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.serialssolution