fludrocortisone. Twenty-eight children have completed 2 yr of follow-up in a subsequent long term randomized parallel study comparing these two treatment regimens. During 2 yr of therapy, compared to children receiving hydrocortisone, and fludrocortisone treatment, children receiving flutamide, testolactone, reduced hydrocortisone dose (average of 8.7 +/- 0.6 mg/m2 x day), and fludrocortisone had significantly (P < or = 0.05) higher plasma 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone levels. Despite elevated androgen levels, children receiving the new treatment regimen had normal linear growth rate (at 2 yr, 0.1 +/- 0.5 SD units), and bone maturation (at 2 yr, 0.7 +/- 0.3 yr bone age/yr chronological age). No significant adverse effects were observed after 2 yr. We conclude that the regimen of flutamide, testolactone, reduced hydrocortisone dose, and fludrocortisone provides effective control of congenital adrenal hyperplasia with reduced risk of glucocorticoid excess. A long term study of this new regimen is ongoing. JF - The Journal of clinical endocrinology and metabolism AU - Merke, D P AU - Keil, M F AU - Jones, J V AU - Fields, J AU - Hill, S AU - Cutler, G B AD - Warren Grant Magnuson Clinical Center, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda Maryland 20892-1862, USA. merked@mail.nih.gov Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 1114 EP - 1120 VL - 85 IS - 3 SN - 0021-972X, 0021-972X KW - Androgen Antagonists KW - 0 KW - Androgens KW - Anti-Inflammatory Agents KW - Antineoplastic Agents, Hormonal KW - Hormones KW - Testolactone KW - 6J9BLA949Q KW - Flutamide KW - 76W6J0943E KW - Hydrocortisone KW - WI4X0X7BPJ KW - Abridged Index Medicus KW - Index Medicus KW - Weight Gain -- drug effects KW - Androgens -- blood KW - Humans KW - Hormones -- blood KW - Follow-Up Studies KW - Child KW - Male KW - Female KW - Child, Preschool KW - Growth -- physiology KW - Testolactone -- adverse effects KW - Testolactone -- administration & dosage KW - Androgen Antagonists -- therapeutic use KW - Hydrocortisone -- adverse effects KW - Bone Development -- physiology KW - Anti-Inflammatory Agents -- adverse effects KW - Anti-Inflammatory Agents -- therapeutic use KW - Hydrocortisone -- administration & dosage KW - Bone Development -- drug effects KW - Anti-Inflammatory Agents -- administration & dosage KW - Hydrocortisone -- therapeutic use KW - Androgen Antagonists -- administration & dosage KW - Adrenal Hyperplasia, Congenital -- pathology KW - Androgen Antagonists -- adverse effects KW - Adrenal Hyperplasia, Congenital -- complications KW - Adrenal Hyperplasia, Congenital -- drug therapy KW - Flutamide -- therapeutic use KW - Antineoplastic Agents, Hormonal -- administration & dosage KW - Testolactone -- therapeutic use KW - Flutamide -- adverse effects KW - Antineoplastic Agents, Hormonal -- adverse effects KW - Antineoplastic Agents, Hormonal -- therapeutic use KW - Flutamide -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70957554?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+endocrinology+and+metabolism&rft.atitle=Flutamide%2C+testolactone%2C+and+reduced+hydrocortisone+dose+maintain+normal+growth+velocity+and+bone+maturation+despite+elevated+androgen+levels+in+children+with+congenital+adrenal+hyperplasia.&rft.au=Merke%2C+D+P%3BKeil%2C+M+F%3BJones%2C+J+V%3BFields%2C+J%3BHill%2C+S%3BCutler%2C+G+B&rft.aulast=Merke&rft.aufirst=D&rft.date=2000-03-01&rft.volume=85&rft.issue=3&rft.spage=1114&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+endocrinology+and+metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-30 N1 - Date created - 2000-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of Smad3 modulates wound healing. AN - 70956448; 10708960 AB - TGF-beta plays a central and critical role in tissue repair. The recent identification of TGF-beta signal transduction pathways involving Smad proteins has now made it possible to explore their contribution to the activities of TGF-beta in vivo. Both Smad3 and its closely related homolog Smad2 act as latent nuclear transcriptional activators and mediate intracellular signaling by TGF-betas and activin, each of which regulates cellular functions pivotal to cutaneous wound healing. Mice null for Smad3 (Smad3(ex8/ex8)) survive into adulthood and show accelerated cutaneous wound healing characterized by an increased rate of re-epithelialization and a reduced local inflammatory infiltrate. These data implicate Smad3 in specific pathways of tissue repair and suggest that it could be a target for the development of therapeutic strategies to modulate wound healing. JF - Cytokine & growth factor reviews AU - Ashcroft, G S AU - Roberts, A B AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. PY - 2000 SP - 125 EP - 131 VL - 11 IS - 1-2 SN - 1359-6101, 1359-6101 KW - DNA-Binding Proteins KW - 0 KW - SMAD2 protein, human KW - SMAD3 protein, human KW - Smad2 Protein KW - Smad2 protein, mouse KW - Smad3 Protein KW - Smad3 protein, mouse KW - Trans-Activators KW - Transforming Growth Factor beta KW - Index Medicus KW - Transforming Growth Factor beta -- pharmacology KW - Animals KW - Keratinocytes -- drug effects KW - Humans KW - Mice KW - Keratinocytes -- metabolism KW - Transforming Growth Factor beta -- metabolism KW - Signal Transduction KW - Trans-Activators -- metabolism KW - Trans-Activators -- genetics KW - Wound Healing -- drug effects KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- drug effects KW - Wound Healing -- physiology KW - Trans-Activators -- drug effects KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70956448?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytokine+%26+growth+factor+reviews&rft.atitle=Loss+of+Smad3+modulates+wound+healing.&rft.au=Ashcroft%2C+G+S%3BRoberts%2C+A+B&rft.aulast=Ashcroft&rft.aufirst=G&rft.date=2000-03-01&rft.volume=11&rft.issue=1-2&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Cytokine+%26+growth+factor+reviews&rft.issn=13596101&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-11 N1 - Date created - 2000-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a cryptic nucleolar-localization signal in MDM2. AN - 70953717; 10707090 JF - Nature cell biology AU - Lohrum, M A AU - Ashcroft, M AU - Kubbutat, M H AU - Vousden, K H AD - NCI-FCRDC, Building 560, Room 22-96, West 7th Street, Frederick, Maryland 21702-1201, USA. Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 179 EP - 181 VL - 2 IS - 3 SN - 1465-7392, 1465-7392 KW - Carrier Proteins KW - 0 KW - Cell Cycle Proteins KW - DNA-Binding Proteins KW - E2F Transcription Factors KW - Nuclear Proteins KW - Proteins KW - Proto-Oncogene Proteins KW - Retinoblastoma-Binding Protein 1 KW - Transcription Factor DP1 KW - Transcription Factors KW - Tumor Suppressor Protein p14ARF KW - Tumor Suppressor Protein p53 KW - MDM2 protein, human KW - EC 2.3.2.27 KW - Proto-Oncogene Proteins c-mdm2 KW - Index Medicus KW - Amino Acid Motifs -- genetics KW - Transcription Factors -- metabolism KW - Humans KW - Gene Expression KW - Intracellular Fluid -- metabolism KW - Tumor Suppressor Protein p53 -- metabolism KW - Proteins -- genetics KW - Mutagenesis, Site-Directed KW - Transfection KW - Protein Binding -- genetics KW - Cell Line KW - Protein Conformation KW - Proto-Oncogene Proteins -- metabolism KW - Proto-Oncogene Proteins -- genetics KW - Cell Nucleolus -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70953717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cell+biology&rft.atitle=Identification+of+a+cryptic+nucleolar-localization+signal+in+MDM2.&rft.au=Lohrum%2C+M+A%3BAshcroft%2C+M%3BKubbutat%2C+M+H%3BVousden%2C+K+H&rft.aulast=Lohrum&rft.aufirst=M&rft.date=2000-03-01&rft.volume=2&rft.issue=3&rft.spage=179&rft.isbn=&rft.btitle=&rft.title=Nature+cell+biology&rft.issn=14657392&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-09 N1 - Date created - 2000-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ongoing research to identify environmental risk factors in breast carcinoma. AN - 70950877; 10705359 AB - Environmental exposures, timing and duration of exposure, and one's genetic susceptibility all contribute to breast carcinoma and its progression. The purpose of this article was to identify known and suspected environmental causes of breast carcinoma, identify some environmental risk factors that may represent significant risk factors for certain groups, and describe current studies, supported by the National Institutes of Health/National Institute of Environmental Health Sciences, that clarify how environmental factors contribute to the development of breast carcinoma. Known and suspected environmental risk factors include organochlorine pesticides and other synthetic chemicals, hormonal factors (including exogenous endocrine disrupters), diet, tobacco and alcohol use, radiation, and magnetic fields. In at least 50% of breast carcinoma cases, none of the known risk factors apply. It is likely that an environmental component accounts for much of the unknown 50% of risk. Knowing the environmental factors for breast carcinoma development is an area that should be investigated intensely because it offers our best hope for prevention. Understanding why African-American women have a more aggressive form of breast carcinoma, whether they receive adequate follow-up treatment, and how these factors contribute to increased mortality rates requires further exploration. Data that demonstrate the lower incidence rate of breast carcinoma in Asian women, the relation to low fat diets and diets high in phytoestrogens, and how this might serve as a model for all women should be investigated. Finally, differences in behavioral and cultural attitudes, ethnicity, economic status, and life-style influences among different groups of women require further study to determine how these factors contribute to enhancing or reducing breast carcinoma risk. Copyright 2000 American Cancer Society. JF - Cancer AU - Johnson-Thompson, M C AU - Guthrie, J AD - Office of the Deputy Director, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000/03/01/ PY - 2000 DA - 2000 Mar 01 SP - 1224 EP - 1229 VL - 88 IS - 5 Suppl SN - 0008-543X, 0008-543X KW - Carcinogens KW - 0 KW - Estrogens, Non-Steroidal KW - Hormones KW - Isoflavones KW - Pesticides KW - Phytoestrogens KW - Plant Preparations KW - Abridged Index Medicus KW - Index Medicus KW - Culture KW - Attitude to Health KW - Humans KW - Alcohol Drinking -- adverse effects KW - Pesticides -- adverse effects KW - Social Class KW - Health Behavior KW - Research KW - Diet, Fat-Restricted KW - Neoplasms, Radiation-Induced -- etiology KW - Continental Population Groups KW - Smoking -- adverse effects KW - Estrogens, Non-Steroidal -- administration & dosage KW - Diet -- adverse effects KW - Life Style KW - Survival Rate KW - Ethnic Groups KW - Risk Factors KW - Plants KW - Magnetics -- adverse effects KW - Follow-Up Studies KW - Female KW - Carcinogens -- adverse effects KW - Hormones -- adverse effects KW - Breast Neoplasms -- genetics KW - Carcinoma -- ethnology KW - Carcinoma -- etiology KW - Breast Neoplasms -- ethnology KW - Carcinoma -- prevention & control KW - Environmental Exposure KW - Breast Neoplasms -- prevention & control KW - Breast Neoplasms -- etiology KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70950877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Ongoing+research+to+identify+environmental+risk+factors+in+breast+carcinoma.&rft.au=Johnson-Thompson%2C+M+C%3BGuthrie%2C+J&rft.aulast=Johnson-Thompson&rft.aufirst=M&rft.date=2000-03-01&rft.volume=88&rft.issue=5+Suppl&rft.spage=1224&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-26 N1 - Date created - 2000-04-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overlapping and specific functions of Braf and Craf-1 proto-oncogenes during mouse embryogenesis. AN - 70950824; 10704835 AB - The three mammalian Raf serine/threonine protein kinases mediate the transduction of proliferative and differentiative signals from cell surface receptors to the nucleus. In vertebrates, Raf signaling has been implicated in the progression of mouse embryos through the two-cell stage and in the induction of posterior mesoderm. However, mouse embryos mutant for each of the Raf genes exhibit no developmental defects before mid-gestation. Here we describe the phenotype of mouse mutants with different combinations of mutant Craf-1 and Braf alleles. Our results show that Raf signaling is indeed indispensable for normal development beyond the blastocyst stage. However, due to a significant redundancy between Craf-1 and Braf, either gene is sufficient for normal development until mid-gestation. The molecular and developmental mechanisms for this redundancy were investigated by monitoring the expression of Raf genes throughout embryogenesis and by biochemical studies in mutant cell lines. JF - Mechanisms of development AU - Wojnowski, L AU - Stancato, L F AU - Larner, A C AU - Rapp, U R AU - Zimmer, A AD - Laboratory on Genetics, National Institute of Mental Health, Bethesda, MD, USA. lwojnowski@epidauros.com Y1 - 2000/03/01/ PY - 2000 DA - 2000 Mar 01 SP - 97 EP - 104 VL - 91 IS - 1-2 SN - 0925-4773, 0925-4773 KW - Isoenzymes KW - 0 KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - Index Medicus KW - Phenotype KW - Animals KW - Embryonic and Fetal Development KW - Cells, Cultured KW - Mice KW - Proto-Oncogenes KW - Isoenzymes -- genetics KW - Gene Expression Regulation, Developmental KW - Mutagenesis KW - Proto-Oncogene Proteins c-raf -- physiology KW - Proto-Oncogene Proteins c-raf -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70950824?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mechanisms+of+development&rft.atitle=Overlapping+and+specific+functions+of+Braf+and+Craf-1+proto-oncogenes+during+mouse+embryogenesis.&rft.au=Wojnowski%2C+L%3BStancato%2C+L+F%3BLarner%2C+A+C%3BRapp%2C+U+R%3BZimmer%2C+A&rft.aulast=Wojnowski&rft.aufirst=L&rft.date=2000-03-01&rft.volume=91&rft.issue=1-2&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Mechanisms+of+development&rft.issn=09254773&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-29 N1 - Date created - 2000-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functions of mammalian Smad genes as revealed by targeted gene disruption in mice. AN - 70949641; 10708952 AB - The Smad genes are the intracellular mediators of TGF-beta signals. Targeted mutagenesis in mice has yielded valuable new insights into the functions of this important gene family. These experiments have shown that Smad2 and Smad4 are needed for gastrulation, Smad5 for angiogenesis, and Smad3 for establishment of the mucosal immune response and proper development of the skeleton. In addition, these experiments have shown us the importance of gene dosage in this family, as several of its members yielded haploinsufficiency phenotypes. These include gastrulation and craniofacial defects for Smad2, accelerated wound healing for Smad3, and the incidence of gastric cancer for Smad4. Combinatorial genetics has also revealed functions of Smads in left/right isomerism and liver development. JF - Cytokine & growth factor reviews AU - Weinstein, M AU - Yang, X AU - Deng, C AD - Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10/9N105, 10 Center Drive, Bethesda, MD 20892, USA. PY - 2000 SP - 49 EP - 58 VL - 11 IS - 1-2 SN - 1359-6101, 1359-6101 KW - DNA-Binding Proteins KW - 0 KW - NODAL protein, human KW - Nodal Protein KW - Nodal protein, mouse KW - Phosphoproteins KW - SMAD2 protein, human KW - SMAD3 protein, human KW - SMAD4 protein, human KW - SMAD5 protein, human KW - Smad2 Protein KW - Smad2 protein, mouse KW - Smad3 Protein KW - Smad3 protein, mouse KW - Smad4 Protein KW - Smad4 protein, mouse KW - Smad5 Protein KW - Smad5 protein, mouse KW - Trans-Activators KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - Mammals KW - Liver -- growth & development KW - Genes, Tumor Suppressor KW - Humans KW - Neoplasms -- genetics KW - Mice, Knockout KW - Embryonic and Fetal Development KW - Gastrula KW - Immune System -- physiology KW - Transforming Growth Factor beta -- genetics KW - Phosphoproteins -- metabolism KW - Liver -- pathology KW - Phosphoproteins -- genetics KW - Wound Healing KW - Neovascularization, Physiologic -- genetics KW - Mice KW - Bone Development KW - Transforming Growth Factor beta -- metabolism KW - Gene Expression Regulation, Developmental KW - Trans-Activators -- metabolism KW - Trans-Activators -- genetics KW - DNA-Binding Proteins -- genetics KW - Trans-Activators -- immunology KW - DNA-Binding Proteins -- immunology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70949641?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytokine+%26+growth+factor+reviews&rft.atitle=Functions+of+mammalian+Smad+genes+as+revealed+by+targeted+gene+disruption+in+mice.&rft.au=Weinstein%2C+M%3BYang%2C+X%3BDeng%2C+C&rft.aulast=Weinstein&rft.aufirst=M&rft.date=2000-03-01&rft.volume=11&rft.issue=1-2&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=Cytokine+%26+growth+factor+reviews&rft.issn=13596101&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-11 N1 - Date created - 2000-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chromosomal aberrations evaluated by CGH, FISH and GTG-banding in a case of AIDS-related Burkitt's lymphoma. AN - 70945089; 10702812 AB - We have previously reported on a complex chromosome rearrangement [der(17)] in a B-cell line, BRG A, established from an AIDS patient with Burkitt's lymphoma (BL). The aim of the present study was the definition of der(17) composition and the identification of complete or partial chromosome gains and losses in two cell clones (BRG A and BRG M) derived from this patient. We applied comparative genome hybridization (CGH) to detect the DNA misrepresentations in the genome of the two cell clones. Findings from CGH and banding analysis could then direct the choice of probes for chromosome painting experiments to elucidate der(17) composition. CGH analysis identified gains of chromosomes 1q, 7q, 12q, 13q, 15q, 17p, 20p,q and losses of chromosomes 3p and 5q in BRG A and gain of chromosome 1q and loss in chromosome 6q in BRG M. Some of the detected alterations had already been described in lymphomas, while others appeared to be new. The combination of these techniques allowed a precise definition of der(17), composed by translocated regions from chromosomes 12 and 15. We demonstrated CGH to be a powerful tool in the identification of recurrent chromosome aberrations in an AIDS-related BL and in ascertaining the origin of marker chromosomes. We were also able to identify a different pattern of aberrations and assess an independent sequence of events leading to the 1p gain in the two subclones. JF - Haematologica AU - Zunino, A AU - Viaggi, S AU - Ottaggio, L AU - Fronza, G AU - Schenone, A AU - Roncella, S AU - Abbondandolo, A AD - Mutagenesis Laboratory, National Cancer Institute (IST), largo Rosanna Benzi 10, 16132 Genova, Italy. zuninoa@hp380.ist.unige.it Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 250 EP - 255 VL - 85 IS - 3 SN - 0390-6078, 0390-6078 KW - Index Medicus KW - AIDS/HIV KW - Karyotyping KW - Clone Cells KW - Chromosomes, Human, Pair 17 KW - Aneuploidy KW - Chromosomes, Human, Pair 15 KW - Chromosome Banding KW - Humans KW - In Situ Hybridization, Fluorescence KW - Chromosomes, Human, Pair 13 KW - Chromosomes, Human, Pair 7 KW - Chromosomes, Human, Pair 12 KW - Chromosomes, Human, Pair 5 KW - Chromosomes, Human, Pair 1 KW - Chromosomes, Human, Pair 3 KW - Tumor Cells, Cultured KW - Chromosomes, Human, Pair 20 KW - In Situ Hybridization -- methods KW - Burkitt Lymphoma -- etiology KW - Burkitt Lymphoma -- genetics KW - Chromosome Aberrations KW - Lymphoma, AIDS-Related -- genetics KW - Cytogenetics -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70945089?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Haematologica&rft.atitle=Chromosomal+aberrations+evaluated+by+CGH%2C+FISH+and+GTG-banding+in+a+case+of+AIDS-related+Burkitt%27s+lymphoma.&rft.au=Zunino%2C+A%3BViaggi%2C+S%3BOttaggio%2C+L%3BFronza%2C+G%3BSchenone%2C+A%3BRoncella%2C+S%3BAbbondandolo%2C+A&rft.aulast=Zunino&rft.aufirst=A&rft.date=2000-03-01&rft.volume=85&rft.issue=3&rft.spage=250&rft.isbn=&rft.btitle=&rft.title=Haematologica&rft.issn=03906078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-16 N1 - Date created - 2000-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Resistance to methotrexate in SKOV-3 cell lines after chronic exposure to carbamazepine is associated with a decreased expression of folate receptor. AN - 70944380; 10699949 AB - The detrimental effect of chronic administration of carbamazepine (CBZ) on serum and erythrocyte folates of patients has been extensively analyzed. However, at present, no data have been reported on the effect of CBZ on the intracellular content and activity of antimetabolite cytotoxic agents that can be used together with CBZ in the treatment of cancer patients. To investigate this issue, we chronically exposed in vitro the human ovarian cancer cell line SKOV-3 (grown under physiological folate concentrations) to CBZ, thus selecting SKOV-CBZ clones (SKOV-CBZ-50-2, SKOV-CBZ-50-5 and SKOV-CBZ-100-2) able to grow in the continuous presence of the antiepileptic drug. All of the SKOV-CBZ clones were more resistant to methotrexate (MTX) than the parental cells. MTX resistance index, as determined by the ratio between MTX concentrations inhibiting cell growth by 50% (MTX IC(50)) in SKOV-CBZ clones and in the parental cells, ranged between 3- and 5-fold. This resistance was related to a reduced intracellular content of MTX. No alteration activity of the cellular enzymes directly involved in MTX cytotoxicity (dihydrofolate reductase, thymidylate synthase [TS] and folylpolyglutamate synthetase) was observed. SKOV-CBZ clones were cross-resistant to the TS inhibitors tomudex and CB3717, but not to the TS inhibitor 5-fluoro-deoxy uridine and other antineoplastic drugs (cisplatin, doxorubicin, vincristine and taxol), whose cellular uptake is derived from transmembrane transport mechanisms different from folate receptor alpha (FRalpha) or reduced folate carrier (RFC). FRalpha mRNA and protein levels were significantly lower in SKOV-CBZ clones than in the parental cells. The reduced level of FRalpha in SKOV-CBZ clones was associated with a decreased binding capacity of folic acid. No variation of mRNA RFC expression in the SKOV-CBZ clones as compared to the parental cells was observed. Thus, after chronic exposure to CBZ, SKOV-CBZ clones develop resistance towards MTX due to defective MTX uptake. Copyright 2000 Wiley-Liss, Inc. JF - International journal of cancer AU - Toffoli, G AU - Corona, G AU - Tolusso, B AU - Sartor, F AU - Sorio, R AU - Mini, E AU - Boiocchi, M AD - Experimental Oncology 1, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy. Y1 - 2000/03/01/ PY - 2000 DA - 2000 Mar 01 SP - 683 EP - 690 VL - 85 IS - 5 SN - 0020-7136, 0020-7136 KW - Carrier Proteins KW - 0 KW - Folate Receptors, GPI-Anchored KW - Receptors, Cell Surface KW - Carbamazepine KW - 33CM23913M KW - Vincristine KW - 5J49Q6B70F KW - Doxorubicin KW - 80168379AG KW - Paclitaxel KW - P88XT4IS4D KW - Cisplatin KW - Q20Q21Q62J KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Ovarian Neoplasms KW - Humans KW - Biological Transport KW - Cell Division -- drug effects KW - Transcription, Genetic KW - Paclitaxel -- toxicity KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Vincristine -- therapeutic use KW - Cisplatin -- toxicity KW - Doxorubicin -- therapeutic use KW - Receptors, Cell Surface -- genetics KW - Female KW - Methotrexate -- pharmacokinetics KW - Carrier Proteins -- genetics KW - Gene Expression Regulation, Neoplastic -- physiology KW - Carbamazepine -- pharmacology KW - Drug Resistance, Neoplasm KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Methotrexate -- toxicity KW - Drug Resistance, Multiple UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70944380?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Resistance+to+methotrexate+in+SKOV-3+cell+lines+after+chronic+exposure+to+carbamazepine+is+associated+with+a+decreased+expression+of+folate+receptor.&rft.au=Toffoli%2C+G%3BCorona%2C+G%3BTolusso%2C+B%3BSartor%2C+F%3BSorio%2C+R%3BMini%2C+E%3BBoiocchi%2C+M&rft.aulast=Toffoli&rft.aufirst=G&rft.date=2000-03-01&rft.volume=85&rft.issue=5&rft.spage=683&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 - 2000-03-22 N1 - Date created - 2000-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reviews in environmental health, 2000. AN - 70940753; 10698718 JF - Environmental health perspectives AU - Goehl, T J AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 3 EP - 5 VL - 108 Suppl 1 SN - 0091-6765, 0091-6765 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - Ecology KW - Public Health KW - Radiation Effects KW - Environmental Pollutants -- toxicity KW - Environmental Health KW - Environmental Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70940753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reviews+in+environmental+health%2C+2000.&rft.au=Goehl%2C+T+J&rft.aulast=Goehl&rft.aufirst=T&rft.date=2000-03-01&rft.volume=108+Suppl+1&rft.issue=&rft.spage=3&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 - 2000-04-25 N1 - Date created - 2000-04-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overview of carcinogenesis: past, present and future. AN - 70931373; 10688853 AB - In the foregoing articles, the editors of Carcinogenesis have identified the major themes of current carcinogenesis research and assembled an outstanding group of authors to review these areas. I have been asked to provide a historical overview of past accomplishments and describe how these contributed to the broader efforts to overcome the burden of human cancer. My assignment also included a look into the future. As scientists we formulate hypotheses that attempt to predict the future. Occasionally we are successful. The pioneers of carcinogenesis research were remarkably successful in predicting the future. Armed with primitive technology relative to today, these scientists studied the biology of carcinogenesis and conceptualized a framework for cancer pathogenesis that virtually everyone working in cancer research follows today. The current generation has been charged with filling in the details. In the details lay the future. Together with past accomplishments, these emerging details form a remarkable picture of progress in understanding and application, creating realistic and imminent promise to achieve victory in the fight against cancer. JF - Carcinogenesis AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, MD 20892, USA. yuspas@dc37a.nci.nih.gov Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 341 EP - 344 VL - 21 IS - 3 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Index Medicus KW - Humans KW - Cell Transformation, Neoplastic -- drug effects KW - Forecasting KW - Neoplasms -- physiopathology KW - Neoplasms -- etiology KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70931373?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Overview+of+carcinogenesis%3A+past%2C+present+and+future.&rft.au=Yuspa%2C+S+H&rft.aulast=Yuspa&rft.aufirst=S&rft.date=2000-03-01&rft.volume=21&rft.issue=3&rft.spage=341&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-11 N1 - Date created - 2000-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 5-Iodo-A-85380, an alpha4beta2 subtype-selective ligand for nicotinic acetylcholine receptors. AN - 70928276; 10692507 AB - In an effort to develop selective radioligands for in vivo imaging of neuronal nicotinic acetylcholine receptors (nAChRs), we synthesized 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-iodo-A-85380) and labeled it with (125)I and (123)I. Here we present the results of experiments characterizing this radioiodinated ligand in vitro. The affinity of 5-[(125)I]iodo-A-85380 for alpha4beta2 nAChRs in rat and human brain is defined by K(d) values of 10 and 12 pM, respectively, similar to that of epibatidine (8 pM). In contrast to epibatidine, however, 5-iodo-A-85380 is more selective in binding to the alpha4beta2 subtype than to other nAChR subtypes. In rat adrenal glands, 5-iodo-A-85380 binds to nAChRs containing alpha3 and beta4 subunits with 1/1000th the affinity of epibatidine, and exhibits 1/60th and 1/190th the affinity of epibatidine at alpha7 and muscle-type nAChRs, respectively. Moreover, unlike epibatidine and cytisine, 5-[(125)I]iodo-A-85380 shows no binding in any brain regions in mice homozygous for a mutation in the beta2 subunit of nAChRs. Binding of 5-[(125)I]iodo-A-85380 in rat brain is reversible, and is characterized by high specificity and a slow rate of dissociation of the receptor-ligand complex (t(1/2) for dissociation approximately 2 h). These properties, along with other features observed previously in in vivo experiments (low toxicity, rapid penetration of the blood-brain barrier, and a high ratio of specific to nonspecific binding), suggest that this compound, labeled with (125)I or (123)I, is superior to other radioligands available for in vitro and in vivo studies of alpha4beta2 nAChRs, respectively. JF - Molecular pharmacology AU - Mukhin, A G AU - Gündisch, D AU - Horti, A G AU - Koren, A O AU - Tamagnan, G AU - Kimes, A S AU - Chambers, J AU - Vaupel, D B AU - King, S L AU - Picciotto, M R AU - Innis, R B AU - London, E D AD - Brain Imaging Center, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland, USA. Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 642 EP - 649 VL - 57 IS - 3 SN - 0026-895X, 0026-895X KW - A 85380 KW - 0 KW - Azetidines KW - Iodine Radioisotopes KW - Receptors, Nicotinic KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Rats, Inbred F344 KW - Humans KW - In Vitro Techniques KW - Binding, Competitive KW - Mice KW - Tissue Distribution KW - Male KW - Azetidines -- chemistry KW - Azetidines -- pharmacokinetics KW - Receptors, Nicotinic -- metabolism KW - Receptors, Nicotinic -- drug effects KW - Brain -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70928276?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=5-Iodo-A-85380%2C+an+alpha4beta2+subtype-selective+ligand+for+nicotinic+acetylcholine+receptors.&rft.au=Mukhin%2C+A+G%3BG%C3%BCndisch%2C+D%3BHorti%2C+A+G%3BKoren%2C+A+O%3BTamagnan%2C+G%3BKimes%2C+A+S%3BChambers%2C+J%3BVaupel%2C+D+B%3BKing%2C+S+L%3BPicciotto%2C+M+R%3BInnis%2C+R+B%3BLondon%2C+E+D&rft.aulast=Mukhin&rft.aufirst=A&rft.date=2000-03-01&rft.volume=57&rft.issue=3&rft.spage=642&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 - 2000-04-10 N1 - Date created - 2000-04-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinogenesis in mouse and human cells: parallels and paradoxes. AN - 70925698; 10688857 AB - It has been known since the last century that genetic changes are important in carcinogenesis [Boveri,T. (1914) Zur Frage der Erstehung Maligner Tumoren. Gustav Fischer, Jena]. Observations of tumor cells growing in tissue culture led to the prediction, even before the true nature of the genetic material was known, that alterations at the chromosomal level were critically involved in the process of neoplastic development. The past 20 years have seen the transition of carcinogenesis studies from the purely observational to the molecular genetic level. Although much more needs to be done, it is nevertheless gratifying to be able to piece together the sequence of events from carcinogen exposure, metabolism of the carcinogen to the activated form, formation of specific carcinogen-DNA adducts, misrepair leading to the fixation of mutations in particular target genes, and the resulting selective outgrowth of neoplastic cells. The nature of many of these steps has been clarified only in the relatively recent past, and only for a small number of specific target genes, but the fact that we can say with confidence that such processes occur and are causal changes in tumorigenesis represents a tremendous advance over the situation pertaining 20 years ago. The purpose of this review is to summarize the advances over this time period in our understanding of some of the genetic alterations that contribute to neoplasia, with particular emphasis on chemical carcinogenesis in rodents and the parallels with transformation of human cells. JF - Carcinogenesis AU - Balmain, A AU - Harris, C C AD - UCSF Cancer Center, 2340 Sutter Street, San Francisco, CA 94115, USA and Laboratory of Human Carcinogenesis, Building 37 Room 2C05, 37 Convent Drive, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. abalmain@cc.ucsf.edu Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 371 EP - 377 VL - 21 IS - 3 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Animals KW - Molecular Epidemiology KW - Humans KW - Mice KW - Genetic Predisposition to Disease KW - Tumor Suppressor Protein p53 -- genetics KW - Neoplasms -- chemically induced KW - Neoplasms -- physiopathology KW - Cell Transformation, Neoplastic -- chemically induced KW - Neoplasms -- genetics KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70925698?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Carcinogenesis+in+mouse+and+human+cells%3A+parallels+and+paradoxes.&rft.au=Balmain%2C+A%3BHarris%2C+C+C&rft.aulast=Balmain&rft.aufirst=A&rft.date=2000-03-01&rft.volume=21&rft.issue=3&rft.spage=371&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-11 N1 - Date created - 2000-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of the Gag matrix domain in targeting human immunodeficiency virus type 1 assembly. AN - 70925566; 10684302 AB - Human immunodeficiency virus type 1 (HIV-1) particle formation and the subsequent initiation of protease-mediated maturation occur predominantly on the plasma membrane. However, the mechanism by which HIV-1 assembly is targeted specifically to the plasma membrane versus intracellular membranes is largely unknown. Previously, we observed that mutations between residues 84 and 88 of the matrix (MA) domain of HIV-1 Gag cause a retargeting of virus particle formation to an intracellular site. In this study, we demonstrate that the mutant virus assembly occurs in the Golgi or in post-Golgi vesicles. These particles undergo core condensation in a protease-dependent manner, indicating that virus maturation can occur not only on the plasma membrane but also in the Golgi or post-Golgi vesicles. The intracellular assembly of mutant particles is dependent on Gag myristylation but is not influenced by p6(Gag) or envelope glycoprotein expression. Previous characterization of viral revertants suggested a functional relationship between the highly basic domain of MA (amino acids 17 to 31) and residues 84 to 88. We now demonstrate that mutations in the highly basic domain also retarget virus particle formation to the Golgi or post-Golgi vesicles. Although the basic domain has been implicated in Gag membrane binding, no correlation was observed between the impact of mutations on membrane binding and Gag targeting, indicating that these two functions of MA are genetically separable. Plasma membrane targeting of Gag proteins with mutations in either the basic domain or between residues 84 and 88 was rescued by coexpression with wild-type Gag; however, the two groups of MA mutants could not rescue each other. We propose that the highly basic domain of MA contains a major determinant of HIV-1 Gag plasma membrane targeting and that mutations between residues 84 and 88 disrupt plasma membrane targeting through an effect on the basic domain. JF - Journal of virology AU - Ono, A AU - Orenstein, J M AU - Freed, E O AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0460, USA. Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 2855 EP - 2866 VL - 74 IS - 6 SN - 0022-538X, 0022-538X KW - Gene Products, env KW - 0 KW - Gene Products, gag KW - HIV Antigens KW - Protein Precursors KW - Viral Proteins KW - gag Gene Products, Human Immunodeficiency Virus KW - p17 protein, Human Immunodeficiency Virus Type 1 KW - p55 gag precursor protein, Human immunodeficiency virus 1 KW - p6 gag protein, Human immunodeficiency virus 1 KW - Myristic Acid KW - 0I3V7S25AW KW - Index Medicus KW - AIDS/HIV KW - Endoplasmic Reticulum -- metabolism KW - Protein Precursors -- metabolism KW - HeLa Cells KW - Humans KW - Protein Precursors -- genetics KW - Gene Expression KW - Binding Sites KW - Mutagenesis KW - Gene Products, env -- metabolism KW - Cell Membrane -- metabolism KW - Golgi Apparatus -- metabolism KW - HIV Antigens -- metabolism KW - HIV Antigens -- genetics KW - Myristic Acid -- metabolism KW - Gene Products, gag -- genetics KW - Gene Products, gag -- physiology KW - Virus Assembly -- physiology KW - HIV-1 -- physiology KW - Gene Products, gag -- metabolism KW - HIV-1 -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70925566?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+the+Gag+matrix+domain+in+targeting+human+immunodeficiency+virus+type+1+assembly.&rft.au=Ono%2C+A%3BOrenstein%2C+J+M%3BFreed%2C+E+O&rft.aulast=Ono&rft.aufirst=A&rft.date=2000-03-01&rft.volume=74&rft.issue=6&rft.spage=2855&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 - 2000-04-03 N1 - Date created - 2000-04-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Virology. 1998 Mar 30;243(1):78-93 [9527917] J Virol. 1998 May;72(5):4116-26 [9557701] EMBO J. 1998 May 1;17(9):2699-708 [9564051] Virology. 1998 Jul 5;246(2):191-8 [9657938] J Virol. 1998 Oct;72(10):7950-9 [9733833] Virology. 1998 Nov 10;251(1):1-15 [9813197] J Virol. 1994 Mar;68(3):1689-96 [8107229] J Virol. 1994 Apr;68(4):2503-12 [8139032] J Virol. 1999 Apr;73(4):2604-12 [10074105] J Virol. 1999 May;73(5):4136-44 [10196310] J Virol. 1999 Jun;73(6):4728-37 [10233933] J Virol. 1999 Jul;73(7):5431-7 [10364290] J Virol. 1999 Jul;73(7):5654-62 [10364315] J Virol. 1999 Sep;73(9):7210-7 [10438808] AIDS Res Hum Retroviruses. 1990 Jun;6(6):721-30 [2194551] Cell. 1990 Oct 5;63(1):77-86 [2170021] J Virol. 1990 Nov;64(11):5306-16 [1698996] Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3195-9 [2014240] Proc Natl Acad Sci U S A. 1991 May 1;88(9):3987-91 [2023946] Exp Cell Res. 1991 Nov;197(1):91-9 [1915668] J Cell Biol. 1991 Oct;115(1):31-43 [1918138] J Virol. 1992 Aug;66(8):4966-71 [1629961] J Cell Biol. 1992 Dec;119(5):1077-96 [1447289] J Virol. 1993 May;67(5):2787-98 [8474175] Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5181-5 [8389472] J Virol. 1993 Aug;67(8):4972-80 [8331736] J Cell Biol. 1980 May;85(2):429-34 [7372714] J Histochem Cytochem. 1982 Nov;30(11):1097-108 [6897257] J Cell Biol. 1982 Dec;95(3):781-92 [6924936] J Cell Biol. 1983 Mar;96(3):835-50 [6682112] J Cell Biol. 1984 Dec;99(6):2011-23 [6094591] J Virol. 1986 Aug;59(2):284-91 [3016298] J Virol. 1987 Apr;61(4):1045-53 [3493352] J Cell Biol. 1987 Sep;105(3):1191-203 [2821009] J Virol. 1988 Aug;62(8):2578-86 [3260631] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580-4 [2849111] Proc Natl Acad Sci U S A. 1989 Aug;86(15):5781-5 [2788277] Cell. 1989 Oct 6;59(1):103-12 [2676191] Proc Natl Acad Sci U S A. 1990 Jan;87(2):523-7 [2405382] J Virol. 1990 May;64(5):2265-79 [2109101] J Virol. 1993 Nov;67(11):6387-94 [8411340] J Virol. 1993 Dec;67(12):7067-76 [7693966] J Virol. 1994 Apr;68(4):2556-69 [8139035] J Virol. 1994 Aug;68(8):4857-61 [8035484] J Virol. 1994 Aug;68(8):5311-20 [8035531] Nature. 1994 Aug 25;370(6491):666-8 [8065455] J Virol. 1994 Oct;68(10):6644-54 [7521919] J Virol. 1994 Oct;68(10):6782-6 [8084015] J Mol Biol. 1994 Nov 25;244(2):198-223 [7966331] Biochem Biophys Res Commun. 1994 Nov 15;204(3):1031-8 [7980574] J Cell Biol. 1994 Dec;127(6 Pt 1):1557-74 [7798312] J Biochem. 1994 Sep;116(3):649-56 [7852286] J Virol. 1995 Mar;69(3):1984-9 [7853546] J Virol. 1995 Jun;69(6):3949-54 [7745752] J Virol. 1995 Nov;69(11):6810-8 [7474093] Nature. 1995 Dec 14;378(6558):743-7 [7501025] Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3099-104 [8610175] J Virol. 1996 Dec;70(12):8540-8 [8970978] J Virol. 1997 Jan;71(1):778-84 [8985416] Cell. 1997 Feb 21;88(4):439-43 [9038335] Virology. 1997 Feb 17;228(2):294-306 [9123837] J Virol. 1997 May;71(5):3474-83 [9094619] J Virol. 1997 Jun;71(6):4409-18 [9151831] Nature. 1997 Jun 5;387(6633):569-72 [9177342] J Virol. 1997 Jul;71(7):5209-17 [9188588] J Virol. 1997 Jul;71(7):5549-59 [9188629] J Virol. 1997 Jul;71(7):5696-702 [9188652] J Virol. 1997 Sep;71(9):6582-92 [9261380] Biochem Biophys Res Commun. 1997 Nov 7;240(1):1-7 [9367871] J Virol. 1998 Apr;72(4):2723-32 [9525590] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of the resident chromosomal copy of c-myc by c-Myb is involved in myeloid leukemogenesis. AN - 70925367; 10688644 AB - c-myb is a frequent target of retroviral insertional mutagenesis in murine leukemia virus-induced myeloid leukemia. Induction of the leukemogenic phenotype is generally associated with inappropriate expression of this transcriptional regulator. Despite intensive investigations, the target genes of c-myb that are specifically involved in development of these myeloid lineage neoplasms are still unknown. In vitro assays have indicated that c-myc may be a target gene of c-Myb; however, regulation of the resident chromosomal gene has not yet been demonstrated. To address this question further, we analyzed the expression of c-myc in a myeloblastic cell line, M1, expressing a conditionally active c-Myb-estrogen receptor fusion protein (MybER). Activation of MybER both prevented the growth arrest induced by interleukin-6 (IL-6) and rapidly restored c-myc expression in nearly terminal differentiated cells that had been exposed to IL-6 for 3 days. Restoration occurred in the presence of a protein synthesis inhibitor but not after a transcriptional block, indicating that c-myc is a direct, transcriptionally regulated target of c-Myb. c-myc is a major target that transduces Myb's proliferative signal, as shown by the ability of a c-Myc-estrogen receptor fusion protein alone to also reverse growth arrest in this system. To investigate the possibility that this regulatory connection contributes to Myb's oncogenicity, we expressed a dominant negative Myb in the myeloid leukemic cell line RI-4-11. In this cell line, c-myb is activated by insertional mutagenesis and cannot be effectively down regulated by cytokine. Myb's ability to regulate c-myc's expression was also demonstrated in these cells, showing a mechanism through which the proto-oncogene c-myb can exert its oncogenic potential in myeloid lineage hematopoietic cells. JF - Molecular and cellular biology AU - Schmidt, M AU - Nazarov, V AU - Stevens, L AU - Watson, R AU - Wolff, L AD - Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 1970 EP - 1981 VL - 20 IS - 6 SN - 0270-7306, 0270-7306 KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Animals KW - Tumor Cells, Cultured KW - Mice KW - Cell Lineage -- genetics KW - Genes, myb KW - Genes, myc KW - Leukemia, Myeloid -- genetics KW - Leukemia, Myeloid -- pathology KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70925367?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regulation+of+the+resident+chromosomal+copy+of+c-myc+by+c-Myb+is+involved+in+myeloid+leukemogenesis.&rft.au=Schmidt%2C+M%3BNazarov%2C+V%3BStevens%2C+L%3BWatson%2C+R%3BWolff%2C+L&rft.aulast=Schmidt&rft.aufirst=M&rft.date=2000-03-01&rft.volume=20&rft.issue=6&rft.spage=1970&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 - 2000-03-23 N1 - Date created - 2000-03-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nucleic Acids Res. 1985 Mar 11;13(5):1431-42 [2987824] Proc Natl Acad Sci U S A. 1985 Oct;82(20):6937-41 [2413449] Nature. 1986 Apr 3-9;320(6061):415-21 [3007997] Proc Natl Acad Sci U S A. 1986 May;83(10):3204-8 [3010282] J Virol. 1986 Aug;59(2):276-83 [3016297] Mol Cell Biol. 1986 Feb;6(2):380-92 [3023843] Proc Natl Acad Sci U S A. 1986 Dec;83(24):9636-40 [3540945] Mol Cell Biol. 1987 Feb;7(2):664-71 [3547079] Cell Growth Differ. 1997 Oct;8(10):1039-48 [9342182] Cell. 1997 Oct 17;91(2):185-95 [9346236] Oncogene. 1997 Dec 11;15(24):2885-98 [9416832] Blood. 1998 Mar 15;91(6):1934-46 [9490676] Curr Opin Genet Dev. 1998 Feb;8(1):76-81 [9529609] Annu Rev Physiol. 1998;60:575-600 [9558477] Blood. 1998 Aug 1;92(3):1003-10 [9680370] J Natl Cancer Inst. 1951 Oct;12(2):447-63 [14889255] Mol Cell Biol. 1991 Dec;11(12):6166-76 [1944282] J Biol Chem. 1991 Dec 15;266(35):23521-4 [1748630] J Virol. 1992 Jan;66(1):512-23 [1309260] Mol Cell Biol. 1992 Jun;12(6):2493-500 [1588953] Biochem Biophys Res Commun. 1992 Jul 31;186(2):715-22 [1497659] J Virol. 1992 Oct;66(10):6035-44 [1527851] J Virol. 1987 Sep;61(9):2754-63 [2441077] J Virol. 1987 Dec;61(12):3721-5 [2824810] Anal Biochem. 1987 Nov 1;166(2):368-79 [2449095] J Virol. 1988 Apr;62(4):1120-4 [2831375] J Virol. 1988 Apr;62(4):1423-32 [2831403] Mol Cell Biol. 1988 Feb;8(2):884-92 [2832742] J Immunol. 1988 Jul 15;141(2):681-9 [2838552] Cell. 1988 Sep 23;54(7):1073-80 [2843290] Virology. 1988 Dec;167(2):400-6 [2462307] J Virol. 1989 Apr;63(4):1630-40 [2538646] Oncogene. 1989 May;4(5):583-92 [2471131] Blood. 1989 Oct;74(5):1517-24 [2506946] Mol Cell Biol. 1990 Feb;10(2):705-10 [2405253] Biotechniques. 1989 Oct;7(9):980-2, 984-6, 989-90 [2631796] Cell. 1990 Oct 19;63(2):313-24 [2208288] Mol Cell Biol. 1990 Nov;10(11):5747-52 [2233716] Cell. 1991 May 17;65(4):677-89 [1709592] Cell. 1991 May 17;65(4):701-13 [1827757] J Cell Physiol. 1991 May;147(2):231-41 [2040657] EMBO J. 1991 Dec;10(12):3713-9 [1718743] Cell Growth Differ. 1996 Oct;7(10):1383-92 [8891342] J Virol. 1996 Nov;70(11):7414-23 [8892859] Genes Dev. 1996 Nov 1;10(21):2720-31 [8946913] Genes Dev. 1996 Nov 1;10(21):2732-44 [8946914] Gene. 1996 Dec 5;182(1-2):123-8 [8982077] Biochim Biophys Acta. 1996 Dec 9;1288(3):F123-39 [9011176] Trends Biochem Sci. 1997 May;22(5):177-81 [9175477] Crit Rev Oncog. 1996;7(3-4):245-60 [9258605] Oncogene. 1997 Sep;15(11):1315-27 [9315100] Oncogene. 1992 Oct;7(10):1999-2006 [1408140] J Biol Chem. 1993 Jan 25;268(3):2255-9 [8420994] Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1619-23 [7679511] Mol Cell Biol. 1993 May;13(5):2858-69 [8474446] Genes Dev. 1994 Apr 1;8(7):770-82 [7926766] Cancer Res. 1995 Feb 1;55(3):501-4 [7834617] Cell Growth Differ. 1995 Jan;6(1):59-68 [7536440] Nucleic Acids Res. 1995 May 25;23(10):1686-90 [7784172] Mol Cell Biol. 1995 Aug;15(8):4623-30 [7623854] Blood. 1995 Sep 1;86(5):1873-80 [7655015] Nucleic Acids Res. 1995 Aug 25;23(16):3357-8 [7545288] Differentiation. 1995 Oct;59(3):171-8 [7589901] Oncogene. 1995 Dec 7;11(11):2273-9 [8570177] Oncogene. 1996 Jan 18;12(2):355-63 [8570212] Biochem J. 1996 Mar 15;314 ( Pt 3):713-21 [8615760] Adv Cancer Res. 1996;68:109-82 [8712067] Proc Natl Acad Sci U S A. 1982 Apr;79(7):2194-8 [6954533] Nature. 1983 Jun 2-8;303(5916):401-6 [6304522] Mol Cell Biol. 1983 May;3(5):787-95 [6865942] Nature. 1983 Nov 24-30;306(5941):395-7 [6316156] Nature. 1984 Jul 19-25;310(5974):249-51 [6205276] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of adeno-associated virus type 2 Rep68 protein endonuclease activity on partially single-stranded substrates. AN - 70923796; 10684315 AB - The endonuclease activity of the Rep68 and Rep78 proteins (Rep68/78) of adeno-associated virus type 2 (AAV) cuts at the terminal resolution site (trs) within the hairpin structure formed by the AAV inverted terminal repeats. Recent studies suggest that a DNA unwinding function of Rep68/78 may be required for endonuclease activity. We demonstrate that several mutant proteins which are endonuclease negative on a fully duplex hairpin substrate are endonuclease positive on a partially single-stranded hairpin substrate. Truncation analysis revealed that the endonuclease function is contained within the first 200 amino acids of Rep68/78. This endonucleolytic cleavage is believed to involve the covalent attachment of Rep68/78 to the trs via a phosphate-tyrosine linkage. A previous report (S. L. Walker, R. S. Wonderling, and R. A. Owens, J. Virol. 71:2722-2730, 1997) suggested that tyrosine 152 was part of the active site. We individually mutated each tyrosine within the first 200 amino acids of the Rep68 moiety of a maltose binding protein-Rep68/78 fusion protein to phenylalanine. Only mutation of tyrosine 156 resulted in a protein incapable of covalent attachment to a partially single-stranded hairpin substrate, suggesting that tyrosine 156 is part of the endonuclease active site. JF - Journal of virology AU - Davis, M D AU - Wu, J AU - Owens, R A AD - Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA. Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 2936 EP - 2942 VL - 74 IS - 6 SN - 0022-538X, 0022-538X KW - DNA, Single-Stranded KW - 0 KW - DNA, Viral KW - DNA-Binding Proteins KW - Recombinant Fusion Proteins KW - Viral Proteins KW - rep proteins, Adeno-associated virus 2 KW - 137750-19-7 KW - Tyrosine KW - 42HK56048U KW - Phenylalanine KW - 47E5O17Y3R KW - Endonucleases KW - EC 3.1.- KW - DNA Helicases KW - EC 3.6.4.- KW - Index Medicus KW - DNA Helicases -- metabolism KW - Humans KW - Gene Expression KW - Mutagenesis, Site-Directed KW - Recombinant Fusion Proteins -- metabolism KW - Base Sequence KW - DNA Helicases -- genetics KW - Molecular Sequence Data KW - Recombinant Fusion Proteins -- genetics KW - Tyrosine -- genetics KW - Phenylalanine -- genetics KW - Substrate Specificity KW - Viral Proteins -- genetics KW - Endonucleases -- metabolism KW - DNA, Single-Stranded -- metabolism KW - Dependovirus -- enzymology KW - Dependovirus -- genetics KW - DNA-Binding Proteins -- genetics KW - Viral Proteins -- metabolism KW - Endonucleases -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70923796?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutational+analysis+of+adeno-associated+virus+type+2+Rep68+protein+endonuclease+activity+on+partially+single-stranded+substrates.&rft.au=Davis%2C+M+D%3BWu%2C+J%3BOwens%2C+R+A&rft.aulast=Davis&rft.aufirst=M&rft.date=2000-03-01&rft.volume=74&rft.issue=6&rft.spage=2936&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 - 2000-04-03 N1 - Date created - 2000-04-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Gene Ther. 1994 May;1(3):165-9 [7584077] J Virol. 1999 Oct;73(10):8235-44 [10482574] Nature. 1991 May 2;351(6321):78-80 [1851252] Genomics. 1991 Jul;10(3):831-4 [1653762] J Virol. 1992 Feb;66(2):1119-28 [1309894] J Virol. 1992 Jul;66(7):4050-7 [1318396] EMBO J. 1992 Dec;11(13):5071-8 [1334463] J Virol. 1993 Feb;67(2):997-1005 [8380475] Virology. 1993 Jun;194(2):509-17 [8503171] Nucleic Acids Res. 1993 Jun 11;21(11):2541-7 [8332451] J Virol. 1993 Oct;67(10):6096-104 [8396670] Biosystems. 1993;30(1-3):241-68 [8374079] J Virol. 1994 Feb;68(2):797-804 [8289383] Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5808-12 [8016070] Proc Natl Acad Sci U S A. 1976 Mar;73(3):742-6 [1062784] Virology. 1977 May 15;78(2):488-99 [867815] J Virol. 1983 Feb;45(2):555-64 [6300419] Cell. 1983 May;33(1):135-43 [6088052] J Mol Biol. 1984 Oct 15;179(1):1-20 [6094825] Nucleic Acids Res. 1986 May 27;14(10):4229-38 [2940511] J Virol. 1986 Dec;60(3):823-32 [3023672] J Virol. 1987 Oct;61(10):3096-101 [3041032] Virology. 1987 Nov;161(1):18-28 [2823460] J Virol. 1989 Jul;63(7):3095-104 [2542617] Virology. 1989 Jul;171(1):239-47 [2545030] Gene. 1989 Apr 15;77(1):51-9 [2744487] Virology. 1989 Nov;173(1):120-8 [2554565] Cell. 1990 Jan 12;60(1):105-13 [2153052] Proc Natl Acad Sci U S A. 1990 Mar;87(6):2211-5 [2156265] Cell. 1990 May 4;61(3):447-57 [2159383] J Virol. 1990 Dec;64(12):6204-13 [2173787] J Mol Biol. 1991 Feb 20;217(4):721-9 [2005621] J Virol. 1994 Aug;68(8):4998-5006 [8035499] J Virol. 1994 Sep;68(9):6029-37 [8057478] Virology. 1994 Oct;204(1):304-11 [8091661] J Virol. 1994 Nov;68(11):7448-57 [7933128] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10039-43 [7937833] J Virol. 1995 Apr;69(4):2038-46 [7884849] J Virol. 1995 Jun;69(6):3542-8 [7538173] Virology. 1995 May 10;209(1):122-35 [7747462] J Virol. 1996 Apr;70(4):2440-8 [8642672] Biochem Biophys Res Commun. 1996 Mar 18;220(2):294-9 [8645299] J Virol. 1996 Mar;70(3):1542-53 [8627673] Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7966-72 [8755586] J Virol. 1997 Mar;71(3):2528-34 [9032395] J Virol. 1997 Apr;71(4):2722-30 [9060625] J Virol. 1997 Apr;71(4):3299-306 [9060699] J Virol. 1997 Sep;71(9):6996-7004 [9261429] J Virol. 1997 Oct;71(10):7361-71 [9311814] J Virol. 1998 Jun;72(6):4874-81 [9573254] J Virol. 1999 Feb;73(2):1580-90 [9882364] J Virol. 1999 Mar;73(3):2084-93 [9971790] J Virol. 1999 Apr;73(4):2682-93 [10074114] Virology. 1995 Dec 20;214(2):360-70 [8553536] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Felbamate block of recombinant N-methyl-D-aspartate receptors: selectivity for the NR2B subunit. AN - 70916879; 10690753 AB - The anticonvulsant felbamate blocks N-methyl-D-asparate (NMDA) receptors but fails to exhibit the neurobehavioral toxicity characteristic of other NMDA receptor antagonists. To investigate the possibility that felbamate's favorable toxicity profile could be related to NMDA receptor subtype selectivity, we examined the specificity of felbamate block of recombinant NMDA receptors composed of the NR1a subunit and various NR2 subunits. Felbamate produced a rapid, concentration-dependent block of currents evoked by 50 microM NMDA and 10 microM glycine in human embryonic kidney 293 cells expressing the rat NR1a subunit, and either the NR2A, NR2B or NR2C subunits; the IC50 values for block were 2.6, 0.52 and 2.4 mM, respectively (holding potential, - 60 mV). The Hill coefficient values were < 1 and, in kinetic analyses, onset and recovery from block were well fit by double exponential functions, indicating binding to more than one blocking site on the NMDA receptor channel complex. The higher affinity of felbamate block of NMDA receptors containing the NR2B subunit could be accounted for by more rapid association and slower dissociation from these sites. We conclude that felbamate exhibits modest selectivity for NMDA receptors composed of NR1a/NR2B subunits. This selectivity could, in part, account for the more favorable clinical profile of felbamate in comparison with NMDA receptor antagonists that do not show subunit selectivity. JF - Epilepsy research AU - Harty, T P AU - Rogawski, M A AD - Neuronal Excitability Section, Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1408, USA. Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 47 EP - 55 VL - 39 IS - 1 SN - 0920-1211, 0920-1211 KW - Anticonvulsants KW - 0 KW - Excitatory Amino Acid Agonists KW - NMDA receptor A1 KW - NR2B NMDA receptor KW - Phenylcarbamates KW - Propylene Glycols KW - Receptors, N-Methyl-D-Aspartate KW - N-Methylaspartate KW - 6384-92-5 KW - felbamate KW - X72RBB02N8 KW - Index Medicus KW - Rats KW - Animals KW - Patch-Clamp Techniques KW - N-Methylaspartate -- pharmacology KW - Humans KW - Transfection -- genetics KW - Membrane Potentials -- physiology KW - Excitatory Amino Acid Agonists -- pharmacology KW - Membrane Potentials -- drug effects KW - Cells, Cultured -- drug effects KW - Propylene Glycols -- pharmacology KW - Anticonvulsants -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70916879?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Felbamate+block+of+recombinant+N-methyl-D-aspartate+receptors%3A+selectivity+for+the+NR2B+subunit.&rft.au=Harty%2C+T+P%3BRogawski%2C+M+A&rft.aulast=Harty&rft.aufirst=T&rft.date=2000-03-01&rft.volume=39&rft.issue=1&rft.spage=47&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 - 2000-05-04 N1 - Date created - 2000-05-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disulfide bonds and membrane topology of the vaccinia virus A17L envelope protein. AN - 70896275; 10666276 AB - The envelope protein encoded by the vaccinia virus A17L open reading frame is essential for virion assembly. Our mutagenesis studies indicated that cysteines 101 and 121 form an intramolecular disulfide bond and that cysteine 178 forms an intermolecular disulfide linking two A17L molecules. This arrangement of disulfide bonds has important implications for the topology of the A17L protein and supports a two-transmembrane model in which cysteines 101 and 121 are intraluminal and cysteine 178 is cytoplasmic. The structure of the A17L protein, however, was not dependent on these disulfide bonds, as a recombinant vaccinia virus with all three cysteine codons mutated to serines retained infectivity. JF - Journal of virology AU - Betakova, T AU - Moss, B AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0445, USA. Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 2438 EP - 2442 VL - 74 IS - 5 SN - 0022-538X, 0022-538X KW - A17L protein, Vaccinia virus KW - 0 KW - Disulfides KW - Membrane Proteins KW - Viral Envelope Proteins KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Cysteine -- chemistry KW - Blotting, Western KW - Transfection KW - Open Reading Frames KW - Mutation KW - Cell Line KW - Vaccinia virus -- genetics KW - Disulfides -- chemistry KW - Viral Envelope Proteins -- chemistry KW - Vaccinia virus -- chemistry KW - Viral Envelope Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70896275?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Disulfide+bonds+and+membrane+topology+of+the+vaccinia+virus+A17L+envelope+protein.&rft.au=Betakova%2C+T%3BMoss%2C+B&rft.aulast=Betakova&rft.aufirst=T&rft.date=2000-03-01&rft.volume=74&rft.issue=5&rft.spage=2438&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 - 2000-11-03 N1 - Date created - 2000-11-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Virology. 1994 Aug 1;202(2):844-52 [8030247] J Virol. 1994 Jan;68(1):130-47 [8254722] J Virol. 1995 Aug;69(8):4640-8 [7609028] J Virol. 1995 Oct;69(10):6376-88 [7666539] J Virol. 1995 Oct;69(10):6581-7 [7666563] Virology. 1968 Aug;35(4):564-83 [5677800] J Virol. 1970 Oct;6(4):519-33 [5497899] J Virol. 1985 Sep;55(3):651-9 [4020961] Virology. 1992 Apr;187(2):643-53 [1546459] Virology. 1994 Apr;200(1):154-61 [8128619] J Virol. 1996 May;70(5):2797-808 [8627754] J Biol Chem. 1996 Jun 21;271(25):14950-8 [8662995] J Virol. 1997 Mar;71(3):1821-33 [9032312] Virology. 1997 Jun 23;233(1):19-42 [9201214] J Virol. 1997 Oct;71(10):7404-20 [9311819] J Virol. 1998 Feb;72(2):1287-96 [9445029] J Virol. 1999 Feb;73(2):1503-17 [9882356] J Cell Biol. 1999 Jan 25;144(2):267-79 [9922453] Annu Rev Genet. 1998;32:163-84 [9928478] J Virol. 1999 May;73(5):3534-43 [10196242] J Virol. 1999 Sep;73(9):7287-96 [10438817] Virology. 1999 Sep 1;261(2):347-56 [10497120] J Biophys Biochem Cytol. 1961 Aug;10:475-503 [13719413] Science. 1992 Sep 11;257(5076):1496-502 [1523409] J Cell Biol. 1993 May;121(3):521-41 [8486734] J Virol. 1993 Jun;67(6):3435-40 [8497059] Curr Opin Struct Biol. 1995 Feb;5(1):85-91 [7773751] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of novel regions of allelic loss from a genomewide scan of esophageal squamous-cell carcinoma in a high-risk Chinese population. AN - 70891034; 10679910 AB - Esophageal cancer is one of the most common fatal cancers worldwide. Deletions of genomic regions are thought to be important in esophageal carcinogenesis. We conducted a genomewide scan for regions of allelic loss using microdissected DNA from 11 esophageal squamous-cell carcinoma patients with a family history of upper gastrointestinal tract cancer from a high-risk region in north central China. Allelic patterns of 366 fluorescently labeled microsatellite markers distributed at 10-cM intervals over the 22 autosomal chromosomes were examined. We identified 14 regions with very high frequency (>/= 75%) loss of heterozygosity (LOH), including broad regions encompassing whole chromosome arms (on 3p, 5q, 9p, 9q, and 13q), regions of intermediate size (on 2q, 4p, 11p, and 15q), and more discrete regions identified by very high frequency LOH for a single marker (on 4q, 6q, 8p, 14q, and 17p). Among these 14 regions were 7 not previously described in esophageal squamous-cell carcinoma as having very high frequency LOH (on 2q, 4p, 4q, 6q, 8p, 14q, and 15q). The very high frequency LOH regions identified here may point to major susceptibility genes, including potential tumor suppressor genes and inherited gene loci, which will assist in understanding the molecular events involved in esophageal carcinogenesis and may help in the development of markers for genetic susceptibility testing and screening for the early detection of this cancer. Genes Chromosomes Cancer 27:217-228, 2000. Published 2000 Wiley-Liss, Inc. JF - Genes, chromosomes & cancer AU - Hu, N AU - Roth, M J AU - Polymeropolous, M AU - Tang, Z Z AU - Emmert-Buck, M R AU - Wang, Q H AU - Goldstein, A M AU - Feng, S S AU - Dawsey, S M AU - Ding, T AU - Zhuang, Z P AU - Han, X Y AU - Ried, T AU - Giffen, C AU - Taylor, P R AD - National Cancer Institute, Bethesda, Maryland, USA. Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 217 EP - 228 VL - 27 IS - 3 SN - 1045-2257, 1045-2257 KW - Genetic Markers KW - 0 KW - Index Medicus KW - Microsatellite Repeats -- genetics KW - Genetic Markers -- genetics KW - Risk Factors KW - Humans KW - China -- epidemiology KW - Adult KW - Middle Aged KW - Male KW - Female KW - Chromosomes, Human -- genetics KW - Genome, Human KW - Carcinoma, Squamous Cell -- epidemiology KW - Esophageal Neoplasms -- genetics KW - Carcinoma, Squamous Cell -- genetics KW - Loss of Heterozygosity -- genetics KW - Esophageal Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70891034?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes%2C+chromosomes+%26+cancer&rft.atitle=Identification+of+novel+regions+of+allelic+loss+from+a+genomewide+scan+of+esophageal+squamous-cell+carcinoma+in+a+high-risk+Chinese+population.&rft.au=Hu%2C+N%3BRoth%2C+M+J%3BPolymeropolous%2C+M%3BTang%2C+Z+Z%3BEmmert-Buck%2C+M+R%3BWang%2C+Q+H%3BGoldstein%2C+A+M%3BFeng%2C+S+S%3BDawsey%2C+S+M%3BDing%2C+T%3BZhuang%2C+Z+P%3BHan%2C+X+Y%3BRied%2C+T%3BGiffen%2C+C%3BTaylor%2C+P+R&rft.aulast=Hu&rft.aufirst=N&rft.date=2000-03-01&rft.volume=27&rft.issue=3&rft.spage=217&rft.isbn=&rft.btitle=&rft.title=Genes%2C+chromosomes+%26+cancer&rft.issn=10452257&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-09 N1 - Date created - 2000-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bcl-2 overexpression attenuates dopamine-induced apoptosis in an immortalized neural cell line by suppressing the production of reactive oxygen species. AN - 70888226; 10657030 AB - Parkinson's disease is a neurodegenerative disease that is consequent to the loss of brain dopamine (DA) cells. These abnormalities are thought, in part, to be a manifestation of increased free radical production during the metabolism of catecholamines. The antiapoptic agent, bcl-2, has been shown to protect cells against the toxic effects of reactive oxygen species (ROS). Thus, we tested whether bcl-2 could attenuate the toxic effects of DA on immortalized neural cells. Our results show that DA caused dose-dependent cell death. The use of confocal microscopy and flow cytometry demonstrated that DA caused cell death through an apoptotic process. Moreover, DA caused a marked increase in ROS in these cells. Furthermore, overexpression of bcl-2 caused significant protection against DA-induced apoptosis. These results are discussed in terms of their support for a role of bcl-2 in the development of Parkinson's disease. Copyright 2000 Wiley-Liss, Inc. JF - Synapse (New York, N.Y.) AU - Cadet, J L AU - Harrington, B AU - Ordonez, S AD - Molecular Neuropsychiatry Section, NIH/NIDA, Intramural Research Program, Baltimore, Maryland 21224, USA. jcadet@intra.nida.nih.gov Y1 - 2000/03/01/ PY - 2000 DA - 2000 Mar 01 SP - 228 EP - 233 VL - 35 IS - 3 SN - 0887-4476, 0887-4476 KW - Cardiotonic Agents KW - 0 KW - Proto-Oncogene Proteins c-bcl-2 KW - Reactive Oxygen Species KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Dopamine -- pharmacology KW - Humans KW - Parkinson Disease -- metabolism KW - Cardiotonic Agents -- pharmacology KW - Reactive Oxygen Species -- metabolism KW - Neurons -- metabolism KW - Proto-Oncogene Proteins c-bcl-2 -- drug effects KW - Neurons -- drug effects KW - Apoptosis -- physiology KW - Proto-Oncogene Proteins c-bcl-2 -- physiology KW - Apoptosis -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70888226?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Bcl-2+overexpression+attenuates+dopamine-induced+apoptosis+in+an+immortalized+neural+cell+line+by+suppressing+the+production+of+reactive+oxygen+species.&rft.au=Cadet%2C+J+L%3BHarrington%2C+B%3BOrdonez%2C+S&rft.aulast=Cadet&rft.aufirst=J&rft.date=2000-03-01&rft.volume=35&rft.issue=3&rft.spage=228&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 - 2000-04-11 N1 - Date created - 2000-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurochemical neutralization of methamphetamine with high-affinity nonselective inhibitors of biogenic amine transporters: a pharmacological strategy for treating stimulant abuse. AN - 70887772; 10657029 AB - The abuse of methamphetamine (METH) and other amphetamine-like stimulants is a growing problem in the United States. METH is a substrate for the 12-transmembrane proteins which function as transporters for the biogenic amines dopamine (DA), serotonin (5-HT), and norepinephrine (NE). Increased release of CNS DA is thought to mediate the addictive effects of METH, whereas increased release of NE in both the peripheral and CNS is thought to mediate its cardiovascular effects. The neurotoxic effects of METH on both dopaminergic and serotonergic nerves requires the transport of METH into the nerve terminals. Thus, transport of METH into nerve terminals is the crucial first step in the production of METH-associated pharmacological and toxicological effects. A single molecular entity which would block the transport of METH at all three biogenic amine transporters might function to neurochemically neutralize METH. This agent would ideally be a high-affinity slowly dissociating agent at all three transporters, and also be amenable to formulation as a long-acting depot medication, such as has been accomplished with an analog of GBR12909. As a first step towards developing such an agent, we established an in vitro assay which selectively detects transporter substrates and used this assay to profile the ability of a lead compound, indatraline, to block the releasing effects of METH and MDMA at the DA, 5-HT, and NE transporters. The major finding reported here is that indatraline blocks the ability of METH and MDMA to release these neurotransmitters. Synapse 35:222-227, 2000. Published 2000 Wiley-Liss, Inc. JF - Synapse (New York, N.Y.) AU - Rothman, R B AU - Partilla, J S AU - Baumann, M H AU - Dersch, C M AU - Carroll, F I AU - Rice, K C AD - Clinical Psychopharmacology Section, Intramural Research Program, NIDA, NIH, Baltimore, Maryland, USA. RROTHMAN@INTRA.NIDA.NIH.GOV Y1 - 2000/03/01/ PY - 2000 DA - 2000 Mar 01 SP - 222 EP - 227 VL - 35 IS - 3 SN - 0887-4476, 0887-4476 KW - Adrenergic Uptake Inhibitors KW - 0 KW - Dopamine Uptake Inhibitors KW - Indans KW - Serotonin Uptake Inhibitors KW - Serotonin KW - 333DO1RDJY KW - Methamphetamine KW - 44RAL3456C KW - Lu 19005 KW - 97229-15-7 KW - N-Methyl-3,4-methylenedioxyamphetamine KW - KE1SEN21RM KW - Dopamine KW - VTD58H1Z2X KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Rats KW - Animals KW - Substance-Related Disorders -- drug therapy KW - Serotonin Uptake Inhibitors -- pharmacokinetics KW - N-Methyl-3,4-methylenedioxyamphetamine -- pharmacokinetics KW - Substance-Related Disorders -- metabolism KW - Methamphetamine -- pharmacokinetics KW - Norepinephrine -- pharmacokinetics KW - Indans -- pharmacokinetics KW - Dopamine -- pharmacokinetics KW - Adrenergic Uptake Inhibitors -- pharmacokinetics KW - Serotonin -- pharmacokinetics KW - Dopamine Uptake Inhibitors -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70887772?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neurochemical+neutralization+of+methamphetamine+with+high-affinity+nonselective+inhibitors+of+biogenic+amine+transporters%3A+a+pharmacological+strategy+for+treating+stimulant+abuse.&rft.au=Rothman%2C+R+B%3BPartilla%2C+J+S%3BBaumann%2C+M+H%3BDersch%2C+C+M%3BCarroll%2C+F+I%3BRice%2C+K+C&rft.aulast=Rothman&rft.aufirst=R&rft.date=2000-03-01&rft.volume=35&rft.issue=3&rft.spage=222&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 - 2000-04-11 N1 - Date created - 2000-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mesothelioma and lung tumors attributable to asbestos among petroleum workers. AN - 70871557; 10642417 AB - Asbestos exposure has been definitively found to be associated with both mesothelioma and lung cancer. Nevertheless, in the overall population of oil refinery workers potentially exposed to asbestos, many studies clearly show a definitely increased risk of mesothelioma, but no proven excess of lung cancer after comparison to the general population. Through the presentation of new data and the re-appraisal of two recent and independent epidemiological studies conducted in Liguria, Italy, and Ontario, Canada, we attempt to shed light on this apparently paradoxical finding. Lung cancer mortality was studied among maintenance workers exposed to asbestos, and among two other subgroups of refinery employees: blue collar and white collar workers. The comparison with blue collar workers was performed in order to take into account the role of healthy worker effect, smoking habit, and the socioeconomic level. The comparison with white collar workers was performed to control for other occupational lung carcinogens. Results reveal a consistency between the two studies and show that 96-100% of the mesotheliomas and 42-49% of the lung tumors arising among maintenance workers were attributable to asbestos exposure. Our new analysis, estimating two cases of asbestos-related lung cancer for each case of mesothelioma, confirms published findings on the magnitude of asbestos-related tumors in oil refineries. Copyright 2000 Wiley-Liss, Inc. JF - American journal of industrial medicine AU - Gennaro, V AU - Finkelstein, M M AU - Ceppi, M AU - Fontana, V AU - Montanaro, F AU - Perrotta, A AU - Puntoni, R AU - Silvano, S AD - Environmental Epidemiology and Biostatistics, National Cancer Institute, Genoa, Italy. gennarov@hp380.ist.unige.it Y1 - 2000/03// PY - 2000 DA - March 2000 SP - 275 EP - 282 VL - 37 IS - 3 SN - 0271-3586, 0271-3586 KW - Petroleum KW - 0 KW - Asbestos KW - 1332-21-4 KW - Index Medicus KW - Pleural Neoplasms -- chemically induced KW - Humans KW - Pleural Neoplasms -- epidemiology KW - Smoking -- adverse effects KW - Data Interpretation, Statistical KW - Italy -- epidemiology KW - Male KW - Female KW - Occupational Diseases -- mortality KW - Occupational Exposure KW - Mesothelioma -- epidemiology KW - Lung Neoplasms -- epidemiology KW - Mesothelioma -- chemically induced KW - Asbestos -- adverse effects KW - Petroleum -- adverse effects KW - Lung Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70871557?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Mesothelioma+and+lung+tumors+attributable+to+asbestos+among+petroleum+workers.&rft.au=Gennaro%2C+V%3BFinkelstein%2C+M+M%3BCeppi%2C+M%3BFontana%2C+V%3BMontanaro%2C+F%3BPerrotta%2C+A%3BPuntoni%2C+R%3BSilvano%2C+S&rft.aulast=Gennaro&rft.aufirst=V&rft.date=2000-03-01&rft.volume=37&rft.issue=3&rft.spage=275&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-15 N1 - Date created - 2000-02-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Ind Med. 2001 May;39(5):524-7 [11333419] Am J Ind Med. 2001 May;39(5):513-4, 522-3; author reply 517-21 [11333415] Am J Ind Med. 2001 May;39(5):515-21; author reply 517-21 [11333416] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Entropic barriers, transition states, funnels, and exponential protein folding kinetics: a simple model. AN - 18143861; 4867671 AB - This paper presents an analytically tractable model that captures the most elementary aspect of the protein folding problem, namely that both the energy and the entropy decrease as a protein folds. In this model, the system diffuses within a sphere in the presence of an attractive spherically symmetric potential. The native state is represented by a small sphere in the center, and the remaining space is identified with unfolded states. The folding temperature, the time-dependence of the populations, and the relaxation rate are calculated, and the folding dynamics is analyzed for both golf-course and funnel-like energy landscapes. This simple model allows us to illustrate a surprising number of concepts including entropic barriers, transition states, funnels, and the origin of single exponential relaxation kinetics. JF - Protein Science AU - Bicout, D J AU - Szabo, A AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.) Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 452 EP - 465 VL - 9 IS - 3 SN - 0961-8368, 0961-8368 KW - Physical Education Index KW - Biochemistry KW - Energy KW - Temperature KW - Proteins KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18143861?accountid=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=Protein+Science&rft.atitle=Entropic+barriers%2C+transition+states%2C+funnels%2C+and+exponential+protein+folding+kinetics%3A+a+simple+model.&rft.au=Bicout%2C+D+J%3BSzabo%2C+A&rft.aulast=Bicout&rft.aufirst=D&rft.date=2000-03-01&rft.volume=9&rft.issue=3&rft.spage=452&rft.isbn=&rft.btitle=&rft.title=Protein+Science&rft.issn=09618368&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Proteins; Biochemistry; Temperature; Energy ER - TY - JOUR T1 - Lack of effect of beta-naphthoflavone on induction of Nramp genes in adult rainbow trout Oncorhynchus mykiss. AN - 18082444; 5147643 AB - Natural resistance-associated macrophage protein (Nramp) genes in rainbow trout, Oncorhynhus mykiss, were identified and characterized. The greatest mRNA level encoding these genes was in the developing ovary of rainbow trout. We evaluated the response of these genes to a certain aromatic hydrocarbon receptor (AHR) agonist. Adult rainbow trout were treated with beta-naphthoflavone (BNF) (50 and 100 mg/kg) for 48 h. Using reverse-transcriptase polymerase chain reaction with ovary and head kidney RNA and specific alpha and beta Nramp primers, a 400 bp Nramp-alpha- and a 400 pb Nramp-beta-specific cDNA were obtained. There were no changes in the alpha and beta Nramp mRNA levels in the ovary following BNF administration. CYP1A1 mRNA was increased in the ovary and kidney, suggesting the presence of AHR in rainbow trout ovary, while the AHR agonist produced no effect on Nramp mRNAs. JF - Marine Environmental Research AU - Dasmahapatra, A K AU - Wimpee, BAB AU - Budsberg, K J AU - Dorschner, MO AU - Phillips, R B AU - Hutz, R J AD - NIEHS Marine and Freshwater Biomedical Sciences Center, University of Wisconsin-Milwaukee Milwaukee, WI 53204 USA Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 147 EP - 151 VL - 50 IS - 1-5 SN - 0141-1136, 0141-1136 KW - Beta-naphthoflavone KW - ASFA 3: Aquatic Pollution & Environmental Quality; ASFA 1: Biological Sciences & Living Resources KW - Marine KW - Cytochromes KW - Genes KW - Polymerase chain reaction KW - Oncorhynchus mykiss KW - Ovaries KW - Q1 08345:Genetics and evolution KW - Q5 08504:Effects on organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18082444?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Marine+Environmental+Research&rft.atitle=Lack+of+effect+of+beta-naphthoflavone+on+induction+of+Nramp+genes+in+adult+rainbow+trout+Oncorhynchus+mykiss.&rft.au=Dasmahapatra%2C+A+K%3BWimpee%2C+BAB%3BBudsberg%2C+K+J%3BDorschner%2C+MO%3BPhillips%2C+R+B%3BHutz%2C+R+J&rft.aulast=Dasmahapatra&rft.aufirst=A&rft.date=2000-03-01&rft.volume=50&rft.issue=1-5&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Marine+Environmental+Research&rft.issn=01411136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - Cytochromes; Genes; Polymerase chain reaction; Ovaries; Oncorhynchus mykiss; Marine ER - TY - JOUR T1 - Construction and function of a recombinant adenovirus encoding a human aquaporin 1-green fluorescent protein fusion product AN - 17905229; 5184551 AB - Transfer of the human aquaporin 1 (hAQP1) gene provides a novel way to potentially correct the severe salivary hypofunction associated with therapeutic radiation for head and neck cancer. To facilitate the study of individual cells transduced with this gene, we have designed a fusion product of the hAQP1 and jellyfish green fluorescent protein (GFP) cDNAs. An expression plasmid, pACCMVhAQP1GFP, and a recombinant adenovirus, AdhAQP1GFP, encoding this fusion product were constructed. Both the recombinant plasmid and virus directed the expression of the encoded, 55-kDa fusion protein (hAQP1GFP), which was detected in the plasma membranes of several epithelial cell lines (293, SMIE, and A5). hAQP1GFP was functionally active and facilitated fluid movement across a polarized salivary epithelial cell monolayer ( similar to 5-fold noninfected controls) in response to an osmotic gradient. In response to a hypotonic challenge, individual epithelial cells expressing the fusion protein exhibited significantly more capacitance (used herein as an indicator of cell swelling) than control cells. Conversely, in response to a hypertonic challenge, individual infected cells shrunk more rapidly ( similar to 2- to 3-fold) and to a greater extent than control cells. We conclude that AdhAQP1GFP is a useful experimental tool to identify and study individual cells expressing a water channel transgene. JF - Cancer Gene Therapy AU - Hoque, ATMS AU - Liu, X AU - Kagami, H AU - Swaim, W D AU - Wellner, R B AU - O'Connell, B C AU - Ambudkar, I S AU - Baum, B J AD - Gene Therapy and Therapeutics Branch, National Institutes of Dental and Craniofacial Research, National Institutes of Health, Building 10, Room 1N113, 10 Center Drive, MSC 1190, Bethesda, MD 20892, USA Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 476 EP - 485 VL - 7 IS - 3 SN - 0929-1903, 0929-1903 KW - man KW - aquaporin 1 KW - green fluorescent protein KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Plasma membranes KW - Gene therapy KW - Gene transfer KW - Adenovirus KW - Epithelium KW - Fusion protein KW - Salivary gland KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17905229?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Gene+Therapy&rft.atitle=Construction+and+function+of+a+recombinant+adenovirus+encoding+a+human+aquaporin+1-green+fluorescent+protein+fusion+product&rft.au=Hoque%2C+ATMS%3BLiu%2C+X%3BKagami%2C+H%3BSwaim%2C+W+D%3BWellner%2C+R+B%3BO%27Connell%2C+B+C%3BAmbudkar%2C+I+S%3BBaum%2C+B+J&rft.aulast=Hoque&rft.aufirst=ATMS&rft.date=2000-03-01&rft.volume=7&rft.issue=3&rft.spage=476&rft.isbn=&rft.btitle=&rft.title=Cancer+Gene+Therapy&rft.issn=09291903&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adenovirus; Fusion protein; Gene therapy; Gene transfer; Plasma membranes; Epithelium; Salivary gland; Expression vectors ER - TY - JOUR T1 - Rat Testicular Src: Normal Distribution and Involvement in Ethylene Glycol Monomethyl Ether-Induced Apoptosis AN - 17897589; 5156992 AB - Kinase activities were previously proposed to be central to germ cell apoptosis induced by ethylene glycol monomethyl ether (EGME) and its active metabolite methoxyacetic acid (MAA). We evaluated the role of tyrosine kinase pp60 super(c-src) in control and EGME-treated adult rat testis in vivo, as well as in vitro using cultured adult rat seminiferous tubules treated with MAA. In normal testicular tissue, immunoreactivity of Src was mostly detected in Sertoli cell cytoplasm and reached the maximum level around the lumen at spermiation. Src localization was confirmed by immunostaining of cocultures of Sertoli and germ cells and was further confirmed by electron microscopic observation that immunoreactivity was predominant in Sertoli cell cytoplasm as well as occasionally at the Sertoli/germ cell junctions. A single dose of 200 mg/kg EGME induced an increase of Src immunoexpression in both epithelium and interstitium in rat testis. Eight hours after treatment, an intensive immunostaining of Src began to be observed specifically in the cytoplasm of the dying spermatocytes. The apoptotic changes were replicated by exposure of 5 mM MAA in the adult rat seminiferous tubule culture model. Furthermore, spermatocyte degeneration was significantly prevented by cotreatment with 0.1 mu M geldanamycin, 10 mu M herbimycin A, or 10 mu M PP2, which are inhibitors of Src activity. These data collectively suggest that pp60 super(c-src) mediates Sertoli-germ cell interaction in physiological events, and may play an important role in EGME/MAA-induced germ cell apoptosis. JF - Toxicology and Applied Pharmacology AU - Wang, W AU - Wine, R N AU - Chapin, R E AD - Laboratory of Toxicology, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, chapin@niehs.nih.gov Y1 - 2000/03/01/ PY - 2000 DA - 2000 Mar 01 SP - 125 EP - 134 PB - Academic Press VL - 163 IS - 2 SN - 0041-008X, 0041-008X KW - rats KW - Src protein KW - ethylene glycol monomethyl ether KW - Toxicology Abstracts KW - Testes KW - Sertoli cells KW - Apoptosis KW - Germ cells KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17897589?accountid=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=Rat+Testicular+Src%3A+Normal+Distribution+and+Involvement+in+Ethylene+Glycol+Monomethyl+Ether-Induced+Apoptosis&rft.au=Wang%2C+W%3BWine%2C+R+N%3BChapin%2C+R+E&rft.aulast=Wang&rft.aufirst=W&rft.date=2000-03-01&rft.volume=163&rft.issue=2&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1006%2Ftaap.1999.8870 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Apoptosis; Sertoli cells; Testes; Germ cells DO - http://dx.doi.org/10.1006/taap.1999.8870 ER - TY - JOUR T1 - Metabolism and disposition of luminol in the rat AN - 17695420; 4784501 AB - The metabolism and disposition of Luminol (LMN, 3-aminophthalhydrazide), a widely used forensic and laboratory reagent that chemiluminesses upon oxidation, was determined as part of its overall toxicological characterization. Radiolabelled LMN was well absorbed, metabolized and excreted following p.o. administration of a range of doses. About 90% of the total dose was recovered within 24 h of administration in urine in the form of two metabolites identified as LMN N super(8)-glucuronide and LMN N super(8)-sulphamic acid. 3-Aminophthalic acid, the oxidative product of LMN in the light-emitting reaction, was apparently not formed in vivo. Metabolism and disposition of an i.v. administered dose was similar to that following gavage. Little or no LMN-derived radioactivity was present in tissue within 12 h post-dosing. Excretion of radioactivity in bile following i.v. injection was minimal ( similar to 8% of the total dose in 6 h) and consisted of the same urinary-excreted glucuronide and sulphate conjugates. LMN was not absorbed dermally in rat, potentially a major route of exposure to human. If the fate of LMN is similar between species, this compound should have little potential for either dermal absorption, bioaccumulation in tissues following other routes of exposure or chronic toxicity in humans. JF - Xenobiotica AU - Sanders, J M AU - Chen, L-J AU - Burka, L T AU - Matthews, H B AD - Laboratory of Pharmacology and Chemistry, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA, sandersm@niehs.nih.gov Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 263 EP - 272 VL - 30 IS - 3 SN - 0049-8254, 0049-8254 KW - rats KW - pharmacokinetics KW - luminol KW - Toxicology Abstracts KW - Urine KW - Radioactive labelling KW - Chemiluminescence KW - X 24153:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17695420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Xenobiotica&rft.atitle=Metabolism+and+disposition+of+luminol+in+the+rat&rft.au=Sanders%2C+J+M%3BChen%2C+L-J%3BBurka%2C+L+T%3BMatthews%2C+H+B&rft.aulast=Sanders&rft.aufirst=J&rft.date=2000-03-01&rft.volume=30&rft.issue=3&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=Xenobiotica&rft.issn=00498254&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Radioactive labelling; Chemiluminescence; Urine ER - TY - JOUR T1 - Emerging Roles of Carbohydrates and Glycomimetics in Anticancer Drug Design AN - 17662524; 4716672 AB - Tumorigenesis is accompanied by marked changes in the expression and presentation of various macromolecules at the cell surface. These tumor-associated adjustments result from the differential expression of genes coding for the production or post-translational modifications of these macromolecules during transformation to a particular tumor phenotype. In turn, tumor cells acquire distinct biophysical properties which set them apart from their normal counterparts. Alterations of carbohydrate structures and their organization on the surface of neoplastic cells is a hallmark of the tumorigenic and, most notably, the metastatic phenotype. Carbohydrate-protein and carbohydrate-carbohydrate interactions are critical events in the progression, dissemination and invasion of cancer cells. Many cell-cell contacts and subsequent remodeling of the tumor microenvironment are mediated by cell-surface glycans. The discovery of agents that modulate these interactions or interfere with the processing of tumor associated oligosaccharides is a fervent area of research today. This review will highlight the current status of the use of carbohydrate-based compounds that are being evaluated as potential anticancer therapeutics. In addition, the use of structures based on glycopeptides and carbohydrate mimetics will also be discussed. JF - Current Pharmaceutical Design AU - Barchi, JJ Jr AD - National Cancer Institute, National Institutes of Health, 37 Convent DR MSC4255, Bldg 37 Rm 5C02, Bethesda, MD 20892-4255, USA, barchi@helix.nih.gov Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 485 EP - 501 VL - 6 IS - 4 SN - 1381-6128, 1381-6128 KW - carbohydrates KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Drug discovery KW - Reviews KW - Tumorigenesis KW - Antitumor agents KW - Cancer KW - W3 33374:Antitumor agents KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17662524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Pharmaceutical+Design&rft.atitle=Emerging+Roles+of+Carbohydrates+and+Glycomimetics+in+Anticancer+Drug+Design&rft.au=Barchi%2C+JJ+Jr&rft.aulast=Barchi&rft.aufirst=JJ&rft.date=2000-03-01&rft.volume=6&rft.issue=4&rft.spage=485&rft.isbn=&rft.btitle=&rft.title=Current+Pharmaceutical+Design&rft.issn=13816128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Molecular Targets for Novel Anticancer Drug Discovery. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Antitumor agents; Cancer; Drug discovery; Tumorigenesis; Reviews ER - TY - JOUR T1 - Molecular Targets in Cancer Drug Discovery: Cell-Based Profiling AN - 17661739; 4716671 AB - The phrase "molecular target-based drug discovery" usually implies an in vitro biochemical assay or battery of assays. One portion of the U.S. National Cancer Institute's drug discovery program, to the contrary, examines molecular targets for cancer therapy in a cell-based format. That approach has a number of significant limitations, but it has produced databases of significant utility on the activities and structures of tested compounds, as well as on molecular characteristics of the cell types used for testing. JF - Current Pharmaceutical Design AU - Weinstein, J N AU - Buolamwini, J K AD - Laboratory of Molecular Pharmacology, National Cancer Institute, Bldg. 37 Rm. 5D-02, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 473 EP - 483 VL - 6 IS - 4 SN - 1381-6128, 1381-6128 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Oxygen KW - Drug discovery KW - Reviews KW - Antitumor agents KW - Cancer KW - W3 33374:Antitumor agents KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17661739?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Pharmaceutical+Design&rft.atitle=Molecular+Targets+in+Cancer+Drug+Discovery%3A+Cell-Based+Profiling&rft.au=Weinstein%2C+J+N%3BBuolamwini%2C+J+K&rft.aulast=Weinstein&rft.aufirst=J&rft.date=2000-03-01&rft.volume=6&rft.issue=4&rft.spage=473&rft.isbn=&rft.btitle=&rft.title=Current+Pharmaceutical+Design&rft.issn=13816128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Molecular Targets for Novel Anticancer Drug Discovery. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cancer; Antitumor agents; Drug discovery; Oxygen; Reviews ER - TY - JOUR T1 - Identification of additional genes belonging to the LexA regulon in Escherichia coli AN - 17616212; 4753527 AB - Exposure of Escherichia coli to a variety of DNA-damaging agents results in the induction of the global 'SOS response'. Expression of many of the genes in the SOS regulon are controlled by the LexA protein. LexA acts as a transcriptional repressor of these unlinked genes by binding to specific sequences (LexA boxes) located within the promoter region of each LexA-regulated gene. Alignment of 20 LexA binding sites found in the E. coli chromosome reveals a consensus of 5'-TACTG(TA) sub(5)CAGTA-3'. DNA sequences that exhibit a close match to the consensus are said to have a low heterology index and bind LexA tightly, whereas those that are more diverged have a high heterology index and are not expected to bind LexA. By using this heterology index, together with other search criteria, such as the location of the putative LexA box relative to a gene or to promoter elements, we have performed computational searches of the entire E. coli genome to identify novel LexA-regulated genes. These searches identified a total of 69 potential LexA-regulated genes/operons with a heterology index of < 15 and included all previously characterized LexA-regulated genes. Probes were made to the remaining genes, and these were screened by Northern analysis for damage-inducible gene expression in a wild-type lexA super(+) cell, constitutive expression in a lexA(Def) cell and basal expression in a non-inducible lexA(Ind super(-)) cell. These experiments have allowed us to identify seven new LexA-regulated genes, thus bringing the present number of genes in the E. coli LexA regulon to 3 The potential function of each newly identified LexA-regulated gene is discussed. JF - Molecular Microbiology AU - Fernandez de Henestrosa, RA AU - Ogi, T AU - Aoyagi, S AU - Chafin, D AU - Hayes, J J AU - Ohmori, H AU - Woodgate, R 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 - 2000/03// PY - 2000 DA - Mar 2000 SP - 1560 EP - 1572 PB - Blackwell Science Ltd VL - 35 IS - 6 SN - 0950-382X, 0950-382X KW - LexA protein KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - DNA damage KW - Gene regulation KW - Transcription factors KW - Escherichia coli KW - Repressors KW - J 02726:RNA and ribosomes KW - G 07320:Bacterial genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17616212?accountid=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=Identification+of+additional+genes+belonging+to+the+LexA+regulon+in+Escherichia+coli&rft.au=Fernandez+de+Henestrosa%2C+RA%3BOgi%2C+T%3BAoyagi%2C+S%3BChafin%2C+D%3BHayes%2C+J+J%3BOhmori%2C+H%3BWoodgate%2C+R&rft.aulast=Fernandez+de+Henestrosa&rft.aufirst=RA&rft.date=2000-03-01&rft.volume=35&rft.issue=6&rft.spage=1560&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2000.01826.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Repressors; DNA damage; Transcription factors; Gene regulation DO - http://dx.doi.org/10.1046/j.1365-2958.2000.01826.x ER - TY - JOUR T1 - Measurement Variability Associated with KXRF Bone Lead Measurement in Young Adults AN - 17609115; 4729346 AB - In vivo bone lead measurement using K X-ray fluorescence (KXRF) has been used to estimate long-term lead exposure, especially in adults. Relatively few studies have been conducted on young subjects with this technique. To explore the measurement variability of KXRF bone lead measurements in young subjects, the tibiae of two male cadavers from Boston, Massachusetts, 17 and 20 years of age, were obtained for repeated bone lead measurements. Bone lead concentrations were measured using a grid of nine locations, 1 cm apart, centered at the midpoint of the tibia. Each location was sampled using five 60-min measurements. Measured concentrations ranged from < 0 to 11.8 mu g Pb/g bone mineral across a tibia with mean concentrations for the midpoint locations of 0.8 mu g Pb/g bone mineral SD = 2.5 and 2.0 mu g Pb/g bone mineral (SD = 1.9) for the left and right legs of the younger subject and 3.6 mu g Pb/g bone mineral (SD = 2.6) and 6.0 mu g Pb/g bone mineral (SD = 3.3) for the left and right legs of the older subject. Although bone lead concentrations did not vary significantly by measurement location in an individual leg, reported measurement uncertainty increased significantly at locations that were 1 cm from the center of the tibia horizontally (p < 0.0001). Symmetry in bone lead concentration between legs was observed for the 17-year-old subject. Potential asymmetry between the left and right legs was suggested for the 20-year-old subject (p = 0.06). These data describe the degree of variability that may be associated with bone lead measurements of young subjects with low bone lead concentrations using a standard spot-source KXRF instrument. Because of the importance of conducting additional research on adolescent lead toxicity, further improvements to the precision of KXRF measurement are needed. JF - Environmental Health Perspectives AU - Hoppin, JA AU - Aro, A AU - Hu, H AU - Ryan, P B AD - National Institute of Environmental Health Sciences (NIEHS), Epidemiology Branch, MD A3-05, PO Box 12233, Research Triangle Park, NC 27709-2233 USA, hoppin1@niehs.nih.gov Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 239 EP - 242 VL - 108 IS - 3 SN - 0091-6765, 0091-6765 KW - man KW - Calcium & Calcified Tissue Abstracts; Toxicology Abstracts KW - X radiation KW - Age KW - Fluorescence KW - Heavy metals KW - Measuring techniques KW - Lead KW - Bone KW - X 24222:Analytical procedures KW - T 20041:Laboratory methods KW - X 24163:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17609115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Measurement+Variability+Associated+with+KXRF+Bone+Lead+Measurement+in+Young+Adults&rft.au=Hoppin%2C+JA%3BAro%2C+A%3BHu%2C+H%3BRyan%2C+P+B&rft.aulast=Hoppin&rft.aufirst=JA&rft.date=2000-03-01&rft.volume=108&rft.issue=3&rft.spage=239&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Lead; Bone; Heavy metals; Age; X radiation; Fluorescence; Measuring techniques ER - TY - JOUR T1 - Comparison of respiratory symptoms among community residents near waste disposal incinerators AN - 17607778; 4729085 AB - A previous survey found that residents near a hazardous waste incinerator reported more respiratory symptoms than residents of a nearby community. To explore the possibility that these findings might have been due to the use of a rural control site, far removed from urban pollution, we expanded the analysis to include reports of respiratory symptoms from residents of six additional communities. Residents of each of four study communities were exposed to the plumes of biomedical, municipal or hazardous waste combustors. For each study community, a comparison community was surveyed that was distant from major point sources of air pollution. Over 4200 respondents were queried by telephone about respiratory symptoms, smoking and other risk factors such as chemical exposures in the workplace and home, and provided a subjective assessment of air quality in their neighborhoods. Differences in symptom prevalence between each study community and its respective control community, as well as a combined control group, were explored, controlling for factors other than community exposure that may affect respiratory health. Results indicate a higher prevalence of all self-reported respiratory symptoms in one community near a hazardous waste incinerator compared with its control community. While this relationship persisted after controlling for perceived air quality and when compared with a combined control group, only respiratory symptoms of long duration remained significant. These results suggest that further examination of the respiratory health of residents living near this waste combustor source is warranted. JF - International Journal of Environmental Health Research AU - Mohan, A K AU - Degnan, D AU - Feigley, CE AU - Shy, C M AU - Hornung, CA AU - Mustafa, T AU - Macera, CA AD - National Institutes of Health, National Cancer Institute, 6120 Executive Blvd, Room 7051, Rockville, MD 20852, USA Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 63 EP - 75 VL - 10 IS - 1 SN - 0960-3123, 0960-3123 KW - man KW - respiratory tract diseases KW - Risk Abstracts; Health & Safety Science Abstracts; Pollution Abstracts; Toxicology Abstracts KW - Pollution effects KW - Public health KW - Waste disposal sites KW - Lung diseases KW - Air pollution KW - Residential areas KW - Incinerators KW - X 24240:Miscellaneous KW - H 11000:Diseases/Injuries/Trauma KW - R2 23060:Medical and environmental health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17607778?accountid=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+Environmental+Health+Research&rft.atitle=Comparison+of+respiratory+symptoms+among+community+residents+near+waste+disposal+incinerators&rft.au=Mohan%2C+A+K%3BDegnan%2C+D%3BFeigley%2C+CE%3BShy%2C+C+M%3BHornung%2C+CA%3BMustafa%2C+T%3BMacera%2C+CA&rft.aulast=Mohan&rft.aufirst=A&rft.date=2000-03-01&rft.volume=10&rft.issue=1&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Environmental+Health+Research&rft.issn=09603123&rft_id=info:doi/10.1080%2F09603120073018 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Residential areas; Incinerators; Public health; Waste disposal sites; Air pollution; Pollution effects; Lung diseases DO - http://dx.doi.org/10.1080/09603120073018 ER - TY - JOUR T1 - Topography of the Surface of the Escherichia coli Phosphotransferase System Protein Enzyme IIA super(glc) that Interacts with Lactose Permease AN - 17602599; 4712904 AB - The unphosphorylated form of enzyme IIA super(glc) of the Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system inhibits transport catalyzed by lactose permease. We previously characterized the area on the cytoplasmic face of lactose permease that interacts with enzyme IIA super(glc), using radioactive enzyme IIA super(glc). Subsequent studies suggested consensus binding sequences on proteins that interact with enzyme IIA super(glc). The present study characterizes a region on the surface of enzyme IIA super(glc) that interfaces with lactose permease. Acetylation of lysine residues by sulfosuccinimidyl acetate treatment of enzyme IIA super(glc), but not lactose permease, reduced the degree of interaction between the two proteins. To localize the lysine residue(s) on enzyme IIA super(glc) that is(are) involved in the regulatory interaction, selected lysine residues were mutagenized. Conversion of nine separate lysines to glutamic acid resulted in proteins that were still capable of phosphoryl acceptance from HPr. Except for Lys69, all the modified proteins were as effective as the wild-type enzyme IIA super(glc) in a test for binding to lactose permease. The Lys69 mutant was also defective in phosphoryl transfer to glucose permease. To derive further information concerning the contact surface, additional selected residues in the vicinity of Lys69 were mutagenized and tested for binding to lactose permease. On the basis of these studies, a model for the region of the surface of enzyme IIA super(glc) that interacts with lactose permease is proposed. JF - Biochemistry (Washington) AU - Sondej, M AU - Seok, Yeong-Jae AU - Badawi, P AU - Koo, Byoung-Mo AU - Nam, Tae-Wook AU - Peterkofsky, A AD - National Institutes of Health, Building 36, Room 4C-11, Bethesda, MD 20892, USA, alan@codon.nih.gov Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 2931 EP - 2939 VL - 39 IS - 11 SN - 0006-2960, 0006-2960 KW - mutants KW - lactose permease KW - phosphotransferase system KW - Microbiology Abstracts B: Bacteriology KW - Cell surface KW - Protein-NP-phosphohistidine-sugar phosphotransferase KW - Escherichia coli KW - Lysine KW - Glutamic acid KW - Active sites KW - Topography KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17602599?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Topography+of+the+Surface+of+the+Escherichia+coli+Phosphotransferase+System+Protein+Enzyme+IIA+super%28glc%29+that+Interacts+with+Lactose+Permease&rft.au=Sondej%2C+M%3BSeok%2C+Yeong-Jae%3BBadawi%2C+P%3BKoo%2C+Byoung-Mo%3BNam%2C+Tae-Wook%3BPeterkofsky%2C+A&rft.aulast=Sondej&rft.aufirst=M&rft.date=2000-03-01&rft.volume=39&rft.issue=11&rft.spage=2931&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/10.1021%2Fbi9919596 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Protein-NP-phosphohistidine-sugar phosphotransferase; Topography; Cell surface; Active sites; Lysine; Glutamic acid DO - http://dx.doi.org/10.1021/bi9919596 ER - TY - JOUR T1 - Evaluation of recombinant alphaviruses as vectors in gene therapy AN - 17587776; 4689292 AB - Alphavirus vectors based on Sindbis virus and Semliki Forest virus (SFV) were characterized as potential gene transfer vectors. Initial studies were performed using vectors engineered to transfer either lacZ or green fluorescent protein (GFP). High levels of gene transfer were achieved in human primary fibroblasts, BHK and 293T cells, with low levels of transduction observed in more than 20 other target cells. Alphavirus-based expression was generally very high, but transient in every cell type. Replication-competent alphavirus was never detected in SFV preparations but could be produced by Sindbis-based vectors at a frequency of up to 3 x 10 super(-3) infectious units per ml. We constructed a human clotting factor IX (hFIX) cDNA-containing Sindbis virus and compared it with hFIX cDNA-harboring adenoviral and retroviral vectors. In most cases, hFIX levels obtained with Sindbis vector were initially at least an order of magnitude higher than those obtained with other viral vectors. These data demonstrate that alphavirus vectors compare favorably with adenovirus vectors as systems to promote high-level transient gene expression and should be considered as an alternative vector for gene transfer and potential gene therapy studies. JF - Gene Therapy AU - Wahlfors, J J AU - Zullo, SA AU - Loimas, S AU - Nelson, D M AU - Morgan, R A AD - Clinical Gene Therapy Branch, National Institutes of Health, 10 Center Drive, Bldg 10, Rm 10C103, Bethesda, MD 20892-1851, USA Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 472 EP - 480 VL - 7 IS - 6 SN - 0969-7128, 0969-7128 KW - Alphavirus KW - LacZ protein KW - Sindbis virus KW - green fluorescent protein KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Gene therapy KW - Fibroblasts KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17587776?accountid=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=Gene+Therapy&rft.atitle=Evaluation+of+recombinant+alphaviruses+as+vectors+in+gene+therapy&rft.au=Wahlfors%2C+J+J%3BZullo%2C+SA%3BLoimas%2C+S%3BNelson%2C+D+M%3BMorgan%2C+R+A&rft.aulast=Wahlfors&rft.aufirst=J&rft.date=2000-03-01&rft.volume=7&rft.issue=6&rft.spage=472&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&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 - Expression vectors; Fibroblasts; Gene therapy ER - TY - JOUR T1 - Butyrylcholinesterase Accelerates Cocaine Metabolism: In Vitro and In Vivo Effects in Nonhuman Primates and Humans AN - 17562478; 4755074 AB - Butyrylcholinesterase (BChE) is known to metabolize cocaine in humans. In the present study, three different experiments were performed to determine whether the addition of horse serum-derived BChE would accelerate the metabolism of cocaine. In the first experiment, the addition of BChE to squirrel monkey plasma in vitro reduced the half-life of cocaine by over 80%, decreased the production of the metabolic product benzoylecgonine, and increased ecgonine methyl ester formation. The effect of BChE on cocaine metabolism was reversed by a specific BChE inhibitor. In the second, in vivo, experiment, exogenously administered BChE reduced peak cocaine concentrations when given to anesthetized squirrel monkeys. Finally, incubation of cocaine with added BChE in human plasma in vitro resulted in a decrease in cocaine half-life similar to that observed with squirrel monkey plasma. The magnitude of the decrease in cocaine half-life was proportional to the amount of added BChE. Together, these results indicate that exogenously administered BChE can accelerate cocaine metabolism in such a way as to potentially lessen the behavioral and toxic effects of cocaine. Therefore, BChE may be useful as a treatment for cocaine addiction and toxicity. JF - Drug Metabolism and Disposition AU - Carmona, G N AU - Jufer, R A AU - Goldberg AU - Gorelick, DA AU - Greig, N H AU - Yu, Qian-Sheng AU - Cone, E J AU - Schindler, C W AD - Preclinical Pharmacology Section, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 367 EP - 371 VL - 28 IS - 3 SN - 0090-9556, 0090-9556 KW - metabolism KW - man KW - monkeys KW - cholinesterase KW - Toxicology Abstracts KW - Cocaine KW - Drug abuse KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17562478?accountid=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=Drug+Metabolism+and+Disposition&rft.atitle=Butyrylcholinesterase+Accelerates+Cocaine+Metabolism%3A+In+Vitro+and+In+Vivo+Effects+in+Nonhuman+Primates+and+Humans&rft.au=Carmona%2C+G+N%3BJufer%2C+R+A%3BGoldberg%3BGorelick%2C+DA%3BGreig%2C+N+H%3BYu%2C+Qian-Sheng%3BCone%2C+E+J%3BSchindler%2C+C+W&rft.aulast=Carmona&rft.aufirst=G&rft.date=2000-03-01&rft.volume=28&rft.issue=3&rft.spage=367&rft.isbn=&rft.btitle=&rft.title=Drug+Metabolism+and+Disposition&rft.issn=00909556&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 - Drug abuse; Cocaine ER - TY - JOUR T1 - Comparison of the acute hematotoxicity of 2-butoxyethanol in male and female F344 rats AN - 17551956; 4737026 AB - Administration of 2-butoxyethanol (BE) to rodents causes acute hemolytic anemia, and metabolic activation of BE to butoxyacetic acid (BAA) is required for the development of this effect. Recent studies have shown that female rats treated with BE exhibit a variety of histopathologic lesions that are absent in males and many of these lesions are attributed to the hemolytic effects of BE. Current studies were designed to compare the acute hematotoxicity of BE in male and female F344 rats. Rats were treated with 250 mg BE/kg body weight or water (control; 5 ml/kg) by gavage. At 4, 8, or 24 h after dosing, rats were anesthetized, blood was collected by cardiac puncture, and various blood parameters were measured. BE resulted in a time-dependent swelling of erythrocytes as evidenced by an early increase in hematocrit (Hct) and mean cell volume (MCV) in male rats. In contrast, increased Hct in female rats did not accompany an increase in MCV. It is likely that hemolysis was so severe at 4 h that Hct exhibited a decline in female rats at that time point. Subsequently, red blood cell (RBCs), hemoglobin concentration (Hgb), and Hct declined as hemolysis progressed. However, the onset of BE-induced hemolysis was faster in female compared to male rats. These effects were also associated with a significant increase in the spleen weight to body weight ratio. Blood smears were also prepared and morphological changes evaluated by light microscopy included stomatocytosis, spherocytosis, and schistocytosis. Furthermore, aggregation of RBCs in female rats as evidenced by increased formation of rouleaux was observed at 24 h after BE administration. These effects were observed earlier and more frequently in female rats. No differences in the sensitivity of RBCs obtained from male and female rats and exposed to butoxyacetic acid (BAA) in vitro was observed as determined by measuring the packed cell volume. In conclusion, these data suggest that female rats are more sensitive to hemolysis and morphological alterations of erythrocytes induced by BE during the first 24 h after exposure compared to males. It is likely that the greater sensitivity of female rats to BE effects on RBCs may account for the reported development of thrombosis and tissue infarction in female rats. JF - Human & Experimental Toxicology AU - Ghanayem, B I AU - Ward, S M AU - Chanas, B AU - Nyska, A AD - National Institute of Environmental Health Sciences (NIEHS), PO Box 12233, Research Triangle Park, NC 27709, USA Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 185 EP - 192 PB - Stockton Press VL - 19 IS - 3 SN - 0960-3271, 0960-3271 KW - rats KW - acute toxicity KW - butyl cellosolve KW - Toxicology Abstracts KW - Erythrocytes KW - Hemolysis KW - Sex differences KW - X 24151:Acute exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17551956?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+%26+Experimental+Toxicology&rft.atitle=Comparison+of+the+acute+hematotoxicity+of+2-butoxyethanol+in+male+and+female+F344+rats&rft.au=Ghanayem%2C+B+I%3BWard%2C+S+M%3BChanas%2C+B%3BNyska%2C+A&rft.aulast=Ghanayem&rft.aufirst=B&rft.date=2000-03-01&rft.volume=19&rft.issue=3&rft.spage=185&rft.isbn=&rft.btitle=&rft.title=Human+%26+Experimental+Toxicology&rft.issn=09603271&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Hemolysis; Erythrocytes; Sex differences ER - TY - JOUR T1 - Genomic Imprinting and Environmental Disease Susceptibility AN - 17542006; 4729351 AB - Genomic imprinting is one of the most intriguing subtleties of modern genetics. The term "imprinting" refers to parent-of-origin-dependent gene expression. The presence of imprinted genes can cause cells with a full parental complement of functional autosomal genes to specifically express one allele but not the other, resulting in monoallelic expression of the imprinted loci. Genomic imprinting plays a critical role in fetal growth and behavioral development, and it is regulated by DNA methylation and chromatin structure. This paper summarizes the Genomic Imprinting and Environmental Disease Susceptibility Conference held 8-10 October 1998 at Duke University, Durham, North Carolina. The conference focused on the importance of genomic imprinting in determining susceptibility to environmentally induced diseases. Conference topics included rationales for imprinting: parental antagonism and speciation; methods for imprinted gene identification: allelic message display and monochromosomal mouse/human hybrids; properties of the imprinted gene cluster human 11p15.5 and mouse distal 7; the epigenetics of X-chromosome inactivation; variability in imprinting: imprint erasure, non-Mendelian inheritance ratios, and polymorphic imprinting; imprinting and behavior: genetics of bipolar disorder, imprinting in Turner syndrome, and imprinting in brain development and social behavior; and aberrant methylation: methylation and chromatin structure, methylation and estrogen exposure, methylation of tumor-suppressor genes, and cancer susceptibility. Environmental factors are capable of causing epigenetic changes in DNA that can potentially alter imprint gene expression and that can result in genetic diseases including cancer and behavioral disorders. Understanding the contribution of imprinting to the regulation of gene expression will be an important step in evaluating environmental influences on human health and disease. JF - Environmental Health Perspectives AU - Jirtle, R L AU - Sander, M AU - Barrett, J C AD - National Institute of Environmental Health Sciences (NIEHS), PO Box 12233, Research Triangle Park, NC 27709 USA, barrett@niehs.nih.gov Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 271 EP - 278 VL - 108 IS - 3 SN - 0091-6765, 0091-6765 KW - diseases KW - man KW - Toxicology Abstracts KW - Genomic imprinting KW - Environmental factors KW - Polluted environments KW - Public health KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17542006?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Genomic+Imprinting+and+Environmental+Disease+Susceptibility&rft.au=Jirtle%2C+R+L%3BSander%2C+M%3BBarrett%2C+J+C&rft.aulast=Jirtle&rft.aufirst=R&rft.date=2000-03-01&rft.volume=108&rft.issue=3&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Genomic imprinting; Polluted environments; Environmental factors; Public health ER - TY - JOUR T1 - Carcinogen macromolecular adducts and their measurement AN - 17535289; 4718140 AB - Damage to DNA induced by carcinogenic chemicals reflects exposure and is directly related to tumor formation, whereas modification of protein provides relatively precise dosimetry for stable adducts of proteins with a known half-life. Sophisticated methods for the detection and quantitation of DNA and protein adducts have been developed during the last similar to 25 years. For DNA adducts the most widely used methods include electrochemical detection, mass spectrometry, fluorescence and phosphorescence spectroscopy, immunoassays and immunohistochemistry and super(32)P-post-labeling. Detection limits for quantitative assays are typically in the range of 1 adduct in 10 super(7) or 10 super(9) nucleotides. However, accelerator mass spectrometry, which is highly sophisticated but less accessible, has a detection limit of similar to 1 adduct in 10 super(12) nucleotides. Methods for the determination of protein adducts include immunoassay and a variety of elegant high-resolution mass spectrometry approaches. The detection limit of similar to 0.1 fmol for protein adducts, is based primarily on method specificity and the availability of large quantities of sample material. Using these highly sensitive methods a major achievement has been the biomonitoring of chemically exposed human populations. Validation of macromolecular adduct formation in humans has been predicated on studies in animal models. Adduct formation in humans appears to be indicative of molecular dosimetry and suggestive of increased human cancer risk. However, despite the large body of literature documenting DNA and protein adduct molecular dosimetry for many carcinogen exposures, the relationship between adduct formation and human cancer risk has been defined for only a few carcinogens. Thus, elucidation of this association remains a compelling challenge. For the future, integration of DNA and protein adduct measurements together with documentation of correlative and subsequent events, and host susceptibility factors, within the context of valid molecular epidemiologic study designs, will further our understanding of human disease mechanisms. JF - Carcinogenesis AU - Poirier, M C AU - Santella, R M AU - Weston, A AD - Carcinogen-DNA Interactions Section, LCCTP, Division of Basic Sciences, NCI, NIH, Building 37, Room 2A05, 37 Convent Drive, MSC-4255, Bethesda, MD 20892, USA Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 353 EP - 359 VL - 21 IS - 3 SN - 0143-3334, 0143-3334 KW - Toxicology Abstracts KW - DNA adducts KW - Dosimetry KW - Proteins KW - Tumorigenicity KW - Carcinogens KW - Cancer KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17535289?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Carcinogen+macromolecular+adducts+and+their+measurement&rft.au=Poirier%2C+M+C%3BSantella%2C+R+M%3BWeston%2C+A&rft.aulast=Poirier&rft.aufirst=M&rft.date=2000-03-01&rft.volume=21&rft.issue=3&rft.spage=353&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Carcinogens; DNA adducts; Tumorigenicity; Proteins; Dosimetry; Cancer ER - TY - JOUR T1 - Repeated Cadmium Exposures Enhance the Malignant Progression of Ensuing Tumors in Rats AN - 17533752; 4721949 AB - Prior studies show that a single subcutaneous (sc) exposure to cadmium (Cd) will induce injection site sarcomas (ISS) in rats. These tumors, thought clearly malignant, do not often metastasize or invade subdermal muscle layers because of their location. Recent evidence indicates that when tumorigenic cells chronically exposed to Cd in vitro are inoculated into mice, tumor progression and invasiveness in the mice are enhanced. Thus, we studied the effects of repeated Cd exposures on tumor incidence, progression, and metastatic potential in rats. Wistar (WF) and Fischer (F344) rats (30 per group) were injected sc in the dorsal thoracic midline with CdCl sub(2) once weekly for 18 weeks with doses of 0, 10, 20, or 30 mu mol Cd/kg. This resulted in total doses of 0, 180, 360, or 540 mu mol/kg. One other group of each strain received a low, loading dose of Cd (3 mu mol/kg) prior to 17 weekly injections of 30 mu mol/kg (total dose 513 mu mol/kg). Rats were observed for 2 years. Many F344 rats (57%) died within one week after the first injection of the highest dose, but WF rats were not affected. The low loading dose prevented acute lethality of the high dose in F344 rats. Surprisingly, latency (time to death by tumor) of ISS was the shortest in the groups given the low loading dose in both strains. ISS in these groups also showed the highest rate of metastasis and subdermal muscle layer invasion. Based on ISS incidence in the groups given the lowest total dose of Cd (180 mu moles/kg), F344 rats were more sensitive to tumor induction, showing an incidence of 37% compared to 3% in WF rats. On the other hand, Cd-induced ISS showed a higher overall metastatic rate in WF rats (18 metastatic ISS/68 total tumors in all treated groups; 27%) compared to F344 rats (6%). Immunohistochemically, the primary ISS showed high levels of metallothionein (MT), a cadmium-binding protein, while metastases were essentially devoid of MT. These results indicate that repeated Cd exposures more rapidly induce ISS. An initial low exposure to Cd further accelerates the appearance and enhances the metastatic potential and invasiveness of these tumors. The primary and metastatic ISS appear to have a differing phenotype, at least with regard to MT production. The association between multiple Cd exposures and enhanced metastatic potential of the ensuing tumors may have important implications in chronic exposures to Cd, or in cases of co-exposure of Cd with organic carcinogens, as in tobacco smoking. JF - Toxicological Sciences AU - Waalkes, M P AU - Rehm, S AU - Cherian, M G AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 110 EP - 120 VL - 54 IS - 1 SN - 1096-6080, 1096-6080 KW - rats KW - Toxicology Abstracts KW - Metallothionein KW - Heavy metals KW - Tumorigenicity KW - Cadmium KW - Tumors KW - X 24162:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17533752?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Repeated+Cadmium+Exposures+Enhance+the+Malignant+Progression+of+Ensuing+Tumors+in+Rats&rft.au=Waalkes%2C+M+P%3BRehm%2C+S%3BCherian%2C+M+G&rft.aulast=Waalkes&rft.aufirst=M&rft.date=2000-03-01&rft.volume=54&rft.issue=1&rft.spage=110&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Heavy metals; Cadmium; Tumors; Metallothionein; Tumorigenicity ER - TY - JOUR T1 - The associations of adolescent cigarette smoking, alcoholic beverage consumption, environmental tobacco smoke, and ionizing radiation with subsequent breast cancer risk (United States) AN - 17520848; 4708940 AB - Objectives: Studies of breast cancer among survivors of the World War II atomic bomb blasts over Japan suggest that the adolescent breast may be particularly sensitive to carcinogenic insult. To further explore that possibility we examined the relationships of cigarette smoking, alcohol consumption, environmental tobacco smoke (ETS) exposure, and medical treatment with ionizing radiation during adolescence with subsequent breast cancer risk. Methods: Data from the Carolina Breast Cancer Study, a population-based, case-control study of breast cancer in North Carolina women aged 20-74 years (864 cases, 790 controls), were analyzed. Results: A modest increase in breast cancer risk was suggested for women who began to smoke cigarettes between the ages of 10 and 14 years (OR: 1.5, CI: 0.9-2.5), and for women exposed to ionizing radiation between ages 10 and 19 years to treat or monitor a medical condition (OR: 1.6, CI: 0.5-2.5). Neither exposure to ETS at home prior to age 18 years (OR: 1.1, CI: 0.9-1.3) nor initiation of alcoholic beverage consumption between ages 10 and 15 years (OR: 1.1, CI: 0.6-1.8) appeared to increase risk. Conclusions: Our results are consistent with previous evidence suggesting that some adolescent exposures could influence future breast cancer risk. JF - Cancer Causes & Control AU - Marcus, P M AU - Newman, B AU - Millikan, R C AU - Moorman, P G AU - Baird, D D AU - Qaqish, B AD - Division of Cancer Prevention, National Cancer Institute, Executive Plaza North, Room 344, MSC 7354, Bethesda, MD 20892, USA Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 271 EP - 278 VL - 11 IS - 3 SN - 0957-5243, 0957-5243 KW - man KW - Risk Abstracts; Health & Safety Science Abstracts; Toxicology Abstracts KW - Risk assessment KW - Cigarette smoking KW - Adolescents KW - Ethanol KW - Alcohol KW - Alcoholic beverages KW - Adolescence KW - Cancer KW - Passive smoking KW - Ionizing radiation KW - X 24210:Radiation & radioactive materials KW - H 11000:Diseases/Injuries/Trauma 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/17520848?accountid=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=Cancer+Causes+%26+Control&rft.atitle=The+associations+of+adolescent+cigarette+smoking%2C+alcoholic+beverage+consumption%2C+environmental+tobacco+smoke%2C+and+ionizing+radiation+with+subsequent+breast+cancer+risk+%28United+States%29&rft.au=Marcus%2C+P+M%3BNewman%2C+B%3BMillikan%2C+R+C%3BMoorman%2C+P+G%3BBaird%2C+D+D%3BQaqish%2C+B&rft.aulast=Marcus&rft.aufirst=P&rft.date=2000-03-01&rft.volume=11&rft.issue=3&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/10.1023%2FA%3A1008911902994 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cancer; Alcohol; Ionizing radiation; Adolescents; Cigarette smoking; Passive smoking; Risk assessment; Alcoholic beverages; Ethanol; Adolescence DO - http://dx.doi.org/10.1023/A:1008911902994 ER - TY - JOUR T1 - Effects in live cells of a c-myc anti-gene PNA linked to a nuclear localization signal AN - 17512641; 4697028 AB - Peptide nucleic acids (PNA) are synthetic homologs of nucleic acids in which the phosphate-sugar polynucleotide backbone is replaced by a flexible polyamide. In this study, a PNA construct was employed as an anti-gene agent in intact cells in culture. The cell lines studied were derived from Burkitt's lymphomas (BL) that presented a translocated and hyperexpressed c-myc oncogene. A 17-mer anti-myc PNA, complementary to a unique sequence located at the beginning of the second exon of the oncogene, and was covalently linked at its N terminus to a nuclear localization signal (NLS) (PNA-myc sub(wt)-NLS). When BL cells were exposed to PNA-myc sub(wt)-NLS, the anti-gene construct was localized predominantly in the cell nuclei and a rapid consequent downregulation of c-myc expression occurred. Under these conditions, both completion of a productive cell cycle and apoptosis were inhibited. JF - Nature Biotechnology AU - Cutrona, G AU - Carpaneto, E M AU - Ulivi, M AU - Roncella, S AU - Landt, O AU - Ferrarini, M AU - Boffa, L C AD - Servizi di Immunologia Clinica & Oncologia Sperimentale, National Cancer Institute, Genoa, Italy, boffa@hp380.ist.unige.it Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 300 EP - 303 VL - 18 IS - 3 SN - 1087-0156, 1087-0156 KW - c-Myc gene KW - insect cells KW - nuclear localization signal KW - peptide nucleic acids KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Antisense KW - Apoptosis KW - Cell cycle KW - W 30965:Miscellaneous, Reviews KW - W3 33380:Antisense UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17512641?accountid=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=Effects+in+live+cells+of+a+c-myc+anti-gene+PNA+linked+to+a+nuclear+localization+signal&rft.au=Cutrona%2C+G%3BCarpaneto%2C+E+M%3BUlivi%2C+M%3BRoncella%2C+S%3BLandt%2C+O%3BFerrarini%2C+M%3BBoffa%2C+L+C&rft.aulast=Cutrona&rft.aufirst=G&rft.date=2000-03-01&rft.volume=18&rft.issue=3&rft.spage=300&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2F73745 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cell cycle; Apoptosis; Antisense DO - http://dx.doi.org/10.1038/73745 ER - TY - JOUR T1 - Phase 1 and phase 2 studies of Salmonella enterica serovar Paratyphi A O-specific polysaccharide-tetanus toxoid conjugates in adults, teenagers, and 2- to 4-year-old children in Vietnam AN - 17493669; 4688318 AB - Salmonella enterica serovar Paratyphi A O-specific polysaccharide (O-SP) was activated with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) and bound to tetanus toxoid (TT) with adipic acid dihydrazide as a linker (SPA-TT sub(1)) or directly (SPA-TT sub(2)). In mice, these two conjugates elicited high levels of immunoglobulin G (IgG) anti-lipopolysaccharide (LPS) in serum with bactericidal activity (E. Konadu, J. Shiloach, D.A. Bryla, J.B. Robbins, and S.C. Szu, Infect. Immun. 64:2709-2715, 1996). The safety and immunogenicity of the two conjugates were then evaluated sequentially in Vietnamese adults, teenagers, and 2- to 4-year-old children. None of the vaccinees experienced significant side effects, and all had preexisting LPS antibodies. At 4 weeks after injection, there were significant increases of the geometric mean IgG and IgM anti-LPS levels in the adults and teenagers: both conjugates elicited a greater than fourfold rise in the IgG anti-LPS level in serum in greater than or equal to 80% of the volunteers. SPA-TT sub(2) elicited slightly higher, though not statistically significantly, levels of IgG anti-LPS than did SPA-TT sub(1) in these age groups. Accordingly, only SPA-TT sub(2) was evaluated in the 2- to 4-year-old children. On a random basis, one or two injections were administered 6 weeks apart to the children. No significant side effects were observed, and the levels of preexisting anti-LPS in serum were similar in children of all ages. A significant rise in the IgG anti-LPS titer was elicited by the first injection (P = 0.0001); a second injection did not elicit a booster response. Representative sera from all groups had bactericidal activity that could be adsorbed by S. enterica serovar Paratyphi A LPS. JF - Infection and Immunity AU - Konadu, E Y AU - Lin, F-YC AU - Ho, V A AU - Thuy, NThTh AU - Bay, PVPh AU - Thanh, T C AU - Khiem, H B AU - Trach, D D AU - Karpas, AB AU - Li, J AU - Bryla, DA AU - Robbins, J B AU - Szu, ShC AD - National Institute of Child Health and Human Development, National Institutes of Health, Bldg. 6, Room 424, Bethesda, MD 20892, USA, scszu@helix.nih.gov Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 1529 EP - 1534 VL - 68 IS - 3 SN - 0019-9567, 0019-9567 KW - adults KW - Adipic acid dihydrazide KW - Tetanus toxoid KW - Microbiology Abstracts B: Bacteriology KW - Adolescence KW - Salmonella enterica KW - Antibody response KW - Vaccines KW - Children KW - Conjugates KW - J 02834:Vaccination and immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17493669?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Phase+1+and+phase+2+studies+of+Salmonella+enterica+serovar+Paratyphi+A+O-specific+polysaccharide-tetanus+toxoid+conjugates+in+adults%2C+teenagers%2C+and+2-+to+4-year-old+children+in+Vietnam&rft.au=Konadu%2C+E+Y%3BLin%2C+F-YC%3BHo%2C+V+A%3BThuy%2C+NThTh%3BBay%2C+PVPh%3BThanh%2C+T+C%3BKhiem%2C+H+B%3BTrach%2C+D+D%3BKarpas%2C+AB%3BLi%2C+J%3BBryla%2C+DA%3BRobbins%2C+J+B%3BSzu%2C+ShC&rft.aulast=Konadu&rft.aufirst=E&rft.date=2000-03-01&rft.volume=68&rft.issue=3&rft.spage=1529&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.68.3.1529-1534.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Salmonella enterica; Vaccines; Conjugates; Adolescence; Children; Antibody response DO - http://dx.doi.org/10.1128/IAI.68.3.1529-1534.2000 ER - TY - JOUR T1 - Comparative genome analysis of the pathogenic spirochetes Borrelia burgdorferi and Treponema pallidum AN - 17491542; 4687950 AB - A comparative analysis of the predicted protein sequences encoded in the complete genomes of Borrelia burgdorferi and Treponema pallidum provides a number of insights into evolutionary trends and adaptive strategies of the two spirochetes. A measure of orthologous relationships between gene sets, termed the orthology coefficient (OC), was developed. The overall OC value for the gene sets of the two spirochetes is about 0.43, which means that less than one-half of the genes show readily detectable orthologous relationships. This emphasizes significant divergence between the two spirochetes, apparently driven by different biological niches. Different functional categories of proteins as well as different protein families show a broad distribution of OC values, from near 1 (a perfect, one-to-one correspondence) to near 0. The proteins involved in core biological functions, such as genome replication and expression, typically show high OC values. In contrast, marked variability is seen among proteins that are involved in specific processes, such as nutrient transport, metabolism, gene-specific transcription regulation, signal transduction, and host response. Differences in the gene complements encoded in the two spirochete genomes suggest active adaptive evolution for their distinct niches. Comparative analysis of the spirochete genomes produced evidence of gene exchanges with other bacteria, archaea, and eukaryotic hosts that seem to have occurred at different points in the evolution of the spirochetes. Examples are presented of the use of sequence profile analysis to predict proteins that are likely to play a role in pathogenesis, including secreted proteins that contain specific protein-protein interaction domains, such as von Willebrand A, YWTD, TPR, and PR1, some of which hitherto have been reported only in eukaryotes. We tentatively reconstruct the likely evolutionary process that has led to the divergence of the two spirochete lineages; this reconstruction seems to point to an ancestral state resembling the symbiotic spirochetes found in insect guts. JF - Infection and Immunity AU - Subramanian, G AU - Koonin, E V AU - Aravind, L AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA, koonin@ncbi.nlm.nih.gov Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 1633 EP - 1648 VL - 68 IS - 3 SN - 0019-9567, 0019-9567 KW - genomes KW - amino acid sequence KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Genomes KW - Borrelia burgdorferi KW - Pathogenesis KW - Genetic relationship KW - Gene regulation KW - Treponema pallidum KW - Proteins KW - Evolution KW - Signal transduction KW - G 07320:Bacterial genetics KW - J 02710:Identification, taxonomy and typing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17491542?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Comparative+genome+analysis+of+the+pathogenic+spirochetes+Borrelia+burgdorferi+and+Treponema+pallidum&rft.au=Subramanian%2C+G%3BKoonin%2C+E+V%3BAravind%2C+L&rft.aulast=Subramanian&rft.aufirst=G&rft.date=2000-03-01&rft.volume=68&rft.issue=3&rft.spage=1633&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.68.3.1633-1648.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Borrelia burgdorferi; Treponema pallidum; Proteins; Gene regulation; Signal transduction; Pathogenesis; Genomes; Genetic relationship; Evolution DO - http://dx.doi.org/10.1128/IAI.68.3.1633-1648.2000 ER - TY - JOUR T1 - Comparative Efficacy of Recombinant Modified Vaccinia Virus Ankara Expressing Simian Immunodeficiency Virus (SIV) Gag-Pol and/or Env in Macaques Challenged with Pathogenic SIV AN - 17463658; 4673796 AB - Prior studies demonstrated that immunization of macaques with simian immunodeficiency virus (SIV) Gag-Pol and Env recombinants of the attenuated poxvirus modified vaccinia virus Ankara (MVA) provided protection from high levels of viremia and AIDS following challenge with a pathogenic strain of SIV. This MVA-SIV recombinant expressed relatively low levels of the Gag-Pol portion of the vaccine. To optimize protection, second-generation recombinant MVAs that expressed high levels of either Gag-Pol (MVA- gag-pol) or Env (MVA-env), alone or in combination (MVA-gag-pol-env), were generated. A cohort of 24 macaques was immunized with recombinant or nonrecombinant MVA (four groups of six animals) and was challenged with 50 times the dose at which 50% of macaques are infected with uncloned pathogenic SIVsmE660. Although all animals became infected postchallenge, plasma viremia was significantly reduced in animals that received the MVA-SIV recombinant vaccines as compared with animals that received nonrecombinant MVA (P = 0.0011 by repeated-measures analysis of variance). The differences in the degree of virus suppression achieved by the three MVA-SIV vaccines were not significant. Most importantly the reduction in levels of viremia resulted in a significant increase in median (P < 0.05 by Student's t test) and cumulative (P = 0.010 by log rank test) survival. These results suggest that recombinant MVA has considerable potential as a vaccine vector for human AIDS. JF - Journal of Virology AU - Ourmanov, I AU - Brown, C R AU - Moss, B AU - Carroll, M AU - Wyatt, L AU - Pletneva, L AU - Goldstein, S AU - Venzon, D AU - Hirsch, V M AD - NIAID Twinbrook II Facility, 12441 Parklawn Dr., Rockville, MD 20852, vhirsch@nih.gov Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 2740 EP - 2751 VL - 74 IS - 6 SN - 0022-538X, 0022-538X KW - Macaques KW - SIV KW - Macaca KW - Simian immunodeficiency virus KW - Vaccinia virus KW - env gene KW - gag gene KW - pol gene KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Recombinants KW - Vaccines KW - W3 33365:Vaccines (other) KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17463658?accountid=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=Comparative+Efficacy+of+Recombinant+Modified+Vaccinia+Virus+Ankara+Expressing+Simian+Immunodeficiency+Virus+%28SIV%29+Gag-Pol+and%2For+Env+in+Macaques+Challenged+with+Pathogenic+SIV&rft.au=Ourmanov%2C+I%3BBrown%2C+C+R%3BMoss%2C+B%3BCarroll%2C+M%3BWyatt%2C+L%3BPletneva%2C+L%3BGoldstein%2C+S%3BVenzon%2C+D%3BHirsch%2C+V+M&rft.aulast=Ourmanov&rft.aufirst=I&rft.date=2000-03-01&rft.volume=74&rft.issue=6&rft.spage=2740&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/10.1128%2FJVI.74.6.2740-2751.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vaccinia virus; Simian immunodeficiency virus; Macaca; Vaccines; Recombinants DO - http://dx.doi.org/10.1128/JVI.74.6.2740-2751.2000 ER - TY - JOUR T1 - Immunization with a Modified Vaccinia Virus Expressing Simian Immunodeficiency Virus (SIV) Gag-Pol Primes for an Anamnestic Gag-Specific Cytotoxic T-Lymphocyte Response and Is Associated with Reduction of Viremia after SIV Challenge AN - 17463573; 4673792 AB - The immunogenicity and protective efficacy of a modified vaccinia virus Ankara (MVA) recombinant expressing the simian immunodeficiency virus (SIV) Gag-Pol proteins (MVA-gag-pol) was explored in rhesus monkeys expressing the major histocompatibility complex (MHC) class I allele, MamuA*01. Macaques received four sequential intramuscular immunizations with the MVA-gag- pol recombinant virus or nonrecombinant MVA as a control. Gag-specific cytotoxic T-lymphocyte (CTL) responses were detected in all MVA-gag-pol-immunized macaques by both functional assays and flow cytometric analyses of CD8 super(+) T cells that bound a specific MHC complex class I-peptide tetramer, with levels peaking after the second immunization. Following challenge with uncloned SIVsmE660, all macaques became infected; however, viral load set points were lower in MVA-gag-pol-immunized macaques than in the MVA-immunized control macaques. MVA-gag-pol- immunized macaques exhibited a rapid and substantial anamnestic CTL response specific for the p11C, C-M Gag epitope. The level at which CTL stabilized after resolution of primary viremia correlated inversely with plasma viral load set point (P = 0.03). Most importantly, the magnitude of reduction in viremia in the vaccinees was predicted by the magnitude of the vaccine-elicited CTL response prior to SIV challenge. JF - Journal of Virology AU - Seth, A AU - Ourmanov, I AU - Schmitz, JE AU - Kuroda, MJ AU - Lifton, MA AU - Nickerson, CE AU - Wyatt, L AU - Carroll, M AU - Moss, B AU - Venzon, D AU - Letvin, N L AU - Hirsch, V M AD - NIAID Twinbrook II Facility, 12441 Parklawn Dr., Rockville, MD 20852, vhirsch@nih.gov Y1 - 2000/03// PY - 2000 DA - Mar 2000 SP - 2502 EP - 2509 VL - 74 IS - 6 SN - 0022-538X, 0022-538X KW - SIV KW - man KW - immunology KW - CD8 antigen KW - Gag protein KW - Pol protein KW - simian immunodeficiency virus KW - vaccinia virus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Virology & AIDS Abstracts KW - Killer cells KW - Vaccinia virus KW - Lymphocytes T KW - Viremia KW - Vaccines KW - Simian immunodeficiency virus KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - F 06756:Function KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17463573?accountid=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=Immunization+with+a+Modified+Vaccinia+Virus+Expressing+Simian+Immunodeficiency+Virus+%28SIV%29+Gag-Pol+Primes+for+an+Anamnestic+Gag-Specific+Cytotoxic+T-Lymphocyte+Response+and+Is+Associated+with+Reduction+of+Viremia+after+SIV+Challenge&rft.au=Seth%2C+A%3BOurmanov%2C+I%3BSchmitz%2C+JE%3BKuroda%2C+MJ%3BLifton%2C+MA%3BNickerson%2C+CE%3BWyatt%2C+L%3BCarroll%2C+M%3BMoss%2C+B%3BVenzon%2C+D%3BLetvin%2C+N+L%3BHirsch%2C+V+M&rft.aulast=Seth&rft.aufirst=A&rft.date=2000-03-01&rft.volume=74&rft.issue=6&rft.spage=2502&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/10.1128%2FJVI.74.6.2502-2509.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vaccinia virus; Simian immunodeficiency virus; Lymphocytes T; Vaccines; Killer cells; Viremia DO - http://dx.doi.org/10.1128/JVI.74.6.2502-2509.2000 ER - TY - JOUR T1 - The xeroderma pigmentosum group C gene leads to selective repair of cyclobutane pyrimidine dimers rather than 6-4 photoproducts. AN - 70945833; 10681431 AB - We investigated the contribution of the xeroderma pigmentosum group C (XPC) gene to DNA repair. We stably transfected XPC cells (XP4PA-SV-EB) with XPC cDNA and selected a partially corrected (XP4PA-SE1) and a fully corrected (XP4PA-SE2) clone. Cell survival after UVC (254 nm) exposure was low for XP4PA-SV-EB, intermediate for XP4PA-SE1, and normal for XP4PA-SE2 cells. XP4PA-SV-EB cells had undetectable XPC mRNA and protein levels. XP4PA-SE1 cells had 130% of normal mRNA but 25% of normal protein levels, whereas XP4PA-SE2 cells had an 18-fold mRNA overexpression and normal XPC protein levels compared with normal cells. We measured cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts (6-4PP) by using specific mAbs and the ELISA technique. XP4PA-SV-EB cells had no detectable removal of CPD or 6-4PP from their global genome by 24 h after 30 J/m(2) UVC exposure. The partially corrected XP4PA-SE1 cells had normal repair of CPD but minimal repair of 6-4PP by 24 h, whereas the fully corrected XP4PA-SE2 cells regained normal CPD and 6-4PP repair capacities. We also exposed pRSVcat plasmid to UVC (to induce CPD and 6-4PP), to UVC + photolyase (to leave only 6-4PP on the plasmid), or to UVB + acetophenone (to induce only CPD). Host cell reactivation of UVB + acetophenone-, but not of UVC + photolyase-treated plasmids was normal in XP4PA-SE1 cells. Thus, increasing XPC gene expression leads to selective repair of CPD in the global genome. Undetectable XPC protein is associated with no repair of CPD or 6-4PP, detectable but subnormal XPC protein levels reconstitute CPD but not 6-4PP repair, and normal XPC protein levels fully reconstitute both CPD and 6-4PP repair. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Emmert, S AU - Kobayashi, N AU - Khan, S G AU - Kraemer, K H AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2000/02/29/ PY - 2000 DA - 2000 Feb 29 SP - 2151 EP - 2156 VL - 97 IS - 5 SN - 0027-8424, 0027-8424 KW - DNA-Binding Proteins KW - 0 KW - Pyrimidine Dimers KW - pyrimidine-pyrimidone dimer KW - XPC protein, human KW - 156533-34-5 KW - Index Medicus KW - Animals KW - Humans KW - Gene Expression KW - DNA Damage -- radiation effects KW - Cell Line KW - Pyrimidine Dimers -- genetics KW - DNA Repair KW - DNA-Binding Proteins -- genetics KW - Xeroderma Pigmentosum -- genetics KW - DNA-Binding Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70945833?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+xeroderma+pigmentosum+group+C+gene+leads+to+selective+repair+of+cyclobutane+pyrimidine+dimers+rather+than+6-4+photoproducts.&rft.au=Emmert%2C+S%3BKobayashi%2C+N%3BKhan%2C+S+G%3BKraemer%2C+K+H&rft.aulast=Emmert&rft.aufirst=S&rft.date=2000-02-29&rft.volume=97&rft.issue=5&rft.spage=2151&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 - 2000-04-11 N1 - Date created - 2000-04-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Photochem Photobiol. 1969 Mar;9(3):291-4 [5772779] Science. 1999 Jul 9;285(5425):263-5 [10398605] Proc Natl Acad Sci U S A. 1985 Oct;82(19):6622-6 [2995975] Photochem Photobiol. 1986 May;43(5):509-13 [3526363] Int J Radiat Biol Relat Stud Phys Chem Med. 1986 Oct;50(4):641-8 [3489687] Arch Dermatol. 1987 Feb;123(2):241-50 [3545087] Mutat Res. 1987 Mar;183(2):185-96 [3029584] Photochem Photobiol. 1988 Jul;48(1):51-7 [3217442] Nucleic Acids Res. 1990 Feb 11;18(3):443-8 [2308842] Mol Cell Biol. 1991 Aug;11(8):4128-34 [1649389] Mutat Res. 1991 Nov;255(3):281-91 [1719400] Photochem Photobiol. 1991 Aug;54(2):225-32 [1780359] Nature. 1992 Sep 3;359(6390):70-3 [1522891] Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7260-4 [8346243] Biochemistry. 1993 Nov 16;32(45):12096-104 [8218288] Nat Genet. 1993 Dec;5(4):413-7 [8298653] EMBO J. 1994 Apr 15;13(8):1831-43 [8168482] Cancer Res. 1994 Jul 15;54(14):3837-44 [8033104] Arch Dermatol. 1994 Aug;130(8):1018-21 [8053698] J Biol Chem. 1994 Sep 9;269(36):22749-57 [8077226] Somat Cell Mol Genet. 1994 Jul;20(4):327-37 [7974007] EMBO J. 1995 Jan 16;14(2):360-7 [7835346] Photochem Photobiol. 1995 Feb;61(2):163-70 [7899505] Carcinogenesis. 1995 May;16(5):1003-9 [7767957] Carcinogenesis. 1995 Jul;16(7):1557-63 [7614689] Biochim Biophys Acta. 1995 Dec 18;1242(2):137-63 [7492568] J Biol Chem. 1997 Mar 21;272(12):7570-3 [9065408] J Biol Chem. 1997 Nov 14;272(46):28971-9 [9360969] EMBO J. 1997 Nov 3;16(21):6559-73 [9351836] J Invest Dermatol. 1998 Feb;110(2):143-8 [9457909] Cancer Res. 1995 Dec 15;55(24):6152-60 [8521407] J Biol Chem. 1996 Aug 9;271(32):19451-6 [8702634] Annu Rev Biochem. 1996;65:43-81 [8811174] Annu Rev Biochem. 1996;65:135-67 [8811177] J Invest Dermatol. 1996 Oct;107(4):647-53 [8823375] Photochem Photobiol. 1996 Apr;63(4):377-9 [8934741] Proc Natl Acad Sci U S A. 1997 Jan 7;94(1):11-4 [8990152] Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6669-74 [9618470] J Mol Biol. 1998 Aug 14;281(2):211-8 [9698541] Mol Cell. 1998 Aug;2(2):223-32 [9734359] J Invest Dermatol. 1998 Nov;111(5):791-6 [9804340] Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):424-8 [9892649] Genes Dev. 1999 Apr 1;13(7):768-85 [10197977] Mol Med Today. 1999 Feb;5(2):86-94 [10200950] EMBO J. 1999 Jun 15;18(12):3491-501 [10369688] J Biol Chem. 1999 Jun 25;274(26):18759-68 [10373492] Nature. 1999 Jun 17;399(6737):700-4 [10385124] Photochem Photobiol. 1974 Jan;19(1):75-8 [4590519] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Benzo[a]pyrene diol epoxide adducts in DNA are potent suppressors of a normal topoisomerase I cleavage site and powerful inducers of other topoisomerase I cleavages. AN - 70931070; 10688881 AB - The catalytic intermediates of DNA topoisomerase I (top1) are cleavage complexes that can relax DNA supercoiling (intramolecular reaction) or mediate recombinations (intermolecular religation). We report here that DNA adducts formed from benzo[a]pyrene bay-region diol epoxides can markedly affect top1 activity. Four oligonucleotide 22-mers of the same sequence were synthesized, each of which contained a stereoisomerically unique benzo[a]pyrene 7, 8-diol 9,10-epoxide adduct at the 2-amino group of a central 2'-deoxyguanosine residue. These four adducts correspond to either cis or trans opening at C-10 of the (+)-(7R, 8S, 9S, 10R)- or (-)-(7S, 8R, 9R, 10S)-7,8-diol 9,10-epoxides. Their solution conformations in duplex DNA (intercalated and minor-groove bound for the cis and trans opened adducts respectively) can be deduced from previous NMR studies. All four adducts completely suppress top1 cleavage activity at the alkylation site and induce the formation of new top1cleavage complexes on both strands of the DNA 3-6 bases away from the alkylation site. The trans opened adduct from the highly carcinogenic (+)-diol epoxide is the most active in inducing top1 cleavage independently of camptothecin, demonstrating that minor groove alkylation can efficiently poison top1. We also found that this isomer of the diol epoxide induces the formation of top1-DNA complexes in mammalian cells, which suggests a possible relationship between induction of top1 cleavage complexes and carcinogenic activity of benzo[a]pyrene diol epoxides. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Pommier, Y AU - Kohlhagen, G AU - Pourquier, P AU - Sayer, J M AU - Kroth, H AU - Jerina, D M AD - Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 2000/02/29/ PY - 2000 DA - 2000 Feb 29 SP - 2040 EP - 2045 VL - 97 IS - 5 SN - 0027-8424, 0027-8424 KW - DNA Adducts KW - 0 KW - Recombinant Fusion Proteins KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Animals KW - Humans KW - Recombination, Genetic KW - CHO Cells KW - Cricetinae KW - Binding Sites KW - DNA Topoisomerases, Type I -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70931070?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Benzo%5Ba%5Dpyrene+diol+epoxide+adducts+in+DNA+are+potent+suppressors+of+a+normal+topoisomerase+I+cleavage+site+and+powerful+inducers+of+other+topoisomerase+I+cleavages.&rft.au=Pommier%2C+Y%3BKohlhagen%2C+G%3BPourquier%2C+P%3BSayer%2C+J+M%3BKroth%2C+H%3BJerina%2C+D+M&rft.aulast=Pommier&rft.aufirst=Y&rft.date=2000-02-29&rft.volume=97&rft.issue=5&rft.spage=2040&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 - 2000-04-11 N1 - Date created - 2000-04-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Anal Biochem. 1975 May 12;65(1-2):125-31 [1130673] Biochim Biophys Acta. 1998 Oct 1;1400(1-3):83-105 [9748515] Cell. 1985 Jun;41(2):541-51 [2985282] J Biol Chem. 1985 Nov 25;260(27):14873-8 [2997227] Cancer Res. 1988 Apr 1;48(7):1722-6 [2832051] Nucleic Acids Res. 1988 Dec 9;16(23):11157-70 [2849758] Cancer Res. 1989 Nov 15;49(22):6318-23 [2553253] Nucleic Acids Res. 1989 Nov 11;17(21):8521-32 [2555774] J Biol Chem. 1990 Jul 25;265(21):12529-35 [2165067] J Biol Chem. 1991 Oct 25;266(30):20418-23 [1657924] J Mol Biol. 1991 Dec 5;222(3):669-78 [1660929] Chem Res Toxicol. 1989 Sep-Oct;2(5):334-40 [2519824] J Biol Chem. 1992 Aug 25;267(24):16755-8 [1324909] J Mol Biol. 1992 Dec 20;228(4):1025-30 [1335513] Cancer Res. 1993 Jul 15;53(14):3294-301 [8324741] Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8131-5 [7690143] J Biol Chem. 1994 Jan 7;269(1):721-9 [8276874] Cancer Res. 1995 Feb 15;55(4):753-60 [7850785] Cancer Res. 1995 May 15;55(10):2097-103 [7743509] Biochemistry. 1995 May 30;34(21):7200-6 [7766631] Nucleic Acids Res. 1995 Jun 25;23(12):2314-9 [7610061] Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8861-5 [7568032] Mutat Res. 1995 Sep;337(2):135-45 [7565862] Annu Rev Biochem. 1996;65:635-92 [8811192] Mol Pharmacol. 1996 Nov;50(5):1095-102 [8913340] Chem Res Toxicol. 1997 Feb;10(2):111-46 [9049424] J Biol Chem. 1997 Mar 21;272(12):7792-6 [9065442] J Biol Chem. 1997 Oct 17;272(42):26441-7 [9334220] Biochemistry. 1997 Oct 28;36(43):13285-91 [9341219] Cancer Res. 1997 Oct 15;57(20):4564-9 [9377570] Science. 1998 Mar 6;279(5356):1504-13 [9488644] Science. 1998 Mar 6;279(5356):1534-41 [9488652] J Biol Chem. 1998 Oct 16;273(42):27245-9 [9765247] Biochemistry. 1999 Jan 12;38(2):569-81 [9888796] EMBO J. 1999 Mar 1;18(5):1397-406 [10064605] J Biol Chem. 1999 Mar 26;274(13):8516-23 [10085084] Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7196-201 [10377391] J Biol Chem. 1999 Aug 20;274(34):23963-8 [10446164] Biochemistry. 1998 Apr 7;37(14):4993-5000 [9538018] J Med Chem. 1998 Jun 18;41(13):2216-26 [9632354] Biochemistry. 1998 Jun 23;37(25):9127-37 [9636059] Proc Natl Acad Sci U S A. 1978 Nov;75(11):5358-61 [281685] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vitamin E reduces chromosomal damage and inhibits hepatic tumor formation in a transgenic mouse model AN - 17646133; 4693544 AB - We have previously shown that chronic activation of mitogenic signaling induced by over-expression of c- myc and transforming growth factor- alpha (TGF alpha ) transgenes in mouse liver induces a state of oxidative stress. We therefore proposed that increased reactive oxygen species (ROS) generation might be responsible for the extensive chromosomal damage and acceleration of hepatocarcinogenesis characteristic for TGF alpha /c-myc mice. In this study, we show that vitamin E (VE), a potent free radical scavenging antioxidant, is able to protect liver tissue against oxidative stress and suppress tumorigenic potential of c-myc oncogene. Dietary supplementation with VE, starting from weaning, decreased ROS generation coincident with a marked inhibition of hepatocyte proliferation while increasing the chromosomal as well as mtDNA stability in the liver. Similarly, dietary VE reduced liver dysplasia and increased viability of hepatocytes. At 6 mo of age, VE treatment decreased the incidence of adenomas by 65% and prevented malignant conversion. These results indicate that ROS generated by over-expression of c-myc and TGF alpha in the liver are the primary carcinogenic agents in this animal model. Furthermore, the data demonstrate that dietary supplementation of VE can effectively inhibit liver cancer development. JF - Proceedings of the National Academy of Sciences, USA AU - Factor, V M AU - Laskowska, D AU - Jensen, M R AU - Woitach, J T AU - Popescu, N C AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255 USA, snorri_thorgeirsson@nih.gov Y1 - 2000/02/29/ PY - 2000 DA - 2000 Feb 29 SP - 2196 EP - 2201 VL - 97 IS - 5 SN - 0027-8424, 0027-8424 KW - transgenic mice KW - c-myc gene KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - Antioxidants KW - Mitochondrial DNA KW - Vitamin E KW - Chromosomes KW - Reactive oxygen species KW - Transforming growth factor-^a KW - Transforming growth factor-a KW - Hepatocellular carcinoma KW - W3 33056:Animal models of human disease KW - G 07444:Animal models KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17646133?accountid=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=Vitamin+E+reduces+chromosomal+damage+and+inhibits+hepatic+tumor+formation+in+a+transgenic+mouse+model&rft.au=Factor%2C+V+M%3BLaskowska%2C+D%3BJensen%2C+M+R%3BWoitach%2C+J+T%3BPopescu%2C+N+C%3BThorgeirsson%2C+S+S&rft.aulast=Factor&rft.aufirst=V&rft.date=2000-02-29&rft.volume=97&rft.issue=5&rft.spage=2196&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.040428797 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chromosomes; Vitamin E; Hepatocellular carcinoma; Reactive oxygen species; Transforming growth factor-a; Antioxidants; Mitochondrial DNA; Transforming growth factor-^a DO - http://dx.doi.org/10.1073/pnas.040428797 ER - TY - JOUR T1 - Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis AN - 17496300; 4684351 AB - Bacterial vaginosis has been associated with preterm birth. In clinical trials, the treatment of bacterial vaginosis in pregnant women who previously had a preterm delivery reduced the risk of recurrence. To determine whether treating women in a general obstetrical population who have asymptomatic bacterial vaginosis (as diagnosed on the basis of vaginal Gram's staining and pH) prevents preterm delivery, we randomly assigned 1953 women who were 16 to less than 24 weeks pregnant to receive two 2-g doses of metronidazole or placebo. The diagnostic studies were repeated and a second treatment was administered to all the women at 24 to less than 30 weeks' gestation. The primary outcome was the rate of delivery before 37 weeks' gestation. Bacterial vaginosis resolved in 657 of 845 women who had follow-up Gram's staining in the metronidazole group (77.8 percent) and 321 of 859 women in the placebo group (37.4 percent). Data on the time and characteristics of delivery were available for 953 women in the metronidazole group and 966 in the placebo group. Preterm delivery occurred in 116 women in the metronidazole group (12.2 percent) and 121 women in the placebo group (12.5 percent) (relative risk, 1.0; 95 percent confidence interval, 0.8 to 1.2). Treatment did not prevent preterm deliveries that resulted from spontaneous labor (5.1 percent in the metronidazole group vs. 5.7 percent in the placebo group) or spontaneous rupture of the membranes (4.2 percent vs. 3.7 percent), nor did it prevent delivery before 32 weeks (2.3 percent vs. 2.7 percent). Treatment with metronidazole did not reduce the occurrence of preterm labor, intraamniotic or postpartum infections, neonatal sepsis, or admission of the infant to the neonatal intensive care unit. The treatment of asymptomatic bacterial vaginosis in pregnant women does not reduce the occurrence of preterm delivery or other adverse perinatal outcomes. JF - New England Journal of Medicine AU - Carey, J C AU - Klebanoff, MA AU - Hauth, J C AU - Hillier, S L AU - Thom, E A AU - Ernest, J M AU - Heine, R P AU - Nugent, R P AU - Fischer, M L AU - Leveno, K J AU - Wapner, R AU - Varner, M AD - NICHD, NIH, 6100 Executive Blvd., Rm. 7B03 MSC 7510, Bethesda, MD 20892- 7510, USA, mk90h@nih.gov. Y1 - 2000/02/24/ PY - 2000 DA - 2000 Feb 24 SP - 534 EP - 540 VL - 342 IS - 8 SN - 0028-4793, 0028-4793 KW - asymptomatic infection KW - man KW - metronidazole KW - Microbiology Abstracts B: Bacteriology KW - Neonates KW - Vaginosis KW - Pregnancy KW - J 02847:Genitourinary tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17496300?accountid=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=New+England+Journal+of+Medicine&rft.atitle=Metronidazole+to+prevent+preterm+delivery+in+pregnant+women+with+asymptomatic+bacterial+vaginosis&rft.au=Carey%2C+J+C%3BKlebanoff%2C+MA%3BHauth%2C+J+C%3BHillier%2C+S+L%3BThom%2C+E+A%3BErnest%2C+J+M%3BHeine%2C+R+P%3BNugent%2C+R+P%3BFischer%2C+M+L%3BLeveno%2C+K+J%3BWapner%2C+R%3BVarner%2C+M&rft.aulast=Carey&rft.aufirst=J&rft.date=2000-02-24&rft.volume=342&rft.issue=8&rft.spage=534&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 N1 - SubjectsTermNotLitGenreText - Vaginosis; Pregnancy; Neonates ER - TY - JOUR T1 - MMTV-induced mammary tumorigenesis: gene discovery, progression to malignancy and cellular pathways. AN - 70983663; 10713682 AB - The study of the mouse mammary tumor virus (MMTV) has provided important insights into the mechanisms of gene transcription regulation by steroid hormones, the mode of action of heritable super antigens and the progressive nature of neoplastic transformation in the mammary gland. Here we describe the current situation with respect to the latter aspect of MMTV biology and the prospects for further advance in our understanding of breast cancer in humans that may be expected from a continued study of MMTV-induced mammary neoplasia. MMTV is a heritable somatic mutagen whose target range is limited. Commonly, the tumorigenic capacity of MMTV is restricted to mammary gland, whereas infection is found in a variety of cell types. In order to replicate, proviral DNA must be inserted into the cell DNA and cell division is required to fix the mutation. Yet only in the mammary epithelium does this lead to neoplastic transformation. This suggests a unique relationship between MMTV and mammary epithelium. In evaluating this relationship, we and others have discovered genes and potential gene pathways that are pertinent in mammary differentiation and neoplasia. In addition, the clonal nature of these progressive events from normal to malignant phenotype has become increasingly clear. The weight of these observations compel us to conclude that mammary neoplasms arise from multipotent mammary epithelial cells through a process of acquired mutations that are reflected in the increasingly malignant nature of the population of progeny produced by these damaged stem cells. JF - Oncogene AU - Callahan, R AU - Smith, G H AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland, MD 20892, USA. Y1 - 2000/02/21/ PY - 2000 DA - 2000 Feb 21 SP - 992 EP - 1001 VL - 19 IS - 8 SN - 0950-9232, 0950-9232 KW - Eukaryotic Initiation Factor-3 KW - 0 KW - FGF8 protein, human KW - Fgf8 protein, mouse KW - NOTCH4 protein, human KW - Peptide Initiation Factors KW - Proto-Oncogene Proteins KW - Receptors, Cell Surface KW - Receptors, Notch KW - Wnt Proteins KW - Zebrafish Proteins KW - Fibroblast Growth Factor 8 KW - 148997-75-5 KW - Fibroblast Growth Factors KW - 62031-54-3 KW - Index Medicus KW - Virus Replication KW - Breast Neoplasms -- genetics KW - Animals KW - Peptide Initiation Factors -- genetics KW - Humans KW - Proto-Oncogene Proteins -- metabolism KW - Disease Models, Animal KW - Mice KW - Fibroblast Growth Factors -- metabolism KW - Gene Expression Regulation, Neoplastic KW - Mice, Inbred Strains KW - Breast Neoplasms -- pathology KW - Incidence KW - Proto-Oncogene Proteins -- genetics KW - Fibroblast Growth Factors -- genetics KW - Signal Transduction KW - Mammary Tumor Virus, Mouse -- pathogenicity KW - Mammary Neoplasms, Experimental -- epidemiology KW - Mammary Neoplasms, Experimental -- genetics KW - Mammary Neoplasms, Experimental -- virology KW - Mammary Tumor Virus, Mouse -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70983663?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=MMTV-induced+mammary+tumorigenesis%3A+gene+discovery%2C+progression+to+malignancy+and+cellular+pathways.&rft.au=Callahan%2C+R%3BSmith%2C+G+H&rft.aulast=Callahan&rft.aufirst=R&rft.date=2000-02-21&rft.volume=19&rft.issue=8&rft.spage=992&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-30 N1 - Date created - 2000-03-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Oncogene. 2000 Feb 21;19(8):966-7 [10713679] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming growth factor alpha and mouse models of human breast cancer AN - 17501363; 4694062 AB - Transforming growth factor alpha (TGF alpha ) is a principal molecule in the normal and neoplastic development of the mammary gland. Binding of TGF alpha to the epidermal growth factor receptor (EGFR), activates the EGFRs' endogenous tyrosine kinase activity and stimulates growth of the epithelium in the virgin and pregnant mouse mammary gland. TGF alpha expression can be detected in breast cancer cells in vivo and in vitro and overexpression can elicit partial transformation or immortalized human and rodent mammary epithelial cells. Despite evidence implicating TGF alpha in the development of mammary neoplasia, the actual mechanism of TGF alpha -induced transformation is unclear. Transgenic mouse models targeting heterologus TGF alpha to the mammary gland have established TGF alpha overexpression can induce hyperproliferation, hyperplasia and occasional carcinoma. These transgenic studies demonstrated a facilitating, proliferative role for TGF alpha in the development of neoplasia and implicated several oncogenes that can cooperate with TGF alpha to transform the mammary epithelium. From studies of EGFR signaling pathways, inhibitory and modulating agents such as anti-EGFR antibodies and specific kinases inhibitors have been used to block the action of this pathway and prevent the development of TGF alpha -induced neoplasia and tumor formation. Studies in Stat5a knockout mice have established that the JAK2/Stat5a pathway can facilitate the survival of the mammary epithelium and can impact the progression of TGF alpha -mandated mammary tumorigenesis. Together these experiments indicate that TGF alpha and the EGFR signaling pathway are potentially amenable to therapies for treatment of human breast disease. JF - Oncogene AU - Humphreys, R C AU - Hennighausen, L AD - National Institutes of Health, National Institute of Digestive, Diabetes and Kidney Disease, Laboratory of Genetics and Physiology, Building 8, Room 111, Bethesda, Maryland, MD 20892, USA Y1 - 2000/02/21/ PY - 2000 DA - 2000 Feb 21 SP - 1085 EP - 1091 VL - 19 IS - 8 SN - 0950-9232, 0950-9232 KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Oncogenes & Growth Factors Abstracts KW - Stat5 protein KW - Animal models KW - Epidermal growth factor receptors KW - Reviews KW - Transforming growth factor-^a KW - Transforming growth factor-a KW - Breast carcinoma KW - B 26020:EGF & EGF receptor family/TGF alpha /Her/ErbB-2 (Neu)/ErbB-3/ErbB-4/amphiregulin KW - W3 33056:Animal models of human disease KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17501363?accountid=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=Oncogene&rft.atitle=Transforming+growth+factor+alpha+and+mouse+models+of+human+breast+cancer&rft.au=Humphreys%2C+R+C%3BHennighausen%2C+L&rft.aulast=Humphreys&rft.aufirst=R&rft.date=2000-02-21&rft.volume=19&rft.issue=8&rft.spage=1085&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Reviews: Mouse Models for Breast Cancer. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Transforming growth factor-a; Stat5 protein; Epidermal growth factor receptors; Breast carcinoma; Animal models; Transforming growth factor-^a ER - TY - JOUR T1 - Use of MMTV-Wnt-1 transgenic mice for studying the genetic basis of breast cancer AN - 17500993; 4694051 AB - Wnt-1 was first identified as a protooncogene activated by viral insertion in mouse mammary tumors. Transgenic expression of this gene using a mouse mammary tumor virus LTR enhancer causes extensive ductal hyperplasia early in life and mammary adenocarcinomas in approximately 50% of the female transgenic (TG) mice by 6 months of age. Metastasis to the lung and proximal lymph nodes is rare at the time tumors are detected but frequent after the removal of the primary neoplasm. The potent mitogenic effect mediated by Wnt-1 expression does not require estrogen stimulation; tumors form after an increased latency in estrogen receptor alpha -null mice. Several genetic lesions, including inactivation of p53 and over-expression of Fgf-3, collaborate with Wnt-1 in leading to mammary tumors, but loss of Sky and inactivation of one allele of Rb do not affect the rate of tumor formation in Wnt-1 TG mice. JF - Oncogene AU - Li, Y AU - Hively, W P AU - Varmus, HE AD - Division of Basic Science, National Cancer Institute, 49 Convent Drive, Building 49, Room 4A56, Bethesda, Maryland, MD 20892, USA Y1 - 2000/02/21/ PY - 2000 DA - 2000 Feb 21 SP - 1002 EP - 1009 VL - 19 IS - 8 SN - 0950-9232, 0950-9232 KW - Wnt-1 gene KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Oncogenes & Growth Factors Abstracts KW - Metastases KW - Estrogens KW - Reviews KW - Breast carcinoma KW - Transgenic mice KW - W3 33056:Animal models of human disease KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews KW - B 26285:Retroviruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17500993?accountid=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=Oncogene&rft.atitle=Use+of+MMTV-Wnt-1+transgenic+mice+for+studying+the+genetic+basis+of+breast+cancer&rft.au=Li%2C+Y%3BHively%2C+W+P%3BVarmus%2C+HE&rft.aulast=Li&rft.aufirst=Y&rft.date=2000-02-21&rft.volume=19&rft.issue=8&rft.spage=1002&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Reviews: Mouse Models for Breast Cancer. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Breast carcinoma; Transgenic mice; Estrogens; Reviews; Metastases ER - TY - JOUR T1 - The C3(1)/SV40 T-antigen transgenic mouse model of mammary cancer: ductal epithelial cell targeting with multistage progression to carcinoma AN - 17499983; 4694053 AB - The 5' flanking region of the C3(1) component of the rat prostate steroid binding protein (PSBP) has been used to successfully target the expression of the SV40 large T-antigen (Tag) to the epithelium of both the mammary and prostate glands resulting in models of mammary and prostate cancers which histologically resemble the human diseases. Atypia of the mammary ductal epithelium develops at about 8 weeks of age, progressing to mammary intraepithelial neoplasia (resembling human ductal carcinoma in situ [DCIS]) at about 12 weeks of age with the development of invasive carcinomas at about 16 weeks of age in 100% of female mice. The carcinomas share features to what has been classified in human breast cancer as infiltrating ductal carcinomas. All FVB/N female mice carrying the transgene develop mammary cancer with about a 15% incidence of lung metastases. Approximately 10% of older male mice develop anaplastic mammary carcinomas. Unlike many other transgenic models in which hormones and pregnancy are used to induce a mammary phenotype, C3(1)/Tag mice develop mammary tumors in the mammary epithelium of virgin animals without hormone supplementation or pregnancy. Although mammary tumor development appears hormone-responsive at early stages, invasive carcinomas are hormone-independent, which corresponds to the loss of estrogen receptor- alpha expression during tumor progression. Molecular and biologic factors related to mammary tumor progression can be studied in this model since lesions evolve over a predictable time course. Genomic alterations have been identified during tumor progression, including an amplification of the distal portion of chromosome 6 containing ki-ras and loss of heterozygosity (LOH) in other chromosomal regions. We have demonstrated that stage specific alterations in the expression of genes which are critical regulators of the cell cycle and apoptosis are functionally important in vivo. C3(1)/Tag mice appear useful for testing particular therapies since growth of the mammary tumors can be reduced using chemopreventive agents, cytokines, and an anti-angiogenesis agent. JF - Oncogene AU - Green, JE AU - Shibata, M-A AU - Yoshidome, K AU - Liu, M-L AU - Jorcyk, C AU - Anver, M R AU - Wigginton, J AU - Wiltrout, R AU - Shibata, E AU - Kaczmarczyk, S AU - Wang, W AU - Liu, Z-Y AU - Calvo, A AU - Couldrey, C AD - Transgenic Oncogenesis Group, Laboratory of Cell Regulation and Carcinogenesis, Building 41, Room C629, NCI, Bethesda, Maryland, MD 20892, USA Y1 - 2000/02/21/ PY - 2000 DA - 2000 Feb 21 SP - 1020 EP - 1027 VL - 19 IS - 8 SN - 0950-9232, 0950-9232 KW - simian virus 40 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Oncogenes & Growth Factors Abstracts KW - Antigen T KW - Mammary gland KW - Animal models KW - Transgenic mice KW - Reviews KW - Carcinogenesis KW - Epithelium KW - W3 33056:Animal models of human disease KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews KW - B 26250:Papovaviruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17499983?accountid=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=Oncogene&rft.atitle=The+C3%281%29%2FSV40+T-antigen+transgenic+mouse+model+of+mammary+cancer%3A+ductal+epithelial+cell+targeting+with+multistage+progression+to+carcinoma&rft.au=Green%2C+JE%3BShibata%2C+M-A%3BYoshidome%2C+K%3BLiu%2C+M-L%3BJorcyk%2C+C%3BAnver%2C+M+R%3BWigginton%2C+J%3BWiltrout%2C+R%3BShibata%2C+E%3BKaczmarczyk%2C+S%3BWang%2C+W%3BLiu%2C+Z-Y%3BCalvo%2C+A%3BCouldrey%2C+C&rft.aulast=Green&rft.aufirst=JE&rft.date=2000-02-21&rft.volume=19&rft.issue=8&rft.spage=1020&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Reviews: Mouse Models for Breast Cancer. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Antigen T; Transgenic mice; Mammary gland; Carcinogenesis; Epithelium; Animal models ER - TY - JOUR T1 - Role of the tumor suppressor gene Brca1 in genetic stability and mammary gland tumor formation AN - 17499834; 4694058 AB - Germline mutations in the tumor suppressor BRCA1 predispose women to breast and ovarian cancers. Current evidence demonstrates that mutations in BRCA1 do not directly result in tumor formation, but instead cause genetic instability, subjecting cells to high risks of malignant transformation. In an animal model in which Brca1 is mutated specifically in mammary epithelium, tumorigenesis occurs in mutant glands at low frequency after a long latency. Notably, introduction of a p53-null allele significantly enhanced mammary gland tumor formation in Brca1 conditional mutant mice. These results are consistent with a model that Brca1 is a caretaker gene, whose absence causes genetic instability and triggers further alterations, including inactivation of tumor suppressor genes and/or activation of oncogenes, leading to tumor formation. JF - Oncogene AU - Deng, C-X AU - Scott, F AD - Genetics of Development and Disease Branch, 10/9N105, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, MD 20892, USA Y1 - 2000/02/21/ PY - 2000 DA - 2000 Feb 21 SP - 1059 EP - 1064 VL - 19 IS - 8 SN - 0950-9232, 0950-9232 KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Oncogenes & Growth Factors Abstracts KW - Mammary gland KW - Reviews KW - Tumorigenesis KW - Animal models KW - BRCA1 protein KW - W3 33056:Animal models of human disease KW - B 26416:Other tumor suppressor genes/antioncogenes KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17499834?accountid=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=Oncogene&rft.atitle=Role+of+the+tumor+suppressor+gene+Brca1+in+genetic+stability+and+mammary+gland+tumor+formation&rft.au=Deng%2C+C-X%3BScott%2C+F&rft.aulast=Deng&rft.aufirst=C-X&rft.date=2000-02-21&rft.volume=19&rft.issue=8&rft.spage=1059&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Reviews: Mouse Models for Breast Cancer. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; BRCA1 protein; Tumorigenesis; Mammary gland; Animal models ER - TY - JOUR T1 - Reduced hematopoietic function and enhanced radiosensitivity of transforming growth factor-beta1 transgenic mice. AN - 70991485; 10725853 AB - The cytokine transforming growth factor-beta1 (TGF-beta1) has been implicated in some tissue responses to radiation. Previous studies have demonstrated that exogenous TGF-beta1 increased the lethality of radiation in mice, but the effects of endogenous TGF-beta1 have not been investigated. To this end, we examined mice that are transgenic for active TGF-beta1 (Alb/TGF-beta1), over-expressed via an albumin promoter in the liver with resultant elevation of circulating levels of this cytokine. Alb/TGF-beta1 mice subjected to 8 Gy of total body irradiation at 3 or 5 weeks of age experienced significantly higher mortality than wild type age- and sex-matched controls by 1 to 2 weeks after irradiation. Alb/TGF-beta1 3 weeks of age also succumbed to 2 and 4 Gy of whole-body irradiation, while no mortality was observed in wild type mice. Four-week-old Alb/TGF-beta1 mice exhibited mild anemia and mild uremia. At one week after whole body irradiation with 2 Gy, 4-week-old Alb/TGF-beta1 mice had significantly reduced white blood cell counts, hematocrit, and platelet counts. Histopathologically, irradiated Alb/TGF-beta1 mice exhibited decreased bone marrow cellularity and decreased splenic extramedullary hematopoiesis. These results suggest that chronic over-expression of active TGF-beta1 is associated with increased radiosensitivity and that this effect may be mediated by increased sensitivity of bone marrow to the suppressive effects of radiation. Since TGF-beta1 levels can be greatly elevated in patients with certain tumors, these findings may be significant for radiotherapy. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 13-21 (2000). Published 2000 Wiley-Liss, Inc. JF - International journal of cancer AU - Vodovotz, Y AU - Lucia, M S AU - DeLucca, A M AU - Mitchell, J B AU - Kopp, J B AD - Radiation Biology Branch, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 2000/02/20/ PY - 2000 DA - 2000 Feb 20 SP - 13 EP - 21 VL - 90 IS - 1 SN - 0020-7136, 0020-7136 KW - Transforming Growth Factor beta KW - 0 KW - Index Medicus KW - Radiation Injuries, Experimental -- pathology KW - Radiation Dosage KW - Animals KW - Age Factors KW - Apoptosis KW - Leukocyte Count -- radiation effects KW - Mice KW - Blood Urea Nitrogen KW - Mice, Transgenic KW - Mice, Inbred CBA KW - Whole-Body Irradiation KW - Lethal Dose 50 KW - Mice, Inbred C57BL KW - Liver -- radiation effects KW - Male KW - Survival Analysis KW - Hematopoiesis -- physiology KW - Radiation Tolerance -- physiology 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/70991485?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reduced+hematopoietic+function+and+enhanced+radiosensitivity+of+transforming+growth+factor-beta1+transgenic+mice.&rft.au=Vodovotz%2C+Y%3BLucia%2C+M+S%3BDeLucca%2C+A+M%3BMitchell%2C+J+B%3BKopp%2C+J+B&rft.aulast=Vodovotz&rft.aufirst=Y&rft.date=2000-02-20&rft.volume=90&rft.issue=1&rft.spage=13&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 - 2000-05-22 N1 - Date created - 2000-05-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bacteriophage T4 Gene 59 Helicase Assembly Protein Binds Replication Fork DNA. The 1.45 Aa Resolution Crystal Structure Reveals a Novel alpha -Helical Two-domain Fold AN - 17917730; 5156812 AB - The bacteriophage T4 gene 59 helicase assembly protein is required for recombination-dependent DNA replication, which is the predominant mode of DNA replication in the late stage of T4 infection. T4 gene 59 helicase assembly protein accelerates the loading of the T4 gene 41 helicase during DNA synthesis by the T4 replication system in vitro. T4 gene 59 helicase assembly protein binds to both T4 gene 41 helicase and T4 gene 32 single-stranded DNA binding protein, and to single and double-stranded DNA. We show here that T4 gene 59 helicase assembly protein binds most tightly to fork DNA substrates, with either single or almost entirely double-stranded arms. Our studies suggest that the helicase assembly protein is responsible for loading T4 gene 41 helicase specifically at replication forks, and that its binding sites for each arm must hold more than six, but not more than 12 nucleotides. The 1.45 Aa resolution crystal structure of the full-length 217-residue monomeric T4 gene 59 helicase assembly protein reveals a novel alpha -helical bundle fold with two domains of similar size. Surface residues are predominantly basic (pI 9.37) with clusters of acidic residues but exposed hydrophobic residues suggest sites for potential contact with DNA and with other protein molecules. The N-terminal domain has structural similarity to the double-stranded DNA binding domain of rat HMG1A. We propose a speculative model of how the T4 gene 59 helicase assembly protein might bind to fork DNA based on the similarity to HMG1, the location of the basic and hydrophobic regions, and the site size of the fork arms needed for tight fork DNA binding. The fork-binding model suggests putative binding sites for the T4 gene 32 single-stranded DNA binding protein and for the hexameric T4 gene 41 helicase assembly. JF - Journal of Molecular Biology AU - Mueser, T C AU - Jones, CE AU - Nossal, NG AU - Hyde, C C AD - Laboratory of Structural Biology Research, Bldg. 6 Room B2-34A, National Institute of Arthritis and Musculoskeletal and Skin Diseases National Institutes of Health, Bethesda, MD, 20892-2717, USA Y1 - 2000/02/19/ PY - 2000 DA - 2000 Feb 19 SP - 597 EP - 612 PB - Academic Press VL - 296 IS - 2 SN - 0022-2836, 0022-2836 KW - assembly protein KW - gene 59 protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts KW - DNA biosynthesis KW - DNA-binding protein KW - Phage T4 KW - Replication forks KW - Crystal structure KW - Escherichia coli KW - DNA helicase KW - N 14651:Virus & phage infections KW - J 02750:Phage-host interactions KW - V 22070:Phage-host interactions including lysogeny & transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17917730?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Bacteriophage+T4+Gene+59+Helicase+Assembly+Protein+Binds+Replication+Fork+DNA.+The+1.45+Aa+Resolution+Crystal+Structure+Reveals+a+Novel+alpha+-Helical+Two-domain+Fold&rft.au=Mueser%2C+T+C%3BJones%2C+CE%3BNossal%2C+NG%3BHyde%2C+C+C&rft.aulast=Mueser&rft.aufirst=T&rft.date=2000-02-19&rft.volume=296&rft.issue=2&rft.spage=597&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1006%2Fjmbi.1999.3438 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Phage T4; Escherichia coli; DNA helicase; DNA biosynthesis; Replication forks; Crystal structure; DNA-binding protein DO - http://dx.doi.org/10.1006/jmbi.1999.3438 ER - TY - JOUR T1 - Activation of human T lymphocytes is inhibited by peroxisome proliferator-activated receptor gamma (PPARgamma) agonists. PPARgamma co-association with transcription factor NFAT. AN - 70904533; 10671476 AB - T lymphocyte activation is highlighted by the induction of interleukin-2 (IL-2) gene expression, which governs much of the early lymphocyte proliferation responses. Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. PPARgamma mRNA expression was found in human peripheral blood T lymphocytes, raising the possibility of PPARgamma involvement in the regulation of T cell function. Here we show that PPARgamma ligands, troglitazone and 15-deoxy-Delta(12,14) prostaglandin J(2), but not PPARalpha agonist Wy14643, inhibited IL-2 production and phytohemagglutinin-inducible proliferation in human peripheral blood T-cells in a dose-dependent manner. This inhibitory effect on IL-2 was restricted to the PPARgamma2-expressing, not the PPARgamma-lacking, subpopulation of transfected Jurkat cells. The activated PPARgamma physically associates with transcriptional factor NFAT regulating the IL-2 promoter, blocking NFAT DNA binding and transcriptional activity. This interaction with T-cell-specific transcription factors indicates an important immunomodulatory role for PPARgamma in T lymphocytes and could suggest a previously unrecognized clinical potential for PPARgamma ligands as immunotherapeutic drugs to treat T-cell-mediated diseases by targeting IL-2 gene expression. JF - The Journal of biological chemistry AU - Yang, X Y AU - Wang, L H AU - Chen, T AU - Hodge, D R AU - Resau, J H AU - DaSilva, L AU - Farrar, W L AD - Intramural Research Support Program, SAIC Frederick, NCI, National Institutes of Health, Frederick, Maryland 21702, USA. Y1 - 2000/02/18/ PY - 2000 DA - 2000 Feb 18 SP - 4541 EP - 4544 VL - 275 IS - 7 SN - 0021-9258, 0021-9258 KW - Chromans KW - 0 KW - DNA Probes KW - DNA-Binding Proteins KW - Interleukin-2 KW - NFATC Transcription Factors KW - Nuclear Proteins KW - Peroxisome Proliferators KW - Pyrimidines KW - Receptors, Cytoplasmic and Nuclear KW - Thiazoles KW - Thiazolidinediones KW - Transcription Factors KW - pirinixic acid KW - 86C4MRT55A KW - troglitazone KW - I66ZZ0ZN0E KW - Index Medicus KW - Thiazoles -- pharmacology KW - Base Sequence KW - Chromans -- pharmacology KW - Humans KW - Pyrimidines -- pharmacology KW - Interleukin-2 -- biosynthesis KW - Interleukin-2 -- genetics KW - Cell Line KW - DNA-Binding Proteins -- metabolism KW - Lymphocyte Activation -- drug effects KW - Receptors, Cytoplasmic and Nuclear -- agonists KW - T-Lymphocytes -- metabolism KW - Transcription Factors -- agonists KW - Transcription Factors -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Peroxisome Proliferators -- pharmacology KW - T-Lymphocytes -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70904533?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activation+of+human+T+lymphocytes+is+inhibited+by+peroxisome+proliferator-activated+receptor+gamma+%28PPARgamma%29+agonists.+PPARgamma+co-association+with+transcription+factor+NFAT.&rft.au=Yang%2C+X+Y%3BWang%2C+L+H%3BChen%2C+T%3BHodge%2C+D+R%3BResau%2C+J+H%3BDaSilva%2C+L%3BFarrar%2C+W+L&rft.aulast=Yang&rft.aufirst=X&rft.date=2000-02-18&rft.volume=275&rft.issue=7&rft.spage=4541&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 - 2000-03-21 N1 - Date created - 2000-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Crystal structure of an active two-domain derivative of Rous sarcoma virus integrase. AN - 70897998; 10669607 AB - Integration of retroviral cDNA is a necessary step in viral replication. The virally encoded integrase protein and DNA sequences at the ends of the linear viral cDNA are required for this reaction. Previous studies revealed that truncated forms of Rous sarcoma virus integrase containing two of the three protein domains can carry out integration reactions in vitro. Here, we describe the crystal structure at 2.5 A resolution of a fragment of the integrase of Rous sarcoma virus (residues 49-286) containing both the conserved catalytic domain and a modulatory DNA-binding domain (C domain). The catalytic domains form a symmetric dimer, but the C domains associate asymmetrically with each other and together adopt a canted conformation relative to the catalytic domains. A binding path for the viral cDNA is evident spanning both domain surfaces, allowing modeling of the larger integration complexes that are known to be active in vivo. The modeling suggests that formation of an integrase tetramer (a dimer of dimers) is necessary and sufficient for joining both viral cDNA ends at neighboring sites in the target DNA. The observed asymmetric arrangement of C domains suggests that they could form a rotationally symmetric tetramer that may be important for bridging integrase complexes at each cDNA end. JF - Journal of molecular biology AU - Yang, Z N AU - Mueser, T C AU - Bushman, F D AU - Hyde, C C AD - Laboratory of Structural Biology Research, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 20892, USA. Y1 - 2000/02/18/ PY - 2000 DA - 2000 Feb 18 SP - 535 EP - 548 VL - 296 IS - 2 SN - 0022-2836, 0022-2836 KW - DNA-Binding Proteins KW - 0 KW - Integrase Inhibitors KW - Peptide Fragments KW - DNA KW - 9007-49-2 KW - HIV Integrase KW - EC 2.7.7.- KW - Integrases KW - Index Medicus KW - AIDS/HIV KW - Crystallization KW - Integrase Inhibitors -- metabolism KW - DNA-Binding Proteins -- chemistry KW - Models, Molecular KW - Mutagenesis, Site-Directed -- genetics KW - DNA -- metabolism KW - Dimerization KW - DNA-Binding Proteins -- genetics KW - Integrase Inhibitors -- chemistry KW - HIV Integrase -- chemistry KW - Amino Acid Sequence KW - Drug Design KW - Binding Sites KW - Base Sequence KW - Amino Acid Substitution -- genetics KW - DNA -- genetics KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Protein Conformation KW - DNA-Binding Proteins -- metabolism KW - Peptide Fragments -- metabolism KW - Integrases -- metabolism KW - Peptide Fragments -- chemistry KW - Peptide Fragments -- genetics KW - Integrases -- chemistry KW - Integrases -- genetics KW - Catalytic Domain -- genetics KW - Avian Sarcoma Viruses -- enzymology KW - Catalytic Domain -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70897998?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+molecular+biology&rft.atitle=Crystal+structure+of+an+active+two-domain+derivative+of+Rous+sarcoma+virus+integrase.&rft.au=Yang%2C+Z+N%3BMueser%2C+T+C%3BBushman%2C+F+D%3BHyde%2C+C+C&rft.aulast=Yang&rft.aufirst=Z&rft.date=2000-02-18&rft.volume=296&rft.issue=2&rft.spage=535&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-23 N1 - Date created - 2000-03-23 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1C1A; PDB; 1C0M N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagenicity of benzo[a]pyrene-deoxyadenosine adducts in a sequence context derived from the p53 gene. AN - 70938989; 10708967 AB - Mutations in the human p53 tumor suppressor gene are prominently linked to sporadic cancers in breast, lung and other tissues. Recent research has shown that tobacco-associated cancer in the human lung is related to mutation of the p53 gene mediated by the carcinogen benzo[a]pyrene (BaP), and the mutations are targeted to DNA "hot spots" at specific codons. In order to gain insight into the relation between the structures of the adducts formed by BaP at these sites and their mutagenic activities, we have synthesized site-specifically modified oligo-nucleotide adducts of the active BaP diol epoxide metabolite (anti-BaPDE). This manuscript reports on the mutagenic consequences of replication past anti-BaPDE-deoxyadenosine adducts located within a sequence context related to codon 157 in exon 5 of the p53 gene. In this sequence context, the adduct derived from the carcinogenic 7R,8S-dihydrodiol 9S,10R-epoxide was much more active as a mutagen than the adduct derived from the noncarcinogenic 7S,8R-dihydrodiol 9R,10S-epoxide and the mutation found most frequently was an A-->G transition. Since previous studies in other sequence contexts have yielded somewhat different findings, these studies further emphasize the key role played by sequence context in determining the mutational properties of carcinogen-DNA adducts. JF - Mutation research AU - Khalili, H AU - Zhang, F J AU - Harvey, R G AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA. Y1 - 2000/02/16/ PY - 2000 DA - 2000 Feb 16 SP - 39 EP - 44 VL - 465 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Carcinogens KW - 0 KW - Codon KW - DNA Adducts KW - Deoxyadenosines KW - Mutagens KW - N(6)-(10-(7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo(a)pyrenyl))-2'-deoxyadenosine KW - Benzo(a)pyrene KW - 3417WMA06D KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - Index Medicus KW - DNA Adducts -- genetics KW - Codon -- genetics KW - Exons KW - Humans KW - Carcinogens -- toxicity KW - Mutagens -- toxicity KW - Escherichia coli -- genetics KW - Neoplasms -- genetics KW - DNA Adducts -- metabolism KW - Base Sequence KW - Mutagenicity Tests KW - Benzo(a)pyrene -- toxicity KW - Neoplasms -- etiology KW - DNA Replication KW - Female 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 - Genes, p53 KW - Deoxyadenosines -- genetics KW - Deoxyadenosines -- metabolism KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70938989?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Mutagenicity+of+benzo%5Ba%5Dpyrene-deoxyadenosine+adducts+in+a+sequence+context+derived+from+the+p53+gene.&rft.au=Khalili%2C+H%3BZhang%2C+F+J%3BHarvey%2C+R+G%3BDipple%2C+A&rft.aulast=Khalili&rft.aufirst=H&rft.date=2000-02-16&rft.volume=465&rft.issue=1-2&rft.spage=39&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-13 N1 - Date created - 2000-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations of the FHIT gene in human hepatocellular carcinoma. AN - 70948491; 10706123 AB - FHIT (fragile histidine triad), a candidate tumor suppressor gene, encompasses FRA3B, a region with the highest fragility in the human genome, and is altered in a large number of human cancers, particularly those of epithelial cell origin and associated with known carcinogenic agents. Human hepatocellular carcinoma (HCC), a major cancer worldwide, is closely related to carcinogenic agents such as hepatitis B and C virus infections, dietary aflatoxin, alcohol consumption, and exposure to chemical carcinogens. To assess the extent and the nature of the FHIT gene alterations and their implications in the development of HCC, several cell lines and primary tumors were cytologically and molecularly examined. The FHIT gene is expressed in normal hepatic cells and is not expressed or is abnormally expressed in cultured tumor cells derived from HCC. Down-regulation of the FHIT gene was detected by Northern blot analysis in 9 of 14 cell lines However, neither abnormal FHIT transcripts nor point mutations in DNA sequences of reverse transcription-PCR products (exons 2-9) were identified. Expression of FHIT protein was not detected by immunostaining in 5 of 10 primary tumors. Four cell lines showing mRNA down-regulation did not express FHIT protein as demonstrated by Western blot analysis. Allelic loss of intron 5 of the FHIT gene was detected in 10 of 34 informative samples from primary tumors. Structural alterations of chromosome 3p were identified in 8 of 13 HCC cell lines. Deletions or translocations involving region 3p14.2 were identified by fluorescence in situ hybridization with a YAC850A6 probe spanning the FHIT locus on chromosomes derived from cell lines with an abnormal FHIT gene expression. These combined results indicate that the FHIT gene is a frequent target and may be implicated in a subset of liver cancers. JF - Cancer research AU - Yuan, B Z AU - Keck-Waggoner, C AU - Zimonjic, D B AU - Thorgeirsson, S S AU - Popescu, N C AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 2000/02/15/ PY - 2000 DA - 2000 Feb 15 SP - 1049 EP - 1053 VL - 60 IS - 4 SN - 0008-5472, 0008-5472 KW - Neoplasm Proteins KW - 0 KW - Proteins KW - RNA, Messenger KW - fragile histidine triad protein KW - Acid Anhydride Hydrolases KW - EC 3.6.- KW - Index Medicus KW - Chromosomes, Human, Pair 3 KW - Tumor Cells, Cultured KW - Humans KW - RNA, Messenger -- analysis KW - Chromosome Aberrations KW - Carcinoma, Hepatocellular -- genetics KW - Proteins -- analysis KW - Proteins -- genetics KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70948491?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alterations+of+the+FHIT+gene+in+human+hepatocellular+carcinoma.&rft.au=Yuan%2C+B+Z%3BKeck-Waggoner%2C+C%3BZimonjic%2C+D+B%3BThorgeirsson%2C+S+S%3BPopescu%2C+N+C&rft.aulast=Yuan&rft.aufirst=B&rft.date=2000-02-15&rft.volume=60&rft.issue=4&rft.spage=1049&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 - 2000-03-20 N1 - Date created - 2000-03-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of topoisomerase I cleavage complexes by 1-beta -D-arabinofuranosylcytosine (ara-C) in vitro and in ara-C-treated cells. AN - 70902634; 10677551 AB - 1-beta-d-Arabinofuranosylcytosine (Ara-C) is a nucleoside analog commonly used in the treatment of leukemias. Ara-C inhibits DNA polymerases and can be incorporated into DNA. Its mechanism of cytotoxicity is not fully understood. Using oligonucleotides and purified human topoisomerase I (top1), we found a 4- to 6-fold enhancement of top1 cleavage complexes when ara-C was incorporated at the +1 position (immediately 3') relative to a unique top1 cleavage site. This enhancement was primarily due to a reversible inhibition of top1-mediated DNA religation. Because ara-C incorporation is known to alter base stacking and sugar puckering at the misincorporation site and at the neighboring base pairs, the observed inhibition of religation at the ara-C site suggests the importance of the alignment of the 5'-hydroxyl end for religation with the phosphate group of the top1 phosphotyrosine bond. This study also demonstrates that ara-C treatment and DNA incorporation trap top1 cleavage complexes in human leukemia cells. Finally, we report that camptothecin-resistant mouse P388/CPT45 cells with no detectable top1 are crossresistant to ara-C, which suggests that top1 poisoning is a potential mechanism for ara-C cytotoxicity. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Pourquier, P AU - Takebayashi, Y AU - Urasaki, Y AU - Gioffre, C AU - Kohlhagen, G AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 2000/02/15/ PY - 2000 DA - 2000 Feb 15 SP - 1885 EP - 1890 VL - 97 IS - 4 SN - 0027-8424, 0027-8424 KW - Antineoplastic Agents KW - 0 KW - Cytarabine KW - 04079A1RDZ KW - DNA KW - 9007-49-2 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Molecular Structure KW - Animals KW - Tumor Cells, Cultured KW - Camptothecin -- pharmacology KW - Humans KW - Drug Resistance KW - Mice KW - Antineoplastic Agents -- pharmacology KW - Cytarabine -- pharmacology KW - Enzyme Induction -- drug effects KW - DNA -- chemistry KW - DNA Topoisomerases, Type I -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70902634?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+topoisomerase+I+cleavage+complexes+by+1-beta+-D-arabinofuranosylcytosine+%28ara-C%29+in+vitro+and+in+ara-C-treated+cells.&rft.au=Pourquier%2C+P%3BTakebayashi%2C+Y%3BUrasaki%2C+Y%3BGioffre%2C+C%3BKohlhagen%2C+G%3BPommier%2C+Y&rft.aulast=Pourquier&rft.aufirst=P&rft.date=2000-02-15&rft.volume=97&rft.issue=4&rft.spage=1885&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 - 2000-03-23 N1 - Date created - 2000-03-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochim Biophys Acta. 1995 May 17;1262(1):1-14 [7772596] Biochemistry. 1995 May 30;34(21):7200-6 [7766631] J Biol Chem. 1996 Mar 22;271(12):6978-86 [8636127] Annu Rev Biochem. 1996;65:635-92 [8811192] Mol Cell Biol. 1996 Dec;16(12):6804-9 [8943335] Adv Pharmacol. 1994;29B:73-92 [8996602] J Biol Chem. 1997 Mar 21;272(12):7792-6 [9065442] J Biol Chem. 1997 Oct 17;272(42):26441-7 [9334220] Adv Cancer Res. 1998;72:197-233 [9338077] Cancer Res. 1997 Oct 15;57(20):4564-9 [9377570] Science. 1998 Mar 6;279(5356):1504-13 [9488644] Science. 1998 Mar 6;279(5356):1534-41 [9488652] J Med Chem. 1998 Jun 18;41(13):2216-26 [9632354] Biochim Biophys Acta. 1998 Oct 1;1400(1-3):83-105 [9748515] J Biol Chem. 1998 Oct 16;273(42):27245-9 [9765247] J Biol Chem. 1999 Mar 26;274(13):8516-23 [10085084] Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7196-201 [10377391] Annu Rev Biochem. 1977;46:641-68 [143235] Mol Pharmacol. 1979 Mar;15(2):367-74 [470933] J Biol Chem. 1980 Oct 10;255(19):8997-900 [7410404] J Biol Chem. 1981 May 25;256(10):4805-9 [6262303] Blood. 1984 Jul;64(1):54-8 [6587917] Cell. 1985 Jun;41(2):541-51 [2985282] Biochemistry. 1991 Oct 15;30(41):9922-31 [1911784] Cancer Res. 1991 Nov 1;51(21):5813-6 [1657371] J Mol Biol. 1991 Dec 5;222(3):669-78 [1660929] J Biol Chem. 1992 Aug 25;267(24):16755-8 [1324909] J Biol Chem. 1993 May 5;268(13):9690-701 [8387503] J Biol Chem. 1994 Jun 3;269(22):15498-504 [8195193] Oncol Res. 1993;5(12):467-74 [8086668] Biochemistry. 1994 Sep 27;33(38):11460-75 [7918360] Protein Expr Purif. 1994 Aug;5(4):364-70 [7950383] Adv Pharmacol. 1994;29A:191-200 [7826858] Cancer Res. 1968 Oct;28(10):2061-7 [5754840] Cancer Res. 1970 Nov;30(11):2627-35 [5530557] Anal Biochem. 1975 May 12;65(1-2):125-31 [1130673] Biochim Biophys Acta. 1977 Jul 15;477(2):144-50 [328050] Cancer Res. 1995 May 15;55(10):2097-103 [7743509] J Biol Chem. 1996 Mar 29;271(13):7593-601 [8631793] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Presenilin-1 mutation increases neuronal vulnerability to focal ischemia in vivo and to hypoxia and glucose deprivation in cell culture: involvement of perturbed calcium homeostasis. AN - 70901522; 10662826 AB - Many cases of early-onset inherited Alzheimer's disease (AD) are caused by mutations in the presenilin-1 (PS1) gene. Studies of cultured neural cells suggest that PS1 mutations result in perturbed cellular calcium homeostasis and may thereby render neurons vulnerable to apoptosis. In light of evidence that metabolic impairment plays a role in AD, that cerebral ischemia may be a risk factor for AD, and that individuals with AD have increased morbidity and mortality after stroke, we examined the impact of a PS1 mutation on neuronal vulnerability to ischemic injury. We report that the extent of brain injury after focal cerebral ischemia reperfusion is increased, and behavioral outcome is worsened, in PS1 mutant knock-in mice compared to wild-type mice. Cultured cortical neurons from PS1 mutant mice exhibit increased vulnerability to glucose deprivation and chemical hypoxia compared to their wild-type counterparts. Calcium imaging studies demonstrated enhanced elevation of intracellular calcium levels after glucose deprivation and chemical hypoxia in neurons from PS1 mutant mice. Agents that block calcium release from IP(3)- and ryanodine-sensitive stores (xestospongin and dantrolene, respectively) protected against the endangering action of the PS1 mutation. Our data suggest that presenilin mutations may promote neuronal degeneration in AD by increasing the sensitivity of neurons to age-related ischemia-like conditions. The data further suggest that drugs that stabilize endoplasmic reticulum calcium homeostasis may prove effective in suppressing the neurodegenerative process in AD patients. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Mattson, M P AU - Zhu, H AU - Yu, J AU - Kindy, M S AD - Sanders-Brown Research Center on Aging, Department of Anatomy, University of Kentucky, Lexington, Kentucky 40536, USA. mattsonm@grc.nia.nih.gov Y1 - 2000/02/15/ PY - 2000 DA - 2000 Feb 15 SP - 1358 EP - 1364 VL - 20 IS - 4 SN - 0270-6474, 0270-6474 KW - Membrane Proteins KW - 0 KW - Presenilin-1 KW - Carbon Dioxide KW - 142M471B3J KW - Dantrolene KW - F64QU97QCR KW - Glucose KW - IY9XDZ35W2 KW - Sodium Cyanide KW - O5DDB9Z95G KW - Oxygen KW - S88TT14065 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Sodium Cyanide -- pharmacology KW - Animals KW - Alzheimer Disease -- genetics KW - Apoptosis KW - Blood Pressure KW - Dantrolene -- pharmacology KW - Mice KW - Homeostasis KW - Cerebrovascular Circulation KW - Hypoglycemia KW - Mice, Knockout KW - Calcium -- metabolism KW - Heart Rate KW - Cells, Cultured KW - Oxygen -- blood KW - Genetic Predisposition to Disease KW - Carbon Dioxide -- blood KW - Embryo, Mammalian KW - Partial Pressure KW - Neocortex -- cytology KW - Neocortex -- physiology KW - Glucose -- physiology KW - Neurons -- drug effects KW - Neurons -- cytology KW - Neocortex -- physiopathology KW - Ischemic Attack, Transient -- genetics KW - Neurons -- physiology KW - Membrane Proteins -- genetics KW - Membrane Proteins -- deficiency KW - Cell Hypoxia KW - Ischemic Attack, Transient -- physiopathology KW - Membrane Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70901522?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Presenilin-1+mutation+increases+neuronal+vulnerability+to+focal+ischemia+in+vivo+and+to+hypoxia+and+glucose+deprivation+in+cell+culture%3A+involvement+of+perturbed+calcium+homeostasis.&rft.au=Mattson%2C+M+P%3BZhu%2C+H%3BYu%2C+J%3BKindy%2C+M+S&rft.aulast=Mattson&rft.aufirst=M&rft.date=2000-02-15&rft.volume=20&rft.issue=4&rft.spage=1358&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=02706474&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-25 N1 - Date created - 2000-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pathogenesis, natural history, treatment, and prevention of hepatitis C. AN - 70897945; 10681285 AB - Approximately 4 million persons in the United States and probably more than 100 million persons worldwide are infected with hepatitis C virus. The virus has the unique ability to cause persistent infection in susceptible hosts after parenteral or percutaneous transmission, and its underlying mechanisms are not well understood. The immunologic correlates of protection and viral clearance and the pathogenesis of liver injury are yet to be defined, but recent studies suggest the importance of cell-mediated immune responses. Although 70% to 80% of infected persons become chronic carriers, most have relatively mild disease with slow progression. However, chronic and progressive hepatitis C carries significant morbidity and mortality and is a major cause of cirrhosis, end-stage liver disease, and liver cancer. Development of an effective hepatitis C virus vaccine is not imminent, but recent advances in technology and basic knowledge of molecular virology and immunology have engendered novel approaches to the fundamental problems encountered in vaccine development. Current therapy for hepatitis C, although effective in some patients, is problematic and still evolving. Advances in modern biology and immunology promise new therapies for this important disease. JF - Annals of internal medicine AU - Liang, T J AU - Rehermann, B AU - Seeff, L B AU - Hoofnagle, J H AD - Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1800, USA. Y1 - 2000/02/15/ PY - 2000 DA - 2000 Feb 15 SP - 296 EP - 305 VL - 132 IS - 4 SN - 0003-4819, 0003-4819 KW - Antiviral Agents KW - 0 KW - Viral Hepatitis Vaccines KW - Ribavirin KW - 49717AWG6K KW - Interferons KW - 9008-11-1 KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Drug Therapy, Combination KW - Antiviral Agents -- therapeutic use KW - Hepacivirus -- physiology KW - Ribavirin -- therapeutic use KW - Immunity, Cellular KW - Humans KW - Antibody Formation KW - Antiviral Agents -- adverse effects KW - Interferons -- therapeutic use KW - Ribavirin -- adverse effects KW - Hepatitis C -- prevention & control KW - Hepatitis C -- drug therapy KW - Hepatitis C -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70897945?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Annals+of+internal+medicine&rft.atitle=Pathogenesis%2C+natural+history%2C+treatment%2C+and+prevention+of+hepatitis+C.&rft.au=Liang%2C+T+J%3BRehermann%2C+B%3BSeeff%2C+L+B%3BHoofnagle%2C+J+H&rft.aulast=Liang&rft.aufirst=T&rft.date=2000-02-15&rft.volume=132&rft.issue=4&rft.spage=296&rft.isbn=&rft.btitle=&rft.title=Annals+of+internal+medicine&rft.issn=00034819&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-17 N1 - Date created - 2000-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Detection of Gene Amplification by Genomic Hybridization to cDNA Microarrays AN - 17550365; 4730935 AB - Gene amplification is one of the major mechanisms of oncogene activation in tumorigenesis. To facilitate the identification of genes mapping to amplified regions, we have used a technique based on the hybridization of total genomic DNA to cDNA microarrays. To aid detection of the weak signals generated in this complex hybridization, we have used a tyramide-based technique that allows amplification of a fluorescent signal up to 1000-fold. Dilution experiment suggests that amplifications of 5-fold and higher can be detected by this approach. The technique was validated using cancer cell lines with several known gene amplifications, such as those affecting MYC, MYCN, ERBB2, and CDK4. In addition to the detection of the known amplifications, we identified a novel amplified gene, ZNF133, in the neuroblastoma cell line NGP. Hybridization of NGP cDNA on an identical array also revealed over expression of ZNF133. Parallel analysis of genomic DNA for copy number and cDNA for expression now provides rapid approach to the identification of amplified genes and chromosomal regions in tumor cells. JF - Cancer Research AU - Heiskanen, MA AU - Bittner, M L AU - Chen, Y AU - Khan, J AU - Adler, KE AU - Trent, J M AU - Meltzer, P S AD - Cancer Genetics Branch, National Human Genome Research Institute, NIH, 49 Convent Drive, MSC 4470, Bethesda, MD 20892, USA Y1 - 2000/02/15/ PY - 2000 DA - 2000 Feb 15 SP - 799 EP - 802 VL - 60 IS - 4 SN - 0008-5472, 0008-5472 KW - cDNA KW - man KW - CDK4 gene KW - DNA microarrays KW - ERBB2 gene KW - MYC gene KW - MYCN gene KW - ZNF133 gene KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Chromosomes KW - Tumor cell lines KW - Gene amplification KW - Hybridization analysis KW - N 14610:Occurrence, isolation & assay KW - W3 33243:Molecular methods KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17550365?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Detection+of+Gene+Amplification+by+Genomic+Hybridization+to+cDNA+Microarrays&rft.au=Heiskanen%2C+MA%3BBittner%2C+M+L%3BChen%2C+Y%3BKhan%2C+J%3BAdler%2C+KE%3BTrent%2C+J+M%3BMeltzer%2C+P+S&rft.aulast=Heiskanen&rft.aufirst=MA&rft.date=2000-02-15&rft.volume=60&rft.issue=4&rft.spage=799&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene amplification; Tumor cell lines; Hybridization analysis; Chromosomes; cDNA ER - TY - JOUR T1 - Aldolases of the DhnA family: a possible solution to the problem of pentose and hexose biosynthesis in archaea AN - 17491248; 4688103 AB - Sequence analysis of the recently identified class I aldolase of Escherichia coli (dhnA gene product) helped to identify its homologs in Chlamydia trachomatis, Chlamydiophyla pneumoniae and in each of the completely sequenced archaeal genomes. Iterative database searches revealed sequence similarities between the DhnA-family enzymes, deoxyribose phosphate aldolases and bacterial (class II) fructose bisphosphate aldolases and allowed prediction of similar three-dimensional structures (TIM-barrel fold) in all these enzymes. The Schiff base-forming lysyl residues of DhnA and deoxyribose phosphate aldolase are conserved in all members of the DhnA and deoxyribose phosphate aldolase families, indicating that these enzymes share common features with both class I and class II aldolases. The DhnA-family enzymes are predicted to possess an aldolase activity and to play a critical role in sugar biosynthesis in archaea. JF - FEMS Microbiology Letters AU - Galperin, MY AU - Aravind, L AU - Koonin, E V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health Bethesda, MD USA Y1 - 2000/02/15/ PY - 2000 DA - 2000 Feb 15 SP - 259 EP - 264 PB - Elsevier VL - 183 IS - 2 SN - 0378-1097, 0378-1097 KW - aldolase KW - Microbiology Abstracts B: Bacteriology KW - Chlamydiophila pneumoniae KW - Deoxyribose-phosphate aldolase KW - Escherichia coli KW - Chlamydia trachomatis KW - Tertiary structure KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17491248?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEMS+Microbiology+Letters&rft.atitle=Aldolases+of+the+DhnA+family%3A+a+possible+solution+to+the+problem+of+pentose+and+hexose+biosynthesis+in+archaea&rft.au=Galperin%2C+MY%3BAravind%2C+L%3BKoonin%2C+E+V&rft.aulast=Galperin&rft.aufirst=MY&rft.date=2000-02-15&rft.volume=183&rft.issue=2&rft.spage=259&rft.isbn=&rft.btitle=&rft.title=FEMS+Microbiology+Letters&rft.issn=03781097&rft_id=info:doi/10.1016%2FS0378-1097%2899%2900612-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Chlamydia trachomatis; Chlamydiophila pneumoniae; Deoxyribose-phosphate aldolase; Tertiary structure DO - http://dx.doi.org/10.1016/S0378-1097(99)00612-6 ER - TY - JOUR T1 - Reduction of diepoxybutane-induced sister chromatid exchanges by glutathione peroxidase and erythrocytes in transgenic Big Blue mouse and rat fibroblasts. AN - 71019180; 10751610 AB - We have investigated the effect of glutathione peroxidase (GSH-Px) and mammalian erythrocytes (RBCs) on spontaneous and diepoxybutane (DEB)-induced sister chromatid exchange (SCE) in primary Big Blue(R) mouse (BBM1) and Big Blue(R) rat (BBR1) fibroblasts. DEB is the putative carcinogenic metabolite of 1,3-butadiene (BD) for which inhalation exposure yields a high rate of malignancies in mice but not in rats. BD is metabolized differently in mice and rats, producing much higher levels of DEB in mice than in rats, which may partly explain the different carcinogenic responses. However, other factors may contribute to the observed differences in the rodent carcinogenic response to BD. DEB is a highly reactive compound. Upon epoxide hydrolysis, DEB can covalently bind to DNA bases. Likewise, DEB generates reactive oxygen species that, in turn, can either damage DNA or produce H(2)O(2). Reduced glutathione (GSH) is known to play a role in the metabolism and detoxification of DEB; and GSH is reduced by GSH-Px in the presence of H(2)O(2). GSH-Px is a constitutive enzyme that is found at high concentrations in mammalian RBCs. Therefore, we were interested in examining the role of RBCs and GSH-Px on DEB-induced SCE in rat and mouse cells for detection of possible differences in the species response. Transgenic BBM1 and BBR1 fibroblasts were treated with either 0, 2 or 4 microM DEB plus 0, 2 or 20 units of GSH-Px with and without 2x10(8) species-specific RBCs. DEB effectively induced SCEs in both rat and mouse cells. The relative induction of SCEs in both cell types was comparable. Both GSH-Px and RBCs alone and in combination were effective in significantly reducing DEB-induced SCEs in both mouse and rat fibroblasts, although there was more variability in the SCE response in rat cells. The present study suggests that GSH-Px may be important in the detoxification of DEB-induced DNA damage that results in the formation of SCEs. JF - Mutation research AU - Erexson, G L AU - Tindall, K R AD - Molecular Mutagenesis Group, Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2000/02/14/ PY - 2000 DA - 2000 Feb 14 SP - 267 EP - 274 VL - 447 IS - 2 SN - 0027-5107, 0027-5107 KW - Epoxy Compounds KW - 0 KW - Mutagens KW - erythritol anhydride KW - 60OB65YNAB KW - Glutathione Peroxidase KW - EC 1.11.1.9 KW - Index Medicus KW - Rats KW - Animals KW - Cytogenetic Analysis KW - Mitotic Index -- drug effects KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Mice KW - Mice, Transgenic KW - Male KW - Epoxy Compounds -- adverse effects KW - Fibroblasts -- drug effects KW - Mutagens -- adverse effects KW - Glutathione Peroxidase -- pharmacology KW - Sister Chromatid Exchange -- drug effects KW - Fibroblasts -- cytology KW - Erythrocytes -- physiology KW - Fibroblasts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71019180?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Reduction+of+diepoxybutane-induced+sister+chromatid+exchanges+by+glutathione+peroxidase+and+erythrocytes+in+transgenic+Big+Blue+mouse+and+rat+fibroblasts.&rft.au=Erexson%2C+G+L%3BTindall%2C+K+R&rft.aulast=Erexson&rft.aufirst=G&rft.date=2000-02-14&rft.volume=447&rft.issue=2&rft.spage=267&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-17 N1 - Date created - 2000-05-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A GATA binding site is involved in the regulation of 15-lipoxygenase-1 expression in human colorectal carcinoma cell line, caco-2. AN - 70914957; 10675566 AB - The data presented implicate a GATA binding site in the transcriptional regulation of 15-lipoxygenase-1 (15-LO-1) gene expression in human colorectal carcinoma Caco-2 cells. High expression of GATA-6 mRNA and protein was observed, while GATA-4 mRNA was expressed at a very low level in Caco-2 cells. The expression of GATA-6 was down-regulated, while 15-LO-1 expression was dramatically up-regulated after treatment with sodium butyrate (NaBT). A study using an electrophoretic mobility shift assay indicated that a GATA binding site of the 15-LO-1 promoter region binds to GATA proteins present in both undifferentiated and, to a lesser extent, NaBT-treated (differentiated) Caco-2 cells. Moreover, that DNA binding shift band was disrupted after the addition of GATA-6 antibody in a supershift assay in the absence of NaBT, suggesting that GATA-6 is bound to the GATA binding site of the 15-LO-1 promoter in undifferentiated cells. In contrast, the addition of GATA-6 antibody did not affect the DNA binding ability in NaBT-induced differentiated cells. On the other hand, mutation of the GATA site of the 15-LO-1 promoter decreased the transactivation of the 15-LO-1 promoter as measured by luciferase activity in both FBS and NaBT cultured cells, indicating an unknown GATA binding protein to up-regulate 15-LO-1 expression. These implicate the GATA site at -240 of the proximal region of the 15-LO-1 promoter in the basic transcription of 15-LO-1 gene expression in Caco-2 cells, with GATA-6 acting to repress 15-LO-1 expression. JF - FEBS letters AU - Kamitani, H AU - Kameda, H AU - Kelavkar, U P AU - Eling, T E AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC, USA. Y1 - 2000/02/11/ PY - 2000 DA - 2000 Feb 11 SP - 341 EP - 347 VL - 467 IS - 2-3 SN - 0014-5793, 0014-5793 KW - DNA-Binding Proteins KW - 0 KW - Erythroid-Specific DNA-Binding Factors KW - GATA4 Transcription Factor KW - GATA6 Transcription Factor KW - GATA6 protein, human KW - RNA, Messenger KW - Transcription Factors KW - Arachidonate 15-Lipoxygenase KW - EC 1.13.11.33 KW - Index Medicus KW - Promoter Regions, Genetic KW - Blotting, Western KW - RNA, Messenger -- metabolism KW - Humans KW - Cell Differentiation KW - Gene Expression Regulation KW - Caco-2 Cells KW - Colorectal Neoplasms KW - Carcinoma KW - Binding Sites KW - Arachidonate 15-Lipoxygenase -- metabolism KW - Transcription Factors -- metabolism KW - Arachidonate 15-Lipoxygenase -- genetics KW - DNA-Binding Proteins -- genetics KW - Transcription Factors -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70914957?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+GATA+binding+site+is+involved+in+the+regulation+of+15-lipoxygenase-1+expression+in+human+colorectal+carcinoma+cell+line%2C+caco-2.&rft.au=Kamitani%2C+H%3BKameda%2C+H%3BKelavkar%2C+U+P%3BEling%2C+T+E&rft.aulast=Kamitani&rft.aufirst=H&rft.date=2000-02-11&rft.volume=467&rft.issue=2-3&rft.spage=341&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 - 2000-03-31 N1 - Date created - 2000-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Phase I Study of Intralesional Administration of an Adenovirus Vector Expressing the HSV-1 Thymidine Kinase Gene (AdV.RSV-TK) in Combination with Escalating Doses of Ganciclovir in Patients with Cutaneous Metastatic Malignant Melanoma AN - 17587606; 4684266 AB - This phase I study will evaluate the toxicity and secondarily the response of cohorts of patients with advanced cutaneous malignant melanoma treated with a combination of a replication defective adenovirus expressing the herpes simplex virus type-1 thymidine kinase (HSV-tk) gene and escalating doses of ganciclovir (GCV). HSV-tk catalyzes the monophosphorylation of the non-toxic prodrug GCV, which is then further phosphorylated by cellular kinases and incorporated into DNA, where it inhibits its synthesis and ultimately results in cell death. Adult patients with metastatic (stage IV) malignant melanoma who are not curable by currently available treatments and who have at least one accessible, discreet, cutaneous or subcutaneous lesion of less than or equal to 3 cm super(3) volume will receive intratumoral injection(s) of 5 x 10 super(11) viral particles/cm super(3). Forty-eight (48) hours after vector administration, patients will receive intravenous GCV every 12 hours for seven (7) days. This study will involve the escalation of the total dose of GCV administered to cohorts of patients. Patients will be closely monitored for local and systemic toxicity. Patients will also be evaluated for response of their malignant melanoma (both the treated lesion and other sites of untreated disease). The goal of this study is to determine the maximum tolerated dose (MTD) of GCV which can be administered in combination with 5 x 10 super(11) viral particles/cm super(3) of AdV.RSV-TK, and the dose limiting toxicity (DLT) of HSV-tk gene therapy in combination with high dose GCV in a cutaneous tumor model before proceeding to clinical trials involving visceral tumors. A secondary goal will be to determine the response rate of the treated lesions and possible immunologic "bystander" effects on remote sites of untreated tumor. JF - Human Gene Therapy AU - Morris, J C AU - Ramsey, W J AU - Wildner, O AU - Muslow, HA AU - Aguilar-Cordova, E AU - Blaese, R M AD - Building 10, Room 10C103, NIH, Bethesda, MD 20814, USA, jmorris@nhgri.nih.gov Y1 - 2000/02/10/ PY - 2000 DA - 2000 Feb 10 SP - 487 EP - 503 VL - 11 IS - 3 SN - 1043-0342, 1043-0342 KW - man KW - Adenovirus KW - Herpes simplex virus 1 KW - ganciclovir KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene therapy KW - Thymidine kinase KW - Tumors KW - Melanoma KW - Cell death KW - Gene transfer KW - W3 33181:Gene therapy vectors KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17587606?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=A+Phase+I+Study+of+Intralesional+Administration+of+an+Adenovirus+Vector+Expressing+the+HSV-1+Thymidine+Kinase+Gene+%28AdV.RSV-TK%29+in+Combination+with+Escalating+Doses+of+Ganciclovir+in+Patients+with+Cutaneous+Metastatic+Malignant+Melanoma&rft.au=Morris%2C+J+C%3BRamsey%2C+W+J%3BWildner%2C+O%3BMuslow%2C+HA%3BAguilar-Cordova%2C+E%3BBlaese%2C+R+M&rft.aulast=Morris&rft.aufirst=J&rft.date=2000-02-10&rft.volume=11&rft.issue=3&rft.spage=487&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/10.1089%2F10430340050015950 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adenovirus; Herpes simplex virus 1; Gene therapy; Gene transfer; Thymidine kinase; Melanoma; Cell death; Tumors DO - http://dx.doi.org/10.1089/10430340050015950 ER - TY - JOUR T1 - Picking two scientific roses for the next century. AN - 85358902; pmid-10739584 JF - Brain and cognition AU - Grafman, J AD - Cognitive Neuroscience Section, National Institutes of Health, Bethesda, MD 20892-1440, USA. jgr@box-j.nih.gov Y1 - 2000/02// PY - 2000 DA - Feb 2000 SP - 10 EP - 12 VL - 42 IS - 1 SN - 0278-2626, 0278-2626 KW - Index Medicus KW - National Library of Medicine KW - Humans KW - Prefrontal Cortex -- physiology KW - Neuronal Plasticity -- physiology KW - Forecasting KW - Language KW - Neurosciences -- trends KW - Brain -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85358902?accountid=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+and+cognition&rft.atitle=Picking+two+scientific+roses+for+the+next+century.&rft.au=Grafman%2C+J&rft.aulast=Grafman&rft.aufirst=J&rft.date=2000-02-01&rft.volume=42&rft.issue=1&rft.spage=10&rft.isbn=&rft.btitle=&rft.title=Brain+and+cognition&rft.issn=02782626&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - Effects of botulinum toxin on pathophysiology in spasmodic dysphonia. AN - 85340067; pmid-10685573 AB - To determine the mechanism of symptom relief with treatment by botulinum toxin injection in persons with adductor spasmodic dysphonia (ADSD), we evaluated the effects of unilateral thyroarytenoid muscle injections on both injected and noninjected muscles in 10 subjects with ADSD, using electromyography on both sides of the larynx before and after treatment. The subjects' speech symptoms were reduced (p = .005) 2 weeks following injection, when the electromyographic study occurred. Muscle activation levels and the numbers of spasmodic muscle bursts decreased significantly (p or = .7) in all muscles. Reductions in laryngeal muscle bursts did not relate to either absolute or normalized levels of muscle activity before or after botulinum toxin injection. The results suggest that changes in the central pathophysiology are responsible for changes in speech symptoms following treatment. JF - The Annals of otology, rhinology, and laryngology AU - Bielamowicz, S AU - Ludlow, C L AD - Laryngeal and Speech Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2000/02// PY - 2000 DA - Feb 2000 SP - 194 EP - 203 VL - 109 IS - 2 SN - 0003-4894, 0003-4894 KW - National Library of Medicine KW - Laryngeal Muscles -- physiopathology KW - Humans KW - Adult KW - Electromyography KW - Laryngeal Muscles -- drug effects KW - Middle Aged KW - Female KW - Male KW - Voice Disorders -- physiopathology KW - Botulinum Toxin Type A -- therapeutic use KW - Voice Disorders -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85340067?accountid=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+Annals+of+otology%2C+rhinology%2C+and+laryngology&rft.atitle=Effects+of+botulinum+toxin+on+pathophysiology+in+spasmodic+dysphonia.&rft.au=Bielamowicz%2C+S%3BLudlow%2C+C+L&rft.aulast=Bielamowicz&rft.aufirst=S&rft.date=2000-02-01&rft.volume=109&rft.issue=2&rft.spage=194&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+otology%2C+rhinology%2C+and+laryngology&rft.issn=00034894&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - Transdisciplinary tobacco use research centers: a model collaboration between public and private sectors. AN - 72405888; 11072437 JF - Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco AU - Turkkan, J S AU - Kaufman, N J AU - Rimer, B K AD - Behavioral Sciences Research Branch, National Institute on Drug Abuse, NIH, Bethesda, MD 20857, USA. jaylan@nih.gov Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 9 EP - 13 VL - 2 IS - 1 SN - 1462-2203, 1462-2203 KW - Index Medicus KW - United States KW - Models, Organizational KW - Public Sector KW - Private Sector KW - Cooperative Behavior KW - Humans KW - Research -- economics KW - Research -- trends KW - Tobacco Use Disorder -- prevention & control KW - Interprofessional Relations KW - Research Support as Topic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72405888?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.atitle=Transdisciplinary+tobacco+use+research+centers%3A+a+model+collaboration+between+public+and+private+sectors.&rft.au=Turkkan%2C+J+S%3BKaufman%2C+N+J%3BRimer%2C+B+K&rft.aulast=Turkkan&rft.aufirst=J&rft.date=2000-02-01&rft.volume=2&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.issn=14622203&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-11-30 N1 - Date created - 2000-11-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Localization, sequence analysis, and ethnic distribution of a 96-bp insertion in the promoter of the human CYP2E1 gene. AN - 71118887; 10729706 JF - Mutation research AU - Fritsche, E AU - Pittman, G S AU - Bell, D A AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 1 EP - 5 VL - 432 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Index Medicus KW - DNA Mutational Analysis KW - Humans KW - African Americans KW - Genotype KW - Promoter Regions, Genetic KW - Base Sequence KW - Sequence Alignment KW - North Carolina KW - Microsomes, Liver -- enzymology KW - Molecular Sequence Data KW - Asian Americans KW - Taiwan -- ethnology KW - African Continental Ancestry Group KW - Cell Line KW - Africa -- ethnology KW - Europe -- ethnology KW - Cytochrome P-450 CYP2E1 -- genetics KW - Mutagenesis, Insertional -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71118887?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Localization%2C+sequence+analysis%2C+and+ethnic+distribution+of+a+96-bp+insertion+in+the+promoter+of+the+human+CYP2E1+gene.&rft.au=Fritsche%2C+E%3BPittman%2C+G+S%3BBell%2C+D+A&rft.aulast=Fritsche&rft.aufirst=E&rft.date=2000-02-01&rft.volume=432&rft.issue=1-2&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-07 N1 - Date created - 2000-06-07 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - J02843; GENBANK; AF153060 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reinforcing and subjective effects of morphine in human opioid abusers: effect of dose and alternative reinforcer. AN - 71022889; 10755740 AB - Although most opioid self-administration research has been conducted with laboratory animals, such research with humans is necessary to answer questions unique to human drug-taking behavior. We investigated the influence of morphine dose and an alternative non-drug reinforcer on choice between morphine versus money and examined the relationship between drug-reinforced behavior and subjective euphoria. Five male opioid users participated in the 7-week study. During the first 5 weeks, a single dose of morphine (0, 4, 8, 16, or 32 mg/70 kg) was available each week. On Monday, subjects received an IM injection of the dose tested that week. On Tuesday, Thursday, and Friday, subjects could work for morphine or money under a second-order, progressive ratio schedule. For each primary ratio completed on the drug lever, subjects earned one-ninth of the available drug dose, and for each ratio completed on the money lever, subjects earned $1. Total amount of drug earned was administered in a single IM injection at the end of the session; money earned was credited to the subject's account. As morphine dose increased, responding for drug increased in an orderly manner and responding for money decreased. During the final phase of the study, the lowest and highest doses that maintained drug responding for each subject were repeated, and the value of the alternative reinforcer was increased to $2 per ratio. This manipulation was associated with decreased drug-maintained responding at the lowest, but not the highest, reinforcing dose of morphine. The progressive ratio, concurrent access procedure may be useful in predicting the outcome of drug abuse treatment interventions that use alternate reinforcement strategies. JF - Psychopharmacology AU - Heishman, S J AU - Schuh, K J AU - Schuster, C R AU - Henningfield, J E AU - Goldberg, S R AD - Clinical Pharmacology and Therapeutics Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA. sheish@intra.nida.nih.gov Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 272 EP - 280 VL - 148 IS - 3 SN - 0033-3158, 0033-3158 KW - Morphine KW - 76I7G6D29C KW - Index Medicus KW - Heart Rate -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Respiration -- drug effects KW - Blood Pressure -- drug effects KW - Male KW - Opioid-Related Disorders -- psychology KW - Reinforcement (Psychology) KW - Morphine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71022889?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Reinforcing+and+subjective+effects+of+morphine+in+human+opioid+abusers%3A+effect+of+dose+and+alternative+reinforcer.&rft.au=Heishman%2C+S+J%3BSchuh%2C+K+J%3BSchuster%2C+C+R%3BHenningfield%2C+J+E%3BGoldberg%2C+S+R&rft.aulast=Heishman&rft.aufirst=S&rft.date=2000-02-01&rft.volume=148&rft.issue=3&rft.spage=272&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-27 N1 - Date created - 2000-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of industrial hygienists' exposure evaluations for an epidemiologic study. AN - 71016664; 10744177 AB - A study was conducted to determine what level of information is required by industrial hygienists before they can develop exposure estimates comparable with those developed from a more in-depth evaluation. Three industrial hygienists evaluated formaldehyde exposures of 300 jobs selected from an earlier epidemiologic study. The jobs were evaluated over the following 6 cycles: (i) job title and industry; (ii) job title, industry, dates; (iii) job and department title and industry; (iv) cycle 3 information with dates; (v) cycle 3 information with a plant report; and (vi) job and department title, industry, dates, and the report. Each hygienist assigned jobs to 1 of 4 exposure categories, which were compared with the categories in the original epidemiologic study. Overall, the mean differences between the hygienists' evaluations and the standard, although small, changed little over the cycles. The kappa statistic was poor to moderate for all the cycles, but the agreement was greater than expected due to chance. There was moderate improvement in overall agreement over the cycles using the weighted kappa statistic, but little improvement in the intraclass correlation coefficients of the hygienists' evaluations, which ranged from 0.4 to 0.5. Department information improved the agreement with the standard by 5--10%, but dates did not the improve agreement. There were some differences by type of plant, job function, exposure level, and date of the estimate. Using a hypothetical exposure-response scenario, this level of misclassification would have resulted in missing an association. Although there was slight improvement with increasing levels of information, these findings suggest that the subjective categorical assessment of exposures by industrial hygienists will not produce exposure estimates comparable to more in-depth evaluations of exposure. JF - Scandinavian journal of work, environment & health AU - Stewart, P A AU - Carel, R AU - Schairer, C AU - Blair, A AD - Environmental Epidemiology Program, National Cancer Institute, Bethesda, Maryland 20892-7240, USA. stewartt@epndce.nci.nih.gov Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 44 EP - 51 VL - 26 IS - 1 SN - 0355-3140, 0355-3140 KW - Formaldehyde KW - 1HG84L3525 KW - Index Medicus KW - Evaluation Studies as Topic KW - Humans KW - Occupational Exposure KW - Occupational Health KW - Epidemiologic Methods KW - Formaldehyde -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71016664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scandinavian+journal+of+work%2C+environment+%26+health&rft.atitle=Comparison+of+industrial+hygienists%27+exposure+evaluations+for+an+epidemiologic+study.&rft.au=Stewart%2C+P+A%3BCarel%2C+R%3BSchairer%2C+C%3BBlair%2C+A&rft.aulast=Stewart&rft.aufirst=P&rft.date=2000-02-01&rft.volume=26&rft.issue=1&rft.spage=44&rft.isbn=&rft.btitle=&rft.title=Scandinavian+journal+of+work%2C+environment+%26+health&rft.issn=03553140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-19 N1 - Date created - 2000-04-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tobacco craving: intensity-related effects of imagery scripts in drug abusers. AN - 71016000; 10743907 AB - Two experiments were conducted to determine whether active imagery would elicit tobacco craving in smokers with histories of drug abuse who were not interested in quitting smoking. In Experiment 1, the authors used scripts that contained positive, negative, or neutral affective content with and without descriptions of smoking urge. Scripts with urge content and negative affect scripts increased subjective reports of tobacco craving. An interaction between affective manipulation and urge content was observed on self-reported mood. In Experiment 2, positive affect scripts that varied in amount of urge content produced an orderly increase in tobacco craving as a function of urge intensity, suggesting that changes were specific to the imagery manipulation. In both experiments, increases in tobacco craving were positively correlated with craving for drug of choice, suggesting that stimuli that engender smoking urges may occasion craving for other drugs of abuse. JF - Experimental and clinical psychopharmacology AU - Taylor, R C AU - Harris, N A AU - Singleton, E G AU - Moolchan, E T AU - Heishman, S J AD - Clinical Pharmacology and Therapeutics Branch, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 75 EP - 87 VL - 8 IS - 1 SN - 1064-1297, 1064-1297 KW - Index Medicus KW - Affect -- drug effects KW - Humans KW - Adult KW - Surveys and Questionnaires KW - Cues KW - Male KW - Female KW - Tobacco Use Cessation -- psychology KW - Substance-Related Disorders -- psychology KW - Imagination -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71016000?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+and+clinical+psychopharmacology&rft.atitle=Tobacco+craving%3A+intensity-related+effects+of+imagery+scripts+in+drug+abusers.&rft.au=Taylor%2C+R+C%3BHarris%2C+N+A%3BSingleton%2C+E+G%3BMoolchan%2C+E+T%3BHeishman%2C+S+J&rft.aulast=Taylor&rft.aufirst=R&rft.date=2000-02-01&rft.volume=8&rft.issue=1&rft.spage=75&rft.isbn=&rft.btitle=&rft.title=Experimental+and+clinical+psychopharmacology&rft.issn=10641297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-02 N1 - Date created - 2000-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Studies of methyl 2-nitroimidazole-1-acetohydroxamate (KIN-804) 2: effect on certain antioxidant enzyme systems in mice bearing Ehrlich ascites carcinoma. AN - 70974850; 10706383 AB - In order to decrease toxicity and/or increase radiosensitizing activity, a new 2-nitroimidazole derivative, methyl 2-nitroimidazole-1-acetohydroxamate (KIN-804), was synthesized to solve the problem of tumor hypoxia. Evaluation of the efficiency of KIN-804 was carried out through studying the antioxidant enzyme system: The superoxide dismutase (SOD), catalase and lipid peroxide levels provide a rough index of the balance between free radical generation and scavenging. Female albino mice were inoculated with Ehrlich ascites carcinoma (EAC) in the thigh. The administration of KIN-804 (i.p. 80 mg/kg body weight) was carried out 20 min before localized irradiation of 10 Gy. In general, the data revealed that KIN-804 administration, followed or not by gamma irradiation, exerted significant inhibition of SOD and catalase activities accompanied by a significant increase in lipid peroxide level in tumor-bearing mice. JF - Biological & pharmaceutical bulletin AU - Abu-Zeid, M AU - Hori, H AU - Nagasawa, H AU - Uto, Y AU - Inayama, S AD - Department of Cancer Biology, National Cancer Institute, Cairo University, Egypt. Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 195 EP - 198 VL - 23 IS - 2 SN - 0918-6158, 0918-6158 KW - Antioxidants KW - 0 KW - Hydroxamic Acids KW - Lipid Peroxides KW - Nitroimidazoles KW - Radiation-Sensitizing Agents KW - 2-nitroimidazole-1-methylacetohydroxamate KW - 140448-30-2 KW - Catalase KW - EC 1.11.1.6 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Index Medicus KW - Animals KW - Liver -- enzymology KW - Lipid Peroxides -- radiation effects KW - Superoxide Dismutase -- blood KW - Superoxide Dismutase -- metabolism KW - Catalase -- radiation effects KW - Mice KW - Hypoxia -- enzymology KW - Catalase -- metabolism KW - Superoxide Dismutase -- radiation effects KW - Lipid Peroxides -- blood KW - Lung -- enzymology KW - Catalase -- blood KW - Lipid Peroxides -- metabolism KW - Female KW - Carcinoma, Ehrlich Tumor -- enzymology KW - Antioxidants -- metabolism KW - Radiation-Sensitizing Agents -- pharmacology KW - Nitroimidazoles -- pharmacology KW - Hydroxamic Acids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70974850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+%26+pharmaceutical+bulletin&rft.atitle=Studies+of+methyl+2-nitroimidazole-1-acetohydroxamate+%28KIN-804%29+2%3A+effect+on+certain+antioxidant+enzyme+systems+in+mice+bearing+Ehrlich+ascites+carcinoma.&rft.au=Abu-Zeid%2C+M%3BHori%2C+H%3BNagasawa%2C+H%3BUto%2C+Y%3BInayama%2C+S&rft.aulast=Abu-Zeid&rft.aufirst=M&rft.date=2000-02-01&rft.volume=23&rft.issue=2&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Biological+%26+pharmaceutical+bulletin&rft.issn=09186158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-13 N1 - Date created - 2000-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A localized interaction surface for voltage-sensing domains on the pore domain of a K+ channel. AN - 70973990; 10719895 AB - Voltage-gated K+ channels contain a central pore domain and four surrounding voltage-sensing domains. How and where changes in the structure of the voltage-sensing domains couple to the pore domain so as to gate ion conduction is not understood. The crystal structure of KcsA, a bacterial K+ channel homologous to the pore domain of voltage-gated K+ channels, provides a starting point for addressing this question. Guided by this structure, we used tryptophan-scanning mutagenesis on the transmembrane shell of the pore domain in the Shaker voltage-gated K+ channel to localize potential protein-protein and protein-lipid interfaces. Some mutants cause only minor changes in gating and when mapped onto the KcsA structure cluster away from the interface between pore domain subunits. In contrast, mutants producing large changes in gating tend to cluster near this interface. These results imply that voltage-sensing domains interact with localized regions near the interface between adjacent pore domain subunits. JF - Neuron AU - Li-Smerin, Y AU - Hackos, D H AU - Swartz, K J AD - Molecular Physiology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 411 EP - 423 VL - 25 IS - 2 SN - 0896-6273, 0896-6273 KW - Potassium Channels KW - 0 KW - Shaker Superfamily of Potassium Channels KW - Index Medicus KW - Animals KW - Membrane Potentials -- physiology KW - Mutagenesis -- physiology KW - Oocytes -- physiology KW - Binding Sites -- physiology KW - Protein Structure, Quaternary KW - Xenopus laevis KW - Patch-Clamp Techniques KW - Molecular Sequence Data KW - Point Mutation KW - Crystallography KW - Protein Structure, Tertiary KW - Sequence Homology, Amino Acid KW - Ion Channel Gating -- physiology KW - Potassium Channels -- metabolism KW - Potassium Channels -- chemistry KW - Potassium Channels -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70973990?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuron&rft.atitle=A+localized+interaction+surface+for+voltage-sensing+domains+on+the+pore+domain+of+a+K%2B+channel.&rft.au=Li-Smerin%2C+Y%3BHackos%2C+D+H%3BSwartz%2C+K+J&rft.aulast=Li-Smerin&rft.aufirst=Y&rft.date=2000-02-01&rft.volume=25&rft.issue=2&rft.spage=411&rft.isbn=&rft.btitle=&rft.title=Neuron&rft.issn=08966273&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-30 N1 - Date created - 2000-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acute alcohol intoxication and gadolinium chloride attenuate endotoxin-induced release of CC chemokines in the rat. AN - 70961013; 10719799 AB - This work tests the hypotheses that Kupffer cells are a major source of CC-chemokines (MIP-1alpha, MCP-1, RANTES) during acute endotoxemia and that acute ethanol intoxication modulates Escherichia coli lipopolysaccharide (LPS, 1 mg/Kg, i.v.)-induced chemokine release in the rat. LPS stimulated the release of CC-chemokines into the circulation, hepatic sequestration of leukocytes and liver injury. LPS-induced serum chemokines peaked at 1-3 h and could not be detected at 24-h posttreatment. Splenectomy significantly suppressed LPS-induced RANTES release, but not MIP-1alpha and MCP-1. Kupffer cell depletion by gadolinium chloride or acute ethanol intoxication significantly attenuated LPS-induced CC-chemokine release and hepatic injury. Hepatic sequestration of leukocytes during endotoxemia was also suppressed by acute ethanol. LPS downregulated the expression of MIP-1alpha and MCP-1 mRNAs and upregulated RANTES mRNA in Kupffer cells at 3-h post endotoxin. The expression of mRNAs was further suppressed in ethanol plus the LPS-treated group. Ethanol also suppressed the LPS-mediated priming of Kupffer cells for enhanced CC-chemokine release in vitro. Ethanol alone significantly upregulated the expression of CC-chemokine mRNA, and primed the Kupffer cells for enhanced RANTES release. CC-chemokine release and mRNA expression in hepatic sinusoidal endothelial cells were not significantly altered by ethanol, except for MCP-1 release. These data show that acute ethanol may be beneficial in tissue injury during acute endotoxemia. JF - Alcohol (Fayetteville, N.Y.) AU - Bukara, M AU - Bautista, A P AD - Department of Physiology and NIAAA-Sponsored Alcohol Research Center, Louisiana State University Health Sciences Ceniter, New Orleans 70112, USA. Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 193 EP - 203 VL - 20 IS - 2 SN - 0741-8329, 0741-8329 KW - Bacterial Toxins KW - 0 KW - Chemokine CCL2 KW - Chemokine CCL3 KW - Chemokine CCL4 KW - Chemokine CCL5 KW - Endotoxins KW - Enterotoxins KW - Escherichia coli Proteins KW - Lipopolysaccharides KW - Macrophage Inflammatory Proteins KW - RNA, Messenger KW - heat-labile enterotoxin, E coli KW - Gadolinium KW - AU0V1LM3JT KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Index Medicus KW - Acute Disease KW - Leukocytes -- metabolism KW - Animals KW - Liver -- cytology KW - Endothelium -- metabolism KW - Alanine Transaminase -- metabolism KW - Lipopolysaccharides -- pharmacology KW - Kupffer Cells -- drug effects KW - Liver -- metabolism KW - RNA, Messenger -- biosynthesis KW - Endothelium -- cytology KW - Leukocytes -- drug effects KW - Rats KW - Bacterial Toxins -- antagonists & inhibitors KW - Flow Cytometry KW - Spleen -- drug effects KW - Male KW - Escherichia coli -- metabolism KW - Splenectomy KW - Spleen -- metabolism KW - Lipopolysaccharides -- antagonists & inhibitors KW - Bacterial Toxins -- pharmacology KW - Endothelium -- drug effects KW - Rats, Sprague-Dawley KW - Enterotoxins -- antagonists & inhibitors KW - Enterotoxins -- pharmacology KW - Kupffer Cells -- metabolism KW - Macrophage Inflammatory Proteins -- metabolism KW - Gadolinium -- pharmacology KW - Chemokine CCL5 -- biosynthesis KW - Endotoxins -- antagonists & inhibitors KW - Chemokine CCL2 -- biosynthesis KW - Chemokine CCL5 -- metabolism KW - Macrophage Inflammatory Proteins -- biosynthesis KW - Endotoxins -- pharmacology KW - Chemokine CCL2 -- metabolism KW - Alcoholic Intoxication -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70961013?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.atitle=Acute+alcohol+intoxication+and+gadolinium+chloride+attenuate+endotoxin-induced+release+of+CC+chemokines+in+the+rat.&rft.au=Bukara%2C+M%3BBautista%2C+A+P&rft.aulast=Bukara&rft.aufirst=M&rft.date=2000-02-01&rft.volume=20&rft.issue=2&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.issn=07418329&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-11 N1 - Date created - 2000-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of oxidative and nitrosative stress in cytotoxicity. AN - 70953397; 10709853 AB - Nitric oxide is a key bioregulatory agent in a wide variety of biological processes, yet it also can have cytotoxic properties. This dichotomy raises the question of how this potentially toxic species can be involved in so many fundamental physiological processes. This articles discusses how the chemistry of nitric oxide might pertain to its observed biology as it relates to oxidative and nitrosative stress in different mechanisms of cytotoxicity. JF - Seminars in perinatology AU - Wink, D A AU - Miranda, K M AU - Espey, M G AD - Radiation Biology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 20 EP - 23 VL - 24 IS - 1 SN - 0146-0005, 0146-0005 KW - Nitrogen Oxides KW - 0 KW - Nitric Oxide KW - 31C4KY9ESH KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Leukocytes -- metabolism KW - Animals KW - Humans KW - Nitrosation KW - Nitrogen Oxides -- toxicity KW - Leukocytes -- drug effects KW - Nitric Oxide -- toxicity KW - Oxygen -- toxicity KW - Oxidative Stress UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70953397?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+perinatology&rft.atitle=Effects+of+oxidative+and+nitrosative+stress+in+cytotoxicity.&rft.au=Wink%2C+D+A%3BMiranda%2C+K+M%3BEspey%2C+M+G&rft.aulast=Wink&rft.aufirst=D&rft.date=2000-02-01&rft.volume=24&rft.issue=1&rft.spage=20&rft.isbn=&rft.btitle=&rft.title=Seminars+in+perinatology&rft.issn=01460005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-29 N1 - Date created - 2000-03-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serum tocopherols, selenium and lung cancer risk among tin miners in China. AN - 70951739; 10710196 AB - To evaluate the association of prediagnostic serum antioxidants and lung cancer risk we conducted a case-control study nested in an occupational cohort of tin miners. Male workers free of cancer enrolled in the cohort. During up to 6 years of follow-up, 339 lung cancer cases were diagnosed and, among these cases, those who donated blood prospectively (n = 108) were eligible for this study. For each case, two controls alive and free of cancer at the time of case diagnosis were matched on age and date of blood collection. Overall, we observed no association between serum alpha-tocopherol, gamma-tocopherol or selenium levels and lung cancer risk. However, a significant gradient of decreasing lung cancer risk with increasing serum alpha-tocopherol was apparent for men less than 60 years old (odds ratio by tertile: 1.0, 0.9, 0.2; trend p = 0.002). Alpha-tocopherol was also protective in men who reported no alcohol drinking (OR by tertile: 1.0, 0.6, 0.3; trend p = 0.008). Although there were no significant overall associations between prospectively collected serum alpha-tocopherol, gamma-tocopherol or selenium and incidence of lung cancer, results from this study suggest that higher alpha-tocopherol levels may be protective in men less than 60 years old and in those who do not drink alcohol. JF - Cancer causes & control : CCC AU - Ratnasinghe, D AU - Tangrea, J A AU - Forman, M R AU - Hartman, T AU - Gunter, E W AU - Qiao, Y L AU - Yao, S X AU - Barett, M J AU - Giffen, C A AU - Erozan, Y AU - Tockman, M S AU - Taylor, P R AD - Cancer Prevention Studies Branch, Division of Clinical Sciences, National Cancer Institute, NIH, Bethesda 20892-7058, MD, USA. DR132K@NIH.gov Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 129 EP - 135 VL - 11 IS - 2 SN - 0957-5243, 0957-5243 KW - Biomarkers, Tumor KW - 0 KW - Vitamin E KW - 1406-18-4 KW - Tin KW - 7440-31-5 KW - Selenium KW - H6241UJ22B KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Sensitivity and Specificity KW - Humans KW - Aged KW - Longitudinal Studies KW - Risk Assessment KW - Age Distribution KW - Environmental Monitoring KW - Logistic Models KW - China -- epidemiology KW - Radon -- analysis KW - Adult KW - Cohort Studies KW - Case-Control Studies KW - Incidence KW - Middle Aged KW - Epidemiological Monitoring KW - Statistics, Nonparametric KW - Male KW - Selenium -- blood KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- diagnosis KW - Lung Neoplasms -- epidemiology KW - Occupational Diseases -- epidemiology KW - Mining KW - Biomarkers, Tumor -- blood KW - Vitamin E -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70951739?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Serum+tocopherols%2C+selenium+and+lung+cancer+risk+among+tin+miners+in+China.&rft.au=Ratnasinghe%2C+D%3BTangrea%2C+J+A%3BForman%2C+M+R%3BHartman%2C+T%3BGunter%2C+E+W%3BQiao%2C+Y+L%3BYao%2C+S+X%3BBarett%2C+M+J%3BGiffen%2C+C+A%3BErozan%2C+Y%3BTockman%2C+M+S%3BTaylor%2C+P+R&rft.aulast=Ratnasinghe&rft.aufirst=D&rft.date=2000-02-01&rft.volume=11&rft.issue=2&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-28 N1 - Date created - 2000-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Accelerated appearance of multiple B cell lymphoma types in NFS/N mice congenic for ecotropic murine leukemia viruses. AN - 70950052; 10701686 AB - Spontaneous lymphomas occur at high frequency in NFS x V+ mice, strains congenic for ecotropic murine leukemia virus (MuLV) proviral genes and expressing virus at high titer. In the present study, a total of 703 NFS x V+ lymphomas were studied by histopathology, immunophenotypic analysis, immunoglobulin heavy chain or T cell receptor beta chain rearrangements, and somatic ecotropic MuLV integrations; 90% of the lymphomas tested were of B cell lineage. Low-grade tumors included small lymphocytic, follicular, and splenic marginal zone lymphomas, while high-grade tumors comprised diffuse large-cell (centroblastic and immunoblastic types), splenic marginal zone, and lymphoblastic lymphomas. Comparison of mice of similar genetic background except for presence (NFS x V+) or absence (NFS x V-) of functional ecotropic MuLV genomes showed that NFS x V-clonal lymphomas developed at about one-half the rate of those occurring in NFS x V+ mice, and most were low-grade B cell lymphomas with extended latent periods. In NFS x V+ mice, clonal outgrowth, defined by Ig gene rearrangements, was associated with acquisition of somatic ecotropic proviral integrations, suggesting that, although generation of B cell clones can be virus independent, ecotropic virus may act to increase the rate of generation of clones and speed their evolution to lymphoma. The mechanism remains undefined, because only rare rearrangements were detected in several cellular loci previously associated with MuLV insertional mutagenesis. JF - Laboratory investigation; a journal of technical methods and pathology AU - Hartley, J W AU - Chattopadhyay, S K AU - Lander, M R AU - Taddesse-Heath, L AU - Naghashfar, Z AU - Morse, H C AU - Fredrickson, T N AD - The Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0760, USA. jhartley@NIAID.NIH.gov Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 159 EP - 169 VL - 80 IS - 2 SN - 0023-6837, 0023-6837 KW - Immunoglobulin Heavy Chains KW - 0 KW - Index Medicus KW - Animals KW - Blotting, Southern KW - Gene Rearrangement, beta-Chain T-Cell Antigen Receptor KW - Mice KW - Genome, Viral KW - Immunohistochemistry KW - Immunoglobulin Heavy Chains -- genetics KW - Leukemia Virus, Murine -- genetics KW - Lymphoma, B-Cell -- virology KW - Lymphoma, B-Cell -- pathology KW - Leukemia Virus, Murine -- isolation & purification KW - Lymphoma, B-Cell -- genetics KW - Lymphoma, B-Cell -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70950052?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.atitle=Accelerated+appearance+of+multiple+B+cell+lymphoma+types+in+NFS%2FN+mice+congenic+for+ecotropic+murine+leukemia+viruses.&rft.au=Hartley%2C+J+W%3BChattopadhyay%2C+S+K%3BLander%2C+M+R%3BTaddesse-Heath%2C+L%3BNaghashfar%2C+Z%3BMorse%2C+H+C%3BFredrickson%2C+T+N&rft.aulast=Hartley&rft.aufirst=J&rft.date=2000-02-01&rft.volume=80&rft.issue=2&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.issn=00236837&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-16 N1 - Date created - 2000-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Perspectives on surrogate end points in the development of drugs that reduce the risk of cancer. AN - 70948216; 10698472 AB - This paper proposes a scientific basis and possible strategy for applying surrogate end points in chemopreventive drug development. The potential surrogate end points for cancer incidence described are both phenotypic (at the tissue, cellular, and molecular levels) and genotypic biomarkers. To establish chemopreventive efficacy in randomized, placebo-controlled clinical trials, it is expected that in most cases it will be critical to ensure that virtually all of the biomarker lesions are prevented or that the lesions prevented are those with the potential to progress. This would require that both the phenotype and genotype of the target tissue in agent-treated subjects, especially in any new or remaining precancers, are equivalent to or show less progression than those of placebo-treated subjects. In the National Cancer Institute chemoprevention program, histological modulation of a precancer (intraepithelial neoplasia) has thus far been the primary phenotypic surrogate end point in chemoprevention trials. Additionally, we give high priority to biomarkers measuring specific and general genotypic changes correlating to the carcinogenesis progression model for the targeted cancer (e.g., progressive genomic instability as measured by loss of heterozygosity or amplification at a specific microsatellite loci). Other potential surrogate end points that may occur earlier in carcinogenesis are being analyzed in these precancers and in nearby normal appearing tissues. These biomarkers include proliferation and differentiation indices, specific gene and general chromosome damage, cell growth regulatory molecules, and biochemical activities (e.g., enzyme inhibition). Serum biomarkers also may be monitored (e.g., prostate-specific antigen) because of their accessibility. Potentially chemopreventive drug effects of the test agent also may be measured (e.g., tissue and serum estrogen levels in studies of steroid aromatase inhibitors). These initial studies are expected to expand the list of validated surrogate end points for future use. Continued discussion and research among the National Cancer Institute, the Food and Drug Administration, industry, and academia are needed to ensure that surrogate end point-based chemoprevention indications are feasible. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Kelloff, G J AU - Sigman, C C AU - Johnson, K M AU - Boone, C W AU - Greenwald, P AU - Crowell, J A AU - Hawk, E T AU - Doody, L A AD - Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 127 EP - 137 VL - 9 IS - 2 SN - 1055-9965, 1055-9965 KW - Antineoplastic Agents KW - 0 KW - Biomarkers, Tumor KW - Index Medicus KW - Humans KW - Treatment Outcome KW - Antineoplastic Agents -- therapeutic use KW - Research Design KW - Cell Transformation, Neoplastic KW - Biomarkers, Tumor -- analysis KW - Neoplasms -- prevention & control KW - Chemoprevention KW - Drug Design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70948216?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Perspectives+on+surrogate+end+points+in+the+development+of+drugs+that+reduce+the+risk+of+cancer.&rft.au=Kelloff%2C+G+J%3BSigman%2C+C+C%3BJohnson%2C+K+M%3BBoone%2C+C+W%3BGreenwald%2C+P%3BCrowell%2C+J+A%3BHawk%2C+E+T%3BDoody%2C+L+A&rft.aulast=Kelloff&rft.aufirst=G&rft.date=2000-02-01&rft.volume=9&rft.issue=2&rft.spage=127&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-29 N1 - Date created - 2000-03-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activity of the antimutagenic enzyme 8-oxo-2'-deoxyguanosine 5'-triphosphate pyrophosphohydrolase (8-oxo-dGTPase) in cultured chinese hamster ovary cells: effects of cell cycle, proliferation rate, and population density. AN - 70947228; 10699744 AB - Mammalian 8-oxo-2'-deoxyguanosine 5'-triphosphate pyrophosphohydrolases (8-oxo-dGTPases), such as MTH1, are believed to play the same antimutagenic role as their bacterial homologues, like MutT. Both decompose promutagenic 8-oxo-dGTP, a product of active oxygen's attack on dGTP. It is not known how 8-oxo-dGTPase expression and function are regulated. Therefore, we investigated the effect of cell population density, proliferation rate, and cell cycle phase on 8-oxo-dGTPase specific activity in cultured Chinese hamster ovary K1-BH4 (CHO) cells. With increasing cell population density (from 30 to 95% confluence), the activity of 8-oxo-dGTPase per milligram protein decreased by 33% (p =.007 by ANOVA) while cells shifted by 9% into the G(0)/G(1) phase, with a 5% drop in cells in S phase. Importantly, inhibition of the cells' proliferation rate by calf serum deprivation caused a more dramatic 23% shift toward the G(0)/G(1) phase and a 25% drop in S phase, but had no effect on 8-oxo-dGTPase activity. Likewise, no differences in the enzyme activity were observed within cell populations of different cell cycle phases separated by centrifugal elutriation. Thus, the present results exclude cell cycle-dependent regulation of 8-oxo-dGTPase activity in CHO cells or its simple dependence on proliferation rate. The observed decrease of 8-oxo-dGTPase activity with increasing cell population density might be related to augmentation of cell-to-cell contact. JF - Free radical biology & medicine AU - Bialkowski, K AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute-FCRDC, Frederick, MD, USA. karolb@monsun.amb.bydgoszcz.pl Y1 - 2000/02/01/ PY - 2000 DA - 2000 Feb 01 SP - 337 EP - 344 VL - 28 IS - 3 SN - 0891-5849, 0891-5849 KW - Antimutagenic Agents KW - 0 KW - Culture Media KW - Culture Media, Serum-Free KW - DNA KW - 9007-49-2 KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - 8-oxodGTPase KW - EC 3.6.1.55 KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Animals KW - Analysis of Variance KW - Kinetics KW - DNA -- metabolism KW - Resting Phase, Cell Cycle KW - CHO Cells KW - G1 Phase KW - DNA -- drug effects KW - Cricetinae KW - Cell Cycle -- physiology KW - Cell Division -- physiology KW - Phosphoric Monoester Hydrolases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70947228?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activity+of+the+antimutagenic+enzyme+8-oxo-2%27-deoxyguanosine+5%27-triphosphate+pyrophosphohydrolase+%288-oxo-dGTPase%29+in+cultured+chinese+hamster+ovary+cells%3A+effects+of+cell+cycle%2C+proliferation+rate%2C+and+population+density.&rft.au=Bialkowski%2C+K%3BKasprzak%2C+K+S&rft.aulast=Bialkowski&rft.aufirst=K&rft.date=2000-02-01&rft.volume=28&rft.issue=3&rft.spage=337&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 - 2000-04-11 N1 - Date created - 2000-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of photodynamic therapy in the treatment of recurrent superficial bladder cancer. AN - 70938843; 10696255 AB - Photodynamic therapy is an exciting area of research for the treatment of superficial bladder cancer. Significant responses have been seen in patients resistant to standard intravesical treatments. New areas of research are focused on the development of new sensitizers and light distribution methods with less dermal and bladder toxicity. JF - The Urologic clinics of North America AU - Walther, M M AD - Urologic Oncology Branch, National Institute of Health, Bethesda, Maryland, USA. macw@nih.gov Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 163 EP - 170 VL - 27 IS - 1 SN - 0094-0143, 0094-0143 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Treatment Outcome KW - Clinical Trials as Topic KW - Neoplasm Recurrence, Local -- therapy KW - Photochemotherapy -- adverse effects KW - Urinary Bladder Neoplasms -- therapy KW - Carcinoma in Situ -- therapy KW - Photochemotherapy -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70938843?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Urologic+clinics+of+North+America&rft.atitle=The+role+of+photodynamic+therapy+in+the+treatment+of+recurrent+superficial+bladder+cancer.&rft.au=Walther%2C+M+M&rft.aulast=Walther&rft.aufirst=M&rft.date=2000-02-01&rft.volume=27&rft.issue=1&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=The+Urologic+clinics+of+North+America&rft.issn=00940143&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-08 N1 - Date created - 2000-03-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Blood levels of organochlorines before and after chemotherapy among non-Hodgkin's lymphoma patients. AN - 70935951; 10698481 AB - Several small studies suggest a link between environmental exposure to organochlorine compounds and risk of non Hodgkin's lymphoma (NHL). Because NHL is uncommon, studies of the topic often use a population-based case-control design, in which cases generally are enrolled after treatment has begun. If chemotherapy affects blood levels of organochlorines, exposure will be misclassified and findings distorted. To determine whether chemotherapy alters serum levels of organochlorines in NHL cases, we compared serum samples before and after treatment in 22 cases diagnosed with NHL between March 1994 and August 1995 and enrolled in a clinical trial at the United States National Cancer Institute's Clinical Center. The time difference between pretreatment and posttreatment samples ranged from 15 to 27 months with an average of 20 months. Laboratory analyses were conducted in blinded pretreatment and posttreatment pairs of the subjects. Pretreatment and posttreatment organochlorine serum levels were compared using Pearson correlation coefficient (r) and paired t test. The pretreatment and posttreatment serum levels were highly correlated for 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and polychlorinated biphenyls (PCBs) PCB-138, PCB-153, PCB-156, and total PCBs (ranging from 0.78 to 0.93). Serum levels of all of these organochlorines significantly decreased between initiation and completion of chemotherapy, 25% for total PCB (P = 0.0044), 28% for DDE (P = 0.0014), 25% for PCB-138 (P = 0.0053), 27% for PCB-153 (P = 0.0031), and 29% for PCB-156 (P = 0.045). Neither weight change nor lipid change was correlated with changes in chemical levels. There was no association between the length of time between blood draws and changes in chemical levels. Our data raise the possibility that lymphoma treatment depresses serum organochlorine levels. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Baris, D AU - Kwak, L W AU - Rothman, N AU - Wilson, W AU - Manns, A AU - Tarone, R E AU - Hartge, P AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892-7240, USA. barisd@epndce.nci.nih.gov Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 193 EP - 197 VL - 9 IS - 2 SN - 1055-9965, 1055-9965 KW - Environmental Pollutants KW - 0 KW - Hydrocarbons, Chlorinated KW - Insecticides KW - Index Medicus KW - Body Weight KW - Risk Factors KW - Humans KW - Adult KW - Environmental Exposure KW - Case-Control Studies KW - Middle Aged KW - Male KW - Female KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Insecticides -- adverse effects KW - Lymphoma, Non-Hodgkin -- blood KW - Lymphoma, Non-Hodgkin -- etiology KW - Insecticides -- pharmacokinetics KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Environmental Pollutants -- blood KW - Environmental Pollutants -- pharmacokinetics KW - Environmental Pollutants -- adverse effects KW - Insecticides -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70935951?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Blood+levels+of+organochlorines+before+and+after+chemotherapy+among+non-Hodgkin%27s+lymphoma+patients.&rft.au=Baris%2C+D%3BKwak%2C+L+W%3BRothman%2C+N%3BWilson%2C+W%3BManns%2C+A%3BTarone%2C+R+E%3BHartge%2C+P&rft.aulast=Baris&rft.aufirst=D&rft.date=2000-02-01&rft.volume=9&rft.issue=2&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-29 N1 - Date created - 2000-03-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hairy cell leukemia, a B-cell neoplasm that is particularly sensitive to the cytotoxic effect of anti-Tac(Fv)-PE38 (LMB-2). AN - 70924619; 10690555 AB - Anti-Tac(Fv)-PE38 (LMB-2) is a recombinant, single-chain immunotoxin composed of the variable domains of the anti-Tac (anti-CD25) monoclonal antibody fused to a truncated form of Pseudomonas exotoxin (PE). Until now, this agent has been reported to be very cytotoxic toward T-cell but not B-cell leukemic cells freshly obtained from patients and is being tested clinically in patients with CD25+ malignancies of both B- and T-cell origin. Hairy cell leukemia (HCL) is a B-cell malignancy in which the cells are usually CD25+ and their ex vivo sensitivity to LMB-2 was unknown. Malignant cells from the first HCL patient to be tested were very sensitive to the cytotoxic effect of LMB-2 in vitro (IC50, 1.1 ng/ml), and this patient responded clinically to LMB-2 administered systemically. Therefore, we decided to assess the potential clinical utility of LMB-2 in other patients with HCL. We tested fresh leukemic cells from nine additional CD25+ HCL patients. LMB-2 was very cytotoxic ex vivo in all patients with IC50s as low as 0.5 ng/ml. Malignant cells freshly obtained from patients with chronic lymphocytic leukemia were also sensitive to LMB-2 but not as sensitive as cells from HCL patients. These results indicate that CD25+ HCL is a B-cell neoplasm that is particularly sensitive to LMB-2, and this agent may be useful in patients who have failed standard therapies. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Robbins, D H AU - Margulies, I AU - Stetler-Stevenson, M AU - Kreitman, R J AD - Laboratory of Clinical Pathology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 693 EP - 700 VL - 6 IS - 2 SN - 1078-0432, 1078-0432 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD KW - B3(Fv)-PE38KDEL recombinant immunotoxin KW - Exotoxins KW - Immunotoxins KW - Index Medicus KW - Antigens, CD -- analysis KW - Humans KW - Aged KW - Leukemia, T-Cell -- blood KW - Leukemia, T-Cell -- immunology KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Adult KW - Middle Aged KW - Flow Cytometry KW - Immunophenotyping KW - Male KW - Female KW - Leukemia, T-Cell -- pathology KW - Leukemia, Hairy Cell -- blood KW - Immunotoxins -- toxicity KW - Leukemia, Lymphocytic, Chronic, B-Cell -- blood KW - Leukemia, Hairy Cell -- pathology KW - Leukemia, Lymphocytic, Chronic, B-Cell -- immunology KW - Leukemia, Lymphocytic, Chronic, B-Cell -- pathology KW - Leukemia, Hairy Cell -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70924619?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hairy+cell+leukemia%2C+a+B-cell+neoplasm+that+is+particularly+sensitive+to+the+cytotoxic+effect+of+anti-Tac%28Fv%29-PE38+%28LMB-2%29.&rft.au=Robbins%2C+D+H%3BMargulies%2C+I%3BStetler-Stevenson%2C+M%3BKreitman%2C+R+J&rft.aulast=Robbins&rft.aufirst=D&rft.date=2000-02-01&rft.volume=6&rft.issue=2&rft.spage=693&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 - 2000-03-28 N1 - Date created - 2000-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence for stimulation of adenylyl cyclase by an activated G(s) heterotrimer in cell membranes: an experimental method for controlling the G(s) subunit composition of cell membranes. AN - 70924440; 10679580 AB - Heterotrimeric (alphabetagamma) G(s) mediates agonist-induced stimulation of adenylyl cyclase (AC). Cholera toxin (CTx) will ADP-ribosylate the alpha-subunit of G(s) (G(s)alpha). G(s)alpha-deficient cyc(-) membranes were "stripped" of Gbeta. When the stripped cyc(-) were incubated with G(s)alpha and/or Gbetagamma, each was incorporated into the membranes independently of the other. Both G(s)alpha and Gbetagamma had to be present in the membranes, and they had to be able to form a heterotrimer in order for CTx to ADP-ribosylate G(s)alpha, indicating that the membrane bound G(s) heterotrimer is a substrate for CTx, but the G(s)alpha subunit by itself is not. When G(s)alpha was completely and irreversibly activated with GTPgammaS and incorporated into stripped cyc(-), it was a poor substrate for CTx and a weak stimulator of AC unless Gbetagamma was also incorporated. Furthermore, the level of AC stimulation corresponded to the amount of G(s) heterotrimer that was formed in the membranes from GTPgammaS-activated G(s)alpha and Gbetagamma. These data suggest that AC is stimulated by an activated G(s) heterotrimer in cell membranes. JF - Cellular signalling AU - Ganpat, M M AU - Nishimura, M AU - Toyoshige, M AU - Okuya, S AU - Pointer, R H AU - Rebois, R V AD - Membrane Biochemistry Section, Laboratory of Molecular and Cellular Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4440, USA. Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 113 EP - 122 VL - 12 IS - 2 SN - 0898-6568, 0898-6568 KW - Adjuvants, Immunologic KW - 0 KW - Detergents KW - G-protein Beta gamma KW - GTP-Binding Protein beta Subunits KW - GTP-Binding Protein gamma Subunits KW - Membrane Proteins KW - polidocanol KW - 0AWH8BFG9A KW - Guanosine Diphosphate KW - 146-91-8 KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - Polyethylene Glycols KW - 30IQX730WE KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Cholera Toxin KW - 9012-63-9 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - GTP-Binding Protein alpha Subunits, Gs KW - EC 3.6.5.1 KW - Heterotrimeric GTP-Binding Proteins KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Index Medicus KW - Cytological Techniques KW - Membrane Proteins -- metabolism KW - Cholera Toxin -- pharmacology KW - GTP-Binding Proteins -- pharmacology KW - Detergents -- pharmacology KW - Adjuvants, Immunologic -- pharmacology KW - Polyethylene Glycols -- pharmacology KW - Guanosine Diphosphate -- pharmacology KW - Adenosine Diphosphate Ribose -- metabolism KW - Guanosine 5'-O-(3-Thiotriphosphate) -- pharmacology KW - Signal Transduction -- physiology KW - Signal Transduction -- drug effects KW - Adenylyl Cyclases -- metabolism KW - Heterotrimeric GTP-Binding Proteins -- metabolism KW - GTP-Binding Protein alpha Subunits, Gs -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70924440?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+signalling&rft.atitle=Evidence+for+stimulation+of+adenylyl+cyclase+by+an+activated+G%28s%29+heterotrimer+in+cell+membranes%3A+an+experimental+method+for+controlling+the+G%28s%29+subunit+composition+of+cell+membranes.&rft.au=Ganpat%2C+M+M%3BNishimura%2C+M%3BToyoshige%2C+M%3BOkuya%2C+S%3BPointer%2C+R+H%3BRebois%2C+R+V&rft.aulast=Ganpat&rft.aufirst=M&rft.date=2000-02-01&rft.volume=12&rft.issue=2&rft.spage=113&rft.isbn=&rft.btitle=&rft.title=Cellular+signalling&rft.issn=08986568&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-24 N1 - Date created - 2000-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radiation dose to otologic structures during head and neck cancer radiation therapy. AN - 70921747; 10680919 AB - Otologic structures are often contained within head and neck cancer radiation treatment ports. The dosimetry to otologic structures has not been routinely analyzed and radiation treatment planning does not currently attempt to specifically avoid the inner ear structures when dosimetry is calculated. Recent studies demonstrate that up to 30% of patients experience sensorineural hearing loss on multimodality therapy with cisplatin and radiation. In the current case series, radiation dosimetry to otologic structures was calculated from computed tomogram treatment plans on patients. Fifteen nasopharyngeal, oral cavity, oropharyngeal, and hypopharyngeal cancer patients were analyzed. Between 8% and 102% of the total dose is delivered to the petrous bone/cochlea, with 4 of 15 patients getting more than 50% of the dose to at least one cochlea The mastoid air cells received between 3% and 75% of the total dose, with higher doses being delivered to patients with bulky high neck metastases or nasopharyngeal tumors. The eustachian tubes received between 20% and 102% of the total dose, with 10 of 15 patients receiving more than 50% of the dose to this anatomic site. We conclude that the cochlea and eustachian tubes receive significant radiation during treatment, particularly in nasopharyngeal cancer patients. Careful design of radiation treatment ports may allow for the reduction of radiation to hearing structures. JF - The Laryngoscope AU - Ondrey, F G AU - Greig, J R AU - Herscher, L AD - Head and Neck Surgery Branch of the National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 217 EP - 221 VL - 110 IS - 2 Pt 1 SN - 0023-852X, 0023-852X KW - Index Medicus KW - Radiometry KW - Radiotherapy Dosage KW - Humans KW - Mastoid -- radiation effects KW - Carcinoma, Squamous Cell -- radiotherapy KW - Radiotherapy -- adverse effects KW - Petrous Bone -- radiation effects KW - Radiotherapy Planning, Computer-Assisted KW - Cochlea -- radiation effects KW - Mouth Neoplasms -- radiotherapy KW - Pharyngeal Neoplasms -- radiotherapy KW - Hearing Loss, Sensorineural -- etiology KW - Eustachian Tube -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70921747?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Laryngoscope&rft.atitle=Radiation+dose+to+otologic+structures+during+head+and+neck+cancer+radiation+therapy.&rft.au=Ondrey%2C+F+G%3BGreig%2C+J+R%3BHerscher%2C+L&rft.aulast=Ondrey&rft.aufirst=F&rft.date=2000-02-01&rft.volume=110&rft.issue=2+Pt+1&rft.spage=217&rft.isbn=&rft.btitle=&rft.title=The+Laryngoscope&rft.issn=0023852X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-01 N1 - Date created - 2000-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pretreatment with DNA-damaging agents permits selective killing of checkpoint-deficient cells by microtubule-active drugs. AN - 70921487; 10683383 AB - Cell-cycle checkpoint mechanisms, including the p53- and p21-dependent G(2) arrest that follows DNA damage, are often lost during tumorigenesis. We have exploited the ability of DNA-damaging drugs to elicit this checkpoint, and we show here that such treatment allows microtubule drugs, which cause cell death secondary to mitotic arrest, to kill checkpoint-deficient tumor cells while sparing checkpoint-competent cells. Low doses of the DNA-damaging drug doxorubicin cause predominantly G(2) arrest without killing HCT116 cells that harbor wt p53. Doxorubicin treatment prevented mitotic arrest, Bcl-2 phosphorylation, and cell death caused by paclitaxel, epothilones, and vinblastine. In contrast, doxorubicin enhanced cytotoxicity of FR901228, an agent that does not affect microtubules. Low doses of doxorubicin did not arrest p21-deficient clones of HCT116 cells and did not protect these cells from cytotoxicity caused by microtubule drugs, but cells in which p21 expression was restored enjoyed partial protection under these conditions. Moreover, in p53-deficient clones of HCT116 cells doxorubicin did not induce either p53 or p21 and provided no protection against paclitaxel-induced cytotoxicity. Therefore, (a) p53-dependent p21 induction caused by doxorubicin protects from microtubule drug-induced cytotoxicity, and (b) pretreatment with cytostatic doses of DNA-damaging drugs before treatment with microtubule drugs results in selective cytotoxicity to cancer cells with defective p53/p21-dependent checkpoint. JF - The Journal of clinical investigation AU - Blagosklonny, M V AU - Robey, R AU - Bates, S AU - Fojo, T AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. mikhailb@box-m.nih.gov Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 533 EP - 539 VL - 105 IS - 4 SN - 0021-9738, 0021-9738 KW - Antineoplastic Agents KW - 0 KW - CDKN1A protein, human KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Epoxy Compounds KW - Mutagens KW - Thiazoles KW - Tumor Suppressor Protein p53 KW - Vinblastine KW - 5V9KLZ54CY KW - Doxorubicin KW - 80168379AG KW - Paclitaxel KW - P88XT4IS4D KW - Abridged Index Medicus KW - Index Medicus KW - Vinblastine -- pharmacology KW - Drug Interactions KW - Humans KW - Cell Division -- drug effects KW - Paclitaxel -- pharmacology KW - Tumor Suppressor Protein p53 -- metabolism KW - Thiazoles -- pharmacology KW - Doxorubicin -- pharmacology KW - Tumor Cells, Cultured KW - Epoxy Compounds -- pharmacology KW - Cyclins -- metabolism KW - Tumor Suppressor Protein p53 -- genetics KW - Colonic Neoplasms KW - Cyclins -- genetics KW - Microtubules -- drug effects KW - Mutagens -- pharmacology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70921487?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pretreatment+with+DNA-damaging+agents+permits+selective+killing+of+checkpoint-deficient+cells+by+microtubule-active+drugs.&rft.au=Blagosklonny%2C+M+V%3BRobey%2C+R%3BBates%2C+S%3BFojo%2C+T&rft.aulast=Blagosklonny&rft.aufirst=M&rft.date=2000-02-01&rft.volume=105&rft.issue=4&rft.spage=533&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 - 2000-03-09 N1 - Date created - 2000-03-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Clin Invest. 1999 Dec;104(11):1503-6 [10587513] Science. 1999 Sep 10;285(5434):1733-7 [10481009] J Clin Invest. 1999 Dec;104(12):1655-61 [10606616] Cell. 1990 Jun 1;61(5):759-67 [2188735] Cancer Res. 1991 Dec 1;51(23 Pt 1):6304-11 [1933891] Trends Pharmacol Sci. 1992 Apr;13(4):134-6 [1350385] Cell. 1992 Aug 21;70(4):523-6 [1505019] Nature. 1993 Apr 29;362(6423):849-52 [8479523] Cell. 1993 Sep 24;74(6):957-67 [8402885] Cell. 1993 Nov 19;75(4):817-25 [8242752] J Antibiot (Tokyo). 1994 Mar;47(3):315-23 [8175484] Cell. 1994 Aug 26;78(4):539-42 [8069905] Science. 1994 Nov 4;266(5186):807-10 [7973635] N Engl J Med. 1995 Apr 13;332(15):1004-14 [7885406] Cancer Metastasis Rev. 1995 Mar;14(1):3-15 [7606818] Cell. 1995 Aug 25;82(4):675-84 [7664346] Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8493-7 [7667317] Nature. 1995 Oct 12;377(6549):552-7 [7566157] Cancer Res. 1995 Nov 15;55(22):5187-90 [7585571] Curr Opin Oncol. 1995 Nov;7(6):547-53 [8547404] Nature. 1996 Jun 20;381(6584):713-6 [8649519] Cell. 1997 Feb 7;88(3):323-31 [9039259] Cancer Res. 1997 Oct 1;57(19):4285-300 [9331090] Oncogene. 1997 Dec 4;15(23):2867-75 [9419978] Curr Opin Cell Biol. 1998 Feb;10(1):123-30 [9484604] Biochem Biophys Res Commun. 1998 Mar 17;244(2):368-73 [9514935] Exp Cell Res. 1998 May 25;241(1):126-33 [9633520] Mol Cell. 1997 Dec;1(1):3-11 [9659898] Cancer Res. 1998 Aug 15;58(16):3620-6 [9721870] Science. 1998 Nov 20;282(5393):1497-501 [9822382] Mol Cell. 1998 Nov;2(5):581-91 [9844631] Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3706-11 [10097101] Mol Pharmacol. 1999 Jun;55(6):1088-93 [10347252] J Clin Invest. 1999 Aug;104(3):263-9 [10430607] Cancer Res. 1999 Aug 1;59(15):3831-7 [10447002] Int J Cancer. 1999 Oct 8;83(2):151-6 [10471519] J Clin Invest. 1999 Dec;104(12):1645-53 [10606615] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I and pharmacokinetic study of farnesyl protein transferase inhibitor R115777 in advanced cancer. AN - 70913551; 10673536 AB - To determine the maximum-tolerated dose, toxicities, and pharmacokinetic profile of the farnesyl protein transferase inhibitor R115777 when administered orally bid for 5 days every 2 weeks. Twenty-seven patients with a median age of 58 years received 85 cycles of R115777 using an intrapatient and interpatient dose escalation schema. Drug was administered orally at escalating doses as a solution (25 to 850 mg bid) or as pellet capsules (500 to 1300 mg bid). Pharmacokinetics were assessed after the first dose and the last dose administered during cycle 1. Dose-limiting toxicity of grade 3 neuropathy was observed in one patient and grade 2 fatigue (decrease in two performance status levels) was seen in four of six patients treated with 1,300 mg bid. The most frequent clinical grade 2 or 3 adverse events in any cycle included nausea, vomiting, headache, fatigue, anemia, and hypotension. Myelosuppression was mild and infrequent. Peak plasma concentrations of R115777 were achieved within 0.5 to 4 hours after oral drug administration. The elimination of R115777 from plasma was biphasic, with sequential half-lives of about 5 hours and 16 hours. There was little drug accumulation after bid dosing, and steady-state concentrations were achieved within 2 to 3 days. The pharmacokinetics were dose proportional in the 25 to 325 mg/dose range for the oral solution. Urinary excretion of unchanged R115777 was less than 0.1% of the oral dose. One patient with metastatic colon cancer treated at the 500-mg bid dose had a 46% decrease in carcinoembryonic antigen levels, improvement in cough, and radiographically stable disease for 5 months. R115777 is bioavailable after oral administration and has an acceptable toxicity profile. Based upon pharmacokinetic data, the recommended dose for phase II trials is 500 mg orally bid (total daily dose, 1, 000 mg) for 5 consecutive days followed by 9 days of rest. Studies of continuous dosing and studies of R115777 in combination with chemotherapy are ongoing. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Zujewski, J AU - Horak, I D AU - Bol, C J AU - Woestenborghs, R AU - Bowden, C AU - End, D W AU - Piotrovsky, V K AU - Chiao, J AU - Belly, R T AU - Todd, A AU - Kopp, W C AU - Kohler, D R AU - Chow, C AU - Noone, M AU - Hakim, F T AU - Larkin, G AU - Gress, R E AU - Nussenblatt, R B AU - Kremer, A B AU - Cowan, K H AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD, USA. Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 927 EP - 941 VL - 18 IS - 4 SN - 0732-183X, 0732-183X KW - Capsules KW - 0 KW - Enzyme Inhibitors KW - Quinolones KW - Solutions KW - Alkyl and Aryl Transferases KW - EC 2.5.- KW - Farnesyltranstransferase KW - EC 2.5.1.29 KW - tipifarnib KW - MAT637500A KW - Index Medicus KW - Hypotension -- chemically induced KW - Administration, Oral KW - Drug Administration Schedule KW - Humans KW - Vomiting -- chemically induced KW - Anemia -- chemically induced KW - Fatigue -- chemically induced KW - Metabolic Clearance Rate KW - Aged KW - Peripheral Nervous System Diseases -- chemically induced KW - Biological Availability KW - Nausea -- chemically induced KW - Headache -- chemically induced KW - Half-Life KW - Adult KW - Middle Aged KW - Bone Marrow -- drug effects KW - Male KW - Female KW - Quinolones -- adverse effects KW - Neoplasms -- drug therapy KW - Enzyme Inhibitors -- adverse effects KW - Enzyme Inhibitors -- therapeutic use KW - Quinolones -- therapeutic use KW - Quinolones -- pharmacokinetics KW - Enzyme Inhibitors -- pharmacokinetics KW - Alkyl and Aryl Transferases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70913551?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+I+and+pharmacokinetic+study+of+farnesyl+protein+transferase+inhibitor+R115777+in+advanced+cancer.&rft.au=Zujewski%2C+J%3BHorak%2C+I+D%3BBol%2C+C+J%3BWoestenborghs%2C+R%3BBowden%2C+C%3BEnd%2C+D+W%3BPiotrovsky%2C+V+K%3BChiao%2C+J%3BBelly%2C+R+T%3BTodd%2C+A%3BKopp%2C+W+C%3BKohler%2C+D+R%3BChow%2C+C%3BNoone%2C+M%3BHakim%2C+F+T%3BLarkin%2C+G%3BGress%2C+R+E%3BNussenblatt%2C+R+B%3BKremer%2C+A+B%3BCowan%2C+K+H&rft.aulast=Zujewski&rft.aufirst=J&rft.date=2000-02-01&rft.volume=18&rft.issue=4&rft.spage=927&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 - 2000-07-13 N1 - Date created - 2000-07-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Combination therapy with amprenavir, abacavir, and efavirenz in human immunodeficiency virus (HIV)-infected patients failing a protease-inhibitor regimen: pharmacokinetic drug interactions and antiviral activity. AN - 70905922; 10671334 AB - Patients with plasma viral RNA >50,000 copies/mL, despite a protease-inhibitor regimen, received abacavir, amprenavir, and efavirenz to assess efavirenz-amprenavir drug interactions and to evaluate safety and antiviral response. Patients first received amprenavir with abacavir and other nucleoside analogs. Amprenavir levels were measured before and after adding efavirenz. Patients then received a second protease inhibitor. There was evidence of genotypic and phenotypic resistance at study entry. No patient had study drugs discontinued because of toxicity. Efavirenz decreased the steady-state area under the curve, maximum plasma concentration, and minimum plasma concentration of amprenavir by 24%, 33%, and 43%, respectively. Three of 10 patients had >1.5 log10 viral response to abacavir and amprenavir. All 8 patients who added efavirenz had >0.5 log10 decline in viral load, and this response lasted >24 weeks for 3 of the patients. A combination regimen that included abacavir, amprenavir, and efavirenz was well tolerated and had sustained activity in some patients. Concomitant efavirenz therapy decreases amprenavir concentrations. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Falloon, J AU - Piscitelli, S AU - Vogel, S AU - Sadler, B AU - Mitsuya, H AU - Kavlick, M F AU - Yoshimura, K AU - Rogers, M AU - LaFon, S AU - Manion, D J AU - Lane, H C AU - Masur, H AD - National Institute of Allergy and Infectious Diseases, Bethesda, MD, 20892-1880, USA. jfalloon@nih.gov Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 313 EP - 318 VL - 30 IS - 2 SN - 1058-4838, 1058-4838 KW - Antiviral Agents KW - 0 KW - Benzoxazines KW - Carbamates KW - Dideoxynucleosides KW - Oxazines KW - RNA, Viral KW - Sulfonamides KW - amprenavir KW - 5S0W860XNR KW - efavirenz KW - JE6H2O27P8 KW - abacavir KW - WR2TIP26VS KW - Index Medicus KW - AIDS/HIV KW - Drug Interactions KW - Area Under Curve KW - Humans KW - Drug Resistance KW - Pilot Projects KW - Viral Load KW - Phenotype KW - Drug Therapy, Combination KW - Genotype KW - Base Sequence KW - Adult KW - Treatment Outcome KW - Molecular Sequence Data KW - Middle Aged KW - Mutation KW - Male KW - RNA, Viral -- analysis KW - Oxazines -- pharmacokinetics KW - Antiviral Agents -- administration & dosage KW - HIV-1 -- genetics KW - Oxazines -- administration & dosage KW - HIV Infections -- virology KW - HIV-1 -- isolation & purification KW - HIV Infections -- mortality KW - Sulfonamides -- administration & dosage KW - Dideoxynucleosides -- pharmacokinetics KW - Sulfonamides -- pharmacokinetics KW - Antiviral Agents -- pharmacokinetics KW - HIV Infections -- drug therapy KW - Dideoxynucleosides -- administration & dosage KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70905922?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Combination+therapy+with+amprenavir%2C+abacavir%2C+and+efavirenz+in+human+immunodeficiency+virus+%28HIV%29-infected+patients+failing+a+protease-inhibitor+regimen%3A+pharmacokinetic+drug+interactions+and+antiviral+activity.&rft.au=Falloon%2C+J%3BPiscitelli%2C+S%3BVogel%2C+S%3BSadler%2C+B%3BMitsuya%2C+H%3BKavlick%2C+M+F%3BYoshimura%2C+K%3BRogers%2C+M%3BLaFon%2C+S%3BManion%2C+D+J%3BLane%2C+H+C%3BMasur%2C+H&rft.aulast=Falloon&rft.aufirst=J&rft.date=2000-02-01&rft.volume=30&rft.issue=2&rft.spage=313&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=10584838&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-12 N1 - Date created - 2000-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopaminergic involvement in the discriminative-stimulus effects of methamphetamine in rats. AN - 70895343; 10663437 AB - Dopamine plays a major role in the behavioral effects of methamphetamine. In the present experiments, the effects of different dopaminergic agonists, antagonists, and uptake inhibitors were evaluated in rats discriminating methamphetamine from saline. In Sprague-Dawley rats trained to discriminate 1.0 mg/kg methamphetamine, i.p., from saline under a fixed-ratio schedule of food delivery, the ability of various dopaminergic agonists and uptake inhibitors to substitute for methamphetamine was evaluated. Subsequently, the ability of various dopaminergic antagonists to block the discriminative-stimulus effects of the training dose of methamphetamine was tested. The dopamine-uptake inhibitors cocaine (10.0 mg/kg), nomifensine (3.0 mg/kg), GBR-12909 (18.0 mg/kg), and bupropion (30.0 mg/kg) fully substituted for the 1.0 mg/kg training dose of methamphetamine. Chloro-APB (SKF-82958), a full agonist at D1 dopamine receptors, produced about 85% methamphetamine-appropriate responding, but the dose required (0.18 mg/kg) markedly decreased rates of responding. Chloro-PB (SKF-81297), another agonist at D1 receptors with a lower intrinsic activity than Chloro-APB, produced only partial generalization (maximum about 55%) at a dose of 1.0 mg/kg. Full substitution for the training dose of methamphetamine was observed with 0.03 mg/kg of the D2 agonist NPA and 0.56 mg/kg of the D3/D2 agonist 7-OH-DPAT. Both NPA and 7-OH-DPAT markedly decreased rates of responding at these doses. The D1 antagonist SCH-23390 (0.056 mg/kg), the D2 antagonist spiperone (0.18 mg/kg), and the mixed D1, D2 antagonist cis-flupenthixol (0.56 mg/kg) all completely blocked the discriminative-stimulus actions of the training dose of methamphetamine. The present findings in rats support previous research findings in other species indicating a major role of dopamine in the discriminative-stimulus effects of methamphetamine. These findings further indicate involvement of dopamine uptake sites as well as D1 and D2 receptors. JF - Psychopharmacology AU - Munzar, P AU - Goldberg, S R AD - Preclinical Pharmacology Section, Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 209 EP - 216 VL - 148 IS - 2 SN - 0033-3158, 0033-3158 KW - Dopamine Agonists KW - 0 KW - Dopamine Antagonists KW - Dopamine D2 Receptor Antagonists KW - Dopamine Uptake Inhibitors KW - Receptors, Dopamine D1 KW - Receptors, Dopamine D2 KW - Methamphetamine KW - 44RAL3456C KW - Index Medicus KW - Substance-Related Disorders -- physiopathology KW - Injections, Intraperitoneal KW - Animals KW - Dose-Response Relationship, Drug KW - Disease Models, Animal KW - Rats KW - Behavior, Animal -- drug effects KW - Rats, Sprague-Dawley KW - Receptors, Dopamine D1 -- agonists KW - Receptors, Dopamine D1 -- antagonists & inhibitors KW - Receptors, Dopamine D2 -- agonists KW - Male KW - Discrimination Learning -- drug effects KW - Methamphetamine -- administration & dosage KW - Dopamine Agonists -- pharmacology KW - Dopamine Antagonists -- pharmacology KW - Methamphetamine -- agonists KW - Methamphetamine -- antagonists & inhibitors KW - Dopamine Uptake Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70895343?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Dopaminergic+involvement+in+the+discriminative-stimulus+effects+of+methamphetamine+in+rats.&rft.au=Munzar%2C+P%3BGoldberg%2C+S+R&rft.aulast=Munzar&rft.aufirst=P&rft.date=2000-02-01&rft.volume=148&rft.issue=2&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-10 N1 - Date created - 2000-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genomic imbalance in rat mammary gland carcinomas induced by 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine. AN - 70894918; 10657900 AB - 2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), a compound found in cooked meat, is a mammary gland carcinogen in female Sprague-Dawley rats. PhIP-induced rat mammary gland carcinomas were examined for mutations in several genes (exons) known to regulate cell growth and apoptosis, including p53 (4-8), p21(Waf1) (coding region), Apc (14, 15), B-catenin (3), E-cadherin (9,13,15), Bcl-x (coding region), Bax (3), IGFIIR (28), and TGFBIIR (3). DNA from 30 carcinomas was examined by single-strand conformation polymorphism analysis, but no mutations were detected in these genes or gene regions. DNA from carcinomas and matching normal tissue were further screened for allelic imbalance by using a polymerase chain reaction-based approach with primers to known microsatellite regions located throughout the rat genome. Of 53 markers examined, 12 revealed allelic imbalance. Microsatellite instability (MSI) was detected at two markers, one on chromosome 4 and one on chromosome 6. Sixty-five percent and 96% of all carcinomas examined (N=23) showed MSI at these loci on chromosomes 4 and 6, respectively, supporting the notion that MSI plays a role in PhIP-induced mammary carcinogenesis. Loss of heterozygosity (LOH), an indication of a possible tumor suppressor gene, was observed at 10 markers distributed on chromosomes 3, 10, 11, 14, and X. The frequency of LOH at these markers was 75-94%, supporting that the regions of allelic imbalance were largely similar for the PhIP-induced carcinomas examined in this study. When PhIP-induced carcinomas from rats placed on high-fat and low-fat diet were compared, no unique regions of allelic imbalance or statistical differences in the frequency of allelic imbalance were observed. Therefore, the high-fat diet, known to be a promoter of PhIP-induced rat mammary carcinogenesis, did not appear to influence allelic imbalance in the carcinomas. Interestingly, 7,12-dimethylbenz[a]-anthracene-induced mammary carcinomas did not show allelic imbalance at 11 of the 12 loci that showed allelic imbalance in PhIP-induced carcinomas. These findings suggest that distinct chemical carcinogens induce different patterns of allelic imbalance during rat mammary carcinogenesis. Since several of the known genes involved in carcinogenesis did not harbor mutations in PhIP-induced carcinomas, further studies are needed to clarify the critical genes involved in PhIP-induced mammary carcinogenesis and to determine whether regions of LOH harbor potentially novel tumor suppressor genes involved in this disease. Copyright 2000 Wiley-Liss, Inc. JF - Molecular carcinogenesis AU - Yu, M AU - Ryu, D Y AU - Snyderwine, E G AD - Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 76 EP - 83 VL - 27 IS - 2 SN - 0899-1987, 0899-1987 KW - Carcinogens KW - 0 KW - DNA, Neoplasm KW - Dietary Fats KW - Imidazoles KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Diet, Fat-Restricted KW - Microsatellite Repeats -- drug effects KW - DNA Mutational Analysis KW - Dietary Fats -- administration & dosage KW - Loss of Heterozygosity -- genetics KW - Trinucleotide Repeat Expansion -- drug effects KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Carcinogens -- pharmacology KW - Imidazoles -- pharmacology KW - Mammary Neoplasms, Experimental -- genetics KW - DNA, Neoplasm -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70894918?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+carcinogenesis&rft.atitle=Genomic+imbalance+in+rat+mammary+gland+carcinomas+induced+by+2-amino-1-methyl-6-phenylimidazo%284%2C5-b%29pyridine.&rft.au=Yu%2C+M%3BRyu%2C+D+Y%3BSnyderwine%2C+E+G&rft.aulast=Yu&rft.aufirst=M&rft.date=2000-02-01&rft.volume=27&rft.issue=2&rft.spage=76&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-25 N1 - Date created - 2000-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Roles of nuclear factor kappaB in neuronal survival and plasticity. AN - 70886786; 10646495 AB - The transcription factor nuclear factor kappaB (NF-kappaB) is moving to the forefront of the fields of apoptosis and neuronal plasticity because of recent findings showing that activation of NF-kappaB prevents neuronal apoptosis in various cell culture and in vivo models and because NF-kappaB is activated in association with synaptic plasticity. Activation of NF-kappaB was first shown to mediate antiapoptotic actions of tumor necrosis factor in cultured neurons and was subsequently shown to prevent death of various nonneuronal cells. NF-kappaB is activated by several cytokines and neurotrophic factors and in response to various cell stressors. Oxidative stress and elevation of intracellular calcium levels are particularly important inducers of NF-kappaB activation. Activation of NF-kappaB can interrupt apoptotic biochemical cascades at relatively early steps, before mitochondrial dysfunction and oxyradical production. Gene targets for NF-kappaB that may mediate its antiapoptotic actions include the antioxidant enzyme manganese superoxide dismutase, members of the inhibitor of apoptosis family of proteins, and the calcium-binding protein calbindin D28k. NF-kappaB is activated by synaptic activity and may play important roles in the process of learning and memory. The available data identify NF-kappaB as an important regulator of evolutionarily conserved biochemical and molecular cascades designed to prevent cell death and promote neuronal plasticity. Because NF-kappaB may play roles in a range of neurological disorders that involve neuronal degeneration and/or perturbed synaptic function, pharmacological and genetic manipulations of NF-kappaB signaling are being developed that may prove valuable in treating disorders ranging from Alzheimer's disease to schizophrenia. JF - Journal of neurochemistry AU - Mattson, M P AU - Culmsee, C AU - Yu, Z AU - Camandola, S AD - Sanders-Brown Research Center on Aging and Department of Anatomy and Neurobiology, University of Kentucky, Lexington, USA. mattsonm@grc.nia.nih.gov Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 443 EP - 456 VL - 74 IS - 2 SN - 0022-3042, 0022-3042 KW - NF-kappa B KW - 0 KW - Neurotoxins KW - Index Medicus KW - Animals KW - Synapses -- physiology KW - Humans KW - Apoptosis -- physiology KW - Neurotoxins -- antagonists & inhibitors KW - Cell Survival -- physiology KW - Neurons -- physiology KW - Neuronal Plasticity -- physiology KW - NF-kappa B -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70886786?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Roles+of+nuclear+factor+kappaB+in+neuronal+survival+and+plasticity.&rft.au=Mattson%2C+M+P%3BCulmsee%2C+C%3BYu%2C+Z%3BCamandola%2C+S&rft.aulast=Mattson&rft.aufirst=M&rft.date=2000-02-01&rft.volume=74&rft.issue=2&rft.spage=443&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 - 2000-02-10 N1 - Date created - 2000-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Profile of genetic alterations and tumorigenicity of human breast cancer cells. AN - 70884431; 10639563 AB - The profile of genetic alterations in four breast carcinoma cell lines, SK-BR-3, BT-474, MDA-MB361 and ZR-75-1 was examined by comparative genomic hybridization, G-band karyotyping, reverse chromosome painting and fluorescence in situ hybridization of single-copy genes. These lines are aneuploid with complex structural rearrangements and have DNA copy-number imbalances involving multiple sites that include amplification of ERBB-2 and MYC proto-oncogenes which are implicated in breast cancer pathogenesis. A novel site of high level amplification was mapped on chromosome 15. All lines were tumorigenic in nude mice, however, the latency and the incidence of tumor formation varied; SK-BR-3 and MDA-MB361 produced tumors in a shorter time and had a higher total number of genomic imbalances compared to BT-474 and ZR-75-1 cells. Tumor cell behavior in vivo was not reflected by the rate of in vitro cell proliferation. Underrepresentation on the long arm of chromosome 18 was the sole alteration that correlated with an increased tumorigenicity. Chromosome 18q is rich in tumor suppressor genes and its loss is prevalent in primary node-positive breast tumors. Cell lines with monoclonal populations preserve the genetic characteristics of the primary tumor and their use may facilitate the detection of specific alterations associated with breast cancer progression. JF - International journal of oncology AU - Zimonjic, D B AU - Keck-Waggoner, C L AU - Yuan, B Z AU - Kraus, M H AU - Popescu, N C AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 221 EP - 230 VL - 16 IS - 2 SN - 1019-6439, 1019-6439 KW - Proto-Oncogene Proteins KW - 0 KW - Index Medicus KW - Karyotyping KW - Chromosome Aberrations -- genetics KW - Animals KW - Genes, Tumor Suppressor -- genetics KW - Humans KW - Proto-Oncogene Proteins -- metabolism KW - Chromosome Disorders KW - Mice, Nude KW - Mice KW - Chromosomes, Human, Pair 18 -- genetics KW - Proto-Oncogene Proteins -- genetics KW - Female KW - Breast Neoplasms -- genetics KW - Tumor Cells, Cultured UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70884431?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+oncology&rft.atitle=Profile+of+genetic+alterations+and+tumorigenicity+of+human+breast+cancer+cells.&rft.au=Zimonjic%2C+D+B%3BKeck-Waggoner%2C+C+L%3BYuan%2C+B+Z%3BKraus%2C+M+H%3BPopescu%2C+N+C&rft.aulast=Zimonjic&rft.aufirst=D&rft.date=2000-02-01&rft.volume=16&rft.issue=2&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=International+journal+of+oncology&rft.issn=10196439&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-07 N1 - Date created - 2000-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genotype influences in vivo dopamine transporter availability in human striatum. AN - 70876919; 10649826 AB - In vivo availability of striatal dopamine transporter (DAT) protein has been reported to be reduced among alcoholics, and allelic variation of the DAT gene (SLC6A3) has been associated with severity of alcohol withdrawal. We examined the VNTR polymorphism of the 3' untranslated region of SLC6A3 and DAT protein availability in 14 abstinent alcoholics and 11 control subjects. Single photon emission computed tomography (SPECT) and plasma levels of the radioligand [I-123]beta-CIT were used to quantify DAT protein availability. Individuals with the 9-repeat/10-repeat genotype had a mean 22% reduction of DAT protein availability in putamen compared with 10-repeat homozygous individuals (t = 2.14, df = 23, p < .05). Consistent with earlier studies, alcoholism, per se, was not significantly associated with either DAT availability or DAT genotype. These findings suggest that the VNTR polymorphism of the DAT gene effects translation of the DAT protein. This effect may explain a variety of clinical associations that have been reported with this polymorphism. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Heinz, A AU - Goldman, D AU - Jones, D W AU - Palmour, R AU - Hommer, D AU - Gorey, J G AU - Lee, K S AU - Linnoila, M AU - Weinberger, D R AD - Clinical Brain Disorders Branch, NIMH, National Institutes of Health, Bethesda, MD 20892-1379, USA. Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 133 EP - 139 VL - 22 IS - 2 SN - 0893-133X, 0893-133X KW - 3' Untranslated Regions KW - 0 KW - Carrier Proteins KW - Dopamine Plasma Membrane Transport Proteins KW - Iodine Radioisotopes KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - SLC6A3 protein, human KW - 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane KW - 4H1Z7121WS KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Genotype KW - Reference Values KW - Tomography, Emission-Computed, Single-Photon KW - Homozygote KW - Cocaine -- analogs & derivatives KW - Humans KW - Adult KW - Cocaine -- pharmacokinetics KW - Temperance KW - 3' Untranslated Regions -- genetics KW - Iodine Radioisotopes -- pharmacokinetics KW - Minisatellite Repeats KW - Corpus Striatum -- diagnostic imaging KW - Carrier Proteins -- metabolism KW - Polymorphism, Genetic KW - Corpus Striatum -- metabolism KW - Carrier Proteins -- genetics KW - Alcoholism -- metabolism KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70876919?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=Genotype+influences+in+vivo+dopamine+transporter+availability+in+human+striatum.&rft.au=Heinz%2C+A%3BGoldman%2C+D%3BJones%2C+D+W%3BPalmour%2C+R%3BHommer%2C+D%3BGorey%2C+J+G%3BLee%2C+K+S%3BLinnoila%2C+M%3BWeinberger%2C+D+R&rft.aulast=Heinz&rft.aufirst=A&rft.date=2000-02-01&rft.volume=22&rft.issue=2&rft.spage=133&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-14 N1 - Date created - 2000-02-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I and pharmacologic study of irinotecan administered as a 96-hour infusion weekly to adult cancer patients. AN - 70870537; 10653882 AB - We conducted a phase I and pharmacologic study of a weekly 96-hour infusion of irinotecan to determine the maximum-tolerated dose, define the toxicity profile, and characterize the clinical pharmacology of irinotecan and its metabolites. In 26 adult patients with solid tumors, the duration and dose rate of infusion were escalated in new patients until toxicity was observed. In 11 patients who were treated with irinotecan at 12.5 mg/m(2)/d for 4 days weekly for 2 of 3 weeks, dose-limiting grade 3 diarrhea occurred in three patients and grade 3 thrombocytopenia occurred in two patients. The recommended phase II dose is 10 mg/m(2)/d for 4 days given weekly for 2 of 3 weeks. At this dose, the steady-state plasma concentration (Css) of total SN-38 (the active metabolite of irinotecan) was 6.42 +/- 1.10 nmol/L, and the Css of total irinotecan was 28.60 +/- 17.78 nmol/L. No patient experienced grade 3 or 4 neutropenia during any cycle. All other toxicities were mild to moderate. The systemic exposure to SN-38 relative to irinotecan was greater than anticipated, with a molar ratio of the area under the concentration curve (AUC) of SN-38 to irinotecan of 0.24 +/- 0.08. One objective response lasting 12 months in duration was observed in a patient with metastatic colon cancer. The recommended phase II dose of irinotecan of 10 mg/m(2)/d for 4 days weekly for 2 of 3 weeks was extremely well tolerated. Further efficacy testing of this pharmacologic strategy of administering intermittent low doses of irinotecan is warranted. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Takimoto, C H AU - Morrison, G AU - Harold, N AU - Quinn, M AU - Monahan, B P AU - Band, R A AU - Cottrell, J AU - Guemei, A AU - Llorens, V AU - Hehman, H AU - Ismail, A S AU - Flemming, D AU - Gosky, D M AU - Hirota, H AU - Berger, S J AU - Berger, N A AU - Chen, A P AU - Shapiro, J D AU - Arbuck, S G AU - Wright, J AU - Hamilton, J M AU - Allegra, C J AU - Grem, J L AD - Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, and Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA. Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 659 EP - 667 VL - 18 IS - 3 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents, Phytogenic KW - 0 KW - SN38-Glu KW - irinotecan KW - 0H43101T0J KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Humans KW - Vomiting -- chemically induced KW - Aged KW - Nausea -- chemically induced KW - Antineoplastic Agents, Phytogenic -- pharmacokinetics KW - Hematologic Diseases -- chemically induced KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Adult KW - Middle Aged KW - Follow-Up Studies KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - Female KW - Male KW - Neoplasms -- drug therapy KW - Camptothecin -- pharmacology KW - Camptothecin -- pharmacokinetics KW - Neoplasms -- blood KW - Camptothecin -- analogs & derivatives KW - Camptothecin -- adverse effects KW - Camptothecin -- blood KW - Camptothecin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70870537?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+I+and+pharmacologic+study+of+irinotecan+administered+as+a+96-hour+infusion+weekly+to+adult+cancer+patients.&rft.au=Takimoto%2C+C+H%3BMorrison%2C+G%3BHarold%2C+N%3BQuinn%2C+M%3BMonahan%2C+B+P%3BBand%2C+R+A%3BCottrell%2C+J%3BGuemei%2C+A%3BLlorens%2C+V%3BHehman%2C+H%3BIsmail%2C+A+S%3BFlemming%2C+D%3BGosky%2C+D+M%3BHirota%2C+H%3BBerger%2C+S+J%3BBerger%2C+N+A%3BChen%2C+A+P%3BShapiro%2C+J+D%3BArbuck%2C+S+G%3BWright%2C+J%3BHamilton%2C+J+M%3BAllegra%2C+C+J%3BGrem%2C+J+L&rft.aulast=Takimoto&rft.aufirst=C&rft.date=2000-02-01&rft.volume=18&rft.issue=3&rft.spage=659&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 - 2000-02-29 N1 - Date created - 2000-02-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HuR regulates p21 mRNA stabilization by UV light. AN - 70866643; 10629032 AB - Expression of the cyclin-dependent kinase inhibitor p21 is highly induced by many stresses, including exposure to short-wavelength UV light (UVC), which increases p21 mRNA stability. Investigation into the mechanisms underlying this stabilization process revealed that proteins present in cytoplasmic lysates of human RKO colorectal carcinoma cells formed complexes with p21 mRNA that were inducible by treatment with UVC and other stress agents. The ubiquitous Elav-type RNA-binding protein HuR was identified within the p21 mRNA-protein complexes, as antibodies recognizing HuR supershifted these complexes and revealed HuR-immunoreactive proteins complexing with p21 mRNA on Western blots. Lowering of endogenous HuR levels through expression of antisense HuR decreased p21 RNA-protein complexes, greatly reduced the UVC inducibility and half-life of p21 mRNA, and prevented UVC-mediated induction of luciferase activity in p21 3' untranslated region-containing reporter constructs. Our findings indicate that HuR plays a major role in regulating stress-induced p21 expression by enhancing p21 mRNA stability and that these effects are coupled to HuR's elevated presence in the cytoplasm. JF - Molecular and cellular biology AU - Wang, W AU - Furneaux, H AU - Cheng, H AU - Caldwell, M C AU - Hutter, D AU - Liu, Y AU - Holbrook, N AU - Gorospe, M AD - Laboratory of Biological Chemistry, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 760 EP - 769 VL - 20 IS - 3 SN - 0270-7306, 0270-7306 KW - Antigens, Surface KW - 0 KW - CDKN1A protein, human KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - ELAV Proteins KW - ELAV-Like Protein 1 KW - ELAVL1 protein, human KW - Enzyme Inhibitors KW - Luminescent Proteins KW - RNA, Messenger KW - RNA-Binding Proteins KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Dactinomycin KW - 1CC1JFE158 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Hydrogen Peroxide KW - BBX060AN9V KW - Index Medicus KW - Transcription, Genetic -- drug effects KW - Transcription, Genetic -- radiation effects KW - Cell Nucleus -- metabolism KW - Humans KW - Hydrogen Peroxide -- pharmacology KW - RNA, Messenger -- radiation effects KW - RNA, Messenger -- genetics KW - Methyl Methanesulfonate -- pharmacology KW - Polymerase Chain Reaction KW - Dactinomycin -- pharmacology KW - Blotting, Western KW - Tumor Cells, Cultured KW - Transfection KW - Cytoplasm -- metabolism KW - Enzyme Inhibitors -- metabolism KW - Luminescent Proteins -- genetics KW - Signal Transduction KW - Colorectal Neoplasms KW - Ultraviolet Rays KW - RNA-Binding Proteins -- metabolism KW - RNA-Binding Proteins -- genetics KW - Gene Expression Regulation, Neoplastic -- physiology KW - Cyclins -- isolation & purification KW - Cyclins -- metabolism KW - Gene Expression Regulation, Neoplastic -- radiation effects KW - RNA-Binding Proteins -- isolation & purification KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Cyclins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70866643?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=HuR+regulates+p21+mRNA+stabilization+by+UV+light.&rft.au=Wang%2C+W%3BFurneaux%2C+H%3BCheng%2C+H%3BCaldwell%2C+M+C%3BHutter%2C+D%3BLiu%2C+Y%3BHolbrook%2C+N%3BGorospe%2C+M&rft.aulast=Wang&rft.aufirst=W&rft.date=2000-02-01&rft.volume=20&rft.issue=3&rft.spage=760&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 - 2000-02-14 N1 - Date created - 2000-02-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genes Dev. 1998 Mar 15;12(6):820-30 [9512516] J Cell Biol. 1998 May 18;141(4):863-74 [9585406] Mol Cell Biol. 1997 Aug;17(8):4611-21 [9234718] Nucleic Acids Res. 1997 Sep 15;25(18):3564-9 [9278474] Nat Med. 1997 Nov;3(11):1233-41 [9359698] Cell Calcium. 1998 Feb-Mar;23(2-3):79-86 [9601602] EMBO J. 1998 Jun 15;17(12):3448-60 [9628880] J Cell Biol. 1984 Dec;99(6):1997-204 [6209285] Cell. 1985 Oct;42(3):889-902 [2414012] Cell. 1986 Aug 29;46(5):659-67 [3488815] Science. 1988 Dec 16;242(4885):1570-2 [3144044] Genes Dev. 1989 Jan;3(1):60-72 [2496006] JAMA. 1989 Oct 6;262(13):1834-41 [2674489] Cell. 1989 Nov 3;59(3):411-9 [2553271] Proc Natl Acad Sci U S A. 1990 Jan;87(2):777-81 [2105489] J Biol Chem. 1991 Feb 15;266(5):3167-71 [1993688] Trends Biochem Sci. 1991 Jun;16(6):214-20 [1716386] Cell. 1991 Oct 18;67(2):325-33 [1655278] Am J Pathol. 1992 Oct;141(4):881-6 [1415481] Proc Natl Acad Sci U S A. 1993 May 1;90(9):3988-92 [8387205] Mol Cell Biol. 1993 Jun;13(6):3494-504 [8497264] Mol Cell Biol. 1993 Aug;13(8):5034-42 [8336733] Cell. 1993 Aug 13;74(3):413-21 [7688664] Cell. 1993 Nov 19;75(4):817-25 [8242752] Mol Cell Biol. 1993 Dec;13(12):7652-65 [8246982] J Neurosci. 1994 Apr;14(4):1943-52 [8158249] J Biol Chem. 1994 Apr 22;269(16):11845-51 [8163483] Cancer Res. 1994 Jul 1;54(13):3391-5 [8012956] J Neurobiol. 1994 Feb;25(2):143-55 [7517436] Science. 1994 Jul 29;265(5172):615-21 [8036511] Mol Cell Biol. 1994 Dec;14(12):7984-95 [7969138] Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11207-11 [7972035] J Clin Invest. 1995 Mar;95(3):973-9 [7883998] Proc Natl Acad Sci U S A. 1995 May 9;92(10):4557-61 [7753842] Cell. 1995 Aug 25;82(4):675-84 [7664346] EMBO J. 1998 Jun 15;17(12):3461-70 [9628881] J Biol Chem. 1998 Aug 7;273(32):20511-6 [9685407] J Biol Chem. 1998 Aug 14;273(33):21137-44 [9694869] J Cell Sci. 1998 Nov;111 ( Pt 21):3145-56 [9763509] Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15293-8 [9860962] Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):5-7 [9874760] Genes Dev. 1999 Jan 15;13(2):188-201 [9925643] J Gen Physiol. 1999 Feb;113(2):239-48 [9925822] Genes Dev. 1999 Feb 15;13(4):449-61 [10049360] J Biol Chem. 1999 Jul 23;274(30):21395-401 [10409701] J Neurobiol. 1995 Sep;28(1):82-101 [8586967] Trends Biochem Sci. 1995 Nov;20(11):465-70 [8578590] J Biol Chem. 1996 Jan 12;271(2):901-6 [8557703] Cancer Res. 1996 Feb 1;56(3):475-9 [8564956] Genes Dev. 1996 Apr 1;10(7):804-15 [8846917] J Biol Chem. 1996 May 10;271(19):11518-24 [8626712] J Biol Chem. 1996 Apr 5;271(14):8144-51 [8626503] Mol Cell Biol. 1996 Apr;16(4):1335-41 [8657106] Nature. 1996 Jun 20;381(6584):713-6 [8649519] Nature. 1996 Jul 25;382(6589):370-3 [8684469] Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8455-9 [8710892] Mol Cell Biol. 1996 Dec;16(12):6654-60 [8943319] Mol Cell Biol. 1997 Feb;17(2):954-62 [9001249] Oncogene. 1997 Feb 27;14(8):929-35 [9050992] Annu Rev Neurosci. 1997;20:269-301 [9056715] J Neurosci. 1997 May 1;17(9):3024-37 [9096138] EMBO J. 1997 Apr 15;16(8):2130-9 [9155038] Curr Opin Cell Biol. 1997 Jun;9(3):420-9 [9159083] Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):492-8 [9435219] Mol Cell Biol. 1998 Mar;18(3):1400-7 [9488455] J Biol Chem. 1998 Mar 13;273(11):6417-23 [9497373] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Propionyl-L-carnitine as potential protective agent against adriamycin-induced impairment of fatty acid beta-oxidation in isolated heart mitochondria. AN - 70829731; 10623482 AB - Propionyl-L-carnitine (PLC), a natural short-chain derivative of L-carnitine, has been tested in this study as a potential protective agent against adriamycin (ADR)-induced cardiotoxicity in isolated rat heart myocytes and mitochondria. In cardiac myocytes, ADR (0.5 mM) caused a significant (70%) inhibition of palmitate oxidation, whereas, PLC (5 mM) induced a significant (49%) stimulation. Addition of PLC to ADR-incubated myocytes induced 79% reversal of ADR-induced inhibition of palmitate oxidation. In isolated rat heart mitochondria, ADR produced concentration-dependent inhibition of both palmitoyl-CoA and palmitoyl-carnitine oxidation, while PLC caused a more than 2.5-fold increase in both substrates. Preincubation of mitochondria with 5 mM PLC caused complete reversal of ADR-induced inhibition in the oxidation of both substrates. Also ADR induced concentration-dependent inhibition of CPT I which is parallel to the inhibition of its substrate palmitoyl-CoA. In rat heart slices, ADR induced a significant (65%) decrease in adenosine triphosphate (ATP) and this effect is reduced to 17% only by PLC. Results of this study revealed that ADR induced its cardiotoxicity by inhibition of CPT I and beta-oxidation of long-chain fatty acids with the consequent depletion of ATP in cardiac tissues, and that PLC can be used as a protective agent against ADR-induced cardiotoxicity. Copyright 2000 Academic Press. JF - Pharmacological research AU - Sayed-Ahmed, M M AU - Shouman, S A AU - Rezk, B M AU - Khalifa, M H AU - Osman, A M AU - El-Merzabani, M M AD - Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Fum El-Khalig, Kasr El-Aini Street, Cairo, Egypt. Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 143 EP - 150 VL - 41 IS - 2 SN - 1043-6618, 1043-6618 KW - Antibiotics, Antineoplastic KW - 0 KW - Cardiotonic Agents KW - Fatty Acids KW - Palmitates KW - Proteins KW - propionylcarnitine KW - 17298-37-2 KW - Palmitoyl Coenzyme A KW - 1763-10-6 KW - Doxorubicin KW - 80168379AG KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Carnitine O-Palmitoyltransferase KW - EC 2.3.1.21 KW - Carnitine KW - S7UI8SM58A KW - Index Medicus KW - Rats KW - Oxidation-Reduction KW - Myocardium -- cytology KW - Carnitine O-Palmitoyltransferase -- metabolism KW - Animals KW - Rats, Sprague-Dawley KW - In Vitro Techniques KW - Adenosine Triphosphate -- metabolism KW - Palmitoyl Coenzyme A -- metabolism KW - Proteins -- metabolism KW - Palmitates -- metabolism KW - Myocardium -- metabolism KW - Male KW - Cardiotonic Agents -- metabolism KW - Doxorubicin -- antagonists & inhibitors KW - Carnitine -- pharmacology KW - Carnitine -- metabolism KW - Mitochondria, Heart -- drug effects KW - Doxorubicin -- toxicity KW - Carnitine -- analogs & derivatives KW - Cardiotonic Agents -- pharmacology KW - Mitochondria, Heart -- metabolism KW - Antibiotics, Antineoplastic -- toxicity KW - Fatty Acids -- metabolism KW - Antibiotics, Antineoplastic -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70829731?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacological+research&rft.atitle=Propionyl-L-carnitine+as+potential+protective+agent+against+adriamycin-induced+impairment+of+fatty+acid+beta-oxidation+in+isolated+heart+mitochondria.&rft.au=Sayed-Ahmed%2C+M+M%3BShouman%2C+S+A%3BRezk%2C+B+M%3BKhalifa%2C+M+H%3BOsman%2C+A+M%3BEl-Merzabani%2C+M+M&rft.aulast=Sayed-Ahmed&rft.aufirst=M&rft.date=2000-02-01&rft.volume=41&rft.issue=2&rft.spage=143&rft.isbn=&rft.btitle=&rft.title=Pharmacological+research&rft.issn=10436618&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-21 N1 - Date created - 2000-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antileukemic activity and mechanism of action of cordycepin against terminal deoxynucleotidyl transferase-positive (TdT+) leukemic cells. AN - 70797782; 10609556 AB - The nucleoside analogue cordycepin (3'-deoxyadenosine, 3'-dA) is substantially more cytotoxic to terminal deoxynucleotidyl transferase positive (TdT+) leukemic cells than to TdT leukemic cells in vitro in the presence of an adenosine deaminase inhibitor, deoxycoformycin (dCF), and has been considered as a therapeutic agent for TdT+ leukemia. The intracellular metabolism of 3'-dA was examined with HPLC, and the mechanism of its anti-TdT+ leukemic activity was analyzed. In the presence of dCF (2.5 microM), TdT+ leukemic cells (N = 5) were sensitive to the cytotoxic effect of 3'-dA, whereas TdT (N = 6) cells were not. A high level of 3'-dA-5'-triphosphate (3'-dATP) formation was detected in TdT+ NALM-6 cells (67 pmol/10(6) cells) and TdT- K562 cells (49 pmol/10(6) cells) when cultured with 1 microM [3'-3H]-labeled 3'-dA. A substantial level of 3'-dATP was detected in TdT HUT-102 cells (27 pmol/10(6) cells), whereas the level of 3'-dATP in TdT+ MOLT-4 cells was low (0.3 pmol/10(6) cells). The mean IC50 values of 3'-dA against phytohemagglutinin (PHA)-activated and resting peripheral blood mononuclear cells (PBM) (N = 5) were 8 and 32 microM, respectively. There was a modest level of 3'-dATP (7 pmol/10(6) cells) in PHA-PBM, whereas a lower level of 3'-dATP was detected in resting PBM (2.5 pmol/10(6) cells). These data suggest that the presence of 3'-dATP is not sufficient for the antileukemic effect of 3'-dA, but that TdT positivity is essential, and that PBM are significantly less sensitive to the cytotoxicity of 3'-dA in vitro. Further development of 3'-dA as a potential antileukemic agent to treat patients with TdT+ leukemia is warranted. JF - Biochemical pharmacology AU - Kodama, E N AU - McCaffrey, R P AU - Yusa, K AU - Mitsuya, H AD - Experimental Retrovirology Section, Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2000/02/01/ PY - 2000 DA - 2000 Feb 01 SP - 273 EP - 281 VL - 59 IS - 3 SN - 0006-2952, 0006-2952 KW - Antineoplastic Agents KW - 0 KW - Deoxyadenosines KW - Phytohemagglutinins KW - 3'-deoxyinosine KW - 13146-72-0 KW - Pentostatin KW - 395575MZO7 KW - Inosine KW - 5A614L51CT KW - DNA Nucleotidylexotransferase KW - EC 2.7.7.31 KW - Adenosine Deaminase KW - EC 3.5.4.4 KW - cordycepin KW - GZ8VF4M2J8 KW - Index Medicus KW - Adenosine Deaminase -- metabolism KW - Leukemia KW - Inosine -- pharmacology KW - Tumor Cells, Cultured KW - Phosphorylation KW - Inosine -- analogs & derivatives KW - Humans KW - Deamination KW - Adenosine Deaminase -- drug effects KW - Leukocytes, Mononuclear -- drug effects KW - Phytohemagglutinins -- pharmacology KW - Pentostatin -- pharmacology KW - DNA Nucleotidylexotransferase -- drug effects KW - Deoxyadenosines -- pharmacology KW - DNA Nucleotidylexotransferase -- metabolism KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70797782?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Antileukemic+activity+and+mechanism+of+action+of+cordycepin+against+terminal+deoxynucleotidyl+transferase-positive+%28TdT%2B%29+leukemic+cells.&rft.au=Kodama%2C+E+N%3BMcCaffrey%2C+R+P%3BYusa%2C+K%3BMitsuya%2C+H&rft.aulast=Kodama&rft.aufirst=E&rft.date=2000-02-01&rft.volume=59&rft.issue=3&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-04 N1 - Date created - 2000-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chimeric toxins in cancer treatment AN - 20378553; 9050598 AB - A chimeric toxin is composed of a protein toxin connected to a binding ligand such as an antibody or growth factor. Chimeric toxins include conventional immunotoxins, in which the ligand is an antibody, growth-factor fusion toxins, in which the growth factor ligand is fused in single-chain fashion to the toxin, and recombinant immunotoxins, in which the Fv fragment of an antibody is fused to the toxin. Toxins kill cells by catalytic inhibition of protein synthesis within the cell cytosol, and are targeted to cells displaying internalising receptors for the ligand. Chimeric toxins have recently been tested clinically in solid tumours expressing the LeY antigen, the transferrin receptor, and the IL-4 receptor, and in haematologic malignancies expressing CD22, CD19, high affinity IL-2 receptors and CD25. Several chimeric toxins have demonstrated potent clinical efficacy in patients with malignant disease refractory to surgery, radiation therapy and chemotherapy, the traditional modalities of cancer treatment. Chimeric toxins are evolving into a separate modality of cancer treatment, which rationally targets cells based on surface markers. Impediments to clinical efficacy include immunogenicity, toxicity to normal antigen positive or negative tissues, and limited penetration of solid masses of tumour. JF - Expert Opinion on Emerging Drugs AU - Kreitman, R J AD - Laboratory of Molecular Biology, Division of Basic Sciences,National Cancer Institute, National Institutes of Health37/4B27, 37 Convent Drive MSC 4255 Bethesda, MD 20892, USA., kreitmar@mail.nih.gov Y1 - 2000/02// PY - 2000 DA - Feb 2000 SP - 61 EP - 71 PB - Informa Healthcare VL - 5 IS - 1 SN - 1472-8214, 1472-8214 KW - Toxicology Abstracts; Immunology Abstracts; Biotechnology and Bioengineering Abstracts KW - diphtheria toxin KW - disulphide-stabilised KW - fusion protein KW - fv KW - growth factor KW - immunotoxins KW - interleukin KW - monoclonal antibody KW - Pseudomonas exotoxin KW - saporin KW - Interleukin 4 KW - Protein biosynthesis KW - Chemotherapy KW - Drug development KW - Toxicity KW - Tumors KW - CD25 antigen KW - Interleukin 2 receptors KW - Fv KW - Immunotoxins KW - Cancer KW - Toxins KW - CD22 antigen KW - Antibodies KW - Malignancy KW - Transferrin receptors KW - Radiation KW - Immunogenicity KW - Surgery KW - Cytosol KW - Growth factors KW - Surface markers KW - CD19 antigen KW - W 30925:Genetic Engineering KW - X 24310:Pharmaceuticals KW - F 06915:Cancer Immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20378553?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+Opinion+on+Emerging+Drugs&rft.atitle=Chimeric+toxins+in+cancer+treatment&rft.au=Kreitman%2C+R+J&rft.aulast=Kreitman&rft.aufirst=R&rft.date=2000-02-01&rft.volume=5&rft.issue=1&rft.spage=61&rft.isbn=&rft.btitle=&rft.title=Expert+Opinion+on+Emerging+Drugs&rft.issn=14728214&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-03-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Interleukin 4; Protein biosynthesis; Chemotherapy; Drug development; Tumors; Toxicity; CD25 antigen; Toxins; Cancer; Immunotoxins; Fv; Interleukin 2 receptors; Malignancy; Antibodies; CD22 antigen; Radiation; Transferrin receptors; Immunogenicity; Surgery; Cytosol; Growth factors; Surface markers; CD19 antigen ER - TY - JOUR T1 - Do Action Potentials Regulate Myelination? AN - 1835541788; 18461153 AB - A variety of anatomical features suggest that functional activity in the nervous system can influence the process of myelination, yet direct evidence of this is lacking. Research by Zalc and colleagues shows that myelination of optic nerve is inhibited by a neurotoxin that blocks action potential activity and is stimulated by a toxin that increases impulse activity, suggesting that impulse activity is necessary for initiating myelination during development of the optic nerve. Research by Fields and colleagues, using electrical stimulation of axons, shows that low frequency impulse activity inhibits myelination of dorsal root ganglion neurons, but high frequency impulse activity has no effect. This results from reduced expression of a cell adhesion molecule on the stimulated axons that is critical for inducing myelination. Together these studies support the conclusion that impulse activity can influence the process of myelination, probably through more than one molecular mechanism operating during discrete steps in the myelination process. JF - The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry AU - Zalc, Bernard AU - Fields, R Douglas AD - Biologie des Interactions Neurones-Glie, Institut National de la Santé et de la Recherche Médicale U-495, Université P. M. Curie, Hôpital de la Salpêtrière, Paris, France (BZ), Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (RDF). Y1 - 2000/02// PY - 2000 DA - February 2000 SP - 5 EP - 13 VL - 6 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835541788?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Neuroscientist+%3A+a+review+journal+bringing+neurobiology%2C+neurology+and+psychiatry&rft.atitle=Do+Action+Potentials+Regulate+Myelination%3F&rft.au=Zalc%2C+Bernard%3BFields%2C+R+Douglas&rft.aulast=Zalc&rft.aufirst=Bernard&rft.date=2000-02-01&rft.volume=6&rft.issue=1&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=The+Neuroscientist+%3A+a+review+journal+bringing+neurobiology%2C+neurology+and+psychiatry&rft.issn=1089-4098&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2009-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recognition of human colon cancer by T cells transduced with a chimeric receptor gene AN - 17908864; 5184577 AB - Transduction with chimeric T-cell receptor genes can be used to redirect primary T lymphocytes to recognize specific antigens (Ags), including ovarian and breast cancer Ags. To extend this approach to colon cancer we report here redirection of T cells using a chimeric receptor recognizing the colon cancer-associated Ag EGP40. Chimeric T cell receptors were constructed by ligating single-chain genes of either of two EGP40-specific monoclonal antibodies (CO17.1A, GA733) to the Fc receptor gamma -signaling chain. Retroviral vectors incorporating these constructs were used to transduce a murine T-cell line and human peripheral blood lymphocytes. These modified T cells were analyzed for specific recognition of colon cancer lines by measuring cytokine release and lytic activity against tumor targets. Murine lymphocytes transduced with the chimeric receptor based on GA733, but not CO17.1A, released cytokine specifically in response to EGP40-expressing colon cancer cell lines. Recognition of colon cancer targets by murine lymphocytes was blocked by the addition of GA733 antibody or soluble EGP40 Ag, confirming that colon cancer recognition is based on specific chimeric receptor-Ag interaction. Human lymphocytes transduced with chimeric GA733 specifically recognized colon carcinoma cells in cytokine release assays and lysed EGP40-expressing tumor cells. Genetic modification of T cells can be used to redirect T cells against EGP40-expressing tumor cells. The expression of chimeric GA733 in the autologous lymphocytes of patients may provide a source of tumor-reactive cells with therapeutic application against colon cancer. JF - Cancer Gene Therapy AU - Daly, T AU - Royal, R E AU - Kershaw, M H AU - Treisman, J AU - Wang, G AU - Li, W AU - Herlyn, D AU - Eshhar, Z AU - Hwu, P AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 2B42, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 2000/02// PY - 2000 DA - Feb 2000 SP - 284 EP - 291 VL - 7 IS - 2 SN - 0929-1903, 0929-1903 KW - man KW - mice KW - double prime Fc receptors KW - chimeric receptors KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - ^AFc receptors KW - ^AT-cell receptor KW - Colon KW - Monoclonal antibodies KW - Lymphocytes T KW - Cytokines KW - Colorectal carcinoma KW - Transduction KW - Cancer KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17908864?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Gene+Therapy&rft.atitle=Recognition+of+human+colon+cancer+by+T+cells+transduced+with+a+chimeric+receptor+gene&rft.au=Daly%2C+T%3BRoyal%2C+R+E%3BKershaw%2C+M+H%3BTreisman%2C+J%3BWang%2C+G%3BLi%2C+W%3BHerlyn%2C+D%3BEshhar%2C+Z%3BHwu%2C+P&rft.aulast=Daly&rft.aufirst=T&rft.date=2000-02-01&rft.volume=7&rft.issue=2&rft.spage=284&rft.isbn=&rft.btitle=&rft.title=Cancer+Gene+Therapy&rft.issn=09291903&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Colorectal carcinoma; Colon; Cancer; Lymphocytes T; ^AT-cell receptor; Cytokines; Transduction; Monoclonal antibodies ER - TY - JOUR T1 - Construction of a recombinant adeno-associated virus (rAAV) vector expressing murine interleukin-12 (IL-12) AN - 17905885; 5184579 AB - IL-12 is a heterodimeric cytokine that is known to induce tumor regression and long-term antitumor immunity. Recombinant adeno-associated virus (rAAV) vectors are advantageous for gene therapy in that they lack pathogenicity in humans, infect dividing as well as nondividing cells, and show a broad range of infectivity. We constructed an rAAV vector expressing interleukin-12 (IL-12) for cancer immunotherapy studies in a mouse model by inserting murine IL-12 (mIL-12) p35 and p40 cDNAs into the plasmid pRep4 and inserting the encephalomyocarditis virus internal ribosomal entry site between the p35 and p40 cDNAs. The mIL-12 expression cassette containing the Rous sarcoma virus promoter and a simian virus 40 polyadenylation signal was subcloned into the AAV plasmid p008Sub/NeoR, which contains two AAV inverted terminal repeat sequences and the NeoR gene driven by the thymidine kinase promoter. rAAV virions (10 super(4) infectious particles/ml) were generated by cotransfection of rAAV-mIL-12 and a helper plasmid (pAAV/Ad) into 293 cells previously infected with adenovirus 5. After infection of D6 fibroblasts with rAAV-mIL-12, G418-resistant clones were isolated. Each of the 1D D6 clones isolated produced up to 5.2 ng/10 super(6) cells/48 hours of mIL-12 as determined by enzyme-linked immunosorbent assay. Induction of interferon- gamma , enhanced lymphocyte proliferation, and cytotoxicity assays confirmed biologically functional IL-12 production by the vector. This is the first report indicating that an rAAV vector expresses mIL-12, which can be used to model the effects of mIL-12 alone and/or in combination with other antitumor agents. JF - Cancer Gene Therapy AU - Paul, D AU - Qazilbash, M H AU - Song, K AU - Xu, H AU - Sinha, B K AU - Liu, J AU - Cowan, KH AD - Medicine Branch, National Cancer Institute, National Institutes of Health, 10/12N/226, Bethesda, MD 20892, USA Y1 - 2000/02// PY - 2000 DA - Feb 2000 SP - 308 EP - 315 VL - 7 IS - 2 SN - 0929-1903, 0929-1903 KW - mice KW - man KW - gamma -Interferon KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - ^g-Interferon KW - Expression vectors KW - Interleukin 12 KW - Enzyme-linked immunosorbent assay KW - Rous sarcoma virus KW - Gene therapy KW - Gene transfer KW - Immunotherapy KW - Adeno-associated virus KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17905885?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Gene+Therapy&rft.atitle=Construction+of+a+recombinant+adeno-associated+virus+%28rAAV%29+vector+expressing+murine+interleukin-12+%28IL-12%29&rft.au=Paul%2C+D%3BQazilbash%2C+M+H%3BSong%2C+K%3BXu%2C+H%3BSinha%2C+B+K%3BLiu%2C+J%3BCowan%2C+KH&rft.aulast=Paul&rft.aufirst=D&rft.date=2000-02-01&rft.volume=7&rft.issue=2&rft.spage=308&rft.isbn=&rft.btitle=&rft.title=Cancer+Gene+Therapy&rft.issn=09291903&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adeno-associated virus; Rous sarcoma virus; Gene therapy; Gene transfer; Interleukin 12; Expression vectors; Enzyme-linked immunosorbent assay; Immunotherapy ER - TY - JOUR T1 - Drug selection of MDR1-transduced hematopoietic cells ex vivo increases transgene expression and chemoresistance in reconstituted bone marrow in mice AN - 17591803; 4681717 AB - The MDR1 (multidrug resistance) gene, transferred to hematopoietic cells, is expected to protect them from anticancer chemotherapy and may serve as a selectable marker, restoring gene expression in vivo. Appropriate selection strategies, however, need to be established. To investigate whether preselection ex vivo affects chemoresistance, murine bone marrow cells were retrovirally transduced with high-titer or, as a model for suboptimal gene expression, low-titer retroviruses and exposed to daunomycin or colchicine for 48-96 h. Selection significantly increased chemoresistance of clonogenic progenitor cells. In tissue culture, the entire target population was rendered highly drug resistant after MDR1 transfer with high-titer viruses. If transduction was performed under suboptimal conditions, drug selection increased the frequency of chemoresistant colonies up to 40% over the number of unselected cells. Colchicine and daunomycin were equally efficient in increasing drug resistance ex vivo, but colchicine-preselected cells rescued lethally irradiated mice under conditions where daunomycin-selected bone marrow cells failed to do so. Hence, while hematopoietic cells can be protected by MDR1, the selection strategy is critical for repopulation of bone marrow with transduced cells. Preselection in culture before transplantation significantly increased P-gp expression and chemoresistance in vivo in mice reconstituted with transduced bone marrow cells. This study may help to facilitate the use of MDR1 as a selectable marker in gene therapy of the hematopoietic system. JF - Gene Therapy AU - Licht, T AU - Goldenberg, S K AU - Vieira, W D AU - Gottesman, M M AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Building 37, Room 4E16, 37 Convent Drive MSC 4255, Bethesda, MD 20892-4255, USA Y1 - 2000/02// PY - 2000 DA - Feb 2000 SP - 348 EP - 358 VL - 7 IS - 4 SN - 0969-7128, 0969-7128 KW - mice KW - MDR1 gene KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene therapy KW - Gene transfer KW - Bone marrow KW - Hemopoiesis KW - Multidrug resistance KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17591803?accountid=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=Gene+Therapy&rft.atitle=Drug+selection+of+MDR1-transduced+hematopoietic+cells+ex+vivo+increases+transgene+expression+and+chemoresistance+in+reconstituted+bone+marrow+in+mice&rft.au=Licht%2C+T%3BGoldenberg%2C+S+K%3BVieira%2C+W+D%3BGottesman%2C+M+M%3BPastan%2C+I&rft.aulast=Licht&rft.aufirst=T&rft.date=2000-02-01&rft.volume=7&rft.issue=4&rft.spage=348&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&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 - Hemopoiesis; Gene transfer; Bone marrow; Multidrug resistance; Gene therapy ER - TY - JOUR T1 - Responses of Transgenic Mouse Lines p53 super(+/-) and Tg-AC to Agents Tested in Conventional Carcinogenicity Bioassays AN - 17516253; 4704038 AB - The haplo-insufficient p53 knockout (p53 super(+/-)) and zetaglobin v-Ha-ras (Tg-AC) transgenic mouse models were compared to the conventional two rodent species carcinogen bioassay by prospectively testing nine chemicals. Seven of the chemicals classified as carcinogens in the conventional bioassay induced tumors in the liver or kidneys of B6C3F sub(1) mice, and one (pentachlorophenol) also induced tumors in other tissues. Only three chemicals, furfuryl alcohol, pyridine, and pentachlorophenol, induced tumors in rats. The tumorigenic effect of pyridine was seen in F344 rats but not in Wistar strain rats. None of the chemicals induced tumors in the P53 super(+/-) transgenic mice, which is consistent with the absence of genotoxicity of these chemicals. Only two of the seven nongenotoxic carcinogens were positive in the Tg times AC model (lauric acid diethanolamine and pentachlorophenol). These results show that these transgenic models do not respond to many chemicals that show strain- or species--specific responses in conventional bioassays. JF - Toxicological Sciences AU - Spalding, J W AU - French, JE AU - Stasiewicz, S AU - Furedi-Machacek, M AU - Conner, F AU - Tice, R R AU - Tennant, R W AD - National Institute of Environmental Health Sciences, Laboratory of Environmental Carcinogenesis and Mutagenesis, Research Triangle Park, North Carolina 27709, USA Y1 - 2000/02// PY - 2000 DA - Feb 2000 SP - 213 EP - 223 PB - Academic Press, Inc. VL - 53 IS - 2 SN - 1096-6080, 1096-6080 KW - Toxicology Abstracts KW - Carcinogenicity KW - Laboratory animals KW - Xenobiotics KW - Transgenic mice KW - Toxicity testing KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17516253?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Responses+of+Transgenic+Mouse+Lines+p53+super%28%2B%2F-%29+and+Tg-AC+to+Agents+Tested+in+Conventional+Carcinogenicity+Bioassays&rft.au=Spalding%2C+J+W%3BFrench%2C+JE%3BStasiewicz%2C+S%3BFuredi-Machacek%2C+M%3BConner%2C+F%3BTice%2C+R+R%3BTennant%2C+R+W&rft.aulast=Spalding&rft.aufirst=J&rft.date=2000-02-01&rft.volume=53&rft.issue=2&rft.spage=213&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Toxicity testing; Carcinogenicity; Laboratory animals; Xenobiotics; Transgenic mice ER - TY - JOUR T1 - Genomic integration and gene expression by a modified adenoviral vector AN - 17500573; 4691237 AB - A replication-deficient recombinant adenovirus encoding luciferase was constructed using 5' and 3' long terminal repeat (LTR) sequences of the Moloney murine leukemia virus. Gene expression was observed in cultured cells in vitro and in submandibular gland, cortex, and caudate nucleus for as long as three months in vivo. The vector integrated randomly into the genome of both dividing and nondividing cells as determined by fluorescence in situ hybridization (FISH) (10-15% of cells in vitro and 5% in rat spleen in vivo), gene walking, Southern hybridization, and polymerase chain reaction (PCR), in the absence of transcomplementing reverse transcriptase or integrase activity. The new vector combines the high titer and versatility of adenoviral vectors with the long-term gene expression and integration of retroviral vectors. JF - Nature Biotechnology AU - Zheng, C AU - Baum, B J AU - Iadarola, MJ AU - O'Connell, B C AD - Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-1190, USA, bbaum@dir.nidcr.nih.gov Y1 - 2000/02// PY - 2000 DA - Feb 2000 SP - 176 EP - 180 VL - 18 IS - 2 SN - 1087-0156, 1087-0156 KW - rats KW - adenovirus KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Adenovirus KW - Caudate nucleus KW - Expression vectors KW - Cortex KW - Retrovirus KW - Reporter gene KW - Gene transfer KW - Submandibular gland KW - W3 33181:Gene therapy vectors KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17500573?accountid=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=Genomic+integration+and+gene+expression+by+a+modified+adenoviral+vector&rft.au=Zheng%2C+C%3BBaum%2C+B+J%3BIadarola%2C+MJ%3BO%27Connell%2C+B+C&rft.aulast=Zheng&rft.aufirst=C&rft.date=2000-02-01&rft.volume=18&rft.issue=2&rft.spage=176&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2F72628 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adenovirus; Retrovirus; Gene transfer; Reporter gene; Caudate nucleus; Cortex; Submandibular gland; Expression vectors DO - http://dx.doi.org/10.1038/72628 ER - TY - JOUR T1 - Characterization of Mycobacterium tuberculosis Isolates from Patients in Houston, Texas, by Spoligotyping AN - 17478660; 4677701 AB - Mycobacterium tuberculosis isolates (n = 1,429) from 1,283 patients collected as part of an ongoing population-based tuberculosis epidemiology study in Houston, Texas, were analyzed by spoligotyping and IS6110 profiling. The isolates were also assigned to one of three major genetic groups on the basis of nucleotide polymorphisms located at codons 463 and 95 in the genes (katG and gyrA) encoding catalase-peroxidase and the A subunit of DNA gyrase, respectively. A total of 225 spoligotypes were identified in the 1,429 isolates. There were 54 spoligotypes identified among 713 isolates (n = 623 patients) assigned to 73 IS6110 clusters. In addition, among 716 isolates (n = 660 patients) with unique IS6110 profiles, 200 spoligotypes were identified. No changes were observed either in the IS6110 profile or in the spoligotype for the 281 isolates collected sequentially from 133 patients. Five instances in which isolates with slightly different spoligotypes had the same IS6110 profile were identified, suggesting that in rare cases isolates with different spoligotypes can be clonally related. Spoligotypes correlated extremely well with major genetic group designations. Only three very similar spoligotypes were shared by isolates from genetic groups 2 and 3, and none was shared by group 1 and group 2 organisms or by group 1 and group 3 organisms. All organisms belonging to genetic groups 2 and 3 failed to hybridize with spacer probes 33 to 36. Taken together, the results support the existence of three distinct genetic groups of M. tuberculosis organisms and provide new information about the relationship between IS6110 profiles, spoligotypes, and major genetic groups of M. tuberculosis. JF - Journal of Clinical Microbiology AU - Soini, H AU - Pan, X AU - Amin, A AU - Graviss, E A AU - Siddiqui, 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 St., Hamilton, MT 59840, USA, jmusser@niaid.nih.gov Y1 - 2000/02// PY - 2000 DA - Feb 2000 SP - 669 EP - 676 VL - 38 IS - 2 SN - 0095-1137, 0095-1137 KW - USA, Texas, Houston KW - insertion sequence IS6110 KW - spoligotyping KW - Microbiology Abstracts B: Bacteriology KW - Genotyping KW - Tuberculosis KW - Mycobacterium tuberculosis KW - J 02710:Identification, taxonomy and typing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17478660?accountid=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=Characterization+of+Mycobacterium+tuberculosis+Isolates+from+Patients+in+Houston%2C+Texas%2C+by+Spoligotyping&rft.au=Soini%2C+H%3BPan%2C+X%3BAmin%2C+A%3BGraviss%2C+E+A%3BSiddiqui%2C+A%3BMusser%2C+J+M&rft.aulast=Soini&rft.aufirst=H&rft.date=2000-02-01&rft.volume=38&rft.issue=2&rft.spage=669&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&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 - Mycobacterium tuberculosis; Tuberculosis; Genotyping ER - TY - JOUR T1 - Molecular genetic analysis of nucleotide polymorphisms associated with ethambutol resistance in human isolates of Mycobacterium tuberculosis AN - 17477370; 4676212 AB - Ethambutol (EMB) is a central component of drug regimens used worldwide for the treatment of tuberculosis. To gain insight into the molecular genetic basis of EMB resistance, approximately 2 Mb of five chromosomal regions with 12 genes in 75 epidemiologically unassociated EMB-resistant and 33 EMB-susceptible Mycobacterium tuberculosis strains isolated from human patients were sequenced. Seventy-six percent of EMB-resistant organisms had an amino acid replacement or other molecular change not found in EMB-susceptible strains. Thirty-eight (51%) EMB-resistant isolates had a resistance-associated mutation in only 1 of the 12 genes sequenced. Nineteen EMB-resistant isolates had resistance-associated nucleotide changes that conferred amino acid replacements or upstream potential regulatory region mutations in two or more genes. Most isolates (68%) with resistance-associated mutations in a single gene had nucleotide changes in embB, a gene encoding an arabinosyltransferase involved in cell wall biosynthesis. The majority of these mutations resulted in amino acid replacements at position 306 or 406 of EmbB. Resistance-associated mutations were also identified in several genes recently shown to be upregulated in response to exposure of M. tuberculosis to EMB in vitro, including genes in the iniA operon. Approximately one-fourth of the organisms studied lacked mutations inferred to participate in EMB resistance, a result indicating that one or more genes that mediate resistance to this drug remain to be discovered. Taken together, the results indicate that there are multiple molecular pathways to the EMB resistance phenotype. JF - Antimicrobial Agents & Chemotherapy AU - Ramaswamy, S V AU - Amin, A G AU - Goksel, S AU - Stager, ChE AU - Dou, Sh-J AU - El Sahly, H AU - Moghazeh, S L AU - Kreiswirth, B N 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 S. 4th St., Hamilton, MT 59840, USA, jmusser@niaid.nih.gov Y1 - 2000/02// PY - 2000 DA - Feb 2000 SP - 326 EP - 336 VL - 44 IS - 2 SN - 0066-4804, 0066-4804 KW - Ethambutol KW - embB gene KW - iniA operon KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Drug resistance KW - Nucleotide sequence KW - Genetic analysis KW - Antibacterial agents KW - Mutation KW - ethambutol KW - Mycobacterium tuberculosis KW - G 07320:Bacterial genetics KW - J 02814:Drug resistance KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17477370?accountid=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=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Molecular+genetic+analysis+of+nucleotide+polymorphisms+associated+with+ethambutol+resistance+in+human+isolates+of+Mycobacterium+tuberculosis&rft.au=Ramaswamy%2C+S+V%3BAmin%2C+A+G%3BGoksel%2C+S%3BStager%2C+ChE%3BDou%2C+Sh-J%3BEl+Sahly%2C+H%3BMoghazeh%2C+S+L%3BKreiswirth%2C+B+N%3BMusser%2C+J+M&rft.aulast=Ramaswamy&rft.aufirst=S&rft.date=2000-02-01&rft.volume=44&rft.issue=2&rft.spage=326&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/10.1128%2FAAC.44.2.326-336.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium tuberculosis; Nucleotide sequence; Drug resistance; Antibacterial agents; ethambutol; Genetic analysis; Mutation DO - http://dx.doi.org/10.1128/AAC.44.2.326-336.2000 ER - TY - JOUR T1 - A Mycobacterium ulcerans toxin, mycolactone, causes apoptosis in guinea pig ulcers and tissue culture cells AN - 17477212; 4676305 AB - Mycobacterium ulcerans is the causative agent of Buruli ulcer, a tropical ulcerative skin disease. One of the most intriguing aspects of this disease is the presence of extensive tissue damage in the absence of an acute inflammatory response. We recently purified and characterized a macrolide toxin, mycolactone, from M. ulcerans. Injection of this molecule into guinea pig skin reproduced cell death and lack of acute inflammatory response similar to that seen following the injection of viable bacteria. We also showed that mycolactone causes a cytopathic effect on mouse fibroblast L929 cells that is characterized by cytoskeletal rearrangements and growth arrest within 48 h. However, these results could not account for the extensive cell death which occurs in Buruli ulcer. The results presented here demonstrate that L929 and J774 mouse macrophage cells die via apoptosis after 3 to 5 days of exposure to mycolactone. Treatment of cells with a pan-caspase inhibitor can inhibit mycolactone-induced apoptosis. We demonstrate that injection of mycolactone into guinea pig skin results in cell death via apoptosis and that the extent of apoptosis increases as the lesion progresses. These results may help to explain why tissue damage in Buruli ulcer is not accompanied by an acute inflammatory response. JF - Infection and Immunity AU - George, K M AU - Pascopella, L AU - Welty, D M AU - Small, PLC AD - Microscopy Branch, NIAID/NIH, Rocky Mountain Laboratories, 903 S 4th St., Hamilton, MT 59840, USA, psmall@niaid.nih.gov Y1 - 2000/02// PY - 2000 DA - Feb 2000 SP - 877 EP - 883 VL - 68 IS - 2 SN - 0019-9567, 0019-9567 KW - Mycolactone KW - Toxicology Abstracts; Microbiology Abstracts B: Bacteriology KW - Macrophages KW - Mycobacterium ulcerans KW - Tissue culture KW - Toxins KW - Cell death KW - Ulcers KW - X 24171:Microbial KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17477212?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=A+Mycobacterium+ulcerans+toxin%2C+mycolactone%2C+causes+apoptosis+in+guinea+pig+ulcers+and+tissue+culture+cells&rft.au=George%2C+K+M%3BPascopella%2C+L%3BWelty%2C+D+M%3BSmall%2C+PLC&rft.aulast=George&rft.aufirst=K&rft.date=2000-02-01&rft.volume=68&rft.issue=2&rft.spage=877&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.68.2.877-883.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium ulcerans; Toxins; Cell death; Macrophages; Tissue culture; Ulcers DO - http://dx.doi.org/10.1128/IAI.68.2.877-883.2000 ER - TY - JOUR T1 - Nonpolar inactivation of the hypervariable streptococcal inhibitor of complement gene (sic) in serotype M1 Streptococcus pyogenes significantly decreases mouse mucosal colonization AN - 17476096; 4676315 AB - Group A Streptococcus (GAS) is a human pathogen that commonly infects the upper respiratory tract. GAS serotype M1 strains are frequently isolated from human infections and contain the gene encoding the hyper-variable streptococcal inhibitor of complement protein (Sic). It was recently shown that Sic variants were rapidly selected on mucosal surfaces in epidemic waves caused by M1 strains, an observation suggesting that Sic participates in host-pathogen interactions on the mucosal surface (N. P. Hoe, K. Nakashima, S. Lukomski, D. Grigsby, M. Liu, P. Kordari, S.-J. Dou, X. Pan, J. Vuopio-Varkila, S. Salmelinna, A. McGeer, D. E. Low, B. Schwartz, A. Schuchat, S. Naidich, D. De Lorenzo, Y.-X. Fu, and J. M. Musser, Nat. Med. 5:924-929, 1999). To test this idea, a new nonpolar mutagenesis method employing a spectinomycin resistance cassette was used to inactivate the sic gene in an M1 GAS strain. The isogenic Sic-negative mutant strain was significantly (P < 0.019) impaired in ability to colonize the mouse mucosal surface after intranasal infection. These results support the hypothesis that the predominance of M1 strains in human infections is related, in part, to a Sic-mediated enhanced colonization ability. JF - Infection and Immunity AU - Lukomski, S AU - Hoe, N P AU - Abdi, I AU - Rurangirwa, J AU - Kordari, P AU - Liu, M AU - Dou, Sh-J AU - Adams, G 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, USA, jmusser@bcm.tmc.edu Y1 - 2000/02// PY - 2000 DA - Feb 2000 SP - 535 EP - 542 VL - 68 IS - 2 SN - 0019-9567, 0019-9567 KW - animal models KW - mice KW - inhibitors KW - mutants KW - Sic protein KW - sic gene KW - streptococcal inhibitor of complement protein KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Colonization KW - Infectivity KW - Host-pathogen interactions KW - Complement KW - Mucosa KW - Streptococcus pyogenes KW - G 07320:Bacterial genetics KW - J 02845:Ear, nose and respiratory tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17476096?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Nonpolar+inactivation+of+the+hypervariable+streptococcal+inhibitor+of+complement+gene+%28sic%29+in+serotype+M1+Streptococcus+pyogenes+significantly+decreases+mouse+mucosal+colonization&rft.au=Lukomski%2C+S%3BHoe%2C+N+P%3BAbdi%2C+I%3BRurangirwa%2C+J%3BKordari%2C+P%3BLiu%2C+M%3BDou%2C+Sh-J%3BAdams%2C+G+G%3BMusser%2C+J+M&rft.aulast=Lukomski&rft.aufirst=S&rft.date=2000-02-01&rft.volume=68&rft.issue=2&rft.spage=535&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.68.2.535-542.2000 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus pyogenes; Mucosa; Host-pathogen interactions; Infectivity; Complement; Colonization DO - http://dx.doi.org/10.1128/IAI.68.2.535-542.2000 ER - TY - JOUR T1 - The salicylate-derived mycobactin siderophores of Mycobacterium tuberculosis are essential for growth in macrophages AN - 17469524; 4672080 AB - Mycobacterium tuberculosis is an important pathogen of mammals that relies on 2-hydroxyphenyloxazoline-containing siderophore molecules called mycobactins for the acquisition of iron in the restrictive environment of the mammalian macrophage. These compounds have been proposed to be biosynthesized through the action of a cluster of genes that include both nonribosomal peptide synthase and polyketide synthase components. One of these genes encodes a protein, MbtB, that putatively couples activated salicylic acid with serine or threonine and then cyclizes this precursor to the phenyloxazoline ring system. We have used gene replacement through homologous recombination to delete the mbtB gene and replace this with a hygromycin-resistance cassette in the virulent strain of M. tuberculosis H37Rv. The resulting mutant is restricted for growth in iron-limited media but grows normally in iron-replete media. Analysis of siderophore production by this organism revealed that the biosynthesis of all salicylate-derived siderophores was interrupted. The mutant was found to be impaired for growth in macrophage-like THP-1 cells, suggesting that siderophore production is required for virulence of M. tuberculosis. These results provide conclusive evidence linking this genetic locus to siderophore production. JF - Proceedings of the National Academy of Sciences, USA AU - De Voss, JJ AU - Rutter, K AU - Schroeder, B G AU - Su, H AU - Zhu, Y AU - Barry III, CE AD - Department of Chemistry, University of Queensland, Brisbane, Queensland, Australia 4067, clifton_barry@nih.gov Y1 - 2000/02/01/ PY - 2000 DA - 2000 Feb 01 SP - 1252 EP - 1257 VL - 97 IS - 3 SN - 0027-8424, 0027-8424 KW - MbtB protein KW - mbtB gene KW - mycobactin KW - mycobactins KW - salicylic acid KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Macrophages KW - Iron KW - Siderophores KW - Mycobacterium tuberculosis KW - G 07320:Bacterial genetics KW - J 02722:Biodegradation, growth, nutrition and leaching UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17469524?accountid=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=The+salicylate-derived+mycobactin+siderophores+of+Mycobacterium+tuberculosis+are+essential+for+growth+in+macrophages&rft.au=De+Voss%2C+JJ%3BRutter%2C+K%3BSchroeder%2C+B+G%3BSu%2C+H%3BZhu%2C+Y%3BBarry+III%2C+CE&rft.aulast=De+Voss&rft.aufirst=JJ&rft.date=2000-02-01&rft.volume=97&rft.issue=3&rft.spage=1252&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.97.3.1252 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium tuberculosis; Macrophages; Iron; Siderophores DO - http://dx.doi.org/10.1073/pnas.97.3.1252 ER - TY - JOUR T1 - Retrovirus mediated gene transfer of the self antigen MBP into the bone marrow of mice alters resistance to experimental autoimmune encephalomyelitis AN - 17444052; 4656133 AB - Experimental autoimmune encephalomyelitis (EAE) is a prototypic model of organ specific autoimmunity. MHC class II restricted T-cells directed against myelin basic protein (MBP) have been shown to cause EAE in susceptible strains of mice. We have asked whether the introduction of a gene encoding an autoantigen (MBP) into the hematopoetic stem cells of mice would result in tolerance to that protein. We have introduced cDNA encoding the 21.5 kDa isoform of MBP into the hematopoetic stem cells of B10.PL (73NS), SJL, and B10 mice by retrovirus-mediated gene transfer. Our experiments show expression of proviral MBP in peripheral blood and thymus following transplantation of genetically modified stem cells. Such expression does not result in deletion of MBP-specific T cells or tolerance to MBP, nor does it alter susceptibility to MBP-induced EAE in susceptible strains B10.PL and SJL. However, retrovirus-mediated gene transfer resulted in resistant B10 mice developing mild EAE. This report demonstrates that autoreactive MBP-specific T cells can be selected in the presence of endogenous antigen or an MBP-encoding retrovirus. JF - Journal of Neuroimmunology AU - Peters, T R AU - Bodine, D M AU - McDonagh, K T AU - Lovett-Racke, A AU - McFarland, H F AU - McFarlin, DE AU - Nienhuis, A W AU - Racke, M K AD - Clinical Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health Bethesda, MD 20892 USA Y1 - 2000/02/01/ PY - 2000 DA - 2000 Feb 01 SP - 51 EP - 62 PB - Elsevier VL - 103 IS - 1 SN - 0165-5728, 0165-5728 KW - mice KW - immunology KW - Retrovirus KW - myelin basic protein KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Gene therapy KW - Neuroimmunology KW - Bone marrow KW - Autoimmunity KW - Stem cells KW - Gene transfer KW - Lymphocytes T KW - Experimental allergic encephalomyelitis KW - Myelin basic protein KW - F 06872:EAE (multiple sclerosis) KW - N3 11110:Neuroimmunology KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17444052?accountid=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+Neuroimmunology&rft.atitle=Retrovirus+mediated+gene+transfer+of+the+self+antigen+MBP+into+the+bone+marrow+of+mice+alters+resistance+to+experimental+autoimmune+encephalomyelitis&rft.au=Peters%2C+T+R%3BBodine%2C+D+M%3BMcDonagh%2C+K+T%3BLovett-Racke%2C+A%3BMcFarland%2C+H+F%3BMcFarlin%2C+DE%3BNienhuis%2C+A+W%3BRacke%2C+M+K&rft.aulast=Peters&rft.aufirst=T&rft.date=2000-02-01&rft.volume=103&rft.issue=1&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neuroimmunology&rft.issn=01655728&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 - Experimental allergic encephalomyelitis; Lymphocytes T; Bone marrow; Gene transfer; Gene therapy; Retrovirus; Neuroimmunology; Myelin basic protein; Stem cells; Autoimmunity ER - TY - JOUR T1 - A novel effect of an opioid receptor antagonist, naloxone, on the production of reactive oxygen species by microglia: a study by electron paramagnetic resonance spectroscopy. AN - 71061712; 10784126 AB - Microglia as the first line of defensive cells in the brain produce free radicals including superoxide and nitric oxide (NO), contributing to neurodegeneration. An opioid receptor antagonist, naloxone, has been considered pharmacologically beneficial to endotoxin shock, experimental cerebral ischemia, and spinal cord injury. However, the mechanisms underlying these beneficial effects of naloxone are still not clear. This study explores the effects of naloxone on the production of superoxide and NO by the murine microglial cell line, BV2, stimulated with lipopolysaccharide (LPS) as measured by electron paramagnetic resonance (EPR). The production of superoxide triggered by phobol-12-myristate-13-acetate (PMA) resulted in superoxide dismutase (SOD)-inhibitable, catalase-uninhibitable 5,5-dimethyl-1-pyrroline N-oxide (DMPO) hydroxyl radical adduct formation. LPS enhanced the production of superoxide and triggered the formation of non-heme iron-nitrosyl complex. Cells pre-treated with naloxone showed significant reduction of superoxide production by 35%. However, it could not significantly reduce the formation of non-heme iron-nitrosyl complex and nitrite. Taken together, the results expand our understanding of the neuroprotective effects of naloxone as it decreases superoxide production by microglia. JF - Brain research AU - Chang, R C AU - Rota, C AU - Glover, R E AU - Mason, R P AU - Hong, J S AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2000/01/31/ PY - 2000 DA - 2000 Jan 31 SP - 224 EP - 229 VL - 854 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Cyclic N-Oxides KW - 0 KW - Lipopolysaccharides KW - Narcotic Antagonists KW - Nitrogen Oxides KW - Reactive Oxygen Species KW - Superoxides KW - 11062-77-4 KW - Nitric Oxide KW - 31C4KY9ESH KW - Hydroxyl Radical KW - 3352-57-6 KW - Naloxone KW - 36B82AMQ7N KW - dinitrosyl iron complex KW - 68586-27-6 KW - 5,5-dimethyl-1-pyrroline-1-oxide KW - 7170JZ1QF3 KW - Iron KW - E1UOL152H7 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Hydroxyl Radical -- metabolism KW - Nitrogen Oxides -- metabolism KW - Lipopolysaccharides -- pharmacology KW - Nitric Oxide -- metabolism KW - Mice KW - Superoxides -- antagonists & inhibitors KW - Iron -- metabolism KW - Superoxides -- metabolism KW - Iron -- antagonists & inhibitors KW - Nitrogen Oxides -- antagonists & inhibitors KW - Electron Spin Resonance Spectroscopy KW - Cyclic N-Oxides -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Line KW - Reactive Oxygen Species -- metabolism KW - Naloxone -- pharmacology KW - Narcotic Antagonists -- pharmacology KW - Microglia -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71061712?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=A+novel+effect+of+an+opioid+receptor+antagonist%2C+naloxone%2C+on+the+production+of+reactive+oxygen+species+by+microglia%3A+a+study+by+electron+paramagnetic+resonance+spectroscopy.&rft.au=Chang%2C+R+C%3BRota%2C+C%3BGlover%2C+R+E%3BMason%2C+R+P%3BHong%2C+J+S&rft.aulast=Chang&rft.aufirst=R&rft.date=2000-01-31&rft.volume=854&rft.issue=1-2&rft.spage=224&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-27 N1 - Date created - 2000-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of the ATPase domain of the Cockayne syndrome group B protein in UV induced apoptosis. AN - 70935075; 10698517 AB - Cockayne syndrome (CS) is a human autosomal recessive disorder characterized by many neurological and developmental abnormalities. CS cells are defective in the transcription coupled repair (TCR) pathway that removes DNA damage from the transcribed strand of active genes. The individuals suffering from CS do not generally develop cancer but show increased neurodegeneration. Two genetic complementation groups (CS-A and CS-B) have been identified. The lack of cancer formation in CS may be due to selective elimination of cells containing DNA damage by a suicidal pathway. In this study, we have evaluated the role of the CSB gene in UV induced apoptosis in human and hamster cells. The hamster cell line UV61 carries a mutation in the homolog of the human CSB gene. We show that both human CS-B and hamster UV61 cells display increased apoptotic response following UV exposure compared with normal cells. The increased sensitivity of UV61 cells to apoptosis is complemented by the transfection of the wild type human CSB gene. In order to determine which functional domain of the CSB gene participates in the apoptotic pathway, we constructed stable cell lines with different CSB domain disruptions. UV61 cells were stably transfected with the human CSB cDNA containing a point mutation in the highly conserved glutamic acid residue in ATPase motif II. This cell line (UV61/ pc3.1-CSBE646Q) showed the same increased apoptosis as the UV61 cells. In contrast, cells containing a deletion in the acidic domain at the N-terminal end of the CSB protein had no effect on apoptosis. This indicates that the integrity of the ATPase domain of CSB protein is critical for preventing the UV induced apoptotic pathway. In primary human CS-B cells, the induction and stabilization of the p53 protein seems to correlate with their increased apoptotic potential. In contrast, no change in the level of either p53 or activation of mdm2 protein by p53 was observed in hamster UV61 cells after UV exposure. This suggests that the CSB dependent apoptotic pathway can occur independently of the transactivation potential of p53 in hamster cells. JF - Oncogene AU - Balajee, A S AU - Proietti De Santis, L AU - Brosh, R M AU - Selzer, R AU - Bohr, V A AD - Laboratory of Molecular Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2000/01/27/ PY - 2000 DA - 2000 Jan 27 SP - 477 EP - 489 VL - 19 IS - 4 SN - 0950-9232, 0950-9232 KW - Nuclear Proteins KW - 0 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Recombinant Fusion Proteins KW - Tumor Suppressor Protein p53 KW - bcl-2-Associated X Protein KW - RNA KW - 63231-63-0 KW - DNA KW - 9007-49-2 KW - MDM2 protein, human KW - EC 2.3.2.27 KW - Proto-Oncogene Proteins c-mdm2 KW - RNA Polymerase II KW - EC 2.7.7.- KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - DNA Helicases KW - EC 3.6.4.- KW - ERCC6 protein, human KW - EC 3.6.4.12 KW - HRAS protein, human KW - EC 3.6.5.2 KW - Proto-Oncogene Proteins p21(ras) KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Animals KW - Tumor Suppressor Protein p53 -- physiology KW - Humans KW - DNA -- biosynthesis KW - Recombinant Fusion Proteins -- physiology KW - Mutagenesis, Site-Directed KW - RNA Polymerase II -- antagonists & inhibitors KW - Genes, p53 KW - Point Mutation KW - Molecular Sequence Data KW - Sequence Deletion KW - Cricetulus KW - Proto-Oncogene Proteins -- analysis KW - Amino Acid Sequence KW - Transcriptional Activation KW - RNA -- biosynthesis KW - Transfection KW - Proto-Oncogene Proteins p21(ras) -- analysis KW - Protein Structure, Tertiary KW - Cell Line KW - Cricetinae KW - Radiation Tolerance -- genetics KW - DNA Repair -- genetics KW - DNA Helicases -- chemistry KW - DNA Helicases -- physiology KW - Adenosine Triphosphatases -- physiology KW - Cockayne Syndrome -- genetics KW - Apoptosis -- physiology KW - Ultraviolet Rays -- adverse effects KW - Apoptosis -- radiation effects KW - Cockayne Syndrome -- enzymology KW - Cockayne Syndrome -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70935075?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+the+ATPase+domain+of+the+Cockayne+syndrome+group+B+protein+in+UV+induced+apoptosis.&rft.au=Balajee%2C+A+S%3BProietti+De+Santis%2C+L%3BBrosh%2C+R+M%3BSelzer%2C+R%3BBohr%2C+V+A&rft.aulast=Balajee&rft.aufirst=A&rft.date=2000-01-27&rft.volume=19&rft.issue=4&rft.spage=477&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-16 N1 - Date created - 2000-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. AN - 70885140; 10659874 AB - Whether menopausal hormone replacement therapy using a combined estrogen-progestin regimen increases risk of breast cancer beyond that associated with estrogen alone is unknown. To determine whether increases in risk associated with the estrogen-progestin regimen are greater than those associated with estrogen alone. Cohort study of follow-up data for 1980-1995 from the Breast Cancer Detection Demonstration Project, a nationwide breast cancer screening program. Twenty-nine screening centers throughout the United States. A total of 46355 postmenopausal women (mean age at start of follow-up, 58 years). Incident breast cancers by recency, duration, and type of hormone use. During follow-up, 2082 cases of breast cancer were identified. Increases in risk with estrogen only and estrogen-progestin only were restricted to use within the previous 4 years (relative risk [RR], 1.2 [95% confidence interval [CI], 1.0-1.4] and 1.4 [95% CI, 1.1-1.8], respectively); the relative risk increased by 0.01 (95% CI, 0.002-0.03) with each year of estrogen-only use and by 0.08 (95% CI, 0.02-0.16) with each year of estrogen-progestin-only use among recent users, after adjustment for mammographic screening, age at menopause, body mass index (BMI), education, and age. The P value associated with the test of homogeneity of these estimates was .02. Among women with a BMI of 24.4 kg/m2 or less, increases in RR with each year of estrogen-only use and estrogen-progestin-only use among recent users were 0.03 (95% CI, 0.01-0.06) and 0.12 (95% CI, 0.02-0.25), respectively. These associations were evident for the majority of invasive tumors with ductal histology and regardless of extent of invasive disease. Risk in heavier women did not increase with use of estrogen only or estrogen-progestin only. Our data suggest that the estrogen-progestin regimen increases breast cancer risk beyond that associated with estrogen alone. JF - JAMA AU - Schairer, C AU - Lubin, J AU - Troisi, R AU - Sturgeon, S AU - Brinton, L AU - Hoover, R AD - National Cancer Institute, Division of Cancer Epidemiology and Genetics, Rockville, MD 20852-7234, USA. schairec@exchange.nih.gov Y1 - 2000/01/26/ PY - 2000 DA - 2000 Jan 26 SP - 485 EP - 491 VL - 283 IS - 4 SN - 0098-7484, 0098-7484 KW - Estrogens KW - 0 KW - Progestins KW - Abridged Index Medicus KW - Index Medicus KW - Risk KW - Humans KW - Middle Aged KW - Follow-Up Studies KW - Poisson Distribution KW - Body Mass Index KW - Likelihood Functions KW - Menopause KW - Female KW - Estrogen Replacement Therapy -- adverse effects KW - Progestins -- adverse effects KW - Progestins -- administration & dosage KW - Breast Neoplasms -- epidemiology KW - Estrogens -- adverse effects KW - Estrogens -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70885140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Menopausal+estrogen+and+estrogen-progestin+replacement+therapy+and+breast+cancer+risk.&rft.au=Schairer%2C+C%3BLubin%2C+J%3BTroisi%2C+R%3BSturgeon%2C+S%3BBrinton%2C+L%3BHoover%2C+R&rft.aulast=Schairer&rft.aufirst=C&rft.date=2000-01-26&rft.volume=283&rft.issue=4&rft.spage=485&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-09 N1 - Date created - 2000-02-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 2000 Aug 9;284(6):692; author reply 693-4 [10927767] JAMA. 2000 Aug 9;284(6):691-2; author reply 693-4 [10927766] JAMA. 2000 Aug 9;284(6):691; author reply 693-4 [10927765] JAMA. 2000 Jan 26;283(4):534-5 [10659883] JAMA. 2000 Aug 9;284(6):692; author reply 693-4 [10927768] JAMA. 2000 Aug 9;284(6):692-3; author reply 693-4 [10927769] JAMA. 2000 Aug 9;284(6):693-4 [10927770] Erratum In: JAMA 2000 Nov 22-29;284(20):2597 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overexpression of neurotrophin receptor p75 contributes to the excitotoxin-induced cholinergic neuronal death in rat basal forebrain. AN - 70892294; 10640615 AB - Both excitotoxicity and altered trophic factor support have been implicated in the pathogenesis of Alzheimer's disease. To determine whether stimulation of p75, the low-affinity receptor for nerve growth factor, contributes to the excitotoxin-induced apoptotic death of cholinergic neurons, we examined the effect of unilateral kainic acid (KA; PBS vehicle, 1.25, 2.5 and 5.0 nmol) administration into rat basal forebrain on neuronal loss and p75 expression. KA (2. 5 nmol) destroyed 43% of Nissl-stained neurons and 70% of choline acetyltransferase (ChAT)-positive neurons 5 days after injection. Agarose gel electrophoresis revealed that KA (2.5 nmol) induced local internucleosomal DNA fragmentation after 6-48 h. Immunohistochemical analysis further showed that KA (2.5 nmol) augmented p75 immunoreactivity at a time when terminal transferase-mediated deoxyuridine trophosphate (d-UTP)-digoxigenin nick end labeling (TUNEL)-positive nuclei were increased. Many fragmented nuclei were co-labeled with ChAT antibody. The chronic administration of anti-rat p75 or the protein synthesis inhibitor, cycloheximide, but not anti-human p75, substantially reduced the KA-induced destruction of cholinergic neurons and the induction of internucleosomal DNA fragmentation. Anti-rat p75, but not cycloheximide, also reversed the spatial memory impairment produced by KA. These findings suggest that overexpression of p75 contributes to the excitotoxin-induced death of rat basal forebrain cholinergic neurons by an apoptotic-like mechanism. JF - Brain research AU - Oh, J D AU - Chartisathian, K AU - Chase, T N AU - Butcher, L L AD - Experimental Therapeutics Branch, Building 10, Room 5C103, National Institute of Neurological Disorders and Stroke, NIH, Bldg. 10, Room 5C211, 90900 Rockville Pike, Bethesda, MD, USA. jdoh@helix.nih.gov Y1 - 2000/01/24/ PY - 2000 DA - 2000 Jan 24 SP - 174 EP - 185 VL - 853 IS - 2 SN - 0006-8993, 0006-8993 KW - Antibodies KW - 0 KW - Neuroprotective Agents KW - Neurotoxins KW - Receptor, Nerve Growth Factor KW - Cycloheximide KW - 98600C0908 KW - Choline O-Acetyltransferase KW - EC 2.3.1.6 KW - Acetylcholine KW - N9YNS0M02X KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Animals KW - Microinjections KW - Cell Death -- drug effects KW - Choline O-Acetyltransferase -- metabolism KW - Neuroprotective Agents -- pharmacology KW - Rats KW - Behavior, Animal -- drug effects KW - Rats, Sprague-Dawley KW - Memory Disorders -- chemically induced KW - Cell Count -- drug effects KW - Antibodies -- pharmacology KW - Cycloheximide -- pharmacology KW - Apoptosis -- drug effects KW - DNA Fragmentation -- drug effects KW - Memory Disorders -- drug therapy KW - Male KW - Kainic Acid -- administration & dosage KW - Acetylcholine -- metabolism KW - Receptor, Nerve Growth Factor -- biosynthesis KW - Kainic Acid -- pharmacology KW - Prosencephalon -- metabolism KW - Neurons -- drug effects KW - Prosencephalon -- drug effects KW - Receptor, Nerve Growth Factor -- antagonists & inhibitors KW - Neurotoxins -- pharmacology KW - Neurons -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70892294?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Overexpression+of+neurotrophin+receptor+p75+contributes+to+the+excitotoxin-induced+cholinergic+neuronal+death+in+rat+basal+forebrain.&rft.au=Oh%2C+J+D%3BChartisathian%2C+K%3BChase%2C+T+N%3BButcher%2C+L+L&rft.aulast=Oh&rft.aufirst=J&rft.date=2000-01-24&rft.volume=853&rft.issue=2&rft.spage=174&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-21 N1 - Date created - 2000-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Smad4 activation domain (SAD) is a proline-rich, p300-dependent transcriptional activation domain. AN - 70876775; 10636916 AB - Transforming growth factor-beta (TGF-beta) family members signal through a unique set of intracellular proteins called Smads. Smad4, previously identified as the tumor suppressor DPC4, is functionally distinct among the Smad family, and is required for the assembly and transcriptional activation of diverse, Smad-DNA complexes. We previously identified a 48-amino acid proline-rich regulatory element within the middle linker domain of this molecule, the Smad4 activation domain (SAD), which is essential for mediating these signaling activities. We now characterize the functional activity of the SAD. Mutants lacking the SAD are still able to form complexes with other Smad family members and associated transcription factors, but cannot activate transcription in these complexes. Furthermore, the SAD itself is able to activate transcription in heterologous reporter assays, identifying it as a proline-rich transcriptional activation domain, and indicating that the SAD is both necessary and sufficient to activate Smad-dependent transcriptional responses. We show that transcriptional activation by the SAD is p300-dependent, and demonstrate that this activity is associated with a physical interaction of the SAD with the amino terminus of p300. These data identify a novel function of the middle linker region of Smad4, and define the role of the SAD as an important locus determining the transcriptional activation of the Smad complex. JF - The Journal of biological chemistry AU - de Caestecker, M P AU - Yahata, T AU - Wang, D AU - Parks, W T AU - Huang, S AU - Hill, C S AU - Shioda, T AU - Roberts, A B AU - Lechleider, R J AD - Laboratory of Cell Regulation and Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892-5055, USA. Y1 - 2000/01/21/ PY - 2000 DA - 2000 Jan 21 SP - 2115 EP - 2122 VL - 275 IS - 3 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Nuclear Proteins KW - SMAD2 protein, human KW - SMAD4 protein, human KW - Smad2 Protein KW - Smad2 protein, mouse KW - Smad4 Protein KW - Smad4 protein, mouse KW - Trans-Activators KW - Proline KW - 9DLQ4CIU6V KW - E1A-Associated p300 Protein KW - EC 2.3.1.48 KW - Ep300 protein, mouse KW - Index Medicus KW - Animals KW - COS Cells KW - Humans KW - Transcription, Genetic KW - Amino Acid Sequence KW - Mice KW - Precipitin Tests KW - Protein Binding KW - Proline -- metabolism KW - Cytoplasm -- metabolism KW - Molecular Sequence Data KW - Protein Structure, Tertiary KW - Fluorescent Antibody Technique KW - Cell Line KW - Trans-Activators -- metabolism KW - DNA-Binding Proteins -- chemistry KW - Trans-Activators -- genetics KW - Trans-Activators -- chemistry KW - DNA-Binding Proteins -- genetics KW - Nuclear Proteins -- metabolism KW - Transcriptional Activation KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70876775?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+Smad4+activation+domain+%28SAD%29+is+a+proline-rich%2C+p300-dependent+transcriptional+activation+domain.&rft.au=de+Caestecker%2C+M+P%3BYahata%2C+T%3BWang%2C+D%3BParks%2C+W+T%3BHuang%2C+S%3BHill%2C+C+S%3BShioda%2C+T%3BRoberts%2C+A+B%3BLechleider%2C+R+J&rft.aulast=de+Caestecker&rft.aufirst=M&rft.date=2000-01-21&rft.volume=275&rft.issue=3&rft.spage=2115&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 - 2000-02-24 N1 - Date created - 2000-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protection against methylation-induced cytotoxicity by DNA polymerase beta-dependent long patch base excision repair. AN - 70863967; 10636928 AB - Using a plasmid-based uracil-containing DNA substrate, we found that the long patch base excision repair (BER) activity of a wild-type mouse fibroblast extract was partially inhibited by an antibody to DNA polymerase beta (beta-pol). This suggests that beta-pol participates in long patch BER, in addition to single-nucleotide BER. In single-nucleotide BER, the deoxyribose phosphate (dRP) in the abasic site is removed by the lyase activity of beta-pol. Methoxyamine (MX) can react with the aldehyde of an abasic site, making it refractory to the beta-elimination step of the dRP lyase mechanism, thus blocking single-nucleotide BER. MX exposure sensitizes wild-type, but not beta-pol null mouse embryonic fibroblasts, to the cytotoxic effects of methyl methanesulfonate (MMS) and methylnitrosourea. Expression of beta-pol in the null cells restores the ability of MX to modulate sensitivity to MMS. The beta-pol null cells are known to be hypersensitive to MMS and methylnitrosourea, and in the presence of MX (i.e. under conditions where single-nucleotide BER is blocked) the null cells are still considerably more sensitive than wild-type. The data are consistent with a role of beta-pol in long patch BER, which helps protect cells against methylation damage-induced cytotoxicity. JF - The Journal of biological chemistry AU - Horton, J K AU - Prasad, R AU - Hou, E AU - Wilson, S H AD - Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000/01/21/ PY - 2000 DA - 2000 Jan 21 SP - 2211 EP - 2218 VL - 275 IS - 3 SN - 0021-9258, 0021-9258 KW - Alkylating Agents KW - 0 KW - Cell Extracts KW - DNA Adducts KW - Hydroxylamines KW - Mutagens KW - Ribosemonophosphates KW - Uracil KW - 56HH86ZVCT KW - Methylnitrosourea KW - 684-93-5 KW - 5-deoxyribose 1-phosphate KW - 86708-78-3 KW - methoxyamine KW - 9TZH4WY30J KW - Methyl Methanesulfonate KW - AT5C31J09G KW - DNA Polymerase beta KW - EC 2.7.7.- KW - Lyases KW - EC 4.- KW - Index Medicus KW - Animals KW - Ultraviolet Rays KW - Plasmids -- metabolism KW - Drug Interactions KW - Cell Extracts -- pharmacology KW - Dose-Response Relationship, Drug KW - Uracil -- metabolism KW - Alkylating Agents -- pharmacology KW - Methylnitrosourea -- pharmacology KW - Cell Division -- drug effects KW - Mice KW - Mutagens -- pharmacology KW - DNA Adducts -- metabolism KW - Gene Deletion KW - Lyases -- metabolism KW - Methyl Methanesulfonate -- pharmacology KW - Phenotype KW - DNA Methylation KW - Models, Genetic KW - Ribosemonophosphates -- metabolism KW - Hydroxylamines -- pharmacology KW - Time Factors KW - DNA Polymerase beta -- pharmacology KW - Fibroblasts -- drug effects KW - DNA Repair KW - DNA Polymerase beta -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70863967?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Protection+against+methylation-induced+cytotoxicity+by+DNA+polymerase+beta-dependent+long+patch+base+excision+repair.&rft.au=Horton%2C+J+K%3BPrasad%2C+R%3BHou%2C+E%3BWilson%2C+S+H&rft.aulast=Horton&rft.aufirst=J&rft.date=2000-01-21&rft.volume=275&rft.issue=3&rft.spage=2211&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 - 2000-02-24 N1 - Date created - 2000-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biological activities of antibodies elicited by lipooligosaccharide based-conjugate vaccines of nontypeable Haemophilus influenzae in an otitis media model AN - 17455453; 4663373 AB - Vaccination of chinchillas with nontypeable Haemophilus influenzae (NTHi) lipooligosaccharide (LOS) conjugates protected against otitis media. Correlations between the levels of conjugate-induced LOS antibodies (Abs) in sera and middle ear fluids (MEFs) and Ab-mediated biological functions and protection were examined. Following parenteral vaccination and middle ear challenge, all vaccinated animals, but none of the controls, had high titers of anti-LOS in their sera and MEFs. There was a correlation between the levels of anti-LOS IgG + M, IgG or IgA in the sera and in the MEFs (P < 0.001). An inverse correlation was found between the level of serum IgG + M and bacterial counts and between the levels of MEF Abs and bacterial counts at the early postchallenge stage (P < 0.05). Of the 39 vaccinated animals, 44% showed complete protection against otitis media, 46% (18/39) of their sera inhibited adherence of NTHi to human epithelial cells, 49% (19/39) demonstrated bactericidal activity and 49% (19/39) showed opsonophagocytic activity. In contrast, none of the controls (19) were protected, none of their sera inhibited bacterial adherence or had bactericidal activity and only 21% showed opsonophagocytosis. Our interpretation is that vaccine-induced LOS Abs transuded into the middle ear and conferred immunity to NTHi by binding to LOS of NTHi, inhibition of NTHi adherence to epithelial cells and complement-mediated bacteriolysis (or opsonophagocytosis). JF - Vaccine AU - Sun, Jianzhong AU - Chen, Jing AU - Cheng, Zhengyi AU - Robbins, J B AU - Battey, J F AU - Gu, Xin-Xing AD - Laboratory of Immunology, National Institute on Deafness and Other Communication Disorders, 5 Research Court, Rm. 2A31, Rockville, MD 20850, USA, guxx@nidcd.nih.gov Y1 - 2000/01/18/ PY - 2000 DA - 2000 Jan 18 SP - 1264 EP - 1272 VL - 18 IS - 13 SN - 0264-410X, 0264-410X KW - animal models KW - immunology KW - Chinchilla laniger KW - Haemophilus influenzae KW - lipooligosaccharides KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Middle ear KW - Antibodies KW - Otitis media KW - Vaccines KW - J 02834:Vaccination and immunization KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17455453?accountid=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=Biological+activities+of+antibodies+elicited+by+lipooligosaccharide+based-conjugate+vaccines+of+nontypeable+Haemophilus+influenzae+in+an+otitis+media+model&rft.au=Sun%2C+Jianzhong%3BChen%2C+Jing%3BCheng%2C+Zhengyi%3BRobbins%2C+J+B%3BBattey%2C+J+F%3BGu%2C+Xin-Xing&rft.aulast=Sun&rft.aufirst=Jianzhong&rft.date=2000-01-18&rft.volume=18&rft.issue=13&rft.spage=1264&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Haemophilus influenzae; Chinchilla laniger; Otitis media; Vaccines; Middle ear; Antibodies ER - TY - JOUR T1 - Vascular protection by chloroquine during brain tumor therapy with Tf-CRM107. AN - 70910832; 10667564 AB - Tf-CRM107 is a conjugate of transferrin and a point mutant of diphtheria toxin that selectively kills cells expressing high levels of the transferrin receptor. Tf-CRM107 has been infused intratumorally into patients with malignant brain tumors. Although approximately half of the patients exhibit tumor responses, patients receiving higher doses of Tf-CRM107 may develop magnetic resonance image (MRI) evidence of toxicity indicative of small vessel thrombosis or petechial hemorrhage. Consistent with these clinical results we found that intracerebral injection of Tf-CRM107 into rats at total doses > or =0.025 microg causes brain damage detectable by MRI and histology. To widen the therapeutic window of Tf-CRM107, we explored ways to prevent this damage to the vasculature. We reasoned that the vasculature may be protected to a greater extent than tumor from Tf-CRM107 infused into brain parenchyma by i.v. injection of reagents with low blood-brain barrier permeability that block the toxicity of Tf-CRM107. Chloroquine, a well-characterized antimalarial drug, blocks the toxicity of diphtheria toxin and Tf-CRM107. Systemic administration of chloroquine blocked the toxicity of Tf-CRM107 infused intracerebrally in rats and changed the maximum tolerated dose of Tf-CRM107 from 0.2 to 0.3 microg. Moreover, chloroquine treatment completely blocked the brain damage detected by MRI caused by intracerebral infusion of 0.05 microg of Tf-CRM107. In nude mice bearing s.c. U251 gliomas, chloroquine treatment had little effect on the antitumor efficacy of Tf-CRM107. Thus, chloroquine treatment may be useful to reduce the toxicity of Tf-CRM107 for normal brain without inhibiting antitumor efficacy and increase the therapeutic window of Tf-CRM107 for brain tumor therapy. JF - Cancer research AU - Hagihara, N AU - Walbridge, S AU - Olson, A W AU - Oldfield, E H AU - Youle, R J AD - Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/01/15/ PY - 2000 DA - 2000 Jan 15 SP - 230 EP - 234 VL - 60 IS - 2 SN - 0008-5472, 0008-5472 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Immunotoxins KW - Tf-CRM107 KW - Transferrin KW - Chloroquine KW - 886U3H6UFF KW - Index Medicus KW - Magnetic Resonance Imaging KW - Animals KW - Gliosarcoma -- drug therapy KW - Dose-Response Relationship, Drug KW - Humans KW - Glioblastoma -- drug therapy KW - Mice KW - Mice, Nude KW - Rats KW - Rats, Inbred F344 KW - Tumor Cells, Cultured KW - Glioblastoma -- pathology KW - Gliosarcoma -- pathology KW - Transplantation, Heterologous KW - Brain Neoplasms -- pathology KW - Brain Neoplasms -- drug therapy KW - Immunotoxins -- toxicity KW - Chloroquine -- pharmacology KW - Cerebrovascular Circulation -- drug effects KW - Bacterial Toxins -- therapeutic use KW - Transferrin -- therapeutic use KW - Immunotoxins -- therapeutic use KW - Transferrin -- toxicity KW - Bacterial Toxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70910832?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Vascular+protection+by+chloroquine+during+brain+tumor+therapy+with+Tf-CRM107.&rft.au=Hagihara%2C+N%3BWalbridge%2C+S%3BOlson%2C+A+W%3BOldfield%2C+E+H%3BYoule%2C+R+J&rft.aulast=Hagihara&rft.aufirst=N&rft.date=2000-01-15&rft.volume=60&rft.issue=2&rft.spage=230&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 - 2000-02-28 N1 - Date created - 2000-02-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of uterine adenocarcinoma in CD-1 mice by catechol estrogens. AN - 70899430; 10667565 AB - Catechol estrogens may mediate estrogen-induced carcinogenesis because 4-hydroxyestradiol induces DNA damage and renal tumors in hamsters, and this metabolite is formed in the kidney and estrogen target tissues by a specific estrogen 4-hydroxylase. We examined the carcinogenic potential of catechol estrogen in an experimental model previously reported to result in a high incidence of uterine adenocarcinoma after neonatal exposure to diethylstilbestrol. Outbred female CD-1 mice were treated with 2- or 4-hydroxyestradiol, 17beta-estradiol, or 17alpha-ethinyl estradiol on days 1-5 of neonatal life (2 microg/pup/day) and sacrificed at 12 or 18 months of age. Mice treated with 17beta-estradiol or 17a-ethinyl estradiol had a total uterine tumor incidence of 7% or 43%, respectively. 2-Hydroxyestradiol induced tumors in 12% of the mice, but 4-hydroxyestradiol was the most carcinogenic estrogen, with a 66% incidence of uterine adenocarcinoma. Both 2- and 4-hydroxylated catechols were estrogenic and increased uterine wet weights in these neonates. These data demonstrate that both 2- and 4-hydroxyestradiol are carcinogenic metabolites. The high tumor incidence induced by 4-hydroxyestradiol supports the postulated role of this metabolite in hormone-associated cancers. JF - Cancer research AU - Newbold, R R AU - Liehr, J G AD - Developmental Endocrinology Section, Reproductive Toxicology Group, Laboratory of Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. newbold1@niehs.nih.gov Y1 - 2000/01/15/ PY - 2000 DA - 2000 Jan 15 SP - 235 EP - 237 VL - 60 IS - 2 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - Estrogens, Catechol KW - Ethinyl Estradiol KW - 423D2T571U KW - Estradiol KW - 4TI98Z838E KW - 2-hydroxyestradiol KW - AYU2L67YUU KW - 4-hydroxyestradiol KW - C3ZO03450E KW - Index Medicus KW - Animals, Newborn KW - Animals KW - Mice KW - Ethinyl Estradiol -- toxicity KW - Female KW - Cricetinae KW - Estradiol -- analogs & derivatives KW - Adenocarcinoma -- chemically induced KW - Uterine Neoplasms -- chemically induced KW - Estradiol -- toxicity KW - Uterus -- pathology KW - Estrogens, Catechol -- toxicity KW - Uterus -- drug effects KW - Uterine Neoplasms -- pathology KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70899430?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+uterine+adenocarcinoma+in+CD-1+mice+by+catechol+estrogens.&rft.au=Newbold%2C+R+R%3BLiehr%2C+J+G&rft.aulast=Newbold&rft.aufirst=R&rft.date=2000-01-15&rft.volume=60&rft.issue=2&rft.spage=235&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 - 2000-02-28 N1 - Date created - 2000-02-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The geldanamycins are potent inhibitors of the hepatocyte growth factor/scatter factor-met-urokinase plasminogen activator-plasmin proteolytic network. AN - 70897058; 10667586 AB - The Met receptor tyrosine kinase and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), have been implicated in human tumor development and metastasis. HGF/SF induces the expression of urokinase plasminogen activator (uPA) and the uPA receptor (uPAR), important mediators of cell invasion and metastasis. We have developed a cell-based assay to screen for inhibitors of this signaling system using the induction of endogenous uPA and uPAR and the subsequent conversion of plasminogen to plasmin as the biological end point. Assay validation was established using a neutralizing antiserum to HGF/SF and a uPA inhibitor (B428), as well as inhibitors of the MKK-MAPK1/2 pathway, shown previously to be important in the induction of uPA and uPAR. Using this assay, we found several classes of molecules that exhibited inhibition of HGF/SF-dependent plasmin activation. However, we discovered that certain members of the geldanamycin family of anisamycin antibiotics are potent inhibitors of HGF/SF-mediated plasmin activation, displaying inhibitory properties at femtomolar concentrations and nine orders of magnitude below their growth inhibitory concentrations. At nanomolar concentrations, the geldanamycins down-regulate Met protein expression, inhibit HGF/SF-mediated cell motility and invasion, and also revert the phenotype of both autocrine HGF/SF-Met transformed cells as well as those transformed by Met proteins with activating mutations. Thus, the geldanamycins may have important therapeutic potential for the treatment of cancers in which Met activity contributes to the invasive/metastatic phenotype. JF - Cancer research AU - Webb, C P AU - Hose, C D AU - Koochekpour, S AU - Jeffers, M AU - Oskarsson, M AU - Sausville, E AU - Monks, A AU - Vande Woude, G F AD - Advanced Bioscience Laboratories-Basic Research Program, National Cancer Institute-Frederick Cancer Research Developmental Center, Frederick, Maryland 21702, USA. craig.webb@vai.org Y1 - 2000/01/15/ PY - 2000 DA - 2000 Jan 15 SP - 342 EP - 349 VL - 60 IS - 2 SN - 0008-5472, 0008-5472 KW - Antibiotics, Antineoplastic KW - 0 KW - Benzoquinones KW - Lactams, Macrocyclic KW - PLAUR protein, human KW - Plaur protein, mouse KW - Quinones KW - Receptors, Cell Surface KW - Receptors, Urokinase Plasminogen Activator KW - Recombinant Proteins KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - Proto-Oncogene Proteins c-met KW - EC 2.7.10.1 KW - Fibrinolysin KW - EC 3.4.21.7 KW - Urokinase-Type Plasminogen Activator KW - EC 3.4.21.73 KW - geldanamycin KW - Z3K3VJ16KU KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Humans KW - Cell Division -- drug effects KW - Mice KW - Structure-Activity Relationship KW - Tumor Cells, Cultured KW - Transfection KW - Recombinant Proteins -- metabolism KW - Cell Line, Transformed KW - Cell Line KW - Signal Transduction KW - Receptors, Cell Surface -- metabolism KW - Quinones -- toxicity KW - Hepatocyte Growth Factor -- metabolism KW - Proto-Oncogene Proteins c-met -- physiology KW - Fibrinolysin -- metabolism KW - Urokinase-Type Plasminogen Activator -- metabolism KW - Antibiotics, Antineoplastic -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70897058?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=The+geldanamycins+are+potent+inhibitors+of+the+hepatocyte+growth+factor%2Fscatter+factor-met-urokinase+plasminogen+activator-plasmin+proteolytic+network.&rft.au=Webb%2C+C+P%3BHose%2C+C+D%3BKoochekpour%2C+S%3BJeffers%2C+M%3BOskarsson%2C+M%3BSausville%2C+E%3BMonks%2C+A%3BVande+Woude%2C+G+F&rft.aulast=Webb&rft.aufirst=C&rft.date=2000-01-15&rft.volume=60&rft.issue=2&rft.spage=342&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 - 2000-02-28 N1 - Date created - 2000-02-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phenolphthalein metabolite inhibits catechol-O-methyltransferase-mediated metabolism of catechol estrogens: a possible mechanism for carcinogenicity. AN - 70842988; 10637136 AB - Phenolphthalein (PT), used in over-the-counter laxatives, has recently been identified as a multisite carcinogen in rodents, but the molecular species responsible for the carcinogenicity is not known. A catechol metabolite of PT, hydroxyphenolphthalein (PT-CAT), was recently identified and may be the molecular species responsible for at least part of the toxicity/carcinogenicity of PT. We hypothesize that PT-CAT inhibits the enzyme catechol-O-methyltransferase (COMT) and therefore potentiates genotoxicity by either PT-CAT itself or the endogenous catechol estrogens (CEs) in susceptible tissues. The present studies were conducted to determine the effects of PT treatment and PT-CAT itself on the COMT-mediated metabolism of 4- and 2-hydroxyestradiol both in vitro and in vivo. Female mice were treated with PT (50 mg/kg/d) for 21 days and then euthanized. PT-CAT concentration in urine reached plateau levels by 7 days of exposure. An O-methylated metabolite of PT-CAT was detected in feces. In vitro experiments demonstrated that PT treatment resulted in an increase in free CEs, which are normally cleared by COMT and a concurrent decrease in the capacity of hepatic catechol clearance by COMT. In vitro, PT-CAT was a substrate of COMT, with kinetic properties within the range measured with endogenous substrates. PT-CAT was an extremely potent mixed-type inhibitor of the O-methylation of the catechol estrogens, with 90-300 nM IC50s. The above data, when taken together, suggest that chronic administration of PT may enhance metabolic redox cycling of both PT-CAT and the catechol estrogens and this, in turn, may contribute to PT-induced tumorigenesis. JF - Toxicology and applied pharmacology AU - Garner, C E AU - Matthews, H B AU - Burka, L T AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. C.Edwin.Garner@Dupontpharma.com Y1 - 2000/01/15/ PY - 2000 DA - 2000 Jan 15 SP - 124 EP - 131 VL - 162 IS - 2 SN - 0041-008X, 0041-008X KW - Carcinogens KW - 0 KW - Catechol O-Methyltransferase Inhibitors KW - Cathartics KW - Enzyme Inhibitors KW - Estrogens, Catechol KW - Phenolphthaleins KW - hydroxyphenolphthalein KW - Estradiol KW - 4TI98Z838E KW - Phenolphthalein KW - 6QK969R2IF KW - 2-hydroxyestradiol KW - AYU2L67YUU KW - 4-hydroxyestradiol KW - C3ZO03450E KW - Catechol O-Methyltransferase KW - EC 2.1.1.6 KW - Index Medicus KW - Swine KW - Estradiol -- analogs & derivatives KW - Mice, Inbred Strains KW - Animals KW - Liver -- enzymology KW - Liver -- drug effects KW - Methylation -- drug effects KW - Kinetics KW - Mice KW - Female KW - Estradiol -- metabolism KW - Catechol O-Methyltransferase -- metabolism KW - Phenolphthaleins -- toxicity KW - Phenolphthalein -- blood KW - Cathartics -- toxicity KW - Enzyme Inhibitors -- urine KW - Enzyme Inhibitors -- toxicity KW - Phenolphthaleins -- metabolism KW - Carcinogens -- toxicity KW - Cathartics -- metabolism KW - Phenolphthaleins -- blood KW - Phenolphthaleins -- urine KW - Carcinogens -- metabolism KW - Phenolphthalein -- metabolism KW - Estrogens, Catechol -- metabolism KW - Phenolphthalein -- urine KW - Phenolphthalein -- toxicity KW - Enzyme Inhibitors -- blood KW - Enzyme Inhibitors -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70842988?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Phenolphthalein+metabolite+inhibits+catechol-O-methyltransferase-mediated+metabolism+of+catechol+estrogens%3A+a+possible+mechanism+for+carcinogenicity.&rft.au=Garner%2C+C+E%3BMatthews%2C+H+B%3BBurka%2C+L+T&rft.aulast=Garner&rft.aufirst=C&rft.date=2000-01-15&rft.volume=162&rft.issue=2&rft.spage=124&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-02 N1 - Date created - 2000-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction of Ly-49D+ NK cells with H-2Dd target cells leads to Dap-12 phosphorylation and IFN-gamma secretion. AN - 70820026; 10623801 AB - Murine Ly-49D augments NK cell function upon recognition of target cells expressing H-2Dd. Ly-49D activation is mediated by the immunoreceptor tyrosine-based activation motif-containing signaling moiety Dap-12. In this report we demonstrate that Ly-49D receptor ligation can lead to the rapid and potent secretion of IFN-gamma. Cytokine secretion can be induced from Ly-49D+ NK cells after receptor ligation with Ab or after interaction with target cells expressing their H-2Dd ligand. Consistent with the dominant inhibitory function of Ly-49G, NK cells coexpressing Ly-49D and Ly-49G show a profound reduction in IFN-gamma secretion after interaction with targets expressing their common ligand, H-2Dd. Importantly, we are able to demonstrate for the first time that effector/target cell interactions using Ly-49D+ NK cells and H-2Dd targets result in the rapid phosphorylation of Dap-12. However, Dap-12 is not phosphorylated when Ly-49D+ NK cells coexpress the inhibitory receptor, Ly-49G. These studies are novel in describing Ly-49 activation vs inhibition, where two Ly-49 receptors recognize the same class I ligand, with the dominant inhibitory receptor down-regulating phosphorylation of Dap-12, cytokine secretion, and cytotoxicity in NK cells. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Mason, L H AU - Willette-Brown, J AU - Mason, A T AU - McVicar, D AU - Ortaldo, J R AD - Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 2000/01/15/ PY - 2000 DA - 2000 Jan 15 SP - 603 EP - 611 VL - 164 IS - 2 SN - 0022-1767, 0022-1767 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Antigens, Ly KW - H-2 Antigens KW - Histocompatibility Antigen H-2D KW - Lectins, C-Type KW - Membrane Glycoproteins KW - Membrane Proteins KW - Phosphoproteins KW - Receptors, Immunologic KW - Receptors, NK Cell Lectin-Like KW - TYROBP protein, human KW - Interferon-gamma KW - 82115-62-6 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Mice KW - Rats KW - Tumor Cells, Cultured KW - Phosphorylation KW - Transfection KW - Mice, Inbred C57BL KW - Cytotoxicity Tests, Immunologic KW - Membrane Glycoproteins -- immunology KW - Cell Line KW - Membrane Glycoproteins -- metabolism KW - Phosphoproteins -- metabolism KW - Interferon-gamma -- antagonists & inhibitors KW - H-2 Antigens -- immunology KW - Cytotoxicity, Immunologic -- immunology KW - Receptors, Immunologic -- antagonists & inhibitors KW - H-2 Antigens -- genetics KW - Killer Cells, Natural -- secretion KW - Receptors, Immunologic -- immunology KW - Interferon-gamma -- secretion KW - H-2 Antigens -- pharmacology KW - Receptors, Immunologic -- metabolism KW - Receptors, Immunologic -- biosynthesis KW - Killer Cells, Natural -- metabolism KW - Killer Cells, Natural -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70820026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interaction+of+Ly-49D%2B+NK+cells+with+H-2Dd+target+cells+leads+to+Dap-12+phosphorylation+and+IFN-gamma+secretion.&rft.au=Mason%2C+L+H%3BWillette-Brown%2C+J%3BMason%2C+A+T%3BMcVicar%2C+D%3BOrtaldo%2C+J+R&rft.aulast=Mason&rft.aufirst=L&rft.date=2000-01-15&rft.volume=164&rft.issue=2&rft.spage=603&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 - 2000-02-10 N1 - Date created - 2000-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Catechol Metabolites of Polychlorinated Biphenyls Inhibit the Catechol-O-methyltransferase-Mediated Metabolism of Catechol Estrogens AN - 17900191; 5156963 AB - The catechol metabolites of estradiol, 2- and 4-hydroxyestradiol (2-OHE sub(2) and 4-OHE sub(2), respectively) are potent signaling molecules and are hypothesized to be central to estrogen-linked carcinogenesis. Methylation by catechol-O-methyltransferase (COMT) is the principal means of catechol estrogen (CE) deactivation in the liver and other tissues. The present studies were conducted to determine the effects of PCBs and catechol metabolites of PCBs on the COMT-mediated catabolism of 4-OHE sub(2) and 2-OHE sub(2) in vitro and in vivo. Liver homogenates of female Sprague-Dawley rats treated with Aroclor 1254 for 21 days (5 mg/kg/day) showed a 30 and 40% reduction of COMT activity toward 2-OHE sub(2) and 4-OHE sub(2), respectively. Incubation of [ super(3)H]- beta -estradiol with these same liver homogenates, followed by HPLC analysis, demonstrated an elevation of CEs and a nearly complete reduction in levels of methylated catechol estrogens. In classical enzyme kinetics studies, COMT was demonstrated to have a high affinity for catechol PCBs, with K sub(m)'s approximately equivalent to those of CEs. Catechol PCBs were also potent inhibitors of CE O-methylation. These data suggest that PCBs may significantly alter the metabolism of catechol estrogens in vivo and that this effect may be mediated by catechol metabolites of PCBs. It is further speculated that methyltransferase inhibition by PCB catechols may contribute to PCB-mediated endocrine effects and liver carcinogenesis. JF - Toxicology and Applied Pharmacology AU - Garner, CE AU - Burka, L T AU - Etheridge, A E AU - Matthews, H B AD - Laboratory of Pharmacology and Chemistry, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, C.Edwin.Garner@Dupontpharma.com Y1 - 2000/01/15/ PY - 2000 DA - 2000 Jan 15 SP - 115 EP - 123 PB - Academic Press VL - 162 IS - 2 SN - 0041-008X, 0041-008X KW - rats KW - catechol KW - methyltransferase KW - Toxicology Abstracts KW - Aroclor KW - Estrogens KW - Carcinogenesis KW - Liver KW - Endocrine system KW - PCB KW - X 24153:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17900191?accountid=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=Catechol+Metabolites+of+Polychlorinated+Biphenyls+Inhibit+the+Catechol-O-methyltransferase-Mediated+Metabolism+of+Catechol+Estrogens&rft.au=Garner%2C+CE%3BBurka%2C+L+T%3BEtheridge%2C+A+E%3BMatthews%2C+H+B&rft.aulast=Garner&rft.aufirst=CE&rft.date=2000-01-15&rft.volume=162&rft.issue=2&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1006%2Ftaap.1999.8823 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Estrogens; PCB; Aroclor; Endocrine system; Liver; Carcinogenesis DO - http://dx.doi.org/10.1006/taap.1999.8823 ER - TY - JOUR T1 - CpG Oligonucleotides Can Prophylactically Immunize Against Th2-Mediated Schistosome Egg-Induced Pathology by an IL-12-Independent Mechanism AN - 17459946; 4663431 AB - Using a Schistosoma mansoni egg-induced granuloma model, we examined the ability of CpG oligodeoxynucleotides (ODN) to suppress Th2-type cytokine expression and to prophylactically immunize against Th2-dependent pulmonary pathology. The mechanism was examined by studying Th2 response regulation in cytokine-deficient mice. Surprisingly, our findings revealed several functions of CpG DNA that were completely IL-12 independent. Most striking was the marked suppression in Th2 cytokine expression and granulomatous inflammation observed in egg/CpG-sensitized IL-12-deficient mice. Immune deviation was not dependent on NK or B cells. However, a role for IL-10, B7.1, and CD40 expression in Th2 response inhibition was suggested. Indeed, CpG ODN up-regulated all three elements in both wild-type and IL-12-deficient mice. The role of IL-10 was demonstrated in mice exhibiting combined deficiencies in IL-12 and IL-10. Here, a marked increase in egg-specific IL-4/IL-5-producing cells confirmed a role for both cytokines in Th2 response inhibition. Nevertheless, the frequency of Th2-producing cells was again reduced by CpG ODN. However, in marked contrast to IL-12-deficient animals, a significant increase in IFN- gamma -producing cells likely explains the reduced Th2 response in IL-10/IL-12-deficient mice. Thus, a novel IL-12-independent type 1-inducing pathway was revealed in the combined absence of IL-12 and IL-10. Together, these data demonstrate 1) that the Th1-promoting activity of CpG DNA is controlled by IL-12 and IL-10, and 2) that Th2 response inhibition by CpG ODN involves IL-12-independent changes in IL-10 and costimulatory molecule expression. These findings illustrate the utility of CpG DNA as adjuvants for vaccines designed to prevent Th2-dependent immunopathology. JF - Journal of Immunology AU - Chiaramonte, M G AU - Hesse, M AU - Cheever, A W AU - Wynn, T A AD - Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Building 4/126, Rockville, MD 20892-0425, USA, twynn@niaid.nih.gov Y1 - 2000/01/15/ PY - 2000 DA - 2000 Jan 15 SP - 973 EP - 985 VL - 164 IS - 2 SN - 0022-1767, 0022-1767 KW - Cpg motifs KW - immunology KW - DNA vaccines KW - Schistosoma mansoni KW - oligonucleotides KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Helper cells KW - Adjuvants KW - Eggs KW - Interleukin 10 KW - Interleukin 12 KW - Lymphocytes T KW - Vaccines KW - F 06807:Active immunization KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17459946?accountid=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+Immunology&rft.atitle=CpG+Oligonucleotides+Can+Prophylactically+Immunize+Against+Th2-Mediated+Schistosome+Egg-Induced+Pathology+by+an+IL-12-Independent+Mechanism&rft.au=Chiaramonte%2C+M+G%3BHesse%2C+M%3BCheever%2C+A+W%3BWynn%2C+T+A&rft.aulast=Chiaramonte&rft.aufirst=M&rft.date=2000-01-15&rft.volume=164&rft.issue=2&rft.spage=973&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&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 - Interleukin 10; Eggs; Lymphocytes T; Helper cells; Vaccines; Adjuvants; Interleukin 12 ER - TY - JOUR T1 - Lethal seizures predicted after aminophylline therapy in cocaine abusers. AN - 70853494; 10650168 AB - Mice with a history of chronic (10 days), but not acute, treatment with a non-convulsant dose of cocaine showed increased sensitivity (P<0.001) to the toxic effects of aminophylline (seizures, lethality) relative to controls even days after the cessation of cocaine treatment. The present finding suggests that individuals with a history of cocaine use may be at increased risk for convulsive and lethal complications associated with the therapeutic use of aminophylline. JF - European journal of pharmacology AU - Gasior, M AU - Ungard, J T AU - Witkin, J M AD - Drug Development Group, Behavioral Neuroscience Research Branch, National Institute on Drug Abuse, NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. mgasior@intra.nida.nih.gov Y1 - 2000/01/10/ PY - 2000 DA - 2000 Jan 10 SP - R15 EP - R16 VL - 387 IS - 2 SN - 0014-2999, 0014-2999 KW - Aminophylline KW - 27Y3KJK423 KW - Index Medicus KW - Animals KW - Mice KW - Male KW - Seizures -- chemically induced KW - Aminophylline -- toxicity KW - Cocaine-Related Disorders -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70853494?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+pharmacology&rft.atitle=Lethal+seizures+predicted+after+aminophylline+therapy+in+cocaine+abusers.&rft.au=Gasior%2C+M%3BUngard%2C+J+T%3BWitkin%2C+J+M&rft.aulast=Gasior&rft.aufirst=M&rft.date=2000-01-10&rft.volume=387&rft.issue=2&rft.spage=R15&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-28 N1 - Date created - 2000-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA vaccination of mice against rabies virus: effects of the route of vaccination and the adjuvant monophosphoryl lipid A (MPL registered ) AN - 17456469; 4663333 AB - Adjuvants are known to strongly enhance immune responses generated by traditional vaccines, but less is known about the effects of adjuvants on vaccination with DNA. In this study, we investigated the use of the immunostimulant monophosphoryl lipid A (MPL registered ) as an adjuvant, and analyzed three routes of DNA vaccination to determine if this adjuvant could enhance anti-rabies virus neutralizing antibody responses. Compared with antibody titers elicited with DNA only, antibody titers were enhanced after initial intradermal (i.d.) and gene gun immunizations with the combination of DNA and MPL registered . Antibody was not detected after primary intramuscular (i.m.) immunization unless MPL registered was included with the DNA. Surprisingly, antibody titers of MPL registered -treated mice decreased after i.d. or i.m. booster vaccinations, but increased after gene gun booster vaccinations. In contrast to these varied responses, booster immunizations without MPL registered via the three different routes consistently increased antibody titers. All mice with detectable levels of neutralizing antibody at the time of challenge survived virus infection. There was no difference in the survival rate between groups of mice that received similar vaccinations with MPL registered /DNA or DNA only. The data suggest that MPL registered can enhance the neutralizing antibody response when used with the initial injection of DNA. Suppression of neutralizing antibody responses after i.d. or i.m. booster vaccinations that included MPL registered suggests that the number of vaccinations, and the route of vaccination, should be carefully considered when MPL registered is used with DNA vaccines. JF - Vaccine AU - Lodmell, D L AU - Ray, N B AU - Ulrich, J T AU - Ewalt, L C AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institutes of Allergy and Infectious Diseases, 903 South Fourth Street, Hamilton, MT 59840, USA, dlodmell@nih.gov Y1 - 2000/01/06/ PY - 2000 DA - 2000 Jan 06 SP - 1059 EP - 1066 VL - 18 IS - 11-12 SN - 0264-410X, 0264-410X KW - mice KW - immunology KW - DNA vaccines KW - Rabies virus KW - monophosphoryl lipid A KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts; Immunology Abstracts KW - Vaccines KW - Adjuvants KW - Antibody response 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/17456469?accountid=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=DNA+vaccination+of+mice+against+rabies+virus%3A+effects+of+the+route+of+vaccination+and+the+adjuvant+monophosphoryl+lipid+A+%28MPL+registered+%29&rft.au=Lodmell%2C+D+L%3BRay%2C+N+B%3BUlrich%2C+J+T%3BEwalt%2C+L+C&rft.aulast=Lodmell&rft.aufirst=D&rft.date=2000-01-06&rft.volume=18&rft.issue=11-12&rft.spage=1059&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Rabies virus; Antibody response; Adjuvants; Vaccines ER - TY - JOUR T1 - HPV DNA testing in cervical cancer screening: results from women in a high-risk province of Costa Rica. AN - 70868357; 10632285 AB - Human papillomaviruses (HPVs) are known to cause most cervical cancer worldwide, but the utility of HPV DNA testing in cervical cancer prevention has not been determined. To provide comprehensive data on the screening performance of HPV testing for the most common carcinogenic types, at different levels of analytic sensitivity. Laboratory analysis conducted during 1993-1995, using 3 cytologic techniques and cervicography, followed by colposcopic examination of women with any abnormal cervical finding, to detect all high-grade intraepithelial lesions and cancer (reference standard of clinically significant disease). The HPV testing was performed subsequently with masking regarding clinical findings. Guanacaste Province, Costa Rica, a region with a high age-adjusted incidence of cervical cancer. Of 11742 randomly selected women, 8554 nonpregnant, sexually active women without hysterectomies underwent initial HPV DNA testing using the original Hybrid Capture Tube test; a stratified subsample of 1119 specimens was retested using the more analytically sensitive second generation assay, the Hybrid Capture II test. Receiver operating characteristic analysis of detection of cervical high-grade intraepithelial lesions and cancer by HPV DNA testing based on different cut points of positivity. An analytic sensitivity of 1.0 pg/mL using the second generation assay would have permitted detection of 88.4% of 138 high-grade lesions and cancers (all 12 cancers were HPV-positive), with colposcopic referral of 12.3% of women. Papanicolaou testing using atypical squamous cells of undetermined significance as a cut point for referral resulted in 77.7% sensitivity and 94.2% specificity, with 6.9% referred. Specificity of the second generation assay for positivity for high-grade lesions and cancer was 89.0%, with 33.8% of remaining HPV DNA-positive subjects having low-grade or equivocal microscopically evident lesions. The higher detection threshold of 10 pg/mL used with the original assay had a sensitivity of 74.8% and a specificity of 93.4%. Lower levels of detection with the second generation assay (<1 pg/mL) proved clinically nonspecific without gains in diagnostic sensitivity. In this study population, a cut point of 1.0 pg/mL using the second generation assay permitted sensitive detection of cervical high-grade lesions and cancer, yielding an apparently optimal trade-off between high sensitivity and reasonable specificity for this test. The test will perform best in settings in which sensitive detection of high-grade lesions and cancer is paramount. Because HPV prevalence varies by population, HPV testing positive predictive value for detection of high-grade lesions and cancer will vary accordingly, with implications for utility relative to other cervical cancer screening methods. JF - JAMA AU - Schiffman, M AU - Herrero, R AU - Hildesheim, A AU - Sherman, M E AU - Bratti, M AU - Wacholder, S AU - Alfaro, M AU - Hutchinson, M AU - Morales, J AU - Greenberg, M D AU - Lorincz, A T AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. schiffmm@exchange.nih.gov Y1 - 2000/01/05/ PY - 2000 DA - 2000 Jan 05 SP - 87 EP - 93 VL - 283 IS - 1 SN - 0098-7484, 0098-7484 KW - DNA, Viral KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Sensitivity and Specificity KW - Humans KW - Costa Rica KW - Adult KW - Vaginal Smears KW - Aged KW - Middle Aged KW - Female KW - Colposcopy KW - Papanicolaou Test KW - Uterine Cervical Neoplasms -- prevention & control KW - Papillomavirus Infections -- diagnosis KW - DNA, Viral -- analysis KW - Tumor Virus Infections -- diagnosis KW - Papillomaviridae -- isolation & purification KW - Cervical Intraepithelial Neoplasia -- prevention & control KW - Uterine Cervical Neoplasms -- diagnosis KW - Cervical Intraepithelial Neoplasia -- virology KW - Papillomaviridae -- genetics KW - Cervical Intraepithelial Neoplasia -- diagnosis KW - Mass Screening -- methods KW - Uterine Cervical Neoplasms -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70868357?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=HPV+DNA+testing+in+cervical+cancer+screening%3A+results+from+women+in+a+high-risk+province+of+Costa+Rica.&rft.au=Schiffman%2C+M%3BHerrero%2C+R%3BHildesheim%2C+A%3BSherman%2C+M+E%3BBratti%2C+M%3BWacholder%2C+S%3BAlfaro%2C+M%3BHutchinson%2C+M%3BMorales%2C+J%3BGreenberg%2C+M+D%3BLorincz%2C+A+T&rft.aulast=Schiffman&rft.aufirst=M&rft.date=2000-01-05&rft.volume=283&rft.issue=1&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-21 N1 - Date created - 2000-01-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 2000 Jan 5;283(1):108-9 [10632290] JAMA. 2000 May 17;283(19):2525-6 [10815110] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prophylactic DNA vaccine for hepatitis C virus (HCV) infection: HCV-specific cytotoxic T lymphocyte induction and protection from HCV-recombinant vaccinia infection in an HLA-A2.1 transgenic mouse model AN - 17441221; 4656423 AB - DNA vaccines express antigens intracellularly and effectively induce cellular immune responses. Because only chimpanzees can be used to model human hepatitis C virus (HCV) infections, we developed a small-animal model using HLA-A2.1- transgenic mice to test induction of HLA-A2.1-restricted cytotoxic T lymphocytes (CTLs) and protection against recombinant vaccinia expressing HCV-core. A plasmid encoding the HCV-core antigen induced CD8 super(+) CTLs specific for three conserved endogenously expressed core peptides presented by human HLA-A2.1. When challenged, DNA- immunized mice showed a substantial (5-12 log sub(10)) reduction in vaccinia virus titer compared with mock-immunized controls. This protection, lasting at least 14 mo, was shown to be mediated by CD8 super(+) cells. Thus, a DNA vaccine expressing HCV-core is a potential candidate for a prophylactic vaccine for HLA-A2.1 super(+) humans. JF - Proceedings of the National Academy of Sciences, USA AU - Arichi, T AU - Saito, T AU - Major, ME AU - Belyakov, I M AU - Shirai, M AU - Engelhard, V H AU - Feinstone, S M AU - Berzofsky, JA AD - Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 USA, berzofsk@helix.nih.gov Y1 - 2000/01/04/ PY - 2000 DA - 2000 Jan 04 SP - 297 EP - 302 VL - 97 IS - 1 SN - 0027-8424, 0027-8424 KW - A2.1 determinant KW - infection KW - transgenic mice KW - immunology KW - DNA vaccines KW - Hepatitis C virus KW - hepatitis C virus KW - histocompatibility antigen HLA KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - Animal models KW - Killer cells KW - Lymphocytes T KW - Vaccines KW - G 07240:Immunogenetics KW - F 06807:Active immunization KW - V 22097:Immunization: Vaccines & vaccination: Human KW - V 22150:Animal models & experimentally-induced viral infections KW - F 06825:Human KW - F 06756:Function KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17441221?accountid=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=Prophylactic+DNA+vaccine+for+hepatitis+C+virus+%28HCV%29+infection%3A+HCV-specific+cytotoxic+T+lymphocyte+induction+and+protection+from+HCV-recombinant+vaccinia+infection+in+an+HLA-A2.1+transgenic+mouse+model&rft.au=Arichi%2C+T%3BSaito%2C+T%3BMajor%2C+ME%3BBelyakov%2C+I+M%3BShirai%2C+M%3BEngelhard%2C+V+H%3BFeinstone%2C+S+M%3BBerzofsky%2C+JA&rft.aulast=Arichi&rft.aufirst=T&rft.date=2000-01-04&rft.volume=97&rft.issue=1&rft.spage=297&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.97.1.297 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Hepatitis C virus; Vaccines; Lymphocytes T; Killer cells; Animal models DO - http://dx.doi.org/10.1073/pnas.97.1.297 ER - TY - JOUR T1 - MUSCULOSKELETAL MORBIDITY WITH UNMODIFIED ECT MAY BE LESS THAN EARLIER BELIEVED AN - 872129081; 14536612 AB - Official guidelines for the practice of electroconvulsive therapy (ECT) recommend routine seizure modification to minimize musculoskeletal complications; nevertheless, unmodified ECT continues to be administered in India. We therefore assessed musculoskeletal morbidity with unmodified ECT with particular reference to the development of vertebral fractures and backache X-rays of the thoracolumbar spine were routinely obtained before and after a course of 6 ECTs in 50 consecutive schizophrenic patients receiving unmodified sinusoidal wave treatment. Backache was reported by 52% of patients; the symptom was severe in 14%. Severe backache developed early during the ECT course and was commoner in older patients. Gender, height and weight did not predict either presence or severity of backache. One patient experienced a vertebral fracture which was not considered serious this contrasts with the 20-40% incidence of adverse orthopedic events described with unmodified ECT in early studies. There were no other untoward events. It is concluded that, with specific reference to Indian patients, musculoskeletal morbidity with unmodified ECT may be less than earlier believed Risks with modified vs unmodified ECT therefore need to be systematically reassessed, and decision-making processes may need to be reformulated taking individual situations into account. The findings, conclusions and recommendations of this study carry much medicolegal significance for practitioners of ECT in India. JF - Indian Journal of Psychiatry AU - Andrade, Chittaranjan AU - Rele, Kiran AU - Sutharshan, R AU - Nilesh, Shah AD - ANDRADE, MD., Additional Professor, Department of Psychopharmacology, National Institute of Mental Health and Neurosciences. B.myjtore-560 029. Y1 - 2000 PY - 2000 DA - 2000 SP - 156 EP - 162 PB - Medknow Publications Pvt. Ltd., A-108/109 Kanara Business Center Mumbai 400075 India VL - 42 IS - 2 SN - 0019-5545, 0019-5545 KW - Risk Abstracts; CSA Neurosciences Abstracts KW - ECS KW - Morbidity KW - Vertebrae KW - India KW - Schizophrenia KW - Mental disorders KW - guidelines KW - Waves KW - spine KW - Seizures KW - Orthopedics KW - Fractures KW - musculoskeletal system KW - Decision making KW - complications KW - Spine KW - Ionizing radiation KW - Gender KW - N3 11001:Behavioral and Cognitive Neuroscience KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/872129081?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Indian+Journal+of+Psychiatry&rft.atitle=MUSCULOSKELETAL+MORBIDITY+WITH+UNMODIFIED+ECT+MAY+BE+LESS+THAN+EARLIER+BELIEVED&rft.au=Andrade%2C+Chittaranjan%3BRele%2C+Kiran%3BSutharshan%2C+R%3BNilesh%2C+Shah&rft.aulast=Andrade&rft.aufirst=Chittaranjan&rft.date=2000-01-01&rft.volume=42&rft.issue=2&rft.spage=156&rft.isbn=&rft.btitle=&rft.title=Indian+Journal+of+Psychiatry&rft.issn=00195545&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-06-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - Schizophrenia; Decision making; Mental disorders; Spine; ECS; Ionizing radiation; Orthopedics; Seizures; Fractures; Waves; Vertebrae; Morbidity; spine; complications; guidelines; Gender; musculoskeletal system; India ER - TY - JOUR T1 - Effects of neonatal inferior prefrontal and medial temporal lesions on learning the rule for delayed nonmatching-to-sample. AN - 85366547; pmid-11385832 AB - The ability of rhesus monkeys to master the rule for delayed nonmatching-to-sample (DNMS) has a protracted ontogenetic development, reaching adult levels of proficiency around 4 to 5 years of age (Bachevalier, 1990). To test the possibility that this slow development could be due, at least in part, to immaturity of the prefrontal component of a temporo-prefrontal circuit important for DNMS rule learning (Kowalska, Bachevalier, & Mishkin, 1991; Weinstein, Saunders, & Mishkin, 1988), monkeys with neonatal lesions of the inferior prefrontal convexity were compared on DNMS with both normal controls and animals given neonatal lesions of the medial temporal lobe. Consistent with our previous results (Bachevalier & Mishkin, 1994; Málková, Mishkin, & Bachevalier, 1995), the neonatal medial temporal lesions led to marked impairment in rule learning (as well as in recognition memory with long delays and list lengths) at both 3 months and 2 years of age. By contrast, the neonatal inferior convexity lesions yielded no impairment in rule-learning at 3 months and only a mild impairment at 2 years, a finding that also contrasts sharply with the marked effects of the same lesion made in adulthood. This pattern of sparing closely resembles the one found earlier after neonatal lesions to the cortical visual area TE (Bachevalier & Mishkin, 1994; Málková et al., 1995). The functional sparing at 3 months probably reflects the fact that the temporo-prefrontal circuit is nonfunctional at this early age, resulting in a total dependency on medial temporal contributions to rule learning. With further development, however, this circuit begins to provide a supplementary route for learning. JF - Developmental neuropsychology AU - Málková, L AU - Bachevalier, J AU - Webster, M AU - Mishkin, M AD - Laboratory of Neuropsychology, National Institute of Mental Health, Bethesda, Maryland, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 399 EP - 421 VL - 18 IS - 3 SN - 8756-5641, 8756-5641 KW - Index Medicus KW - National Library of Medicine KW - Animals KW - Animals, Newborn KW - Macaca mulatta KW - Models, Neurological KW - Female KW - Male KW - Temporal Lobe -- pathology KW - Learning KW - Recognition (Psychology) KW - Brain Injuries -- psychology KW - Prefrontal Cortex -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85366547?accountid=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=Developmental+neuropsychology&rft.atitle=Effects+of+neonatal+inferior+prefrontal+and+medial+temporal+lesions+on+learning+the+rule+for+delayed+nonmatching-to-sample.&rft.au=M%C3%A1lkov%C3%A1%2C+L%3BBachevalier%2C+J%3BWebster%2C+M%3BMishkin%2C+M&rft.aulast=M%C3%A1lkov%C3%A1&rft.aufirst=L&rft.date=2000-01-01&rft.volume=18&rft.issue=3&rft.spage=399&rft.isbn=&rft.btitle=&rft.title=Developmental+neuropsychology&rft.issn=87565641&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - The PDS gene, Pendred syndrome and non-syndromic deafness DFNB4. AN - 85362114; pmid-10868226 JF - Advances in oto-rhino-laryngology AU - Wilcox, E R AU - Everett, L A AU - Li, X C AU - Lalwani, A K AU - Green, E D AD - Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Md., USA. wilcoxe@nidcd.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 145 EP - 151 VL - 56 SN - 0065-3071, 0065-3071 KW - Index Medicus KW - National Library of Medicine KW - Sulfates -- metabolism KW - Humans KW - Syndrome KW - Goiter -- genetics KW - Hearing Loss, Sensorineural -- genetics KW - Membrane Transport Proteins KW - Carrier Proteins -- genetics KW - Deafness -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85362114?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+oto-rhino-laryngology&rft.atitle=The+PDS+gene%2C+Pendred+syndrome+and+non-syndromic+deafness+DFNB4.&rft.au=Wilcox%2C+E+R%3BEverett%2C+L+A%3BLi%2C+X+C%3BLalwani%2C+A+K%3BGreen%2C+E+D&rft.aulast=Wilcox&rft.aufirst=E&rft.date=2000-01-01&rft.volume=56&rft.issue=&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Advances+in+oto-rhino-laryngology&rft.issn=00653071&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - DFNB3 families and Shaker-2 mice: mutations in an unconventional myosin, myo 15. AN - 85357319; pmid-10868225 JF - Advances in oto-rhino-laryngology AU - Friedman, T B AU - Hinnant, J T AU - Fridell, R A AU - Wilcox, E R AU - Raphael, Y AU - Camper, S A AD - Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Md., USA. Friedman@nidcd.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 131 EP - 144 VL - 56 SN - 0065-3071, 0065-3071 KW - Index Medicus KW - National Library of Medicine KW - Animals KW - Hair Cells, Auditory -- abnormalities KW - Humans KW - Mice, Neurologic Mutants KW - Mice KW - Chromosome Mapping KW - Genes, Recessive KW - Chromosomes, Human, Pair 17 KW - Deafness -- genetics KW - Myosins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85357319?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+oto-rhino-laryngology&rft.atitle=DFNB3+families+and+Shaker-2+mice%3A+mutations+in+an+unconventional+myosin%2C+myo+15.&rft.au=Friedman%2C+T+B%3BHinnant%2C+J+T%3BFridell%2C+R+A%3BWilcox%2C+E+R%3BRaphael%2C+Y%3BCamper%2C+S+A&rft.aulast=Friedman&rft.aufirst=T&rft.date=2000-01-01&rft.volume=56&rft.issue=&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Advances+in+oto-rhino-laryngology&rft.issn=00653071&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - Patterns of care for dysphagic patients with degenerative neurological diseases. AN - 85351787; pmid-11085257 AB - Several of the most common neurodegenerative conditions associated with dysphagia are Parkinsons's disease, progressive supranuclear palsy, postpolio syndrome, and amyotrophic lateral sclerosis. The best clinical practices for treating dysphagic patients with these common conditions are discussed in relation to medication, surgery, diagnosis, and clinical management. Best practice patterns are explained as they relate to the following concepts of care, including comprehension and cognition; interaction with caregivers; dependence-independence during therapy; matching treatment plans to changes in physiology; and establishing realistic expectations including consideration of personal, cultural, and family needs for continuance or termination of care. JF - Seminars in speech and language AU - Sonies, B C AD - Speech-Language Pathology Section, Oral Pharyngeal Imaging Laboratory, W.G. Magnuson Clinical Center, Department of Rehabilitation Medicine, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 333 EP - 44; quiz 334-5 VL - 21 IS - 4 SN - 0734-0478, 0734-0478 KW - Index Medicus KW - National Library of Medicine KW - Severity of Illness Index KW - Deglutition Disorders -- therapy KW - Humans KW - Deglutition Disorders -- diagnosis KW - Deglutition Disorders -- etiology KW - Professional Practice -- standards KW - Neurodegenerative Diseases -- complications KW - Feeding Methods -- standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85351787?accountid=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=Seminars+in+speech+and+language&rft.atitle=Patterns+of+care+for+dysphagic+patients+with+degenerative+neurological+diseases.&rft.au=Sonies%2C+B+C&rft.aulast=Sonies&rft.aufirst=B&rft.date=2000-01-01&rft.volume=21&rft.issue=4&rft.spage=333&rft.isbn=&rft.btitle=&rft.title=Seminars+in+speech+and+language&rft.issn=07340478&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - Physiology of human posthypoxic myoclonus. AN - 85343747; pmid-10755266 AB - There are two types of posthypoxic myoclonus, acute and chronic. The acute type has not been intensively studied but is likely to be brain stem in origin. Chronic posthypoxic myoclonus is most commonly cortical reflex myoclonus, but reticular reflex myoclonus and exaggerated startle may also occur. These three conditions have characteristic physiological features. In assessing the relevance of an animal model, it would be appropriate to identify the myoclonus with one of these three patterns. JF - Movement disorders : official journal of the Movement Disorder Society AU - Hallett, M AD - Human Motor Control Section, NINDS, NIH, Bethesda, Maryland 20892-1428, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 8 EP - 13 VL - 15 Suppl 1 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Reflex, Abnormal -- physiology KW - Animals KW - Humans KW - Electroencephalography KW - Electromyography KW - Disease Models, Animal KW - Brain Stem -- physiopathology KW - Reticular Formation -- physiopathology KW - Cerebral Cortex -- physiopathology KW - Hypoxia, Brain -- physiopathology KW - Epilepsies, Myoclonic -- physiopathology KW - Myoclonus -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85343747?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Physiology+of+human+posthypoxic+myoclonus.&rft.au=Hallett%2C+M&rft.aulast=Hallett&rft.aufirst=M&rft.date=2000-01-01&rft.volume=39&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+Indian+Anthropological+Society&rft.issn=00194387&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - Developmental changes of distortion product and transient evoked otoacoustic emissions in different age groups. AN - 85339579; pmid-10761833 AB - The developmental changes of distortion product otoacoustic emissions (DPOAEs) and transient evoked otoacoustic emissions (TEOAEs) were evaluated in 275 normal subjects aged from 1 month to 39 years. The DP-grams showed an M-shaped pattern with peaks at 1587 Hz and 5042 Hz for all age groups. In subjects younger than 3 years, low frequency DPOAEs did not rise above the noise floor. The DP levels at high frequency (5042 Hz) did not change much from infancy to young adulthood (12.9-16.5 dB SPL), however, those at low and middle frequency significantly decreased with age. Total echo power (TEP) of TEOAE was greatest in early infancy, decreased rapidly before 6-7 years old, and then decreased gradually (TEP = 16.6 - 1.9 X ln (age)). Wave reproducibility was constant across age. The frequency area peak power (FAPP) to middle and high frequency sounds changed little with age, however, FAPP at low frequency sounds dramatically increased with age. FAPP at 5000 Hz was relatively depressed levels at each age. The TEOAE value was more prominent at middle and low frequencies while DPOAE was predominant at high frequencies. These two measurements may reflect different functions of outer hair cells in the developing cochlea. JF - Brain & development AU - Kon, K AU - Inagaki, M AU - Kaga, M AD - Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Ichikawa, Japan. Y1 - 2000/01// PY - 2000 DA - Jan 2000 SP - 41 EP - 46 VL - 22 IS - 1 SN - 0387-7604, 0387-7604 KW - Index Medicus KW - National Library of Medicine KW - Infant KW - Age Factors KW - Audiometry KW - Humans KW - Adult KW - Infant, Newborn KW - Child KW - Adolescent KW - Child, Preschool KW - Hair Cells, Auditory, Outer -- physiology KW - Auditory Pathways -- physiology KW - Otoacoustic Emissions, Spontaneous -- physiology KW - Auditory Pathways -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85339579?accountid=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=Developmental+changes+of+distortion+product+and+transient+evoked+otoacoustic+emissions+in+different+age+groups.&rft.au=Kon%2C+K%3BInagaki%2C+M%3BKaga%2C+M&rft.aulast=Kon&rft.aufirst=K&rft.date=2000-01-01&rft.volume=22&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Brain+%26+development&rft.issn=03877604&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - Child Language with Mother and with Stranger at Home and in the Laboratory: A Methodological Study AN - 85289234; llba-200011446 AB - This methodological study in 33 two-year-olds shows that child speech (total utterances, word roots, mean length of utterance) occurs at about the same level in different settings (the familiar home vs the unfamiliar laboratory), but that children speak more & in more differentiated ways with different people (mother vs stranger). Child speech also shows significant short-term stability. Girls use more different word roots & speak in longer utterances than do boys. In spontaneous child speech, cross-context generalizations appear warranted, but they also depend on conversational partner & gender of child. 2 Tables, 36 References. Adapted from the source document JF - Journal of Child Language AU - Bornstein, Marc H AU - Maurice, Haynes O AU - Painter, Kathleen M AU - Genevro, Janice L AD - Child & Family Research, National Instit Child Health & Human Development, Bethesda, MD Marc_H_Bornstein@nih.gov PY - 2000 SP - 407 EP - 420 VL - 27 IS - 2 SN - 0305-0009, 0305-0009 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85289234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Child+Language&rft.atitle=Child+Language+with+Mother+and+with+Stranger+at+Home+and+in+the+Laboratory%3A+A+Methodological+Study&rft.au=Bornstein%2C+Marc+H%3BMaurice%2C+Haynes+O%3BPainter%2C+Kathleen+M%3BGenevro%2C+Janice+L&rft.aulast=Bornstein&rft.aufirst=Marc&rft.date=2000-01-01&rft.volume=27&rft.issue=2&rft.spage=407&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Language&rft.issn=03050009&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Chronic intermittent stimulation of the thyroarytenoid muscle maintains dynamic control of glottal adduction. AN - 85280783; pmid-10590405 AB - Patients with laryngeal motor control disorders need improved dynamic glottal closure for speech and swallowing. To evaluate the functional outcome of intermittent chronic thyroarytenoid muscle stimulation in an animal model, 6 canines were implanted with bilateral Medtronic Xtrel systems containing Peterson-type electrodes in the inferior and superior portions of the thyroarytenoid muscle. Stimulation was on one side only at 60 Hz, for 5 s on and 5 s off, over 8 h, 5 days per week, up to 8 months. Monthly videorecordings were done under anesthesia to measure the voltage threshold for detectable movement on each side, and vocal fold displacement and velocity during maximal stimulation of each side. Movement thresholds were lower in the inferior portion of the thyroarytenoid muscle (P 50-fold activity versus butyrylcholinesterase (BChE), in clinical trials for the treatment of Alzheimer's disease (AD). Compared to physostigmine and tacrine, it is less toxic and robustly enhances cognition in animal models. To determine the time-dependent effects of phenserine on cholinergic function, AChE activity, brain and plasma drug levels and brain extracellular acetylcholine (ACh) concentrations were measured in rats before and after phenserine administration. Additionally, its maximum tolerated dose, compared to physostigmine and tacrine, was determined. Following i.v. dosing, brain drug levels were 10-fold higher than those achieved in plasma, peaked within 5 min and rapidly declined with half-lives of 8.5 and 12.6 min, respectively. In contrast, a high (> 70%) and long-lasting inhibition of AChE was achieved (half-life > 8.25 h). A comparison between the time-dependent plasma AChE inhibition achieved after similar oral and i.v. doses provided an estimate of oral bioavailability of 100%. Striatal, in vivo microdialysis in conscious, freely-moving phenserine-treated rats demonstrated > 3-fold rise in brain ACh levels. Phenserine thus is rapidly absorbed and cleared from the body, but produces a long-lasting stimulation of brain cholinergic function at well tolerated doses and hence has superior properties as a drug candidate for AD. It selectively inhibits AChE, minimizing potential BChE side effects. Its long duration of action, coupled with its short pharmacokinetic half-life, reduces dosing frequency, decreases body drug exposure and minimizes the dependence of drug action on the individual variations of drug metabolism commonly found in the elderly. JF - Acta neurologica Scandinavica. Supplementum AU - Greig, N H AU - De Micheli, E AU - Holloway, H W AU - Yu, Q S AU - Utsuki, T AU - Perry, T A AU - Brossi, A AU - Ingram, D K AU - Deutsch, J AU - Lahiri, D K AU - Soncrant, T T AD - Laboratory of Neurosciences, Intramural Research Program, National Institute of Aging, Gerontology Research Center, Baltimore, MD 21224, USA. Greign@vax.grc.nia.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 74 EP - 84 VL - 176 SN - 0065-1427, 0065-1427 KW - Cholinesterase Inhibitors KW - 0 KW - phenserine KW - Tacrine KW - 4VX7YNB537 KW - Physostigmine KW - 9U1VM840SP KW - Index Medicus KW - Rats KW - Administration, Oral KW - Animals KW - Rats, Inbred F344 KW - Infusions, Intravenous KW - Half-Life KW - Brain -- drug effects KW - Tacrine -- pharmacology KW - Disease Models, Animal KW - Tacrine -- pharmacokinetics KW - Brain -- physiology KW - Tacrine -- administration & dosage KW - Male KW - Cholinesterase Inhibitors -- pharmacology KW - Cholinesterase Inhibitors -- administration & dosage KW - Physostigmine -- pharmacology KW - Physostigmine -- administration & dosage KW - Alzheimer Disease -- drug therapy KW - Physostigmine -- analogs & derivatives KW - Cholinesterase Inhibitors -- pharmacokinetics KW - Physostigmine -- pharmacokinetics KW - Alzheimer Disease -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72582420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+neurologica+Scandinavica.+Supplementum&rft.atitle=The+experimental+Alzheimer+drug+phenserine%3A+preclinical+pharmacokinetics+and+pharmacodynamics.&rft.au=Greig%2C+N+H%3BDe+Micheli%2C+E%3BHolloway%2C+H+W%3BYu%2C+Q+S%3BUtsuki%2C+T%3BPerry%2C+T+A%3BBrossi%2C+A%3BIngram%2C+D+K%3BDeutsch%2C+J%3BLahiri%2C+D+K%3BSoncrant%2C+T+T&rft.aulast=Greig&rft.aufirst=N&rft.date=2000-01-01&rft.volume=176&rft.issue=&rft.spage=74&rft.isbn=&rft.btitle=&rft.title=Acta+neurologica+Scandinavica.+Supplementum&rft.issn=00651427&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-17 N1 - Date created - 2001-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased cell survival by inhibition of BRCA1 using an antisense approach in an estrogen responsive ovarian carcinoma cell line. AN - 72581621; 11056686 AB - STATEMENT OF FINDINGS: We tested the hypothesis that BRCA1 may play a role in the regulation of ovarian tumor cell death as well as the inhibition of ovarian cell proliferation. Introduction of BRCA1 antisense retroviral constructs into BG-1 estrogen-dependent ovarian adenocarcinoma cells resulted in reduced BRCA1 expression. BRCA1 antisense pooled populations and derived subclones were able to proliferate in monolayer culture without estrogen, whereas control cells began to die after 10 days of estrogen deprivation. In addition, both populations and subclones of BRCA1 antisense infected cells demonstrated a growth advantage in monolayer culture in the presence of estrogen and were able to proliferate in monolayer culture without estrogen, while control cells did not. Furthermore, clonal studies demonstrated that reduced levels of BRCA1 protein correlated with growth in soft agar and greater tumor formation in nude mice in the absence of estrogen. These data suggest that reduction of BRCA1 protein in BG-1 ovarian adenocarcinoma cells may have an effect on cell survival during estrogen deprivation both in vitro and in vivo. JF - Breast cancer research : BCR AU - Annab, L A AU - Hawkins, R E AU - Solomon, G AU - Barrett, J C AU - Afshari, C A AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Annab@NIEHS.NIH.GOV Y1 - 2000 PY - 2000 DA - 2000 SP - 139 EP - 148 VL - 2 IS - 2 SN - 1465-5411, 1465-5411 KW - BRCA1 Protein KW - 0 KW - Estrogens KW - RNA, Antisense KW - RNA, Messenger KW - Receptors, Estrogen KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured -- drug effects KW - Genes, Tumor Suppressor KW - Humans KW - Retroviridae KW - Mice KW - Mice, Nude KW - Cell Survival KW - Estrogens -- pharmacology KW - RNA, Messenger -- metabolism KW - Transfection KW - Cell Transformation, Neoplastic KW - Female KW - Ovarian Neoplasms -- metabolism KW - BRCA1 Protein -- antagonists & inhibitors KW - Adenocarcinoma -- metabolism KW - Ovarian Neoplasms -- genetics KW - Ovarian Neoplasms -- pathology KW - BRCA1 Protein -- genetics KW - BRCA1 Protein -- metabolism KW - Adenocarcinoma -- genetics KW - Receptors, Estrogen -- metabolism KW - RNA, Antisense -- pharmacology KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72581621?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Breast+cancer+research+%3A+BCR&rft.atitle=Increased+cell+survival+by+inhibition+of+BRCA1+using+an+antisense+approach+in+an+estrogen+responsive+ovarian+carcinoma+cell+line.&rft.au=Annab%2C+L+A%3BHawkins%2C+R+E%3BSolomon%2C+G%3BBarrett%2C+J+C%3BAfshari%2C+C+A&rft.aulast=Annab&rft.aufirst=L&rft.date=2000-01-01&rft.volume=2&rft.issue=2&rft.spage=139&rft.isbn=&rft.btitle=&rft.title=Breast+cancer+research+%3A+BCR&rft.issn=14655411&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-05 N1 - Date created - 2001-03-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Endocrinol. 1997 Apr;153(1):169-78 [9135581] Nat Genet. 1999 Feb;21(2):236-40 [9988281] Eur J Cancer. 1997 Mar;33(3):362-71 [9155518] Proc Natl Acad Sci U S A. 1997 May 27;94(11):5605-10 [9159119] Genes Dev. 1997 May 15;11(10):1226-41 [9171368] Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7138-43 [9207057] Nat Med. 1997 Jul;3(7):721-2 [9212093] Cell Growth Differ. 1997 Jul;8(7):801-9 [9218874] Int J Cancer. 1997 Jun 20;74(3):322-5 [9221812] Cancer. 1997 Aug 1;80(3):435-41 [9241077] J Biol Chem. 1997 Aug 22;272(34):20994-7 [9261099] Cell. 1997 Aug 8;90(3):425-35 [9267023] Cancer Res. 1997 Aug 15;57(16):3347-50 [9269993] Nature. 1997 Sep 11;389(6647):187-90 [9296497] Adv Exp Med Biol. 1997;424:279-89 [9361806] Oncogene. 1998 Jan 8;16(1):61-8 [9467943] Oncogene. 1998 Apr 2;16(13):1713-21 [9582019] Int J Cancer. 1998 Jul 3;77(1):1-6 [9639385] Mol Carcinog. 1998 Jun;22(2):102-9 [9655254] Oncogene. 1998 Jun 11;16(23):3069-82 [9662340] Cancer. 1989 Jan 15;63(2):280-8 [2910432] Biotechniques. 1989 Oct;7(9):980-2, 984-6, 989-90 [2631796] Eur J Biochem. 1990 Jul 5;190(3):477-82 [2197089] Lancet. 1994 Mar 19;343(8899):692-5 [7907678] Science. 1994 Oct 7;266(5182):120-2 [7939630] Science. 1994 Oct 7;266(5182):66-71 [7545954] Science. 1995 Mar 10;267(5203):1456-62 [7878464] Nat Genet. 1995 Apr;9(4):343-4 [7795636] Nat Genet. 1995 Apr;9(4):439-43 [7795652] Nat Genet. 1995 Apr;9(4):444-50 [7795653] Biochem Cell Biol. 1994 Nov-Dec;72(11-12):531-6 [7654326] Cancer Res. 1995 Oct 15;55(20):4561-5 [7553629] Nat Genet. 1995 Sep;11(1):17-26 [7550308] Nat Genet. 1995 Dec;11(4):428-33 [7493024] Nat Genet. 1996 Feb;12(2):191-4 [8563759] Nat Genet. 1996 Mar;12(3):298-302 [8589721] Oncogene. 1996 Feb 1;12(3):523-8 [8637708] Cell. 1996 Jun 28;85(7):1009-23 [8674108] Oncogene. 1996 Jul 4;13(1):1-7 [8700535] Nature. 1996 Aug 22;382(6593):678-9 [8751436] Cell Growth Differ. 1996 Jun;7(6):717-23 [8780885] Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13078-83 [8917547] Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13595-9 [8942979] Nat Genet. 1996 Dec;14(4):430-40 [8944023] Biol Reprod. 1997 Jan;56(1):186-93 [9002648] Cell. 1997 Jan 24;88(2):265-75 [9008167] Oncogene. 1997 Jan 9;14(1):115-21 [9010238] Annu Rev Physiol. 1997;59:349-63 [9074768] Lab Invest. 1997 Mar;76(3):419-25 [9121124] N Engl J Med. 1997 May 15;336(20):1401-8 [9145676] Int J Cancer. 1998 Aug 21;79(4):334-42 [9699523] In Vitro Cell Dev Biol Anim. 1998 Sep;34(8):649-54 [9769151] Cancer. 1997 May 15;79(10):1944-50 [9149021] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metastases: the glycan connection. AN - 72580617; 11250723 AB - An association between protein glycosylation and tumorigenesis has been recognized for over 10 years. Associations linking the importance of glycosylation events to tumor biology, especially the progression to metastatic disease, have been noted over many years, Recently, a mouse model in which beta1,6-N-acetylglucosaminyltransferase V (a rate-limiting enzyme in the N-glycan pathway) has been knocked out, was used to demonstrate the importance of glycosylation in tumor progression. By crossing mice lacking this enzyme with a transgenic mouse model of metastatic breast cancer, metastatic progression of the disease was dramatically reduced. These experiments provide in vivo evidence for the role of N-linked glycosylation in metastatic breast cancer and have significant implications for the development of new treatment strategies. JF - Breast cancer research : BCR AU - Couldrey, C AU - Green, J E AD - Laboratory of Cell Regulation and Carcinogenesis, Division of Basic Science, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 321 EP - 323 VL - 2 IS - 5 SN - 1465-5411, 1465-5411 KW - Polysaccharides KW - 0 KW - N-Acetylglucosaminyltransferases KW - EC 2.4.1.- KW - alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase KW - EC 2.4.1.155 KW - Index Medicus KW - Animals KW - Neoplasm Metastasis KW - Disease Models, Animal KW - Mice KW - Glycosylation KW - Mice, Transgenic KW - Female KW - Mice, Knockout KW - Polysaccharides -- metabolism KW - N-Acetylglucosaminyltransferases -- physiology KW - Mammary Neoplasms, Experimental -- metabolism KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72580617?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Breast+cancer+research+%3A+BCR&rft.atitle=Metastases%3A+the+glycan+connection.&rft.au=Couldrey%2C+C%3BGreen%2C+J+E&rft.aulast=Couldrey&rft.aufirst=C&rft.date=2000-01-01&rft.volume=2&rft.issue=5&rft.spage=321&rft.isbn=&rft.btitle=&rft.title=Breast+cancer+research+%3A+BCR&rft.issn=14655411&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-05 N1 - Date created - 2001-03-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1998 Dec 1;58(23):5559-64 [9850094] Oncogene. 1998 Oct 22;17(16):2087-93 [9798679] Biochim Biophys Acta. 1999 Dec 6;1473(1):21-34 [10580127] Cell. 2000 Jan 7;100(1):57-70 [10647931] Carcinogenesis. 2000 Mar;21(3):505-15 [10688871] Nat Med. 2000 Mar;6(3):306-12 [10700233] Biochemistry. 1971 May 25;10(11):2176-80 [4327402] J Biol Chem. 1982 Nov 25;257(22):13421-7 [6216250] Science. 1987 May 1;236(4801):582-5 [2953071] Science. 1989 May 12;244(4905):707-12 [2470152] Oncogene. 1989 Jul;4(7):853-60 [2666906] J Natl Cancer Inst. 1989 Dec 6;81(23):1780-6 [2685334] Cancer Res. 1991 Jan 15;51(2):718-23 [1985789] Mol Cell Biol. 1992 Mar;12(3):954-61 [1312220] Glycobiology. 1992 Feb;2(1):49-56 [1550989] Lancet. 1994 Mar 19;343(8899):692-5 [7907678] EMBO J. 1994 May 1;13(9):2056-65 [8187759] J Cell Biol. 1995 Jul;130(2):383-92 [7615638] J Clin Oncol. 1996 Aug;14(8):2197-205 [8708708] Important Adv Oncol. 1996;:57-67 [8791128] Int J Oncol. 1998 Mar;12(3):499-507 [9472085] J Pathol. 1999 Nov;189(3):300-8 [10547590] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Towards agreement on ways to measure and report drinking patterns and alcohol-related problems in adult general population surveys: the Skarpö conference overview. AN - 72579940; 11288465 AB - A thematic conference of the Kettil Bruun Society (KBS) for Social and Epidemiological Research on Alcohol was held in Skarpö, near Stockholm, on April 3-7, 2000. The goals of the meeting were to develop consensus sets of questionnaire items for measuring alcohol consumption and social harm, to delineate statistical and practical concerns related to the aggregation of consumption and harm data and to identify summary measures to be used for descriptive purposes and in analyses of the association between alcohol intake and alcohol-related outcomes. The results of the conference discussions are summarized below, with emphasis on both areas where the conference yielded recommendations for measures and methods of aggregation for analysis, and on areas where consensus could not be obtained and/or where additional research is needed. JF - Journal of substance abuse AU - Dawson, D A AU - Room, R AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Suite 514, Willco Building, 6000 Executive Boulevard, MSC 7003, Bethesda, MD 20892-7003, USA. ddawson@willco.niaaa.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 1 EP - 21 VL - 12 IS - 1-2 SN - 0899-3289, 0899-3289 KW - Index Medicus KW - Humans KW - Health Surveys KW - Sweden -- epidemiology KW - Data Collection -- statistics & numerical data KW - Alcoholism -- epidemiology KW - Social Problems -- statistics & numerical data KW - Alcohol Drinking -- adverse effects KW - Alcohol Drinking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72579940?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Journal+of+substance+abuse&rft.atitle=Towards+agreement+on+ways+to+measure+and+report+drinking+patterns+and+alcohol-related+problems+in+adult+general+population+surveys%3A+the+Skarp%C3%B6+conference+overview.&rft.au=Dawson%2C+D+A%3BRoom%2C+R&rft.aulast=Dawson&rft.aufirst=D&rft.date=2000-01-01&rft.volume=12&rft.issue=1-2&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-07-26 N1 - Date created - 2001-04-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neovascularisation offers a new perspective to glutamine related therapy. AN - 72576265; 11233093 AB - Angiogenesis or the generation of new blood vessel, is an important factor in the growth of a solid tumor. Hence, it becomes a necessary parameter of any kind of therapeutic study. Glutamine is an essential nutrient of tumor tissue and glutamine related therapy involves clearance of circulatory glutamine by glutaminase. Therefore, using different murine solid tumor models, the present study was undertaken to find out whether the S-180 cell glutaminase has any effect on angiogenesis of solid tumor, or not. Result indicates that the purified S-180 cell glutaminase reduces tumor volume and restrict the generation of neo blood vessels. Therefore, it can be concluded that this enzyme may be an effective device against the cancer metastasis. JF - Indian journal of experimental biology AU - Maity, P AU - Chakraborty, S AU - Bhattacharya, P AD - Department of Metabolic Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Calcutta-700 026, India. Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 88 EP - 90 VL - 38 IS - 1 SN - 0019-5189, 0019-5189 KW - Angiogenesis Inhibitors KW - 0 KW - Carcinogens KW - Neoplasm Proteins KW - Glutamine KW - 0RH81L854J KW - Methylcholanthrene KW - 56-49-5 KW - Glutaminase KW - EC 3.5.1.2 KW - Index Medicus KW - Injections, Intraperitoneal KW - Drug Screening Assays, Antitumor KW - Carcinoma, Ehrlich Tumor -- blood supply KW - Animals KW - Carcinoma, Ehrlich Tumor -- drug therapy KW - Mice KW - Male KW - Angiogenesis Inhibitors -- therapeutic use KW - Neoplasm Proteins -- administration & dosage KW - Glutamine -- physiology KW - Sarcoma 180 -- enzymology KW - Sarcoma 180 -- drug therapy KW - Glutaminase -- administration & dosage KW - Glutaminase -- therapeutic use KW - Sarcoma 180 -- blood supply KW - Angiogenesis Inhibitors -- administration & dosage KW - Glutaminase -- isolation & purification KW - Neoplasms, Experimental -- blood supply KW - Neovascularization, Pathologic -- drug therapy KW - Neoplasm Proteins -- isolation & purification KW - Neoplasm Proteins -- therapeutic use KW - Neoplasms, Experimental -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72576265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Indian+journal+of+experimental+biology&rft.atitle=Neovascularisation+offers+a+new+perspective+to+glutamine+related+therapy.&rft.au=Maity%2C+P%3BChakraborty%2C+S%3BBhattacharya%2C+P&rft.aulast=Maity&rft.aufirst=P&rft.date=2000-01-01&rft.volume=38&rft.issue=1&rft.spage=88&rft.isbn=&rft.btitle=&rft.title=Indian+journal+of+experimental+biology&rft.issn=00195189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-31 N1 - Date created - 2001-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A molecular element of neuronal response to lysolecithin-induced focal, experimental demyelination in rat. AN - 72575305; 11225520 JF - Neurobiology (Budapest, Hungary) AU - Lovas, G AU - Palkovits, M AU - Komoly, S AD - Laboratory of Developmental Neurogenetics, NINDS, NIH, Bethesda, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 273 EP - 275 VL - 8 IS - 3-4 SN - 1216-8068, 1216-8068 KW - Lysophosphatidylcholines KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Brain -- drug effects KW - Brain -- metabolism KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Lysophosphatidylcholines -- pharmacology KW - Demyelinating Diseases -- metabolism KW - Genes, jun -- drug effects KW - Demyelinating Diseases -- chemically induced KW - Genes, jun -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72575305?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurobiology+%28Budapest%2C+Hungary%29&rft.atitle=A+molecular+element+of+neuronal+response+to+lysolecithin-induced+focal%2C+experimental+demyelination+in+rat.&rft.au=Lovas%2C+G%3BPalkovits%2C+M%3BKomoly%2C+S&rft.aulast=Lovas&rft.aufirst=G&rft.date=2000-01-01&rft.volume=8&rft.issue=3-4&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=Neurobiology+%28Budapest%2C+Hungary%29&rft.issn=12168068&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-31 N1 - Date created - 2001-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development of a plant-derived subunit vaccine candidate against hepatitis C virus. AN - 72550352; 11205105 AB - Hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis with over 180 million cases worldwide. Vaccine development for HCV has been difficult. Presently, the virus cannot be grown in tissue culture and there is no vaccine or effective therapy against this virus. In this research, we describe the development of an experimental plant-derived subunit vaccine against HCV. A tobamoviral vector was engineered to encode a consensus sequence of hypervariable region 1 (HVR1), a potential neutralizing epitope of HCV, genetically fused to the C-terminal of the B subunit of cholera toxin (CTB). This epitope was selected from among the amino acid sequences of HVR1 "mimotopes" previously derived by phage display technology. The nucleotide sequence encoding this epitope was designed utilizing optimal plant codons. This mimotope is capable of inducing cross-neutralizing antibodies against different variants of the virus. Plants infected with recombinant tobacco mosaic virus (TMV) engineered to express the HVR1/CTB chimeric protein, contained intact TMV particles and produced the HVR1 consensus peptide fused to the functionally active, pentameric B subunit of cholera toxin. Plant-derived HVR1/CTB reacted with HVR1-specific monoclonal antibodies and immune sera from individuals infected with virus from four of the major genotypes of HCV. Intranasal immunization of mice with a crude plant extract containing the recombinant HVR1/CTB protein elicited both anti-CTB serum antibody and anti-HVR1 serum antibody which specifically bound to HCV virus-like particles. Using plant-virus transient expression to produce this unique chimeric antigen will facilitate the development and production of an experimental HCV vaccine. A plant-derived recombinant HCV vaccine can potentially reduce expenses normally associated with production and delivery of conventional vaccines. JF - Archives of virology AU - Nemchinov, L G AU - Liang, T J AU - Rifaat, M M AU - Mazyad, H M AU - Hadidi, A AU - Keith, J M AD - Vaccine and Therapeutic Development Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892-4350, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 2557 EP - 2573 VL - 145 IS - 12 SN - 0304-8608, 0304-8608 KW - Epitopes KW - 0 KW - HVR1 protein, Hepatitis C virus KW - Plant Proteins KW - Recombinant Fusion Proteins KW - Vaccines, Subunit KW - Viral Hepatitis Vaccines KW - Viral Proteins KW - Cholera Toxin KW - 9012-63-9 KW - Index Medicus KW - Viral Proteins -- immunology KW - Viral Proteins -- genetics KW - Hepatitis C -- prevention & control KW - Animals KW - Epitopes -- genetics KW - Mice KW - Amino Acid Sequence KW - Reverse Transcriptase Polymerase Chain Reaction KW - Vaccination KW - Vaccines, Subunit -- biosynthesis KW - Base Sequence KW - Blotting, Western KW - Protein Engineering KW - Cholera Toxin -- immunology KW - Cholera Toxin -- genetics KW - Administration, Intranasal KW - Genetic Vectors KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Enzyme-Linked Immunosorbent Assay KW - Vaccines, Subunit -- immunology KW - Epitopes -- immunology KW - Female KW - Tobacco Mosaic Virus -- genetics KW - Recombinant Fusion Proteins -- biosynthesis KW - Plant Proteins -- biosynthesis KW - Plant Proteins -- immunology KW - Viral Hepatitis Vaccines -- administration & dosage KW - Hepacivirus -- immunology KW - Recombinant Fusion Proteins -- immunology KW - Hepacivirus -- genetics KW - Viral Hepatitis Vaccines -- immunology KW - Viral Hepatitis Vaccines -- biosynthesis KW - Recombinant Fusion Proteins -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72550352?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+virology&rft.atitle=Development+of+a+plant-derived+subunit+vaccine+candidate+against+hepatitis+C+virus.&rft.au=Nemchinov%2C+L+G%3BLiang%2C+T+J%3BRifaat%2C+M+M%3BMazyad%2C+H+M%3BHadidi%2C+A%3BKeith%2C+J+M&rft.aulast=Nemchinov&rft.aufirst=L&rft.date=2000-01-01&rft.volume=145&rft.issue=12&rft.spage=2557&rft.isbn=&rft.btitle=&rft.title=Archives+of+virology&rft.issn=03048608&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-15 N1 - Date created - 2001-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Malaria control stymied in 2010, mastered in 2025. AN - 72541657; 11196493 JF - Bulletin of the World Health Organization AU - Breman, J G AD - Division of International Training and Research, Fogarty International Center, National Institutes of Health, Bldg 31, Room B2C39, 31 Center Drive, MSC 2220, Bethesda, MD 20892-2220, USA. jbreman@nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 1450 EP - 1452 VL - 78 IS - 12 SN - 0042-9686, 0042-9686 KW - Antimalarials KW - 0 KW - Insecticides KW - Index Medicus KW - Global Health KW - International Cooperation KW - Cost of Illness KW - Africa -- epidemiology KW - Insecticides -- therapeutic use KW - Humans KW - Incidence KW - Antimalarials -- therapeutic use KW - Prevalence KW - Malaria -- prevention & control KW - Malaria -- epidemiology KW - Endemic Diseases -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72541657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bulletin+of+the+World+Health+Organization&rft.atitle=Malaria+control+stymied+in+2010%2C+mastered+in+2025.&rft.au=Breman%2C+J+G&rft.aulast=Breman&rft.aufirst=J&rft.date=2000-01-01&rft.volume=78&rft.issue=12&rft.spage=1450&rft.isbn=&rft.btitle=&rft.title=Bulletin+of+the+World+Health+Organization&rft.issn=00429686&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-22 N1 - Date created - 2001-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Future directions in alcoholism research. Genomics and gene transfer. AN - 72537254; 11199290 AB - Alcohol affects the process by which genes direct the synthesis of proteins (i.e., expression). Therefore, patterns of gene expression in the presence of alcohol can help scientists identify the specific molecular sites of alcohol's actions within the brain. New technologies can detect and quantify changes in the expression of thousands of genes simultaneously by scanning microscopic gene arrays applied to glass or silicon chips an inch or so square. However, genes whose activity is altered in the presence of alcohol may either be contributing to alcoholism development or may be reacting to alcohol's presence. This question can be researched by observing the effects of manipulating the level of specific gene products. One way to accomplish this end is by means of viruses that have been engineered to express a specific gene in infected cells. This technique has been applied successfully in studying addictive behaviors. It is suggested that patterns of gene expression may become a diagnostic tool, with different disease states being characterized by distinct expression profiles. JF - Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism AU - Brooks, P J AU - Lipsky, R H AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 189 EP - 192 VL - 24 IS - 3 SN - 1535-7414, 1535-7414 KW - Index Medicus KW - Humans KW - Genetic Vectors KW - Forecasting KW - Gene Expression Regulation -- genetics KW - Genome, Human KW - Gene Transfer Techniques -- trends KW - Alcoholism -- diagnosis KW - Alcoholism -- therapy KW - Research -- trends KW - Alcoholism -- genetics KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72537254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+research+%26+health+%3A+the+journal+of+the+National+Institute+on+Alcohol+Abuse+and+Alcoholism&rft.atitle=Future+directions+in+alcoholism+research.+Genomics+and+gene+transfer.&rft.au=Brooks%2C+P+J%3BLipsky%2C+R+H&rft.aulast=Brooks&rft.aufirst=P&rft.date=2000-01-01&rft.volume=24&rft.issue=3&rft.spage=189&rft.isbn=&rft.btitle=&rft.title=Alcohol+research+%26+health+%3A+the+journal+of+the+National+Institute+on+Alcohol+Abuse+and+Alcoholism&rft.issn=15357414&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-22 N1 - Date created - 2001-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interacting signaling pathways in the pathogenesis of squamous cell carcinoma. AN - 72535306; 11188883 JF - Medicina AU - Yuspa, S H AU - Hansen, L AU - Li, L AU - Joseloff, E AU - Weinberg, W AU - Fernandez-Salas, E AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health and Laboratory of Immunobiology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 689 EP - 692 VL - 60 IS - 5 Pt 2 SN - 0025-7680, 0025-7680 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Keratinocytes -- physiology KW - Cell Death -- physiology KW - Animals KW - Precancerous Conditions -- genetics KW - Hair -- growth & development KW - Precancerous Conditions -- etiology KW - Humans KW - Apoptosis -- physiology KW - Cell Division -- physiology KW - Mice KW - Mutation KW - Skin Neoplasms -- genetics KW - Signal Transduction -- physiology KW - Carcinoma, Squamous Cell -- etiology KW - Skin Neoplasms -- etiology KW - Carcinoma, Squamous Cell -- genetics KW - Receptor, Epidermal Growth Factor -- physiology KW - Protein Kinase C -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72535306?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medicina&rft.atitle=Interacting+signaling+pathways+in+the+pathogenesis+of+squamous+cell+carcinoma.&rft.au=Yuspa%2C+S+H%3BHansen%2C+L%3BLi%2C+L%3BJoseloff%2C+E%3BWeinberg%2C+W%3BFernandez-Salas%2C+E&rft.aulast=Yuspa&rft.aufirst=S&rft.date=2000-01-01&rft.volume=60&rft.issue=5+Pt+2&rft.spage=689&rft.isbn=&rft.btitle=&rft.title=Medicina&rft.issn=00257680&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-29 N1 - Date created - 2001-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - What we have learned about addiction from animal models of drug self-administration. AN - 72533773; 11155784 AB - Self-administration of addictive drugs in laboratory animals has been widely used for decades as a tool for studying behavioral, neurobiological, and genetic factors in addiction. From such studies has come an enormous amount of information on brain mechanisms involved in addiction, on vulnerability factors in the addictive process, and on possible pharmacotherapeutic treatments for addiction. Modifications of the laboratory animal self-administration paradigm--including progressive ratio break-point models and the "reinstatement" model of relapse to drug-seeking behavior--are currently increasing our knowledge of incentive motivational factors in addiction and of the mechanisms underlying relapse to drug self-administration behavior. JF - The American journal on addictions AU - Gardner, E L AD - Intramural Research Program, National Institute on Drug Abuse, Building C-Room 272, 5500 Nathan Shock Dr., Baltimore, MD 21224, USA. egardner@intra.nida.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 285 EP - 313 VL - 9 IS - 4 SN - 1055-0496, 1055-0496 KW - Street Drugs KW - 0 KW - Index Medicus KW - Animals KW - Motivation KW - Humans KW - Brain -- drug effects KW - Self Administration -- psychology KW - Disease Models, Animal KW - Substance-Related Disorders -- rehabilitation KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72533773?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+on+addictions&rft.atitle=What+we+have+learned+about+addiction+from+animal+models+of+drug+self-administration.&rft.au=Gardner%2C+E+L&rft.aulast=Gardner&rft.aufirst=E&rft.date=2000-01-01&rft.volume=9&rft.issue=4&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=The+American+journal+on+addictions&rft.issn=10550496&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-05 N1 - Date created - 2001-01-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug abuse and developmental psychopathology. AN - 72530140; 11202044 AB - Drug abuse research and theory has become much more sophisticated over the last 2 decades, and some of the advancements parallel concepts that are part of the developmental psychopathology approach. The application of the developmental psychopathology perspective to recent drug abuse research findings can provide a greater understanding of that information and point to important areas of future research. Among the drug abuse research areas discussed here and viewed from this perspective are antecedent and co-occurring psychopathological conditions and other problem behaviors; the diversity of the nature of, paths to, and processes and outcomes related to drug abuse; the role of intermediary influences; the interaction of individual and environmental predisposing and protective factors; the role of families and other social institutions in intervention; and developmental stage characteristics. Directions for future research are also discussed. JF - Development and psychopathology AU - Glantz, M D AU - Leshner, A I AD - Division of Epidemiology, Services, and Prevention Research, National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD 20892-9589, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 795 EP - 814 VL - 12 IS - 4 SN - 0954-5794, 0954-5794 KW - Index Medicus KW - Cognition Disorders -- etiology KW - Humans KW - Temperament KW - Child KW - Affect KW - Adolescent KW - Male KW - Female KW - Social Environment KW - Substance-Related Disorders -- diagnosis KW - Mental Disorders -- etiology KW - Child Development -- physiology KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72530140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Development+and+psychopathology&rft.atitle=Drug+abuse+and+developmental+psychopathology.&rft.au=Glantz%2C+M+D%3BLeshner%2C+A+I&rft.aulast=Glantz&rft.aufirst=M&rft.date=2000-01-01&rft.volume=12&rft.issue=4&rft.spage=795&rft.isbn=&rft.btitle=&rft.title=Development+and+psychopathology&rft.issn=09545794&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-26 N1 - Date created - 2001-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Myeloma proteins that bind Hsp65 (GroEL) are polyreactive and are found in high incidence in pristine induced plasmacytomas. AN - 72523820; 11125484 AB - The myeloma proteins produced by 44 plasmacytomas (PCTs) recently induced by pristane in BALB/cAnPt and closely related PCT susceptible congenic strains of mice were isolated chromatographically and screened against a panel of 10 protein, nucleic acid and lipid antigens. This sample was highly unusual because 82% of the proteins had IgG isotopes. Nine of the proteins bound to Hsp65 (GroEL), and all of these were polyreactative. Twenty-one of the myeloma proteins were polyreactive and bound two or more antigens in the panel, and five were monoreactive. Thus, an antigen binding activity was determined for 59% of these myeloma proteins. JF - Current topics in microbiology and immunology AU - Potter, M AU - Jones, G AU - Dubois, W AU - Williams, K AU - Mushinski, E AD - Laboratory of Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD 20892 USA Y1 - 2000 PY - 2000 DA - 2000 SP - 265 EP - 271 VL - 252 SN - 0070-217X, 0070-217X KW - Bacterial Proteins KW - 0 KW - Chaperonin 60 KW - Immunoglobulin Heavy Chains KW - Myeloma Proteins KW - Terpenes KW - heat-shock protein 65, Mycobacterium KW - pristane KW - 26HZV48DT1 KW - Chaperonins KW - EC 3.6.1.- KW - Index Medicus KW - Immunoglobulin Heavy Chains -- immunology KW - Antigen-Antibody Reactions KW - Antibody Specificity KW - Animals KW - Ascitic Fluid -- chemistry KW - Enzyme-Linked Immunosorbent Assay KW - Arthritis -- immunology KW - Mice KW - Arthritis -- chemically induced KW - Mice, Inbred BALB C KW - Immunoglobulin Heavy Chains -- genetics KW - Cross Reactions KW - Terpenes -- toxicity KW - Plasmacytoma -- chemically induced KW - Myeloma Proteins -- immunology KW - Chaperonins -- immunology KW - Plasmacytoma -- immunology KW - Myeloma Proteins -- metabolism KW - Chaperonins -- metabolism KW - Chaperonin 60 -- metabolism KW - Chaperonin 60 -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72523820?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+topics+in+microbiology+and+immunology&rft.atitle=Myeloma+proteins+that+bind+Hsp65+%28GroEL%29+are+polyreactive+and+are+found+in+high+incidence+in+pristine+induced+plasmacytomas.&rft.au=Potter%2C+M%3BJones%2C+G%3BDubois%2C+W%3BWilliams%2C+K%3BMushinski%2C+E&rft.aulast=Potter&rft.aufirst=M&rft.date=2000-01-01&rft.volume=252&rft.issue=&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=Current+topics+in+microbiology+and+immunology&rft.issn=0070217X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-15 N1 - Date created - 2000-12-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular and biological determinants of the cytotoxic actions of camptothecins. Perspective for the development of new topoisomerase I inhibitors. AN - 72521656; 11193886 AB - Camptothecin, originally discovered in 1957 as an antitumor activity in plant extracts, has recently become one of the most promising leads to new anticancer drugs. After lingering for many years, interest in camptothecin was revitalized in 1985 upon discovery of its specific action on topoisomerase I. Detailed elucidation of action mechanisms at the molecular, cellular, and pharmacologic levels has made camptothecin and its congeners perhaps the best understood among clinical anticancer drugs. Promising chemical variants of camptothecin, and recently other chemical categories of topoisomerase I-targeted drugs, provide unusually rich opportunities for rational drug selection and design. This is made possible by current concepts based, for the most part, on a sound experimental foundation, which points the way towards optimally effective therapy. JF - Annals of the New York Academy of Sciences AU - Kohn, K W AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. kohnk@dc37a.nci.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 11 EP - 26 VL - 922 SN - 0077-8923, 0077-8923 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Enzyme Inhibitors KW - Topoisomerase I Inhibitors KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Animals KW - Humans KW - Drug Design KW - Structure-Activity Relationship KW - Camptothecin -- chemistry KW - Antineoplastic Agents, Phytogenic -- toxicity KW - Antineoplastic Agents, Phytogenic -- chemistry KW - Enzyme Inhibitors -- toxicity KW - Enzyme Inhibitors -- chemistry KW - Camptothecin -- toxicity KW - Camptothecin -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72521656?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+and+biological+determinants+of+the+cytotoxic+actions+of+camptothecins.+Perspective+for+the+development+of+new+topoisomerase+I+inhibitors.&rft.au=Kohn%2C+K+W%3BPommier%2C+Y&rft.aulast=Kohn&rft.aufirst=K&rft.date=2000-01-01&rft.volume=922&rft.issue=&rft.spage=11&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 - 2001-02-01 N1 - Date created - 2001-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The clinical development of 9-aminocamptothecin. AN - 72520689; 11193898 AB - 9-Aminocamptothecin (9-AC) is a topoisomerase I-targeting agent first synthesized by Wani and Wall in 1986. Because of its potent in vitro effects and promising preclinical activity in colorectal cancer animal models, it was designated a high-priority compound for further drug development by the NCI. In 1993, 9-AC first entered clinical trials as a 72-hour intravenous (i.v.) infusion. Predictable myelosuppression was the major dose-limiting toxicity, and pharmacokinetic studies showed a relatively short plasma half-life and unstable lactone ring. Unfortunately, phase II studies using this schedule showed minimal or no activity in tumors such as colorectal and lung cancer. Modest activity was observed in ovarian cancer and in refractory lymphomas. Efforts to improve systemic drug exposure by utilizing alternative schedules of administration of 9-AC such as prolonged, continuous intravenous infusions have also been tested. However, phase II studies of 120-hour weekly infusions of 9-AC have not shown improved activity against solid tumors such as colorectal cancer. More recently, a daily times 5 days i.v. administration schedule has been tested. Currently, further development of intravenously administered 9-AC for the treatment of colorectal cancer is not promising. Thus, topotecan and irinotecan remain the only two successfully developed topoisomerase I-targeting drugs in the United States. This experience with 9-AC raises important questions regarding how to best select new topoisomerase I-targeting drugs for future clinical development. JF - Annals of the New York Academy of Sciences AU - Takimoto, C H AU - Thomas, R AD - Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland 20889, USA. takimotoc@oncology.uthscsa.edu Y1 - 2000 PY - 2000 DA - 2000 SP - 224 EP - 236 VL - 922 SN - 0077-8923, 0077-8923 KW - Antineoplastic Agents KW - 0 KW - 9-aminocamptothecin KW - 5MB77ICE2Q KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Drug Screening Assays, Antitumor KW - Animals KW - Clinical Trials, Phase II as Topic KW - Humans KW - Clinical Trials, Phase I as Topic KW - Neoplasms -- drug therapy KW - Camptothecin -- pharmacology KW - Camptothecin -- analogs & derivatives KW - Camptothecin -- therapeutic use KW - Camptothecin -- adverse effects KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72520689?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=The+clinical+development+of+9-aminocamptothecin.&rft.au=Takimoto%2C+C+H%3BThomas%2C+R&rft.aulast=Takimoto&rft.aufirst=C&rft.date=2000-01-01&rft.volume=922&rft.issue=&rft.spage=224&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 - 2001-02-01 N1 - Date created - 2001-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amino acid residues in alpha-helix-3 of human uteroglobin are critical for its phospholipase A2 inhibitory activity. AN - 72517657; 11193767 JF - Annals of the New York Academy of Sciences AU - Chowdhury, B AU - Mantile-Selvaggi, G AU - Kundu, G C AU - Miele, L AU - Cordella-Miele, E AU - Zhang, Z AU - Mukherjee, A B AD - Section on Developmental Genetics, Human Genetics Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1830, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 307 EP - 311 VL - 923 SN - 0077-8923, 0077-8923 KW - Amino Acids KW - 0 KW - Uteroglobin KW - 9060-09-7 KW - Phospholipases A KW - EC 3.1.1.32 KW - Phospholipases A2 KW - EC 3.1.1.4 KW - Index Medicus KW - Animals KW - Humans KW - Amino Acid Sequence -- genetics KW - Mutagenesis, Site-Directed -- physiology KW - Protein Structure, Secondary -- genetics KW - Uteroglobin -- metabolism KW - Uteroglobin -- genetics KW - Amino Acids -- genetics KW - Amino Acids -- metabolism KW - Phospholipases A -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72517657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Amino+acid+residues+in+alpha-helix-3+of+human+uteroglobin+are+critical+for+its+phospholipase+A2+inhibitory+activity.&rft.au=Chowdhury%2C+B%3BMantile-Selvaggi%2C+G%3BKundu%2C+G+C%3BMiele%2C+L%3BCordella-Miele%2C+E%3BZhang%2C+Z%3BMukherjee%2C+A+B&rft.aulast=Chowdhury&rft.aufirst=B&rft.date=2000-01-01&rft.volume=923&rft.issue=&rft.spage=307&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 - 2001-03-01 N1 - Date created - 2001-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of CC10 in pulmonary carcinogenesis: from a marker to tumor suppression. AN - 72517177; 11193761 AB - CC10 is infrequently expressed in human non-small cell lung cancers (NSCLCs), despite being abundantly produced by progenitor cells for normal and neoplastic epithelium. Many abnormalities in the surrounding lung associated with field carcinogenesis, which reflect prolonged exposure to such carcinogens as tobacco smoke, also revealed altered expression of CC10. Exposure of hamsters and mice to the tobacco-specific carcinogen NNK led to reduced CC10 expression, which was partially reversible. Overexpression of CC10 in immortalized bronchial epithelial cells delayed the induction of anchorage-independent growth in response to NNK. The data suggest that downregulation of CC10 contributes to carcinogenesis because CC10 antagonizes the neoplastic phenotype. JF - Annals of the New York Academy of Sciences AU - Linnoila, R I AU - Szabo, E AU - DeMayo, F AU - Witschi, H AU - Sabourin, C AU - Malkinson, A AD - Cell and Cancer Biology Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, NIH, 9610 Medical Center Drive, Suite 300, Rockville, MD 20850, USA. ill7h@nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 249 EP - 267 VL - 923 SN - 0077-8923, 0077-8923 KW - Antineoplastic Agents KW - 0 KW - Biomarkers, Tumor KW - Proteins KW - SCGB1A1 protein, human KW - Scgb1a1 protein, mouse KW - Synaptophysin KW - Uteroglobin KW - 9060-09-7 KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured -- metabolism KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Antineoplastic Agents -- metabolism KW - Gene Expression Regulation, Neoplastic -- physiology KW - Disease Models, Animal KW - Mice KW - Mice, Transgenic KW - Synaptophysin -- genetics KW - Down-Regulation -- genetics KW - Synaptophysin -- metabolism KW - Signal Transduction -- genetics KW - Tumor Cells, Cultured -- pathology KW - Biomarkers, Tumor -- genetics KW - Respiratory Mucosa -- drug effects KW - Lung -- pathology KW - Proteins -- genetics KW - Proteins -- metabolism KW - Respiratory Mucosa -- pathology KW - Biomarkers, Tumor -- metabolism KW - Respiratory Mucosa -- metabolism KW - Lung Neoplasms -- etiology KW - Genes, Tumor Suppressor -- drug effects KW - Lung -- drug effects KW - Genes, Tumor Suppressor -- physiology KW - Lung -- physiopathology KW - Lung Neoplasms -- physiopathology KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72517177?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=The+role+of+CC10+in+pulmonary+carcinogenesis%3A+from+a+marker+to+tumor+suppression.&rft.au=Linnoila%2C+R+I%3BSzabo%2C+E%3BDeMayo%2C+F%3BWitschi%2C+H%3BSabourin%2C+C%3BMalkinson%2C+A&rft.aulast=Linnoila&rft.aufirst=R&rft.date=2000-01-01&rft.volume=923&rft.issue=&rft.spage=249&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 - 2001-03-01 N1 - Date created - 2001-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Therapeutic applications of antiflammin peptides in experimental ocular inflammation. AN - 72517093; 11193752 AB - Antiflammins are synthetic peptides derived from the region of highest local similarity between uteroglobulin and lipocortin. These peptides have shown anti-inflammatory activity on carrageenan-induced rat footpad edema. They are potent inhibitors for phospholipase A2 activation both in vitro and in vivo. Previously, we have demonstrated the effectiveness of topical antiflammins in suppressing acute ocular inflammation and allergic response in rodent endotoxin-induced uveitis and murine allergic conjunctivitis. The mechanisms by which antiflammins protect against inflammation and allergy in these ocular models may involve inhibition of phospholipase A2 and inducible nitric oxide synthase (iNOS) as well as the production of proinflammatory cytokine, interleukin-6. JF - Annals of the New York Academy of Sciences AU - Chan, C C AU - Tuaillon, N AU - Li, Q AU - Shen, D F AD - Section of Immunopathology, Laboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Drive, Building 10, Room 10N103, Bethesda, MD 20892-1857, USA. ccc@helix.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 141 EP - 146 VL - 923 SN - 0077-8923, 0077-8923 KW - Endotoxins KW - 0 KW - Oligopeptides KW - Peptide Fragments KW - antiflammin P1 KW - 118850-71-8 KW - antiflammin P2 KW - 118850-72-9 KW - Uteroglobin KW - 9060-09-7 KW - Index Medicus KW - Animals KW - Conjunctivitis, Allergic -- physiopathology KW - Endotoxins -- adverse effects KW - Uveitis -- physiopathology KW - Mice KW - Conjunctivitis, Allergic -- immunology KW - Uveitis -- drug therapy KW - Uveitis -- chemically induced KW - Conjunctivitis, Allergic -- drug therapy KW - Inflammation -- physiopathology KW - Eye Diseases -- drug therapy KW - Eye Diseases -- metabolism KW - Uteroglobin -- pharmacology KW - Peptide Fragments -- pharmacology KW - Eye Diseases -- physiopathology KW - Inflammation -- drug therapy KW - Disease Models, Animal KW - Oligopeptides -- pharmacology KW - Inflammation -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72517093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Therapeutic+applications+of+antiflammin+peptides+in+experimental+ocular+inflammation.&rft.au=Chan%2C+C+C%3BTuaillon%2C+N%3BLi%2C+Q%3BShen%2C+D+F&rft.aulast=Chan&rft.aufirst=C&rft.date=2000-01-01&rft.volume=923&rft.issue=&rft.spage=141&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 - 2001-03-01 N1 - Date created - 2001-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemokines released from astroglia by vasoactive intestinal peptide. Mechanism of neuroprotection from HIV envelope protein toxicity. AN - 72514983; 11193813 AB - The mechanism through which VIP prevents neurotoxicity associated with HIV envelope protein has been shown to involve the release of a beta-chemokine, MIP-1 alpha. Astrocytes stimulated with subnanomolar concentrations of VIP caused the release of MIP-1 alpha and RANTES, both of which have been shown to prevent neuronal cell death associated with gp120. It is further proposed that gp120 causes neuronal cell death, in part, by competing with endogenous chemokines at various chemokines receptors in the brain that are necessary for neuronal survival. Although the chemokines are known to be mediators of inflammation, our studies suggest that these compounds have additional roles as neuroprotective agents that depend on the concentration of chemokine, cellular microenvironment, and stage of development of target neurons. Our studies further imply that in a developing system, stimulation with a MIP-1 alpha like substance is necessary for neuronal survival and interference with this action results in neuronal cell death. JF - Annals of the New York Academy of Sciences AU - Brenneman, D E AU - Hauser, J AU - Spong, C Y AU - Phillips, T M AD - Section on Developmental and Molecular Pharmacology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health Bethesda, Maryland 20892, USA. dbrenn@codon.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 109 EP - 114 VL - 921 SN - 0077-8923, 0077-8923 KW - Antibodies KW - 0 KW - Chemokine CCL4 KW - Chemokine CCL5 KW - Chemokines KW - Chemokines, CC KW - HIV Envelope Protein gp120 KW - Macrophage Inflammatory Proteins KW - Neuroprotective Agents KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - Index Medicus KW - Chemokine CCL5 -- physiology KW - Animals KW - Macrophage Inflammatory Proteins -- antagonists & inhibitors KW - Cell Death -- drug effects KW - Chemokine CCL5 -- antagonists & inhibitors KW - Neuroprotective Agents -- pharmacology KW - Rats KW - Cells, Cultured KW - Antibodies -- pharmacology KW - Neutralization Tests KW - Chemokines, CC -- physiology KW - Cell Survival -- physiology KW - Macrophage Inflammatory Proteins -- physiology KW - Vasoactive Intestinal Peptide -- pharmacology KW - Astrocytes -- drug effects KW - HIV Envelope Protein gp120 -- toxicity KW - Astrocytes -- secretion KW - Chemokines -- secretion KW - Astrocytes -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72514983?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chemokines+released+from+astroglia+by+vasoactive+intestinal+peptide.+Mechanism+of+neuroprotection+from+HIV+envelope+protein+toxicity.&rft.au=Brenneman%2C+D+E%3BHauser%2C+J%3BSpong%2C+C+Y%3BPhillips%2C+T+M&rft.aulast=Brenneman&rft.aufirst=D&rft.date=2000-01-01&rft.volume=921&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 - 2001-02-01 N1 - Date created - 2001-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nonmyeloablative allogeneic stem cell transplantation: early promise and limitations. AN - 72464166; 11110600 AB - Allogeneic stem cell transplantation is used to treat a variety of malignant and nonmalignant hematologic diseases. Conventionally, high-dose chemoradiotherapy-based preparative regimens were considered essential both for tumor eradication and facilitation of donor stem cell engraftment. It is now apparent that an immune-mediated graft-versus-tumor effect has a pivotal role in the curative potential of allogeneic stem cell transplantation. This has prompted the development of less toxic, nonmyeloablative but profoundly immunosuppressive preparative regimens, often fludarabine- or radiation-based. Full donor engraftment can be achieved; however, a significant number of patients achieve a mixed chimeric state. Mixed hematopoietic chimerism provides a platform for the use of adoptive immunotherapy using donor lymphocyte infusions to maximize the immune-mediated antitumor effect, but the optimal usage has yet to be determined. Immediate procedure-related mortality with nonmyeloablative regimens has been low, but graft-versus-host disease remains a major clinical concern and treatment challenge. Major tumor responses have been seen in many hematologic malignancies primarily including patients with highly chemorefractory disease. Follow-up data have been short and additional time is needed to determine the efficacy and toxicities of this immunotherapy. This approach has potential for widespread clinical application including HLA mismatched and matched unrelated donor transplantation, exploration of a graft-versus-solid tumor effect, and correction of phenotypic expression in nonmalignant disorders. JF - The oncologist AU - McCarthy, N J AU - Bishop, M R AD - Department of Experimental Transplantation and Immunology, National Cancer Institute, Medicine Branch, Bethesda, Maryland 20892, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 487 EP - 496 VL - 5 IS - 6 SN - 1083-7159, 1083-7159 KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Index Medicus KW - Vidarabine -- analogs & derivatives KW - Leukemia -- therapy KW - Whole-Body Irradiation KW - Histocompatibility Testing KW - Humans KW - Transplantation, Homologous KW - Vidarabine -- therapeutic use KW - Graft vs Host Disease -- etiology KW - Hematopoietic Stem Cell Transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72464166?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+oncologist&rft.atitle=Nonmyeloablative+allogeneic+stem+cell+transplantation%3A+early+promise+and+limitations.&rft.au=McCarthy%2C+N+J%3BBishop%2C+M+R&rft.aulast=McCarthy&rft.aufirst=N&rft.date=2000-01-01&rft.volume=5&rft.issue=6&rft.spage=487&rft.isbn=&rft.btitle=&rft.title=The+oncologist&rft.issn=10837159&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-03 N1 - Date created - 2001-01-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Kappa-opioid receptor activation prevents alterations in mesocortical dopamine neurotransmission that occur during abstinence from cocaine. AN - 72462093; 11113311 AB - In vivo microdialysis was used to characterize basal dopamine dynamics and cocaine-evoked dopamine levels in the medial prefrontal cortex of male Sprague-Dawley rats that had previously received once daily injections of cocaine (days 1-5; 20mg/kg, i.p.) in combination with the selective kappa-opioid receptor agonist U-69593 (days 3-5; 0.32mg/kg, s.c.) or its vehicle. The influence of these treatments on [3H]dopamine uptake in medial prefrontal cortex synaptosomes was also determined. Three days following the cessation of drug treatment, animals with prior history of cocaine administration exhibited enhanced psychomotor stimulation in response to a subsequent cocaine challenge. This effect was not apparent in animals that had previously received the cocaine treatment regimen in combination with the kappa-opioid receptor agonist U-69593. Cocaine challenge increased prefrontal dopamine levels in all pretreatment groups, but cocaine-pre-exposed animals had lower cocaine-evoked dopamine levels and higher basal in vivo extraction fraction, indicative of an increase in basal dopamine uptake relative to controls. Pretreatment with U-69593 prevented these effects of cocaine. Measurement of [3H]dopamine uptake in synaptosomes revealed a significant increase in uptake three days after the cessation of cocaine treatment. No increase in uptake was observed in animals that had received the cocaine treatment regimen in combination with U-69593. These results demonstrate that the early phase of abstinence from cocaine is associated with marked alterations in medial prefrontal cortex dopamine neurotransmission and that these neuroadaptations are prevented by the activation of kappa-opioid receptors. Furthermore, they raise the possibility that mesocortical dopamine neurons may be an important neural substrate upon which kappa-opioid agonists act to prevent the development of cocaine-induced behavioral sensitization. JF - Neuroscience AU - Chefer, V I AU - Morón, J A AU - Hope, B AU - Rea, W AU - Shippenberg, T S AD - Behavioral Neuroscience Laboratory, NIH/NIDA Intramural Research Program, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. vchefer@intra.nida.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 619 EP - 627 VL - 101 IS - 3 SN - 0306-4522, 0306-4522 KW - Analgesics KW - 0 KW - Benzeneacetamides KW - Pyrrolidines KW - Receptors, Opioid, kappa KW - Cocaine KW - I5Y540LHVR KW - U 69593 KW - J5S4K6TKTG KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Synaptosomes -- drug effects KW - Analgesics -- pharmacology KW - Motor Activity -- physiology KW - Drug Interactions -- physiology KW - Microdialysis KW - Rats KW - Rats, Sprague-Dawley KW - Extracellular Space -- metabolism KW - Pyrrolidines -- pharmacology KW - Motor Activity -- drug effects KW - Extracellular Space -- drug effects KW - Synaptosomes -- metabolism KW - Male KW - Substance Withdrawal Syndrome -- physiopathology KW - Substance Withdrawal Syndrome -- metabolism KW - Neurons -- metabolism KW - Prefrontal Cortex -- metabolism KW - Synaptic Transmission -- drug effects KW - Neural Pathways -- metabolism KW - Neurons -- drug effects KW - Receptors, Opioid, kappa -- metabolism KW - Dopamine -- metabolism KW - Synaptic Transmission -- physiology KW - Prefrontal Cortex -- drug effects KW - Neural Pathways -- drug effects KW - Substance Withdrawal Syndrome -- pathology KW - Receptors, Opioid, kappa -- agonists KW - Cocaine-Related Disorders -- pathology KW - Neurons -- cytology KW - Cocaine-Related Disorders -- physiopathology KW - Ventral Tegmental Area -- metabolism KW - Ventral Tegmental Area -- drug effects KW - Ventral Tegmental Area -- cytology KW - Cocaine -- pharmacology KW - Cocaine-Related Disorders -- metabolism KW - Prefrontal Cortex -- cytology KW - Neural Pathways -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72462093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Kappa-opioid+receptor+activation+prevents+alterations+in+mesocortical+dopamine+neurotransmission+that+occur+during+abstinence+from+cocaine.&rft.au=Chefer%2C+V+I%3BMor%C3%B3n%2C+J+A%3BHope%2C+B%3BRea%2C+W%3BShippenberg%2C+T+S&rft.aulast=Chefer&rft.aufirst=V&rft.date=2000-01-01&rft.volume=101&rft.issue=3&rft.spage=619&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-01 N1 - Date created - 2001-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo neuroprotection of injured CNS neurons by a single injection of a DNA plasmid encoding the Bcl-2 gene. AN - 72451560; 11105694 JF - Progress in brain research AU - Saavedra, R A AU - Murray, M AU - de Lacalle, S AU - Tessler, A AD - Department of Neurobiology and Anatomy, MCP Hahnemann University, Philadelphia, PA 19129, USA. saavedra@nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 365 EP - 372 VL - 128 SN - 0079-6123, 0079-6123 KW - Immunotoxins KW - 0 KW - Neuroprotective Agents KW - Proto-Oncogene Proteins c-bcl-2 KW - Index Medicus KW - Animals KW - Red Nucleus -- metabolism KW - Septal Nuclei -- metabolism KW - Spinal Cord -- metabolism KW - Humans KW - Immunotoxins -- adverse effects KW - Septal Nuclei -- injuries KW - Mice KW - Red Nucleus -- cytology KW - Red Nucleus -- injuries KW - Apoptosis -- genetics KW - Septal Nuclei -- cytology KW - Axotomy -- adverse effects KW - Spinal Cord -- cytology KW - Spinal Cord Injuries -- therapy KW - Neurons -- metabolism KW - Genetic Therapy -- trends KW - Plasmids -- genetics KW - Neurons -- drug effects KW - Genes, bcl-2 -- genetics KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - Genetic Therapy -- methods KW - Proto-Oncogene Proteins c-bcl-2 -- genetics KW - Plasmids -- pharmacology KW - Neuroprotective Agents -- pharmacology KW - Neurons -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72451560?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+brain+research&rft.atitle=In+vivo+neuroprotection+of+injured+CNS+neurons+by+a+single+injection+of+a+DNA+plasmid+encoding+the+Bcl-2+gene.&rft.au=Saavedra%2C+R+A%3BMurray%2C+M%3Bde+Lacalle%2C+S%3BTessler%2C+A&rft.aulast=Saavedra&rft.aufirst=R&rft.date=2000-01-01&rft.volume=128&rft.issue=&rft.spage=365&rft.isbn=&rft.btitle=&rft.title=Progress+in+brain+research&rft.issn=00796123&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-04 N1 - Date created - 2000-12-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic haloperidol-induced alterations in pallidal GABA and striatal D(1)-mediated dopamine turnover as measured by dual probe microdialysis in rats. AN - 72436026; 11098113 AB - Using dual probe microdialysis, assessment of extracellular neurotransmitter levels in the corpus striatum and globus pallidus was performed in ovariectomized and gonadally intact female, Sprague-Dawley rats following chronic (24 weeks) oral haloperidol administration. Vacuous chewing movements, an animal analog of orofacial dyskinesia, were also recorded at several time points during haloperidol administration and throughout the dialysis sampling session. Basal GABA levels were significantly elevated in the globus pallidus of haloperidol-treated rats compared with vehicle animals. Injection of the dopamine D(1) agonist dihydrexidine (3mg/kg, s.c.) decreased striatal dopamine levels in both vehicle and haloperidol-treated rats, with a larger decrease seen in haloperidol-treated rats. Furthermore, dihydrexidine reduced striatal 3,4-dihydroxyphenylacetic acid and homovanillic acid levels only in haloperidol-treated rats. Gonadal status had no effect on any neurochemical measure. Vacuous chewing movements were significantly elevated in haloperidol-treated groups by the sixth week of treatment, with higher counts seen in gonadally intact rats. Vacuous chewing movements were significantly elevated above baseline in all groups following dihydrexidine, with no differential effect of prior haloperidol treatment or gonadal status. These results indicate a tonic increase in pallidal GABA levels and a hypersensitivity of D(1)-mediated striatal dopamine and dopamine metabolite decreases following chronic haloperidol treatment. While not found to be correlated with neurochemical measures, the heightened vacuous chewing movements in gonadally intact vs ovariectomized rats may serve as a model of hormone-mediated differences in neuroleptic-induced oral dyskinesia. JF - Neuroscience AU - Grimm, J W AU - See, R E AD - Intramural Research Program, National Institute on Drug Abuse, PO Box 5180, Baltimore, MD 21224, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 507 EP - 514 VL - 100 IS - 3 SN - 0306-4522, 0306-4522 KW - Dopamine Antagonists KW - 0 KW - Receptors, Dopamine D1 KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Haloperidol KW - J6292F8L3D KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Microdialysis KW - Animals KW - Rats, Sprague-Dawley KW - Mastication KW - Dyskinesia, Drug-Induced -- physiopathology KW - Time Factors KW - Female KW - Globus Pallidus -- metabolism KW - Receptors, Dopamine D1 -- physiology KW - Dopamine Antagonists -- pharmacology KW - Corpus Striatum -- metabolism KW - Haloperidol -- pharmacology KW - Dopamine -- metabolism KW - gamma-Aminobutyric Acid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72436026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Chronic+haloperidol-induced+alterations+in+pallidal+GABA+and+striatal+D%281%29-mediated+dopamine+turnover+as+measured+by+dual+probe+microdialysis+in+rats.&rft.au=Grimm%2C+J+W%3BSee%2C+R+E&rft.aulast=Grimm&rft.aufirst=J&rft.date=2000-01-01&rft.volume=100&rft.issue=3&rft.spage=507&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-11 N1 - Date created - 2000-12-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 tumor suppressor gene: at the crossroads of molecular carcinogenesis, molecular epidemiology, and human risk assessment. AN - 72421463; 11083100 AB - The molecular archaeology of the mutation spectra of tumor suppressor genes generates hypotheses concerning the etiology and molecular pathogenesis of human cancer. The spectrum of somatic mutations in the p53 gene implicates environmental carcinogens and both endogenous agents and processes in the etiology of human cancer. JF - Annals of the New York Academy of Sciences AU - Hussain, S P AU - Hollstein, M H AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 79 EP - 85 VL - 919 SN - 0077-8923, 0077-8923 KW - Carcinogens KW - 0 KW - Mutagens KW - Aflatoxin B1 KW - 9N2N2Y55MH KW - Index Medicus KW - Carcinogens -- pharmacology KW - Sunlight -- adverse effects KW - DNA Mutational Analysis KW - Humans KW - Skin Neoplasms -- etiology KW - Liver Neoplasms -- chemically induced KW - Mutagens -- pharmacology KW - Risk Assessment KW - Skin Neoplasms -- genetics KW - Oncogenes -- genetics KW - Aflatoxin B1 -- toxicity KW - Genetic Predisposition to Disease KW - Liver Neoplasms -- etiology KW - Liver Neoplasms -- genetics KW - Genes, p53 -- physiology KW - Neoplasms -- chemically induced KW - Genes, p53 -- genetics KW - Neoplasms -- epidemiology KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72421463?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p53+tumor+suppressor+gene%3A+at+the+crossroads+of+molecular+carcinogenesis%2C+molecular+epidemiology%2C+and+human+risk+assessment.&rft.au=Hussain%2C+S+P%3BHollstein%2C+M+H%3BHarris%2C+C+C&rft.aulast=Hussain&rft.aufirst=S&rft.date=2000-01-01&rft.volume=919&rft.issue=&rft.spage=79&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 - 2000-12-06 N1 - Date created - 2000-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The "rodent carcinogen" dilemma: formidable challenge for the technologies of the new millennium. AN - 72413605; 11083119 JF - Annals of the New York Academy of Sciences AU - Johnson, F M AD - Toxicology Operations Branch, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 288 EP - 299 VL - 919 SN - 0077-8923, 0077-8923 KW - Carcinogens KW - 0 KW - Mutagens KW - Index Medicus KW - United States KW - Rats KW - Salmonella -- drug effects KW - Animals KW - Salmonella -- genetics KW - Rats, Inbred F344 KW - Humans KW - National Institutes of Health (U.S.) KW - Mutagens -- toxicity KW - Male KW - Carcinogenicity Tests -- standards KW - Neoplasms, Experimental -- chemically induced KW - Carcinogens -- toxicity KW - Carcinogenicity Tests -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72413605?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=The+%22rodent+carcinogen%22+dilemma%3A+formidable+challenge+for+the+technologies+of+the+new+millennium.&rft.au=Johnson%2C+F+M&rft.aulast=Johnson&rft.aufirst=F&rft.date=2000-01-01&rft.volume=919&rft.issue=&rft.spage=288&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 - 2000-12-06 N1 - Date created - 2000-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sex differences in workplace smoking policies: results from the current population survey. AN - 72398614; 11070655 AB - To determine the prevalence of smoking policies in indoor work environments in the United States, with a special focus on sex differences in the provision of these policies. Information on the prevalence and restrictiveness of workplace smoking policies was obtained from 86,490 currently employed indoor workers (50,865 women and 35,625 men) 15 years of age and older who responded to the National Cancer Institute's Tobacco Use Supplement to the Current Population Survey, a cross-sectional survey of households in all 50 states and the District of Columbia conducted between 1995 and 1996. Eighty-six percent of respondents reported that their workplaces had official smoking policies, and 63% reported that their workplaces were smoke free. Women reported significantly higher rates of both official smoking policies and smoke-free workplaces than men, regardless of racial/ethnic or age group. The overall rates of worksite smoking restrictions, including the establishment of smoke-free workplaces, were higher than those reported in earlier surveys. Disparities in coverage will need to be reduced if all workers, regardless of sex, race, age, or industry of employment, are to be protected from the demonstrated hazards of environmental tobacco smoke. JF - Journal of the American Medical Women's Association (1972) AU - Sweeney, C T AU - Shopland, D R AU - Hartman, A M AU - Gibson, J T AU - Anderson, C M AU - Gower, K B AU - Burns, D M AD - Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD, USA. csweeney@pinneyassociates.com Y1 - 2000 PY - 2000 DA - 2000 SP - 311 EP - 315 VL - 55 IS - 5 SN - 0098-8421, 0098-8421 KW - Tobacco Smoke Pollution KW - 0 KW - Index Medicus KW - Age Factors KW - Sex Factors KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Data Collection KW - Adolescent KW - Male KW - Female KW - Smoking -- legislation & jurisprudence KW - Tobacco Smoke Pollution -- prevention & control KW - Tobacco Smoke Pollution -- legislation & jurisprudence KW - Workplace KW - Public Policy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72398614?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Medical+Women%27s+Association+%281972%29&rft.atitle=Sex+differences+in+workplace+smoking+policies%3A+results+from+the+current+population+survey.&rft.au=Sweeney%2C+C+T%3BShopland%2C+D+R%3BHartman%2C+A+M%3BGibson%2C+J+T%3BAnderson%2C+C+M%3BGower%2C+K+B%3BBurns%2C+D+M&rft.aulast=Sweeney&rft.aufirst=C&rft.date=2000-01-01&rft.volume=55&rft.issue=5&rft.spage=311&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Medical+Women%27s+Association+%281972%29&rft.issn=00988421&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-07 N1 - Date created - 2000-11-13 N1 - Date revised - 2017-02-06 N1 - Last updated - 2017-02-07 ER - TY - JOUR T1 - Micronucleated erythrocyte frequency in peripheral blood of B6C3F(1) mice from short-term, prechronic, and chronic studies of the NTP carcinogenesis bioassay program. AN - 72356662; 11044899 AB - The mouse peripheral blood micronucleus (MN) test was performed on samples collected from 20 short-term, 67 subchronic, and 5 chronic toxicity and carcinogenicity studies conducted by the National Toxicology Program (NTP). Data are presented for studies not previously published. Aspects of protocol that distinguish this test from conventional short-term bone marrow MN tests are duration of exposure, and absence of repeat tests and concurrent positive controls. Furthermore, in contrast to short-term bone marrow MN tests where scoring is limited to polychromatic erythrocytes (PCE), longer term studies using peripheral blood may evaluate MN in both, or either, the normochromatic (NCE) or PCE populations. The incidence of MN-PCE provides an index of damage induced within 72 hr of sampling, whereas the incidence of MN in the NCE population at steady state provides an index of average damage during the 30-day period preceding sampling. The mouse peripheral blood MN test has been proposed as a useful adjunct to rodent toxicity tests and has been effectively incorporated as a routine part of overall toxicity testing by the NTP. Data derived from peripheral blood MN analyses of dosed animals provide a useful indication of the in vivo potential for induced genetic damage and supply an important piece of evidence to be considered in the overall assessment of toxicity and health risk of a particular chemical. Although results indicate that the test has low sensitivity for prediction of carcinogenicity, a convincingly positive result in this assay appears to be highly predictive of rodent carcinogenicity. Copyright 2000 Wiley-Liss, Inc. JF - Environmental and molecular mutagenesis AU - Witt, K L AU - Knapton, A AU - Wehr, C M AU - Hook, G J AU - Mirsalis, J AU - Shelby, M D AU - MacGregor, J T AD - ILS, Inc., Research Triangle Park, North Carolina 27709, USA. witt@niehs.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 163 EP - 194 VL - 36 IS - 3 SN - 0893-6692, 0893-6692 KW - Carcinogens KW - 0 KW - Mutagens KW - Index Medicus KW - Animals KW - Drug Administration Schedule KW - Blood Specimen Collection -- methods KW - Mice KW - Bone Marrow Cells -- cytology KW - Micronucleus Tests KW - Carcinogens -- administration & dosage KW - Mice, Inbred Strains -- blood KW - Erythrocytes -- cytology KW - Carcinogens -- toxicity KW - Mutagens -- toxicity KW - Mutagens -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72356662?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+molecular+mutagenesis&rft.atitle=Micronucleated+erythrocyte+frequency+in+peripheral+blood+of+B6C3F%281%29+mice+from+short-term%2C+prechronic%2C+and+chronic+studies+of+the+NTP+carcinogenesis+bioassay+program.&rft.au=Witt%2C+K+L%3BKnapton%2C+A%3BWehr%2C+C+M%3BHook%2C+G+J%3BMirsalis%2C+J%3BShelby%2C+M+D%3BMacGregor%2C+J+T&rft.aulast=Witt&rft.aufirst=K&rft.date=2000-01-01&rft.volume=36&rft.issue=3&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Environmental+and+molecular+mutagenesis&rft.issn=08936692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-22 N1 - Date created - 2000-12-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequential intermediate high-dose therapy with etoposide, ifosfamide and cisplatin for patients with germ cell tumors. AN - 72354591; 11043829 AB - Intermediate high dose VIP (etoposide, ifosfamide, cisplatin) achieved comparable efficacy and improved tolerance in comparison with high-dose chemotherapy plus PBSC in poor risk germ cell tumors. The aim of this study was to confirm the effectivity and tolerance of this regimen in clinical practice. Twenty-five consecutive patients, 9 previously untreated with poor prognosis and 16 relapsed, were treated with 1.6 VIP or 1.9 VIP+PBSC. A relative dose intensity of 1.6 VIP was used in 14 patients and 11 patients received the intensity of 1.9 VIP. Clinical response was achieved in 56% of patients. Fifty-eight percent of patients have survived more than 1 year and 44% more than 2 years. No significant difference was noted between previously treated and untreated patients, as well as between the patients on 1.6 VIP and 1.9 VIP, with the exception of improved 1-year survival of patients on 1.9 VIP. One of four cisplatin-refractory patients achieved durable partial remission with a normal level of tumor markers. Serious non-hematological toxicity was rare. Myelotoxicity of 1.9 VIP was less serious in comparison with 1.6 VIP regimen, but the difference was not significant. Sequential intermediate high-dose therapy is an effective and tolerable regimen for patients with poor risk germ cell tumor as well as for relapsed patients. JF - Neoplasma AU - Mardiak, J AU - Fuchsberger, P AU - Lakota, J AU - Sálek, T AU - Sycová-Milá, Z AU - Drahokoupilová, M AU - Baláz, M AU - Koza, I AD - Department of Medicine, National Cancer Institute, Bratislava, Slovak Republic. mardiak.joezef@ba.telecom.sk Y1 - 2000 PY - 2000 DA - 2000 SP - 239 EP - 243 VL - 47 IS - 4 SN - 0028-2685, 0028-2685 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Etoposide KW - 6PLQ3CP4P3 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Cisplatin KW - Q20Q21Q62J KW - Ifosfamide KW - UM20QQM95Y KW - Index Medicus KW - Drug Administration Schedule KW - Combined Modality Therapy KW - Dose-Response Relationship, Drug KW - Humans KW - Salvage Therapy KW - Prognosis KW - Ifosfamide -- adverse effects KW - Cisplatin -- administration & dosage KW - Granulocyte-Macrophage Colony-Stimulating Factor -- administration & dosage KW - Etoposide -- administration & dosage KW - Adult KW - Hematopoietic Stem Cell Transplantation KW - Etoposide -- adverse effects KW - Middle Aged KW - Granulocyte Colony-Stimulating Factor -- administration & dosage KW - Cisplatin -- adverse effects KW - Adolescent KW - Male KW - Ifosfamide -- administration & dosage KW - Testicular Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Germinoma -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72354591?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neoplasma&rft.atitle=Sequential+intermediate+high-dose+therapy+with+etoposide%2C+ifosfamide+and+cisplatin+for+patients+with+germ+cell+tumors.&rft.au=Mardiak%2C+J%3BFuchsberger%2C+P%3BLakota%2C+J%3BS%C3%A1lek%2C+T%3BSycov%C3%A1-Mil%C3%A1%2C+Z%3BDrahokoupilov%C3%A1%2C+M%3BBal%C3%A1z%2C+M%3BKoza%2C+I&rft.aulast=Mardiak&rft.aufirst=J&rft.date=2000-01-01&rft.volume=47&rft.issue=4&rft.spage=239&rft.isbn=&rft.btitle=&rft.title=Neoplasma&rft.issn=00282685&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-26 N1 - Date created - 2000-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carboplatin and cyclophosphamide in the treatment of metastatic seminoma. AN - 72352670; 11043830 AB - Cisplatin-based chemotherapy is highly effective in advanced seminoma, but at the cost of a considerable toxicity. The response rate of carboplatin is comparable with cisplatin combinations but the relapse rate is higher. Our study assesses the efficacy and the toxicity of the combination of carboplatin and cyclophosphamide in patients with advanced seminoma. Nineteen consecutive patients received 6 cycles of intravenous cyclophosphamide 750 mg/m2 and carboplatin 350 mg/m2, repeated every 21 days. The overall objective response rate was 100%, 11 patients (58%) achieved a complete response and 8 patients (42%) showed a partial response. At median follow up of 4.2 years 3 patients (15%) relapsed. The 2-year disease-free survival and the overall survival are 72 and 94%, respectively. This outpatient treatment was well tolerated and the toxicity was mild. One patient had granulocytopenic fever and one patient had grade 3 cystitis. The combination therapy with carboplatin and cyclophosphamide is an effective and tolerable regimen in advanced seminoma. JF - Neoplasma AU - Mardiak, J AU - Sálek, T AU - Sycova-Milá, Z AU - Sufliarsky, J AU - Baláz, M AU - Koza, I AD - Department of Medicine, National Cancer Institute, Bratislava, Slovak Republic. mardiak.jozef@ba.telecom.sk Y1 - 2000 PY - 2000 DA - 2000 SP - 244 EP - 247 VL - 47 IS - 4 SN - 0028-2685, 0028-2685 KW - Cyclophosphamide KW - 8N3DW7272P KW - Carboplatin KW - BG3F62OND5 KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Disease-Free Survival KW - Humans KW - Adult KW - Neoplasm Metastasis KW - Middle Aged KW - Adolescent KW - Carboplatin -- adverse effects KW - Carboplatin -- administration & dosage KW - Male KW - Cyclophosphamide -- adverse effects KW - Testicular Neoplasms -- drug therapy KW - Seminoma -- pathology KW - Testicular Neoplasms -- pathology KW - Seminoma -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72352670?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neoplasma&rft.atitle=Carboplatin+and+cyclophosphamide+in+the+treatment+of+metastatic+seminoma.&rft.au=Mardiak%2C+J%3BS%C3%A1lek%2C+T%3BSycova-Mil%C3%A1%2C+Z%3BSufliarsky%2C+J%3BBal%C3%A1z%2C+M%3BKoza%2C+I&rft.aulast=Mardiak&rft.aufirst=J&rft.date=2000-01-01&rft.volume=47&rft.issue=4&rft.spage=244&rft.isbn=&rft.btitle=&rft.title=Neoplasma&rft.issn=00282685&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-26 N1 - Date created - 2000-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Low affinity channel blocking (uncompetitive) NMDA receptor antagonists as therapeutic agents--toward an understanding of their favorable tolerability. AN - 72321414; 11026482 AB - Studies in experimental models have suggested that NMDA receptor antagonists may have utility in the treatment of a wide variety of neurological and psychiatric disorders. However, clinical trials have not been encouraging largely because the antagonists evaluated to date have exhibited unacceptable neurobehavioral side effects. In animals, therapeutic doses of some low-affinity channel blocking (uncompetitive) NMDA receptor antagonists are associated with less gross neurological impairment and behavioral toxicity than other types of NMDA receptor antagonists. Favorable clinical experiences with several such agents has bolstered confidence in the neurotherapeutic potential of low affinity NMDA antagonists. This article reviews current research attempting to explain the improved tolerability of such antagonists. While no single mechanism appears to account for the reduced toxicity of such agents, kinetic properties, particularly rapid blocking rate, seem to be of key importance. Other factors include partial trapping, reduced agonist-independent (closed channel) block, subunit selectivity (particularly for receptors that do not contain the NR2A subunit), combined block at allosteric (voltage-independent) sites, and synergistic therapeutic effects produced by additional actions at receptor targets apart from NMDA receptors (e.g., weak positive allosteric modulation of GABA(A) receptors or state-dependent Na+ channel block). JF - Amino acids AU - Rogawski, M A AD - Neuronal Excitability Section, Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1408, USA. rogawski@nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 133 EP - 149 VL - 19 IS - 1 SN - 0939-4451, 0939-4451 KW - Excitatory Amino Acid Antagonists KW - 0 KW - Receptors, N-Methyl-D-Aspartate KW - Index Medicus KW - Animals KW - Nervous System Diseases -- drug therapy KW - Kinetics KW - Protein Binding KW - Binding Sites KW - Excitatory Amino Acid Antagonists -- metabolism KW - Excitatory Amino Acid Antagonists -- therapeutic use KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Excitatory Amino Acid Antagonists -- adverse effects KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Excitatory Amino Acid Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72321414?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Amino+acids&rft.atitle=Low+affinity+channel+blocking+%28uncompetitive%29+NMDA+receptor+antagonists+as+therapeutic+agents--toward+an+understanding+of+their+favorable+tolerability.&rft.au=Rogawski%2C+M+A&rft.aulast=Rogawski&rft.aufirst=M&rft.date=2000-01-01&rft.volume=19&rft.issue=1&rft.spage=133&rft.isbn=&rft.btitle=&rft.title=Amino+acids&rft.issn=09394451&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-01 N1 - Date created - 2001-01-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thrombopoietin and chemokine mRNA expression in patient post-chemotherapy and in vitro cytokine-treated marrow stromal cell layers. AN - 72307240; 11007917 AB - CD34(+) cells and megakaryocyte progenitors were lower in marrow from patients after hematological recovery from the first cycle of 5-fluorouracil, leucovorin, adriamycin, cyclophosphamide (FLAC) chemotherapy plus PIXY321 (GM-CSF/interleukin 3; IL-3 hybrid) than in FLAC + GM-CSF or pre-FLAC marrows. Marrow stromal layers, an in vitro model of the marrow microenvironment, express a combination of stimulatory and inhibitory factors that modulate hematopoietic progenitor cell proliferation and differentiation. The TaqMan assay and quantitative reverse transcriptase-polymerase chain reaction were used to measure monocyte chemoattractant protein-1 (MCP-1), melanoma stimulatory growth activity, and monokine inducible by interferon-gamma (Mig) (inhibitory chemokines for primitive or megakaryocyte progenitors) mRNA levels in in vitro PIXY and GM-CSF-treated and patient post-FLAC marrow stromal layers. Chemokine mRNA was increased after in vitro GM-CSF and to a lesser extent after PIXY treatment. MCP-1 mRNA levels were fivefold higher in FLAC + PIXY than in FLAC + GM-CSF layers, and Mig mRNA was elevated in FLAC + GM-CSF layers. Thrombopoietin (TPO), insulin-like growth factor I (IGF-I), and IGF-II (stimulatory factors for primitive and megakaryocyte progenitors) mRNA were also measured. TPO mRNA levels were 30% lower in GM-CSF and PIXY-pretreated than in control layers with no decrease in IGF mRNA. TPO mRNA in stromal layers of patients who developed grade 3 thrombocytopenia (platelets < 20 x 10(9)/l) during the third cycle of FLAC was only 24% of levels in stromal layers of marrow from other post-FLAC patients. Results demonstrate that patient and in vitro treatment had modulatory effects on TPO and chemokine mRNA expression in marrow stromal layers. JF - Stem cells (Dayton, Ohio) AU - Schwartz, G N AU - Kammula, U AU - Warren, M K AU - Park, M K AU - Yan, X Y AU - Marincola, F M AU - Gress, R E AD - Department of Experimental Transplantation and Immunology, Medicine Branch and Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA. gnschwar@cpcug.org Y1 - 2000 PY - 2000 DA - 2000 SP - 331 EP - 342 VL - 18 IS - 5 SN - 1066-5099, 1066-5099 KW - Chemokine CCL2 KW - 0 KW - Chemokines KW - Cytokines KW - Interleukin-3 KW - PIXY321 fusion protein, recombinant KW - RNA, Messenger KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Insulin-Like Growth Factor II KW - 67763-97-7 KW - Doxorubicin KW - 80168379AG KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Cyclophosphamide KW - 8N3DW7272P KW - Thrombopoietin KW - 9014-42-0 KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Chemokine CCL2 -- genetics KW - Humans KW - Leucovorin -- administration & dosage KW - Insulin-Like Growth Factor II -- genetics KW - Doxorubicin -- administration & dosage KW - Granulocyte Colony-Stimulating Factor -- pharmacology KW - RNA, Messenger -- genetics KW - Fluorouracil -- administration & dosage KW - Insulin-Like Growth Factor I -- genetics KW - Cells, Cultured KW - Recombinant Fusion Proteins -- therapeutic use KW - Female KW - Breast Neoplasms -- drug therapy KW - Transcription, Genetic -- drug effects KW - Cytokines -- pharmacology KW - Chemokines -- genetics KW - Stromal Cells -- physiology KW - Interleukin-3 -- pharmacology KW - Gene Expression Regulation -- immunology KW - Transcription, Genetic -- immunology KW - Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology KW - Granulocyte-Macrophage Colony-Stimulating Factor -- therapeutic use KW - Thrombopoietin -- genetics KW - Interleukin-3 -- therapeutic use KW - Breast Neoplasms -- pathology KW - Stromal Cells -- drug effects KW - Bone Marrow Cells -- pathology KW - Gene Expression Regulation -- drug effects KW - Bone Marrow Cells -- cytology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Stromal Cells -- cytology KW - Bone Marrow Cells -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72307240?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+cells+%28Dayton%2C+Ohio%29&rft.atitle=Thrombopoietin+and+chemokine+mRNA+expression+in+patient+post-chemotherapy+and+in+vitro+cytokine-treated+marrow+stromal+cell+layers.&rft.au=Schwartz%2C+G+N%3BKammula%2C+U%3BWarren%2C+M+K%3BPark%2C+M+K%3BYan%2C+X+Y%3BMarincola%2C+F+M%3BGress%2C+R+E&rft.aulast=Schwartz&rft.aufirst=G&rft.date=2000-01-01&rft.volume=18&rft.issue=5&rft.spage=331&rft.isbn=&rft.btitle=&rft.title=Stem+cells+%28Dayton%2C+Ohio%29&rft.issn=10665099&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-13 N1 - Date created - 2000-10-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protective peptides derived from novel glial proteins. AN - 72208245; 10961938 AB - In studying the mediators of VIP neurotrophism in the central nervous system, two glial proteins have been discovered. Both of these proteins contain short peptides that exhibit femtomolar potency in preventing neuronal cell death from a wide variety of neurotoxic substances. Extension of these peptides to models of oxidative stress or neurodegeneration in vivo have indicated significant efficacy in protection. These peptides, both as individual agents and in combination, have promise as possible protective agents in the treatment of human neurodegenerative disease and in pathologies involving oxidative stress. JF - Biochemical Society transactions AU - Brenneman, D E AU - Spong, C Y AU - Gozes, I AD - Section on Developmental and Molecular Pharmacology, Laboratory of Developmental Neurobiology, National Institute on Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. dbrenn@codon.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 452 EP - 455 VL - 28 IS - 4 SN - 0300-5127, 0300-5127 KW - ADNP protein, human KW - 0 KW - Homeodomain Proteins KW - Nerve Tissue Proteins KW - Neuropeptides KW - Neuroprotective Agents KW - Oligopeptides KW - Peptides KW - activity-dependent neurotrophic factor KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - Tetrodotoxin KW - 4368-28-9 KW - Index Medicus KW - Animals KW - Central Nervous System -- metabolism KW - Dose-Response Relationship, Drug KW - Humans KW - Neurons -- pathology KW - Tetrodotoxin -- metabolism KW - Cells, Cultured KW - Cell Death KW - Neurodegenerative Diseases -- metabolism KW - Oxidative Stress KW - Time Factors KW - Blood-Brain Barrier KW - Vasoactive Intestinal Peptide -- metabolism KW - Peptides -- chemistry KW - Neuroglia -- chemistry KW - Oligopeptides -- pharmacology KW - Nerve Tissue Proteins -- pharmacology KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72208245?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Society+transactions&rft.atitle=Protective+peptides+derived+from+novel+glial+proteins.&rft.au=Brenneman%2C+D+E%3BSpong%2C+C+Y%3BGozes%2C+I&rft.aulast=Brenneman&rft.aufirst=D&rft.date=2000-01-01&rft.volume=28&rft.issue=4&rft.spage=452&rft.isbn=&rft.btitle=&rft.title=Biochemical+Society+transactions&rft.issn=03005127&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-02-15 N1 - Date created - 2000-12-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Biochem Soc Trans 2000 Dec;28(6):983 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Factors critical to the design and execution of epidemiologic studies and description of an innovative technology to follow the progression from normal to cancer tissue. AN - 72208057; 10963626 AB - The results obtained from experimental studies of estrogen carcinogenesis need validation in epidemiologic studies. Such studies present additional challenges, however, because variations in human populations are much greater than those in experimental systems and in animal models. Because epidemiologic studies are often used to evaluate modest differences in risk factors, it is essential to minimize sources of errors and to maximize sensitivity, reproducibility, and specificity. In the first part of this chapter, critical factors in designing and executing epidemiologic studies, as well as the influence of sample collection, processing, and storage on data reliability, are discussed. One of the most important requirements is attaining sufficient statistical power to assess small genetic effects and to evaluate interactions between genetic and environmental factors. The second part of this chapter describes innovative technology, namely, Fourier transform-infrared (FT-IR) spectra of DNA that reveal major structural differences at various stages of the progression from normal to cancer tissue. The structural differences become evident from wavenumber-by-wavenumber statistical comparisons of the mean FT-IR spectra of DNA from normal to cancer tissues. This analysis has allowed distinguishing benign tissues from cancer and metastatic tissues in human breast, prostate, and ovarian cancers. This analysis, which requires less than 1 microg of DNA, is predicted to be used for detecting early cancer-related changes at the level of DNA, rather than at the cellular level. JF - Journal of the National Cancer Institute. Monographs AU - Garcia-Closas, M AU - Hankinson, S E AU - Ho, S AU - Malins, D C AU - Polissar, N L AU - Schaefer, S N AU - Su, Y AU - Vinson, M A AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 147 EP - 156 IS - 27 SN - 1052-6773, 1052-6773 KW - DNA, Neoplasm KW - 0 KW - Gonadal Steroid Hormones KW - Index Medicus KW - Gonadal Steroid Hormones -- analysis KW - Polymorphism, Genetic KW - Risk Factors KW - Humans KW - Models, Statistical KW - DNA, Neoplasm -- analysis KW - Male KW - Female KW - Precancerous Conditions -- genetics KW - Fourier Analysis KW - Precancerous Conditions -- epidemiology KW - Epidemiologic Research Design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72208057?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute.+Monographs&rft.atitle=Factors+critical+to+the+design+and+execution+of+epidemiologic+studies+and+description+of+an+innovative+technology+to+follow+the+progression+from+normal+to+cancer+tissue.&rft.au=Garcia-Closas%2C+M%3BHankinson%2C+S+E%3BHo%2C+S%3BMalins%2C+D+C%3BPolissar%2C+N+L%3BSchaefer%2C+S+N%3BSu%2C+Y%3BVinson%2C+M+A&rft.aulast=Garcia-Closas&rft.aufirst=M&rft.date=2000-01-01&rft.volume=&rft.issue=27&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute.+Monographs&rft.issn=10526773&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-04 N1 - Date created - 2000-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relapsing arthritis induced by cell transfer from collagen-immunised mice. AN - 72206534; 10958172 AB - Collagen-induced arthritis is a well-established model of chronic inflammatory arthritis. We here introduce a development of this model which combines the benefits of adoptive transfer and sequential relapse. DBA/1 x B10.Q F1 hybrid mice were immunised with bovine type II collagen, and those which developed a sufficiently high level of arthritis served as donors of spleen cells transferred into BALB/c SCID hosts. After boosting with 500 microg collagen, the development of host arthritis was monitored over a period of up to 256 days, during which up to three successive peaks were detected. In comparison with bovine collagen, mouse collagen used for boosting induced a lower initial peak but higher relapses. As expected, the transferred disease was more uniform than the freshly induced one. Previous information suggests that a shifting cytokine balance between protective and aggressive T cells may account for the relapse and remission. This study provides a model of relapsing polyarthritis, obtained with normal immunocytes boosted with a well-defined protein antigen in animals not themselves treated with adjuvant. As such it is relevant to the etiology of inflammatory arthritis in man, and, if further developed, could be of value for testing new therapeutic strategies. JF - Autoimmunity AU - Hesse, M AU - Mitchison, N A AD - Deutsches RheumaForschungsZentrumn, Berlin, Germany. mhesse@atlas.niaid.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 27 EP - 32 VL - 32 IS - 1 SN - 0891-6934, 0891-6934 KW - Collagen KW - 9007-34-5 KW - Index Medicus KW - Animals KW - Spleen -- cytology KW - Disease Models, Animal KW - Autoimmunity KW - Mice KW - Mice, SCID KW - Recurrence KW - Immunization KW - Spleen -- transplantation KW - Adoptive Transfer KW - Arthritis -- immunology KW - Arthritis -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72206534?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Autoimmunity&rft.atitle=Relapsing+arthritis+induced+by+cell+transfer+from+collagen-immunised+mice.&rft.au=Hesse%2C+M%3BMitchison%2C+N+A&rft.aulast=Hesse&rft.aufirst=M&rft.date=2000-01-01&rft.volume=32&rft.issue=1&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Autoimmunity&rft.issn=08916934&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-22 N1 - Date created - 2000-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gender differences in the EEG of abstinent cocaine abusers. AN - 71746867; 10940764 AB - Gender differences in the EEG were explored in cocaine-abusing individuals not seeking treatment. Twenty currently abstinent cocaine-abusing females aged 21-41 were studied. Their cocaine use history was matched to 20 currently abstinent cocaine-abusing males. Twelve female and 20 male non-drug-abusing individuals served as a control group. Resting eyes closed EEG was recorded from 8 leads. The males who used cocaine had elevated EEG beta (p<0.0125) and reduced alpha (p<0.0125) when compared to the cocaine-abusing females and control subjects. These findings suggest that the EEG of cocaine-abusing women may be more normal than that of cocaine-abusing men. Such gender-specific differences for cocaine-abusing populations may require gender-specific treatment to improve outcome. Copyright 2000 S. Karger AG, Basel. JF - Neuropsychobiology AU - King, D E AU - Herning, R I AU - Gorelick, D A AU - Cadet, J L AD - Molecular Neuropsychiatry Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 93 EP - 98 VL - 42 IS - 2 SN - 0302-282X, 0302-282X KW - Index Medicus KW - Psychiatric Status Rating Scales KW - Sex Characteristics KW - Humans KW - Adult KW - Male KW - Female KW - Substance Withdrawal Syndrome -- physiopathology KW - Cocaine-Related Disorders -- physiopathology KW - Electroencephalography -- drug effects KW - Substance Withdrawal Syndrome -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71746867?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychobiology&rft.atitle=Gender+differences+in+the+EEG+of+abstinent+cocaine+abusers.&rft.au=King%2C+D+E%3BHerning%2C+R+I%3BGorelick%2C+D+A%3BCadet%2C+J+L&rft.aulast=King&rft.aufirst=D&rft.date=2000-01-01&rft.volume=42&rft.issue=2&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Neuropsychobiology&rft.issn=0302282X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-15 N1 - Date created - 2000-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evolution of cancer epidemiology. AN - 71742772; 10939006 JF - Epidemiologic reviews AU - Linet, M S AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7238, USA. linetm@epndce.nci.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 35 EP - 56 VL - 22 IS - 1 SN - 0193-936X, 0193-936X KW - Index Medicus KW - Registries KW - Global Health KW - Statistics as Topic -- methods KW - Risk Factors KW - Humans KW - Environmental Exposure KW - Genetic Predisposition to Disease KW - Epidemiologic Research Design KW - Neoplasms -- epidemiology KW - Neoplasms -- prevention & control KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71742772?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiologic+reviews&rft.atitle=Evolution+of+cancer+epidemiology.&rft.au=Linet%2C+M+S&rft.aulast=Linet&rft.aufirst=M&rft.date=2000-01-01&rft.volume=22&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Epidemiologic+reviews&rft.issn=0193936X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-02 N1 - Date created - 2001-01-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Why I continue to support community water fluoridation. AN - 71270254; 10929563 JF - Journal of public health dentistry AU - Horowitz, H S AD - Dental Research and Public Health, Bethesda, MD 20817, USA. alice.horowitz@nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 67 EP - 71 VL - 60 IS - 2 SN - 0022-4006, 0022-4006 KW - Cariostatic Agents KW - 0 KW - Dietary Sucrose KW - Fluorides KW - Q80VPU408O KW - Dentistry KW - Index Medicus KW - Global Health KW - Dietary Sucrose -- administration & dosage KW - Cariostatic Agents -- adverse effects KW - Humans KW - Safety KW - National Institutes of Health (U.S.) KW - Public Health Dentistry KW - United States -- epidemiology KW - Research Design KW - New Zealand -- epidemiology KW - Fluorides -- adverse effects KW - Prevalence KW - Fluoridation -- economics KW - Dental Caries -- epidemiology KW - Dental Caries -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71270254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+public+health+dentistry&rft.atitle=Why+I+continue+to+support+community+water+fluoridation.&rft.au=Horowitz%2C+H+S&rft.aulast=Horowitz&rft.aufirst=H&rft.date=2000-01-01&rft.volume=60&rft.issue=2&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Journal+of+public+health+dentistry&rft.issn=00224006&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-14 N1 - Date created - 2000-11-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Public Health Dent. 2002 Spring;62(2):67-9 [11989208] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DRM/GREMLIN (CKTSF1B1) maps to human chromosome 15 and is highly expressed in adult and fetal brain. AN - 71254632; 10894942 AB - We have mapped and characterized the human homolog of Drm/Gremlin (CKTFS1B1), a member of a family of BMP antagonists that have been linked to both developmental and transformation-related functions. By screening a human cDNA library, we isolated a 3.3-kb cDNA containing the 552-bp region encoding the human DRM protein. CKTFS1B1 was localized on human chromosome 15q13--> q15 by somatic cell hybrid analysis and, more precisely, using radiation hybrids, to a region of markers linked to SGNE1, secretory granule neuroendocrine protein 1 and RYR3, the ryanodyne receptor 3. Northern blot analysis showed the presence of a single DRM-specific mRNA expressed in different human tissues, including brain, ovary, intestine and colon. In the brain, DRM expression is associated with the region localized around the internal capsule in the large subcortical nuclei. DRM appears to be predominantly expressed in normal cells and tissues, including normal neurons, astrocytes and fibroblasts. Interestingly, we detected DRM expression in normal cells obtained from several patients, but not in tumor cell lines established from the same patients. The data suggest that down-regulation of DRM is associated with tumor progression, and support the hypothesis that human DRM may play an important role during both neuroembryological development and carcinogenesis. Copyright 2000 S. Karger AG, Basel. JF - Cytogenetics and cell genetics AU - Topol, L Z AU - Modi, W S AU - Koochekpour, S AU - Blair, D G AD - Intramural Research Support Program, SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 79 EP - 84 VL - 89 IS - 1-2 SN - 0301-0171, 0301-0171 KW - Bone Morphogenetic Proteins KW - 0 KW - GREM1 protein, human KW - Intercellular Signaling Peptides and Proteins KW - Proteins KW - RNA, Messenger KW - Recombinant Fusion Proteins KW - Index Medicus KW - Aging -- metabolism KW - Humans KW - RNA, Messenger -- analysis KW - RNA, Messenger -- genetics KW - Neoplasms -- genetics KW - Cloning, Molecular KW - Recombinant Fusion Proteins -- metabolism KW - Gene Expression Profiling KW - Neoplasms -- pathology KW - Genetic Linkage -- genetics KW - Tumor Cells, Cultured KW - Physical Chromosome Mapping KW - Bone Morphogenetic Proteins -- metabolism KW - Recombinant Fusion Proteins -- genetics KW - Hybrid Cells KW - Molecular Sequence Data KW - Aging -- genetics KW - Cell Line KW - Neoplasms -- metabolism KW - Brain -- cytology KW - Brain -- embryology KW - Brain -- metabolism KW - Chromosomes, Human, Pair 15 -- genetics KW - Proteins -- metabolism KW - Proteins -- genetics KW - Brain -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71254632?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytogenetics+and+cell+genetics&rft.atitle=DRM%2FGREMLIN+%28CKTSF1B1%29+maps+to+human+chromosome+15+and+is+highly+expressed+in+adult+and+fetal+brain.&rft.au=Topol%2C+L+Z%3BModi%2C+W+S%3BKoochekpour%2C+S%3BBlair%2C+D+G&rft.aulast=Topol&rft.aufirst=L&rft.date=2000-01-01&rft.volume=89&rft.issue=1-2&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Cytogenetics+and+cell+genetics&rft.issn=03010171&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-09 N1 - Date created - 2000-08-09 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF154054; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sale of street food in Latin America. The Mexican case: joy or jeopardy? AN - 71253285; 10912387 AB - Have you ever visited a public market in Mexico, Guatemala, Panama, Colombia, Venezuela, Peru or Brazil? Have you ever stopped to eat delicious Mayan-style pork tacos, turnovers filled with corn fungus or squash flower, octopus stuffed crepes, crab, cassava, 'alcapurrias' or grasshoppers with lime juice and chili, agave worms or a 'come back to life' seafood cocktail? If you have not, you have been missing a large part of the Mexican, Guatemalan, Panamanian, Colombian, Venezuelan, Peruvian and Brazilian folklore, taste, smell and color. And if you have visited these countries, it will be easier for you to understand the information in this chapter. JF - World review of nutrition and dietetics AU - Muñoz de Chávez, M AU - Chávez Villasana, A AU - Chávez Muñoz, M AU - Eichin Vuskovic, I AD - National Cancer Institute, National Nutrition Institute S.Z., National School of Anthropology and History, Metropolitan University, Xochimilco, Mexico. Y1 - 2000 PY - 2000 DA - 2000 SP - 138 EP - 154 VL - 86 SN - 0084-2230, 0084-2230 KW - Index Medicus KW - Obesity KW - Mexico KW - Nutritive Value KW - Social Class KW - Humans KW - Urban Population KW - Male KW - Female KW - Food Handling -- economics KW - Food Microbiology KW - Food Handling -- legislation & jurisprudence KW - Food -- economics KW - Feeding Behavior -- ethnology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71253285?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=World+review+of+nutrition+and+dietetics&rft.atitle=Sale+of+street+food+in+Latin+America.+The+Mexican+case%3A+joy+or+jeopardy%3F&rft.au=Mu%C3%B1oz+de+Ch%C3%A1vez%2C+M%3BCh%C3%A1vez+Villasana%2C+A%3BCh%C3%A1vez+Mu%C3%B1oz%2C+M%3BEichin+Vuskovic%2C+I&rft.aulast=Mu%C3%B1oz+de+Ch%C3%A1vez&rft.aufirst=M&rft.date=2000-01-01&rft.volume=86&rft.issue=&rft.spage=138&rft.isbn=&rft.btitle=&rft.title=World+review+of+nutrition+and+dietetics&rft.issn=00842230&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-16 N1 - Date created - 2000-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of therapist characteristics in training effects in cognitive, supportive-expressive, and drug counseling therapies for cocaine dependence. AN - 71245253; 10896736 AB - The role of therapist characteristics in therapy training was examined for 62 therapists in a multisite psychotherapy outcome study that included cognitive therapy (CT), supportive-expressive (SE) psychodynamic therapy, and individual drug counseling (IDC) for cocaine-dependent patients. Demographic variables and experience and competence ratings prior to training were correlated with measures of change in competence during the training phase. Higher competence ratings before training were associated with greater change in competence for SE and higher average competence for IDC. More years of experience were associated with greater change in competence for CT therapists, but more hours of pre-training supervision in the CT treatment modality were associated with less change. JF - The Journal of psychotherapy practice and research AU - Siqueland, L AU - Crits-Christoph, P AU - Barber, J P AU - Butler, S F AU - Thase, M AU - Najavits, L AU - Onken, L S AD - National Institute on Drug Abuse Collaborative Cocaine Treatment Study, USA. siquelal@landrup.cpr.upenn.edu Y1 - 2000 PY - 2000 DA - 2000 SP - 123 EP - 130 VL - 9 IS - 3 SN - 1055-050X, 1055-050X KW - Index Medicus KW - Humans KW - Curriculum KW - Adult KW - Treatment Outcome KW - Professional Competence KW - Middle Aged KW - Male KW - Female KW - Psychotherapy -- education KW - Cognitive Therapy -- education KW - Cocaine-Related Disorders -- psychology KW - Psychoanalytic Therapy -- education KW - Cocaine-Related Disorders -- rehabilitation KW - Psychotherapeutic Processes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71245253?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+psychotherapy+practice+and+research&rft.atitle=The+role+of+therapist+characteristics+in+training+effects+in+cognitive%2C+supportive-expressive%2C+and+drug+counseling+therapies+for+cocaine+dependence.&rft.au=Siqueland%2C+L%3BCrits-Christoph%2C+P%3BBarber%2C+J+P%3BButler%2C+S+F%3BThase%2C+M%3BNajavits%2C+L%3BOnken%2C+L+S&rft.aulast=Siqueland&rft.aufirst=L&rft.date=2000-01-01&rft.volume=9&rft.issue=3&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+psychotherapy+practice+and+research&rft.issn=1055050X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-12-05 N1 - Date created - 2000-12-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Consult Clin Psychol. 1986 Jun;54(3):381-5 [3722567] Compr Psychiatry. 1986 Jul-Aug;27(4):364-71 [3524986] J Consult Clin Psychol. 1993 Jun;61(3):434-40 [8326044] J Consult Clin Psychol. 1993 Jun;61(3):441-7 [8326045] Addiction. 1994 Jun;89(6):679-88 [8069169] J Consult Clin Psychol. 1982 Feb;50(1):49-62 [7056920] J Consult Clin Psychol. 1996 Jun;64(3):619-22 [8698958] Drug Alcohol Depend. 1996 Dec 11;43(3):125-32 [9023068] Arch Gen Psychiatry. 1997 Aug;54(8):721-6 [9283507] J Consult Clin Psychol. 1998 Jun;66(3):484-92 [9642886] J Consult Clin Psychol. 1995 Apr;63(2):182-96 [7751479] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genomic structure and chromosome location of the mouse RelA p65 gene (Rela). AN - 71237149; 10894954 AB - The RelA (p65) subunit of transcription factor NF-kappaB plays a critical role in development, and rela(-/-) knockout mice die in utero from massive liver apoptosis. Only partial sequences of the mouse Rela gene are available. We have determined the genomic structure of mouse Rela and promoter, and have mapped the gene to chromosome 19B1-3. Copyright 2000 S. Karger AG, Basel. JF - Cytogenetics and cell genetics AU - Lemmer, E R AU - Welch, J L AU - Tsai, T AU - Keck-Waggoner, C L AU - Huh, C AU - Zimonjic, D B AU - Popescu, N C AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 129 EP - 132 VL - 89 IS - 1-2 SN - 0301-0171, 0301-0171 KW - NF-kappa B KW - 0 KW - Transcription Factor RelA KW - Index Medicus KW - Animals KW - Base Sequence KW - Chromosome Banding KW - Humans KW - Chromosomes, Human, Pair 11 -- genetics KW - Molecular Sequence Data KW - In Situ Hybridization, Fluorescence KW - Promoter Regions, Genetic -- genetics KW - Mice KW - Cloning, Molecular KW - Exons -- genetics KW - Physical Chromosome Mapping KW - NF-kappa B -- genetics KW - Introns -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71237149?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytogenetics+and+cell+genetics&rft.atitle=Genomic+structure+and+chromosome+location+of+the+mouse+RelA+p65+gene+%28Rela%29.&rft.au=Lemmer%2C+E+R%3BWelch%2C+J+L%3BTsai%2C+T%3BKeck-Waggoner%2C+C+L%3BHuh%2C+C%3BZimonjic%2C+D+B%3BPopescu%2C+N+C%3BThorgeirsson%2C+S+S&rft.aulast=Lemmer&rft.aufirst=E&rft.date=2000-01-01&rft.volume=89&rft.issue=1-2&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Cytogenetics+and+cell+genetics&rft.issn=03010171&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-09 N1 - Date created - 2000-08-09 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF199371; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergistic cell killing by combination therapy of retinoic acid and hyperthermia in human epidermoid laryngeal carcinoma cells in culture. AN - 71234086; 10870689 AB - In vitro monolayer culture and clonogenic assay were used to investigate the individual and combined effect of temperature and retinoic acid (RA) on cellular morphology and colony forming ability of human epidermoid laryngeal carcinoma (HEp-2) cells. 20 micromol. RA alone inhibited multilayer formation and induced cell flattening. Hyperthermia (42 degrees C) individually caused formation of cytoplasmic processes and irregularities in cellular shape and size. Combined effect of hyperthermia (42 degrees C) and 20 micromol. RA treatment caused bleb formation on cell surfaces and lysis of cytoplasmic and nuclear membrane. RA treatment also caused dose-dependent reduction of colony growth. Heat-induced cell killing was only observed at lethal temperatures of 43 degrees C and above. RA in combination with heat synergistically inhibited colony formation even at non lethal temperatures of 41 and 42 degrees C. These results indicate that RA in combination with hyperthermia may facilitate the therapy of human epidermoid larynx carcinoma. JF - Neoplasma AU - Mukherjee, P AU - Banerjee, K AU - Das, S K AD - Unit of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 2000 PY - 2000 DA - 2000 SP - 60 EP - 67 VL - 47 IS - 1 SN - 0028-2685, 0028-2685 KW - Antineoplastic Agents KW - 0 KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Dose-Response Relationship, Drug KW - Combined Modality Therapy KW - Humans KW - Cell Division -- drug effects KW - Tretinoin -- pharmacology KW - Hot Temperature KW - Antineoplastic Agents -- administration & dosage KW - Carcinoma, Squamous Cell -- pathology KW - Tretinoin -- administration & dosage KW - Carcinoma, Squamous Cell -- metabolism KW - Laryngeal Neoplasms -- metabolism KW - Laryngeal Neoplasms -- pathology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71234086?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neoplasma&rft.atitle=Synergistic+cell+killing+by+combination+therapy+of+retinoic+acid+and+hyperthermia+in+human+epidermoid+laryngeal+carcinoma+cells+in+culture.&rft.au=Mukherjee%2C+P%3BBanerjee%2C+K%3BDas%2C+S+K&rft.aulast=Mukherjee&rft.aufirst=P&rft.date=2000-01-01&rft.volume=47&rft.issue=1&rft.spage=60&rft.isbn=&rft.btitle=&rft.title=Neoplasma&rft.issn=00282685&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-10 N1 - Date created - 2000-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthetic peptide mimics of a predicted topographical interaction surface: the cytochrome P450 2B1 recognition domain for NADPH-cytochrome P450 reductase. AN - 71228945; 10882169 AB - In order to identify the cytochrome P450-binding domain for NADPH-cytochrome P450 reductase, synthetic peptide mimics of predicted surface regions of rat cytochrome P450 2B 1 were constructed and evaluated for inhibition of the P450-reductase interaction. A peptide corresponding to residues 116-134, which includes the C helix, completely inhibited reductase-mediated benzphetamine demethylation by purified P450 2B1. Replacement of Arg-125 by Glu yielded a noninhibitory peptide, suggesting that this residue significantly contributes to the reductase-P450 interaction. Additional P450 peptides were prepared which correspond to combinations of regions distant in primary sequence, but predicted to be spatially proximate. A peptide derived from segments of the C and L helices was a more potent inhibitor than peptides derived from either segment alone. This topographically designed peptide not only inhibited P450 2B1 in its purified form, but also when membrane-bound in rat liver microsomes. The peptide also inhibited microsomal aryl hydrocarbon hydroxylase, aniline hydroxylase, and erythromycin demethylase activities derived from other P450s. These results indicate that the C and L helices contribute to a reductase-binding site common to multiple P450s, and present a peptide mimic for this region that is useful for inhibition of P450-mediated microsomal activities. JF - Journal of protein chemistry AU - Omata, Y AU - Dai, R AU - Smith, S V AU - Robinson, R C AU - Friedman, F K AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 23 EP - 32 VL - 19 IS - 1 SN - 0277-8033, 0277-8033 KW - Detergents KW - 0 KW - Peptides KW - Surface-Active Agents KW - Cytochrome P-450 CYP2B1 KW - EC 1.14.14.1 KW - NADPH-Ferrihemoprotein Reductase KW - EC 1.6.2.4 KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - Models, Molecular KW - Amino Acid Sequence KW - Detergents -- pharmacology KW - Surface-Active Agents -- pharmacology KW - Binding Sites KW - Sequence Analysis, Protein KW - Rats KW - Sequence Alignment KW - Protein Binding -- drug effects KW - Molecular Sequence Data KW - Protein Structure, Tertiary KW - Male KW - Peptides -- chemical synthesis KW - Cytochrome P-450 CYP2B1 -- antagonists & inhibitors KW - NADPH-Ferrihemoprotein Reductase -- chemistry KW - Microsomes, Liver -- enzymology KW - Microsomes, Liver -- drug effects KW - Cytochrome P-450 CYP2B1 -- metabolism KW - Peptides -- metabolism KW - Peptides -- chemistry KW - NADPH-Ferrihemoprotein Reductase -- metabolism KW - NADPH-Ferrihemoprotein Reductase -- isolation & purification KW - Peptides -- pharmacology KW - Cytochrome P-450 CYP2B1 -- chemistry KW - Cytochrome P-450 CYP2B1 -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71228945?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+protein+chemistry&rft.atitle=Synthetic+peptide+mimics+of+a+predicted+topographical+interaction+surface%3A+the+cytochrome+P450+2B1+recognition+domain+for+NADPH-cytochrome+P450+reductase.&rft.au=Omata%2C+Y%3BDai%2C+R%3BSmith%2C+S+V%3BRobinson%2C+R+C%3BFriedman%2C+F+K&rft.aulast=Omata&rft.aufirst=Y&rft.date=2000-01-01&rft.volume=19&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Journal+of+protein+chemistry&rft.issn=02778033&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-11 N1 - Date created - 2000-10-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ifosfamide and vinorelbine in advanced pretreated ovarian cancer: a phase II study. AN - 71205667; 10854141 AB - The response rate to salvage chemotherapy in advanced ovarian cancer (AOC) has been disappointing in patients who do not respond or relapse after platinum-containing regimens. Ifosfamide (IFO) showed an overall response rate of 20% and vinorelbine (VNR) 15.6%. Trials of the association of these two drugs for AOC have not yet been published. Between April 1996 and August 1997, 17 patients with AOC were treated with intravenous IFO 2000 mg/m2 per day, days 1 to 3, with mesna uroprotection, and VNR 25 mg/m2 per day, days 1 and 8, every 3 weeks. All patients but one had been heavily pretreated. All patients had been treated with platinum compounds and 16/17 with taxanes. All 17 patients were evaluable for toxicity, and 16 for response (one lost to follow-up). One patient showed a partial response, 12 progressive disease and three stable disease. No complete responses were observed. The main toxicity was neutropenia (grade 3-4 in 82% of patients) with neutropenic fever in 17.6% of patients. In 70.5% of patients (19/59 of courses) VNR was not administered on day 8. In four patients (10/59 courses) the dose was reduced by 25% for persistent leukopenia grade 2-3. Other toxicities were not significant. This combination showed no activity in this set of patients. The poor outcome, as compared with the significant activity reported with the agents used singly, could be ascribed to the patients' characteristics, the low dose intensity of VNR administered and possible cross-resistance between the study drugs and previously used agents. JF - Cancer chemotherapy and pharmacology AU - Nardi, M AU - De Marco, S AU - Fabi, A AU - Aloe, A AU - Magnani, E AU - Grandinetti, P AU - Cognetti, F AD - Division of Medical Oncology I, Regina Elena National, Cancer Institute, Rome, Italy. mdb@crs.ifo.it Y1 - 2000 PY - 2000 DA - 2000 SP - 513 EP - 515 VL - 45 IS - 6 SN - 0344-5704, 0344-5704 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Antineoplastic Agents, Phytogenic KW - Vinblastine KW - 5V9KLZ54CY KW - vinorelbine KW - Q6C979R91Y KW - Ifosfamide KW - UM20QQM95Y KW - Index Medicus KW - Drug Therapy, Combination KW - Humans KW - Salvage Therapy KW - Adult KW - Aged KW - Middle Aged KW - Female KW - Vinblastine -- therapeutic use KW - Vinblastine -- analogs & derivatives KW - Antineoplastic Agents, Alkylating -- therapeutic use KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Vinblastine -- administration & dosage KW - Ifosfamide -- therapeutic use KW - Antineoplastic Agents, Alkylating -- administration & dosage KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - Ovarian Neoplasms -- drug therapy KW - Ifosfamide -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71205667?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=Ifosfamide+and+vinorelbine+in+advanced+pretreated+ovarian+cancer%3A+a+phase+II+study.&rft.au=Nardi%2C+M%3BDe+Marco%2C+S%3BFabi%2C+A%3BAloe%2C+A%3BMagnani%2C+E%3BGrandinetti%2C+P%3BCognetti%2C+F&rft.aulast=Nardi&rft.aufirst=M&rft.date=2000-01-01&rft.volume=45&rft.issue=6&rft.spage=513&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-27 N1 - Date created - 2000-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fifty years of radical ideas. AN - 71199196; 10863525 AB - My role in the free radical theory of oxygen toxicity is discussed. Rebeca Gerschman and I published several papers on this subject. This sparked my interest in geochemistry and I developed the idea that oxygen was the best qualified biological potential energy source for the following reasons: great abundance, easily accessible, possession of a high thermodynamic potential, and its slow reaction rate. Ionization radiation can be viewed as a catalyst for reactive oxygen species since a killing dose imparts an infinitesimal small amount of energy. Next, Carol A. Colton and I showed that in the mammalian brain that stimulated microglia produce the superoxide radical anion and its implications in Alzheimer's disease is discussed. More recently, I have become interested in the role of sulfhydryl groups in transcription factors. JF - Annals of the New York Academy of Sciences AU - Gilbert, D L AD - Unit on Reactive Oxygen Species, BNP, NINDS, National Institutes of Health, Bethesda, Maryland 20892-4156, USA. dangil@helix.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 1 EP - 14 VL - 899 SN - 0077-8923, 0077-8923 KW - Reactive Oxygen Species KW - 0 KW - Index Medicus KW - History of medicine KW - Gilbert KW - United States KW - Animals KW - Second Messenger Systems KW - History, 20th Century KW - Humans KW - Hippocampus -- metabolism KW - Alzheimer Disease -- metabolism KW - Alzheimer Disease -- history KW - Synapses -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71199196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Fifty+years+of+radical+ideas.&rft.au=Gilbert%2C+D+L&rft.aulast=Gilbert&rft.aufirst=D&rft.date=2000-01-01&rft.volume=899&rft.issue=&rft.spage=1&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 - 2000-07-13 N1 - Date created - 2000-07-13 N1 - Date revised - 2017-01-13 N1 - People - Gilbert N1 - Last updated - 2017-01-18 N1 - SubjectsTermNotLitGenreText - Gilbert ER - TY - JOUR T1 - Mechanisms of cell death governed by the balance between nitrosative and oxidative stress. AN - 71198487; 10863541 AB - Many cellular functions in physiology are regulated by the direct interaction of NO with target biomolecules. In many pathophysiologic and toxicologic mechanisms, NO first reacts with oxygen, superoxide or other nitrogen oxides to subsequently elicit indirect effects. The balance between nitrosative stress and oxidative stress within a specific biological compartment can determine whether the presence of NO will be ultimately deleterious or beneficial. Nitrosative stress can be defined primarily through reactions mediated by N2O3, a reactive nitrogen oxide species generated by high fluxes of NO in an aerobic environment. In contrast, oxidative stress is mediated primarily by superoxide and peroxides. In addition to reactive oxygen species, several reactive nitrogen oxide species such as peroxynitrite, nitroxyl, and nitrogen dioxide can also impose oxidative stress to a cell. We here describe how the mechanisms of cell death are interwoven in the balance between the different chemical intermediates involved in nitrosative and oxidative stress. JF - Annals of the New York Academy of Sciences AU - Espey, M G AU - Miranda, K M AU - Feelisch, M AU - Fukuto, J AU - Grisham, M B AU - Vitek, M P AU - Wink, D A AD - Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. SP@nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 209 EP - 221 VL - 899 SN - 0077-8923, 0077-8923 KW - Nitric Oxide KW - 31C4KY9ESH KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Index Medicus KW - Animals KW - Humans KW - Nitric Oxide Synthase -- metabolism KW - Oxidative Stress KW - Cell Death KW - Nitric Oxide -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71198487?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mechanisms+of+cell+death+governed+by+the+balance+between+nitrosative+and+oxidative+stress.&rft.au=Espey%2C+M+G%3BMiranda%2C+K+M%3BFeelisch%2C+M%3BFukuto%2C+J%3BGrisham%2C+M+B%3BVitek%2C+M+P%3BWink%2C+D+A&rft.aulast=Espey&rft.aufirst=M&rft.date=2000-01-01&rft.volume=899&rft.issue=&rft.spage=209&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 - 2000-07-13 N1 - Date created - 2000-07-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuroprotective antioxidants from marijuana. AN - 71197113; 10863546 AB - Cannabidiol and other cannabinoids were examined as neuroprotectants in rat cortical neuron cultures exposed to toxic levels of the neurotransmitter, glutamate. The psychotropic cannabinoid receptor agonist delta 9-tetrahydrocannabinol (THC) and cannabidiol, (a non-psychoactive constituent of marijuana), both reduced NMDA, AMPA and kainate receptor mediated neurotoxicities. Neuroprotection was not affected by cannabinoid receptor antagonist, indicating a (cannabinoid) receptor-independent mechanism of action. Glutamate toxicity can be reduced by antioxidants. Using cyclic voltametry and a fenton reaction based system, it was demonstrated that Cannabidiol, THC and other cannabinoids are potent antioxidants. As evidence that cannabinoids can act as an antioxidants in neuronal cultures, cannabidiol was demonstrated to reduce hydroperoxide toxicity in neurons. In a head to head trial of the abilities of various antioxidants to prevent glutamate toxicity, cannabidiol was superior to both alpha-tocopherol and ascorbate in protective capacity. Recent preliminary studies in a rat model of focal cerebral ischemia suggest that cannabidiol may be at least as effective in vivo as seen in these in vitro studies. JF - Annals of the New York Academy of Sciences AU - Hampson, A J AU - Grimaldi, M AU - Lolic, M AU - Wink, D AU - Rosenthal, R AU - Axelrod, J AD - Laboratory of Cellular and Molecular Regulation, NIMH, Bethesda, Maryland 20892, USA. aidan@codon.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 274 EP - 282 VL - 899 SN - 0077-8923, 0077-8923 KW - Antioxidants KW - 0 KW - Cannabinoids KW - Neuroprotective Agents KW - Index Medicus KW - Rats KW - Animals KW - Cerebral Cortex -- drug effects KW - Neurons -- drug effects KW - Antioxidants -- pharmacology KW - Cannabis -- chemistry KW - Cannabinoids -- pharmacology KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71197113?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neuroprotective+antioxidants+from+marijuana.&rft.au=Hampson%2C+A+J%3BGrimaldi%2C+M%3BLolic%2C+M%3BWink%2C+D%3BRosenthal%2C+R%3BAxelrod%2C+J&rft.aulast=Hampson&rft.aufirst=A&rft.date=2000-01-01&rft.volume=899&rft.issue=&rft.spage=274&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 - 2000-07-13 N1 - Date created - 2000-07-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduction by naloxone of lipopolysaccharide-induced neurotoxicity in mouse cortical neuron-glia co-cultures. AN - 71172004; 10842020 AB - An inflammatory response in the CNS mediated by activation of microglia is a key event in the early stages of the development of neurodegenerative diseases. Using mouse cortical mixed glia cultures, we have previously demonstrated that the bacterial endotoxin lipopolysaccharide induces the activation of microglia and the production of proinflammatory factors. Naloxone, an opioid receptor antagonist, inhibits the lipopolysaccharide-induced activation of microglia and the production of proinflammatory factors. Using neuron-glia co-cultures, we extended our study to determine if naloxone has a neuroprotective effect against lipopolysaccharide-induced neuronal damage and analysed the underlying mechanism of action for its potential neuroprotective effect. Pretreatment of cultures with naloxone (1 microM) followed by treatment with lipopolysaccharide significantly inhibited the lipopolysaccharide-induced production of nitric oxide and the release of tumor necrosis factor-alpha, and significantly reduced the lipopolysaccharide-induced damage to neurons. More importantly, both naloxone and its opioid-receptor ineffective enantiomer (+)-naloxone were equally effective in inhibiting the lipopolysaccharide-induced generation of proinflammatory factors and the activation of microglia, as well as in the protection of neurons. These results indicate that the neuroprotective effect of naloxone is mediated by its inhibition of microglial activity and may be unrelated to its binding to the classical opioid receptors. JF - Neuroscience AU - Liu, B AU - Du, L AU - Kong, L Y AU - Hudson, P M AU - Wilson, B C AU - Chang, R C AU - Abel, H H AU - Hong, J S AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, NC 27709, Research Triangle Park, USA. liu3@niehs.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 749 EP - 756 VL - 97 IS - 4 SN - 0306-4522, 0306-4522 KW - Lipopolysaccharides KW - 0 KW - Neuroprotective Agents KW - Neurotoxins KW - Nitrites KW - Tumor Necrosis Factor-alpha KW - Naloxone KW - 36B82AMQ7N KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Index Medicus KW - Coculture Techniques KW - Animals KW - Stereoisomerism KW - Cell Survival -- drug effects KW - Nitrites -- metabolism KW - Cells, Cultured KW - L-Lactate Dehydrogenase -- analysis KW - Mice KW - Embryo, Mammalian KW - Tumor Necrosis Factor-alpha -- secretion KW - Neuroglia -- cytology KW - Naloxone -- pharmacology KW - Cerebral Cortex -- cytology KW - Cerebral Cortex -- physiology KW - Lipopolysaccharides -- antagonists & inhibitors KW - Neurons -- drug effects KW - Neurons -- cytology KW - Neurons -- physiology KW - Lipopolysaccharides -- toxicity KW - Neuroglia -- drug effects KW - Neurotoxins -- toxicity KW - Neuroglia -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71172004?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Reduction+by+naloxone+of+lipopolysaccharide-induced+neurotoxicity+in+mouse+cortical+neuron-glia+co-cultures.&rft.au=Liu%2C+B%3BDu%2C+L%3BKong%2C+L+Y%3BHudson%2C+P+M%3BWilson%2C+B+C%3BChang%2C+R+C%3BAbel%2C+H+H%3BHong%2C+J+S&rft.aulast=Liu&rft.aufirst=B&rft.date=2000-01-01&rft.volume=97&rft.issue=4&rft.spage=749&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-24 N1 - Date created - 2000-07-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug abusers show impaired performance in a laboratory test of decision making. AN - 71156666; 10838152 AB - A defining feature of drug addiction is persistent drug use despite long-term adverse consequences. This study examined the performance of drug abusers on a neuropsychological test that requires evaluation of long-term outcomes in the presence of a complex set of mixed reward/punishment contingencies (the Gambling Task). In order to control for generalized deficits related to choice and planning, subjects were also administered the Wisconsin Card Sorting Task. Thirty polysubstance abusers were compared to a comparison group of 24 subjects who did not use illicit drugs of abuse. Drug abusers performed much more poorly on the Gambling Task (net score = 10.2 +/- 4.7, mean +/- s.e.m.) than controls (26.0 +/- 5.3), but did not differ from controls on the Wisconsin Card Sorting Task. The results show that drug abusers are more likely to make maladaptive decisions in the Gambling Task that result in long-term losses exceeding short-term gains. These findings indicate that the Gambling Task may be a useful model in laboratory studies of cognitive dysfunctions associated with drug abuse. JF - Neuropsychologia AU - Grant, S AU - Contoreggi, C AU - London, E D AD - Intramural Research Program, National Institute on Drug Abuse, Brain Imaging Center, 5500 Nathan Shock Drive, MD 21224, Baltimore, USA. sgrant@nida.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 1180 EP - 1187 VL - 38 IS - 8 SN - 0028-3932, 0028-3932 KW - Street Drugs KW - 0 KW - Index Medicus KW - Gambling -- psychology KW - Probability Learning KW - Motivation KW - Humans KW - Adult KW - Neuropsychological Tests KW - Problem Solving -- drug effects KW - Male KW - Female KW - Substance-Related Disorders -- diagnosis KW - Street Drugs -- adverse effects KW - Decision Making -- drug effects KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71156666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychologia&rft.atitle=Drug+abusers+show+impaired+performance+in+a+laboratory+test+of+decision+making.&rft.au=Grant%2C+S%3BContoreggi%2C+C%3BLondon%2C+E+D&rft.aulast=Grant&rft.aufirst=S&rft.date=2000-01-01&rft.volume=38&rft.issue=8&rft.spage=1180&rft.isbn=&rft.btitle=&rft.title=Neuropsychologia&rft.issn=00283932&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-28 N1 - Date created - 2000-08-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assignment of WDR7 (alias TRAG, TGF-beta resistance associated gene) to orthologous regions of human chromosome 18q21.1-->q22 and mouse chromosome 18D.1-E.3 by fluorescence in situ hybridization. AN - 71141291; 10828621 JF - Cytogenetics and cell genetics AU - Sanders, S AU - Keck-Waggoner, C L AU - Zimonjic, D B AU - Popescu, N C AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 324 EP - 325 VL - 88 IS - 3-4 SN - 0301-0171, 0301-0171 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - WDR7 protein, human KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Animals KW - Sequence Homology, Nucleic Acid KW - Chromosome Banding KW - Humans KW - Mice KW - Physical Chromosome Mapping KW - In Situ Hybridization, Fluorescence KW - Chromosomes, Human, Pair 18 -- genetics KW - GTP-Binding Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71141291?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytogenetics+and+cell+genetics&rft.atitle=Assignment+of+WDR7+%28alias+TRAG%2C+TGF-beta+resistance+associated+gene%29+to+orthologous+regions+of+human+chromosome+18q21.1--%26gt%3Bq22+and+mouse+chromosome+18D.1-E.3+by+fluorescence+in+situ+hybridization.&rft.au=Sanders%2C+S%3BKeck-Waggoner%2C+C+L%3BZimonjic%2C+D+B%3BPopescu%2C+N+C%3BThorgeirsson%2C+S+S&rft.aulast=Sanders&rft.aufirst=S&rft.date=2000-01-01&rft.volume=88&rft.issue=3-4&rft.spage=324&rft.isbn=&rft.btitle=&rft.title=Cytogenetics+and+cell+genetics&rft.issn=03010171&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-26 N1 - Date created - 2000-06-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New drugs and novel targets for treatment of invasive fungal infections in patients with cancer. AN - 71128613; 10794803 AB - Invasive fungal infections have emerged as important causes of morbidity and mortality in profoundly immunocompromised patients with cancer. Current treatment strategies for these infections are limited by antifungal resistance, toxicity, drug interactions, and expense. In order to overcome these limitations, new antifungal compounds are being developed, which may improve our therapeutic armamentarium for prevention and treatment of invasive mycoses in high-risk patients with neoplastic diseases. JF - The oncologist AU - Chiou, C C AU - Groll, A H AU - Walsh, T J AD - National Cancer Institute, Bethesda, Maryland, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 120 EP - 135 VL - 5 IS - 2 SN - 1083-7159, 1083-7159 KW - Antifungal Agents KW - 0 KW - Echinocandins KW - Lipopeptides KW - Lipoproteins KW - Peptides, Cyclic KW - Pyrimidines KW - Triazoles KW - anidulafungin KW - 9HLM53094I KW - Voriconazole KW - JFU09I87TR KW - micafungin KW - R10H71BSWG KW - Index Medicus KW - Lipoproteins -- pharmacology KW - Pyrimidines -- therapeutic use KW - Lipoproteins -- therapeutic use KW - Humans KW - Pyrimidines -- pharmacology KW - Triazoles -- pharmacology KW - Pyrimidines -- pharmacokinetics KW - Opportunistic Infections -- drug therapy KW - Triazoles -- pharmacokinetics KW - Lipoproteins -- pharmacokinetics KW - Peptides, Cyclic -- therapeutic use KW - Immunocompromised Host KW - Triazoles -- therapeutic use KW - Peptides, Cyclic -- pharmacokinetics KW - Peptides, Cyclic -- pharmacology KW - Antifungal Agents -- pharmacokinetics KW - Antifungal Agents -- adverse effects KW - Neoplasms -- complications KW - Antifungal Agents -- pharmacology KW - Mycoses -- drug therapy KW - Neoplasms -- microbiology KW - Mycoses -- etiology KW - Antifungal Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71128613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+oncologist&rft.atitle=New+drugs+and+novel+targets+for+treatment+of+invasive+fungal+infections+in+patients+with+cancer.&rft.au=Chiou%2C+C+C%3BGroll%2C+A+H%3BWalsh%2C+T+J&rft.aulast=Chiou&rft.aufirst=C&rft.date=2000-01-01&rft.volume=5&rft.issue=2&rft.spage=120&rft.isbn=&rft.btitle=&rft.title=The+oncologist&rft.issn=10837159&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-16 N1 - Date created - 2000-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activator protein-1 mediates induced but not basal epidermal growth factor receptor gene expression. AN - 71116958; 10803405 AB - The epidermal growth factor receptor (EGFR) is expressed at different levels in many cell types and found overexpressed in many cancers. EGFR expression is increased or decreased in response to extracellular stimuli. We examined the effect of increased c-Jun expression on EGFR promoter activity. We used DNAse I foot-printing analysis to determine the binding of activator protein 1 (AP-1) to the promoter region. We also used cotransfection experiments and western blotting analysis to determine the effect of AP-1 family members on EGFR expression. AP-1 was able to bind to at least seven sites in the EGFR promoter region. Cotransfection of MCF-7 cells with a c-Jun expression vector and the EGFR promoter reporter resulted in a 7-fold increase in promoter activity. JunB, but not c-fos, also enhanced the EGFR promoter activity. An A-Fos-dominant negative shown to inhibit Jun-dependent transactivation was able to prevent c-Jun induction of the promoter activity, but only slightly decreased the basal activity of the promoter. Furthermore, the A-Fos dominant negative was able to inhibit phorbol ester induction of the EGFR promoter. Examination of EGFR expression of MCF-7 stable cell lines that overexpress c-Jun revealed an increase in EGFR expression. Additionally, a cisplatin-resistant cell line, A2780/CP70, which has an increase in AP-1 activity compared with the parental cell line, A2780, was found to have an increase in EGFR level. These results indicate that AP-1 can act to increase the expression of EGFR and may play a role in upregulation of EGFR in cancer cells. JF - Molecular medicine (Cambridge, Mass.) AU - Johnson, A C AU - Murphy, B A AU - Matelis, C M AU - Rubinstein, Y AU - Piebenga, E C AU - Akers, L M AU - Neta, G AU - Vinson, C AU - Birrer, M AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. aj2e@nih.gov Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 17 EP - 27 VL - 6 IS - 1 SN - 1076-1551, 1076-1551 KW - Phorbol Esters KW - 0 KW - Proto-Oncogene Proteins c-fos KW - Proto-Oncogene Proteins c-jun KW - Transcription Factor AP-1 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Deoxyribonuclease I KW - EC 3.1.21.1 KW - Index Medicus KW - Breast Neoplasms -- genetics KW - 3T3 Cells KW - Animals KW - Humans KW - Mice KW - Protein Binding KW - Phorbol Esters -- pharmacology KW - Proto-Oncogene Proteins c-fos -- genetics KW - DNA Footprinting KW - Proto-Oncogene Proteins c-jun -- genetics KW - Gene Expression Regulation KW - Female KW - Promoter Regions, Genetic KW - Receptor, Epidermal Growth Factor -- genetics KW - Transcription Factor AP-1 -- metabolism KW - Receptor, Epidermal Growth Factor -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71116958?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+medicine+%28Cambridge%2C+Mass.%29&rft.atitle=Activator+protein-1+mediates+induced+but+not+basal+epidermal+growth+factor+receptor+gene+expression.&rft.au=Johnson%2C+A+C%3BMurphy%2C+B+A%3BMatelis%2C+C+M%3BRubinstein%2C+Y%3BPiebenga%2C+E+C%3BAkers%2C+L+M%3BNeta%2C+G%3BVinson%2C+C%3BBirrer%2C+M&rft.aulast=Johnson&rft.aufirst=A&rft.date=2000-01-01&rft.volume=6&rft.issue=1&rft.spage=17&rft.isbn=&rft.btitle=&rft.title=Molecular+medicine+%28Cambridge%2C+Mass.%29&rft.issn=10761551&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-12 N1 - Date created - 2000-06-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An immunoablative regimen of fludarabine and cyclophosphamide prevents fully MHC-mismatched murine marrow graft rejection independent of GVHD. AN - 71116079; 10816026 AB - The prevention of graft rejection in the setting of nonmyeloablative transplant approaches might be mediated by chemotherapy-induced host immunoablation and by the graft-promoting effects of graft-versus-host disease (GVHD). To evaluate whether host immunoablation alone might allow for alloengraftment, we developed an F1-into-parent murine marrow rejection model using host preparative regimens of lethal total body irradiation (TBI; 950 cGy), sublethal irradiation (600 cGy), or combinations of fludarabine (Flu) and cyclophosphamide (Cy). A preparative regimen selectivity index (SI) was calculated to determine whether host lymphocytes were preferentially depleted relative to myeloid cells (SI = number of host myeloid/number host T lymphoid cells remaining after preparative regimen administration). Saline-treated recipients were assigned an SI value of 1.0. Recipients of lethal TBI had reduced myeloid cells relative to T cells (SI = 0.6). In contrast, all Flu/Cy regimens preferentially depleted host T cells: recipients of Flu (100 mg/kg per day)/Cy (50 mg/kg per day) for 10 days (SI = 28.1); recipients of Flu (100 mg/kg per day)/Cy (100 mg/kg per day) for 10 days (SI = 64.1); and recipients of Flu (100 mg/kg per day)/Cy (50 mg/kg per day) for 19 or 27 days (SI = 74.6). The 10-day regimen of Flu/Cy (50 mg/kg per day) did not severely reduce host T cell numbers, nor did it prevent F1 marrow rejection (<1% chimerism, n = 14). In contrast, the 10-day regimen of Flu/Cy (100 mg/kg per day) reduced T-cell numbers below that of lethal TBI recipients and prevented F1 marrow rejection (11.4% chimerism, n = 15); donor chimerism was predominant in lymphoid cells and was stable through day 240 post-BMT. Additionally, the 19- or 27-day regimen of Flu/Cy, which most selectively depleted host T cells, also prevented F1 marrow rejection (6.3% chimerism, n = 15). These results therefore demonstrate that optimized Flu-containing, immunoablative preparative regimens can prevent fully MHC-disparate marrow rejection independent of GVHD. JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation AU - Petrus, M J AU - Williams, J F AU - Eckhaus, M A AU - Gress, R E AU - Fowler, D H AD - Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 182 EP - 189 VL - 6 IS - 2A SN - 1083-8791, 1083-8791 KW - Antineoplastic Agents KW - 0 KW - Immunosuppressive Agents KW - Cyclophosphamide KW - 8N3DW7272P KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - CD8-Positive T-Lymphocytes -- drug effects KW - Cell Lineage KW - Transplantation Chimera KW - Disease Models, Animal KW - Mice KW - Transplantation, Homologous KW - CD4-Positive T-Lymphocytes -- drug effects KW - Hematopoietic Stem Cells -- drug effects KW - Whole-Body Irradiation KW - Lymphocyte Depletion KW - Mice, Inbred C57BL KW - CD4-Positive T-Lymphocytes -- radiation effects KW - Graft vs Host Disease KW - Antineoplastic Agents -- therapeutic use KW - Hematopoietic Stem Cells -- radiation effects KW - Immunosuppressive Agents -- therapeutic use KW - CD8-Positive T-Lymphocytes -- radiation effects KW - Vidarabine -- analogs & derivatives KW - Bone Marrow Transplantation -- immunology KW - Graft Rejection -- drug therapy KW - Bone Marrow Transplantation -- adverse effects KW - Vidarabine -- pharmacology KW - Histocompatibility -- drug effects KW - Graft Rejection -- prevention & control KW - Cyclophosphamide -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71116079?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biology+of+blood+and+marrow+transplantation+%3A+journal+of+the+American+Society+for+Blood+and+Marrow+Transplantation&rft.atitle=An+immunoablative+regimen+of+fludarabine+and+cyclophosphamide+prevents+fully+MHC-mismatched+murine+marrow+graft+rejection+independent+of+GVHD.&rft.au=Petrus%2C+M+J%3BWilliams%2C+J+F%3BEckhaus%2C+M+A%3BGress%2C+R+E%3BFowler%2C+D+H&rft.aulast=Petrus&rft.aufirst=M&rft.date=2000-01-01&rft.volume=6&rft.issue=2A&rft.spage=182&rft.isbn=&rft.btitle=&rft.title=Biology+of+blood+and+marrow+transplantation+%3A+journal+of+the+American+Society+for+Blood+and+Marrow+Transplantation&rft.issn=10838791&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-09-14 N1 - Date created - 2000-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced vulnerability to oxidative stress by alpha-synuclein mutations and C-terminal truncation. AN - 71097886; 10799759 AB - alpha-Synuclein is a key component of Lewy bodies found in the brains of patients with Parkinson's disease and two point mutations in this protein, Ala53Thr and Ala30Pro, are associated with rare familial forms of the disease. Several lines of evidence suggest the involvement of oxidative stress in the pathogenesis of nigral neuronal death in Parkinson's disease. In the present work we studied the effects of changes in the alpha-synuclein sequence on the susceptibility of cells to reactive oxygen species. Human dopaminergic neuroblastoma SH-SY5Y cells were stably transduced with various isoforms of alpha-synuclein and their survival following exposure to hydrogen peroxide or to the dopaminergic neurotoxin MPP(+) was assessed. Cells expressing the two point mutant isoforms of alpha-synuclein were significantly more vulnerable to oxidative stress, with the Ala53Thr engineered cells faring the worst. In addition, cells expressing C-terminally truncated alpha-synuclein, particularly the 1-120 residue protein, were more susceptible than control beta-galactosidase engineered cells. The present experiments indicate that point mutations and C-terminal truncation of alpha-synuclein exaggerate the susceptibility of dopaminergic cells to oxidative damage. Thus, these observations provide a pathogenetic link between alpha-synuclein aberrations and a putative cell death mechanism in Parkinson's disease. JF - Neuroscience AU - Kanda, S AU - Bishop, J F AU - Eglitis, M A AU - Yang, Y AU - Mouradian, M M AD - Genetic Pharmacology Unit, Experimental Therapeutics Branch, NINDS, NIH, Bethesda, MD 20892-1406, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 279 EP - 284 VL - 97 IS - 2 SN - 0306-4522, 0306-4522 KW - Nerve Tissue Proteins KW - 0 KW - Phosphoproteins KW - Recombinant Proteins KW - SNCA protein, human KW - Synucleins KW - alpha-Synuclein KW - Hydrogen Peroxide KW - BBX060AN9V KW - 1-Methyl-4-phenylpyridinium KW - R865A5OY8J KW - Index Medicus KW - 1-Methyl-4-phenylpyridinium -- toxicity KW - Humans KW - Hydrogen Peroxide -- pharmacology KW - Phosphoproteins -- physiology KW - Neuroblastoma KW - Mutagenesis, Site-Directed KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Transfection KW - Recombinant Proteins -- metabolism KW - Recombinant Proteins -- chemistry KW - Amino Acid Substitution KW - Sequence Deletion KW - Nerve Tissue Proteins -- physiology KW - Oxidative Stress -- drug effects KW - Brain -- metabolism KW - Nerve Tissue Proteins -- genetics KW - Nerve Tissue Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71097886?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Enhanced+vulnerability+to+oxidative+stress+by+alpha-synuclein+mutations+and+C-terminal+truncation.&rft.au=Kanda%2C+S%3BBishop%2C+J+F%3BEglitis%2C+M+A%3BYang%2C+Y%3BMouradian%2C+M+M&rft.aulast=Kanda&rft.aufirst=S&rft.date=2000-01-01&rft.volume=97&rft.issue=2&rft.spage=279&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-27 N1 - Date created - 2000-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TOXNET: A computerized collection of toxicological and environmental health information. AN - 71091681; 10798381 AB - The Toxicology and Environmental Health Information Program, managed by the National Library of Medicine's Division of Specialized Information Services, provides access to a number of online bibliographic and factual computer files concerned with the toxicology, safety and handling, and environmental fate of chemicals, along with other files that cover genetic toxicology, developmental and reproductive toxicology, mutagenesis, carcinogenesis and toxic chemical releases. JF - Toxicology and industrial health AU - Fonger, G C AU - Stroup, D AU - Thomas, P L AU - Wexler, P AD - National Library of Medicine, Division of Specialized Information Services, Toxicology and Environmental Health Information Program, Bethesda, Maryland 20894, USA. gfonger@toxnetmail.nlm.nih.gov Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 4 EP - 6 VL - 16 IS - 1 SN - 0748-2337, 0748-2337 KW - Index Medicus KW - United States KW - Animals KW - Humans KW - National Library of Medicine (U.S.) -- organization & administration KW - Environmental Health KW - Information Systems -- organization & administration KW - Databases, Factual KW - Toxicology -- organization & administration UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71091681?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+industrial+health&rft.atitle=TOXNET%3A+A+computerized+collection+of+toxicological+and+environmental+health+information.&rft.au=Fonger%2C+G+C%3BStroup%2C+D%3BThomas%2C+P+L%3BWexler%2C+P&rft.aulast=Fonger&rft.aufirst=G&rft.date=2000-01-01&rft.volume=16&rft.issue=1&rft.spage=4&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+industrial+health&rft.issn=07482337&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-29 N1 - Date created - 2000-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Continuous infusion fluorouracil in the management of advanced breast cancer: a phase II study. AN - 71088349; 10778765 AB - The evaluation of unconventional schedules of well-known drugs represents a promising avenue in the search for new regimens with a better therapeutic index in metastatic breast cancer. In particular, protracted continuous infusion (PCI) of 5-fluorouracil (5-FU) has yielded interesting results in gastrointestinal malignancies and in breast cancer. From March 1996 30 consecutive patients with heavily pretreated breast cancer were treated with PCI 5-FU at a daily dose of 250 mg/m2 by means of disposable elastomeric pumps until progression or toxicity. The median age was 54 years (range, 28-71) and median performance status was 1 (range, 0-3). All patients but four were pretreated with anthracycline-containing regimens or taxanes; the median number of chemotherapy lines was 3 (range, 2-4). Metastatic sites were predominantly visceral in 60% of the patient population. All 30 patients were evaluable for response and toxicity. The median duration of PCI was 20 weeks (range, 2-36 weeks). Two complete responses (7%) and eight partial remissions (26%) were observed, giving an overall response rate of 33%. The median duration of response was six months (range, 4-9 months). Stabilization was observed in seven patients (23%) with a median duration of seven months (range, 3-9 months). The main toxic effects were grade I-II mucositis and hematologic toxicity, while grade 3 hand-foot syndrome was observed in eight patients (27%). This study confirms the efficacy and safety of 5-FU at this dosage and schedule in heavily pretreated women with advanced breast cancer. In order to improve on these results further studies are needed in a less advanced stage of the disease and together with other active drugs. JF - Tumori AU - Crivellari, D AU - Magri, M D AU - Buonadonna, A AU - Lombardi, D AU - Paolello, C AU - De Cicco, M AU - Fantin, D AU - Veronesi, A AD - Division of Medical Oncology C, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy. PY - 2000 SP - 42 EP - 45 VL - 86 IS - 1 SN - 0300-8916, 0300-8916 KW - Antimetabolites, Antineoplastic KW - 0 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Female KW - Fluorouracil -- administration & dosage KW - Breast Neoplasms -- drug therapy KW - Fluorouracil -- adverse effects KW - Antimetabolites, Antineoplastic -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71088349?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tumori&rft.atitle=Continuous+infusion+fluorouracil+in+the+management+of+advanced+breast+cancer%3A+a+phase+II+study.&rft.au=Crivellari%2C+D%3BMagri%2C+M+D%3BBuonadonna%2C+A%3BLombardi%2C+D%3BPaolello%2C+C%3BDe+Cicco%2C+M%3BFantin%2C+D%3BVeronesi%2C+A&rft.aulast=Crivellari&rft.aufirst=D&rft.date=2000-01-01&rft.volume=86&rft.issue=1&rft.spage=42&rft.isbn=&rft.btitle=&rft.title=Tumori&rft.issn=03008916&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-04 N1 - Date created - 2000-05-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vaccines for preventing typhoid fever. AN - 71088024; 10796623 AB - Whole cell vaccines, consisting of relatively crude preparations of Salmonella typhi administered parenterally, are effective but have a high incidence of adverse effects. Two vaccines have been developed more recently. Ty21a (an attenuated strain of S. typhi administered orally) and Vi (the purified bacterial capsule, given parenterally), have appeared less toxic than the older whole cell vaccines and are thought to be equally effective. The objective of this review was to assess the effects of typhoid fever vaccines. We searched the Cochrane Library, Medline, Index Medicus, Embase and reference lists of articles. Randomised trials comparing typhoid vaccines to other types of vaccine or placebo. Two reviewers independently assessed trial quality and extracted data. Seventeen studies, involving nearly two million people, were included. For the whole cell vaccines single dose regimens provided significant protection for the first two years. Two dose regimens provided significant protection for five years. For the Ty21a vaccine, both two and three dose regimens provided statistically significant protection for two years. The three dose regimen provided protection in the third and fourth years, but protection was not statistically significant in the fifth year. The Vi vaccine provided protection for two years, but the protection in the third year was not significant. The three year cumulative efficacy of two doses of whole cell vaccines was 73% (95% confidence interval 65-80), three doses of Ty21a was 51%, (95% confidence interval 35 to 63) and one dose of Vi was 55% (95% confidence interval 30 to 71). Data on adverse effects were limited, but indicate that whole cell vaccines are more toxic than the newer Ty21a and Vi vaccines. The whole cell vaccines provided more prolonged protection than either the Ty21a vaccine or the Vi vaccine. However whole cell vaccines are associated with higher toxicity. JF - The Cochrane database of systematic reviews AU - Engels, E A AU - Lau, J AD - Viral Epidemiology Branch, National Cancer Institute, 6130 Executive Blvd, EPN 434, Rockville, MD, USA. engelse@exchange.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 1 IS - 2 KW - Typhoid-Paratyphoid Vaccines KW - 0 KW - Vaccines, Attenuated KW - Index Medicus KW - Vaccines, Attenuated -- therapeutic use KW - Vaccines, Attenuated -- administration & dosage KW - Humans KW - Adult KW - Salmonella typhi -- immunology KW - Child KW - Adolescent KW - Child, Preschool KW - Typhoid Fever -- prevention & control KW - Typhoid-Paratyphoid Vaccines -- therapeutic use KW - Typhoid-Paratyphoid Vaccines -- administration & dosage KW - Typhoid Fever -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71088024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Cochrane+database+of+systematic+reviews&rft.atitle=Vaccines+for+preventing+typhoid+fever.&rft.au=Engels%2C+E+A%3BLau%2C+J&rft.aulast=Engels&rft.aufirst=E&rft.date=2000-01-01&rft.volume=&rft.issue=2&rft.spage=CD001261&rft.isbn=&rft.btitle=&rft.title=The+Cochrane+database+of+systematic+reviews&rft.issn=1469-493X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-06 N1 - Date created - 2000-07-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Update In: Cochrane Database Syst Rev. 2007;(3):CD001261 [17636661] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of varying concentrations of bleach on in vitro HIV-1 replication and the relevance to injection drug use. AN - 71086726; 10773730 AB - The use of bleach (hypochlorite) as a disinfectant for drug injection equipment in the intravenous-drug-using population was recommended early in the HIV-1/AIDS epidemic. Epidemiological studies have challenged the use of bleach as an effective measure to prevent HIV-1 transmission. However, in vitro HIV-1 coculture studies have shown that a high concentration of bleach is an effective cytotoxic and potentially virucidal agent. In this study, we demonstrate that HIV-1 peripheral blood mononuclear cell cocultures containing low concentrations of hypochlorite in the media showed earlier conversion to HIV-1 positivity, as measured by the presence of p24 antigen. HIV-1 cocultures with high concentrations of hypochlorite in the culture media, which appeared to be highly cytotoxic, and HIV-1 cocultures without bleach in the media did not exhibit this early p24 antigen positivity. Hypochlorite chemically disinfects by releasing free chlorine that is a potent oxidant. In injection drug equipment, a low residual concentration of bleach is likely to remain in cleaned equipment despite rinsing with water. Low concentrations of oxidants have been shown to enhance tissue inflammation, in vivo, as well as HIV-1 replication in vitro. Previous studies have shown that despite vigorous cleaning of blood-contaminated injection syringes with bleach followed by water, microaggregates of residual blood remained in bleach-cleaned blood-contaminated syringes. Hypothetically, oxidant effects of the residual bleach in the bleach-cleaned syringes could enhance the possibility of infection by remaining HIV-1 contained in a contaminated syringe. We suggest that the likelihood of an injection drug user contracting HIV-1 through the sharing of a bleach-cleaned blood-contaminated syringe may be increased by the cotransmission of residual bleach and its localized tissue-inflammatory effects; however, this has not been statistically proven in epidemiological studies. Copyright 2000 S. Karger AG, Basel. JF - Intervirology AU - Contoreggi, C AU - Jones, S AU - Simpson, P AU - Lange, W R AU - Meyer, W A AD - National Institutes of Health, National Institute on Drug Abuse, Intramural Research Program, Baltimore, Md., USA. ccontore@intra.nida.nih.gvo Y1 - 2000 PY - 2000 DA - 2000 SP - 1 EP - 5 VL - 43 IS - 1 SN - 0300-5526, 0300-5526 KW - Disinfectants KW - 0 KW - HIV Core Protein p24 KW - Oxidants KW - Sodium Hypochlorite KW - DY38VHM5OD KW - Index Medicus KW - AIDS/HIV KW - Disinfection KW - Coculture Techniques KW - Equipment Contamination KW - Oxidants -- pharmacology KW - Cell Survival -- drug effects KW - Virus Replication -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Needles -- virology KW - HIV Core Protein p24 -- analysis KW - Substance Abuse, Intravenous -- complications KW - Leukocytes, Mononuclear -- virology KW - HIV Infections -- transmission KW - Sodium Hypochlorite -- pharmacology KW - Syringes -- virology KW - HIV-1 -- physiology KW - Leukocytes, Mononuclear -- drug effects KW - HIV-1 -- drug effects KW - Disinfectants -- pharmacology KW - Leukocytes, Mononuclear -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71086726?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Intervirology&rft.atitle=Effects+of+varying+concentrations+of+bleach+on+in+vitro+HIV-1+replication+and+the+relevance+to+injection+drug+use.&rft.au=Contoreggi%2C+C%3BJones%2C+S%3BSimpson%2C+P%3BLange%2C+W+R%3BMeyer%2C+W+A&rft.aulast=Contoreggi&rft.aufirst=C&rft.date=2000-01-01&rft.volume=43&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Intervirology&rft.issn=03005526&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-21 N1 - Date created - 2000-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potentiation of the anti-HIV activity of zalcitabine and lamivudine by a CTP synthase inhibitor, 3-deazauridine. AN - 71046541; 10772721 AB - Low levels of the CTP synthase inhibitor 3-deazauridine (3-DU) strongly potentiated the anti-HIV-1 activity of the 5'-triphosphates of the cytidine-based analogues [-]2'-deoxy-3'-thiacytidine (3TC; lamivudine) and 2',3'-dideoxycytidine (ddC). The potentiation was associated with a 3-DU-induced decrease in dCTP pool size; no changes were seen in cellular pool sizes of dATP, dGTP or dTTP. JF - Nucleosides, nucleotides & nucleic acids AU - Gao, W Y AU - Johns, D G AU - Mitsuya, H AD - Experimental Retrovirology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. PY - 2000 SP - 371 EP - 377 VL - 19 IS - 1-2 SN - 1525-7770, 1525-7770 KW - Anti-HIV Agents KW - 0 KW - Enzyme Inhibitors KW - Reverse Transcriptase Inhibitors KW - 3-Deazauridine KW - 263CU738ZY KW - Lamivudine KW - 2T8Q726O95 KW - Zalcitabine KW - 6L3XT8CB3I KW - Deoxycytidine Kinase KW - EC 2.7.1.74 KW - Carbon-Nitrogen Ligases KW - EC 6.3.- KW - CTP synthetase KW - EC 6.3.4.2 KW - Index Medicus KW - AIDS/HIV KW - Leukocytes, Mononuclear -- virology KW - Virus Replication -- drug effects KW - Humans KW - In Vitro Techniques KW - Deoxycytidine Kinase -- metabolism KW - Leukocytes, Mononuclear -- drug effects KW - Drug Synergism KW - HIV-1 -- drug effects KW - Carbon-Nitrogen Ligases -- antagonists & inhibitors KW - Reverse Transcriptase Inhibitors -- pharmacology KW - Anti-HIV Agents -- pharmacology KW - Zalcitabine -- pharmacology KW - Lamivudine -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - 3-Deazauridine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71046541?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleosides%2C+nucleotides+%26+nucleic+acids&rft.atitle=Potentiation+of+the+anti-HIV+activity+of+zalcitabine+and+lamivudine+by+a+CTP+synthase+inhibitor%2C+3-deazauridine.&rft.au=Gao%2C+W+Y%3BJohns%2C+D+G%3BMitsuya%2C+H&rft.aulast=Gao&rft.aufirst=W&rft.date=2000-01-01&rft.volume=19&rft.issue=1-2&rft.spage=371&rft.isbn=&rft.btitle=&rft.title=Nucleosides%2C+nucleotides+%26+nucleic+acids&rft.issn=15257770&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-31 N1 - Date created - 2000-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phosphorylation status and function of P53 are inversely related to protein kinase C activation. AN - 71043423; 10769627 AB - The role of phosphorylation in the regulation of p53 protein function is little understood. We have addressed the role of protein kinase C (PKC) in the phosphorylation. Exposure to the protein kinase inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7), increased the phosphorylation of wild type p53 protein, whereas exposure to the tumor promoter phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), decreased it in vivo following 3 hours incubation with mouse epidermal JB6 cells. Exposure to the c-AMP dependent protein kinase (PKA) activator, forskolin, did not decrease the phosphorylation of p53 protein. In the transient transfection/luciferase reporter transactivation assay, H7 modestly increased the mouse double minute (MDM) 2 reporter transactivation activity of p53 protein after 24 hours treatment, and TPA completely blocked it. These results suggest that the accelerated phosphorylation of wild type p53 protein is inversely related to PKC activation, and that p53 phosphorylation may have some relation to transcription factor function. JF - Anticancer research AU - Nakamura, K AU - Sun, Y AU - Yokoyama, Y AU - Ferris, D AU - Singh, N AU - Ichikawa, T AU - Shinozuka, K AU - Kunitomo, M AU - Colburn, N AD - Gene Regulation Section, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA. lfp51193@mwu.mukogawa-u.ac.jp PY - 2000 SP - 1 EP - 5 VL - 20 IS - 1A SN - 0250-7005, 0250-7005 KW - Tumor Suppressor Protein p53 KW - 0 KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine KW - 84477-87-2 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 - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine -- pharmacology KW - Animals KW - Enzyme Activation KW - Transcription, Genetic KW - Mice KW - Mice, Inbred BALB C KW - Epidermis KW - Phosphorylation KW - Cyclic AMP-Dependent Protein Kinases -- antagonists & inhibitors KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Cycle KW - Cell Line KW - Protein Kinase C -- metabolism KW - Tumor Suppressor Protein p53 -- physiology KW - Protein Kinase C -- antagonists & inhibitors KW - MAP Kinase Signaling System KW - Protein Processing, Post-Translational KW - Tumor Suppressor Protein p53 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71043423?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Phosphorylation+status+and+function+of+P53+are+inversely+related+to+protein+kinase+C+activation.&rft.au=Nakamura%2C+K%3BSun%2C+Y%3BYokoyama%2C+Y%3BFerris%2C+D%3BSingh%2C+N%3BIchikawa%2C+T%3BShinozuka%2C+K%3BKunitomo%2C+M%3BColburn%2C+N&rft.aulast=Nakamura&rft.aufirst=K&rft.date=2000-01-01&rft.volume=20&rft.issue=1A&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-11 N1 - Date created - 2000-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - cis-hydroxyproline stimulates the growth of rat mammary carcinoma cells. AN - 71028078; 10757055 AB - With the ever-increasing evidence that the extracellular matrix (ECM) can stimulate tumor growth, it follows that inhibiting the synthesis of tumor-derived stroma may be a potential therapeutic target of cancer progression. The proline analog cis-hydroxyproline (CHP), an inhibitor of collagen deposition, was examined for its effects on the growth of clonal tumor cells that differentially produce type IV collagen and laminin. Two separate clones derived from rat mammary carcinoma cells that produce high and low amounts of type IV collagen and laminin were injected into the flanks of nude mice. Tumors in animals receiving CHP treatment grew faster than tumors in control animals receiving saline, although statistically not significant. Furthermore, upon administration of CHP to these clones in culture, increased proliferation rates of both cell types were observed. These results show that CHP is not useful in preventing stromal development and growth of rat mammary tumor xenografts. JF - In vivo (Athens, Greece) AU - Buck, T B AU - Hall, A L AU - Sinha, C C AU - Bunce, O R AU - Thorgeirsson, U P AD - Tumor Biology and Carcinogenesis Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. PY - 2000 SP - 7 EP - 11 VL - 14 IS - 1 SN - 0258-851X, 0258-851X KW - Proliferating Cell Nuclear Antigen KW - 0 KW - Tissue Inhibitor of Metalloproteinase-1 KW - Collagen KW - 9007-34-5 KW - Hydroxyproline KW - RMB44WO89X KW - Index Medicus KW - Rats KW - Neoplasm Transplantation KW - Gene Expression Regulation, Neoplastic KW - Animals KW - Tumor Cells, Cultured KW - Dose-Response Relationship, Drug KW - Humans KW - Collagen -- analysis KW - Transplantation, Heterologous KW - Proliferating Cell Nuclear Antigen -- analysis KW - Mice, Nude KW - Mice KW - Immunohistochemistry KW - Tissue Inhibitor of Metalloproteinase-1 -- genetics KW - Hydroxyproline -- pharmacology KW - Cell Division -- drug effects KW - Mammary Neoplasms, Experimental -- genetics KW - Mammary Neoplasms, Experimental -- metabolism KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71028078?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+vivo+%28Athens%2C+Greece%29&rft.atitle=cis-hydroxyproline+stimulates+the+growth+of+rat+mammary+carcinoma+cells.&rft.au=Buck%2C+T+B%3BHall%2C+A+L%3BSinha%2C+C+C%3BBunce%2C+O+R%3BThorgeirsson%2C+U+P&rft.aulast=Buck&rft.aufirst=T&rft.date=2000-01-01&rft.volume=14&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=In+vivo+%28Athens%2C+Greece%29&rft.issn=0258851X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-16 N1 - Date created - 2000-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Susceptibility of nonhuman primates to carcinogens of human relevance. AN - 71022052; 10757072 AB - Nonhuman primates are a valuable experimental model for the evaluation of human carcinogenic risk but have not been widely used for various reasons, such as high cost and lack of availability. The present review discusses the findings from a long-term carcinogenesis study in nonhuman primates that was carried out under contract by the National Cancer Institute from 1961 to 1997. Among the classes of compounds investigated were model rodent carcinogens, food additives, food and environmental contaminants, heterocyclic amines, N-nitroso compounds, and antineoplastic and immunosuppressives. Of the model rodent carcinogens tested, only urethane was carcinogenic in monkeys. Long-term administration of saccharin or cyclamate did not result in toxicity or carcinogenicity in nonhuman primates, which is commonly seen in rodent models. Similar to rodent models and suspected in the human population, the fungal toxins, aflatoxin B1 and sterimatocystin, induced malignant liver tumors in monkeys. Relatively few animals administered DDT developed malignant tumors, however, hepatic and CNS toxicity was commonly observed. Hepatocellular carcinoma developed in a majority of monkeys administered the heterocyclic amine, IQ but not the structurally similar MeIQx. Resultant toxicity and carcinogenicity from N-nitroso compounds was variable. While diethylnitrosamine proved to be the most potent hepatocarcinogen tested, no malignant tumors were seen in animals administered N-methyl-N-nitro-N-nitrosoquanidine. Susceptibility of nonhuman primates to chemotherapeutic agents was also variable. Only procarbazine and N-methyl-N-nitrosourea were highly carcinogenic, whereas few tumors were seen as a result of cyclophosphamide, Adriamycin, melphalan, or azathioprine. JF - In vivo (Athens, Greece) AU - Schoeffner, D J AU - Thorgeirsson, U P AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, MD 20892, USA. PY - 2000 SP - 149 EP - 156 VL - 14 IS - 1 SN - 0258-851X, 0258-851X KW - Carcinogens KW - 0 KW - Index Medicus KW - Animals KW - Macaca fascicularis KW - Disease Susceptibility KW - Humans KW - Cercopithecus aethiops KW - Disease Models, Animal KW - Macaca mulatta KW - Neoplasms -- pathology KW - Neoplasms, Experimental -- chemically induced KW - Neoplasms -- chemically induced KW - Neoplasms, Experimental -- pathology KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71022052?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+vivo+%28Athens%2C+Greece%29&rft.atitle=Susceptibility+of+nonhuman+primates+to+carcinogens+of+human+relevance.&rft.au=Schoeffner%2C+D+J%3BThorgeirsson%2C+U+P&rft.aulast=Schoeffner&rft.aufirst=D&rft.date=2000-01-01&rft.volume=14&rft.issue=1&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=In+vivo+%28Athens%2C+Greece%29&rft.issn=0258851X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-16 N1 - Date created - 2000-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pathological assessment of the response of locally advanced breast cancer to neoadjuvant chemotherapy and its implications for surgical management. AN - 71000062; 10752778 AB - The effectiveness of breast-conserving surgery for patients with locally advanced breast cancer (LABC) after neoadjuvant chemotherapy (NACT) is still a controversial issue, and variable incidences of locoregional failures have been reported. The present study was conducted to pathologically assess the response of LABC to NACT, and also to evaluate the efficacy of preoperative clinical examination and mammography in detecting these pathological changes. A total of 38 patients with LABC received NACT in the form of three cycles of fluorouracil/adriamycin/cyclophosphamide and were then subjected to a mastectomy. The residual tumors in the mastectomy specimens were measured, mapped, and compared to the pretreatment and preoperative clinical and mammographic findings for evaluation. An objective response to NACT was observed in 70.4% of the patients; however, only 26.7% of them were suitable candidates for conservative surgery. The rest of the responders showed an increased incidence of multifocality and in situ lesions localized within the original tumor-bearing area. Both clinical examinations and mammography were inadequate for the selection of candidates for breast conservation. Tumor regression by NACT is probably induced by a process of tumor segmentation. It is also associated with an increased incidence of multifocality and in situ lesions. JF - Surgery today AU - El-Didi, M H AU - Moneer, M M AU - Khaled, H M AU - Makarem, S AD - Department of Pathology, National Cancer Institute, Cairo, Egypt. Y1 - 2000 PY - 2000 DA - 2000 SP - 249 EP - 254 VL - 30 IS - 3 SN - 0941-1291, 0941-1291 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Fluorouracil -- administration & dosage KW - Cyclophosphamide -- administration & dosage KW - Neoplasm Staging KW - Humans KW - Neoadjuvant Therapy KW - Adult KW - Treatment Outcome KW - Prognosis KW - Patient Care Planning KW - Middle Aged KW - Doxorubicin -- administration & dosage KW - Female KW - Breast Neoplasms -- drug therapy KW - Breast Neoplasms -- pathology KW - Mastectomy, Segmental KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Breast Neoplasms -- surgery KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71000062?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Surgery+today&rft.atitle=Pathological+assessment+of+the+response+of+locally+advanced+breast+cancer+to+neoadjuvant+chemotherapy+and+its+implications+for+surgical+management.&rft.au=El-Didi%2C+M+H%3BMoneer%2C+M+M%3BKhaled%2C+H+M%3BMakarem%2C+S&rft.aulast=El-Didi&rft.aufirst=M&rft.date=2000-01-01&rft.volume=30&rft.issue=3&rft.spage=249&rft.isbn=&rft.btitle=&rft.title=Surgery+today&rft.issn=09411291&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-26 N1 - Date created - 2000-04-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anti-HIV and anti-tumor protein MAP30, a 30 kDa single-strand type-I RIP, shares similar secondary structure and beta-sheet topology with the A chain of ricin, a type-II RIP. AN - 70991336; 10739256 AB - MAP30 is a 30 kDa single-stranded, type-I ribosome inactivating protein (RIP) possessing anti-tumor and anti-HIV activities. It binds both ribosomal RNA and the HIV-1 long-terminal repeat DNA. To understand the structural basis for MAP30 activities, we undertook the study of MAP30 by solution NMR spectroscopy. We report nearly complete 1H, 13C, and 15N chemical shift assignments of its 263 amino acids. Based upon an analysis of secondary 13C chemical shifts, 3J(HNHA) coupling constants, hydrogen exchange data, and nuclear Overhauser effect patterns, we find that the secondary structure and beta-sheet topology of MAP30 are very similar to those of the ricin A chain, a subunit of the well-known type-II RIP, even though two proteins display distinct activities. We therefore suggest that MAP30 and ricin A chain share a similar three-dimensional fold, and that the reported functional differences between two proteins arise primarily from differences in local three-dimensional structure and other structural properties such as surface electrostatic potentials. JF - Protein science : a publication of the Protein Society AU - Wang, Y X AU - Jacob, J AU - Wingfield, P T AU - Palmer, I AU - Stahl, S J AU - Kaufman, J D AU - Huang, P L AU - Lee-Huang, S AU - Torchia, D A AD - Molecular Structural Biology Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 138 EP - 144 VL - 9 IS - 1 SN - 0961-8368, 0961-8368 KW - Anti-HIV Agents KW - 0 KW - Antineoplastic Agents KW - MAP30 protein, Momordica charantia KW - Proteins KW - Ribosome Inactivating Proteins, Type 2 KW - Ricin KW - 9009-86-3 KW - Ribosome Inactivating Proteins KW - EC 3.2.2.22 KW - Index Medicus KW - AIDS/HIV KW - Protein Structure, Secondary KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Ricin -- chemistry KW - Anti-HIV Agents -- chemistry KW - Proteins -- chemistry KW - Antineoplastic Agents -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70991336?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.atitle=Anti-HIV+and+anti-tumor+protein+MAP30%2C+a+30+kDa+single-strand+type-I+RIP%2C+shares+similar+secondary+structure+and+beta-sheet+topology+with+the+A+chain+of+ricin%2C+a+type-II+RIP.&rft.au=Wang%2C+Y+X%3BJacob%2C+J%3BWingfield%2C+P+T%3BPalmer%2C+I%3BStahl%2C+S+J%3BKaufman%2C+J+D%3BHuang%2C+P+L%3BLee-Huang%2C+S%3BTorchia%2C+D+A&rft.aulast=Wang&rft.aufirst=Y&rft.date=2000-01-01&rft.volume=9&rft.issue=1&rft.spage=138&rft.isbn=&rft.btitle=&rft.title=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.issn=09618368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-05 N1 - Date created - 2000-05-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1999 Nov 12;99(4):433-42 [10571185] Nature. 1990 Sep 6;347(6288):92-5 [1975641] FEBS Lett. 1990 Oct 15;272(1-2):12-8 [1699801] FEBS Lett. 1991 Oct 7;291(1):139-44 [1936243] Protein Sci. 1993 Mar;2(3):429-35 [8453380] J Biomol NMR. 1993 Mar;3(2):185-204 [8477186] J Biomol NMR. 1999 Jun;14(2):181-4 [10427744] Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12208-12 [7527556] J Biomol NMR. 1995 Jan;5(1):67-81 [7881273] Gene. 1995 Aug 19;161(2):151-6 [7665070] Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8818-22 [7568024] Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3866-71 [9108070] Biochim Biophys Acta. 1993 Dec 21;1154(3-4):237-82 [8280743] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergistic effects of 8-Cl-cAMP and retinoic acids in the inhibition of growth and induction of apoptosis in ovarian cancer cells: induction of retinoic acid receptor beta. AN - 70973195; 10718618 AB - Both cAMP and retinoids play a role in cell differentiation and the control of cell growth. A site-selective cAMP analog, 8-Cl-cAMP and retinoic acid synergistically inhibit growth and induce apoptosis in certain cancer cells. In advanced or recurrent malignant diseases, retinoic acid (RA) is not effective even at doses that are toxic to the host. The objective of our present study was to examine the mechanism(s) of synergistic effects of retinoic acid (9-cis, 13-cis or all-trans RA) and 8-Cl-cAMP on apoptosis in human ovarian cancer NIH: OVCAR-3 and OVCAR-8 cells. RA induced growth inhibition and apoptosis in OVCAR-3 and OVCAR-8 cells. 8-Cl-cAMP acted synergistically with RA in inducing and activating retinoic acid receptor beta (RARbeta) which correlates with growth inhibition and apoptosis in both cell types. In addition, induction of apoptosis by RA plus 8-Cl-cAMP requires caspase-3 activation followed by cleavage of anti-poly(ADP-ribose) polymerase. Furthermore, mutations in CRE-related motif within the RARbeta promoter resulted in loss of both transcriptional activation of RARbeta and synergy between RA and 8-Cl-cAMP. RARbeta expression appears to be associated with induction of apoptosis. Introduction of the RARbeta gene into OVCAR-3 cells resulted in gain of RA sensitivity. Loss of RARbeta expression, therefore, may contribute to the tumorigenicity of human ovarian cancer cells. Thus, combined treatment with RA and 8-Cl-cAMP may provide an effective means for inducing RARbeta expression leading to apoptosis in ovarian cancer cells. JF - Molecular and cellular biochemistry AU - Srivastava, R K AU - Srivastave, A R AU - Cho-Chung, Y S AD - Cellular Biochemistry Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD 20892-1750, USA. Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 1 EP - 9 VL - 204 IS - 1-2 SN - 0300-8177, 0300-8177 KW - Antineoplastic Agents KW - 0 KW - Receptors, Retinoic Acid KW - retinoic acid receptor beta KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - 8-chloro-cyclic adenosine monophosphate KW - 41941-56-4 KW - Tretinoin KW - 5688UTC01R KW - CASP3 protein, human KW - EC 3.4.22.- KW - Caspase 3 KW - Caspases KW - Index Medicus KW - Tumor Cells, Cultured KW - Caspases -- physiology KW - Humans KW - Cell Division -- drug effects KW - Drug Synergism KW - Female KW - Tretinoin -- pharmacology KW - Receptors, Retinoic Acid -- biosynthesis KW - 8-Bromo Cyclic Adenosine Monophosphate -- analogs & derivatives KW - Apoptosis KW - Ovarian Neoplasms -- pathology KW - Antineoplastic Agents -- pharmacology KW - 8-Bromo Cyclic Adenosine Monophosphate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70973195?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Synergistic+effects+of+8-Cl-cAMP+and+retinoic+acids+in+the+inhibition+of+growth+and+induction+of+apoptosis+in+ovarian+cancer+cells%3A+induction+of+retinoic+acid+receptor+beta.&rft.au=Srivastava%2C+R+K%3BSrivastave%2C+A+R%3BCho-Chung%2C+Y+S&rft.aulast=Srivastava&rft.aufirst=R&rft.date=2000-01-01&rft.volume=204&rft.issue=1-2&rft.spage=1&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 - 2000-04-11 N1 - Date created - 2000-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An interesting state of affairs in genetic toxicology. AN - 70963338; 10712741 JF - Environmental and molecular mutagenesis AU - Zeiger, E AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. errol.zeiger@oecd.org Y1 - 2000 PY - 2000 DA - 2000 SP - 82 EP - 85 VL - 35 IS - 2 SN - 0893-6692, 0893-6692 KW - Carcinogens KW - 0 KW - Mutagens KW - Index Medicus KW - Rats KW - Animals KW - Mice KW - Male KW - Female KW - Cell Line KW - Salmonella -- genetics KW - Mutagenicity Tests KW - Carcinogens -- toxicity KW - Mutagens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70963338?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+molecular+mutagenesis&rft.atitle=An+interesting+state+of+affairs+in+genetic+toxicology.&rft.au=Zeiger%2C+E&rft.aulast=Zeiger&rft.aufirst=E&rft.date=2000-01-01&rft.volume=35&rft.issue=2&rft.spage=82&rft.isbn=&rft.btitle=&rft.title=Environmental+and+molecular+mutagenesis&rft.issn=08936692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-12 N1 - Date created - 2000-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression and function of EGF-related peptides and their receptors in gynecological cancer--from basic science to therapy. AN - 70956128; 10711495 AB - EGF-related peptides and their receptors play an important, but not fully understood role, both, in epithelial physiology and pathophysiology but also in human tumor carcinogenesis and tumor behavior, respectively. Overexpression of EGF-related growth factors from normal epithelium to carcinomas has been demonstrated for several human tissues such as breast, endometrium, cervix and ovary. Additionally, the differential overexpression of EGFR or erb B-2 in various malignancies has already proven to be efficacious in stratifying patients with respect to a poor prognosis. These data suggest that EGF-related growth factors, erb B receptors or signaling proteins that function either upstream or downstream from these receptors may represent novel targets for selective tumor therapy. In the future, conventional chemotherapy regimes will ultimately be wedded to more biologically-oriented therapies. One important target for these novel therapeutic approaches in solid tumors will be the EGF-related growth factors and their receptors. JF - Journal of receptor and signal transduction research AU - Ebert, A D AU - Wechselberger, C AU - Martinez-Lacaci, I AU - Bianco, C AU - Weitzel, H K AU - Salomon, D S AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda Maryland 20892, USA. Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 1 EP - 46 VL - 20 IS - 1 SN - 1079-9893, 1079-9893 KW - RNA, Messenger KW - 0 KW - Transforming Growth Factor alpha KW - Epidermal Growth Factor KW - 62229-50-9 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Receptor, ErbB-2 KW - Index Medicus KW - Animals KW - Humans KW - RNA, Messenger -- analysis KW - Female KW - Receptor, ErbB-2 -- genetics KW - Genital Neoplasms, Female -- chemistry KW - Genital Neoplasms, Female -- therapy KW - Epidermal Growth Factor -- genetics KW - Transforming Growth Factor alpha -- analysis KW - Receptor, Epidermal Growth Factor -- physiology KW - Receptor, Epidermal Growth Factor -- analysis KW - Receptor, ErbB-2 -- analysis KW - Receptor, ErbB-2 -- physiology KW - Transforming Growth Factor alpha -- genetics KW - Receptor, Epidermal Growth Factor -- genetics KW - Transforming Growth Factor alpha -- physiology KW - Epidermal Growth Factor -- analysis KW - Epidermal Growth Factor -- physiology KW - Genital Neoplasms, Female -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70956128?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+receptor+and+signal+transduction+research&rft.atitle=Expression+and+function+of+EGF-related+peptides+and+their+receptors+in+gynecological+cancer--from+basic+science+to+therapy.&rft.au=Ebert%2C+A+D%3BWechselberger%2C+C%3BMartinez-Lacaci%2C+I%3BBianco%2C+C%3BWeitzel%2C+H+K%3BSalomon%2C+D+S&rft.aulast=Ebert&rft.aufirst=A&rft.date=2000-01-01&rft.volume=20&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+receptor+and+signal+transduction+research&rft.issn=10799893&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-23 N1 - Date created - 2000-03-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Proadrenomedullin NH(2)-terminal 20 peptide (PAMP) and adrenomedullin bind to teratocarcinoma cells. AN - 70954317; 10704725 AB - Proadrenomedullin NH(2-)terminal 20 peptide (PAMP) and adrenomedullin (ADM) bind to teratocarcinoma cells. The effects of PAMP and ADM on teratocarcinoma cells were investigated. (125)I-PAMP bound to PA1 cells with moderate affinity (K(d) = 110 nM) to a single class of sites (B(max) = 110 000/cell). Specific (125)I-PAMP binding was inhibited by PAMP (IC(50) of 100 nM) but not ADM, calcitonin gene-related peptide (CGRP), or amylin. Specific (125)I-ADM binding was inhibited with high affinity by ADM, CGRP, and CGRP(8-37) (IC(50) values of 10, 10, and 15 nM respectively) but not PAMP or amylin. ADM elevated cAMP (ED(50) value of 100 nM), whereas PAMP had no effect on basal cAMP but inhibited the increase in cAMP caused by 10 nM ADM. Also, the increase in cAMP caused by ADM was inhibited CGRP(8-37), suggesting that ADM is binding to CGRP receptors. ADM (100 nM) stimulated transiently c-fos mRNA, whereas PAMP (1000 nM) had little effect; however, PAMP inhibited the increase in c-fos mRNA caused by ADM. ADM stimulated [(3)H]thymidine uptake into PA1 cells, whereas PAMP inhibited the increase in thymidine uptake caused by ADM. These results indicate that ADM and PAMP are both biologically active in teratocarcinoma cells. JF - Peptides AU - Moody, T W AU - Coy, D AU - Cuttitta, F AU - Montuenga, L M AD - Department of Cell and Cancer Biology, Medicine Branch, National Cancer Institute, Rockville, MD 20850, USA. moodyt@bprb.nci.nih.gov Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 101 EP - 107 VL - 21 IS - 1 SN - 0196-9781, 0196-9781 KW - Peptide Fragments KW - 0 KW - Peptides KW - Proteins KW - RNA, Messenger KW - RNA, Neoplasm KW - calcitonin gene-related peptide (8-37) KW - 119911-68-1 KW - Adrenomedullin KW - 148498-78-6 KW - Calcitonin Gene-Related Peptide KW - 83652-28-2 KW - Cyclic AMP KW - E0399OZS9N KW - Index Medicus KW - Humans KW - Cell Division -- drug effects KW - RNA, Neoplasm -- genetics KW - RNA, Messenger -- genetics KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Kinetics KW - Binding, Competitive KW - Cyclic AMP -- metabolism KW - Calcitonin Gene-Related Peptide -- pharmacology KW - Genes, fos KW - RNA, Neoplasm -- metabolism KW - Proteins -- pharmacology KW - Peptide Fragments -- metabolism KW - Peptide Fragments -- pharmacology KW - Peptides -- metabolism KW - Teratocarcinoma -- metabolism KW - Peptides -- pharmacology KW - Proteins -- metabolism KW - Teratocarcinoma -- pathology KW - Teratocarcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70954317?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Proadrenomedullin+NH%282%29-terminal+20+peptide+%28PAMP%29+and+adrenomedullin+bind+to+teratocarcinoma+cells.&rft.au=Moody%2C+T+W%3BCoy%2C+D%3BCuttitta%2C+F%3BMontuenga%2C+L+M&rft.aulast=Moody&rft.aufirst=T&rft.date=2000-01-01&rft.volume=21&rft.issue=1&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Peptides&rft.issn=01969781&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-24 N1 - Date created - 2000-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficacy of homeopathic treatment of skin reactions during radiotherapy for breast cancer: a randomised, double-blind clinical trial. AN - 70942044; 10703904 AB - The aim of this study was to assess the effects of Belladonna 7cH and X-ray 15cH associated in the treatment of acute radiodermatitis. A randomized double-blind placebo-controlled clinical trial involving 66 patients who had been operated on for breast cancer and were undergoing radiotherapy was conducted. The following parameters were assessed over ten weeks: breast skin colour, warmth, swelling and pigmentation. The efficacy of the treatment was assessed by the comparison of these parameters taken individually and by calculating an Index of Total Severity (sum of the scores of the four parameters) during radiotherapy, and during recovery, 15 and 30 d after the end of the radiotherapy. The differences of the scores of the Index of Total Severity during Radiotherapy were not statistically significant, but showed a trend towards a better activity of the homoeopathic medicine compared to placebo. Analysis of the data on Total Severity during recovery, showed a statistically significant benefit of the active medicines over placebo. The homeopathic medicines had particular effectiveness on the heat of the skin. The limited number of patients observed and the posology employed could have interfered with the significance of the results. Chemotherapy and hormonotherapy do not seem to affect the results. JF - The British homoeopathic journal AU - Balzarini, A AU - Felisi, E AU - Martini, A AU - De Conno, F AD - Rehabilitation and Palliative Care Department, National Cancer Institute, Milan, Italy. Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 8 EP - 12 VL - 89 IS - 1 SN - 0007-0785, 0007-0785 KW - Index Medicus KW - Phytotherapy KW - Double-Blind Method KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Female KW - Plants, Toxic KW - Homeopathy KW - Plants, Medicinal KW - Atropa belladonna KW - Radiodermatitis -- therapy KW - Breast Neoplasms -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70942044?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+British+homoeopathic+journal&rft.atitle=Efficacy+of+homeopathic+treatment+of+skin+reactions+during+radiotherapy+for+breast+cancer%3A+a+randomised%2C+double-blind+clinical+trial.&rft.au=Balzarini%2C+A%3BFelisi%2C+E%3BMartini%2C+A%3BDe+Conno%2C+F&rft.aulast=Balzarini&rft.aufirst=A&rft.date=2000-01-01&rft.volume=89&rft.issue=1&rft.spage=8&rft.isbn=&rft.btitle=&rft.title=The+British+homoeopathic+journal&rft.issn=00070785&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-16 N1 - Date created - 2000-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High exposure to neuroleptics in bipolar patients: a retrospective review. AN - 70933218; 10695653 AB - Acute and long-term use of neuroleptics to treat bipolar disorder remains prevalent despite safety concerns. Neuroleptic-treated patients with bipolar disorder have been reported to have rates of tardive dyskinesia, akathisia, and acute dystonia as high as or higher than patients with schizophrenia. Moreover, the pattern of repeated, intermittent use of neuroleptics in bipolar disorder may increase rather than decrease the risk of tardive dyskinesia. Retrospective life charts of 133 treatment-refractory patients with bipolar disorder (diagnosed according to Research Diagnostic Criteria or a clinical interview with the Schedule for Affective Disorders and Schizophrenia-Lifetime Version or the Structured Clinical Interview for DSM-IV Axis I Disorders) admitted to the National Institute of Mental Health (NIMH) were reviewed for prior neuroleptic use, medication exposure, and course of illness variables. Patients' medication response and degree of improvement while at NIMH were also assessed. A total of 72.2% (N = 96) of the bipolar patients examined had exposure to neuroleptics prior to referral to NIMH. Neuroleptic-treated patients had a mean of 5.6 neuroleptic trials with a mean duration of 166.4 days for each trial and a dose range of 25 to 960 mg in chlorpromazine equivalents. Life chart data showed that the neuroleptic-exposed and nonexposed bipolar patients were distinguished by 1 course-of-illness variable: increased suicidality in the neuroleptic-treated group. Patients with and without prior neuroleptic exposure experienced the same high degree of improvement at discharge from NIMH. Only 12.5% (N = 12) of the group previously treated with typical neuroleptics (N = 96) required neuroleptics at discharge. Our data suggest that the majority of even treatment-refractory bipolar patients can be stabilized without neuroleptics. Given the high risk of tardive dyskinesia and the availability of other novel agents, the routine intermittent use of typical neuroleptics to treat patients with bipolar disorder should be minimized. JF - The Journal of clinical psychiatry AU - Brotman, M A AU - Fergus, E L AU - Post, R M AU - Leverich, G S AD - Biological Psychiatry Branch, National Institute of Mental Health, and the National Institutes of Health, Bethesda, MD 20892-1272, USA. Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 68 EP - 72; quiz 73 VL - 61 IS - 1 SN - 0160-6689, 0160-6689 KW - Antipsychotic Agents KW - 0 KW - Index Medicus KW - United States KW - Drug Administration Schedule KW - Humans KW - National Institute of Mental Health (U.S.) KW - Retrospective Studies KW - Hospitalization KW - Suicide, Attempted -- statistics & numerical data KW - Risk Factors KW - Adult KW - Treatment Outcome KW - Psychiatric Status Rating Scales -- statistics & numerical data KW - Female KW - Male KW - Survival Analysis KW - Antipsychotic Agents -- administration & dosage KW - Movement Disorders -- epidemiology KW - Antipsychotic Agents -- therapeutic use KW - Bipolar Disorder -- drug therapy KW - Movement Disorders -- etiology KW - Bipolar Disorder -- psychology KW - Antipsychotic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70933218?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+psychiatry&rft.atitle=High+exposure+to+neuroleptics+in+bipolar+patients%3A+a+retrospective+review.&rft.au=Brotman%2C+M+A%3BFergus%2C+E+L%3BPost%2C+R+M%3BLeverich%2C+G+S&rft.aulast=Brotman&rft.aufirst=M&rft.date=2000-01-01&rft.volume=61&rft.issue=1&rft.spage=68&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+psychiatry&rft.issn=01606689&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-07 N1 - Date created - 2000-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Caffeic acid phenethyl ester induces leukocyte apoptosis, modulates nuclear factor-kappa B and suppresses acute inflammation. AN - 70922206; 10686520 AB - Nuclear factor kappa-B (NF-kappaB) is a heterodimeric transcription factor with a pivotal role in orchestrating immune and inflammatory processes. Inflammatory cytokines and prostanoids activate NF-kappaB, which, in turn, stimulates expression of cytokines, proteases, adhesion molecules and other inflammatory mediators. Caffeic acid phenethyl ester (CAPE) is a compound that modulates nuclear binding of the NF-kappaB p65 subunit (RelA). To determine whether CAPE decreases the viability of cells participating in host defense, we first tested its in vitro effect on a glucocorticoid-sensitive and -resistant cell line of lymphoid origin. CAPE induced apoptotic cell death in a dose-dependent fashion and to a similar extent in both cell lines. Furthermore, a low concentration of CAPE decreased the LD(50) of dexamethasone by 3- to 5-fold. Since therapeutic induction of apoptosis of activated inflammatory cells holds the attraction of destroying effector cells safely without secondary tissue damage, we examined the effects of CAPE in a rat model of carrageenin-induced subcutaneous inflammation. Local administration of CAPE resulted in increased leukocyte apoptosis and marked reduction in exudate leukocyte, neutrophil and monocyte concentrations at the inflammatory site. CAPE decreased expression of cytosolic IkappaBalpha and increased nuclear translocation of p65. These findings may suggest that novel anti-inflammatory therapies can be based upon activation of NF-kappaB-mediated transcription of genes curbing the inflammatory response and that CAPE or its analogs hold therapeutic promise. Copyright 2000 S. Karger AG, Basel. JF - Neuroimmunomodulation AU - Orban, Z AU - Mitsiades, N AU - Burke, T R AU - Tsokos, M AU - Chrousos, G P AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Md., USA. orbanz@mail.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 99 EP - 105 VL - 7 IS - 2 SN - 1021-7401, 1021-7401 KW - Caffeic Acids KW - 0 KW - DNA-Binding Proteins KW - I-kappa B Proteins KW - NF-kappa B KW - NFKBIA protein, human KW - Nfkbia protein, rat KW - Transcription Factor RelA KW - NF-KappaB Inhibitor alpha KW - 139874-52-5 KW - Dexamethasone KW - 7S5I7G3JQL KW - Carrageenan KW - 9000-07-1 KW - caffeic acid phenethyl ester KW - G960R9S5SK KW - Phenylethyl Alcohol KW - ML9LGA7468 KW - Index Medicus KW - Acute Disease KW - Animals KW - Neutrophils -- pathology KW - Neutrophils -- immunology KW - Dose-Response Relationship, Drug KW - Dexamethasone -- pharmacology KW - Humans KW - Rats KW - Neutrophils -- metabolism KW - Neutrophils -- drug effects KW - Carrageenan -- pharmacology KW - Leukocyte Count -- drug effects KW - Rats, Sprague-Dawley KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Monocytes -- immunology KW - Monocytes -- metabolism KW - Monocytes -- pathology KW - Lethal Dose 50 KW - Monocytes -- drug effects KW - DNA-Binding Proteins -- metabolism KW - Leukocytes -- metabolism KW - Phenylethyl Alcohol -- administration & dosage KW - Caffeic Acids -- chemistry KW - Leukocytes -- immunology KW - Phenylethyl Alcohol -- analogs & derivatives KW - Inflammation -- chemically induced KW - Phenylethyl Alcohol -- chemistry KW - Inflammation -- drug therapy KW - Leukocytes -- drug effects KW - Phenylethyl Alcohol -- therapeutic use KW - Phenylethyl Alcohol -- pharmacology KW - Leukocytes -- pathology KW - Caffeic Acids -- pharmacology KW - Apoptosis -- drug effects KW - Caffeic Acids -- administration & dosage KW - Inflammation -- immunology KW - Caffeic Acids -- therapeutic use KW - NF-kappa B -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70922206?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroimmunomodulation&rft.atitle=Caffeic+acid+phenethyl+ester+induces+leukocyte+apoptosis%2C+modulates+nuclear+factor-kappa+B+and+suppresses+acute+inflammation.&rft.au=Orban%2C+Z%3BMitsiades%2C+N%3BBurke%2C+T+R%3BTsokos%2C+M%3BChrousos%2C+G+P&rft.aulast=Orban&rft.aufirst=Z&rft.date=2000-01-01&rft.volume=7&rft.issue=2&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Neuroimmunomodulation&rft.issn=10217401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-31 N1 - Date created - 2000-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cyclophosphamide and other new agents for the treatment of severe aplastic anemia. AN - 70914622; 10676915 AB - Severe aplastic anemia (SAA) has a poor prognosis in the absence of treatment. Current accepted therapeutic strategies include allogeneic stem-cell transplantation and immunosuppression, both resulting in long-term survival in the majority of patients. Although human leukocyte antigen (HLA)-matched sibling stem-cell transplantation is highly effective, the 25% probability of finding a suitable sibling donor within a family renders this approach available to only a minority of patients. Transplantation using HLA-matched, unrelated donors carries a high risk of treatment failure along with considerable toxicity. While combined immunosuppression with both antithymocyte globulin (ATG) and cyclosporine A (CSA) produces hematologic improvement in most patients, relapse is common. Late evolution of aplastic anemia to other serious hematologic disorders, including paroxysmal nocturnal hemoglobinuria (PNH), myelodysplasia, and acute leukemia, is also a significant problem following treatment with ATG/CSA. Recently, results of immunosuppression in SAA with another potent immunosuppressive agent, cyclophosphamide, were reported in a small number of patients. The overall response rate was similar to that seen with ATG/CSA, but relapse and late clonal disease were not observed during a long period of follow-up. A larger randomized trial comparing sustained hematologic response rates to either conventional immunosuppression with ATG/CSA or high-dose cyclophosphamide and CSA is now underway; secondary end points include response duration, event-free survival, and overall survival. Additionally, a number of protocols designed to test the efficacy of alternative immunosuppressive or immunomodulatory agents are being developed. JF - Seminars in hematology AU - Tisdale, J F AU - Dunn, D E AU - Maciejewski, J AD - Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 102 EP - 109 VL - 37 IS - 1 SN - 0037-1963, 0037-1963 KW - Antibodies, Monoclonal KW - 0 KW - Immunosuppressive Agents KW - Receptors, Interleukin-2 KW - Cyclophosphamide KW - 8N3DW7272P KW - Mycophenolic Acid KW - HU9DX48N0T KW - Sirolimus KW - W36ZG6FT64 KW - Tacrolimus KW - WM0HAQ4WNM KW - Index Medicus KW - Tacrolimus -- therapeutic use KW - Mycophenolic Acid -- analogs & derivatives KW - Mycophenolic Acid -- therapeutic use KW - Humans KW - Receptors, Interleukin-2 -- antagonists & inhibitors KW - Sirolimus -- therapeutic use KW - Receptors, Interleukin-2 -- immunology KW - Antibodies, Monoclonal -- therapeutic use KW - Cyclophosphamide -- therapeutic use KW - Anemia, Aplastic -- drug therapy KW - Immunosuppressive Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70914622?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+hematology&rft.atitle=Cyclophosphamide+and+other+new+agents+for+the+treatment+of+severe+aplastic+anemia.&rft.au=Tisdale%2C+J+F%3BDunn%2C+D+E%3BMaciejewski%2C+J&rft.aulast=Tisdale&rft.aufirst=J&rft.date=2000-01-01&rft.volume=37&rft.issue=1&rft.spage=102&rft.isbn=&rft.btitle=&rft.title=Seminars+in+hematology&rft.issn=00371963&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-25 N1 - Date created - 2000-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tobacco control research in managed care: opportunities at the National Cancer Institute. AN - 70911813; 10688952 JF - Tobacco control AU - Morgan, G D AD - Tobacco Control Research Branch, Behavioral Research Program, National Cancer Institute, Executive Plaza North, Room 241, 6130 Executive Blvd, MSC 7337, Bethesda, MD 20892-7337, USA. gmorgan@nih. gov Y1 - 2000 PY - 2000 DA - 2000 SP - 1 VL - 9 Suppl 1 SN - 0964-4563, 0964-4563 KW - Index Medicus KW - Neoplasms KW - Humans KW - Health Promotion KW - Managed Care Programs KW - Smoking Cessation KW - Research -- economics KW - Tobacco Use Disorder -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70911813?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tobacco+control&rft.atitle=Tobacco+control+research+in+managed+care%3A+opportunities+at+the+National+Cancer+Institute.&rft.au=Morgan%2C+G+D&rft.aulast=Morgan&rft.aufirst=G&rft.date=2000-01-01&rft.volume=9+Suppl+1&rft.issue=&rft.spage=I75&rft.isbn=&rft.btitle=&rft.title=Tobacco+control&rft.issn=09644563&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-19 N1 - Date created - 2000-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of carbon disulfide neurotoxicity in C57BL6 mice: behavioral, morphologic, and molecular effects. AN - 70910381; 10669001 AB - Female C57BL6 mice were exposed to 0 or 800 ppm carbon disulfide (CS2), 6 h/d, 5 d/wk for 20 weeks. The neurologic function of all mice was assessed once at the end of exposures using a functional observational battery. General health effects included a decrease in body weight gain, piloerection, hunched body posture, and ptosis. Treatment-related effects included altered gait (uncoordinated placement of hind limbs and ataxia) and impaired function on an inverted screen test. In addition, rearing and locomotor movement were decreased in treated mice. Focal to multifocal axonal swelling was seen predominantly in the muscular branch of the posterior tibial nerve, and occasionally giant axonal swelling was detected in the lumbar segment of the spinal cord. Electron microscopic examination revealed swollen axons with massive accumulation of neurofilament proteins within the axoplasm. Covalent cross-linking of erythrocyte spectrin (surrogate protein to neurofilament protein) was demonstrated in mice exposed to CS2 but not in mice receiving filtered air. These data provide supportive evidence that covalent cross-linking of neurofilament proteins is a significant feature of the axonal swellings in mice produced by inhalation exposure to CS2. JF - Toxicologic pathology AU - Sills, R C AU - Valentine, W M AU - Moser, V AU - Graham, D G AU - Morgan, D L AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. sills@niehs.nih.gov PY - 2000 SP - 142 EP - 148 VL - 28 IS - 1 SN - 0192-6233, 0192-6233 KW - Cross-Linking Reagents KW - 0 KW - Spectrin KW - 12634-43-4 KW - Carbon Disulfide KW - S54S8B99E8 KW - Index Medicus KW - Animals KW - Peripheral Nervous System -- pathology KW - Spectrin -- drug effects KW - Cross-Linking Reagents -- toxicity KW - Peripheral Nervous System -- drug effects KW - Mice KW - Peripheral Nervous System -- ultrastructure KW - Spectrin -- chemistry KW - Behavior, Animal -- drug effects KW - Psychomotor Performance -- drug effects KW - Central Nervous System -- drug effects KW - Mice, Inbred C57BL KW - Central Nervous System -- pathology KW - Motor Activity -- drug effects KW - Microscopy, Electron KW - Administration, Inhalation KW - Gait -- drug effects KW - Central Nervous System -- ultrastructure KW - Female KW - Carbon Disulfide -- toxicity KW - Nervous System Diseases -- psychology KW - Nervous System Diseases -- chemically induced KW - Nervous System Diseases -- pathology KW - Carbon Disulfide -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70910381?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Characterization+of+carbon+disulfide+neurotoxicity+in+C57BL6+mice%3A+behavioral%2C+morphologic%2C+and+molecular+effects.&rft.au=Sills%2C+R+C%3BValentine%2C+W+M%3BMoser%2C+V%3BGraham%2C+D+G%3BMorgan%2C+D+L&rft.aulast=Sills&rft.aufirst=R&rft.date=2000-01-01&rft.volume=28&rft.issue=1&rft.spage=142&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-06 N1 - Date created - 2000-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective loss of the transforming growth factor-beta apoptotic signaling pathway in mutant NRP-154 rat prostatic epithelial cells. AN - 70906211; 10672898 AB - Retroviral insertional mutagenesis was used to select mutant NRP-154 rat prostate carcinoma cells resistant to transforming growth factor (TGF)-beta-induced cell death. Similar to the parental cells, a mutant clone, M-NRP1, expressed TGF-beta receptors and was still responsive to induction both of direct target genes by TGF-beta and of apoptosis by staurosporine or okadaic acid. In contrast, indicators of cell growth, strongly suppressed by TGF-beta in the parental cells, were unaffected in M-NRP1 cells. M-NRP1 cells overexpress the antiapoptotic protein, Bcl-xL, and show dysregulated expression and localization of a protein related to a novel human septin, ARTS (designation of apoptotic response to TGF-beta signals), cloned by homology to an exonic sequence flanked by the viral long terminal repeats in M-NRP1 cells and shown to make cells competent to undergo apoptosis in response to TGF-beta. We propose that ARTS might operate within the same apoptotic pathway as Bcl-xL and that M-NRP1 cells could serve as a useful model for characterization of this pathway. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Larisch-Bloch, S AU - Danielpour, D AU - Roche, N S AU - Lotan, R AU - Hsing, A Y AU - Kerner, H AU - Hajouj, T AU - Lechleider, R J AU - Roberts, A B AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-5055, USA. Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 1 EP - 10 VL - 11 IS - 1 SN - 1044-9523, 1044-9523 KW - Bcl2l1 protein, rat KW - 0 KW - Proto-Oncogene Proteins c-bcl-2 KW - RNA, Messenger KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor beta KW - bcl-X Protein KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Staurosporine KW - H88EPA0A3N KW - Index Medicus KW - Animals KW - Cell Division -- drug effects KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Rats KW - In Situ Nick-End Labeling KW - Staurosporine -- pharmacology KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Transfection KW - Okadaic Acid -- pharmacology KW - Proto-Oncogene Proteins c-bcl-2 -- genetics KW - Retroviridae -- genetics KW - Prostate KW - Male KW - Mutagenesis, Insertional KW - Transforming Growth Factor beta -- pharmacology KW - Apoptosis -- genetics KW - Apoptosis -- drug effects KW - Signal Transduction -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70906211?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Selective+loss+of+the+transforming+growth+factor-beta+apoptotic+signaling+pathway+in+mutant+NRP-154+rat+prostatic+epithelial+cells.&rft.au=Larisch-Bloch%2C+S%3BDanielpour%2C+D%3BRoche%2C+N+S%3BLotan%2C+R%3BHsing%2C+A+Y%3BKerner%2C+H%3BHajouj%2C+T%3BLechleider%2C+R+J%3BRoberts%2C+A+B&rft.aulast=Larisch-Bloch&rft.aufirst=S&rft.date=2000-01-01&rft.volume=11&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-14 N1 - Date created - 2000-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - (N-stearyl, norleucine17) VIP hybrid inhibits the growth of pancreatic cancer cell lines. AN - 70901097; 10670826 AB - The effects vasoactive intestinal peptide (VIP) antagonists were investigated on pancreatic cancer cell lines. (N-Stearyl, Norleucine17) VIP hybrid ((SN)VIPhyb) inhibited 125I-VIP binding to human Capan-2 cells with an IC50 value of 0.01 microM whereas VIP hybrid had an IC50 value of 0.2 microM. By RT-PCR and Northern blot, VPAC1 receptor mRNA was detected in CAPAN-2 cells. One microM (SN)VIPhyb and 10 microM VIPhyb inhibited the ability of 30 nM VIP to elevate cyclic AMP and increase c-fos mRNA. (SN)VIPhyb, 1 microM inhibited the clonal growth of CAPAN-2 cells in vitro. In vivo, (SN)VIPhyb (10 microg/day s.c.) inhibited CAPAN-2 xenograft growth in nude mice. These results indicate that (SN)VIPhyb is a pancreatic cancer VPAC receptor antagonist. JF - Life sciences AU - Zia, H AU - Leyton, J AU - Casibang, M AU - Hau, V AU - Brenneman, D AU - Fridkin, M AU - Gozes, I AU - Moody, T W AD - Cell and Cancer Biology Dept., Medicine Branch, National Cancer Institute, Rockville, MD 20850, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 379 EP - 387 VL - 66 IS - 5 SN - 0024-3205, 0024-3205 KW - RNA, Messenger KW - 0 KW - Receptors, Vasoactive Intestinal Peptide KW - Receptors, Vasoactive Intestinal Polypeptide, Type I KW - stearyl-norleucine(17)-vasoactive intestinal peptide KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - Cyclic AMP KW - E0399OZS9N KW - Index Medicus KW - Animals KW - Humans KW - Cell Division -- drug effects KW - Amino Acid Sequence KW - Genes, fos -- genetics KW - Mice KW - Mice, Nude KW - RNA, Messenger -- genetics KW - Protein Binding KW - Neoplasm Transplantation KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Binding, Competitive KW - Cyclic AMP -- metabolism KW - Molecular Sequence Data KW - Transplantation, Heterologous KW - Inhibitory Concentration 50 KW - Vasoactive Intestinal Peptide -- pharmacology KW - Vasoactive Intestinal Peptide -- antagonists & inhibitors KW - Pancreatic Neoplasms -- pathology KW - Pancreatic Neoplasms -- metabolism KW - Vasoactive Intestinal Peptide -- metabolism KW - Receptors, Vasoactive Intestinal Peptide -- metabolism KW - Receptors, Vasoactive Intestinal Peptide -- genetics KW - Vasoactive Intestinal Peptide -- therapeutic use KW - Receptors, Vasoactive Intestinal Peptide -- antagonists & inhibitors KW - Pancreatic Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70901097?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=%28N-stearyl%2C+norleucine17%29+VIP+hybrid+inhibits+the+growth+of+pancreatic+cancer+cell+lines.&rft.au=Zia%2C+H%3BLeyton%2C+J%3BCasibang%2C+M%3BHau%2C+V%3BBrenneman%2C+D%3BFridkin%2C+M%3BGozes%2C+I%3BMoody%2C+T+W&rft.aulast=Zia&rft.aufirst=H&rft.date=2000-01-01&rft.volume=66&rft.issue=5&rft.spage=379&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 - 2000-02-17 N1 - Date created - 2000-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carbachol-stimulated chloride secretion in mouse colon: evidence of a role for autocrine prostaglandin E2 release. AN - 70891568; 10662895 AB - We used the short-circuit current technique to investigate the possible facilitatory role of epithelium-derived prostaglandin E2 (PGE2) release on Cl- secretion in the mouse colon. Carbachol- (CCh)-stimulated Cl- secretion was reduced by pretreatment with either indomethacin (10 microM), or TTX (1 microM), and when added together, these inhibitors revealed net CCh-stimulated K+ secretion. CCh-stimulated Cl- secretion was partially restored to TTX/indomethacin-treated colons by addition of a subsecretory concentration of PGE2 (1 nM). In acutely isolated, unstimulated crypt cells, we measured PGE2 release at a similar level. We conclude that autocrine release of PGs from epithelial cells is sufficient to support the CCh-induced Cl- secretory response and is a likely co-factor in this response. JF - Experimental physiology AU - Carew, M A AU - Thorn, P AD - Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QJ, UK. carew@niehs.nih.gov Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 67 EP - 72 VL - 85 IS - 1 SN - 0958-0670, 0958-0670 KW - Chlorides KW - 0 KW - Muscarinic Agonists KW - Tetrodotoxin KW - 4368-28-9 KW - Carbachol KW - 8Y164V895Y KW - Prostaglandin-Endoperoxide Synthases KW - EC 1.14.99.1 KW - Dinoprostone KW - K7Q1JQR04M KW - Indomethacin KW - XXE1CET956 KW - Index Medicus KW - Epithelial Cells -- metabolism KW - Animals KW - Epithelial Cells -- drug effects KW - Prostaglandin-Endoperoxide Synthases -- pharmacology KW - Mice KW - Epithelium -- metabolism KW - Electrophysiology KW - Tetrodotoxin -- pharmacology KW - Male KW - Epithelium -- drug effects KW - Indomethacin -- pharmacology KW - Muscarinic Agonists -- pharmacology KW - Dinoprostone -- metabolism KW - Colon -- metabolism KW - Colon -- drug effects KW - Autocrine Communication -- drug effects KW - Chlorides -- metabolism KW - Carbachol -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70891568?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+physiology&rft.atitle=Carbachol-stimulated+chloride+secretion+in+mouse+colon%3A+evidence+of+a+role+for+autocrine+prostaglandin+E2+release.&rft.au=Carew%2C+M+A%3BThorn%2C+P&rft.aulast=Carew&rft.aufirst=M&rft.date=2000-01-01&rft.volume=85&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Experimental+physiology&rft.issn=09580670&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-06 N1 - Date created - 2000-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New prospects for treatment of lupus nephritis. AN - 70888805; 10651216 AB - Systemic lupus erythematosus (SLE) is envisioned to arise from hyperactivate helper T-cells that cause polyclonal B-cell secretion of pathogenic autoantibodies and formation of immune complexes which deposit in sites such as the kidney. The most widely used immunosuppressive drugs, notably corticosteroids and cyclophosphamide, are often criticized as being nonspecific. In fact, these agents may be effective in SLE and lupus nephritis because broad, rather than highly selective, effects are required to control the aberrant immune system. Nonetheless, these agents are not uniformly effective and are associated with substantial toxicities. The lack of universal efficacy raises the specter that lupus is a heterogeneous disorder with different etiopathogenesis in different subsets of patients (as in lupus-prone mice). Therapeutic prospects for the upcoming millennium include new forms and combinations of chemotherapeutic agents (mycophenolate and adenosine analogues), attempts to achieve immunological reconstitution using near-ablative chemotherapy (with or without bone marrow or stem cell rescue), monoclonal antibodies, and other inhibitors of T-cell costimulatory pathways (e.g., anti-CD154 and/or CTLA4-Ig). The prospect for gene therapy has already been realized in some animal models of SLE. In human SLE, the feasibility of gene therapy will depend on further definition of lupus-promoting genes and availability of methods to establish stable expression of potentially corrective genes. JF - Seminars in nephrology AU - Balow, J E AU - Boumpas, D T AU - Austin, H A AD - National Institutes of Health, Bethesda, MD 20892-1818, USA. james_e_balow@nih.gov Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 32 EP - 39 VL - 20 IS - 1 SN - 0270-9295, 0270-9295 KW - Immunologic Factors KW - 0 KW - Immunosuppressive Agents KW - Oligonucleotides KW - abetimus KW - Index Medicus KW - Drug Therapy, Combination KW - Animals KW - Oligonucleotides -- therapeutic use KW - Risk Factors KW - Immunologic Factors -- therapeutic use KW - Humans KW - Disease Models, Animal KW - Mice KW - Genetic Therapy KW - Plasmapheresis KW - Immunosuppressive Agents -- therapeutic use KW - Bone Marrow Transplantation KW - Lupus Nephritis -- therapy KW - Lupus Nephritis -- etiology KW - Lupus Nephritis -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70888805?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nephrology&rft.atitle=New+prospects+for+treatment+of+lupus+nephritis.&rft.au=Balow%2C+J+E%3BBoumpas%2C+D+T%3BAustin%2C+H+A&rft.aulast=Balow&rft.aufirst=J&rft.date=2000-01-01&rft.volume=20&rft.issue=1&rft.spage=32&rft.isbn=&rft.btitle=&rft.title=Seminars+in+nephrology&rft.issn=02709295&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-02 N1 - Date created - 2000-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol consumption, alcohol dependence, and all-cause mortality. AN - 70886141; 10656196 AB - This study examined the effects of alcohol consumption and DSM-IV alcohol dependence on the risk of mortality. Data from the 1988 National Health Interview Survey Alcohol Supplement were matched to the National Death Index for the years 1988 to 1995 (baseline n = 37,682 U.S. adults age > or =25 linked to 3,586 deaths). All mortality analyses were based on proportional hazards models that adjusted for age, sex, race/ethnicity, marital status, education, income, labor force status, body mass index, smoking status, and poor health indicators at baseline. When dependence was not considered and all past-year abstainers were used as the reference group, both light and moderate drinkers exhibited a reduced risk of mortality, with hazards ratios of 0.76 (0.68-0.84) and 0.84 (0.74-0.96). Heavy drinkers had about the same risk of dying as did past-year abstainers, and very heavy drinkers had an increased risk that was not significant (OR = 1.17, CI = 0.93-1.47). When lifetime abstainers were used as the reference category, the protective effect of moderate drinking fell short of significance, and there were nearly significant increased risks among former drinkers and very heavy drinkers. When dependence was considered, light and moderate drinkers without dependence had a reduced mortality risk regardless of reference group, and there was no significant effect among heavy or very heavy drinkers without dependence. Among dependent drinkers, there was no protective effect of light or moderate drinking, and very heavy drinkers had a significantly increased risk (OR = 1.56 relative to past-year abstainers and 1.65 relative to lifetime abstainers). Because alcohol dependence nullifies the protective effect of light and moderate drinking, it is important to understand its role as an independent risk factor for mortality. Differences between dependent and nondependent drinkers who drank comparable amounts suggest that this risk may result from longer and heavier drinking histories before baseline, more severe health problems at baseline, more heavy episodic drinking, and, possibly, differences in beverage preference. JF - Alcoholism, clinical and experimental research AU - Dawson, D A AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse & Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-7003, USA. ddawson@willco.niaaa.nih.gov Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 72 EP - 81 VL - 24 IS - 1 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Humans KW - Longevity -- drug effects KW - Aged KW - Risk KW - Adult KW - Health Surveys KW - Follow-Up Studies KW - Middle Aged KW - United States -- epidemiology KW - Temperance -- statistics & numerical data KW - Female KW - Male KW - Proportional Hazards Models KW - Alcohol Drinking -- mortality KW - Alcoholism -- mortality KW - Cause of Death UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70886141?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Alcohol+consumption%2C+alcohol+dependence%2C+and+all-cause+mortality.&rft.au=Dawson%2C+D+A&rft.aulast=Dawson&rft.aufirst=D&rft.date=2000-01-01&rft.volume=24&rft.issue=1&rft.spage=72&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-29 N1 - Date created - 2000-02-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Alcohol Clin Exp Res 2000 Mar;24(3):395 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association of Helicobacter pylori infection with gastric cancer. AN - 70880565; 10658423 AB - Helicobacter pylori has generated public health interest since its identification in 1983. Past studies have suggested that the bacterium plays a role in the pathogenesis of gastric cancer. More recent studies support the conclusion that the association of H. pylori with gastric cancer is causal. The purpose of this article is to review the available evidence supporting the association of H. pylori with gastric cancer. We performed a critical review of the relevant literature published in the English language on H. pylori and gastric cancer using MEDLINE, Index Medicus for the years 1985 to 1997. The reference lists of selected articles also were reviewed to capture citations for further pertinent studies. H. pylori is thought to be the major cause of chronic atrophic gastritis. H. pylori gastritis is worldwide in distribution. H. pylori is now categorized by the International Agency for Cancer Research as a group 1 carcinogen, i.e., an agent that is carcinogenic to humans. Several reports from the United States have found the highest frequencies of gastric cancer in geographic areas and populations with the highest rates of acquisition of H. pylori infection. The high prevalence of H. pylori infection has been documented most notably in blacks and Hispanics, who also are at high risk for gastric cancer. New studies that focus on the epidemiology and pathology of H. pylori improve our understanding of its relationship with gastric cancer and advance the development of gastric cancer prevention and control strategies that are proposed. JF - Military medicine AU - Alexander, G A AU - Brawley, O W AD - National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7161, USA. Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 21 EP - 27 VL - 165 IS - 1 SN - 0026-4075, 0026-4075 KW - Index Medicus KW - United States KW - Gastritis, Atrophic -- microbiology KW - Hispanic Americans KW - Risk Factors KW - Humans KW - European Continental Ancestry Group KW - Adult KW - Chronic Disease KW - Child KW - African Continental Ancestry Group KW - Prevalence KW - Stomach Neoplasms -- microbiology KW - Helicobacter Infections -- diagnosis KW - Helicobacter pylori KW - Helicobacter Infections -- transmission KW - Helicobacter Infections -- complications KW - Stomach Neoplasms -- prevention & control KW - Helicobacter Infections -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70880565?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Military+medicine&rft.atitle=Association+of+Helicobacter+pylori+infection+with+gastric+cancer.&rft.au=Alexander%2C+G+A%3BBrawley%2C+O+W&rft.aulast=Alexander&rft.aufirst=G&rft.date=2000-01-01&rft.volume=165&rft.issue=1&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Military+medicine&rft.issn=00264075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-24 N1 - Date created - 2000-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular analysis of 5-azacytidine-induced variants in mammalian cells. AN - 70877288; 10640527 AB - 5-azacytidine induces 6-thioguanine resistance in AS52 cells. To characterize these resistant clones, we isolated 148 of them from 50 independently treated flasks. Less than nine (6%) of the 148 variants were spontaneous. PCR amplification of the DNA primers flanking the gpt gene produced no product in 15 clones (10%). Of the 133 remaining clones, 52 showed sequence alterations in the gpt structural gene. Of these 52, 34 (65%) were GC-->CG transversions. Only seven were located in CpG sequences. Thus, methyltransferase complexes are not major contributors to 5-azacytidine-induced point mutations in AS52 cells. The remaining 81 clones had no sequence alterations within the coding region of the gpt gene. Southern blot analysis of a sample of these variants (37/81) indicated that the 6-thioguanine-resistant phenotype was not due to local rearrangements or deletions (resolution 50 bp). Sequence analysis of the early promoter region of another sample of these variants (24/81) indicated that lesions in the promoter could not be responsible for the 6-thioguanine resistance observed. Thus, a majority of these variants were formed via a mechanism other than small genomic rearrangements, point mutations or deletions of the gpt structural gene or its promoter. Neither the mechanisms leading to these variants nor the biological and morphological consequences of these variants are known. JF - Mutagenesis AU - Kelecsényi, Z AU - Spencer, D L AU - Caspary, W J AD - Cancer Genetics Group, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 25 EP - 31 VL - 15 IS - 1 SN - 0267-8357, 0267-8357 KW - Mutagens KW - 0 KW - Tetrahydrofolate Dehydrogenase KW - EC 1.5.1.3 KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - Azacitidine KW - M801H13NRU KW - Index Medicus KW - Animals KW - Amino Acid Sequence KW - Sequence Analysis, DNA KW - Polymerase Chain Reaction KW - Base Sequence KW - Promoter Regions, Genetic KW - Blotting, Southern KW - CpG Islands KW - Molecular Sequence Data KW - Point Mutation KW - CHO Cells KW - Tetrahydrofolate Dehydrogenase -- genetics KW - Cricetinae KW - Hypoxanthine Phosphoribosyltransferase -- genetics KW - Azacitidine -- toxicity KW - Mutagens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70877288?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutagenesis&rft.atitle=Molecular+analysis+of+5-azacytidine-induced+variants+in+mammalian+cells.&rft.au=Kelecs%C3%A9nyi%2C+Z%3BSpencer%2C+D+L%3BCaspary%2C+W+J&rft.aulast=Kelecs%C3%A9nyi&rft.aufirst=Z&rft.date=2000-01-01&rft.volume=15&rft.issue=1&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=Mutagenesis&rft.issn=02678357&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-11 N1 - Date created - 2000-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A risk-benefit assessment of interleukin-2 as an adjunct to antiviral therapy in HIV infection. AN - 70873907; 10647974 AB - Immunomodulation has become a major focus of HIV research in an effort to augment, boost or restore the patient's damaged immune system. Recombinant interleukin-2 is currently being studied in phase II/III trials in HIV-infected patients. Several clinical studies have demonstrated that intermittent regimens are associated with marked rises in CD4+ cell counts without an increase in viral load. Most of these studies employ 5 consecutive days of interleukin-2 therapy by continuous intravenous infusion or subcutaneous injection, repeated every 8 weeks. An alternative strategy is the daily administration of low doses of interleukin-2, but clinical experience with this regimen is limited. Interleukin-2 administration can adversely affect virtually every organ system, requiring aggressive supportive care. A variety of administration strategies and interventions are being evaluated to minimise toxicity. Currently, no clinical end-point data are available for interleukin-2 in HIV-infected patients. Until phase III studies are completed, interleukin-2 can be used in the research setting as an immunomodulator and adjunct to antiretroviral therapy. Its potential to activate latently infected cells and promote HIV eradication from reservoir sites is also an important area for further study. If clinical benefit can be demonstrated, interleukin-2 could be useful as an adjunct to antiretroviral therapy if adverse effects can be minimised and therapy can be given infrequently on an outpatient basis. JF - Drug safety AU - Piscitelli, S C AU - Bhat, N AU - Pau, A AD - Clinical Center Pharmacy Department, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. spisc@nih.gov Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 19 EP - 31 VL - 22 IS - 1 SN - 0114-5916, 0114-5916 KW - Anti-HIV Agents KW - 0 KW - Interleukin-2 KW - Index Medicus KW - AIDS/HIV KW - Risk KW - Humans KW - CD4 Lymphocyte Count KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - HIV Infections -- virology KW - Anti-HIV Agents -- therapeutic use KW - Interleukin-2 -- therapeutic use KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70873907?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+safety&rft.atitle=A+risk-benefit+assessment+of+interleukin-2+as+an+adjunct+to+antiviral+therapy+in+HIV+infection.&rft.au=Piscitelli%2C+S+C%3BBhat%2C+N%3BPau%2C+A&rft.aulast=Piscitelli&rft.aufirst=S&rft.date=2000-01-01&rft.volume=22&rft.issue=1&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Drug+safety&rft.issn=01145916&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-07 N1 - Date created - 2000-02-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The use of case-parent triads to study joint effects of genotype and exposure. AN - 70873768; 10631155 AB - Most noninfectious disease is caused by low-penetrance alleles interacting with other genes and environmental factors. Consider the simple setting where a diallelic autosomal candidate gene and a binary exposure together affect disease susceptibility. Suppose that one has genotyped affected probands and their parents and has determined each proband's exposure status. One proposed method for assessment of etiologic interaction of genotype and exposure, an extension of the transmission/disequilibrium test, tests for differences in transmission of the variant allele from heterozygous parents to exposed versus unexposed probands. We show that this test is not generally valid. An alternative approach compares the conditional genotype distribution of unexposed cases, given parental genotypes, versus that of exposed cases. This approach provides maximum-likelihood estimators for genetic relative-risk parameters and genotype-exposure-interaction parameters, as well as a likelihood-ratio test (LRT) of the no-interaction null hypothesis. We show how to apply this approach, using log-linear models. When a genotype-exposure association arises solely through incomplete mixing of subpopulations that differ in both exposure prevalence and allele frequency, the LRT remains valid. The LRT becomes invalid, however, if offspring genotypes do not follow Mendelian proportions in each parental mating type-for example, because of genotypic differences in survival-or if a genotype-exposure association reflects an influence of genotype on propensity for exposure-for example, through behavioral mechanisms. Because the needed assumptions likely hold in many situations, the likelihood-based approach should be broadly applicable for diseases in which probands commonly have living parents. JF - American journal of human genetics AU - Umbach, D M AU - Weinberg, C R AD - Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709-2233, USA. umbach@niehs.nih.gov Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 251 EP - 261 VL - 66 IS - 1 SN - 0002-9297, 0002-9297 KW - Index Medicus KW - Genotype KW - Risk Factors KW - Models, Genetic KW - Humans KW - Disease Susceptibility -- etiology KW - Genetic Predisposition to Disease KW - Environmental Exposure -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70873768?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+human+genetics&rft.atitle=The+use+of+case-parent+triads+to+study+joint+effects+of+genotype+and+exposure.&rft.au=Umbach%2C+D+M%3BWeinberg%2C+C+R&rft.aulast=Umbach&rft.aufirst=D&rft.date=2000-01-01&rft.volume=66&rft.issue=1&rft.spage=251&rft.isbn=&rft.btitle=&rft.title=American+journal+of+human+genetics&rft.issn=00029297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-09 N1 - Date created - 2000-03-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Reprod Immunol. 1998 Nov;40(2):147-57 [9881742] Am J Epidemiol. 1998 Nov 1;148(9):893-901 [9801020] Genet Epidemiol. 1999;16(3):250-60 [10096688] Genet Epidemiol. 1999;16(3):261-73 [10096689] Am J Epidemiol. 1999 Apr 15;149(8):693-705 [10206618] Am J Hum Genet. 1999 Jul;65(1):229-35 [10364536] Alcohol Clin Exp Res. 1991 Feb;15(1):141-4 [2024727] Biometrics. 1991 Mar;47(1):53-61 [2049513] Am J Hum Genet. 1993 Mar;52(3):506-16 [8447318] Am J Hum Genet. 1993 Nov;53(5):1114-26 [8213835] Am J Hum Genet. 1994 Aug;55(2):414-5 [8080552] Am J Epidemiol. 1996 Aug 1;144(3):207-13 [8686689] Genet Epidemiol. 1995;12(6):607-12 [8787981] Am J Epidemiol. 1996 Oct 1;144(7):696-703 [8823066] Am J Hum Genet. 1996 Nov;59(5):983-9 [8900224] Alcohol Clin Exp Res. 1997 Oct;21(7):1272-7 [9347089] Epidemiol Rev. 1997;19(1):44-51 [9360901] Am J Med Genet. 1997 Dec 19;73(3):337-44 [9415696] Am J Hum Genet. 1998 Apr;62(4):969-78 [9529360] Alcohol Clin Exp Res. 1998 Aug;22(5):1048-52 [9726271] Am J Hum Genet. 1999 Apr;64(4):1186-93 [10090904] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clonidine blocks stress-induced reinstatement of heroin seeking in rats: an effect independent of locus coeruleus noradrenergic neurons. AN - 70873491; 10651884 AB - Using a reinstatement procedure, it has been shown that intermittent footshock stress reliably reinstates extinguished drug-taking behaviour in rats. Here we studied the role of noradrenaline (NE), one of the main brain neurotransmitters involved in responses to stress, in reinstatement of heroin seeking. We first determined the effect of clonidine, an alpha-2 adrenergic receptor agonist that decreases NE cell firing and release, on stress-induced reinstatement of heroin seeking. Rats were trained to self-administer heroin (0.1 mg/kg per infusion, IV, three 3-h sessions per day) for 9-10 days. Extinction sessions were given for up to 11 days during which saline was substituted for the drug. Tests for reinstatement were then conducted after exposure to intermittent footshock (5, 15 and 30 min, 0.5 mA). During testing, clonidine was injected systemically (10-40 microgram/kg, i.p.) or directly into the lateral or fourth ventricles (1-3 microram). Clonidine (1-2 microgram per site) or its charged analogue, 2-[2, 6-diethylphenylamino]-2-imidazole (ST-91, 0.5-1 microgram per site), was also injected bilaterally into the locus coeruleus (LC), the main noradrenergic cell group in the brain. Clonidine blocked stress-induced reinstatement of drug seeking when injected systemically or into the cerebral ventricles. In contrast, neither clonidine nor ST-91 consistently altered stress-induced reinstatement when injected into the locus coeruleus. We therefore studied the effect of lesions of the lateral tegmental NE neurons on stress-induced reinstatement. 6-Hydroxydopamine (6-OHDA) lesions performed after training for heroin self-administration had no effect on extinction of heroin-taking behaviour, but significantly attenuated reinstatement induced by intermittent footshock. These data suggest that: (i) clonidine prevents stress-induced relapse to heroin seeking by its action on neurons other than those of the locus coeruleus; and (ii) activation of the lateral tegmental NE neurons contributes to stress-induced reinstatement of heroin seeking. JF - The European journal of neuroscience AU - Shaham, Y AU - Highfield, D AU - Delfs, J AU - Leung, S AU - Stewart, J AD - Behavioural Neuroscience Branch, IRP/NIDA/NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Yshaham@intra.nida.nih.gov Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 292 EP - 302 VL - 12 IS - 1 SN - 0953-816X, 0953-816X KW - Parasympathomimetics KW - 0 KW - ST 91 KW - 4751-48-8 KW - Heroin KW - 70D95007SX KW - Oxidopamine KW - 8HW4YBZ748 KW - Clonidine KW - MN3L5RMN02 KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Rats KW - Animals KW - Extinction, Psychological KW - Self Administration KW - Rats, Long-Evans KW - Parasympathomimetics -- pharmacology KW - Medial Forebrain Bundle -- physiology KW - Electroshock KW - Parasympathomimetics -- administration & dosage KW - Male KW - Injections, Intraventricular KW - Cerebral Ventricles -- physiopathology KW - Clonidine -- administration & dosage KW - Clonidine -- analogs & derivatives KW - Stress, Psychological -- physiopathology KW - Neurons -- drug effects KW - Heroin Dependence -- physiopathology KW - Cerebral Ventricles -- drug effects KW - Norepinephrine -- physiology KW - Locus Coeruleus -- drug effects KW - Cerebral Ventricles -- physiology KW - Neurons -- physiology KW - Heroin Dependence -- prevention & control KW - Clonidine -- pharmacology KW - Locus Coeruleus -- physiopathology KW - Heroin Dependence -- psychology KW - Locus Coeruleus -- physiology KW - Heroin -- administration & dosage KW - Stress, Psychological -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70873491?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+European+journal+of+neuroscience&rft.atitle=Clonidine+blocks+stress-induced+reinstatement+of+heroin+seeking+in+rats%3A+an+effect+independent+of+locus+coeruleus+noradrenergic+neurons.&rft.au=Shaham%2C+Y%3BHighfield%2C+D%3BDelfs%2C+J%3BLeung%2C+S%3BStewart%2C+J&rft.aulast=Shaham&rft.aufirst=Y&rft.date=2000-01-01&rft.volume=12&rft.issue=1&rft.spage=292&rft.isbn=&rft.btitle=&rft.title=The+European+journal+of+neuroscience&rft.issn=0953816X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-16 N1 - Date created - 2000-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A farnesyl transferase inhibitor suppresses TPA-mediated skin tumor development without altering hyperplasia in the ras transgenic Tg.AC mouse. AN - 70868537; 10642434 AB - The Tg.AC mouse carries an activated v-Ha-ras oncogene fused to an embryonic zeta-globin promoter and develops cutaneous papillomas in response to specific chemicals, full thickness wounding, and ultraviolet radiation. Papilloma development in these mice has been suggested to be dependent upon activation of ras transgene expression, thus providing a potential model for studying ras-inhibitory compounds. Farnesyl transferase inhibitors (FTIs) prevent a critical posttranslational modification step necessary for activation of ras proteins. Our studies demonstrated that a tricyclic FTI (SCH 56582) applied directly to the skin of homozygous Tg.AC mice 1 h prior to administration of the tumor promoter TPA decreased tumor multiplicity compared to TPA-only controls. In addition, a reduction of TPA-induced tumor development was seen in similarly treated hemizygous Tg.AC mice either on an FVB/N strain background or 50% C57BL/6. Histological examination of skin from Tg. AC(+/-):FVB/N mice revealed no differences with respect to 12-O-tetradecamoylpharbol-13-acetate (TPA)-mediated hyperplasia. Keratinocytes isolated from treated and control skin were assayed for ras transgene expression by reverse transcription-polymerase chain reaction, and expression was detected in both TPA- and FTI+TPA-treated tissue, although the appearance of transgene positive pre-papillomas was observed only in histological sections taken 21 d after the first treatment. In summary, we have used a regimen of topical application of an FTI (SCH 56582) to suppress TPA-mediated papillomagenesis in v-Ha-ras transgenic Tg.AC mice. These studies demonstrate that TPA-induced epidermal hyperplasia is a ras-independent process, while papilloma development in response to TPA treatment requires the function of activated ras. Copyright 2000 Wiley-Liss, Inc. JF - Molecular carcinogenesis AU - Trempus, C S AU - Bishop, W R AU - Njoroge, F G AU - Doll, R J AU - Battalora, M S AU - Mahler, J F AU - Haseman, J K AU - Tennant, R W AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. trempus@niehs.nih.gov Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 24 EP - 33 VL - 27 IS - 1 SN - 0899-1987, 0899-1987 KW - Benzazepines KW - 0 KW - Enzyme Inhibitors KW - SCH 56582 KW - Globins KW - 9004-22-2 KW - Alkyl and Aryl Transferases KW - EC 2.5.- KW - Farnesyltranstransferase KW - EC 2.5.1.29 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Homozygote KW - Keratinocytes -- drug effects KW - Globins -- genetics KW - Mice KW - Mice, Transgenic KW - Mice, Inbred Strains KW - Promoter Regions, Genetic KW - Hyperplasia KW - Mice, Inbred C57BL KW - Crosses, Genetic KW - Keratinocytes -- pathology KW - Time Factors KW - Female KW - Male KW - Tetradecanoylphorbol Acetate -- toxicity KW - Benzazepines -- pharmacology KW - Papilloma -- prevention & control KW - Skin -- pathology KW - Alkyl and Aryl Transferases -- antagonists & inhibitors KW - Papilloma -- genetics KW - Skin Neoplasms -- prevention & control KW - Genes, ras KW - Skin Neoplasms -- genetics KW - Skin -- drug effects KW - Skin Neoplasms -- chemically induced KW - Enzyme Inhibitors -- pharmacology KW - Papilloma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70868537?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+carcinogenesis&rft.atitle=A+farnesyl+transferase+inhibitor+suppresses+TPA-mediated+skin+tumor+development+without+altering+hyperplasia+in+the+ras+transgenic+Tg.AC+mouse.&rft.au=Trempus%2C+C+S%3BBishop%2C+W+R%3BNjoroge%2C+F+G%3BDoll%2C+R+J%3BBattalora%2C+M+S%3BMahler%2C+J+F%3BHaseman%2C+J+K%3BTennant%2C+R+W&rft.aulast=Trempus&rft.aufirst=C&rft.date=2000-01-01&rft.volume=27&rft.issue=1&rft.spage=24&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-18 N1 - Date created - 2000-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methotrexate distribution within the subarachnoid space after intraventricular and intravenous administration. AN - 70867904; 10663645 AB - Intrathecal methotrexate achieves high concentrations in cerebrospinal fluid (CSF), but drug distribution throughout the subarachnoid space after an intralumbar dose is limited. The objective of this study was to quantify methotrexate distribution in CSF after intraventricular and intravenous administration and to identify factors that influence CSF distribution. Nonhuman primates (Macaca mulatta) with permanently implanted catheters in the lateral and fourth ventricles received methotrexate by bolus injection (0.5 mg) and infusion (0.05 to 0.5 mg/day over 24 to 168 h) into the lateral ventricle, as well as intravenous infusions. CSF was sampled from the lumbar space, fourth ventricle and the subarachnoid space at the vertex. Methotrexate in CSF and plasma was measured with the dihydrofolate reductase inhibition assay. After bolus intraventricular injection, methotrexate exposure in lumbar CSF ranged from 11% to 69% of that achieved in the fourth ventricle. During continuous intraventricular infusions, methotrexate steady-state concentrations (C(ss)) in lumbar CSF and CSF from the vertex were only 20% to 25% of the ventricular CSF C(ss). The dose, duration of infusion, and infusate volume did not influence drug distribution to the lumbar CSF, but probenicid increased the lumbar to ventricular C(ss) ratio, suggesting the involvement of a probenicid-sensitive transport pump in the efflux of MTX from the CSF. During the intravenous infusions, the ventricular methotrexate C(ss) was lower than the lumbar C(ss) and the C(ss) in CSF from the vertex. Methotrexate CSF distribution after intraventricular injection was uneven, and at steady-state CSF methotrexate concentrations were lower at sites that were more distant from the injection site. JF - Cancer chemotherapy and pharmacology AU - Balis, F M AU - Blaney, S M AU - McCully, C L AU - Bacher, J D AU - Murphy, R F AU - Poplack, D G AD - Pediatric Oncology Branch, Bldg. 10/Rm. 13N20, 10 Center Drive, MSC 1928, National Cancer Institute, NIH, Bethesda, MD 20892-1928, USA. balisf@nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 259 EP - 264 VL - 45 IS - 3 SN - 0344-5704, 0344-5704 KW - Antimetabolites, Antineoplastic KW - 0 KW - Uricosuric Agents KW - Probenecid KW - PO572Z7917 KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Animals KW - Infusions, Intravenous KW - Dose-Response Relationship, Drug KW - Brain -- drug effects KW - Metabolic Clearance Rate KW - Brain -- metabolism KW - Infusions, Parenteral KW - Cerebral Ventricles -- drug effects KW - Injections, Intraventricular KW - Macaca mulatta KW - Probenecid -- pharmacology KW - Uricosuric Agents -- pharmacology KW - Male KW - Methotrexate -- pharmacokinetics KW - Antimetabolites, Antineoplastic -- cerebrospinal fluid KW - Subarachnoid Space -- metabolism KW - Methotrexate -- cerebrospinal fluid KW - Antimetabolites, Antineoplastic -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70867904?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=Methotrexate+distribution+within+the+subarachnoid+space+after+intraventricular+and+intravenous+administration.&rft.au=Balis%2C+F+M%3BBlaney%2C+S+M%3BMcCully%2C+C+L%3BBacher%2C+J+D%3BMurphy%2C+R+F%3BPoplack%2C+D+G&rft.aulast=Balis&rft.aufirst=F&rft.date=2000-01-01&rft.volume=45&rft.issue=3&rft.spage=259&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-09 N1 - Date created - 2000-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Construction of gene therapy vectors targeting adrenocortical cells: enhancement of activity and specificity with agents modulating the cyclic adenosine 3',5'-monophosphate pathway. AN - 70859451; 10634396 AB - In preliminary studies we demonstrated that the CYP11B1 (11beta-hydroxylase) promoter could direct specific expression of a suicide gene in adrenocortical cancer cells, providing a potentially specific therapeutic option for adrenocortical cancer. In this present study we describe our attempts to enhance the activity of the CYP11B1 promoter while maintaining its specificity for adrenal cells. Using a putative enhancer element from the cholesterol side-chain cleavage (P450scc) gene, the activity of the CYP11B1 promoter in and its specificity for adrenocortical cells were enhanced. Treatment with 8-bromo-cAMP or forskolin resulted in further enhancement. In stably transfected Y-1 cells, in which the herpes simplex virus thymidine kinase (HSV-TK) gene was driven by the CYP11B1 promoter with the P450scc enhancer element, HSV-TK expression and ganciclovir sensitivity were augmented by treatment with 8-bromo-cAMP, forskolin, and ACTH. In summary, we report the construction of a suicide HSV-TK vector with preferential toxicity to adrenocortical cells. We propose that a similar strategy using differentiating agents may be useful in the gene therapy of tumors with unique differentiated properties, including those arising from other endocrine organs. JF - The Journal of clinical endocrinology and metabolism AU - Chuman, Y AU - Zhan, Z AU - Fojo, T AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 253 EP - 262 VL - 85 IS - 1 SN - 0021-972X, 0021-972X KW - RNA, Messenger KW - 0 KW - Cyclic AMP KW - E0399OZS9N KW - Luciferases KW - EC 1.13.12.- KW - Steroid 11-beta-Hydroxylase KW - EC 1.14.15.4 KW - Abridged Index Medicus KW - Index Medicus KW - Cell Survival -- genetics KW - Plasmids -- genetics KW - Humans KW - Steroid 11-beta-Hydroxylase -- metabolism KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Cloning, Molecular KW - Polymerase Chain Reaction KW - Blotting, Western KW - Tumor Cells, Cultured KW - Enhancer Elements, Genetic KW - Transfection -- genetics KW - Promoter Regions, Genetic -- genetics KW - Luciferases -- genetics KW - Steroid 11-beta-Hydroxylase -- genetics KW - Adrenal Cortex -- physiology KW - Genetic Vectors KW - Cyclic AMP -- metabolism KW - Genetic Therapy KW - Adrenal Cortex -- metabolism KW - Adrenal Cortex -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70859451?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+endocrinology+and+metabolism&rft.atitle=Construction+of+gene+therapy+vectors+targeting+adrenocortical+cells%3A+enhancement+of+activity+and+specificity+with+agents+modulating+the+cyclic+adenosine+3%27%2C5%27-monophosphate+pathway.&rft.au=Chuman%2C+Y%3BZhan%2C+Z%3BFojo%2C+T&rft.aulast=Chuman&rft.aufirst=Y&rft.date=2000-01-01&rft.volume=85&rft.issue=1&rft.spage=253&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+endocrinology+and+metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-03 N1 - Date created - 2000-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant human thyrotropin for the diagnosis and treatment of a highly functional metastatic struma ovarii. AN - 70859395; 10634393 AB - The optimal treatment of metastatic thyroid cancer that produces high amounts of thyroid hormone has not been well defined. A 46-yr-old woman presented with a follicular thyroid carcinoma arising from a struma ovarii with hepatic metastases. After the removal of both the struma and the thyroid gland, the liver metastases showed evidence of a high degree of hormonogenesis. Brain, chest, abdomen, and bone imaging was negative for additional metastases. Because iodine uptake by most thyroid carcinomas is quite low in the absence of high levels of ambient TSH, we used recombinant human TSH (rhTSH) (Thyrogen) to achieve a concentration of 131I activity in the tumor high enough for a significant cytotoxic effect. After rhTSH administration (0.9 mg im daily for 2 consecutive days), a 131I diagnostic whole body scan confirmed the existence of 17 discrete hepatic foci of 131I uptake. To calculate the amount of 131I that would deliver an absorbed radiation dose that would be optimally cytotoxic to the metastases (>8000 rad/lesion) and not to the normal liver, we performed lesion dosimetry. Analysis of dosimetric data showed that 15 of 17 lesions would receive an adequate radiation dose following the administration of 65 mCi of 131I. Additionally, we performed whole body dosimetry to assure that this dose would not cause bone marrow toxicity. The patient was reevaluated 6 months after therapy; the liver metastases showed significant, but partial, response. In conclusion, we used the combination of rhTSH with lesional and whole body dosimetry for the treatment of highly functional metastases from follicular thyroid carcinoma arising within a struma ovarii. This strategy can be applied to determine a safe and effective dose of 131I for the treatment of any thyroid cancer metastases that produce enough TH to preclude stimulation of endogenous pituitary TSH secretion. JF - The Journal of clinical endocrinology and metabolism AU - Rotman-Pikielny, P AU - Reynolds, J C AU - Barker, W C AU - Yen, P M AU - Skarulis, M C AU - Sarlis, N J AD - Clinical Endocrinology Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 237 EP - 244 VL - 85 IS - 1 SN - 0021-972X, 0021-972X KW - Iodine Radioisotopes KW - 0 KW - Recombinant Proteins KW - Thyrotropin KW - 9002-71-5 KW - Abridged Index Medicus KW - Index Medicus KW - Magnetic Resonance Imaging KW - Iodine Radioisotopes -- therapeutic use KW - Liver Neoplasms -- pathology KW - Humans KW - Middle Aged KW - Liver Neoplasms -- secondary KW - Recombinant Proteins -- therapeutic use KW - Female KW - Ovarian Neoplasms -- secondary KW - Struma Ovarii -- radiotherapy KW - Ovarian Neoplasms -- radiotherapy KW - Teratoma -- pathology KW - Thyroid Neoplasms -- pathology KW - Struma Ovarii -- diagnosis KW - Thyrotropin -- therapeutic use KW - Struma Ovarii -- secondary KW - Ovarian Neoplasms -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70859395?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+endocrinology+and+metabolism&rft.atitle=Recombinant+human+thyrotropin+for+the+diagnosis+and+treatment+of+a+highly+functional+metastatic+struma+ovarii.&rft.au=Rotman-Pikielny%2C+P%3BReynolds%2C+J+C%3BBarker%2C+W+C%3BYen%2C+P+M%3BSkarulis%2C+M+C%3BSarlis%2C+N+J&rft.aulast=Rotman-Pikielny&rft.aufirst=P&rft.date=2000-01-01&rft.volume=85&rft.issue=1&rft.spage=237&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+endocrinology+and+metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-03 N1 - Date created - 2000-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - IFN-gamma-dependent delay of in vivo tumor progression by Fas overexpression on murine renal cancer cells. AN - 70825245; 10605016 AB - The role of Fas in the regulation of solid tumor growth was investigated. Murine renal carcinoma (Renca) cells were constitutively resistant to Fas-mediated killing in vitro, but exhibited increased expression of Fas and sensitivity to Fas-mediated killing after exposure to IFN-gamma and TNF. Transfected Renca cells overexpressing Fas were efficiently killed in vitro upon exposure to anti-Fas Ab (Jo2). When Fas-overexpressing Renca cells were injected into syngenic BALB/c mice, there was a consistent and significant delay in tumor progression, reduced metastasis, and prolonged survival that was not observed for Renca cells that overexpressed a truncated nonfunctional Fas receptor. The delay of in vivo tumor growth induced by Fas overexpression was not observed in IFN-gamma-/- mice, indicating that IFN-gamma is required for the delay of in vivo tumor growth. However, there was a significant increase of infiltrated T cells and in vivo apoptosis in Fas-overexpressing Renca tumors, and Fas-overexpressing Renca cells were also efficiently killed in vitro by T cells. In addition, a strong therapeutic effect was observed on Fas-overexpressing tumor cells by in vivo administration of anti-Fas Ab, confirming that overexpressed Fas provides a functional target in vivo for Fas-specific ligands. Therefore, our findings demonstrate that Fas overexpression on solid tumor cells can delay tumor growth and provides a rationale for therapeutic manipulation of Fas expression as a means of inducing tumor regression in vivo. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Lee, J K AU - Sayers, T J AU - Brooks, A D AU - Back, T C AU - Young, H A AU - Komschlies, K L AU - Wigginton, J M AU - Wiltrout, R H AD - Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 2000/01/01/ PY - 2000 DA - 2000 Jan 01 SP - 231 EP - 239 VL - 164 IS - 1 SN - 0022-1767, 0022-1767 KW - Antigens, CD95 KW - 0 KW - Immune Sera KW - Recombinant Proteins KW - Tumor Necrosis Factor-alpha KW - Interferon-gamma KW - 82115-62-6 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Injections, Intralesional KW - Recombinant Proteins -- biosynthesis KW - Apoptosis -- immunology KW - Tumor Necrosis Factor-alpha -- physiology KW - Immunity, Innate KW - Mice KW - Mice, Inbred BALB C KW - Mice, Knockout KW - Tumor Cells, Cultured KW - Cell Division -- immunology KW - Immune Sera -- administration & dosage KW - Up-Regulation -- immunology KW - Drug Synergism KW - Time Factors KW - T-Lymphocytes -- immunology KW - Cell Division -- genetics KW - Sequence Deletion KW - Kidney Neoplasms -- genetics KW - Kidney Neoplasms -- pathology KW - Antigens, CD95 -- genetics KW - Kidney Neoplasms -- prevention & control KW - Adenocarcinoma -- genetics KW - Adenocarcinoma -- immunology KW - Adenocarcinoma -- pathology KW - Antigens, CD95 -- immunology KW - Antigens, CD95 -- biosynthesis KW - Antigens, CD95 -- physiology KW - Interferon-gamma -- physiology KW - Adenocarcinoma -- prevention & control KW - Kidney Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70825245?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=IFN-gamma-dependent+delay+of+in+vivo+tumor+progression+by+Fas+overexpression+on+murine+renal+cancer+cells.&rft.au=Lee%2C+J+K%3BSayers%2C+T+J%3BBrooks%2C+A+D%3BBack%2C+T+C%3BYoung%2C+H+A%3BKomschlies%2C+K+L%3BWigginton%2C+J+M%3BWiltrout%2C+R+H&rft.aulast=Lee&rft.aufirst=J&rft.date=2000-01-01&rft.volume=164&rft.issue=1&rft.spage=231&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 - 2000-01-19 N1 - Date created - 2000-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sustained intracellular retention of dolastatin 10 causes its potent antimitotic activity. AN - 70823396; 10617693 AB - Dolastatin 10 is a highly cytotoxic antimitotic peptide in phase II clinical trials. Its cytotoxicity has been as much as 50-fold greater than that of vinblastine, despite quantitatively similar effects of the two drugs on tubulin polymerization. We compared uptake and efflux of radiolabeled dolastatin 10 and vinblastine in human Burkitt lymphoma CA46 cells to gain an understanding of the greater cytotoxicity of the peptide. In the Burkitt cells, dolastatin 10 was 20-fold more cytotoxic than vinblastine (IC(50) values, 50 pM and 1.0 nM). When drug uptake at 24 h was compared at IC(50) values of the two drugs, the intracellular concentrations were almost identical (50-100 nM). The accumulation factor observed for dolastatin 10 was 900 to 1800 versus 60 to 100 for vinblastine. The two drugs showed very divergent uptake kinetics, however. Vinblastine and dolastatin 10 reached maximum intracellular concentrations after 20 min and 6 h, respectively. Depletion of cellular ATP content did not alter the uptake of either drug, indicating passive uptake of both. When drug-preloaded cells were transferred to drug-free medium, there was no loss of dolastatin 10 for at least 2 h, whereas vinblastine exited the cells rapidly (approximate intracellular half-life, 10 min), with less than 10% of the initial drug remaining in the cells after the 2-h incubation. The potency of dolastatin 10 probably derives from its tenacious binding to tubulin, a property that in cells becomes translated into prolonged intracellular retention of the drug. Optimal clinical use of dolastatin 10 may require administration by infusion rather than by bolus. JF - Molecular pharmacology AU - Verdier-Pinard, P AU - Kepler, J A AU - Pettit, G R AU - Hamel, E AD - Laboratory of Drug Discovery Research, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland, USA. Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 180 EP - 187 VL - 57 IS - 1 SN - 0026-895X, 0026-895X KW - Antineoplastic Agents KW - 0 KW - Depsipeptides KW - Oligopeptides KW - Tritium KW - 10028-17-8 KW - dolastatin 10 KW - 110417-88-4 KW - Vinblastine KW - 5V9KLZ54CY KW - Index Medicus KW - Vinblastine -- pharmacology KW - Tumor Cells, Cultured KW - Kinetics KW - Humans KW - Burkitt Lymphoma KW - Cell Division -- drug effects KW - Biological Transport KW - Inhibitory Concentration 50 KW - Antineoplastic Agents -- metabolism KW - Oligopeptides -- metabolism KW - Oligopeptides -- pharmacology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70823396?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Sustained+intracellular+retention+of+dolastatin+10+causes+its+potent+antimitotic+activity.&rft.au=Verdier-Pinard%2C+P%3BKepler%2C+J+A%3BPettit%2C+G+R%3BHamel%2C+E&rft.aulast=Verdier-Pinard&rft.aufirst=P&rft.date=2000-01-01&rft.volume=57&rft.issue=1&rft.spage=180&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 - 2000-01-20 N1 - Date created - 2000-01-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - alpha-helical structural elements within the voltage-sensing domains of a K(+) channel. AN - 70820882; 10613917 AB - Voltage-gated K(+) channels are tetramers with each subunit containing six (S1-S6) putative membrane spanning segments. The fifth through sixth transmembrane segments (S5-S6) from each of four subunits assemble to form a central pore domain. A growing body of evidence suggests that the first four segments (S1-S4) comprise a domain-like voltage-sensing structure. While the topology of this region is reasonably well defined, the secondary and tertiary structures of these transmembrane segments are not. To explore the secondary structure of the voltage-sensing domains, we used alanine-scanning mutagenesis through the region encompassing the first four transmembrane segments in the drk1 voltage-gated K(+) channel. We examined the mutation-induced perturbation in gating free energy for periodicity characteristic of alpha-helices. Our results are consistent with at least portions of S1, S2, S3, and S4 adopting alpha-helical secondary structure. In addition, both the S1-S2 and S3-S4 linkers exhibited substantial helical character. The distribution of gating perturbations for S1 and S2 suggest that these two helices interact primarily with two environments. In contrast, the distribution of perturbations for S3 and S4 were more complex, suggesting that the latter two helices make more extensive protein contacts, possibly interfacing directly with the shell of the pore domain. JF - The Journal of general physiology AU - Li-Smerin, Y AU - Hackos, D H AU - Swartz, K J AD - Molecular Physiology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 33 EP - 50 VL - 115 IS - 1 SN - 0022-1295, 0022-1295 KW - Delayed Rectifier Potassium Channels KW - 0 KW - Potassium Channels KW - Potassium Channels, Voltage-Gated KW - Index Medicus KW - Point Mutation -- physiology KW - Xenopus laevis KW - Animals KW - Molecular Sequence Data KW - Periodicity KW - Amino Acid Sequence KW - Ion Channel Gating -- physiology KW - Potassium Channels -- chemistry KW - Potassium Channels -- genetics KW - Protein Structure, Secondary -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70820882?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+general+physiology&rft.atitle=alpha-helical+structural+elements+within+the+voltage-sensing+domains+of+a+K%28%2B%29+channel.&rft.au=Li-Smerin%2C+Y%3BHackos%2C+D+H%3BSwartz%2C+K+J&rft.aulast=Li-Smerin&rft.aufirst=Y&rft.date=2000-01-01&rft.volume=115&rft.issue=1&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+general+physiology&rft.issn=00221295&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-24 N1 - Date created - 2000-02-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1991 Feb 22;251(4996):942-4 [2000495] Nature. 1991 Mar 21;350(6315):232-5 [1706481] Nature. 1991 Oct 24;353(6346):752-6 [1944534] Neuron. 1992 Nov;9(5):861-71 [1419000] Biophys J. 1994 Feb;66(2 Pt 1):345-54 [8161688] Biochemistry. 1994 May 10;33(18):5607-13 [8180185] Biochemistry. 1994 Jun 14;33(23):7211-9 [8003486] Biophys J. 1994 Apr;66(4):1061-7 [8038378] Neuron. 1995 Jun;14(6):1293-301 [7605638] Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9422-6 [7568145] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] J Mol Biol. 1982 May 5;157(1):105-32 [7108955] J Mol Biol. 1987 Jun 5;195(3):659-85 [3656427] Nature. 1988 Jan 14;331(6152):137-42 [2448635] Proc Natl Acad Sci U S A. 1988 Dec;85(23):9012-6 [3057498] Science. 1989 Feb 17;243(4893):943-7 [2493160] Science. 1989 Aug 4;245(4917):510-3 [2667138] Nature. 1989 Aug 24;340(6235):642-5 [2770868] Annu Rev Biochem. 1989;58:607-33 [2673018] Science. 1989 Sep 22;245(4924):1382-5 [2476850] FEBS Lett. 1989 Oct 23;257(1):113-7 [2553484] EMBO J. 1989 Nov;8(11):3235-44 [2555158] Science. 1990 Oct 12;250(4978):276-9 [2218530] Science. 1990 Oct 26;250(4980):533-8 [2122519] Pflugers Arch. 1996 Nov-Dec;433(1-2):91-7 [9019737] Biophys J. 1997 Apr;72(4):1489-500 [9083655] Neuron. 1997 Apr;18(4):665-73 [9136774] Neuron. 1997 Apr;18(4):675-82 [9136775] Neuron. 1997 Nov;19(5):1127-40 [9390525] J Gen Physiol. 1998 Mar;111(3):399-420 [9482708] J Gen Physiol. 1998 Mar;111(3):421-39 [9482709] Science. 1998 Apr 3;280(5360):69-77 [9525859] Science. 1998 Apr 3;280(5360):106-9 [9525854] Neuron. 1998 Mar;20(3):371-80 [9539115] J Struct Biol. 1998;121(2):263-84 [9615442] Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8585-9 [9671721] J Gen Physiol. 1999 Mar;113(3):389-414 [10051516] J Gen Physiol. 1999 Mar;113(3):415-23 [10051517] Nat Neurosci. 1998 Dec;1(8):668-74 [10196582] Science. 1990 Oct 26;250(4980):568-71 [2122520] Nature. 1991 Jan 24;349(6307):305-10 [1846229] Nature. 1991 Feb 21;349(6311):700-4 [1899917] Science. 1991 Feb 22;251(4996):939-42 [2000494] EMBO J. 1995 Nov 1;14(21):5170-8 [7489706] Science. 1996 Jan 12;271(5246):213-6 [8539623] Neuron. 1996 Jan;16(1):113-22 [8562074] Neuron. 1996 Jan;16(1):131-9 [8562077] J Mol Biol. 1996 May 17;258(4):672-87 [8637001] Biochemistry. 1996 May 28;35(21):6828-38 [8639634] Neuron. 1996 Jun;16(6):1159-67 [8663992] Neuron. 1996 Jun;16(6):1169-77 [8663993] Neuron. 1996 Feb;16(2):387-97 [8789953] J Gen Physiol. 1996 Sep;108(3):195-206 [8882863] Comment In: J Gen Physiol. 2000 Jan;115(1):29-32 [10613916] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nonconserved residues in the second transmembrane-spanning domain of the D(4) dopamine receptor are molecular determinants of D(4)-selective pharmacology. AN - 70819279; 10617689 AB - The molecular determinants that govern selective ligand binding to the rat D(4) dopamine receptor were investigated by substituting D(2) dopamine receptor sequences into a D(4) dopamine receptor background. The resulting mutant D(4) dopamine receptors were then screened with a panel of 10 selective and nonselective ligands, which included two allosteric modulators as sensitive measures of protein conformational changes. Mutation of a phenylalanine at position 88 in the second transmembrane-spanning domain (TMS2) of the D(4) receptor to the corresponding valine in the D(2) receptor D(4)-F88V resulted in an approximately 100-fold decrease in the affinity of the highly D(4)-selective drug 3-([4-(4-iodophenyl) piperazin-1-yl]methyl)-1H-pyrrolo[2,3-b]pyridine (L-750,667) without substantially affecting the binding of the other ligands. Mutations at the extracellular side of D(4)-TMS3 produced moderate decreases in L-750,667 binding affinities with concomitant increases in binding affinity for the D(2)/D(3)-selective antagonist (-)-raclopride. However, the binding affinities of these same D(4)-TMS3 mutants for the allosteric modulator isomethylbutylamiloride also were an anomalous 6- to 20-fold higher than either wild-type receptor. In the combined D(4)-F88V/TMS3 mutants, L-750,667 binding affinity was further decreased, but this decrease was not additive. More importantly, the combined D(4)-F88V/TMS3 mutants had (-)-raclopride and isomethylbutylamiloride binding properties that reverted back to those of the wild-type D(4)-receptor. In contrast to the D(4)-F88V mutant, the adjacent D(4)-L87W mutant had an increased affinity for ligands with extended structures, but had essentially no effect on ligands with compact structures. These findings demonstrate that two residues near the extracellular side of D(4)-TMS2 are critical molecular determinants for the selective binding of L-750,667 and ligands with extended structures. JF - Molecular pharmacology AU - Schetz, J A AU - Benjamin, P S AU - Sibley, D R AD - Molecular Neuropharmacology Section, Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. jacks@helix.nih.gov Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 144 EP - 152 VL - 57 IS - 1 SN - 0026-895X, 0026-895X KW - Dopamine Antagonists KW - 0 KW - Dopamine D2 Receptor Antagonists KW - Drd4 protein, rat KW - L 750667 KW - Ligands KW - Membrane Proteins KW - Pyridines KW - Pyrroles KW - Receptors, Dopamine D2 KW - Receptors, Dopamine D4 KW - 137750-34-6 KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - COS Cells KW - Transfection KW - Membrane Proteins -- metabolism KW - Membrane Proteins -- antagonists & inhibitors KW - Structure-Activity Relationship KW - Protein Conformation KW - Binding Sites KW - Dopamine Antagonists -- metabolism KW - Receptors, Dopamine D2 -- chemistry KW - Pyrroles -- metabolism KW - Pyridines -- metabolism KW - Receptors, Dopamine D2 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70819279?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nonconserved+residues+in+the+second+transmembrane-spanning+domain+of+the+D%284%29+dopamine+receptor+are+molecular+determinants+of+D%284%29-selective+pharmacology.&rft.au=Schetz%2C+J+A%3BBenjamin%2C+P+S%3BSibley%2C+D+R&rft.aulast=Schetz&rft.aufirst=J&rft.date=2000-01-01&rft.volume=57&rft.issue=1&rft.spage=144&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 - 2000-01-20 N1 - Date created - 2000-01-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Strategies for assessing the implications of malformed frogs for environmental health. AN - 70816331; 10620528 AB - The recent increase in the incidence of deformities among natural frog populations has raised concern about the state of the environment and the possible impact of unidentified causative agents on the health of wildlife and human populations. An open workshop on Strategies for Assessing the Implications of Malformed Frogs for Environmental Health was convened on 4-5 December 1997 at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina. The purpose of the workshop was to share information among a multidisciplinary group with scientific interest and responsibility for human and environmental health at the federal and state level. Discussions highlighted possible causes and recent findings directly related to frog deformities and provided insight into problems and strategies applicable to continuing investigation in several areas. Possible causes of the deformities were evaluated in terms of diagnostics performed on field amphibians, biologic mechanisms that can lead to the types of malformations observed, and parallel laboratory and field studies. Hydrogeochemistry must be more integrated into environmental toxicology because of the pivotal role of the aquatic environment and the importance of fates and transport relative to any potential exposure. There is no indication of whether there may be a human health factor associated with the deformities. However, the possibility that causal agents may be waterborne indicates a need to identify the relevant factors and establish the relationship between environmental and human health in terms of hazard assessment. JF - Environmental health perspectives AU - Burkhart, J G AU - Ankley, G AU - Bell, H AU - Carpenter, H AU - Fort, D AU - Gardiner, D AU - Gardner, H AU - Hale, R AU - Helgen, J C AU - Jepson, P AU - Johnson, D AU - Lannoo, M AU - Lee, D AU - Lary, J AU - Levey, R AU - Magner, J AU - Meteyer, C AU - Shelby, M D AU - Lucier, G Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 83 EP - 90 VL - 108 IS - 1 KW - Water Pollutants, Chemical KW - 0 KW - Xenobiotics KW - Index Medicus KW - Environmental Monitoring KW - Animals KW - Public Health KW - Humans KW - Risk Assessment KW - Ranidae -- embryology KW - Congenital Abnormalities -- veterinary KW - Water Pollutants, Chemical -- adverse effects KW - Ranidae -- anatomy & histology KW - Xenobiotics -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70816331?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Environmental+health+perspectives&rft.atitle=Strategies+for+assessing+the+implications+of+malformed+frogs+for+environmental+health.&rft.au=Burkhart%2C+J+G%3BAnkley%2C+G%3BBell%2C+H%3BCarpenter%2C+H%3BFort%2C+D%3BGardiner%2C+D%3BGardner%2C+H%3BHale%2C+R%3BHelgen%2C+J+C%3BJepson%2C+P%3BJohnson%2C+D%3BLannoo%2C+M%3BLee%2C+D%3BLary%2C+J%3BLevey%2C+R%3BMagner%2C+J%3BMeteyer%2C+C%3BShelby%2C+M+D%3BLucier%2C+G&rft.aulast=Burkhart&rft.aufirst=J&rft.date=2000-01-01&rft.volume=108&rft.issue=1&rft.spage=83&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 - 2000-02-22 N1 - Date created - 2000-02-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Exp Zool. 1999 Jul 1;284(2):207-16 [10404649] J Exp Zool. 1990 Apr;254(1):38-47 [2348164] Nature. 1992 Jan 23;355(6358):352-3 [1731249] Dev Biol. 1992 Jul;152(1):1-25 [1628749] Ann Clin Lab Sci. 1993 Mar-Apr;23(2):121-9 [8457141] Dev Biol. 1993 Oct;159(2):379-91 [8405665] Science. 1999 Apr 30;284(5415):802-4 [10221912] Dev Genet. 1996;19(1):85-93 [8792612] J Wildl Dis. 1997 Jan;33(1):95-104 [9027696] Nucleic Acids Res. 1997 May 15;25(10):1903-12 [9115356] Mol Cell Biol. 1997 Aug;17(8):4738-49 [9234730] Environ Health Perspect. 1998 Dec;106(12):841-8 [9831545] Science. 1999 Apr 30;284(5415):800-2 [10221911] Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5436-40 [8202504] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identifying populations potentially exposed to agricultural pesticides using remote sensing and a Geographic Information System. AN - 70815762; 10622770 AB - Pesticides used in agriculture may cause adverse health effects among the population living near agricultural areas. However, identifying the populations most likely to be exposed is difficult. We conducted a feasibility study to determine whether satellite imagery could be used to reconstruct historical crop patterns. We used historical Farm Service Agency records as a source of ground reference data to classify a late summer 1984 satellite image into crop species in a three-county area in south central Nebraska. Residences from a population-based epidemiologic study of non-Hodgkin lymphoma were located on the crop maps using a geographic information system (GIS). Corn, soybeans, sorghum, and alfalfa were the major crops grown in the study area. Eighty-five percent of residences could be located, and of these 22% had one of the four major crops within 500 m of the residence, an intermediate distance for the range of drift effects from pesticides applied in agriculture. We determined the proximity of residences to specific crop species and calculated crop-specific probabilities of pesticide use based on available data. This feasibility study demonstrated that remote sensing data and historical records on crop location can be used to create historical crop maps. The crop pesticides that were likely to have been applied can be estimated when information about crop-specific pesticide use is available. Using a GIS, zones of potential exposure to agricultural pesticides and proximity measures can be determined for residences in a study. JF - Environmental health perspectives AU - Ward, M H AU - Nuckols, J R AU - Weigel, S J AU - Maxwell, S K AU - Cantor, K P AU - Miller, R S AD - Occupational Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 5 EP - 12 VL - 108 IS - 1 SN - 0091-6765, 0091-6765 KW - Pesticides KW - 0 KW - Index Medicus KW - Space life sciences KW - Feasibility Studies KW - Humans KW - Adult KW - Environmental Exposure KW - Aged KW - Middle Aged KW - Spacecraft KW - Male KW - Female KW - Pesticides -- analysis KW - Agriculture KW - Public Health KW - Pesticides -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70815762?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identifying+populations+potentially+exposed+to+agricultural+pesticides+using+remote+sensing+and+a+Geographic+Information+System.&rft.au=Ward%2C+M+H%3BNuckols%2C+J+R%3BWeigel%2C+S+J%3BMaxwell%2C+S+K%3BCantor%2C+K+P%3BMiller%2C+R+S&rft.aulast=Ward&rft.aufirst=M&rft.date=2000-01-01&rft.volume=108&rft.issue=1&rft.spage=5&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 - 2000-02-22 N1 - Date created - 2000-02-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Arch Environ Contam Toxicol. 1981;10(2):133-49 [7224666] Am J Ind Med. 1998 Dec;34(6):581-7 [9816416] Arch Environ Contam Toxicol. 1984 Sep;13(5):551-63 [6486883] Am J Public Health. 1988 Jun;78(6):654-8 [3369595] Epidemiology. 1990 Sep;1(5):349-56 [2078610] Cancer Res. 1992 May 1;52(9):2447-55 [1568215] Arch Environ Contam Toxicol. 1994 Jan;26(1):37-46 [8110022] Am J Trop Med Hyg. 1994 Sep;51(3):271-80 [7943544] Am J Public Health. 1995 Jul;85(7):944-8 [7604918] Cancer. 1996 Feb 15;77(4):763-70 [8616770] Environ Health Perspect. 1995 Dec;103(12):1126-34 [8747019] Am J Public Health. 1996 Sep;86(9):1289-96 [8806382] Occup Med. 1997 Apr-Jun;12(2):221-37 [9220483] Occup Med. 1997 Apr-Jun;12(2):269-89 [9220486] Occup Med. 1997 Apr-Jun;12(2):291-304 [9220487] Occup Med. 1997 Apr-Jun;12(2):305-25 [9220488] Environ Health Perspect. 1997 Dec;105(12):1344-53 [9405329] Environ Health Perspect. 1998 Nov;106(11):721-4 [9799187] Arch Environ Health. 1981 Sep-Oct;36(5):213-21 [6271079] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ligand-activation of the adenosine A2a receptors inhibits IL-12 production by human monocytes. AN - 70813155; 10605040 AB - Adenosine (ADO) exerts potent anti-inflammatory and immunosuppressive effects. In this paper we address the possibility that these effects are partly mediated by inhibition of the secretion of IL-12, a proinflammatory cytokine and a major inducer of Th1 responses. We demonstrate that 5'-N-ethylcarboxamidoadenosine (NECA), a nonspecific ADO analogue, and 2-p-(2-carbonyl-ethyl)phenylethylamino-5'-N-ethylcarboxamidoadenos ine (CGS-21680), a specific A2a receptor agonist, dose-dependently inhibited, in whole blood ex vivo and monocyte cultures, the production of human IL-12 induced by LPS and Stapholococcus aureus Cowan strain 1. However, the A1 receptor agonist 2-Chloro-N6-cyclopentyladenosine and the A3 receptor agonists N6-Benzyl-NECA and 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-be ta-d -ribofuranuronamide expressed only weak inhibitory effects. On the other hand, NECA and CGS-21680 dose-dependently potentiated the production of IL-10. The differential effect of these drugs on monocyte IL-12 and IL-10 production implies that these effects are mediated by A2a receptor signaling rather than by intracellular toxicity of ADO analogue's metabolites. Moreover, CGS-21680 inhibited IL-12 production independently of endogenous IL-10 induction, because anti-IL-10 Abs failed to prevent its effect. The selective A2a antagonist 8-(3-Chlorostyryl) caffeine prevented the inhibitory effect of CGS-21680 on IL-12 production. The phosphodiesterase inhibitor Ro 20-1724 dose-dependently potentiated the inhibitory effect of CGS-21680 and, furthermore, Rp-cAMPS, a protein kinase A inhibitor, reversed the inhibitory effect of CGS-21680, implicating a cAMP/protein kinase A pathway in its action. Thus, ligand activation of A2a receptors simultaneously inhibits IL-12 and stimulates IL-10 production by human monocytes. Through this mechanism, ADO released in excess during inflammatory and ischemic conditions, or tissue injury, may contribute to selective suppression of Th1 responses and cellular immunity. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Link, A A AU - Kino, T AU - Worth, J A AU - McGuire, J L AU - Crane, M L AU - Chrousos, G P AU - Wilder, R L AU - Elenkov, I J AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. Y1 - 2000/01/01/ PY - 2000 DA - 2000 Jan 01 SP - 436 EP - 442 VL - 164 IS - 1 SN - 0022-1767, 0022-1767 KW - Immunosuppressive Agents KW - 0 KW - Ligands KW - Lipopolysaccharides KW - Phenethylamines KW - Purinergic P1 Receptor Agonists KW - Purinergic P1 Receptor Antagonists KW - Receptor, Adenosine A2A KW - Receptor, Adenosine A3 KW - Receptors, Purinergic P1 KW - 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine KW - 120225-54-9 KW - Interleukin-10 KW - 130068-27-8 KW - 8-(3-chlorostyryl)caffeine KW - 148589-13-3 KW - Interleukin-12 KW - 187348-17-0 KW - Adenosine-5'-(N-ethylcarboxamide) KW - 35920-39-9 KW - Caffeine KW - 3G6A5W338E KW - Cyclic AMP KW - E0399OZS9N KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Adenosine KW - K72T3FS567 KW - Abridged Index Medicus KW - Index Medicus KW - Cyclic AMP-Dependent Protein Kinases -- physiology KW - Lipopolysaccharides -- antagonists & inhibitors KW - Interleukin-10 -- secretion KW - Lipopolysaccharides -- pharmacology KW - Adenosine-5'-(N-ethylcarboxamide) -- pharmacology KW - Humans KW - Caffeine -- pharmacology KW - Cyclic AMP -- physiology KW - Phenethylamines -- antagonists & inhibitors KW - Caffeine -- analogs & derivatives KW - Dose-Response Relationship, Immunologic KW - Signal Transduction -- drug effects KW - Interleukin-10 -- biosynthesis KW - Interleukin-10 -- blood KW - Phenethylamines -- pharmacology KW - Male KW - Female KW - Adenosine -- physiology KW - Adenosine -- pharmacology KW - Receptors, Purinergic P1 -- physiology KW - Interleukin-12 -- biosynthesis KW - Monocytes -- immunology KW - Adenosine -- analogs & derivatives KW - Monocytes -- metabolism KW - Monocytes -- drug effects KW - Receptors, Purinergic P1 -- metabolism KW - Interleukin-12 -- blood KW - Adenosine -- antagonists & inhibitors KW - Interleukin-12 -- antagonists & inhibitors KW - Immunosuppressive Agents -- pharmacology KW - Adenosine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70813155?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Ligand-activation+of+the+adenosine+A2a+receptors+inhibits+IL-12+production+by+human+monocytes.&rft.au=Link%2C+A+A%3BKino%2C+T%3BWorth%2C+J+A%3BMcGuire%2C+J+L%3BCrane%2C+M+L%3BChrousos%2C+G+P%3BWilder%2C+R+L%3BElenkov%2C+I+J&rft.aulast=Link&rft.aufirst=A&rft.date=2000-01-01&rft.volume=164&rft.issue=1&rft.spage=436&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 - 2000-01-19 N1 - Date created - 2000-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural requirements for catalysis and dimerization of human methionine adenosyltransferase I/III. AN - 70812622; 10620323 AB - We have used site-directed mutagenesis to probe the structural requirements for catalysis and dimerization of human hepatic methionine adenosyltransferase (hMAT). We built a homology model of the dimeric hMAT III inferred by the crystal structure of the highly homologous Escherichia coli MAT dimer. The active sites of both enzymes comprise the same amino acids and are located in the inter-subunit interface. All of the amino acids predicted to be in the hMAT III active site were mutated, as well as residues in a conserved ATP binding region. All of the mutations except one severely affected catalytic activity. On the other hand, dimerization was affected only by single mutations of three different residues, all on one monomer. The homology model suggested that the side chains of these residues stabilized the monomer and participated in a bridge between subunits consisting of a network of metal and phosphate ions. In agreement with this observation, we demonstrated that dimerization cannot occur in the absence of phosphate. Copyright 2000 Academic Press. JF - Archives of biochemistry and biophysics AU - Chamberlin, M E AU - Ubagai, T AU - Pao, V Y AU - Pearlstein, R A AU - Yang Chou, J AD - Heritable Disorders Branch, National Institute of Child Health and Human Development, Bethesda, Maryland, 20892, USA. Y1 - 2000/01/01/ PY - 2000 DA - 2000 Jan 01 SP - 56 EP - 62 VL - 373 IS - 1 SN - 0003-9861, 0003-9861 KW - Codon KW - 0 KW - Isoenzymes KW - Phosphates KW - Methionine Adenosyltransferase KW - EC 2.5.1.6 KW - Index Medicus KW - Codon -- genetics KW - Models, Molecular KW - Phosphates -- chemistry KW - Dimerization KW - Humans KW - Escherichia coli -- genetics KW - Amino Acid Sequence KW - Escherichia coli -- enzymology KW - Protein Structure, Quaternary KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Conserved Sequence KW - Kinetics KW - In Vitro Techniques KW - Molecular Sequence Data KW - Catalytic Domain -- genetics KW - Sequence Homology, Amino Acid KW - Species Specificity KW - Isoenzymes -- chemistry KW - Methionine Adenosyltransferase -- metabolism KW - Methionine Adenosyltransferase -- genetics KW - Methionine Adenosyltransferase -- chemistry KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70812622?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Structural+requirements+for+catalysis+and+dimerization+of+human+methionine+adenosyltransferase+I%2FIII.&rft.au=Chamberlin%2C+M+E%3BUbagai%2C+T%3BPao%2C+V+Y%3BPearlstein%2C+R+A%3BYang+Chou%2C+J&rft.aulast=Chamberlin&rft.aufirst=M&rft.date=2000-01-01&rft.volume=373&rft.issue=1&rft.spage=56&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 - 2000-02-09 N1 - Date created - 2000-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Perturbations in eosinophil homeostasis following treatment of lymphatic filariasis. AN - 70812232; 10603373 AB - Treatment of patients with patent Wuchereria bancrofti infection results in an acute clinical reaction and peripheral eosinophilia. To investigate the dynamics of the eosinophil response, changes in eosinophil activation and degranulation and plasma levels of eosinophil-active chemokines and cytokines were studied in 15 microfilaremic individuals in south India by sequential blood sampling before and after administration of 300 mg of diethylcarbamazine (DEC). Clinical symptoms occurred within 24 h. Plasma interleukin-5 (IL-5) and RANTES levels peaked 1 to 2 days posttreatment, preceding a peak peripheral eosinophil count at day 4. Major basic protein secretion from eosinophils paralleled IL-5 secretion, while levels of eosinophil-derived neurotoxin peaked at day 13 after treatment. Expression of the activation markers HLA-DR and CD25 on eosinophils rose markedly immediately after treatment, while expression of VLA-4 and alpha4beta7 showed an early peak within 24 h and a second peak at day 13. Thus, the posttreatment reactions seen in filarial infections can be divided into an early phase with killing of microfilariae, clinical symptomatology, increases in plasma IL-5 and RANTES levels, and eosinophil activation and degranulation and a later phase with expression of surface integrins on eosinophils, recruitment of eosinophils from the bone marrow to tissues, and clearance of parasite antigen. JF - Infection and immunity AU - Gopinath, R AU - Hanna, L E AU - Kumaraswami, V AU - Perumal, V AU - Kavitha, V AU - Vijayasekaran, V AU - Nutman, T B AD - Helminth Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. rgopinath@niaid.nih.gov Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 93 EP - 99 VL - 68 IS - 1 SN - 0019-9567, 0019-9567 KW - Chemokine CCL5 KW - 0 KW - Chemokines KW - Cytokines KW - Filaricides KW - Interleukin-5 KW - Diethylcarbamazine KW - V867Q8X3ZD KW - Index Medicus KW - Cytokines -- blood KW - Animals KW - Humans KW - Homeostasis KW - Diethylcarbamazine -- therapeutic use KW - Chemokine CCL5 -- blood KW - Filaricides -- therapeutic use KW - Cell Degranulation -- drug effects KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Flow Cytometry KW - Time Factors KW - Interleukin-5 -- blood KW - Male KW - Chemokines -- blood KW - Wuchereria bancrofti KW - Eosinophils -- physiology KW - Eosinophils -- drug effects KW - Elephantiasis, Filarial -- blood KW - Elephantiasis, Filarial -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70812232?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Perturbations+in+eosinophil+homeostasis+following+treatment+of+lymphatic+filariasis.&rft.au=Gopinath%2C+R%3BHanna%2C+L+E%3BKumaraswami%2C+V%3BPerumal%2C+V%3BKavitha%2C+V%3BVijayasekaran%2C+V%3BNutman%2C+T+B&rft.aulast=Gopinath&rft.aufirst=R&rft.date=2000-01-01&rft.volume=68&rft.issue=1&rft.spage=93&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 - 2000-01-11 N1 - Date created - 2000-01-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 1979 Jan;122(1):221-9 [570202] J Clin Invest. 1991 Oct;88(4):1418-21 [1918387] Am J Trop Med Hyg. 1979 Sep;28(5):860-3 [484767] J Exp Med. 1979 Dec 1;150(6):1456-71 [390086] J Immunol. 1981 Sep;127(3):1093-8 [7021674] Lab Invest. 1984 Jan;50(1):51-61 [6363816] J Exp Med. 1992 Dec 1;176(6):1489-95 [1281207] J Infect Dis. 1993 Jun;167(6):1396-400 [8501330] Am J Trop Med Hyg. 1993 Dec;49(6):804-11 [8279647] J Immunol Methods. 1993 Dec 3;166(2):183-90 [8288872] J Exp Med. 1994 Feb 1;179(2):703-8 [8294877] Am J Trop Med Hyg. 1994 Feb;50(2):206-9 [8116814] J Immunol. 1994 Sep 1;153(5):2153-60 [7519642] J Allergy Clin Immunol. 1994 Dec;94(6 Pt 2):1183-8 [7798558] Trans R Soc Trop Med Hyg. 1995 Jan-Feb;89(1):98-102 [7747322] Clin Exp Allergy. 1995 Aug;25(8):713-9 [7584682] Parasitol Res. 1995;81(5):398-402 [7501639] J Infect Dis. 1996 May;173(5):1277-80 [8627086] J Allergy Clin Immunol. 1996 Jun;97(6):1272-8 [8648023] Scand J Immunol. 1996 Sep;44(3):229-38 [8795716] Clin Exp Immunol. 1996 Dec;106(3):462-7 [8973613] J Immunol. 1997 Feb 1;158(3):1332-44 [9013977] Acta Trop. 1996 Dec 16;62(3):171-82 [9025985] J Clin Invest. 1997 Mar 1;99(5):1064-71 [9062365] Int Arch Allergy Immunol. 1997 May-Jul;113(1-3):206-8 [9130524] Br J Haematol. 1997 Aug;98(2):312-4 [9266926] Int Arch Allergy Immunol. 1997 Oct;114 Suppl 1:14-7 [9363918] Int Arch Allergy Immunol. 1997 Oct;114 Suppl 1:81-3 [9363934] Cytometry. 1997 Dec 15;30(6):313-6 [9440823] J Immunol. 1998 Jan 1;160(1):351-60 [9551991] Parasitol Res. 1998 Aug;84(8):607-15 [9747932] Tropenmed Parasitol. 1984 Sep;35(3):177-82 [6495386] Am J Trop Med Hyg. 1985 May;34(3):529-36 [4003668] Am J Trop Med Hyg. 1985 Jul;34(4):735-45 [4025686] JAMA. 1988 Jun 3;259(21):3150-3 [3285045] Science. 1989 Jul 21;245(4915):308-10 [2787531] J Immunol. 1990 Apr 15;144(8):3166-73 [2324497] J Immunol. 1990 May 15;144(10):3961-9 [2332637] J Exp Med. 1990 Jul 1;172(1):399-402 [2193099] J Infect Dis. 1979 Mar;139(3):343-7 [448186] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytochrome P4502E (CYP2E) in brain: constitutive expression, induction by ethanol and localization by fluorescence in situ hybridization. AN - 70811203; 10620320 AB - Cytochrome P4502E (P4502E), the major ethanol-inducible P450 metabolizes ethanol to acetaldehyde and bioactivates procarcinogens to ultimate carcinogens. Metabolism of ethanol to acetaldehyde in the brain could be deleterious since it can react with cytoskeletal proteins, forming adducts. In the present study, rats were administered ethanol chronically to evaluate its effect on chlorzoxazone hydroxylation in rat brain regions. Chlorzoxazone hydroxylation in brains from the treated rats was induced in hippocampus and cortex, downregulated in brainstem, and unchanged in cerebellum, striatum, and thalamus. The presence of functionally active P4502E was also seen in human brain regions obtained at autopsy from traffic accident victims. Northern blot analysis of rat and human brain poly(A)(+) RNA hybridized with cDNA to rat CYP2E1 revealed the constitutive presence of a corresponding transcript in rat and human brain. Localization of CYP2E by fluorescence in situ hybridization demonstrated the constitutive expression of CYP2E preferentially in the neuronal cells in rat and human brain. CYP2E expression was seen in neurons within the cerebral cortex, Purkinje and granule cell layers of cerebellum, granule cell layer of dentate gyrus, and pyramidal neurons of CA1, CA2, and CA3 subfields of hippocampus in both rat and human brain. The present studies demonstrate constitutive expression of P4502E1 in brain, its differential induction in rat brain regions by chronic ethanol treatment, and its topographic distribution in rat and human brain. Copyright 2000 Academic Press. JF - Archives of biochemistry and biophysics AU - Upadhya, S C AU - Tirumalai, P S AU - Boyd, M R AU - Mori, T AU - Ravindranath, V AD - Department of Neurochemistry, National Institute of Mental Health & Neurosciences, Hosur Road, Bangalore, 560 029, India. Y1 - 2000/01/01/ PY - 2000 DA - 2000 Jan 01 SP - 23 EP - 34 VL - 373 IS - 1 SN - 0003-9861, 0003-9861 KW - DNA Primers KW - 0 KW - RNA, Messenger KW - Ethanol KW - 3K9958V90M KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Chlorzoxazone KW - H0DE420U8G KW - Index Medicus KW - Animals KW - DNA Primers -- genetics KW - Ethanol -- pharmacology KW - Humans KW - Gene Expression KW - In Situ Hybridization, Fluorescence KW - Microsomes -- enzymology KW - Tissue Distribution KW - RNA, Messenger -- genetics KW - Hydroxylation KW - Rats KW - Base Sequence KW - RNA, Messenger -- metabolism KW - Enzyme Induction -- drug effects KW - Adult KW - Rats, Wistar KW - Middle Aged KW - Chlorzoxazone -- metabolism KW - Male KW - Female KW - Brain -- enzymology KW - Cytochrome P-450 CYP2E1 -- biosynthesis KW - Cytochrome P-450 CYP2E1 -- metabolism KW - Cytochrome P-450 CYP2E1 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70811203?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cytochrome+P4502E+%28CYP2E%29+in+brain%3A+constitutive+expression%2C+induction+by+ethanol+and+localization+by+fluorescence+in+situ+hybridization.&rft.au=Upadhya%2C+S+C%3BTirumalai%2C+P+S%3BBoyd%2C+M+R%3BMori%2C+T%3BRavindranath%2C+V&rft.aulast=Upadhya&rft.aufirst=S&rft.date=2000-01-01&rft.volume=373&rft.issue=1&rft.spage=23&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 - 2000-02-09 N1 - Date created - 2000-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular determinants of polyreactive antibody binding: HCDR3 and cyclic peptides. AN - 70809844; 10606966 AB - Human monoclonal antibody 63 (mAb63) is an IgM/lambda polyreactive antibody that binds to multiple self and non-self antigens. The molecular basis of polyreactivity is still unclear. The present study was initiated to prepare a recombinant Fab of mAb63 and use it to study the determinants involved in polyreactivity. The baculovirus system was employed to express large amounts of mAb63 Fab in Sf9 cells. Our experiments showed that infected Sf9 cells secreted a soluble 50-kD Fab heterodimer that bound to multiple self and non-self antigens. The antigen-binding activity of mAb63 Fab was inhibited by both homologous and heterologous antigens. To study in more detail the molecular determinants involved in polyreactivity, the heavy chain complementarity-determining region 3 (HCDR3), which is known to play a key role in the binding of monoreactive antibodies to antigens, was subjected to site-directed mutagenesis. A single substitution, alanine for arginine, at position 100A resulted in complete loss of antigen-binding activity. The 19 amino acids comprising the HCDR3 of mAb63 were then synthesized and a cyclic peptide prepared. The cyclic peptide showed the same antigen-binding pattern as the parental mAb63 and the recombinant mAb63 Fab. A five amino acid motif (RFLEW), present in the HCDR3 of mAb63, was found by searching the GenBank in three of 50 other human polyreactive antibodies, but in none of nearly 2500 human antibodies thought to be monoreactive. It is concluded that HCDR3 plays a major role in polyreactivity and that in some cases cyclic peptides comprising the HCDR3, by themselves, may be polyreactive. JF - Clinical and experimental immunology AU - Deng, Y J AU - Notkins, A L AD - Experimental Medicine Section, Oral Infection and Immunity Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD, USA. ydeng@yoda.nidr.nih.gov Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 69 EP - 76 VL - 119 IS - 1 SN - 0009-9104, 0009-9104 KW - Antibodies, Monoclonal KW - 0 KW - Complementarity Determining Regions KW - DNA Primers KW - Immunoglobulin Heavy Chains KW - Immunoglobulin Variable Region KW - Peptides, Cyclic KW - Recombinant Proteins KW - Index Medicus KW - Peptides, Cyclic -- genetics KW - Immunoglobulin Variable Region -- genetics KW - Animals KW - Spodoptera KW - Peptides, Cyclic -- metabolism KW - DNA Primers -- genetics KW - Humans KW - Peptides, Cyclic -- immunology KW - Amino Acid Sequence KW - Recombinant Proteins -- genetics KW - Immunoglobulin Heavy Chains -- metabolism KW - Immunoglobulin Heavy Chains -- genetics KW - Antibody Specificity KW - Baculoviridae -- genetics KW - Base Sequence KW - Amino Acid Motifs KW - Recombinant Proteins -- metabolism KW - Immunoglobulin Variable Region -- metabolism KW - In Vitro Techniques KW - Recombinant Proteins -- immunology KW - Molecular Sequence Data KW - Cell Line KW - Antibodies, Monoclonal -- metabolism KW - Antibodies, Monoclonal -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70809844?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+and+experimental+immunology&rft.atitle=Molecular+determinants+of+polyreactive+antibody+binding%3A+HCDR3+and+cyclic+peptides.&rft.au=Deng%2C+Y+J%3BNotkins%2C+A+L&rft.aulast=Deng&rft.aufirst=Y&rft.date=2000-01-01&rft.volume=119&rft.issue=1&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Clinical+and+experimental+immunology&rft.issn=00099104&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-07 N1 - Date created - 2000-02-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1974 Apr;71(4):1427-30 [4524646] Glycobiology. 1994 Aug;4(4):491-6 [7827411] N Engl J Med. 1983 Jul 28;309(4):217-20 [6866036] Nature. 1983 Jul 7-13;304(5921):73-6 [6346104] Eur J Immunol. 1995 Feb;25(2):579-86 [7533091] J Clin Immunol. 1994 Nov;14(6):375-81 [7883865] J Immunol. 1995 May 1;154(9):4526-35 [7722307] J Immunol. 1983 Nov;131(5):2267-72 [6631010] Science. 1986 Aug 15;233(4765):747-53 [2426778] Science. 1987 Apr 3;236(4797):77-81 [3105056] Science. 1987 Apr 3;236(4797):81-3 [3105057] J Exp Med. 1988 Dec 1;168(6):1979-92 [3264319] J Biol Chem. 1989 Jan 5;264(1):259-65 [2909518] Annu Rev Immunol. 1989;7:513-35 [2469441] J Immunol. 1989 Jun 1;142(11):4054-61 [2497188] J Immunol. 1989 Dec 1;143(11):3476-83 [2479680] J Exp Med. 1990 Jan 1;171(1):265-92 [2104919] J Biol Chem. 1991 Mar 15;266(8):5182-90 [2002053] Gene. 1991 Feb 15;98(2):177-83 [2016060] Science. 1991 Aug 16;253(5021):792-5 [1876837] J Immunol. 1991 Oct 1;147(7):2359-67 [1918968] Int Immunol. 1991 Sep;3(9):865-75 [1718404] J Exp Med. 1992 Apr 1;175(4):983-91 [1552291] Mol Immunol. 1992 Jul-Aug;29(7-8):847-56 [1378929] Biotechniques. 1992 Aug;13(2):186 [1389145] Mol Immunol. 1993 Jan;30(1):111-2 [8417370] Proc Natl Acad Sci U S A. 1993 May 15;90(10):4374-8 [7685100] J Immunol. 1993 Oct 1;151(7):3604-16 [8376796] Int Immunol. 1993 Dec;5(12):1523-33 [8312222] J Immunol. 1994 Jun 15;152(12):5988-96 [8207223] J Exp Med. 1994 Sep 1;180(3):885-95 [8064239] J Exp Med. 1994 Sep 1;180(3):925-32 [8064241] FEBS Lett. 1994 Nov 7;354(2):169-72 [7957919] J Biol Chem. 1994 Dec 30;269(52):32788-95 [7806501] J Biochem. 1995 Feb;117(2):452-7 [7608138] J Biol Chem. 1995 Jul 14;270(28):16660-5 [7542651] Clin Exp Immunol. 1995 Aug;101(2):383-6 [7648724] Lancet. 1995 Dec 23-30;346(8991-8992):1662-6 [8551823] J Immunol. 1996 Jul 15;157(2):739-49 [8752924] Proteins. 1996 May;25(1):130-3 [8727325] Eur J Immunol. 1996 Dec;26(12):2916-23 [8977286] Hum Antibodies Hybridomas. 1996;7(3):106-12 [9057058] Science. 1997 Jun 13;276(5319):1665-9 [9180069] J Comput Aided Mol Des. 1997 Sep;11(5):453-61 [9385549] Cell. 1997 Dec 12;91(6):799-809 [9413989] Eur J Immunol. 1998 Mar;28(3):989-94 [9541594] Int Immunol. 1998 Mar;10(3):341-6 [9576622] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serum dioxin level in relation to diabetes mellitus among Air Force veterans with background levels of exposure. AN - 70807572; 10615842 AB - Data from several epidemiologic studies suggest that exposure to unusually high amounts of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) increases the risk of diabetes mellitus, and experimental data suggest that the mechanism for this is decreased cellular glucose uptake. To investigate the dose-response relation more closely, we examined the association of serum dioxin level with prevalence of diabetes mellitus and with levels of serum insulin and glucose among 1,197 veterans in the Air Force Health Study who never had contact with dioxin-contaminated herbicides and whose serum dioxin level was within the range of background exposure typically seen in the United States ( or =5.2 ng/kg lipid) was 1.71 (95% confidence interval = 1.00-2.91). The association was slightly attenuated after adjustment for serum triglycerides. Whether adjustment for serum triglycerides was appropriate, however, cannot be determined with available data. The association of background-level dioxin exposure with the prevalence of diabetes in these data may well be due to reasons other than causality, although a causal contribution cannot be wholly dismissed. JF - Epidemiology (Cambridge, Mass.) AU - Longnecker, M P AU - Michalek, J E AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 44 EP - 48 VL - 11 IS - 1 SN - 1044-3983, 1044-3983 KW - Blood Glucose KW - 0 KW - Environmental Pollutants KW - Insulin KW - Polychlorinated Dibenzodioxins KW - Triglycerides KW - Index Medicus KW - Warfare KW - Triglycerides -- blood KW - Glucose Tolerance Test KW - Odds Ratio KW - Blood Glucose -- metabolism KW - Insulin -- blood KW - Humans KW - Gas Chromatography-Mass Spectrometry KW - Incidence KW - Middle Aged KW - United States -- epidemiology KW - Male KW - Occupational Diseases -- diagnosis KW - Occupational Diseases -- blood KW - Polychlorinated Dibenzodioxins -- adverse effects KW - Diabetes Mellitus -- chemically induced KW - Diabetes Mellitus -- epidemiology KW - Diabetes Mellitus -- diagnosis KW - Occupational Diseases -- chemically induced KW - Veterans KW - Military Personnel KW - Diabetes Mellitus -- blood KW - Occupational Exposure -- adverse effects KW - Polychlorinated Dibenzodioxins -- blood KW - Occupational Diseases -- epidemiology KW - Environmental Pollutants -- blood KW - Environmental Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70807572?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Serum+dioxin+level+in+relation+to+diabetes+mellitus+among+Air+Force+veterans+with+background+levels+of+exposure.&rft.au=Longnecker%2C+M+P%3BMichalek%2C+J+E&rft.aulast=Longnecker&rft.aufirst=M&rft.date=2000-01-01&rft.volume=11&rft.issue=1&rft.spage=44&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 - 2000-01-19 N1 - Date created - 2000-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Histone H1 is a specific repressor of core histone acetylation in chromatin. AN - 70805905; 10611231 AB - Although a link between histone acetylation and transcription has been established, it is not clear how acetylases function in the nucleus of the cell and how they access their targets in a chromatin fiber containing H1 and folded into a highly condensed structure. Here we show that the histone acetyltransferase (HAT) p300/CBP-associated factor (PCAF), either alone or in a nuclear complex, can readily acetylate oligonucleosomal substrates. The linker histones, H1 and H5, specifically inhibit the acetylation of mono- and oligonucleosomes and not that of free histones or histone-DNA mixtures. We demonstrate that the inhibition is due mainly to steric hindrance of H3 by the tails of linker histones and not to condensation of the chromatin fiber. Cellular PCAF, which is complexed with accessory proteins in a multiprotein complex, can overcome the linker histone repression. We suggest that linker histones hinder access of PCAF, and perhaps other HATs, to their target acetylation sites and that perturbation of the linker histone organization in chromatin is a prerequisite for efficient acetylation of the histone tails in nucleosomes. JF - Molecular and cellular biology AU - Herrera, J E AU - West, K L AU - Schiltz, R L AU - Nakatani, Y AU - Bustin, M AD - Protein Section, Laboratory of Molecular Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. herr@helix.nih.gov Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 523 EP - 529 VL - 20 IS - 2 SN - 0270-7306, 0270-7306 KW - Cell Cycle Proteins KW - 0 KW - Chromatin KW - Histones KW - Nucleosomes KW - Recombinant Proteins KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Acetyltransferases KW - EC 2.3.1.- KW - Histone Acetyltransferases KW - EC 2.3.1.48 KW - p300-CBP Transcription Factors KW - p300-CBP-associated factor KW - Micrococcal Nuclease KW - EC 3.1.31.1 KW - Index Medicus KW - Animals KW - DNA -- metabolism KW - Nucleosomes -- metabolism KW - Nucleosomes -- chemistry KW - Acetylation KW - Cattle KW - Chickens KW - Recombinant Proteins -- metabolism KW - Binding, Competitive KW - DNA -- genetics KW - Nucleosomes -- genetics KW - Micrococcal Nuclease -- metabolism KW - DNA -- chemistry KW - Molecular Conformation KW - Protein Structure, Tertiary KW - Recombinant Proteins -- antagonists & inhibitors KW - Histones -- deficiency KW - Cell Cycle Proteins -- antagonists & inhibitors KW - Chromatin -- metabolism KW - Cell Cycle Proteins -- genetics KW - Acetyltransferases -- metabolism KW - Histones -- metabolism KW - Chromatin -- chemistry KW - Histones -- chemistry KW - Acetyltransferases -- genetics KW - Chromatin -- genetics KW - Cell Cycle Proteins -- metabolism KW - Acetyltransferases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70805905?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Histone+H1+is+a+specific+repressor+of+core+histone+acetylation+in+chromatin.&rft.au=Herrera%2C+J+E%3BWest%2C+K+L%3BSchiltz%2C+R+L%3BNakatani%2C+Y%3BBustin%2C+M&rft.aulast=Herrera&rft.aufirst=J&rft.date=2000-01-01&rft.volume=20&rft.issue=2&rft.spage=523&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 - 2000-01-27 N1 - Date created - 2000-01-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1998 Dec 4;273(49):32388-92 [9829967] EMBO J. 1997 Apr 15;16(8):2096-107 [9155035] J Biol Chem. 1999 Jan 15;274(3):1189-92 [9880483] Genes Dev. 1997 Jul 1;11(13):1640-50 [9224714] J Biol Chem. 1997 Oct 24;272(43):27253-8 [9341171] J Biol Chem. 1997 Nov 7;272(45):28171-4 [9353261] Cell Mol Life Sci. 1998 Jan;54(1):6-20 [9487383] EMBO J. 1998 Mar 2;17(5):1454-66 [9482742] Genes Dev. 1998 Mar 1;12(5):599-606 [9499396] Genes Dev. 1998 Mar 1;12(5):627-39 [9499399] Genes Dev. 1998 Mar 1;12(5):640-53 [9499400] Nature. 1998 May 7;393(6680):88-91 [9590696] Cell. 1998 Jul 10;94(1):35-44 [9674425] J Biol Chem. 1998 Sep 18;273(38):24414-9 [9733731] Prog Nucleic Acid Res Mol Biol. 1998;61:379-422 [9752726] Annu Rev Biochem. 1998;67:545-79 [9759497] Biochemistry. 1998 Oct 20;37(42):14776-87 [9778352] Nucleic Acids Res. 1999 Feb 1;27(3):711-20 [9889264] Biochemistry. 1998 Dec 22;37(51):17637-41 [9922128] Trends Biochem Sci. 1999 Jan;24(1):4-7 [10087913] Methods Enzymol. 1999;304:675-96 [10372390] J Biol Chem. 1999 Aug 6;274(32):22563-8 [10428834] J Biol Chem. 1969 Oct 10;244(19):5291-4 [5344136] Nat New Biol. 1973 Oct 17;245(146):207-9 [4126973] Biochemistry. 1975 Jul;14(13):2915-20 [1148184] Proc Natl Acad Sci U S A. 1976 Feb;73(2):505-9 [1061151] Biochemistry. 1978 Dec 12;17(25):5524-31 [728412] J Biol Chem. 1979 Nov 25;254(22):11751-60 [500671] Nature. 1980 Dec 25;288(5792):675-9 [7453800] Eur J Biochem. 1981 Nov;120(2):371-7 [7318833] J Mol Biol. 1985 Sep 20;185(2):329-39 [4057250] EMBO J. 1986 Feb;5(2):293-300 [3011400] J Mol Biol. 1986 Feb 20;187(4):591-601 [3458926] Nucleic Acids Res. 1987 Feb 11;15(3):1081-96 [3822820] J Mol Biol. 1988 Oct 20;203(4):997-1007 [3210247] Biochemistry. 1989 Feb 7;28(3):958-63 [2713375] J Mol Biol. 1989 Apr 5;206(3):451-63 [2716057] Nucleic Acids Res. 1989 Jun 12;17(11):4275-91 [2740216] Methods Enzymol. 1989;170:3-14 [2770543] Biochem J. 1989 Oct 1;263(1):179-86 [2604693] Cell. 1990 Jan 12;60(1):73-83 [2295090] J Biol Chem. 1990 Mar 25;265(9):5150-6 [2318888] Exp Cell Res. 1991 Oct;196(2):337-45 [1893943] Science. 1991 Oct 11;254(5029):238-45 [1718039] Nucleic Acids Res. 1992 Jan 25;20(2):187-94 [1741245] Nucleic Acids Res. 1992 Jan 25;20(2):273-8 [1311071] Biochemistry. 1994 Feb 15;33(6):1300-10 [8312247] J Biol Chem. 1994 Jun 10;269(23):16284-9 [8206934] Annu Rev Biochem. 1994;63:265-97 [7979240] EMBO J. 1994 Dec 15;13(24):6031-40 [7813441] Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6364-8 [7603997] J Biol Chem. 1995 Oct 27;270(43):25359-62 [7592700] Semin Cell Biol. 1995 Aug;6(4):229-36 [8562915] Biochemistry. 1996 Apr 2;35(13):4009-15 [8672434] Nature. 1996 Jul 25;382(6589):319-24 [8684459] Nature. 1996 Sep 19;383(6597):269-72 [8805705] J Biol Chem. 1996 Oct 18;271(42):25742-5 [8824200] Crit Rev Eukaryot Gene Expr. 1996;6(2-3):149-88 [8855387] Bioessays. 1998 Aug;20(8):615-26 [9780836] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant human interleukin-10 fails to alter proinflammatory cytokine production or physiologic changes associated with the Jarisch-Herxheimer reaction. AN - 70803273; 10608768 AB - Interleukin (IL)-10 may have a role in the treatment of cytokine-associated inflammatory syndromes. The Jarisch-Herxheimer reaction (J-HR), which follows antibiotic treatment of Borrelia recurrentis infection, is a useful model of acute systemic inflammation associated with a cytokine surge and characteristic pathophysiologic changes. In a double-blind, placebo-controlled study, 49 Ethiopian men with B. recurrentis infection were randomized to receive a single intravenous bolus of either 25 microg/kg of recombinant human (rh) IL-10 or vehicle control shortly before receiving intramuscular penicillin. Patients were monitored for physiologic changes, and plasma samples were taken repeatedly for 24 h after treatment. rhIL-10 had no impact on changes in any of the physiologic parameters of J-HR, plasma cytokine levels, or the rate of spirochete clearance. A single intravenous bolus of 25 microgram/kg of rhIL-10 does not seem to have a useful role in the treatment of the J-HR associated with B. recurrentis infection. JF - The Journal of infectious diseases AU - Cooper, P J AU - Fekade, D AU - Remick, D G AU - Grint, P AU - Wherry, J AU - Griffin, G E AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0425, USA. pcooper@niaid.nih.gov Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 203 EP - 209 VL - 181 IS - 1 SN - 0022-1899, 0022-1899 KW - Anti-Bacterial Agents KW - 0 KW - Recombinant Proteins KW - Interleukin-10 KW - 130068-27-8 KW - Abridged Index Medicus KW - Index Medicus KW - Ethiopia KW - Shock, Septic -- drug therapy KW - Humans KW - Adult KW - Inflammation -- drug therapy KW - Adolescent KW - Recurrence KW - Recombinant Proteins -- therapeutic use KW - Male KW - Relapsing Fever -- drug therapy KW - Interleukin-10 -- therapeutic use KW - Anti-Bacterial Agents -- adverse effects KW - Fever -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70803273?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Recombinant+human+interleukin-10+fails+to+alter+proinflammatory+cytokine+production+or+physiologic+changes+associated+with+the+Jarisch-Herxheimer+reaction.&rft.au=Cooper%2C+P+J%3BFekade%2C+D%3BRemick%2C+D+G%3BGrint%2C+P%3BWherry%2C+J%3BGriffin%2C+G+E&rft.aulast=Cooper&rft.aufirst=P&rft.date=2000-01-01&rft.volume=181&rft.issue=1&rft.spage=203&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 - 2000-03-03 N1 - Date created - 2000-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Compound 48/80 activates mast cell phospholipase D via heterotrimeric GTP-binding proteins. AN - 70798688; 10604938 AB - Previous studies have indicated the presence of a cholera toxin-sensitive phospholipase D (PLD) in cultured RBL-2H3 mast cells that is synergistically activated via calcium, protein kinase C, and another unidentified signal. Here we identify a third potential signal for activation transduced by a pertussis toxin-sensitive trimeric GTP-binding protein, most likely via G(i2) or G(i3). Quercetin-treated RBL-2H3 cells in which expression of G(alphai2) and G(alphai3) is enhanced more than 7-fold respond to the G(i) stimulant compound 48/80 with the activation of PLD, a transient activation of phospholipase C, and enhanced membrane GTPase activity. The activation of PLD was blocked in pertussis toxin-treated cells and, as with other stimulants of PLD, was enhanced in cholera toxin-treated cells. The PLD response to compound 48/80 was only partially inhibited by calcium deprivation and inhibition of protein kinase C to indicate a component of the response that was independent of calcium, protein kinase C, and, presumably, phospholipase C. Based on these and other data, we hypothesized that betagamma-subunits, released from G(i2) or G(i3) by compound 48/80 or from G(s) by cholera toxin, provide an additional signal for the activation of PLD. Consistent with this hypothesis, recombinant G(beta2gamma2) subunits, but not G(alphai-3) subunits, at concentrations of 50 to 300 nM markedly synergized PLD activation by compound 48/80 in permeabilized RBL-2H3 cells. JF - The Journal of pharmacology and experimental therapeutics AU - Chahdi, A AU - Fraundorfer, P F AU - Beaven, M A AD - Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1760, USA. Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 122 EP - 130 VL - 292 IS - 1 SN - 0022-3565, 0022-3565 KW - Virulence Factors, Bordetella KW - 0 KW - p-Methoxy-N-methylphenethylamine KW - 4091-50-3 KW - Cholera Toxin KW - 9012-63-9 KW - Quercetin KW - 9IKM0I5T1E KW - Pertussis Toxin KW - EC 2.4.2.31 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Type C Phospholipases KW - EC 3.1.4.- KW - Phospholipase D KW - EC 3.1.4.4 KW - GTP Phosphohydrolases KW - EC 3.6.1.- KW - Heterotrimeric GTP-Binding Proteins KW - EC 3.6.5.1 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Drug Interactions KW - Electrophoresis KW - Calcium -- deficiency KW - Type C Phospholipases -- metabolism KW - Permeability KW - Blotting, Western KW - Protein Kinase C -- antagonists & inhibitors KW - Cells, Cultured KW - GTP Phosphohydrolases -- metabolism KW - Time Factors KW - Signal Transduction KW - Quercetin -- pharmacology KW - Phospholipase D -- metabolism KW - Cell Membrane -- enzymology KW - Cell Membrane -- drug effects KW - Mast Cells -- metabolism KW - Heterotrimeric GTP-Binding Proteins -- physiology KW - p-Methoxy-N-methylphenethylamine -- pharmacology KW - Mast Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70798688?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Compound+48%2F80+activates+mast+cell+phospholipase+D+via+heterotrimeric+GTP-binding+proteins.&rft.au=Chahdi%2C+A%3BFraundorfer%2C+P+F%3BBeaven%2C+M+A&rft.aulast=Chahdi&rft.aufirst=A&rft.date=2000-01-01&rft.volume=292&rft.issue=1&rft.spage=122&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 - 2000-01-27 N1 - Date created - 2000-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genotoxic markers among butadiene polymer workers in China. AN - 70798619; 10607734 AB - While 1,3-butadiene is carcinogenic in rodents, cancer causation in humans is less certain. We examined a spectrum of genotoxic outcomes in 41 butadiene polymer production workers and 38 non-exposed controls, in China, to explore the role of butadiene in human carcinogenesis. Because in vitro studies suggest that genetic polymorphisms in glutathione S-transferase enzymes influence genotoxic effects of butadiene, we also related genotoxicity to genetic polymorphisms in GSTT1 and GSTM1. Among butadiene-exposed workers, median air exposure was 2 p.p.m. (6 h time-weighted average), due largely to intermittent high level exposures. Compared with unexposed subjects, butadiene-exposed workers had greater levels of hemoglobin N-(2,3,4-trihydroxybutyl)valine (THBVal) adducts (P < 0.0001) and adduct levels tended to correlate, among butadiene-exposed workers, with air measures (P = 0.03). Butadiene-exposed workers did not differ, however, from unexposed workers with respect to frequency of uninduced or diepoxybutane-induced sister chromatid exchanges, aneuploidy as measured by fluorescence in situ hybridization of chromosomes 1, 7, 8 and 12, glycophorin A variants or lymphocyte hprt somatic mutation. Also among the exposed, greater THBVal levels were not associated with increases in uninduced sister chromatid exchanges, aneuploidy, glycophorin A or hprt mutations. Butadiene-exposed workers had greater lymphocyte (P = 0.002) and platelet counts (P = 0.07) and lymphocytes as a percentage of white blood cells were moderately correlated with greater THBVal levels (Spearman's phi = 0.32, P = 0.07). Among butadiene-exposed workers, neither GSTM1 nor GSTT1 genotype status predicted urinary mercapturic acid butanediol formation, THBVal adducts, uninduced sister chromatid exchanges, aneuploidy or mutations in the glycophorin A or hprt genes. Overall, the study demonstrated exposure to butadiene in these workers, by a variety of short-term and long-term measures, but did not show specific genotoxic effects, at the chromosomal or gene levels, related to that exposure. JF - Carcinogenesis AU - Hayes, R B AU - Zhang, L AU - Yin, S AU - Swenberg, J A AU - Xi, L AU - Wiencke, J AU - Bechtold, W E AU - Yao, M AU - Rothman, N AU - Haas, R AU - O'Neill, J P AU - Zhang, D AU - Wiemels, J AU - Dosemeci, M AU - Li, G AU - Smith, M T AD - Occupational Studies Branch, National Cancer Institute, Bethesda, MD, USA. hayesr@exchange.nih.gov Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 55 EP - 62 VL - 21 IS - 1 SN - 0143-3334, 0143-3334 KW - Biomarkers KW - 0 KW - Butadienes KW - Hemoglobins KW - Mutagens KW - N-(2,3,4-trihydroxybutyl)valine KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Valine KW - HG18B9YRS7 KW - Index Medicus KW - Hemoglobins -- metabolism KW - Sister Chromatid Exchange KW - Humans KW - Adult KW - Chromosome Aberrations KW - Valine -- analogs & derivatives KW - Glutathione Transferase -- genetics KW - Valine -- metabolism KW - Male KW - Female KW - Occupational Exposure KW - Butadienes -- toxicity KW - Mutagens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70798619?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genotoxic+markers+among+butadiene+polymer+workers+in+China.&rft.au=Hayes%2C+R+B%3BZhang%2C+L%3BYin%2C+S%3BSwenberg%2C+J+A%3BXi%2C+L%3BWiencke%2C+J%3BBechtold%2C+W+E%3BYao%2C+M%3BRothman%2C+N%3BHaas%2C+R%3BO%27Neill%2C+J+P%3BZhang%2C+D%3BWiemels%2C+J%3BDosemeci%2C+M%3BLi%2C+G%3BSmith%2C+M+T&rft.aulast=Hayes&rft.aufirst=R&rft.date=2000-01-01&rft.volume=21&rft.issue=1&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-18 N1 - Date created - 2000-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative chemopreventive mechanisms of green tea, black tea and selected polyphenol extracts measured by in vitro bioassays. AN - 70792022; 10607735 AB - Black tea extracts (hot aqueous, polyphenols and theaflavins) and green tea extracts (hot aqueous, polyphenols, epicatechin, epicatechin gallate, epigallocatechin and epigallocatechin gallate) were tested in nine standardized cell culture assays for comparative cancer chemopreventive properties. Most black and green tea extracts strongly inhibited neoplastic transformation in mouse mammary organ cultures, rat tracheal epithelial cells and human lung tumor epithelial cells. Nearly all tea fractions strongly inhibited benzo[a]pyrene adduct formation with human DNA. Induction of phase II enzymes, glutathione-S-transferase and quinone reductase, were enhanced by nearly all tea fractions, while glutathione was induced by only a few fractions. Ornithine decarboxylase activity was inhibited by nearly all the green tea fractions, but none of the black tea fractions. 12-O-tetradecanoylphorbol-13-acetate-induced free radicals were inhibited by most tea fractions. These results provide strong evidence of both anti-mutagenic, anti-proliferative and anti-neoplastic activities for both black and green tea extracts. Such anticancer mechanisms may well be responsible for the cancer preventive efficacies seen in both experimental and human studies. JF - Carcinogenesis AU - Steele, V E AU - Kelloff, G J AU - Balentine, D AU - Boone, C W AU - Mehta, R AU - Bagheri, D AU - Sigman, C C AU - Zhu, S AU - Sharma, S AD - Chemoprevention Branch, Division of Cancer Prevention, National Cancer Institute, NIH, Bethesda, MD 20892, USA. vsly@nih.gov Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 63 EP - 67 VL - 21 IS - 1 SN - 0143-3334, 0143-3334 KW - Anticarcinogenic Agents KW - 0 KW - Flavonoids KW - Free Radicals KW - Ornithine Decarboxylase Inhibitors KW - Phenols KW - Plant Extracts KW - Polymers KW - Polyphenols KW - Tea KW - NAD(P)H Dehydrogenase (Quinone) KW - EC 1.6.5.2 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Animals KW - Humans KW - Mice KW - NAD(P)H Dehydrogenase (Quinone) -- metabolism KW - Rats KW - Plant Extracts -- pharmacology KW - Rats, Inbred F344 KW - Tumor Cells, Cultured KW - Glutathione Transferase -- biosynthesis KW - Male KW - Polymers -- pharmacology KW - Phenols -- pharmacology KW - Anticarcinogenic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70792022?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparative+chemopreventive+mechanisms+of+green+tea%2C+black+tea+and+selected+polyphenol+extracts+measured+by+in+vitro+bioassays.&rft.au=Steele%2C+V+E%3BKelloff%2C+G+J%3BBalentine%2C+D%3BBoone%2C+C+W%3BMehta%2C+R%3BBagheri%2C+D%3BSigman%2C+C+C%3BZhu%2C+S%3BSharma%2C+S&rft.aulast=Steele&rft.aufirst=V&rft.date=2000-01-01&rft.volume=21&rft.issue=1&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-18 N1 - Date created - 2000-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuroprotective strategies in Parkinson's disease: protection against progressive nigral damage induced by free radicals. AN - 70617389; 16787846 AB - Brain undergoes neurodegeneration when excess free radicals overwhelm antioxidative defense systems during senescence, head trauma and/or neurotoxic insults. A site-specific accumulation of ferrous citrate-iron complexes in the substantia nigra dopaminergic neurons could lead to exaggerated dopamine turnover, dopamine auto-oxidation, free radical generation, and oxidant stress. Eventually, this iron-catalyzed dopamine auto-oxidation results in the accumulation of neuromelanin, a progressive loss of nigral neurons, and the development of Parkinson's disease when brain dopamine depletion is greater than 80%. Emerging evidence indicates that free radicals such as hydroxyl radicals ((.-)OH) and nitric oxide ((.-)NO) may play opposite role in cell and animal models of parkinsonism. (.-)OH is a cytotoxic oxidant whereas oNO is an atypical neuroprotective antioxidant. (.-)NO and S-nitrosoglutathione (GSNO) protect nigral neurons against oxidative stress caused by 1-methyl-4-phenylpyridinium (MPP(+)), dopamine, ferrous citrate, hemoglobin, sodium nitroprusside and peroxynitrite. MPP(+), the toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), increases the nigral uptake of iron complexes and dopamine overflow leading to the generation of (.-)OH, protein oxidation, lipid peroxidation, and associated retrograde degeneration. In addition to GSNO, MPP(+)-induced oxidative neurotoxicity can be prevented by antioxidants including selegiline, 7-nitroindazole, 17beta-estradiol, melatonin, alpha-phenyl-tert-butylnitrone and U78517F. Similar to selegiline, 7-nitroindazole is a MAO-B inhibitor, which blocks the bio-activation of MPTP and oxidative stress. Freshly prepared but not light exposed, (.-)NO-exhausted GSNO is about 100 times more potent than the classic antioxidant glutathione. Via S-nitrosylation, GSNO also inhibits proteolysis and cytotoxicity caused by caspases and HIV-1 protease. Furthermore, in addition to protection against serum deprivation stress, the induction of neuronal NOS1 in human cells increases tolerance to MPP(+)-induced neuro-toxicity since newly synthesized (.-)NO prevents apoptosis possibly through up-regulation of bcl-2 and down regulation of p66(shc). In conclusion, reactive oxygen species are unavoidable by-products of iron-catalyzed dopamine auto-oxidation, which can initiate lipid peroxidation, protein oxidation, DNA damage, and nigral loss, all of which can be prevented by endogenous and exogenous (.-)NO. Natural and man-made antioxidants can be employed as part of preventative or neuroprotective treatments in Parkinson's disease and perhaps dementia complexes as well. For achieving neuroprotection and neuro-rescue in early clinical parkinsonian stages, a cocktail therapy of multiple neuroprotective agents may be more effective than the current treatment with extremely high doses of a single antioxidative agent. JF - Neurotoxicity research AU - Chiueh, C C AU - Andoh, T AU - Lai, A R AU - Lai, E AU - Krishna, G AD - Unit on Neurodegeneration and Neuroprotection, Laboratory of Clinical Science, National Institute of Mental Health, NIH, Building 10, Room 3D-41, Bethesda, MD 20892-1264, USA. chiueh@helix.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 293 EP - 310 VL - 2 IS - 2-3 SN - 1029-8428, 1029-8428 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70617389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicity+research&rft.atitle=Neuroprotective+strategies+in+Parkinson%27s+disease%3A+protection+against+progressive+nigral+damage+induced+by+free+radicals.&rft.au=Chiueh%2C+C+C%3BAndoh%2C+T%3BLai%2C+A+R%3BLai%2C+E%3BKrishna%2C+G&rft.aulast=Chiueh&rft.aufirst=C&rft.date=2000-01-01&rft.volume=2&rft.issue=2-3&rft.spage=293&rft.isbn=&rft.btitle=&rft.title=Neurotoxicity+research&rft.issn=10298428&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2007-07-09 N1 - Date created - 2006-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA polymerase beta and mammalian base excision repair. AN - 70542605; 12760029 JF - Cold Spring Harbor symposia on quantitative biology AU - Wilson, S H AU - Sobol, R W AU - Beard, W A AU - Horton, J K AU - Prasad, R AU - Vande Berg, B J AD - Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 143 EP - 155 VL - 65 SN - 0091-7451, 0091-7451 KW - Mutagens KW - 0 KW - DNA Polymerase beta KW - EC 2.7.7.- KW - Index Medicus KW - Genotype KW - Animals KW - Mammals KW - Models, Molecular KW - Humans KW - Protein Conformation KW - DNA Repair -- genetics KW - DNA Polymerase beta -- genetics KW - DNA Polymerase beta -- chemistry KW - DNA Polymerase beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70542605?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cold+Spring+Harbor+symposia+on+quantitative+biology&rft.atitle=DNA+polymerase+beta+and+mammalian+base+excision+repair.&rft.au=Wilson%2C+S+H%3BSobol%2C+R+W%3BBeard%2C+W+A%3BHorton%2C+J+K%3BPrasad%2C+R%3BVande+Berg%2C+B+J&rft.aulast=Wilson&rft.aufirst=S&rft.date=2000-01-01&rft.volume=65&rft.issue=&rft.spage=143&rft.isbn=&rft.btitle=&rft.title=Cold+Spring+Harbor+symposia+on+quantitative+biology&rft.issn=00917451&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-18 N1 - Date created - 2003-05-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selection and expansion of T cell from untreated patients with CLL: source of cells for immune reconstitution? AN - 70535295; 12042041 AB - Lymphocyte-derived malignancies can be treated with combinations of drugs that efficiently eradicate normal and malignant lymphocytes. Lack of T lymphocytes after treatment of B lymphocyte CLL (B-CLL) makes the patients susceptible to serious infections and may limit the benefit of the therapy. The aim of the study was to purify and culture-expand normal T lymphocytes from B-CLL patients prior to therapy. These cells could be frozen and given to the patients in the lymphopenic period post-chemotherapy. T lymphocytes were isolated from the mononuclear cell apheresis products from five patients with previously untreated B-CLL. The apheresis products were red-cell depleted by density gradient centrifugation. B-lymphocyte purging was performed by incubating with MAbs to four different B-cell epitopes, followed by magnetic-bead depletion. One round of negative selection removed >90% of the B lymphocytes. The T-lymphocyte enriched cell suspension was cultured for 10/11 days in the presence of IL-2 and the anti-T cell receptor Ab OKT3. In addition, in some cultures anti-CD22 ricin immunotoxin was added. T cells from CLL patients expanded 4.7-21-fold over a 10/11 days culture interval. After culture, CLL cells could no longer be identified by flow cytometric evaluation. The cultured T lymphocytes were predominantly CD8(+), and were capable of lysing autologous CLL cells through a fas-dependent mechanism. Selection and expansion of T lymphocytes by this method may represent a strategy for enhancing immunity in the lymphopenic period following CLL treatment. JF - Cytotherapy AU - Husebekk, A AU - Fellowes, V AU - Read, E J AU - Williams, J AU - Petrus, M J AU - Gress, R E AU - Fowler, D H AD - Department of Transfusion Medicine, Clinical Center, National Cancer Institute/NIH, Bethesda, MD, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 187 EP - 193 VL - 2 IS - 3 SN - 1465-3249, 1465-3249 KW - Epitopes KW - 0 KW - Chromium KW - 0R0008Q3JB KW - Index Medicus KW - Cells, Cultured KW - CD8-Positive T-Lymphocytes -- metabolism KW - Humans KW - Chromium -- metabolism KW - Flow Cytometry KW - Time Factors KW - Immunophenotyping KW - Male KW - Cell Line KW - T-Lymphocytes -- cytology KW - Leukemia, Lymphocytic, Chronic, B-Cell -- blood KW - Leukemia, Lymphocytic, Chronic, B-Cell -- immunology KW - T-Lymphocytes -- physiology KW - Leukemia, Lymphocytic, Chronic, B-Cell -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70535295?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytotherapy&rft.atitle=Selection+and+expansion+of+T+cell+from+untreated+patients+with+CLL%3A+source+of+cells+for+immune+reconstitution%3F&rft.au=Husebekk%2C+A%3BFellowes%2C+V%3BRead%2C+E+J%3BWilliams%2C+J%3BPetrus%2C+M+J%3BGress%2C+R+E%3BFowler%2C+D+H&rft.aulast=Husebekk&rft.aufirst=A&rft.date=2000-01-01&rft.volume=2&rft.issue=3&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Cytotherapy&rft.issn=14653249&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-13 N1 - Date created - 2002-06-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidative DNA damage in liver of mice with different susceptibility to hepatocarcinogenesis. AN - 70494912; 11712422 AB - Susceptibility to spontaneous or chemically-induced liver tumors in mice has been demonstrated to be strain dependent, with the tumor development or promotion phase contributing most to variability. Since reactive oxygen species are thought to play a role in carcinogenesis, especially tumor promotion, we investigated steady-state levels of 8-hydroxy-2'-deoxyguanosine (8-oxo-dG) in hepatic DNA from age matched (7 months), untreated mice of three inbred strains, that differ significantly in their susceptibility to liver carcinogenesis. Male mice of strain C3H, highly sensitive to liver tumorigenesis, had significantly higher levels of hepatic 8-oxo-dG (3.3 SE 0.2 8-oxo-dG/10(5) dG) than resistant strains C57BL (2.1 SE 0.3/10(5) dG; p < 0.01) and A/JCr (2.5 SE 0.1/10(5) dG; p < 0.015). In contrast, levels of 8-oxo-dG in livers of female A/JCr mice (3.1 SE 0.3/10(5) dG) were higher than in those of C3H (2.2 SE 0.1/10(5) dG; p < 0.025) and C57BL females (2.5 SE 0.3/10(5) dG; p = NS). Male C3H livers presented significantly more 8-oxo-dG than those of C3H females (p < 0.002). These results suggest that steady-state levels of 8-oxo-dG may contribute to the inherent differences in susceptibility to hepatocarcinogenesis in inbred strains of mice, especially the high sensitivity of C3H males. JF - Roczniki Akademii Medycznej w Bialymstoku (1995) AU - Sipowicz, M A AU - Anderson, L M AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, FCRDC, Frederick, MD 21702, USA. Y1 - 2000 PY - 2000 DA - 2000 SP - 116 EP - 121 VL - 45 KW - 8-oxo-7-hydrodeoxyguanosine KW - 88847-89-6 KW - DNA KW - 9007-49-2 KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Sex Factors KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Oxidative Stress -- genetics KW - Mice KW - Carcinoma, Hepatocellular -- physiopathology KW - Species Specificity KW - Male KW - Female KW - Deoxyguanosine -- metabolism KW - DNA Damage -- physiology KW - Genetic Predisposition to Disease -- genetics KW - DNA -- metabolism KW - Liver -- metabolism KW - Liver Neoplasms -- physiopathology KW - Deoxyguanosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70494912?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Roczniki+Akademii+Medycznej+w+Bialymstoku+%281995%29&rft.atitle=Oxidative+DNA+damage+in+liver+of+mice+with+different+susceptibility+to+hepatocarcinogenesis.&rft.au=Sipowicz%2C+M+A%3BAnderson%2C+L+M%3BKasprzak%2C+K+S&rft.aulast=Sipowicz&rft.aufirst=M&rft.date=2000-01-01&rft.volume=45&rft.issue=&rft.spage=116&rft.isbn=&rft.btitle=&rft.title=Roczniki+Akademii+Medycznej+w+Bialymstoku+%281995%29&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-20 N1 - Date created - 2001-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Racial Differences in Self-Assessed Health: Biological or Social? T2 - American Sociological Association AN - 61745197; 2000S39692 AB - Previous research suggests that older African-Americans base their self-assessed health (SAH) on cultural factors, racial oppression, & health problems, while older Whites base their health on physical functioning. This paper investigates whether older African-American adults are more likely to report their health as fair or poor compared with White adults, & if the previous factors & race have a significant influence on fair or poor SAH. The sample consists of 13,666 African-Americans & Whites, ages 70 & over, from the 1984 Supplement on Aging & the 1995 Second Supplement on Aging. Three logistic regression models were run to consider each group separately & then combined. In model one, African-Americans who were less active & those who had a stroke or cerebrovascular disease were about two to three times more likely to report fair/poor health rather than good/better. In model two, Whites who were less active & those with difficulty eating were about two to three times more likely to report fair/poor health. In model three, after controls, African-Americans were 54% more likely to report fair/poor SAH compared with Whites. In conclusion, the previous factors decreased but did not explain away the significant racial effect on fair/poor SAH. JF - American Sociological Association AU - Rooks, Ronica Nicole Y1 - 2000///0, PY - 2000 DA - 0, 2000 KW - Whites KW - Black White Differences KW - Black Americans KW - Self Evaluation KW - Health Problems KW - Elderly KW - Health KW - proceeding KW - 0410: group interactions; social group identity & intergroup relations (groups based on race & ethnicity, age, & sexual orientation) KW - 2045: sociology of health and medicine; sociology of medicine & health care UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61745197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=American+Sociological+Association&rft.atitle=Racial+Differences+in+Self-Assessed+Health%3A+Biological+or+Social%3F&rft.au=Rooks%2C+Ronica+Nicole&rft.aulast=Rooks&rft.aufirst=Ronica&rft.date=2000-01-01&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=American+Sociological+Association&rft.issn=&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2009-03-10 N1 - Publication note - 2000 N1 - Last updated - 2016-09-28 ER - TY - JOUR T1 - Nature over Nurture: Temperament, Personality, and Life Span Development AN - 60389601; 200107185 AB - Temperaments are often regarded as biologically based psychological tendencies with intrinsic paths of development. It is argued that this definition applies to the personality traits of the five-factor model. Evidence for the endogenous nature of traits is summarized from studies of behavior genetics, parent-child relations, personality structure, animal personality, & the longitudinal stability of individual differences. New evidence for intrinsic maturation is offered from analyses of NEO Five-Factor Inventory scores for men & women age 14 & over in German, British, Spanish, Czech, & Turkish samples (N = 5,085). These data support strong conceptual links to child temperament despite modest empirical associations. The intrinsic maturation of personality is complemented by the culturally conditioned development of characteristic adaptations that express personality: interventions in human development are best addressed to these. 1 Table, 6 Figures, 95 References. [Copyright 2000 The American Psychological Association.] JF - Journal of Personality and Social Psychology AU - McCrae, Robert R AU - Costa, Paul T, Jr AU - Ostendorf, Fritz AU - Angleitner, Alois AU - Hrebickova AU - Avia, Maria D AU - Sanz, Jesus AU - Sanchez-Bernardos, Maria L AU - Kusdil, M Ersin AU - Woodfield, Ruth AU - Saunders, Peter R AU - Smith, Peter B AD - National Instit Aging Gerontology Research Center, Baltimore, MD e-mail:Jeffm@mvx.grc.nia.nih.gov Y1 - 2000/01// PY - 2000 DA - January 2000 SP - 173 EP - 186 VL - 78 IS - 1 SN - 0022-3514, 0022-3514 KW - Psychological Development KW - Czech Republic KW - Personality Traits KW - Spain KW - Federal Republic of Germany KW - Psychosocial Factors KW - Child Development KW - Turkey KW - United Kingdom KW - article KW - 1844: demography and human biology; human biology/sociobiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/60389601?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Personality+and+Social+Psychology&rft.atitle=Nature+over+Nurture%3A+Temperament%2C+Personality%2C+and+Life+Span+Development&rft.au=McCrae%2C+Robert+R%3BCosta%2C+Paul+T%2C+Jr%3BOstendorf%2C+Fritz%3BAngleitner%2C+Alois%3BHrebickova%3BAvia%2C+Maria+D%3BSanz%2C+Jesus%3BSanchez-Bernardos%2C+Maria+L%3BKusdil%2C+M+Ersin%3BWoodfield%2C+Ruth%3BSaunders%2C+Peter+R%3BSmith%2C+Peter+B&rft.aulast=McCrae&rft.aufirst=Robert&rft.date=2000-01-01&rft.volume=78&rft.issue=1&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Journal+of+Personality+and+Social+Psychology&rft.issn=00223514&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Last updated - 2016-09-28 N1 - CODEN - JPSPB2 N1 - SubjectsTermNotLitGenreText - Psychosocial Factors; Child Development; Personality Traits; Psychological Development; Federal Republic of Germany; United Kingdom; Spain; Czech Republic; Turkey ER - TY - JOUR T1 - Curved DNA in Promoter Sequences AN - 19799452; 8720595 AB - Sequence-dependent DNA curvature is known to play an important role in initiation of transcription of many genes.We compared the distribution of predicted intrinsic curvature of Escherichia coli and human promoter sequences with the distribution of curvature of randomly selected coding and non-coding fragments from these organisms.Different methods of curvature calculation were found to yield mostly similar overall tendencies of DNA curvature in all groups of sequences.According to all methods of calculation, E. coli promoters were found to be more curved than coding sequences from the same genome and random sequences with the same nucleotide composition.By contrast, the average curvature of human promoter sequences was only marginally greater than the average curvature of human coding sequences.Non-coding intron sequences were found to be the most curved of the human sequences examined.Based on these observations, we hypothesize about the role of DNA curvature in promoter sequences. JF - In Silico Biology AU - Gabrielian, Andrei E AU - Landsman, David AU - Bolshoy, Alexander AD - Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA Y1 - 2000 PY - 2000 DA - 2000 SP - 183 EP - 196 PB - IOS Press, Nieuwe Hemweg 6B VL - 1 IS - 4 SN - 1386-6338, 1386-6338 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - DNA curvature KW - bendability KW - sequence analysis KW - Genomes KW - Promoters KW - Nucleotide sequence KW - Escherichia coli KW - DNA KW - Introns KW - Transcription KW - W 30940:Products KW - N 14810:Methods KW - J 02450:Ecology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19799452?accountid=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=In+Silico+Biology&rft.atitle=Curved+DNA+in+Promoter+Sequences&rft.au=Gabrielian%2C+Andrei+E%3BLandsman%2C+David%3BBolshoy%2C+Alexander&rft.aulast=Gabrielian&rft.aufirst=Andrei&rft.date=2000-01-01&rft.volume=1&rft.issue=4&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=In+Silico+Biology&rft.issn=13866338&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-01-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Genomes; Promoters; Nucleotide sequence; Introns; DNA; Transcription; Escherichia coli ER - TY - JOUR T1 - Immunological Aspects of Acute Stroke: Therapeutic Implications AN - 19376964; 7478613 AB - Recent studies strongly suggest that cerebral ischaemia initiates a focal inflammatory response that results in significant secondary injury to brain tissue, thereby extending the ultimate size of a stroke. Factors involved in this cascade include the release of cytokines that cause a pro-inflammatory and prothrombotic state on cerebral vessel endothelium, the expression of leucocyte adhesion molecules, and the release of chemotactic factors allowing the migration of leucocytes into the area of injured brain tissue causing further damage. Animal studies have clearly demonstrated the detrimental effects of these inflammatory mediators in stroke models and additionally have shown dramatic reduction in infarct size using leucocyte adhesion modification and cytokine receptor blockade. The approach of modifying the effects of inflammatory cytokines and/or limiting leucocyte adhesion and migration into the region of injury holds great promise for identifying agents that will give significant neuronal protection following a stroke. JF - BioDrugs AU - DeGraba, T J AD - Head of the Clinical Stroke Research Unit, Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2000/01/01/ PY - 2000 DA - 2000 Jan 01 SP - 1 EP - 8 PB - Adis International Ltd., 41 Centorian Drive Private Bay 65901, Mairangi Bay Auckland 10 New Zealand, [mailto:sportsmed@adis.co.nz], [URL:http://www.adis.com] VL - 13 IS - 1 SN - 1173-8804, 1173-8804 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts KW - Immune function KW - Reviews on disease KW - Stroke, pathogenesis KW - Brain injury KW - Injuries KW - Leukocytes KW - Stroke KW - Brain KW - Ischemia KW - Immunological aspects KW - Inflammation KW - Leukocyte migration KW - Endothelium KW - Chemotactic factors KW - Cytokine receptors KW - Cytokines KW - Cell migration KW - F 06955:Immunomodulation & Immunopharmacology KW - W 30940:Products UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19376964?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BioDrugs&rft.atitle=Immunological+Aspects+of+Acute+Stroke%3A+Therapeutic+Implications&rft.au=DeGraba%2C+T+J&rft.aulast=DeGraba&rft.aufirst=T&rft.date=2000-01-01&rft.volume=13&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=BioDrugs&rft.issn=11738804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Brain injury; Injuries; Stroke; Leukocytes; Brain; Ischemia; Immunological aspects; Inflammation; Leukocyte migration; Chemotactic factors; Endothelium; Cytokine receptors; Cytokines; Cell migration ER - TY - JOUR T1 - Oral Consumption of Bitter Gourd and Tomato Prevents Lipid Peroxidation in Liver Associated with DMBA Induced Skin Carcinogenesis in Mice. AN - 1859396207; 12718665 AB - The protective role of two commonly consumed natural dietary items- bitter gourd and tomato against endogenous as well as 7,12- dimethylbenz(a)anthracene (DMBA) induced lipid peroxidation in the livers of mice was investigated. The rationale for such an approach is that lipid peroxidation has been suggested to play a key role in human cancer development. There was a sharp rise in lipid peroxidation (measured as thiobarbituric acid reactive substances formation) during skin carcinogenesis induced by DMBA in mice. Aqueous extracts of bitter gourd and tomato juice were found to be very potent inhibitors of lipid peroxidation both in normal and DMBA treated mice. Our observations support the hypothesis that natural combinations of phytochemicals present in the fruit juices exert cancer-protective effects via a decrease in lipid peroxidation. JF - Asian Pacific journal of cancer prevention : APJCP AU - De, Sarmishtha AU - Chakraborty, Jamuna AU - Das, Sukta AD - Dept. of Cancer Chemoprevention Chittaranjan National Cancer Institute, Calcutta- 7000 26, India. Y1 - 2000 PY - 2000 DA - 2000 SP - 203 EP - 206 VL - 1 IS - 3 SN - 1513-7368, 1513-7368 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859396207?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.atitle=Oral+Consumption+of+Bitter+Gourd+and+Tomato+Prevents+Lipid+Peroxidation+in+Liver+Associated+with+DMBA+Induced+Skin+Carcinogenesis+in+Mice.&rft.au=De%2C+Sarmishtha%3BChakraborty%2C+Jamuna%3BDas%2C+Sukta&rft.aulast=De&rft.aufirst=Sarmishtha&rft.date=2000-01-01&rft.volume=1&rft.issue=3&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.issn=15137368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2003-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specific Expansion of Protein Families in the Radioresistant Bacterium Deinococcus Radiodurans AN - 18388132; 5381994 AB - Computer analysis of the complete genome of Deinococcus radiodurans R1 reveals a number of protein families, which are over-represented in this organism, compared to most other bacteria with known genome sequences. These families include both previously characterized and uncharacterized proteins. Most of the families whose functions are known or could be predicted seem to be related to stress-response and elimination of damage products (cell-cleaning). The two most prominent family expansions are the Nudix (MutT) family of pyrophosphohydrolases and a previously unnoticed family of proteins related to Bacillus subtilis DinB that could possess a metal-dependent enzymatic activity whose exact nature remains to be determined. Several proteins of the expanded families, particularly the Nudix family, are fused to other domains and form multidomain proteins that are so far unique for Deinococcus. The domain composition of some of these proteins indicates that they could be involved in novel DNA-repair pathways. Such unique proteins are good targets for knockout and gene expression studies, which are aimed to shed light on the unusual features of this interesting 10.6pt bacterium. JF - Genetica AU - Makarova, K S AU - Aravind, L AU - Daly, MJ AU - Koonin, E V AD - National Center for Biotechnology Information National Library of Medicine, The National Institutes of Health, Bethesda, MD 20814, USA, makarova@ncbi.nlm.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 25 EP - 34 VL - 108 IS - 1 SN - 0016-6707, 0016-6707 KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - G 07320:Bacterial genetics KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18388132?accountid=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=Genetica&rft.atitle=Specific+Expansion+of+Protein+Families+in+the+Radioresistant+Bacterium+Deinococcus+Radiodurans&rft.au=Makarova%2C+K+S%3BAravind%2C+L%3BDaly%2C+MJ%3BKoonin%2C+E+V&rft.aulast=Makarova&rft.aufirst=K&rft.date=2000-01-01&rft.volume=108&rft.issue=1&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=Genetica&rft.issn=00166707&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The epidemiology of typhoid fever in the Dong Thap Province, Mekong Delta Region of Vietnam AN - 18213104; 5281557 AB - A population-based surveillance for typhoid fever was conducted in three rural communes of Dong Thap Province in southern Vietnam (population 28,329) for a 12-month-period starting on December 4, 1995. Cases of typhoid fever were detected by obtaining blood for culture from residents with fever greater than or equal to 3 days. Among 658 blood cultures, 56 (8.5%) were positive for Salmonella typhi with an overall incidence of 198 per 10 super(5) population per year. The peak occurrence was at the end of the dry season in March and April. The attack rate was highest among 5-9 year-olds (531/10 super(5)/year), and lowest in > 30 year-olds (39/10 super(5)/year). The attack rate was 358/10 super(5)/year in 2-4 year-olds. The isolation of S. typhi from blood cultures was highest (17.4%) in patients with 5 to 6 days of fever. Typhoid fever is highly endemic in Vietnam and is a significant disease in both preschool and school-aged children. JF - American Journal of Tropical Medicine and Hygiene AU - Lin, Feng-Ying C AU - Vo, AH AU - Phan, V B AU - Nguyen, TTT AU - Bryla, D AU - Tran, C T AU - Ha, B K AU - Dang, D T AU - Robbins, J B AD - National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA Y1 - 2000 PY - 2000 DA - 2000 SP - 644 EP - 648 VL - 62 IS - 5 SN - 0002-9637, 0002-9637 KW - Microbiology Abstracts B: Bacteriology KW - Epidemiology KW - Salmonella typhi KW - Children KW - Population dynamics KW - Typhoid fever KW - Vietnam KW - J 02846:Gastrointestinal tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18213104?accountid=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=American+Journal+of+Tropical+Medicine+and+Hygiene&rft.atitle=The+epidemiology+of+typhoid+fever+in+the+Dong+Thap+Province%2C+Mekong+Delta+Region+of+Vietnam&rft.au=Lin%2C+Feng-Ying+C%3BVo%2C+AH%3BPhan%2C+V+B%3BNguyen%2C+TTT%3BBryla%2C+D%3BTran%2C+C+T%3BHa%2C+B+K%3BDang%2C+D+T%3BRobbins%2C+J+B&rft.aulast=Lin&rft.aufirst=Feng-Ying&rft.date=2000-01-01&rft.volume=62&rft.issue=5&rft.spage=644&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Tropical+Medicine+and+Hygiene&rft.issn=00029637&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 - Salmonella typhi; Vietnam; Typhoid fever; Epidemiology; Population dynamics; Children ER - TY - JOUR T1 - Estimates of US children exposed to alcohol abuse and dependence in the family AN - 18162820; 4674946 AB - This study sought to provide direct estimates of the number of US children younger than 18 years who are exposed to alcohol abuse or alcohol dependence in the family. Data were derived from the National Longitudinal Alcohol Epidemiologic Survey. Approximately 1 in 4 children younger than 18 years in the United States is exposed to alcohol abuse or alcohol dependence in the family. There is a need for approaches that integrate systems of services to enhance the lives of these children. JF - American Journal of Public Health AU - Grant, B F AD - Division of Biometry and Epidemiology, Suite 514, National Institute on Alcohol Abuse and Alcoholism, MSC 7003, Bethesda, MD 20892-7003, USA, bgrant@willco.niaaa.nih.gov Y1 - 2000/01// PY - 2000 DA - Jan 2000 SP - 112 EP - 115 VL - 90 IS - 1 SN - 0090-0036, 0090-0036 KW - family studies KW - substance abuse KW - Risk Abstracts KW - Alcohol KW - USA KW - Epidemiology KW - Children KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18162820?accountid=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+Public+Health&rft.atitle=Estimates+of+US+children+exposed+to+alcohol+abuse+and+dependence+in+the+family&rft.au=Grant%2C+B+F&rft.aulast=Grant&rft.aufirst=B&rft.date=2000-01-01&rft.volume=90&rft.issue=1&rft.spage=112&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Public+Health&rft.issn=00900036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - USA; Alcohol; Children; Epidemiology ER - TY - JOUR T1 - Physical activity-related injuries in walkers and runners in the aerobics center longitudinal study AN - 18145737; 5154310 AB - OBJECTIVE: To examine the association between physical activity-related injuries and participation in walking versus running. DESIGN: Nested case- control study. SETTING: Cooper Clinic Preventive Medicine Center, Dallas. Texas. PARTICIPANTS: 5,327 men and women undergoing exams between 1987 and 1995 and completing follow-up health history questionnaires in 1990 or 1995. Participants were classified as those reporting regular participation in walking or jogging/running at baseline. Those reporting both or neither activity were excluded from the study (n = 1404). Cases (698 men, 169 women) were those reporting physical activity-related injuries requiring physician visits in the previous year on the follow-up questionnaire. Controls (2,358 men, 698 women) were randomly selected from the remaining population. MAIN OUTCOME MEASURES: Logistic regression was used to examine the risk of injury in walkers versus runners and risk of injury by exercise dose while considering age, body mass index, previous injury, and strength training. RESULTS: There was a significantly lower risk of injury for walkers compared with runners in young ( or = 45 years) men (OR = 0.64, 95% CI = 0.49-0.82), and a nonsignificantly lower risk among young (OR = 0.73, 95% CI = 0.39-1.37) and older women (OR = 0.72, 95% CI = 0.38-1.35). There was no effect of greater amounts of walking on injuries for either gender; however, there was a higher injury risk associated with running 15-30 min/day (OR = 1.36, 95% CI = 1.07- 1.73) and 30+ min/day (OR = 1.52, 95% CI = 1.14-2.04) compared with <15 min/day among men, but not among women. CONCLUSIONS: This low risk of musculoskeletal injury suggests that participation in walking can be safely recommended as a way to improve health and fitness. JF - Clinical Journal in Sports Medicine AU - Colbert, L H AU - Hootman, J M AU - Macera, CA AD - Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2000 PY - 2000 DA - 2000 SP - 259 EP - 263 VL - 10 IS - 4 SN - 1050-642X, 1050-642X KW - Physical Education Index KW - Aerobics KW - Injuries KW - Running KW - Walking KW - Exercise KW - Exercise (programs) KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18145737?accountid=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=Clinical+Journal+in+Sports+Medicine&rft.atitle=Physical+activity-related+injuries+in+walkers+and+runners+in+the+aerobics+center+longitudinal+study&rft.au=Colbert%2C+L+H%3BHootman%2C+J+M%3BMacera%2C+CA&rft.aulast=Colbert&rft.aufirst=L&rft.date=2000-01-01&rft.volume=10&rft.issue=4&rft.spage=259&rft.isbn=&rft.btitle=&rft.title=Clinical+Journal+in+Sports+Medicine&rft.issn=1050642X&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Exercise; Injuries; Aerobics; Walking; Running; Exercise (programs) ER - TY - JOUR T1 - Vaccinia as a vector for tumor-directed gene therapy: Biodistribution of a thymidine kinase-deleted mutant AN - 17908941; 5184592 AB - Tumor-directed gene therapy, such as "suicide gene" therapy, requires high levels of gene expression in a high percentage of tumor cells in vivo to be effective. Current vector strategies have been ineffective in achieving these goals. This report introduces the attenuated (thymidine kinase (TK)-negative) replication-competent vaccinia virus (VV) as a potential vector for tumor-directed gene therapy by studying the biodistribution of VV in animal tumor models. A TK-deleted recombinant VV (Western Reserve strain) expressing luciferase on a synthetic promoter was constructed. Luciferase activity was measured in vitro after transduction of a variety of human and murine tumor cell lines and in vivo after intraperitoneal (i.p.) delivery in C57BL/6 mice with 7-day i.p. tumors (10 super(6) MC-38 cells). Three other in vivo tumor models were examined for tumor-specific gene expression after intravenous delivery of VV (human melanoma in nude mice, adenocarcinoma liver metastasis in immunocompetent mice, and subcutaneous sarcoma in the rat). In addition, a replication-incompetent vaccinia (1 mu g of psoralen and ultraviolet light, 365 nm, 4 minutes) was tested in vitro and in vivo and compared with active virus. Luciferase activity in i.p. tumors at 4 days after i.p. injection of VV was >7000-fold higher than lung, >3000-fold higher than liver, and >250-fold higher than ovary. In addition, intravenous injection of VV resulted in markedly higher tumor luciferase activity compared with any other organ in every model tested (up to 188,000-fold higher than liver and 77,000-fold higher than lung). Inactivation of the virus resulted in negligible gene expression in vivo. In summary, VV has a high transduction efficiency in tumor cells with high levels of gene expression. The results suggest a selective in vivo replication of TK-deleted VV in tumor cells. Replication competent, TK-deleted VV appears to be an ideal vector for testing the in vivo delivery of toxic genes to tumor cells. JF - Cancer Gene Therapy AU - Puhlmann, M AU - Brown, C K AU - Gnant, M AU - Huang, J AU - Libutti, S K AU - Alexander, H R AU - Bartlett, D L AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA Y1 - 2000/01// PY - 2000 DA - Jan 2000 SP - 66 EP - 73 VL - 7 IS - 1 SN - 0929-1903, 0929-1903 KW - C57BL/6 mice KW - man KW - rats KW - nude mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Vaccinia virus KW - Gene therapy KW - Gene transfer KW - Liver KW - Thymidine kinase KW - Adenocarcinoma KW - Tumor cells KW - Melanoma KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17908941?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Gene+Therapy&rft.atitle=Vaccinia+as+a+vector+for+tumor-directed+gene+therapy%3A+Biodistribution+of+a+thymidine+kinase-deleted+mutant&rft.au=Puhlmann%2C+M%3BBrown%2C+C+K%3BGnant%2C+M%3BHuang%2C+J%3BLibutti%2C+S+K%3BAlexander%2C+H+R%3BBartlett%2C+D+L&rft.aulast=Puhlmann&rft.aufirst=M&rft.date=2000-01-01&rft.volume=7&rft.issue=1&rft.spage=66&rft.isbn=&rft.btitle=&rft.title=Cancer+Gene+Therapy&rft.issn=09291903&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vaccinia virus; Gene therapy; Gene transfer; Thymidine kinase; Expression vectors; Tumor cells; Melanoma; Adenocarcinoma; Liver ER - TY - JOUR T1 - Attenuating the growth of tumors by intratumoral administration of DNA encoding Pseudomonas exotoxin via cationic liposomes AN - 17906765; 5184595 AB - A gene therapy approach was taken to inhibit tumor growth by transfecting tumor cells with a plasmid encoding a truncated but active form of Pseudomonas exotoxin A (PE), using cationic lipids as the transfection reagent. Cells transfected with this plasmid express PE intracellularly and undergo apoptosis. Transfection was optimized in vitro using two cationic lipids, DOGS and DOSPER. A ratio of between 1:4 and 1:10 (wt/wt) was found to be optimal for DOSPER, and the ratio 1:4 was used for the in vivo study when a smaller injection volume was desired. Estimating the activity of the PE-encoding plasmid was done both directly, by counting cells in vitro after transfection, and by using a cytotoxicity assay, and indirectly, by cotransfecting the plasmid with a plasmid carrying a reporter beta -galactosidase gene and observing a reduction in beta -galactosidase activity with increasing amounts of the PE-encoding plasmid. The cotransfection method was found to be very sensitive, and showed transfection of cells even with 1-2 ng of the PE-encoding plasmid per 10 super(5) cells. Complexes of the PE-encoding plasmid together with cationic lipid were injected into tumor xenografts in athymic nude mice. The tumor growth of transfected tumors was attenuated compared with control untreated tumors or tumors transfected with a nontoxin-expressing vector. These results indicate the potential of such a treatment for attenuating solid tumor growth in vivo.. JF - Cancer Gene Therapy AU - Yerushalmi, N AU - Brinkmann, U AU - Brinkmann, E AU - Pai, L AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA Y1 - 2000/01// PY - 2000 DA - Jan 2000 SP - 91 EP - 96 VL - 7 IS - 1 SN - 0929-1903, 0929-1903 KW - nude mice KW - cationic lipids KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene therapy KW - Transfection KW - Reporter gene KW - Gene transfer KW - Lipids KW - Pseudomonas KW - Tumors KW - Plasmids KW - ^a-Galactosidase KW - Liposomes KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17906765?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Gene+Therapy&rft.atitle=Attenuating+the+growth+of+tumors+by+intratumoral+administration+of+DNA+encoding+Pseudomonas+exotoxin+via+cationic+liposomes&rft.au=Yerushalmi%2C+N%3BBrinkmann%2C+U%3BBrinkmann%2C+E%3BPai%2C+L%3BPastan%2C+I&rft.aulast=Yerushalmi&rft.aufirst=N&rft.date=2000-01-01&rft.volume=7&rft.issue=1&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Cancer+Gene+Therapy&rft.issn=09291903&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pseudomonas; Tumors; Liposomes; Gene therapy; Gene transfer; ^a-Galactosidase; Reporter gene; Plasmids; Transfection; Lipids ER - TY - JOUR T1 - Dose-response analyses of experimental cancer data AN - 17892283; 5855461 AB - Dose-response analysis provides a powerful tool to determine causality from experimental cancer data, estimate low-dose risk, and evaluate mechanistic hypotheses. However, the interpretation of cancer dose-response data can be influenced by how the dose and response terms are characterized. Using the poly-3 quantal response method to adjust for the extensive and early development of lethal lymphomas in butadiene-exposed mice provided a means of obtaining a better representation of dose-response relationships for late-developing tumors induced by this chemical. Fitting a Weibull model to survival-adjusted tumor data for chloroprene and butadiene indicated similar carcinogenic potencies for these chemicals in mice. In conjunction with the rodent toxicity and carcinogenicity studies conducted by the National Toxicology Program, toxicokinetic studies are performed to characterize relationships between exposure and tissue concentrations of parent compound and metabolites. A physiologically based pharmacokinetic model (PBPK) of butadiene dosimetry indicated that differences in carcinogenic response between rats and mice are not simply due to differences in tissue concentrations of epoxybutene, a mutagenic metabolic intermediate. Thus, factors beyond tissue dosimetry of this metabolite must be important in butadiene-induced carcinogenesis. A PBPK model for isoprene indicated that blood concentrations of isoprene epoxides are a better indicator of kidney cancer risk than are measurements of isoprene-exposure concentrations. An evaluation of dose-response relationships for cytotoxicity, regenerative hyperplasia, and tumor induction by trihalomethanes indicates that for this family of chemicals, cell proliferation is not a reliable predictor of tumor response. JF - Drug Metabolism Reviews AU - Melnick, R L AU - Kohn, M C AD - National Institute of Environmental Health Sciences, MD A3-06, P.O. Box 12233, Research Triangle Park, NC 27709, USA, melnickr@niehs.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 193 EP - 209 VL - 32 IS - 2 SN - 0360-2532, 0360-2532 KW - Toxicology Abstracts KW - Mathematical models KW - Carcinogenicity KW - Reviews KW - Dose-response effects KW - Carcinogens KW - Xenobiotics KW - Pharmacokinetics KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17892283?accountid=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=Drug+Metabolism+Reviews&rft.atitle=Dose-response+analyses+of+experimental+cancer+data&rft.au=Melnick%2C+R+L%3BKohn%2C+M+C&rft.aulast=Melnick&rft.aufirst=R&rft.date=2000-01-01&rft.volume=32&rft.issue=2&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=Drug+Metabolism+Reviews&rft.issn=03602532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Mathematical models; Carcinogenicity; Dose-response effects; Reviews; Xenobiotics; Carcinogens; Pharmacokinetics ER - TY - JOUR T1 - Laboratory animal tests and human cancer AN - 17891324; 5855460 AB - The use of the results of laboratory animal tests to predict human cancer is effective in identifying potential human carcinogens before human exposure, permitting measures to be taken to prevent that exposure, a foolproof way to prevent human cancer. The purported, and highly publicized, faults of these tests, when examined critically, are shown not to be significant. Most chemicals are not carcinogenic; only about 1 in 10 are truly carcinogenic. The high doses used to maximize sensitivity do not produce false positives. All human carcinogens are carcinogenic in laboratory animals, and almost all animal carcinogens for which there is human exposure, when analyzed by epidemiological studies, show responses that are not statistically different. Most carcinogens are not banned, some are regulated, but many are not. The claimed costs of these health regulations are typically overestimated, and often greatly overestimated. Using the results of laboratory animal studies is good science and good public health. JF - Drug Metabolism Reviews AU - Rall, D P AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA Y1 - 2000 PY - 2000 DA - 2000 SP - 119 EP - 128 VL - 32 IS - 2 SN - 0360-2532, 0360-2532 KW - man KW - Toxicology Abstracts KW - Animals KW - Reviews KW - Dosage KW - Carcinogens KW - Toxicity testing KW - Cancer KW - Public health KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17891324?accountid=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=Drug+Metabolism+Reviews&rft.atitle=Laboratory+animal+tests+and+human+cancer&rft.au=Rall%2C+D+P&rft.aulast=Rall&rft.aufirst=D&rft.date=2000-01-01&rft.volume=32&rft.issue=2&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Drug+Metabolism+Reviews&rft.issn=03602532&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 - Carcinogens; Public health; Dosage; Reviews; Toxicity testing; Cancer; Animals ER - TY - JOUR T1 - Using the NTP database to assess the value of rodent carcinogenicity studies for determining human cancer risk AN - 17891274; 5855455 AB - The large database of carcinogenicity results generated by the National Toxicology Program (NTP) provides a unique opportunity to critically evaluate important scientific issues such as (1) the frequency of positive outcomes, (2) the interspecies correlation in carcinogenic response between rats and mice, (3) the correlation between body weight and tumor incidence, (4) estimates of the false-positive and false-negative rates, and (5) the frequency of decreasing tumor incidences. Such database evaluations enable us to better understand the value and limitations of rodent carcinogenicity studies for determining human cancer risk. However, as the NTP database becomes increasingly accessible to the general scientific community, there is also increased opportunity for misuse of the database. This article reexamines and updates previous database evaluations, presents four scientific principles that should be employed by anyone attempting to use this database, and illustrates how failure to apply these principles can lead to misleading results. JF - Drug Metabolism Reviews AU - Haseman, J K AD - National Institute of Environmental Health Sciences, Biostatistics Branch, Mail Drop A3-03, P.O. Box 12233, Research Triangle Park, North Carolina 27709, USA Y1 - 2000 PY - 2000 DA - 2000 SP - 169 EP - 186 VL - 32 IS - 2 SN - 0360-2532, 0360-2532 KW - man KW - Toxicology Abstracts KW - Risk assessment KW - Animals KW - Databases KW - Carcinogenicity KW - Cancer KW - Toxicology KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17891274?accountid=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=Drug+Metabolism+Reviews&rft.atitle=Using+the+NTP+database+to+assess+the+value+of+rodent+carcinogenicity+studies+for+determining+human+cancer+risk&rft.au=Haseman%2C+J+K&rft.aulast=Haseman&rft.aufirst=J&rft.date=2000-01-01&rft.volume=32&rft.issue=2&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=Drug+Metabolism+Reviews&rft.issn=03602532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Risk assessment; Databases; Animals; Carcinogenicity; Toxicology; Cancer ER - TY - JOUR T1 - Doses in rodent cancer studies: Sorting fact from fiction AN - 17890808; 5855462 AB - The belief that rodent cancer bioassays predict for human cancers is a fundamental public health precept based on sound biological principles. Nonetheless, it is appropriate to periodically debate this point as scientific understanding of cancer causation advances. This presentation addresses one of the many factors that determines the predictive value of rodent tumor bioassay results for human health. This is the issue of dose. Examination of several recent National Toxicology Program (NTP) studies demonstrates that the applied dose often far overestimates the actual effective dose, or maximum blood concentration attained in a rodent, when compared with similar relationships in humans. Further examination of the NTP database on rodent toxicity and carcinogenicity studies revealed summary information on factors that were pivotal in prechronic studies for selecting doses for chronic studies. Contrary to popular belief, target organ toxicity was a determining factor in only about half of the studies. The typically minimal nature of the lesions which limit doses for chronic studies is described for several common target sites. Taken together, these facts paint a far different picture than the common public perception of the "massive" doses used in chronic rodent studies and suggest that, in some cases, dose limitations are actually so severe as to limit the sensitivity of a chronic bioassay to detect a carcinogenic effect. JF - Drug Metabolism Reviews AU - Bucher, J R AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA Y1 - 2000 PY - 2000 DA - 2000 SP - 153 EP - 163 VL - 32 IS - 2 SN - 0360-2532, 0360-2532 KW - rats KW - mice KW - Toxicology Abstracts KW - Carcinogenicity KW - Reviews KW - Dosage KW - Tumors KW - Toxicity testing KW - Cancer KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17890808?accountid=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=Drug+Metabolism+Reviews&rft.atitle=Doses+in+rodent+cancer+studies%3A+Sorting+fact+from+fiction&rft.au=Bucher%2C+J+R&rft.aulast=Bucher&rft.aufirst=J&rft.date=2000-01-01&rft.volume=32&rft.issue=2&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Drug+Metabolism+Reviews&rft.issn=03602532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Dosage; Cancer; Carcinogenicity; Tumors; Toxicity testing ER - TY - JOUR T1 - The use of a rapid ELISPOT assay to analyze peptide-specific immune responses in carcinoma patients to peptide vs. recombinant poxvirus vaccines AN - 17867295; 5110888 AB - An enzyme-linked immunosorbent spot (ELISPOT) assay for interferon gamma production has been used to analyze specific T cell responses to a Flu 9-mer peptide, and a 9-mer peptide of carcinoembryonic antigen (CEA). Assays were performed on peripheral blood mononuclear cells (PBMC) of HLA-A2-positive patients with CEA-expressing carcinomas, both before and after vaccination with CEA-based vaccines, and from HLA-A2-positive healthy blood donors. The ELISPOT assay utilized aliquots of frozen PBMC, and assays were performed after 24 h in culture with peptide to rule out any artifacts due to long-term in vitro stimulation cycles. An internal standard was used for each assay to define reproducibility of the assay, and all samples from a given patient (pre- and post-vaccination, with both the Flu and CEA peptides) were analyzed simultaneously. The results indicated a trend towards healthy blood donors having higher levels of Flu-specific T cell precursors than do colon carcinoma patients, but these results were not statistically significant (P = 0.06). On the other hand, slightly higher CEA-specific T cell responses were observed in cancer patients with CEA-expressing carcinomas than in healthy blood donors. PBMC from two CEA-based vaccine clinical trials were analyzed for T cell responses to the same CEA peptide and to the Flu control peptide. The first trial consisted of three monthly vaccinations of CEA peptide (designated PPP) in adjuvant. The second trial consisted of cohorts receiving three monthly vaccinations of avipox-CEA recombinant (designated AAA) or cohorts receiving a primary vaccination with recombinant vaccinia-CEA followed by two monthly vaccinations with avipox-CEA (designated VAA). Few, if any, CEA-specific T cell responses were seen in the PPP vaccinations, while the majority of patients receiving the poxvirus CEA recombinants demonstrated increases in CEA-specific T cell responses and no increases in Flu-specific responses. CEA-specific IgG responses were also demonstrated in patients following recombinant CEA poxvirus vaccinations. Statistical analyses of the T cell responses to the same CEA peptide demonstrated a P value of 0.028 for the recombinant poxvirus vaccines, as compared with the peptide vaccine. There were no differences seen (P = 0.37) in Flu-specific responses after these two types of CEA vaccination. These results thus provide the first evidence that poxvirus recombinant-based vaccines are more potent in the initiation of tumor-antigen-specific T cell responses than vaccines employing peptide in adjuvant, when assays are conducted in an identical manner, and in defining responses to the same peptide. These results also demonstrate for the first time that an ELISPOT assay, performed over a 24-h period and without in vitro sensitization, can be successfully used to monitor immune responses to a tumor-associated antigen in cancer patients. JF - Cancer Immunology, Immunotherapy AU - Arlen, P AU - Tsang, Kwong-Yok AU - Marshall, J L AU - Chen, A AU - Steinberg, S M AU - Poole, D AU - Hand, PH AU - Schlom, J AU - Hamilton, J M AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892-1750, USA Y1 - 2000 PY - 2000 DA - 2000 SP - 517 EP - 529 VL - 49 IS - 10 SN - 0340-7004, 0340-7004 KW - man KW - Poxvirus KW - carcinoembryonic antigen KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Enzyme-linked immunosorbent assay KW - Immunotherapy KW - Adjuvants KW - Carcinoma KW - Recombinants KW - Lymphocytes T KW - Cancer patients KW - Immune response KW - Vaccines KW - Immunoassays KW - W3 33240:Immunology KW - F 06723:Other labelling methods KW - V 22091:Immunological techniques & reagents KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17867295?accountid=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+Immunology%2C+Immunotherapy&rft.atitle=The+use+of+a+rapid+ELISPOT+assay+to+analyze+peptide-specific+immune+responses+in+carcinoma+patients+to+peptide+vs.+recombinant+poxvirus+vaccines&rft.au=Arlen%2C+P%3BTsang%2C+Kwong-Yok%3BMarshall%2C+J+L%3BChen%2C+A%3BSteinberg%2C+S+M%3BPoole%2C+D%3BHand%2C+PH%3BSchlom%2C+J%3BHamilton%2C+J+M&rft.aulast=Arlen&rft.aufirst=P&rft.date=2000-01-01&rft.volume=49&rft.issue=10&rft.spage=517&rft.isbn=&rft.btitle=&rft.title=Cancer+Immunology%2C+Immunotherapy&rft.issn=03407004&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 - Poxvirus; Vaccines; Cancer patients; Enzyme-linked immunosorbent assay; Immunotherapy; Immunoassays; Adjuvants; Recombinants; Immune response; Lymphocytes T; Carcinoma ER - TY - JOUR T1 - N-acetyl-L-Cysteine Simultaneously Increases Mitogenesis and Suppresses Apoptosis in Mitogen-Stimulated B-Lymphocytes from p53 Haploinsufficient Tg.AC (v-Ha-ras) Mice AN - 17866227; 5109140 AB - Recent epidemiological evidence suggests that antioxidants may enhance carcinogenesis by promoting cellular proliferation and/or impeding programmed cell death. We examined the effect of N-acetyl-L-cysteine (NAC) on mitogenesis and apoptosis in splenocytes from p53 haploinsufficient Tg.AC (v-Ha-ras) mice. This model contains genetic lesions found frequently in human cancer and is predisposed to develop carcinogen-induced cancer. Splenocytes were incubated with NAC alone or with the B- and T-cell-specific mitogens Concanavalin A (Con A) and E. coli lipopolysaccharide (LPS), respectively. Mitogenesis increased 17-fold in mitogen-stimulated cultures and 10-fold in cultures incubated with NAC alone. Co-incubation with both NAC (1000 mu g/mL) and mitogen increased mitogenesis by 33-fold without changing apoptosis rates. Strikingly, incubation with NAC and LPS attenuated LPS-induced apoptosis. Mitogen alone did not affect GSH levels but NAC-induced increases were significantly depleted by co-incubation with mitogen. Furthermore, NAC increased the number of CD45R super(+) B cells, but decreased CD3 super(+) T cells showing enhanced survival of B cells under these conditions. These results demonstrate concurrent reduced apoptosis and increased mitogenesis in B lymphocytes that may favor clonal selection of preneoplastic cells. JF - In Vitro & Molecular Toxicology AU - Martin, K R AU - Kari, F W AU - Barrett, J C AU - French, JE AD - Laboratory of Environmental Carcinogenesis & Mutagenesis, NIEHS/NIH, 111 T.W. Alexander Drive, P.O. Box 12233; MD F1-05, USA, french@niehs.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 237 EP - 247 VL - 13 IS - 4 SN - 1097-9336, 1097-9336 KW - mice KW - N-Acetyl-L-cysteine KW - Toxicology Abstracts KW - Apoptosis KW - Antioxidants KW - Lymphocytes B KW - Carcinogenesis KW - Mitogens KW - Cell proliferation KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17866227?accountid=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=In+Vitro+%26+Molecular+Toxicology&rft.atitle=N-acetyl-L-Cysteine+Simultaneously+Increases+Mitogenesis+and+Suppresses+Apoptosis+in+Mitogen-Stimulated+B-Lymphocytes+from+p53+Haploinsufficient+Tg.AC+%28v-Ha-ras%29+Mice&rft.au=Martin%2C+K+R%3BKari%2C+F+W%3BBarrett%2C+J+C%3BFrench%2C+JE&rft.aulast=Martin&rft.aufirst=K&rft.date=2000-01-01&rft.volume=13&rft.issue=4&rft.spage=237&rft.isbn=&rft.btitle=&rft.title=In+Vitro+%26+Molecular+Toxicology&rft.issn=10979336&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 - Antioxidants; Carcinogenesis; Cell proliferation; Apoptosis; Mitogens; Lymphocytes B ER - TY - JOUR T1 - Recovery of mouse endostatin produced by Pichia pastoris using expanded bed adsorption AN - 17864741; 5107894 AB - Endostatin, a 20 KDa fragment of collagen XVIII, was shown to have an inhibitory effect on angiogenesis and can potentially be used as a tumor growth suppressor. To obtain the amount needed for testing, the protein was successfully cloned and expressed in Pichia pastoris. At the end of the fermentation process, the concentration of the endostatin in the culture was 50 mg per liter, accompanied by 400 gr per liter (wet weight) of biomass. Before the protein can be captured and purified on a packed bed of heparin-Sepharose, the biomass must be removed. Because of the high biomass concentration, conventional biomass removal techniques like centrifugation or filtration are inefficient and cumbersome. Therefore, the expanded-bed adsorption technique was chosen as an alternative approach. An efficient procedure for the initial recovery and purification of the endostatin was developed. The process utilized a cation- exchanger resin instead of a heparin-based affinity resin, because its dynamic capacity was higher, even though it was affected by the high linear flow on the expanded bed. After adjusting the conductivity, pH and biomass concentration, the complete broth was pumped directly on the expanded-bed matrix (Streamline SP XL). Though the yields of protein are similar, the expanded-bed approach is superior to the packed-bed method for several reasons. The expanded-bed process was shorter (only 8 hours compared to 16 hours for the packed bed), it is cheaper, and the product has higher specific activity (29% compared with 18%). Endostatin produced by the expanded-bed adsorption method showed the expected bioactivity and is currently being tested for its potential as a tumor suppressor. JF - Bioseparation AU - Trinh, L AU - Noronha, S B AU - Fannon, M AU - Shiloach, J AD - Biotechnology Unit, NIH, NIDDK, Bethesda, MD 20892, USA Y1 - 2000 PY - 2000 DA - 2000 SP - 223 EP - 230 VL - 9 IS - 4 SN - 0923-179X, 0923-179X KW - mice KW - recovery KW - endostatin KW - Biotechnology and Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts KW - Centrifugation KW - Filtration KW - Fermentation KW - Angiogenesis KW - Adsorption KW - Biomass KW - Pichia pastoris KW - pH effects KW - W2 32340:Other peptides, proteins, amino acids KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17864741?accountid=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=Bioseparation&rft.atitle=Recovery+of+mouse+endostatin+produced+by+Pichia+pastoris+using+expanded+bed+adsorption&rft.au=Trinh%2C+L%3BNoronha%2C+S+B%3BFannon%2C+M%3BShiloach%2C+J&rft.aulast=Trinh&rft.aufirst=L&rft.date=2000-01-01&rft.volume=9&rft.issue=4&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=Bioseparation&rft.issn=0923179X&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 - Pichia pastoris; Adsorption; Angiogenesis; Biomass; pH effects; Fermentation; Centrifugation; Filtration ER - TY - JOUR T1 - How many genes can make a cell: The minimal-gene-set concept AN - 17768001; 4825798 AB - Several theoretical and experimental studies have endeavored to derive the minimal set of genes that are necessary and sufficient to sustain a functioning cell under ideal conditions, that is, in the presence of unlimited amounts of all essential nutrients and in the absence of any adverse factors, including competition. A comparison of the first two completed bacterial genomes, those of the parasites Haemophilus influenzae and Mycoplasma genitalium, produced a version of the minimal gene set consisting of similar to 250 genes. Very similar estimates were obtained by analyzing viable gene knockouts in Bacillus subtilis, M. genitalium, and Mycoplasma pneumoniae. With the accumulation and comparison of multiple complete genome sequences, it became clear that only similar to 80 genes of the 250 in the original minimal gene set are represented by orthologs in all life forms. For similar to 15% of the genes from the minimal gene set, viable knockouts were obtained in M. genitalium; unexpectedly, these included even some of the universal genes. Thus, some of the genes that were included in the first version of the minimal gene set, based on a limited genome comparison, could be, in fact, dispensable. The majority of these genes, however, are likely to encode essential functions but, in the course of evolution, are subject to nonorthologous gene displacement, that is, recruitment of unrelated or distantly related proteins for the same function. Further theoretical and experimental studies within the framework of the minimal-gene-set concept and the ultimate construction of a minimal genome are expected to advance our understanding of the basic principles of cell functioning by systematically detecting nonorthologous gene displacement and deciphering the roles of essential but functionally uncharacterized genes. JF - Annual Review of Genomics & Human Genetics AU - Koonin, E V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA, koonin@ncbi.nlm.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 99 EP - 116 VL - 1 SN - 1527-8204, 1527-8204 KW - J1L KW - nonorthologous gene displacement KW - gene knockouts KW - minimal gene-set KW - minimial gene-set KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Genomes KW - Bacillus subtilis KW - Haemophilus influenzae KW - Cells KW - Reviews KW - Mycoplasma genitalium KW - Mycoplasma pneumoniae KW - Metabolism KW - G 07300:Theoretical genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17768001?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+Review+of+Genomics+%26+Human+Genetics&rft.atitle=How+many+genes+can+make+a+cell%3A+The+minimal-gene-set+concept&rft.au=Koonin%2C+E+V&rft.aulast=Koonin&rft.aufirst=E&rft.date=2000-01-01&rft.volume=1&rft.issue=&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Annual+Review+of+Genomics+%26+Human+Genetics&rft.issn=15278204&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 - Mycoplasma genitalium; Haemophilus influenzae; Bacillus subtilis; Mycoplasma pneumoniae; Genomes; Reviews; Metabolism; Cells ER - TY - JOUR T1 - Oral microbial communities: Biofilms, Interactions, and Genetic Systems AN - 17737196; 4790095 AB - Oral microbial-plaque communities are biofilms composed of numerous genetically distinct types of bacteria that live in close juxtaposition on host surfaces. These bacteria communicate through physical interactions called coaggregation and coadhesion, as well as other physiological and metabolic interactions. Streptococci and actinomyces are the major initial colonizers of the tooth surface, and the interactions between them and their substrata help establish the early biofilm community. Fusobacteria play a central role as physical bridges that mediate coaggregation of cells and as physiological bridges that promote anaerobic microenvironments which protect coaggregating strict anaerobes in an aerobic atmosphere. New technologies for investigating bacterial populations with 16S rDNA probes have uncovered previously uncultured bacteria and have offered an approach to in situ examination of the spatial arrangement of the participant cells in oral-plaque biofilms. Flow cells with saliva-coated surfaces are particularly useful for studies of biofilm formation and observation. The predicted sequential nature of colonization of the tooth surface by members of different genera can be investigated by using these new technologies and imaging the cells in situ with confocal scanning laser microscopy. Members of at least seven genera now can be subjected to genetic studies owing to the discovery of gene-transfer systems in these genera. Identification of contact-inducible genes in streptococci offers an avenue to explore bacterial responses to their environment and leads the way toward understanding communication among inhabitants of a multispecies biofilm. JF - Annual Review of Microbiology AU - Kolenbrander, P E AD - Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA, pkolenbrander@dir.nidcr.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 413 EP - 437 VL - 54 SN - 0066-4227, 0066-4227 KW - streptococci KW - Microbiology Abstracts B: Bacteriology KW - Streptococcus KW - Colonization KW - Cell aggregation KW - Oral microflora KW - DNA probes KW - Microscopy KW - Fusobacterium KW - Population studies KW - Saliva KW - Biofilms KW - rRNA 16S KW - J 02841:Microflora KW - J 02710:Identification, taxonomy and typing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17737196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+Review+of+Microbiology&rft.atitle=Oral+microbial+communities%3A+Biofilms%2C+Interactions%2C+and+Genetic+Systems&rft.au=Kolenbrander%2C+P+E&rft.aulast=Kolenbrander&rft.aufirst=P&rft.date=2000-01-01&rft.volume=54&rft.issue=&rft.spage=413&rft.isbn=&rft.btitle=&rft.title=Annual+Review+of+Microbiology&rft.issn=00664227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus; Fusobacterium; Oral microflora; Biofilms; Cell aggregation; DNA probes; rRNA 16S; Saliva; Colonization; Microscopy; Population studies ER - TY - JOUR T1 - Roles of the glutathione- and thioredoxin-dependent reduction systems in the Escherichia coli and Saccharomyces cerevisiae responses to oxidative stress AN - 17721524; 4790096 AB - The glutathione- and thioredoxin-dependent reduction systems are responsible for maintaining the reduced environment of the Escherichia coli and Saccharomyces cerevisiae cytosol. Here we examine the roles of these two cellular reduction systems in the bacterial and yeast defenses against oxidative stress. The transcription of a subset of the genes encoding glutathione biosynthetic enzymes, glutathione reductases, glutaredoxins, thioredoxins, and thioredoxin reductases, as well as glutathione- and thioredoxin-dependent peroxidases is clearly induced by oxidative stress in both organisms. However, only some strains carrying mutations in single genes are hypersensitive to oxidants. This is due, in part, to the redundant effects of the gene products and the overlap between the two reduction systems. The construction of strains carrying mutations in multiple genes is helping to elucidate the different roles of glutathione and thioredoxin, and studies with such strains have recently revealed that these two reduction systems modulate the activities of the E. coli OxyR and SoxR and the S. cerevisiae Yap1p transcriptional regulators of the adaptive responses to oxidative stress. JF - Annual Review of Microbiology AU - Carmel-Harel, O AU - Storz, G AD - National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA, ornah@box-o.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 439 EP - 461 VL - 54 SN - 0066-4227, 0066-4227 KW - budding yeast KW - OxyR protein KW - SoxR protein KW - Yap1 protein KW - glutaredoxin KW - glutathione reductase KW - thioredoxin KW - thioredoxin reductase KW - thioredoxins KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Microbiology Abstracts B: Bacteriology KW - Reduction KW - Oxidative stress KW - Peroxidase KW - Escherichia coli KW - Transcription KW - Saccharomyces cerevisiae KW - K 03020:Fungi KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17721524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+Review+of+Microbiology&rft.atitle=Roles+of+the+glutathione-+and+thioredoxin-dependent+reduction+systems+in+the+Escherichia+coli+and+Saccharomyces+cerevisiae+responses+to+oxidative+stress&rft.au=Carmel-Harel%2C+O%3BStorz%2C+G&rft.aulast=Carmel-Harel&rft.aufirst=O&rft.date=2000-01-01&rft.volume=54&rft.issue=&rft.spage=439&rft.isbn=&rft.btitle=&rft.title=Annual+Review+of+Microbiology&rft.issn=00664227&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 - Saccharomyces cerevisiae; Escherichia coli; Reduction; Oxidative stress; Transcription; Peroxidase ER - TY - JOUR T1 - Enhancement of Tumor-specific Immune Response with Plasmid DNA Replicon Vectors AN - 17665290; 4730349 AB - To enhance the immunogenicity of nucleic acid vaccines, we used plasmid DNA vectors that contained replicons derived from the prototype alphavirus, Sindbis, and another alphavirus, Semliki Forest virus. When transfected into cells or injected directly into animal muscle, these plasmids launch a self-replicating RNA vector (replicon) which in turn directs the expression of a model tumor antigen. Immunization with plasmid DNA replicons elicited immune responses at doses 100 to 1000-fold lower than conventional DNA plasmids and effectively treated mice bearing an experimental tumor expressing the model antigen. Significantly, replicon-based DNA plasmids did not produce a greater quantity of antigen; instead, antigen production differed qualitatively. Plasmid DNA replicons mediated antigen production that was homogeneous in all transfected cells and associated with the apoptotic death of the host cells. Because of their safety and efficacy, plasmid DNA replicons may be useful in the development of recombinant vaccines for infectious diseases and cancer. JF - Cancer Research AU - Leitner, W W AU - Ying, H AU - Driver, DA AU - Dubensky, T W AU - Restifo, N P AD - National Cancer Institute, Building 10, Room 2B46, Bethesda, MD 20892-1502, USA, Wolfgang_Leitner@nih.gov Y1 - 2000/01// PY - 2000 DA - Jan 2000 SP - 51 EP - 55 VL - 60 IS - 1 SN - 0008-5472, 0008-5472 KW - mice KW - Semliki Forest virus KW - Sindbis virus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Infectious diseases KW - Vaccines KW - Plasmids KW - Cancer KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17665290?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Enhancement+of+Tumor-specific+Immune+Response+with+Plasmid+DNA+Replicon+Vectors&rft.au=Leitner%2C+W+W%3BYing%2C+H%3BDriver%2C+DA%3BDubensky%2C+T+W%3BRestifo%2C+N+P&rft.aulast=Leitner&rft.aufirst=W&rft.date=2000-01-01&rft.volume=60&rft.issue=1&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Expression vectors; Plasmids; Vaccines; Cancer; Infectious diseases ER - TY - JOUR T1 - beta -Carotene Fails to Act as a Tumor Promoter, Induces RAR Expression, and Prevents Carcinoma Formation in a Two-Stage Model of Skin Carcinogenesis in Male Sencar Mice AN - 17623593; 4766115 AB - Clinical trials have shown a significant increase in incidence of lung cancer among smokers and asbestos workers supplemented with beta -carotene, suggesting a tumor-promoting activity for this agent. We set out to test possible tumor-promoting and chemopreventive activities of dietary and topical beta -carotene in the two-stage 7,12-dimethylbenz[a]anthracene-12-O-tetradecanoylphorbol 13-acetate (TPA) model of mouse skin carcinogenesis. In the first study, the effects of three levels of dietary beta -carotene (6, 60, and 600 mu g/g purified diet containing no other retinoid or carotenoid) were assessed over a period of 42 weeks. Carcinoma yield was reduced by similar to 50% in the 600 mu g/g diet group (mean 0.22 carcinomas/mouse) compared with the 6 mu g/g diet group (mean 0.44 carcinomas/mouse, p = 0.003). The 60 mu g/g diet group showed a pattern of inhibition similar to the 600 mu g/g diet group. A protective effect (25% reduction) of beta -carotene (in the 600 mu g/g diet group) on papilloma formation was also found. However, the intermediate 60 mu g/g diet group showed the same incidence as the low 6 mu g/g diet group. This points to a lack of correlation between papilloma and carcinoma incidence, as we also found in previous work on dietary retinoids and carotenoids. The purpose of the second study was to assess whether topical beta -carotene (2 mu g) has tumor-promoting or chemopreventive activity in the two-stage protocol. In the absence of TPA, beta -carotene had no significant tumor-promoting activity. Instead, papilloma yield induced by TPA was decreased by topical beta -carotene from an average of 20 to similar to 10 papillomas/mouse (p = 2.5 x 10 super(-7)). The effect of topical beta -carotene persisted beyond the treatment period (Week 24) until the termination of the study at Week 42. Western blot analysis of mouse skin extracts showed that topical beta -carotene upregulated retinoic acid receptor- alpha and - gamma expression in the dorsal skin. This finding suggests that beta -carotene may work as a chemopreventive agent by upregulating the expression of retinoid receptors in mouse skin. In conclusion, our data show that beta -carotene prevents skin carcinoma formation, induces retionic acid receptor expression, and fails to act as a tumor promoter in the two-stage model of skin tumorigenesis. JF - Nutrition and Cancer AU - Ponnamperuma, R M AU - Shimizu, Y AU - Kirchhof, S M AU - De Luca, LM AD - Bldg. 37 Rm. 3A-17, 37 Convent Dr., National Cancer Institute, Bethesda, MD 20892-4255, USA Y1 - 2000 PY - 2000 DA - 2000 SP - 82 EP - 88 VL - 37 IS - 1 SN - 0163-5581, 0163-5581 KW - chemopreventive agents KW - Toxicology Abstracts KW - ^b-Carotene KW - Retinoic acid receptors KW - Phorbol esters KW - Skin KW - 9,10-Dimethyl-1,2-benzanthracene KW - Tumorigenesis KW - Tumor-promoting agents KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17623593?accountid=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=Nutrition+and+Cancer&rft.atitle=beta+-Carotene+Fails+to+Act+as+a+Tumor+Promoter%2C+Induces+RAR+Expression%2C+and+Prevents+Carcinoma+Formation+in+a+Two-Stage+Model+of+Skin+Carcinogenesis+in+Male+Sencar+Mice&rft.au=Ponnamperuma%2C+R+M%3BShimizu%2C+Y%3BKirchhof%2C+S+M%3BDe+Luca%2C+LM&rft.aulast=Ponnamperuma&rft.aufirst=R&rft.date=2000-01-01&rft.volume=37&rft.issue=1&rft.spage=82&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+Cancer&rft.issn=01635581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Tumor-promoting agents; ^b-Carotene; Retinoic acid receptors; Skin; Tumorigenesis; 9,10-Dimethyl-1,2-benzanthracene; Phorbol esters ER - TY - JOUR T1 - Possible Roles of Nitric Oxide and Redox Cell Signaling in Metal-Induced Toxicity and Carcinogenesis: A Review AN - 17622168; 4762036 AB - Toxic doses of transition metals are capable of disturbing the natural oxidation/reduction balance in cells through various mechanisms stemming from their own complex redox reactions with endogenous oxidants and effects on cellular antioxidant systems. The resulting oxidative stress may damage redox-sensitive signaling molecules, such as NO, S-nitrosothiols, AP-1, NF- Kappa B, I Kappa B, p53, p21 super(ras), and others, and thus derange the cell signaling and gene expression systems. This, in turn, may produce a variety of toxic effects, including carcinogenesis. Experimental support for the relevance of oxidative damage to the mechanisms of metal toxicity and carcinogenicity is particularly strong for two essential (but toxic when overdosed) metals--iron and copper--and three well-established human metal carcinogens--nickel, chromium, and cadmium. However, along with more specific effects of toxic metals associated with their selective binding to particular cell constituents and affecting calcium signaling, oxidative damage seems to become important as well in explaining mechanisms of pathogenicity of other metals, such as lead, mercury, and arsenic. JF - Journal of Environmental Pathology, Toxicology and Oncology AU - Buzard, G S AU - Kasprzak, K S AD - Bldg. 538, Rm. 205E, NCI-FCRDC, Frederick MD 21702, USA Y1 - 2000 PY - 2000 DA - 2000 SP - 179 EP - 199 VL - 19 IS - 3 SN - 0731-8898, 0731-8898 KW - Toxicology Abstracts KW - Metals KW - Intracellular signalling KW - Oxidative stress KW - Reviews KW - Carcinogenesis KW - Nitric oxide KW - Copper KW - Iron KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17622168?accountid=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+Environmental+Pathology%2C+Toxicology+and+Oncology&rft.atitle=Possible+Roles+of+Nitric+Oxide+and+Redox+Cell+Signaling+in+Metal-Induced+Toxicity+and+Carcinogenesis%3A+A+Review&rft.au=Buzard%2C+G+S%3BKasprzak%2C+K+S&rft.aulast=Buzard&rft.aufirst=G&rft.date=2000-01-01&rft.volume=19&rft.issue=3&rft.spage=179&rft.isbn=&rft.btitle=&rft.title=Journal+of+Environmental+Pathology%2C+Toxicology+and+Oncology&rft.issn=07318898&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special issue: Mechanism of metal carcinogenesis. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Intracellular signalling; Carcinogenesis; Reviews; Nitric oxide; Oxidative stress; Iron; Metals; Copper ER - TY - JOUR T1 - Spontaneous Transformation of Cultured Rat Liver (TRL 1215) Cells Is Associated with Down-Regulation of Metallothionein: Implications for Sensitivity to Cadmium Cytotoxicity and Genotoxicity AN - 17620073; 4762042 AB - Previously, we found cadmium (Cd) to be effective in suppressing liver and lung tumors in rodents. Thus, this study investigated the susceptibility of cultured cells to Cd during spontaneous transformation. The TRL 1215 cell line is an epithelial-like liver cell normally nontumorigenic. However, continuous passage can occasionally result in spontaneous transformation. In this study, we found that continuous passage (p) of TRL 1215 cells through p24-28 (high passage; HP) resulted in a spontaneous transformant. In contrast to low-passage (LP) cells (p15-19), the HP transformant had a fibroblast-like morphology and grew in soft agar. A passage-dependent decrease in Cd-induced DNA single-strand damage (SSD) was seen, indicating that HP cells were resistant to Cd genotoxicity. Both LP and HP cells exhibited similar sensitivity to gamma -irradiation-induced SSD, suggesting that resistance to Cd genotoxicity in HP cells was not indicative of generalized tolerance to DNA damage. In contrast to genotoxicity, HP cells were more sensitive to Cd-induced cytotoxicity than were LP cells. The LC sub(50) for a 2-hour Cd exposure was similar to 1,060 mu M for LP and 660 mu M for HP cells. At genotoxic concentrations (500 mu M) of Cd, LP cells accumulated similar to 1.8-fold more Cd than did HP cells, which may account for the reduced genotoxicity in HP cells but is not consistent with the enhanced cytotoxicity in the transformants. In contrast, LP cells had 7.4-fold greater basal metallothionein (MT) protein levels than did HP cells, which probably accounts for the increased cytotoxicity in HP cells. Basal levels of MT mRNA were similarly greater in LP cells. Thus, during spontaneous transformation of TRL 1215 cells, MT gene expression decreased, thereby increasing the susceptibility of these cells to Cd-induced cytotoxicity, which is consistent with an antitumor effect of Cd in some tumors that poorly express MT. However, MT expression, generally accepted to prevent almost all aspects of Cd toxicity, actually facilitated Cd genotoxicity, at least as assessed by SSD in LP cells. JF - Journal of Environmental Pathology, Toxicology and Oncology AU - Coogan, T P AU - Achanzar, W E AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, National Cancer Institute at NIEHS, 111 Alexander Drive, P.O. Box 12233, MD FO-O9, Research Triangle Park, NC 27709, USA Y1 - 2000 PY - 2000 DA - 2000 SP - 261 EP - 273 VL - 19 IS - 3 SN - 0731-8898, 0731-8898 KW - rats KW - cell lines KW - metallothionein KW - Toxicology Abstracts KW - Transformation KW - Metals KW - Liver KW - Cadmium KW - X 24163:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17620073?accountid=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+Environmental+Pathology%2C+Toxicology+and+Oncology&rft.atitle=Spontaneous+Transformation+of+Cultured+Rat+Liver+%28TRL+1215%29+Cells+Is+Associated+with+Down-Regulation+of+Metallothionein%3A+Implications+for+Sensitivity+to+Cadmium+Cytotoxicity+and+Genotoxicity&rft.au=Coogan%2C+T+P%3BAchanzar%2C+W+E%3BWaalkes%2C+M+P&rft.aulast=Coogan&rft.aufirst=T&rft.date=2000-01-01&rft.volume=19&rft.issue=3&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Journal+of+Environmental+Pathology%2C+Toxicology+and+Oncology&rft.issn=07318898&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special issue: Mechanism of metal carcinogenesis. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Metals; Cadmium; Transformation; Liver ER - TY - JOUR T1 - The US-Japan Cooperative Medical Science Program Tuberculosis-Leprosy Panel's 34th Annual Research Conference, San Francisco, California: 27-30 June 1999 AN - 17607581; 4729318 AB - On June 27-30, 1999, the US-Japan Cooperative Medical Science Program (USJCMSP) Tuberculosis-Leprosy Panel held its 34th Annual Research Conference, in San Francisco, California, hosted by Dr Philip Hopewell of the University of California, San Francisco. The USJCMSP was initiated in the early 1960s as a joint effort between the USA and Japan to develop a biomedical research program directed towards diseases of public health concern for the people of Southeast Asia. The USJCMSP is currently focused on 10 areas of emphasis (Panels), one of which is a joint Tuberculosis-Leprosy Panel. The Tuberculosis-Leprosy Panel holds an annual meeting, alternating meeting sites between Japan and the USA. The conference is meant as a forum for mycobacterial investigators to share the latest research advances and to stimulate collaborations between USA and Japanese scientists in combating tuberculosis and leprosy. JF - Tubercle and Lung Disease AU - Ginsberg, A M AD - National Institutes of Health, National Institute for Allergy and Infectious Diseases, USA Y1 - 2000 PY - 2000 DA - 2000 SP - 85 EP - 108 VL - 80 IS - 2 SN - 0962-8479, 0962-8479 KW - Microbiology Abstracts B: Bacteriology KW - Conferences KW - Mycobacterium leprae KW - Tuberculosis KW - USA, California KW - Leprosy KW - Mycobacterium tuberculosis KW - J 02855:Human Bacteriology: Others KW - J 02930:Proceedings UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17607581?accountid=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=Tubercle+and+Lung+Disease&rft.atitle=The+US-Japan+Cooperative+Medical+Science+Program+Tuberculosis-Leprosy+Panel%27s+34th+Annual+Research+Conference%2C+San+Francisco%2C+California%3A+27-30+June+1999&rft.au=Ginsberg%2C+A+M&rft.aulast=Ginsberg&rft.aufirst=A&rft.date=2000-01-01&rft.volume=80&rft.issue=2&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Tubercle+and+Lung+Disease&rft.issn=09628479&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 - Mycobacterium tuberculosis; Mycobacterium leprae; USA, California; Tuberculosis; Leprosy; Conferences ER - TY - JOUR T1 - Six high-priority organochlorine pesticides, either singly or in combination, are nonestrogenic in transfected HeLa cells AN - 17541831; 4729331 AB - There have been increasing concerns that environmental chemicals may adversely affect the health of humans and wildlife by acting as endocrine modulators. These concerns have been augmented by the realization that human exposure occurs not just to single chemical agents, but typically to mixtures of chemicals that could exhibit estrogenic activity qualitatively and/or quantitatively different from that of individual components. To address these concerns, we have evaluated the ability of six organochlorine pesticides (4,4'-DDT, 4,4'-DDD, 4,4'-DDE, aldrin, dieldrin, or endrin, all classified high priority by ATSDR) to modulate transcriptional activation of an estrogen-responsive reporter gene in transfected HeLa cells. In these assays, HeLa cells cotransfected with an expression vector encoding estrogen receptor and an estrogen-responsive chloramphenicol acetyltransferase (CAT) reporter plasmid were exposed to these pesticides individually and in defined combinations. While estradiol consistently elicited 10- to 23-fold dose-dependent inductions in these assays, the six organochlorine pesticides showed no detectable dose-related response when tested individually. When tested in binary combinations, the pesticide mixtures showed no additional estrogenicity. Thus, the pesticides tested, singly or as mixtures, showed virtually no evidence of estrogenicity. JF - Reproductive Toxicology AU - Tully, D B AU - Cox, V T AU - Mumtaz, M M AU - Davis, V L AU - Chapin, R E AD - Laboratory of Toxicology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, 111 TW Alexander Drive, Bldg. 101, Room E-145, Research Triangle Park, NC 27709-2233, USA, dtully@mindspring.com Y1 - 2000 PY - 2000 DA - 2000 SP - 95 EP - 102 VL - 14 IS - 2 SN - 0890-6238, 0890-6238 KW - man KW - tumor cell lines KW - aldrin KW - endrin KW - Toxicology Abstracts KW - Estrogens KW - HeLa cells KW - Dieldrin KW - Pesticides (organochlorine) KW - 17^b-Estradiol KW - X 24135:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17541831?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+Toxicology&rft.atitle=Six+high-priority+organochlorine+pesticides%2C+either+singly+or+in+combination%2C+are+nonestrogenic+in+transfected+HeLa+cells&rft.au=Tully%2C+D+B%3BCox%2C+V+T%3BMumtaz%2C+M+M%3BDavis%2C+V+L%3BChapin%2C+R+E&rft.aulast=Tully&rft.aufirst=D&rft.date=2000-01-01&rft.volume=14&rft.issue=2&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Reproductive+Toxicology&rft.issn=08906238&rft_id=info:doi/10.1016%2FS0890-6238%2800%2900060-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pesticides (organochlorine); HeLa cells; 17^b-Estradiol; Dieldrin; Estrogens DO - http://dx.doi.org/10.1016/S0890-6238(00)00060-5 ER - TY - JOUR T1 - Lactoferrin is an estrogen responsive protein in the uterus of mice and rats AN - 17541108; 4729332 AB - To identify lactoferrin (LF) and determine its estrogen-responsiveness in the rat uterus, immature Sprague-Dawley rats were untreated or subcutaneously injected with 17 beta -estradiol (500 mu g/kg) for 3 days and uterine tissues collected. Outbred immature CD-1 mice, treated with 17 beta -estradiol, provided the positive control. By using a polyclonal antibody raised against mouse LF, minimal detectable protein was immunolocalized in uterine epithelial cells of untreated immature rats and mice. After estrogen treatment, LF was localized in all uterine epithelial cells of both species, although staining was more intense in mice than rats. In mice, LF was evenly distributed throughout the cytoplasm with intense staining in some cells, while in rats, it was seen mainly in the apical cytoplasm. For comparison to another well-known estrogen responsive protein in rats, complement C3 was immunolocalized within epithelial cells and it showed a different staining pattern than LF. Uterine tissue homogenates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blots showed cross-reactivity with the mouse LF antibody. These findings indicate that LF is present in the rat uterus, and is induced by estrogens as reported in other species. Thus, LF is an important marker of estrogenic activity across species and will, therefore, have utility in screening for effects of environmental estrogenic compounds. JF - Reproductive Toxicology AU - Jefferson, W N AU - Padilla-Banks, E AU - Newbold, R R AD - Developmental Endocrinology Section, Reproductive Toxicology Group, Laboratory of Toxicology, Environmental Toxicology Program, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27709, USA, newbold1@niehs.nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 103 EP - 110 VL - 14 IS - 2 SN - 0890-6238, 0890-6238 KW - mice KW - rats KW - lactoferrin KW - Toxicology Abstracts KW - Estrogens KW - Uterus KW - Polyclonal antibodies KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17541108?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+Toxicology&rft.atitle=Lactoferrin+is+an+estrogen+responsive+protein+in+the+uterus+of+mice+and+rats&rft.au=Jefferson%2C+W+N%3BPadilla-Banks%2C+E%3BNewbold%2C+R+R&rft.aulast=Jefferson&rft.aufirst=W&rft.date=2000-01-01&rft.volume=14&rft.issue=2&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Reproductive+Toxicology&rft.issn=08906238&rft_id=info:doi/10.1016%2FS0890-6238%2800%2900061-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Uterus; Estrogens; Polyclonal antibodies DO - http://dx.doi.org/10.1016/S0890-6238(00)00061-7 ER - TY - JOUR T1 - DNA vaccines: Immunology, application, and optimization AN - 17541008; 4719716 AB - The development and widespread use of vaccines against infectious agents have been a great triumph of medical science. One reason for the success of currently available vaccines is that they are capable of inducing long-lived antibody responses, which are the principal agents of immune protection against most viruses and bacteria. Despite these successes, vaccination against intracellular organisms that require cell-mediated immunity, such as the agents of tuberculosis, malaria, leishmaniasis, and human immunodeficiency virus infection, are either not available or not uniformly effective. Owing to the substantial morbidity and mortality associated with these diseases worldwide, an understanding of the mechanisms involved in generating long-lived cellular immune responses has tremendous practical importance. For these reasons, a new form of vaccination, using DNA that contains the gene for the antigen of interest, is under intensive investigation, because it can engender both humoral and cellular immune responses. This review focuses on the mechanisms by which DNA vaccines elicit immune responses. In addition, a list of potential applications in a variety of preclinical models is provided. JF - Annual Review of Immunology AU - Gurunathan, S AU - Klinman, D M AU - Seder, R A AD - Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA, seder@nih.gov Y1 - 2000 PY - 2000 DA - 2000 SP - 927 EP - 974 VL - 18 SN - 0732-0582, 0732-0582 KW - immunology KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Immune response (cell-mediated) KW - DNA vaccines KW - Reviews KW - Vaccines KW - F 06807:Active immunization KW - W3 33345:DNA vaccines KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17541008?accountid=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=Annual+Review+of+Immunology&rft.atitle=DNA+vaccines%3A+Immunology%2C+application%2C+and+optimization&rft.au=Gurunathan%2C+S%3BKlinman%2C+D+M%3BSeder%2C+R+A&rft.aulast=Gurunathan&rft.aufirst=S&rft.date=2000-01-01&rft.volume=18&rft.issue=&rft.spage=927&rft.isbn=&rft.btitle=&rft.title=Annual+Review+of+Immunology&rft.issn=07320582&rft_id=info:doi/10.1146%2Fannurev.immunol.18.1.927 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vaccines; DNA vaccines; Reviews; Immune response (cell-mediated) DO - http://dx.doi.org/10.1146/annurev.immunol.18.1.927 ER - TY - CONF T1 - Effects of TCDD on thyroid hormone homeostasis in the rat AN - 17528087; 4708007 AB - A physiological dosimetric model was constructed to describe the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on circulating thyroid hormones in the rat and to test the hypothesis that these hormonal changes cause chronically elevated serum thyrotropin (thyroid stimulating hormone, TSH), which mediates growth promotion and may lead to thyroid tumors in TCDD-treated rats. The model included diffusion restricted distribution of TCDD among compartments for liver, kidney, white fat, slowly and rapidly perfused tissues, and the thyroxine-sensitive tissues brown fat, pituitary, and thyroid. Blood was distributed among major vessels and the capillary beds of the tissues. Metabolism of TCDD was limited to the liver. Secretion of 3,5,3'-triiodothyronine (T sub(3)) and thyroxine (3,5,3',5'-tetraiodothyronine, T sub(4)) from the thyroid was modeled as stimulated by circulating TSH, whose release from the pituitary was regulated by the hypothalamic peptides thyrotropin releasing hormone (activating) and somatostatin (inhibiting). Release of these peptides was represented as inhibited and activated, respectively, by circulating T sub(4). Binding proteins for T sub(3) and T sub(4) and metabolism of the hormones by deiodination were included in thyroxine-sensitive tissues. Induction of hepatic UDP-glucuronosyltransferase-1*6 (UGT), the enzyme which glucuronidates T sub(4), was modeled as induced by the complex formed between TCDD and the aryl hydrocarbon receptor. The computed extent of deiodination, primacy of the thyroid in generating T sub(3) from T sub(4), dependence of liver and kidney on locally produced T sub(3), and export of T sub(3) formed in the pituitary agreed with experimental observations. The model reproduced the observed decrease in circulating T sub(4) and elevated serum TSH following chronic administration of TCDD. The altered levels were attributed to the increased clearance of T sub(4) by the induced UGT and the consequent modification of feedback control of hormone releases. These results are consistent with the hypothesis of growth stimulation by elevated TSH, but measured values of this hormone in blood of rats vary over a large range, and the change induced by TCDD is often small. Measured UGT levels are less variable and the increase in this protein is much greater, suggesting that this response may be a more reliable biomarker for effects of TCDD on the thyroid. JF - Drug and Chemical Toxicology AU - Kohn, M C Y1 - 2000 PY - 2000 DA - 2000 SP - 259 EP - 277 PB - Marcel Dekker Journals, 270 Madison Ave. New York NY 10016-0602 USA VL - 23 IS - 1 KW - triiodothyronine KW - rats KW - TSH KW - liothyronine KW - thyroid-stimulating hormone KW - thyroxine KW - Toxicology Abstracts KW - Liver KW - TCDD KW - Thyroid hormone KW - Homeostasis KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17528087?accountid=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=Drug+and+Chemical+Toxicology&rft.atitle=Effects+of+TCDD+on+thyroid+hormone+homeostasis+in+the+rat&rft.au=Kohn%2C+M+C&rft.aulast=Kohn&rft.aufirst=M&rft.date=2000-01-01&rft.volume=23&rft.issue=1&rft.spage=259&rft.isbn=&rft.btitle=&rft.title=Drug+and+Chemical+Toxicology&rft.issn=01480545&rft_id=info:doi/10.1081%2FDCT-100100114 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1081/DCT-100100114 ER - TY - JOUR T1 - Growth, pigment production and protease activity of Monascus purpureus as affected by salt, sodium nitrite, polyphosphate and various sugars AN - 17511615; 4697398 AB - The effect of different levels of salt, sodium nitrite, polyphosphate and various sugars on growth, pigment production, protease activity and culture pH caused by Monascus purpureus was studied in broth medium and ground meat. The addition of sodium chloride (> 50.0 g l super(-1)) and polyphosphate (> 3.0 g l super(-1)) to broth medium decreased mycelial growth, pigment production and protease activity of M. purpureus, whereas low concentrations of sodium nitrite (< 0.2 g l super(-1)) promoted mycelial growth and pigment production. When the basal medium and ground meat contained salt, 150.0 g l super(-1), the mould growth was stopped. The medium with fructose as carbon source proved to be the most suitable for mycelium growth and pigment production, with maltose and glucose being the second most productive. When sucrose and lactose were used as carbon sources, mycelium growth and pigment production were inhibited but the protease activity increased significantly. The mould showed more tolerance to salt and polyphosphate in ground meat than in broth medium and used sucrose as a carbon source as well as glucose for growth and pigment production in the meat mixture. JF - Journal of Applied Microbiology AU - Tseng, Y Y AU - Chen, M T AU - Lin, C F AD - Department of Animal Science, National Pingtung University of Science and Technology, 1 Hsueh-Fu Road, Loa-pi, Nei-pu, Pingtung 91207, Taiwan Y1 - 2000/01// PY - 2000 DA - Jan 2000 SP - 31 EP - 37 VL - 88 IS - 1 SN - 1364-5072, 1364-5072 KW - polyphosphate KW - Microbiology Abstracts A: Industrial & Applied Microbiology KW - Meat KW - Sugar KW - Monascus purpureus KW - Pigments KW - Proteinase KW - Sodium nitrite KW - Carbon sources KW - Mycelia KW - pH effects KW - Sodium chloride KW - A 01017:Human foods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17511615?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Applied+Microbiology&rft.atitle=Growth%2C+pigment+production+and+protease+activity+of+Monascus+purpureus+as+affected+by+salt%2C+sodium+nitrite%2C+polyphosphate+and+various+sugars&rft.au=Tseng%2C+Y+Y%3BChen%2C+M+T%3BLin%2C+C+F&rft.aulast=Tseng&rft.aufirst=Y&rft.date=2000-01-01&rft.volume=88&rft.issue=1&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Journal+of+Applied+Microbiology&rft.issn=13645072&rft_id=info:doi/10.1046%2Fj.1365-2672.2000.00821.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Monascus purpureus; Proteinase; Pigments; pH effects; Mycelia; Sugar; Carbon sources; Sodium nitrite; Sodium chloride; Meat DO - http://dx.doi.org/10.1046/j.1365-2672.2000.00821.x ER - TY - JOUR T1 - Production process for recombinant human angiostatin in Pichia pastoris AN - 17498680; 4683003 AB - A pilot-scale production method of recombinant human angiostatin, a 38-kD fragment of plasminogen which has been reported to have antiangiogenic activity, has been successfully established by expressing the protein in the methylotrophic yeast Pichia pastoris. The secreted protein inhibited cultured endothelial cell proliferation in vitro and Lewis lung carcinoma growth in mice. The fermentation process was carried out using an on-line methanol control, administering methanol to the growing culture and keeping its concentration under 2 g L super(-1). The fermentation lasted 90 h, of which 70 h were growth on methanol. During growth on methanol the culture volume increased 64%, from 7 L to 11.5 L, producing 200 mg angiostatin and 5 kg of biomass. JF - Journal of Industrial Microbiology & Biotechnology AU - Lin, J AU - Panigraphy, D AU - Trinh, L B AU - Folkman, J AU - Shiloach, J AD - Biotechnology Unit, Bldg 6 Rm B1-33, NIH, Bethesda, MD 20892, USA, ljs@helix.nih.gov Y1 - 2000/01// PY - 2000 DA - Jan 2000 SP - 31 EP - 35 VL - 24 IS - 1 SN - 1367-5435, 1367-5435 KW - man KW - Pichia pastoris KW - angiostatin KW - lung carcinoma KW - plasminogen KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Recombinants KW - Gene expression KW - Fermentation KW - Culture systems KW - Cell proliferation KW - K 03079:Fungi KW - W3 33580:Process engineering KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17498680?accountid=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+process+for+recombinant+human+angiostatin+in+Pichia+pastoris&rft.au=Lin%2C+J%3BPanigraphy%2C+D%3BTrinh%2C+L+B%3BFolkman%2C+J%3BShiloach%2C+J&rft.aulast=Lin&rft.aufirst=J&rft.date=2000-01-01&rft.volume=24&rft.issue=1&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Journal+of+Industrial+Microbiology+%26+Biotechnology&rft.issn=13675435&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 - Pichia pastoris; Culture systems; Cell proliferation; Fermentation; Gene expression; Recombinants ER - TY - JOUR T1 - Arthropod-frog connection: Decahydroquinoline and pyrrolizidine alkaloids common to microsympatric myrmicine ants and dendrobatid frogs AN - 17488298; 4682947 AB - Neotropical poison frogs (Dendrobatidae) contain a wide variety of lipophilic alkaloids, apparently accumulated unchanged into skin glands from dietary sources. Panamanian poison frogs (Dendrobates auratus) raised in a large, screened, outdoor cage and provided for six months with leaf-litter from the frog's natural habitat, accumulated a variety of alkaloids into the skin. These included two isomers of the ant pyrrolizidine 251K; two isomers of the 3,5-disubstituted indolizidine 195B; an alkaloid known to occur in myrmicine ants; another such indolizidine, 211E; two pyrrolidines, 197B and 223N, the former known to occur in myrmicine ants; two tricyclics, 193C and 219I, the former known to occur as precoccinelline in coccinellid beetles; and three spiropyrrolizidines, 222, 236, and 252A, representatives of an alkaloid class known to occur in millipedes. The alkaloids 211E, 197B, and 223N appear likely to derive in part from ants that entered the screened cage. In addition, the frog skin extracts contained trace amounts of four alkaloids, 205D, 207H, 219H, and 231H, of unknown structures and source. Wild-caught frogs from the leaf-litter site contained nearly 40 alkaloids, including most of the above alkaloids. Pumiliotoxins and histrionicotoxins were major alkaloids in wild-caught frogs, but were absent in captive-raised frogs. Ants microsympatric with the poison frog at the leaf-litter site and at an island site nearby in the Bay of Panama were examined for alkaloids. The decahydroquinoline (-)-cis-195A and two isomers of the pyrrolizidine 251K were found to be shared by microsympatric myrmicine ants and poison frogs. The proportions of the two isomers of 251K were the same in ant and frog. JF - Journal of Chemical Ecology AU - Daly, J W AU - Garraffo, H M AU - Jain, P AU - Spande, T F AU - Snelling, R R AU - Jaramillo, C AU - Rand, A S AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0820, USA Y1 - 2000/01// PY - 2000 DA - Jan 2000 SP - 73 EP - 86 VL - 26 IS - 1 SN - 0098-0331, 0098-0331 KW - Alkaloids KW - Ants KW - Dart poison frog KW - Dendrobatids KW - Green and black poison dart frog KW - Poison frogs KW - Poison-dart frogs KW - ASFA 1: Biological Sciences & Living Resources; Ecology Abstracts; Entomology Abstracts KW - Panama KW - Diets KW - Skin KW - Formicidae KW - Metabolites KW - Dendrobatidae KW - Freshwater KW - Defence mechanisms KW - Chemical defence KW - Toxins KW - Biochemical composition KW - Myrmicinae KW - Defense mechanisms KW - Dendrobates auratus KW - Q1 08326:Physiology, biochemistry, biophysics KW - D 04659:Insects KW - Z 05183:Toxicology & resistance KW - D 04669:Amphibians UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17488298?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Chemical+Ecology&rft.atitle=Arthropod-frog+connection%3A+Decahydroquinoline+and+pyrrolizidine+alkaloids+common+to+microsympatric+myrmicine+ants+and+dendrobatid+frogs&rft.au=Daly%2C+J+W%3BGarraffo%2C+H+M%3BJain%2C+P%3BSpande%2C+T+F%3BSnelling%2C+R+R%3BJaramillo%2C+C%3BRand%2C+A+S&rft.aulast=Daly&rft.aufirst=J&rft.date=2000-01-01&rft.volume=26&rft.issue=1&rft.spage=73&rft.isbn=&rft.btitle=&rft.title=Journal+of+Chemical+Ecology&rft.issn=00980331&rft_id=info:doi/10.1023%2FA%3A1005437427326 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - Diets; Biochemical composition; Alkaloids; Skin; Metabolites; Defence mechanisms; Chemical defence; Defense mechanisms; Toxins; Myrmicinae; Formicidae; Dendrobatidae; Dendrobates auratus; Panama; Freshwater DO - http://dx.doi.org/10.1023/A:1005437427326 ER - TY - JOUR T1 - Drinking Patterns among Individuals with and without DSM-IV Alcohol Use Disorders AN - 17486216; 4684792 AB - Objective: The purpose of this study was to compare alcohol consumption patterns among individuals with and without alcohol use disorders, using a representative sample of the general population that would not exaggerate differences as a result of selection biases associated with treatment for alcohol problems. Method: Based on data from 18,352 past-year drinkers selected from a nationally representative sample of U.S. households, 11 measures of past-year alcohol consumption were compared for three diagnostic groups: (1) individuals who did not meet the criteria for either alcohol abuse or dependence, i.e., those without a DSM-IV alcohol use disorder (AUD); (2) those classified with abuse only; and (3) those classified with alcohol dependence, with or without abuse. Results: For all measures reflecting frequency and quantity of drinking, frequency of heavy drinking and intoxication, and frequency of atypical temporal drinking patterns, the values for abusers lay midway between those for individuals without an AUD and those with dependence. Individuals with alcohol use disorders drank a greater proportion of their ethanol intake in the form of beer and a lower proportion in the form of wine than did those without an AUD. Of all the consumption measures considered, frequency of intoxication showed the strongest association with the probability of having an AUD, followed by frequency of drinking 5+ drinks, prevalence of morning drinking and total volume of intake. The ratios of consumption measures for individuals with disorders relative to those without an AUD showed relatively little significant variation across demographic subgroups of the population. Conclusions: The findings supported the distinction between the disorders of alcohol abuse and dependence, and implicated loss of control as an important element of this distinction. They also indicated that even among individuals with alcohol use disorders, demographic differentials reflecting cultural, physiological and normative forces were maintained and should be considered in approaches to treatment. JF - Journal of Studies on Alcohol AU - Dawson, DA AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Willco Building, Suite 514, 6000 Executive Boulevard MSC 7003, Bethesda, Maryland 20892-7003, USA Y1 - 2000/01// PY - 2000 DA - Jan 2000 SP - 111 EP - 120 VL - 61 IS - 1 SN - 0096-882X, 0096-882X KW - Toxicology Abstracts KW - Alcoholism KW - Drinking behavior KW - Ethanol KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17486216?accountid=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+Studies+on+Alcohol&rft.atitle=Drinking+Patterns+among+Individuals+with+and+without+DSM-IV+Alcohol+Use+Disorders&rft.au=Dawson%2C+DA&rft.aulast=Dawson&rft.aufirst=DA&rft.date=2000-01-01&rft.volume=61&rft.issue=1&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Journal+of+Studies+on+Alcohol&rft.issn=0096882X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Ethanol; Drinking behavior; Alcoholism ER - TY - JOUR T1 - Long-term toxicity and carcinogenicity study of cyclamate in nonhuman primates AN - 17482101; 4678176 AB - Twenty-one monkeys (cynomolgus, rhesus, African green) were fed cyclamate (100 mg/kg and 500 mg/kg) in the diet five times per week from a few days after birth and continuing for up to 24 years. Malignant tumors were diagnosed in three 24-year-old cyclamate monkeys; these were metastatic colon carcinoma (rhesus; 500 mg/kg), metastatic hepatocellular carcinoma (cynomolgus; 500 mg/kg), and a small, well differentiated adenocarcinoma of the prostate (cynomolgus; 100 mg/kg). Benign tumors were found at necropsy in three females; these were adenoma of the thyroid gland (rhesus; 100 mg/kg) and two cases of leiomyoma of the uterus (rhesus; 100 mg/kg and 500 mg/kg). No tumors were detected in an age-matched control group of 16 monkeys. Examination of the testes revealed complete testicular atrophy in one of the old cyclamate monkeys, and focal germ cell aplasia (Sertoli-only tubules) in two other cyclamate monkeys. Focal spermatogenic interruption (maturation arrest) at various germ cell levels mixed with normal spermatogenesis was observed in both the cyclamate-treated and the control monkeys, all of which were over 20 years old. Measurements of terminal cyclohexylamine concentrations showed that three of the males dosed with cyclamate at 500 mg/kg were high converters, with plasma concentrations comparable to the levels that produce testicular atrophy in rats. However, only one of the three high converters showed histologic evidence of irregular spermatogenesis. The overall conclusion is that the testicular abnormalities and the sporadic cases of different malignancies found after more than 20 years of dosing do not provide clear evidence of a toxic or carcinogenic effect of sodium cyclamate in monkeys. JF - Toxicological Sciences AU - Takayama, S AU - Renwick, A G AU - Johansson, S L AU - Thorgeirsson, U P AU - Tsutsumi, M AU - Dalgard, D W AU - Sieber, S M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Division of Basic Sciences, National Cancer Institute, Building 37, Room 2D02, Bethesda, MD 20892, USA, thorgeiu@dc37a.nci.nih.gov Y1 - 2000/01// PY - 2000 DA - Jan 2000 SP - 33 EP - 39 VL - 53 IS - 1 SN - 1096-6080, 1096-6080 KW - sodium cyclamate KW - monkeys KW - cyclamate KW - Toxicology Abstracts KW - Testes KW - Sweeteners KW - Carcinogenicity KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17482101?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Long-term+toxicity+and+carcinogenicity+study+of+cyclamate+in+nonhuman+primates&rft.au=Takayama%2C+S%3BRenwick%2C+A+G%3BJohansson%2C+S+L%3BThorgeirsson%2C+U+P%3BTsutsumi%2C+M%3BDalgard%2C+D+W%3BSieber%2C+S+M&rft.aulast=Takayama&rft.aufirst=S&rft.date=2000-01-01&rft.volume=53&rft.issue=1&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Sweeteners; Carcinogenicity; Testes ER - TY - JOUR T1 - Fishing for mutations AN - 17477886; 4678900 AB - In this issue Amanuma et al. report a system for using transgenic zebra fish (Brachydanio rerio) to test water environments for potential mutagens. Their system uses a shuttle plasmid that can be moved from zebra fish to bacteria, which will detect mutagens based on the acquisition of mutation-induced streptomycin resistance. The endeavor is quite important when we consider the dependency of life on water quality, and could be an important tool for understanding the mechanisms of mutagenesis in a whole organism. JF - Nature Biotechnology AU - Burkhart, J G AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA, burkhart@niehs.nih.gov Y1 - 2000/01// PY - 2000 DA - Jan 2000 SP - 21 EP - 22 VL - 18 IS - 1 SN - 1087-0156, 1087-0156 KW - Zebra danio KW - transgenic fish KW - Genetics Abstracts; ASFA Marine Biotechnology Abstracts; ASFA 3: Aquatic Pollution & Environmental Quality KW - Mutagens KW - Pollution detection KW - Mutations KW - Test organisms KW - Freshwater KW - Plasmids KW - Aquatic environment KW - Water pollution KW - Danio rerio KW - Genes KW - Reviews KW - Benzo(a)pyrene KW - Pollution indicators KW - G 07371:Fish KW - Q5 08502:Methods and instruments KW - Q4 27210:Fish UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17477886?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=Fishing+for+mutations&rft.au=Burkhart%2C+J+G&rft.aulast=Burkhart&rft.aufirst=J&rft.date=2000-01-01&rft.volume=18&rft.issue=1&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2F71869 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - Genes; Pollution detection; Mutations; Test organisms; Pollution indicators; Mutagens; Reviews; Benzo(a)pyrene; Plasmids; Water pollution; Aquatic environment; Danio rerio; Freshwater DO - http://dx.doi.org/10.1038/71869 ER - TY - JOUR T1 - Identification of Nocardia species by restriction endonuclease analysis of an amplified portion of the 16S rRNA gene AN - 17471978; 4669547 AB - Identification of clinical isolates of Nocardia to the species level is important for defining the spectrum of disease produced by each species and for predicting antimicrobial susceptibility. We evaluated the usefulness of PCR amplification of a portion of the Nocardia 16S rRNA gene and subsequent restriction endonuclease analysis (REA) for species identification. Unique restriction fragment length polymorphism (RFLP) patterns were found for Nocardia sp. type strains (except for the N. asteroides type strain) and representative isolates of the drug pattern types of Nocardia asteroides (except for N. asteroides drug pattern type IV, which gave inconsistent amplification). A variant RFLP pattern for Nocardia nova was also observed. Twenty-eight clinical isolates were evaluated both by traditional biochemical identification and by amplification and REA of portions of the 16S rRNA gene and the 65-kDa heat shock protein (HSP) gene. There was complete agreement among the three methods on identification of 24 of these isolates. One isolate gave a 16S rRNA RFLP pattern consistent with the biochemical identification but was not identifiable by its HSP gene RFLP patterns. Three isolates gave 16S rRNA RFLP patterns which were inconsistent with the identification obtained by both biochemical tests and HSP gene RFLP; sequence analysis suggested that two of these isolates may belong to undefined species. The PCR and REA technique described appears useful both for the identification of clinical isolates of Nocardia and for the detection of new or unusual species. JF - Journal of Clinical Microbiology AU - Conville, P S AU - Fischer, SH AU - Cartwright, ChP AU - Witebsky, F G AD - Microbiology Service, Clinical Pathology Department, National Institutes of Health, 10 Center Drive, MSC 1508, Bethesda, MD 20892-1508, USA, pconville@nih.gov Y1 - 2000/01// PY - 2000 DA - Jan 2000 SP - 158 EP - 164 VL - 38 IS - 1 SN - 0095-1137, 0095-1137 KW - HSP gene KW - rRNA 16S KW - Microbiology Abstracts B: Bacteriology KW - Genotyping KW - Restriction fragment length polymorphism KW - Restriction endonuclease mapping KW - Polymerase chain reaction KW - Nocardia nova KW - Nocardia KW - Nocardia asteroides KW - J 02704:Enumeration UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17471978?accountid=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=Identification+of+Nocardia+species+by+restriction+endonuclease+analysis+of+an+amplified+portion+of+the+16S+rRNA+gene&rft.au=Conville%2C+P+S%3BFischer%2C+SH%3BCartwright%2C+ChP%3BWitebsky%2C+F+G&rft.aulast=Conville&rft.aufirst=P&rft.date=2000-01-01&rft.volume=38&rft.issue=1&rft.spage=158&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&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 - Nocardia; Nocardia asteroides; Nocardia nova; Polymerase chain reaction; Restriction endonuclease mapping; Restriction fragment length polymorphism; Genotyping ER - TY - JOUR T1 - Aflatoxin B1-induced mitotic recombination in L5178Y mouse lymphoma cells AN - 17471461; 4678080 AB - Aflatoxin B1 is a human hepatocarcinogen. It is also a known point mutagen in bacteria and mammalian cells. This mutagenic activity may be at least partly responsible for its carcinogenic activity. However, recent studies show that aflatoxin B1 induces mitotic recombination in the yeast Saccharomyces cerevisiae. Because numerous reports have implicated mitotic recombination in mechanisms leading to carcinogenesis and because no one has shown that aflatoxin B1 induces recombination in mammalian cells, we decided to examine the ability of aflatoxin B1 to induce recombination in a mammalian cell line. We used a combination of methods, analysis for loss of heterozygosity and whole chromosome in situ hybridization, to identify mechanisms of chromosome mutation, including mitotic recombination in the mammalian L5178Y mouse lymphoma cell system. Our experiments revealed that mitotic recombination caused similar to 60% or more of the aflatoxin B1-induced mutagenic lesions in this cell system. Thus, mitotic recombination plays an important role in aflatoxin B1-induced mutagenesis in mammalian cells and possibly in chemically induced mutagenesis and carcinogenesis. This work suggests that multiple genetic lesions may be involved in aflatoxin B1-induced pathology. JF - Mutagenesis AU - Preisler, V AU - Caspary, W J AU - Hoppe, F AU - Hagen, R AU - Stopper, H AD - National Institutes of Health, Research Triangle Park, NC 27709, USA, caspary@niehs.nih.gov Y1 - 2000/01// PY - 2000 DA - Jan 2000 SP - 91 EP - 97 VL - 15 IS - 1 SN - 0267-8357, 0267-8357 KW - mice KW - Toxicology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Genetics Abstracts KW - Aflatoxin B1 KW - Mutagenesis KW - Mycotoxins KW - Chromosomes KW - Mitosis KW - Carcinogenesis KW - K 03082:Mycotoxins KW - X 24171:Microbial KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17471461?accountid=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=Mutagenesis&rft.atitle=Aflatoxin+B1-induced+mitotic+recombination+in+L5178Y+mouse+lymphoma+cells&rft.au=Preisler%2C+V%3BCaspary%2C+W+J%3BHoppe%2C+F%3BHagen%2C+R%3BStopper%2C+H&rft.aulast=Preisler&rft.aufirst=V&rft.date=2000-01-01&rft.volume=15&rft.issue=1&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Mutagenesis&rft.issn=02678357&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 - Aflatoxin B1; Mitosis; Chromosomes; Mutagenesis; Carcinogenesis; Mycotoxins ER - TY - JOUR T1 - The Bacterial Replicative Helicase DnaB Evolved from a RecA Duplication AN - 17466269; 4672369 AB - The RecA/Rad51/DCM1 family of ATP-dependent recombinases plays a crucial role in genetic recombination and double-stranded DNA break repair in Archaea, Bacteria, and Eukaryota. DnaB is the replication fork helicase in all Bacteria. We show here that DnaB shares significant sequence similarity with RecA and Rad51/DMC1 and two other related families of ATPases, Sms and KaiC. The conserved region spans the entire ATP- and DNA-binding domain that consists of about 250 amino acid residues and includes 7 distinct motifs. Comparison with the three-dimensional structure of Escherichia coli RecA and phage T7 DnaB (gp4) reveals that the area of sequence conservation includes the central parallel beta -sheet and most of the connecting helices and loops as well as a smaller domain that consists of a amino-terminal helix and a carboxy-terminal beta -meander. Additionally, we show that animals, plants, and the malarial Plasmodium but not Saccharomyces cerevisiae encode a previously undetected DnaB homolog that might function in the mitochondria. The DnaB homolog from Arabidopsis also contains a DnaG-primase domain and the DnaB homolog from the nematode seems to contain an inactivated version of the primase. This domain organization is reminiscent of bacteriophage primases-helicases and suggests that DnaB might have been horizontally introduced into the nuclear eukaryotic genome via a phage vector. We hypothesize that DnaB originated from a duplication of a RecA-like ancestor after the divergence of the bacteria from Archaea and eukaryotes, which indicates that the replication fork helicases in Bacteria and Archaea/Eukaryota have evolved independently. JF - Genome Research AU - Leipe, D D AU - Aravind, L AU - Grishin, N V AU - Koonin, E V AD - National Center for Biotechnology Information (NCBI), National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA, koonin@ncbi.nlm.nih.gov Y1 - 2000/01// PY - 2000 DA - Jan 2000 SP - 5 EP - 16 VL - 10 IS - 1 SN - 1054-9803, 1054-9803 KW - Plasmodium KW - Saccharomyces cerevisiae KW - budding yeast KW - Bacteria KW - DCM1 protein KW - DNA helicase KW - DnaB protein KW - DnaG protein KW - KaiC protein KW - Rad51 protein KW - RecA protein KW - Sms protein KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Adenosinetriphosphatase KW - Archaea KW - Escherichia coli KW - ATP KW - J 02728:Enzymes KW - G 07320:Bacterial genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17466269?accountid=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=Genome+Research&rft.atitle=The+Bacterial+Replicative+Helicase+DnaB+Evolved+from+a+RecA+Duplication&rft.au=Leipe%2C+D+D%3BAravind%2C+L%3BGrishin%2C+N+V%3BKoonin%2C+E+V&rft.aulast=Leipe&rft.aufirst=D&rft.date=2000-01-01&rft.volume=10&rft.issue=1&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=Genome+Research&rft.issn=10549803&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; Archaea; Plasmodium; Saccharomyces cerevisiae; Bacteria; ATP; Adenosinetriphosphatase ER - TY - JOUR T1 - The promise of nucleic acid vaccines AN - 17465734; 4672579 AB - Establishing the effective use of 'naked' nucleic acids as vaccines would undoubtedly be one of the most important advances in the history of vaccinology. While nucleic acids show much promise for use as vaccine vectors in experimental animals, not a single naked nucleic acid vector has been approved for use in humans. Indeed, data from human clinical trials is scant: nucleic acid vaccines have not been clearly demonstrated to have any convincing efficacy in the prevention or treatment of infectious disease or cancer. Here we illustrate possible mechanisms underlying effective nucleic acid vaccination. We focus on progress that has been made in the improvement of their function. Additionally, we identify promising new strategies and try to forecast future developments that could lead to the real success of nucleic acid vaccines in the prevention and treatment of human disease. JF - Gene Therapy AU - Restifo, N P AU - Ying, H AU - Hwang, L AU - Leitner, W W AD - Surgery Branch, NCI, Bldg 10, Room 2B42, 10 Center Dr, Bethesda, MD 20892, USA Y1 - 2000/01// PY - 2000 DA - Jan 2000 SP - 89 EP - 92 VL - 7 IS - 2 SN - 0969-7128, 0969-7128 KW - nucleic acids KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Infectious diseases KW - DNA vaccines KW - Vaccines KW - Cancer KW - W3 33345:DNA vaccines KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17465734?accountid=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=Gene+Therapy&rft.atitle=The+promise+of+nucleic+acid+vaccines&rft.au=Restifo%2C+N+P%3BYing%2C+H%3BHwang%2C+L%3BLeitner%2C+W+W&rft.aulast=Restifo&rft.aufirst=N&rft.date=2000-01-01&rft.volume=7&rft.issue=2&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&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 - Vaccines; DNA vaccines; Infectious diseases; Cancer ER - TY - JOUR T1 - Temporal changes in outer surface proteins A and C of the Lyme disease-associated spirochete, Borrelia burgdorferi, during the chain of infection in ticks and mice AN - 17465056; 4669638 AB - The Lyme disease-associated spirochete, Borrelia burgdorferi, is maintained in enzootic cycles involving Ixodes ticks and small mammals. Previous studies demonstrated that B. burgdorferi expresses outer surface protein A (OspA) but not OspC when residing in the midgut of unfed ticks. However, after ticks feed on blood, some spirochetes stop making OspA and express OspC. Our current work examined the timing and frequency of OspA and OspC expression by B. burgdorferi in infected Ixodes scapularis nymphs as they fed on uninfected mice and in uninfected I. scapularis larvae and nymphs as they first acquired spirochetes from infected mice. Smears of midguts from previously infected ticks were prepared at 12- or 24-h intervals following attachment through repletion at 96 h, and spirochetes were stained for immunofluorescence for detection of antibodies to OspA and OspC. As shown previously, prior to feeding spirochetes in nymphs expressed OspA but not OspC. During nymphal feeding, however, the proportion of spirochetes expressing OspA decreased, while spirochetes expressing OspC became detectable. In fact, spirochetes rapidly began to express OspC, with the greatest proportion of spirochetes having this protein at 48 h of attachment and then with the proportion decreasing significantly by the time that the ticks had completed feeding. In vitro cultivation of the spirochete at different temperatures showed OspC to be most abundant when the spirochetes were grown at 37 degree C. Yet, the synthesis of this protein waned with continuous passage at this temperature. Immunofluorescence staining of spirochetes in smears of midguts from larvae and nymphs still attached or having completed feeding on infected mice demonstrated that OspA but not OspC was produced by these spirochetes recently acquired from mice. Therefore, the temporal synthesis of OspC by spirochetes only in feeding ticks that were infected prior to the blood meal suggests that this surface protein is involved in transmission from tick to mammal but not from mammal to tick. JF - Journal of Clinical Microbiology AU - Schwan, T G AU - Piesman, J AD - Rocky Mountain Laboratories, 903 S. Fourth St., Hamilton, MT, USA, tom_schwan@nih.gov Y1 - 2000/01// PY - 2000 DA - Jan 2000 SP - 382 EP - 388 VL - 38 IS - 1 SN - 0095-1137, 0095-1137 KW - Acari KW - mice KW - OspA protein KW - OspC protein KW - Entomology Abstracts; Microbiology Abstracts B: Bacteriology KW - Nymphs KW - Ixodes KW - Feeding KW - Borrelia burgdorferi KW - Ixodidae KW - Larvae KW - Immunofluorescence KW - Blood meals KW - Ixodes scapularis KW - Infection KW - Disease transmission KW - Antibodies KW - Midgut KW - Lyme disease KW - J 02870:Invertebrate bacteriology KW - Z 05206:Medical & veterinary entomology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17465056?accountid=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=Temporal+changes+in+outer+surface+proteins+A+and+C+of+the+Lyme+disease-associated+spirochete%2C+Borrelia+burgdorferi%2C+during+the+chain+of+infection+in+ticks+and+mice&rft.au=Schwan%2C+T+G%3BPiesman%2C+J&rft.aulast=Schwan&rft.aufirst=T&rft.date=2000-01-01&rft.volume=38&rft.issue=1&rft.spage=382&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&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 - Borrelia burgdorferi; Ixodes; Ixodidae; Ixodes scapularis; Lyme disease; Infection; Blood meals; Midgut; Larvae; Nymphs; Immunofluorescence; Antibodies; Feeding; Disease transmission ER - TY - JOUR T1 - Correction of Glycogen Storage Disease Type 1a in a Mouse Model by Gene Therapy AN - 17455093; 4666430 AB - Glycogen storage disease type 1a (GSD-1a), characterized by hypoglycemia, liver and kidney enlargement, growth retardation, hyperlipidemia, and hyperuricemia, is caused by a deficiency in glucose-6-phosphatase (G6Pase), a key enzyme in glucose homeostasis. To evaluate the feasibility of gene replacement therapy for GSD-1a, we have infused adenoviral vector containing the murine G6Pase gene (Ad-mG6Pase) into G6Pase-deficient (G6Pase super(-/-)) mice that manifest symptoms characteristic of human GSD-1a. Whereas <15% of G6Pase super(-/-) mice under glucose therapy survived weaning, a 100% survival rate was achieved when G6Pase super(-/-) mice were infused with Ad-mG6Pase, 90% of which lived to 3 months of age. Hepatic G6Pase activity in Ad-mG6Pase-infused mice was restored to 19% of that in G6Pase super(+/+) mice at 7-14 days post-infusion; the activity persisted for at least 70 days. Ad-mG6Pase infusion also greatly improved growth of G6Pase super(-/-) mice and normalized plasma glucose, cholesterol, triglyceride, and uric acid profiles. Furthermore, liver and kidney enlargement was less pronounced with near-normal levels of glycogen depositions in both organs. Our data demonstrate that a single administration of a recombinant adenoviral vector can alleviate the pathological manifestations of GSD-1a in mice, suggesting that this disorder in humans can potentially be corrected by gene therapy. JF - Journal of Biological Chemistry AU - Zingone, A AU - Hiraiwa, H AU - Pan, C AU - Lin, B AU - Chen, H AU - Ward, J M AU - Chou, J Y AD - Heritable Disorders Branch, NICHD, National Institutes of Health, Bethesda, MD 20892-1830 USA, chou@helix.nih.gov Y1 - 2000/01// PY - 2000 DA - Jan 2000 SP - 828 EP - 832 VL - 275 IS - 2 SN - 0021-9258, 0021-9258 KW - mice KW - Adenovirus KW - G6Pase gene KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - Gene therapy KW - Glucose-6-phosphatase KW - Glucose KW - Glycogen KW - Gene transfer KW - Glycogenosis KW - G 07444:Animal models KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17455093?accountid=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+Biological+Chemistry&rft.atitle=Correction+of+Glycogen+Storage+Disease+Type+1a+in+a+Mouse+Model+by+Gene+Therapy&rft.au=Zingone%2C+A%3BHiraiwa%2C+H%3BPan%2C+C%3BLin%2C+B%3BChen%2C+H%3BWard%2C+J+M%3BChou%2C+J+Y&rft.aulast=Zingone&rft.aufirst=A&rft.date=2000-01-01&rft.volume=275&rft.issue=2&rft.spage=828&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/10.1074%2Fjbc.275.2.828 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adenovirus; Gene therapy; Gene transfer; Glycogenosis; Glucose; Glucose-6-phosphatase; Glycogen DO - http://dx.doi.org/10.1074/jbc.275.2.828 ER - TY - JOUR T1 - Subclinical chlamydial infection of the female mouse genital tract generates a potent protective immune response: Implications for development of live attenuated chlamydial vaccine strains AN - 17443845; 4652742 AB - Chlamydia trachomatis is a major cause of sexually transmitted disease (STD) for which a vaccine is needed. CD4 super(+) T-helper type 1 (Th1) cell-mediated immunity is an important component of protective immunity against murine chlamydial genital infection. Conventional vaccine approaches have not proven effective in eliciting chlamydial-specific CD4 Th1 immunity at the genital mucosa. Thus, it is possible that the development of a highly efficacious vaccine against genital infection will depend on the generation of a live attenuated C. trachomatis vaccine. Attenuated strains of C. trachomatis do not exist, so their potential utility as vaccines cannot be tested in animal models of infection. We have developed a surrogate model to study the effect of chlamydial attenuation on infection and immunity of the female genital tract by treating mice with a subchlamydiacidal concentration of oxytetracycline following vaginal infection. Compared to untreated control mice, antibiotic-treated mice shed significantly fewer infectious organisms (3 log sub(10)) from the cervico-vagina, produced a minimal inflammatory response in urogenital tissue, and did not experience infection-related sequelae. Antibiotic-treated mice generated levels of chlamydia-specific antibody and cell-mediated immunity equivalent to those of control mice. Importantly, antibiotic-treated mice were found to be as immune as control untreated mice when rechallenged vaginally. These findings demonstrate that subclinical chlamydial infection of the murine female genital tract is sufficient to stimulate a potent protective immune response. They also present indirect evidence supporting the possible use of live attenuated chlamydial organisms in the development of vaccines against chlamydial STDs. JF - Infection and Immunity AU - Su, H AU - Messer, R AU - Whitmire, W AU - Hughes, S AU - Caldwell, H D AD - Laboratory of Intracellular Parasites, National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratory, 903 South Fourth St., Hamilton, MT 59840, USA, hcaldwell@atlas.niaid.nih.gov Y1 - 2000/01// PY - 2000 DA - Jan 2000 SP - 192 EP - 196 VL - 68 IS - 1 SN - 0019-9567, 0019-9567 KW - mice KW - immunology KW - Chlamydia trachomatis KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Sexually-transmitted diseases KW - Helper cells KW - Animal models KW - Antibodies KW - Immune response (cell-mediated) KW - Lymphocytes T KW - Genital tract KW - Vaccines KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17443845?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Subclinical+chlamydial+infection+of+the+female+mouse+genital+tract+generates+a+potent+protective+immune+response%3A+Implications+for+development+of+live+attenuated+chlamydial+vaccine+strains&rft.au=Su%2C+H%3BMesser%2C+R%3BWhitmire%2C+W%3BHughes%2C+S%3BCaldwell%2C+H+D&rft.aulast=Su&rft.aufirst=H&rft.date=2000-01-01&rft.volume=68&rft.issue=1&rft.spage=192&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia trachomatis; Sexually-transmitted diseases; Vaccines; Immune response (cell-mediated); Genital tract; Lymphocytes T; Helper cells; Animal models; Antibodies ER -